Endovascular Therapy of M2 Occlusion in IMS III: Role of M2 Segment Definition and Location on Clinical and Revascularization Outcomes.

BACKGROUND AND PURPOSE: Uncertainty persists regarding the safety and efficacy of endovascular therapy of M2 occlusions following IV tPA. We reviewed the impact of revascularization on clinical outcomes in 83 patients with M2 occlusions in the Interventional Management of Stroke III trial according to specific M1-M2 segment anatomic features. MATERIALS AND METHODS: Perfusion of any M2 branch distinguished M2-versus-M1 occlusion. Prespecified modified TICI and arterial occlusive lesion revascularization and clinical mRS 0-2 end points at 90 days for endovascular therapy-treated M2 occlusions were analyzed. Post hoc analyses of the relationship of outcomes to multiple baseline angiographic M2 and M1 subgroup characteristics were performed. RESULTS: Of 83 participants with M2 occlusion who underwent endovascular therapy, 41.0% achieved mRS 0-2 at 90 days, including 46.6% with modified TICI 2-3 reperfusion compared with 26.1% with modified TICI 0-1 reperfusion (risk difference, 20.6%; 95% CI, -1.4%-42.5%). mRS 0-2 outcome was associated with reperfusion for M2 trunk (n = 9) or M2 division (n = 42) occlusions, but not for M2 branch occlusions (n = 28). Of participants with trunk and division occlusions, 63.2% with modified TICI 2a and 42.9% with modified TICI 2b reperfusion achieved mRS 0-2 outcomes; mRS 0-2 outcomes for M2 trunk occlusions (33%) did not differ from distal (38.2%) and proximal (26.9%) M1 occlusions. CONCLUSIONS: mRS 0-2 at 90 days was dependent on reperfusion for M2 trunk but not for M2 branch occlusions. For M2 division occlusions, good outcome with modified TICI 2b reperfusion did not differ from that in modified TICI 2a. M2 segment definition and occlusion location may contribute to differences in revascularization and good outcome between Interventional Management of Stroke III and other endovascular therapy studies.

Outcome Differences between Intra-Arterial Iso- and Low-Osmolality Iodinated Radiographic Contrast Media in the Interventional Management of Stroke III Trial.

BACKGROUND AND PURPOSE: Intracarotid arterial infusion of nonionic, low-osmolal iohexol contrast medium has been associated with increased intracranial hemorrhage in a rat middle cerebral artery occlusion model compared with saline infusion. Iso-osmolal iodixanol (290 mOsm/kg H2O) infusion demonstrated smaller infarcts and less intracranial hemorrhage compared with low-osmolal iopamidol and saline. No studies comparing iodinated radiographic contrast media in human stroke have been performed, to our knowledge. We hypothesized that low-osmolal contrast media may be associated with worse outcomes compared with iodixanol in the Interventional Management of Stroke III Trial (IMS III). MATERIALS AND METHODS: We reviewed prospective iodinated radiographic contrast media data for 133 M1 occlusions treated with endovascular therapy. We compared 5 prespecified efficacy and safety end points (mRS 0-2 outcome, modified TICI 2b-3 reperfusion, asymptomatic and symptomatic intracranial hemorrhage, and mortality) between those receiving iodixanol (n = 31) or low-osmolal contrast media (n = 102). Variables imbalanced between iodinated radiographic contrast media types or associated with outcome were considered potential covariates for the adjusted models. In addition to the iodinated radiographic contrast media type, final covariates were those selected by using the stepwise method in a logistic regression model. Adjusted relative risks were then estimated by using a log-link regression model. RESULTS: Of baseline or endovascular therapy variables potentially linked to outcome, prior antiplatelet agent use was more common and microcatheter iodinated radiographic contrast media injections were fewer with iodixanol. Relative risk point estimates are in favor of iodixanol for the 5 prespecified end points with M1 occlusion. The percentage of risk differences are numerically greater for microcatheter injections with iodixanol. CONCLUSIONS: While data favoring the use of iso-osmolal iodixanol for reperfusion of M1 occlusion following IV rtPA are inconclusive, potential pathophysiologic mechanisms suggesting clinical benefit warrant further investigation.

