Onset and Evolution of Southern Annular Mode-Like Changes at Centennial Timescale.

The Southern Westerly Winds (SWW) are the surface expression of geostrophic winds that encircle the southern mid-latitudes. In conjunction with the Southern Ocean, they establish a coupled system that not only controls climate in the southern third of the world, but is also closely connected to the position of the Intertropical Convergence Zone and CO2 degassing from the deep ocean. Paradoxically, little is known about their behavior since the last ice age and relationships with mid-latitude glacier history and tropical climate variability. Here we present a lake sediment record from Chilean Patagonia (51°S) that reveals fluctuations of the low-level SWW at mid-latitudes, including strong westerlies during the Antarctic Cold Reversal, anomalously low intensity during the early Holocene, which was unfavorable for glacier growth, and strong SWW since ~7.5 ka. We detect nine positive Southern Annular Mode-like events at centennial timescale since ~5.8 ka that alternate with cold/wet intervals favorable for glacier expansions (Neoglaciations) in southern Patagonia. The correspondence of key features of mid-latitude atmospheric circulation with shifts in tropical climate since ~10 ka suggests that coherent climatic shifts in these regions have driven climate change in vast sectors of the Southern Hemisphere at centennial and millennial timescales.

Inspiratory muscle training during pulmonary rehabilitation in chronic obstructive pulmonary disease: A randomized trial.

Although recommended by international guidelines, the benefit of inspiratory muscle training (IMT) in addition to rehabilitation remains uncertain. The objective was to demonstrate the effectiveness of IMT on dyspnea using Borg scale and multidimensional dyspnea profile questionnaire at the end of a 6-minute walk test (6MWT) in patients with chronic obstructive pulmonary disease (COPD) with preserved average maximum inspiratory pressure (PImax) of 85 cm H2O (95% of predicted (pred.) value) and admitted for a rehabilitation program in a dedicated center. In a randomized trial, comparing IMT versus no IMT in 32 COPD patients without inspiratory muscle weakness (PImax >60 cm H2O) who were admitted for pulmonary rehabilitation (PR) for 3 weeks, we evaluated the effect of IMT on dyspnea, using both Borg scale and multidimensional dyspnea profile (MDP) at the end of the 6MWT, and on functional parameters included inspiratory muscle function (PImax) and 6MWT. All testings were performed at the start and the end of PR. In unadjusted analysis, IMT was not found to be associated with an improvement of either dyspnea or PImax. After adjustment on confounders (initial Borg score) and variables of interaction (forced expiratory volume in 1 second (FEV1)), we found a trend toward an improvement of "dyspnea sensory intensity", items from MDP and a significant improvement on the variation in the 2 items of MDP ("tight or constricted" and "breathing a lot"). In the subgroup of patients with FEV1 < 50% pred., 5 items of MDP were significantly improved, whereas no benefit was observed in patients with FEV1 > 50% pred. IMT did not significantly improve dyspnea or functional parameter in COPD patients with PImax > 60 cm H2O. However, in the subgroup of patients with FEV1 < 50% pred., MDP was significantly improved.

Neuro-QOL: brief measures of health-related quality of life for clinical research in neurology.

OBJECTIVE: To address the need for brief, reliable, valid, and standardized quality of life (QOL) assessment applicable across neurologic conditions. METHODS: Drawing from larger calibrated item banks, we developed short measures (8-9 items each) of 13 different QOL domains across physical, mental, and social health and evaluated their validity and reliability. Three samples were utilized during short form development: general population (Internet-based, n = 2,113); clinical panel (Internet-based, n = 553); and clinical outpatient (clinic-based, n = 581). All short forms are expressed as T scores with a mean of 50 and SD of 10. RESULTS: Internal consistency (Cronbach α) of the 13 short forms ranged from 0.85 to 0.97. Correlations between short form and full-length item bank scores ranged from 0.88 to 0.99 (0.82-0.96 after removing common items from banks). Online respondents were asked whether they had any of 19 different chronic health conditions, and whether or not those reported conditions interfered with ability to function normally. All short forms, across physical, mental, and social health, were able to separate people who reported no health condition from those who reported 1-2 or 3 or more. In addition, scores on all 13 domains were worse for people who acknowledged being limited by the health conditions they reported, compared to those who reported conditions but were not limited by them. CONCLUSION: These 13 brief measures of self-reported QOL are reliable and show preliminary evidence of concurrent validity inasmuch as they differentiate people based upon number of reported health conditions and whether those reported conditions impede normal function.