Clinical trial design in the neurocritical care unit.

Clinical trials provide a robust mechanism to advance science and change clinical practice across the widest possible spectrum. Fundamental in the Neurocritical Care Society's mission is to promote Quality Patient Care by identifying and implementing best medical practices for acute neurological disorders that are consistent with the current scientific knowledge. The next logical step will be to foster rapid growth of our scientific body of evidence, to establish and disseminate these best practices. In this manuscript, five invited experts were impaneled to address questions, identified by the conference organizing committee as fundamental issues for the design of clinical trials in the neurological intensive care unit setting.

Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) II: design, methods, and rationale.

The December 2003 report from the National Institute of Neurological Disorders and Stroke (NINDS) Workshop on priorities for clinical research in intracerebral hemorrhage (ICH) recommended clinical trials for evaluation of blood pressure management in acute ICH as a leading priority. The Special Writing Group of the Stroke Council of the American Heart Association in 1999 and 2007 emphasized the need for clinical trials to ensure evidence-based treatment of acute hypertensive response in ICH. To address important gaps in knowledge, we conducted a pilot study funded by the NINDS, Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) I Trial, during 2004-2008 to determine the appropriate level of systolic blood pressure (SBP) reduction. We now have initiated a multi-center, randomized Phase III trial, the ATACH II Trial, to definitively determine the efficacy of early, intensive, antihypertensive treatment using intravenous (IV) nicardipine initiated within 3 h of onset of ICH and continued for the next 24 h in subjects with spontaneous supratentorial ICH. The primary hypothesis of this large (N = 1,280), streamlined, and focused trial is that SBP reduction to ≤140 mm Hg reduces the likelihood of death or disability at 3 months after ICH, defined by modified Rankin scale score of 4-6, by at least 10% absolute compared to standard SBP reduction to ≤180 mm Hg. The ATACH II trial is a natural extension of numerous case series, the subsequent ATACH I pilot trial, and a preliminary, randomized, and controlled trial in this patient population funded by the Australian National Health and Medical Research Council. Both trials recently confirmed the safety and tolerability of both the regimen and goals of antihypertensive treatment in acutely hypertensive patients with ICH, as proposed in the present trial. The underlying mechanism for this expected beneficial effect of intensive treatment is presumably mediated through reduction of the rate and magnitude of hematoma expansion observed in approximately 73% of the patients with acute ICH. The Australian trial provided preliminary evidence of attenuation of hematoma expansion with intensive SBP reduction. The ATACH II trial will have important public health implications by providing evidence of, or lack thereof, regarding the efficacy and safety of acute antihypertensive treatment in subjects with ICH. This treatment represents a strategy that can be made widely available without the need for specialized equipment and personnel, and therefore, can make a major impact upon clinical practice for treating patients with ICH.

Revascularization results in the Interventional Management of Stroke II trial.

BACKGROUND AND PURPOSE: Our aim was to detail revascularization results, including impact on outcome and mortality, in the Interventional Management of Stroke (IMS) II trial. MATERIALS AND METHODS: IMS II was designed to obtain estimates of the efficacy and safety of reduced-dose intravenous recombinant tissue plasminogen activator (rtPA) followed by additional intra-arterial rtPA and low-energy sonography via the EKOS Primo Micro-Infusion Catheter at the occlusion in selected patients with ischemic stroke treated within 3 hours of onset. Revascularization outcomes were detailed and compared with modified Rankin Scale scores 0-2, mortality outcomes, and results from IMS I. RESULTS: Complete recanalization at 60 minutes occurred in 12 of 29 (41.4%) sonography microcatheter-treated occlusions. Complete recanalization was achieved at 2 hours or procedure end in 20/29 (68.9%) in the ultrasound catheter-treated group, and final thrombolysis in cerebral infarction (TICI) 2/3 reperfusion was achieved in 18/29 (62.0%) ultrasound-treated subjects. Fifteen-minute angiograms demonstrated some recanalization in 69/145 (46.7%) sonography microcatheter treatment intervals, compared with 39/111 (35.1%) in IMS I treatments in 23 subjects with reliable 15-minute angiograms (P = .046). Pooled IMS I-II data demonstrated that partial or complete recanalization occurred in 56/75 (74.6%) and good reperfusion (TICI 2/3) occurred in 46/75 (61.3%) of internal carotid artery T and M1 occlusions. Revascularization correlated with good outcome for TICI 2/3 reperfusion (P = .0004), TICI 2B/3 reperfusion (P = .0002), and arterial occlusive lesion 2/3 recanalization (P = .03). CONCLUSION: IMS II provides evidence that the EKOS Primo sonography microcatheter exhibits a trend toward improved recanalization of the occlusion compared with a standard microcatheter and again confirms the correlation between recanalization and reperfusion with good clinical outcome and reduced mortality.

The ALIAS (ALbumin In Acute Stroke) Phase III randomized multicentre clinical trial: design and progress report.

High-dose human ALB (albumin) therapy is highly neuroprotective in animal models of ischaemic stroke. A recently completed 82-subject pilot-phase dose-escalation trial has shown that ALB is safe, with strong preliminary suggestions of possible efficacy. We are now proceeding to a large randomized, double-blinded, placebo-controlled multicentre trial funded by the NIH (National Institutes of Health), the ALIAS (Albumin In Acute Stroke) Phase III Trial, which is designed to ascertain definitively whether high-dose ALB therapy confers neuroprotection in subjects with acute ischaemic stroke treated within 5 h of stroke onset. The primary efficacy outcome measure is a favourable outcome, defined as an NIHSS (NIH Stroke Scale) score of 0-1 or a modified Rankin Scale score of 0-1 at 3 months post-randomization. Separate randomization (1:1) to ALB or placebo therapy will be carried out in two cohorts of 900 subjects each, one that receives standard-of-care thrombolytic therapy and the other that does not. Approx. 60 North American clinical sites will participate. Subject enrollment is expected to commence in July 2006.

Using the baseline CT scan to select acute stroke patients for IV-IA therapy.

BACKGROUND: Intra-arterial therapies for acute ischemic stroke are increasingly available. Intravenous therapy (IV) followed immediately by intra-arterial therapy (IA) has been shown to be safe, but such therapy is resource intensive. Selecting the best patients for this therapy may be accomplished with the use of baseline neuroimaging. METHODS: We used data from the IMS-1 and National Institute for Neurological Disorders and Stroke tissue plasminogen activator (tPA) stroke studies to compare outcomes among IV-IA tPA, IV-tPA, and placebo treatment stratified by the baseline CT scan appearance. The CT scans were scored using the Alberta Stroke Program Early CT (ASPECT) score and dichotomized into ASPECT score > 7 (favorable scan) and ASPECT score < or = 7 (unfavorable scan). Logistic regression was used to assess for an ASPECT score by treatment interaction. RESULTS: A total of 460 patients was included. Age and sex were similar among the 3 groups. The IV-IA tPA cohort had a higher median National Institutes of Health stroke scale (NIHSS) score (18 versus 17) compared with the IV tPA cohort. The proportion of patients with favorable CT scans (ASPECT score > 7) was lowest in the IV-IA tPA group. A multiplicative interaction effect was shown indicating that patients with an ASPECT score > 7 in the IV-IA cohort were more likely to have a good outcome compared with IV tPA and with placebo. Harm may accrue to patients treated with IV-IA therapy who have an unfavorable baseline CT scan appearance. CONCLUSIONS: Patients with a favorable baseline CT scan appearance are the most likely to benefit from IV-IA therapy. This hypothesis will be tested in the IMS-3 study.

Optimizing the ongoing search for new treatments for Parkinson disease: using futility designs.