Vascular risk factors and cognitive impairment in a stroke-free cohort.

OBJECTIVE: To examine vascular risk factors, as measured by the Framingham Stroke Risk Profile (FSRP), to predict incident cognitive impairment in a large, national sample of black and white adults age 45 years and older. METHODS: Participants included subjects without stroke at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with at least 2 cognitive function assessments during the follow-up (n = 23,752). Incident cognitive impairment was defined as decline from a baseline score of 5 or 6 (of possible 6 points) to the most recent follow-up score of 4 or less on the Six-item Screener (SIS). Subjects with suspected stroke during follow-up were censored. RESULTS: During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment. Baseline FSRP score was associated with incident cognitive impairment. An adjusted model revealed that male sex (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.43-1.77), black race (OR = 2.09, 95% CI 1.88-2.35), less education (less than high school graduate vs college graduate, OR = 2.21, 95% CI 1.88-2.60), older age (10-year increments, OR = 2.11, per 10-year increase in age, 95% CI 2.05-2.18), and presence of left ventricular hypertrophy (LVH, OR = 1.29, 95% CI 1.06-1.58) were related to development of cognitive impairment. When LVH was excluded from the model, elevated systolic blood pressure was related to incident cognitive impairment. CONCLUSIONS: Total FSRP score, elevated blood pressure, and LVH predict development of clinically significant cognitive dysfunction. Prevention and treatment of high blood pressure may be effective in preserving cognitive health.

[The effects of a pulmonary rehabilitation program in relation to the severity of COPD]. / Effets d'un programme de réhabilitation respiratoire selon la sévérité de la BPCO.

INTRODUCTION: The aim of this study is to assess the effects of in-patient pulmonary rehabilitation in relation to the stages of COPD according to GOLD and the BODE index. METHOD: A prospective cohort study over 4 weeks. The 6-minute walk test, the relationship dyspnoea (EVA)/walking distance, dyspnoea (MRC scale), the Saint-George's respiratory questionnaire and the BODE index were estimated at the beginning and end of a pulmonary rehabilitation programme. RESULTS: Fifty patients with COPD were included, distributed according to GOLD (II: 30%; III: 32%; IV: 38%) and BODE (quartile 1: 22%; quartile 2: 36%; quartile 3: 26%; quartile 4: 16%). All the patients benefited from the programme. For the GOLD classification, there was no significant difference between stages. For the BODE classification, a significant difference existed between quartiles concerning the evolution of dyspnoea (P=0,025), the relationship dyspnoea/walking distance (P<0,001) and BODE index (P<0,001), to the advantage of patients in quartiles 3 and 4. CONCLUSION: All patients benefit from rehabilitation in hospital; the most severe benefit the most. The BODE index seems to predict those who make the greatest improvement.

Association of higher diastolic blood pressure levels with cognitive impairment.

BACKGROUND: We evaluated the cross-sectional relationship of blood pressure (BP) components with cognitive impairment after adjusting for potential confounders. METHODS: Reasons for Geographic and Racial Differences in Stroke (REGARDS) is a national, longitudinal population cohort evaluating stroke risk in 30,228 black and white men and women >or=45 years old. During the in-home visit, BP measurements were taken as the average of 2 measurements using a standard aneroid sphygmomanometer. Excluding participants with prior stroke or TIA, the present analysis included 19,836 participants (enrolled from December 2003 to March 2007) with complete baseline physical and cognitive evaluations. Incremental logistic models examined baseline relationships between BP components (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) and impaired cognitive status (score of

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.

The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, II: characteristics of patients enrolled and not enrolled. COMS Report No. 17.