Many agents are being considered for treatment of Parkinson disease (PD). Given the large number of agents and the limited resources to evaluate new agents, it is essential to reduce the likelihood of advancing ineffective agents into large, long-term Phase III trials. Futility design methodology addresses this goal. The authors describe how a single-arm Phase II futility study uses a short-term outcome to compare a treatment group response to a predetermined hypothesized or historically based control response. The authors present advantages and limitations of futility designs along with examples derived from the data archive of a large Phase III efficacy study of treatments to delay PD progression, the Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) trial. Using the same control progression rate and treatment effect assumptions used to power the original DATATOP trial, the authors calculated the number of subjects needed to conduct two 12-month futility studies. DATATOP was designed to enroll 800 patients. Using data on 124 consecutive subjects randomized into each of the DATATOP treatment groups, the authors identified tocopherol as futile and deprenyl as worthy of further study. Using Phase II information, DATATOP could have been simplified from a 2 x 2 factorial design to a comparison of deprenyl vs placebo. While not testing efficacy, futility designs provide a strategy for discarding treatments unlikely to be effective in Phase III. A limitation is the dependence on historical data or hypothesized outcomes for untreated controls. Futility studies may decrease the time to identify treatments unworthy of further pursuit and reduce subjects' exposure to futile treatments.

The role of radiotracer imaging in Parkinson disease.

Radiotracer imaging (RTI) of the nigrostriatal dopaminergic system is a widely used but controversial biomarker in Parkinson disease (PD). Here the authors review the concepts of biomarker development and the evidence to support the use of four radiotracers as biomarkers in PD: [18F]fluorodopa PET, (+)-[11C]dihydrotetrabenazine PET, [123I]beta-CIT SPECT, and [18F]fluorodeoxyglucose PET. Biomarkers used to study disease biology and facilitate drug discovery and early human trials rely on evidence that they are measuring relevant biologic processes. The four tracers fulfill this criterion, although they do not measure the number or density of dopaminergic neurons. Biomarkers used as diagnostic tests, prognostic tools, or surrogate endpoints must not only have biologic relevance but also a strong linkage to the clinical outcome of interest. No radiotracers fulfill these criteria, and current evidence does not support the use of imaging as a diagnostic tool in clinical practice or as a surrogate endpoint in clinical trials. Mechanistic information added by RTI to clinical trials may be difficult to interpret because of uncertainty about the interaction between the interventions and the tracer.

Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel.

Real-time RT-PCR is a relatively new technology that uses an online fluorescence detection system to determine gene expression levels. It has the potential to significantly improve detection of breast cancer metastasis by virtue of its exquisite sensitivity, high throughput capacity and quantitative readout system. To assess the utility of this technology in breast cancer staging, we determined the relative expression levels of 12 cancer-associated genes (mam, PIP, mamB, CEA, CK19, VEGF, erbB2, muc1, c-myc, p97, vim and Ki67) in 51 negative-control normal lymph nodes and in 17 histopathology-positive ALNs. We then performed a receiver operating characteristic (ROC) curve analysis to determine the sensitivity and specificity levels of each gene. Areas under the ROC curve indicated that the most accurate diagnostic markers were mam (99.6%), PIP (93.3%), CK19 (91.0%), mamB (87.9%), muc1 (81.5%) and CEA (79.4.0%). mam was overexpressed in 16 of 17 lymph nodes known to contain metastatic breast cancer at levels ranging from 22- to 2.8 x 10(5)-fold above normal mean expression, whereas PIP was overexpressed from 30- to 2.2 x 10(6)-fold above normal in 13 lymph nodes. Real-time RT-PCR analysis of pathology-negative LN from breast cancer patients revealed evidence of overexpression of PIP (6 nodes), mam (3 nodes) and CEA (1 node) in 8 of 21 nodes (38%). Our results provide evidence that mam, PIP, CK19, mamB, muc1 and CEA can be applied as a panel for detection of metastatic and occult micrometastatic disease.

Age and alarm symptoms do not predict endoscopic findings among patients with dyspepsia: a multicentre database study.