OBJECTIVES: To describe characteristics of patients evaluated for the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy for choroidal melanoma by enrollment status, and to compare characteristics of patients enrolled with those of patients with tumors of eligible size who did not enroll in order to assess the extent to which findings from the clinical trial can be generalized to future patients. METHODS: For all patients diagnosed with choroidal melanoma and evaluated for the clinical trial at COMS centers from November 1986 through July 31, 1998, selected data were transmitted to the COMS Coordinating Center, Baltimore, Md, where they were integrated and analyzed. Data included ophthalmic and medical history, examination findings, and visual acuity measurements recorded prior to enrollment; standardized A- and B-scan echographic examination findings; and wide-angle fundus photographs and fluorescein angiograms. RESULTS: Of 8712 patients with choroidal melanoma, 5046 had tumors of eligible size; of these, 2882 (57%) were eligible for enrollment, and 1317 (46% of eligible patients, 26% of patients with tumors of eligible size) enrolled. Most differences between eligible and ineligible patients corresponded to eligibility and exclusion criteria. However, ineligible patients were older and had thicker tumors than eligible patients. Eligible patients who enrolled were slightly older and had larger tumors than those who did not enroll. Nearly half (48%) of enrolled patients had choroidal melanoma with the apex located temporal to the fovea, compared with 40% of eligible patients not enrolled and 29% of ineligible patients. CONCLUSIONS: This trial was designed to yield internally valid treatment comparisons through random assignment to treatment at time of enrollment. Information from this and other studies document that enrolled patients were similar to other patients with choroidal melanoma who were treated with 125I brachytherapy. These findings support the external validity of the trial and applicability of treatment findings to all patients who meet the criteria used to judge eligibility for the trial.

The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18.

OBJECTIVES: To report initial mortality findings from the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy vs enucleation for treatment of choroidal melanoma. METHODS: Patients were evaluated for eligibility at 43 participating clinical centers in the United States and Canada. Eligible consenting patients were assigned randomly at the time of enrollment to enucleation or 125I brachytherapy. Patients were examined at specified intervals after enrollment for data collection purposes. Findings presented herein are based on data received by September 30, 2000. Data for each patient were analyzed with the treatment group to which the patient was assigned randomly at the time of enrollment. RESULTS: During the 11(1/2)-year accrual period, 1317 patients enrolled; 660 were assigned randomly to enucleation and 657 to 125I brachytherapy. Only 2 patients in the enucleation arm were found to have been misdiagnosed when histopathology was reviewed centrally. All but 17 patients (1.3%) received the assigned treatment. Adherence to the brachytherapy protocol was excellent, with 91% of patients treated per protocol. Based on time since enrollment, 1072 patients (81%) had been followed for mortality for 5 years and 416 (32%) for 10 years. A total of 364 patients had died: 188 (28%) of 660 patients in the enucleation arm and 176 (27%) of 657 patients in the brachytherapy arm. The unadjusted estimated 5-year survival rates were 81% and 82%, respectively; there was no clinically or statistically significant difference in survival rates overall (P =.48, log-rank test). The adjusted estimated risk ratio for 125I brachytherapy vs enucleation was 0.99 (95% confidence interval [CI], 0.80-1.22). Five-year rates of death with histopathologically confirmed melanoma metastasis were 11% and 9% following enucleation and brachytherapy, respectively; after adjustment, the estimated risk ratio was 0.91 (95% CI, 0.66-1.24). CONCLUSIONS: Mortality rates following 125I brachytherapy did not differ from mortality rates following enucleation for up to 12 years after treatment of patients with choroidal melanoma who enrolled in this COMS trial. The power of the study was sufficient to indicate that neither treatment is likely to increase or decrease mortality rates by as much as 25% relative to the other.

Cause-specific mortality coding. methods in the collaborative ocular melanoma study coms report no. 14.