INTRODUCTION: Symptoms of dyspepsia are common but most patients do not have major upper gastrointestinal pathology. Endoscopy is recommended for dyspeptic patients over the age of 45, or those with certain "alarm" symptoms. We have evaluated the effectiveness of age and "alarm" symptoms for predicting major endoscopic findings in six practising endoscopy centres. METHODS: Clinical variables of consecutive patients with dyspepsia symptoms undergoing upper endoscopy examinations were recorded using a common endoscopy database. Patients who had no previous upper endoscopy or barium radiography were included. Stepwise multivariate logistic regression was used to identify predictors of endoscopic findings. The accuracy of these for predicting endoscopic findings was evaluated with receiver operating characteristic analysis. The sensitivity and specificity of age thresholds from 30 to 70 years were evaluated. RESULTS: Major pathology (tumour, ulcer, or stricture) was found at endoscopy in 787/3815 (21%) patients with dyspepsia. Age, male sex, bleeding, and anaemia were found to be significant but weak independent predictors of endoscopic findings. A multivariate prediction rule based on these factors had poor predictive accuracy (c statistic=0.62). Using a simplified prediction rule of age > or =45 years or the presence of any "alarm" symptom, sensitivity was 87% and specificity was 26%. Increasing or decreasing the age cut off did not significantly improve the predictive accuracy. CONCLUSIONS: Age and the presence of "alarm" symptoms are not effective predictors of endoscopic findings among patients with dyspepsia. Better clinical prediction strategies are needed to identify patients with significant upper gastrointestinal pathology.

Polymorphic cytokine genotypes as markers of disease severity in adult periodontitis.

The distributions of the bi-allelic interleukin-1beta+3953 and tumor necrosis factor-alpha-308 genotypes were determined in 20 patients with advanced adult periodontitis, 20 patients with plaque associated gingivitis, and 45 referent population subjects. A significant increase in IL-1beta+3953 allele 2 frequency was found in patients with advanced periodontitis compared to referent subjects (the Fisher exact test; p=0.013). Furthermore, the frequency of TNF-alpha-308 allele 1 was significantly greater in patients with advanced disease compared to those with plaque associated gingivitis (the Fisher exact test; p=0.014). No significant correlation was observed between genotype and cytokine production in these patient populations.

Association between cigarette and alcohol consumption and Raynaud's phenomenon.

The association between alcohol and cigarette consumption and Raynaud's Phenomenon (RP) was examined by using data from an American-French collaborative, cross-sectional, epidemiological study in five geographically varied regions (Charleston, South Carolina, USA; and Grenoble, Tarentaise, Nyons, and Toulon, France). Using logistic regression models that take into account the sampling weights, the association was examined stratified by gender and adjusted for age, body mass index, self-perceived health, and education. Overall, neither cigarette nor alcohol consumption showed a significant association with RP. In men, however, a V-shaped relationship between drinking and RP was observed, with mild consumption (1 to 7 drinks per week) exhibiting a protective effect over abstinence, whereas occasional (less than 1 drink per week), moderate (8 to 18 drinks per week) and heavy consumption (more than 18 drinks per week) did not. Among the participants with RP, no significant association was observed between RP attack frequencies and the amount of either alcohol or cigarette consumption. These negative findings suggest that having RP is not strongly affected by alcohol or cigarette consumption.

Contribution of interleukin 1beta and KM loci to alopecia areata.

Alopecia areata is a common skin disease in which proinflammatory cytokines such as IL-1beta may play a pathogenic role. In this study, we examined the distribution of genotypes of an IL-1beta single base change polymorphism at position +3953 in patients with alopecia areata. The distribution of immunoglobulin kappa light chain (KM) genotypes was similarly examined. The data obtained showed that the IL-1beta and KM loci act cooperatively to significantly increase susceptibility to alopecia areata.

Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction.

BACKGROUND & AIMS: Patients with sphincter of Oddi dysfunction are at high risk of developing pancreatitis after endoscopic biliary sphincterotomy. Impaired pancreatic drainage caused by pancreatic sphincter hypertension is the likely explanation for this increased risk. A prospective, randomized controlled trial was conducted to determine if ductal drainage with pancreatic stenting protects against pancreatitis after biliary sphincterotomy in patients with pancreatic sphincter hypertension. METHODS: Eligible patients with pancreatic sphincter hypertension were randomized to groups with pancreatic duct stents (n = 41) or no stents (n = 39) after biliary sphincterotomy. The primary measured outcome was pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Pancreatic stenting significantly decreased the risk of pancreatitis from 26% to 7% (10 of 39 in the no stent group and 3 of 41 in the stent group; P = 0.03). Only 1 patient in the stent group developed pancreatitis after sphincterotomy, and 2 others developed pancreatitis at the time of stent extraction. Patients in the no stent group were 10 times more likely to develop pancreatitis immediately after sphincterotomy than those in the stent group (relative risk, 10.5; 95% confidence interval, 1.4-78.3). CONCLUSIONS: Pancreatic duct stenting protects significantly against post-ERCP pancreatitis in patients with pancreatic sphincter hypertension undergoing biliary sphincterotomy. Stenting of the pancreatic duct should be strongly considered after biliary sphincterotomy for sphincter of Oddi dysfunction; pancreatic sphincter of Oddi manometry identifies which high-risk patients may benefit from pancreatic stenting.

Interleukin-1beta+3953 allele 2: association with disease status in adult periodontitis.

Adult periodontitis is a complex multifactorial disease whose etiology is not well defined. The pro-inflammatory and bone resorptive properties of interleukin-1 beta (IL-1beta) strongly suggest a role for this cytokine in the pathogenesis of periodontal disease. In the study reported here, the frequency of IL-1beta genotypes including allele 2 of the IL-1beta+3953 restriction fragment length bi-allelic polymorphism was significantly increased in patients with advanced adult periodontitis compared to those with early and moderate disease. Furthermore, allele 2 was associated with increased production of IL-1beta by activated peripheral blood polymorphonuclear cells of patients with advanced disease, although this increase failed to reach statistical significance. Finally, the data obtained revealed significant linkage disequilibrium between allele 2 of the IL-1beta+3953 polymorphism and allele 2 of the bi-allelic IL-1alpha-889 polymorphism in both patients and orally healthy controls. These findings provide new insight into the possible role of IL-1alpha and beta gene polymorphisms in the susceptibility to adult periodontitis.

The body mass index-mortality relationship in white and African American women.

OBJECTIVE: To examine the association of body mass index to all-cause and cardiovascular disease (CVD) mortality in white and African American women. RESEARCH METHODS AND PROCEDURES: Women who were members of the American Cancer Society Prevention Study I were examined in 1959 to 1960 and then followed 12 years for vital status. Data for this analysis were from 8,142 black and 100,000 white women. Body mass index (BMI) was calculated from reported height and weight. Associations were examined using Cox proportional hazards modeling with some analyses stratified by smoking (current or never) and educational status (less than complete high school or high school graduate). RESULTS: There was a significant interaction between ethnicity and BMI for both all-cause (p<0.05) and CVD mortality (p<0.001). BMI (as a continuous variable) was associated with all-cause mortality in white women in all four groups defined by smoking and education. In black women with less than a high school education, there were no significant associations between BMI mortality. For high school-educated black women, there was a significant association between BMI and all-cause mortality. Among never smoking women with at least a high school education, models using the lowest BMI as the reference indicated a 40% higher risk of all-cause mortality at a BMI of 35.9 in black women vs. 27.3 in white women. DISCUSSION: The impact of BMI on mortality was modified by educational level in black women; however, BMI was a less potent risk factor in black women than in white women in the same category of educational status.

The effectiveness of a magnetized water oral irrigator (Hydro Floss) on plaque, calculus and gingival health.

The purpose of this study was to evaluate the effects of a magnetized water oral irrigator on plaque, calculus and gingival health. 29 patients completed this double-blind crossover study. Each patient was brought to baseline via an oral prophylaxis with a plaque index < or = 1 and a gingival index < or = 1. Subjects used the irrigator for a period of 3 months with the magnet and 3 months without the magnet. After each 3 month interval, data were collected using the plaque index, gingival index, and accretions index. The repeated measures analysis on plaque, gingival and calculus indices yielded a statistically-significant period effect for PlI (p=0.0343), GI (p=0.0091), and approached significance for calculus (p=0.0593). This meant that the effect of irrigation resulted in a decrease of all indices over time. Therefore, the treatment effect on each index was evaluated using only the measurements obtained at the end of the first period (i.e., assuming a parallel design). Irrigation with magnetized water resulted in 64% less calculus compared to the control group. The reduction was statistically significant (p< or =0.02). The reduction by 27% in gingival index was not statistically significant. The reduction in plaque was minimal (2.2%). A strong positive correlation between the plaque index and the Watt accretion index was observed. The magnetized water oral irrigator could be a useful adjunct in the prevention of calculus accumulation in periodontal patients, but appears to have minimal effect on plaque reduction. The results indicated a clinical improvement in the gingival index, but this was not a statistically significant finding.

Symptoms of depression in residents: a South Carolina Family Practice Research Consortium study.

PURPOSE: To determine correlations between residents' scores on psychological inventories and their demographics and personal histories. METHOD: The authors followed all family practice residents in South Carolina from July 1993 to January 1996. They invited the residents to take a battery of psychological inventories every July and January during the study. The inventories included the Beck Depression Inventory (BDI) and the Profile of Mood States (POMS). The participating residents also filled out personal and family history questionnaires at each test administration. RESULTS: Of the 350 residents in family practice training during the study, 284 took the BDI at least once and 280 took the POMS at least once. Cross-sectional data indicated that 3% of those taking the BDI and 7% of those taking the POMS showed significant depressive or mood-disturbance symptoms, levels similar to those found in previous studies. Analyses found correlations between residents' descriptions of poor physical or emotional health, unhappy childhoods, current high stress in training, or doubt about specialty choice and high scores on the two inventories. No such correlation was found between high inventory scores and age, sex, race, duration of training, season of the year, exercise pattern, recent life events, income, or level of indebtedness. CONCLUSIONS: Although the results of this study may not be generalizable, medical educators and those who counsel physicians during graduate training may want to take note of the correlations between certain answers to questions about personal history and higher levels of depression and mood disturbance as measured by psychological inventories.

Geographic variation in the prevalence of Raynaud's phenomenon: a 5 region comparison.

OBJECTIVE: To determine the population based prevalence of Raynaud's phenomenon (RP) in 5 geographic regions: one in South Carolina, USA, and 4 in France; to explore the relationship of RP to the climate; to investigate possible risk factors; and to describe the characteristics of RP+ subjects in the general population. METHODS: The study consisted of 2 phases: a telephone survey of a randomly drawn sample of households, with 10,149 completed interviews; these were followed by a face to face interview and clinical evaluation (n = 1,534), including diagnosis of RP. The same methodology was used in all 5 regions: for recruitment of subjects, criteria for RP, method of RP diagnosis, and for gathering additional information. RESULTS: The prevalence of RP was found to be related to the climate. The relationship between RP and climate was complicated, however, by the fact that many subjects had moved between climate zones. The relationship of RP to a cold climate became more evident after taking the migration patterns into account: the majority of RP+ subjects in the 2 coldest regions had lived all their lives in the same or a similar climate zone; the majority of RP+ subjects in the 2 warmest regions had previously lived in a colder climate. Other factors associated with RP were family history of RP, cardiovascular diseases, older age, a low body mass index, use of vibrating tools, and outings of a day or more. The classical triphasic RP was rarely encountered in the general population and the most frequently observed signs and symptoms during an RP attack were blanching accompanied by numbness. CONCLUSION: In addition to being a triggering factor for RP attacks, cold also appears to be an etiologic factor in the pathogenesis of RP. A subclinical cold injury, more likely to occur in colder climates, may be responsible for the "local fault" that has been implicated in the pathogenesis of RP and, in association with other risk factors, may predispose subjects to develop clinical RP.