Ascertainment of cause of death is often sought in clinical trials in which mortality is an outcome of interest. Standardized methods of coding all-cause and disease-specific mortality were developed and evaluated in the Collaborative Ocular Melanoma Study randomized trial of pre-enucleation radiation of large choroidal melanoma. All available clinical and pathologic materials documenting events prior to each reported death were reviewed systematically by a Mortality Coding Committee (MCC) to determine whether melanoma metastasis or local recurrence was present at the time of death. A level of certainty was assigned based on availability of local or central review of pathology materials. The outcome of the mortality coding protocol was evaluated both by assessing agreement between the judgment of the MCC and the presumed cause of death reported by the clinical center and, for a subset of patients, by assessing agreement between the MCC classification and the cause of death reported on the death certificate. As of July 31, 1997 (the cutoff date for the initial mortality report), 435 (95%) of 457 deceased patient files had been reviewed. The MCC classified 269 patients (62%) as dead with melanoma metastasis, 22 (5%) as dead with another malignant tumor, and 92 (21%) as dead with a malignant tumor of uncertain origin. Thirty-eight patients (9%) died with no evidence of malignancy; in 14 cases (3%), the presence or absence of malignancy could not be established due to lack of clinical information. Fair agreement (kappa = 0.34) was observed between the determinations of the MCC based on detailed review of materials and the cause of death reported on the death certificate, but death certificates alone underestimated the proportion of deaths due to metastatic choroidal melanoma. Detailed mortality coding identified difficulties associated with accurate reporting of cause-specific mortality in patients with choroidal melanoma.

Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16.

OBJECTIVE: To report visual acuity during the first three years after iodine 125 (I(125)) brachytherapy for medium-sized choroidal melanoma and to identify important baseline and treatment factors associated with posttreatment visual acuity in a group of patients who were treated and observed prospectively as part of a large, randomized clinical trial. DESIGN: Observational case series within a randomized, multicenter study. PARTICIPANTS: Patients enrolled in the Collaborative Ocular Melanoma Study randomized trial of I(125) brachytherapy versus enucleation had choroidal melanoma of at least 2.5 mm but no more than 10.0 mm in apical height, and no more than 16.0 mm in largest basal dimension. One thousand three hundred seventeen patients enrolled from February 1987 through July 1998; 657 patients were assigned to I(125) brachytherapy. Visual acuity data for 623 patients who received I(125) brachytherapy as randomly assigned and who have been observed for at least 1 year were analyzed for this report. METHODS: Under study protocol, an ophthalmic evaluation, including best-corrected visual acuity measurement of each eye, was performed at baseline, every 6 months thereafter for 5 years, and once yearly thereafter. Two poor vision outcomes, visual acuity of 20/200 or worse that was confirmed at the next follow-up examination and loss of six lines or more of visual acuity from baseline that was confirmed at the next follow-up examination, were analyzed to identify baseline and treatment characteristics that were associated with posttreatment visual acuity. RESULTS: At baseline, median visual acuity in the eye with choroidal melanoma was 20/32, with 70% of eyes having 20/40 or better and 10% of eyes having 20/200 or worse visual acuity. Three years after I(125) brachytherapy, median visual acuity was 20/125, with 34% having 20/40 or better and 45% having 20/200 or worse visual acuity, including eyes that were enucleated within 3 years of treatment. Life-table estimates of percentages of patients who lost six or more lines of visual acuity from baseline, a quadrupling of the minimum angle of resolution, with this finding confirmed at the next 6-month follow-up examination, were 18% by 1 year, 34% by 2 years, and 49% by 3 years after treatment. Life-table estimates of percentages of patients with baseline visual acuity better than 20/200 whose visual acuity decreased to 20/200 or worse, confirmed at the next follow-up examination, were 17% by 1 year, 33% by 2 years, and 43% by 3 years after treatment. As soon as a poor vision outcome was observed, improvement of visual acuity to a level that no longer met the definition for a poor vision outcome was rare. Greater baseline tumor apical height and shorter distance between the tumor and the foveal avascular zone (FAZ) were the factors most strongly associated with loss of six or more lines of visual acuity after treatment. These two factors and baseline visual acuity also were strongly associated with visual acuity 20/200 or worse after treatment. Patient history of diabetes, presence of tumor-associated retinal detachment, and tumors that were not dome shaped also were associated with greater risk for both of the poor vision outcomes. CONCLUSIONS: Forty-three percent to 49% of treated eyes had substantial impairment in visual acuity by 3 years after I(125) brachytherapy, defined as a loss of six or more lines of visual acuity from the pretreatment level (49% of eyes) or visual acuity of 20/200 or worse (43% of eyes) that was confirmed at the next 6-month examination. Patients with a history of diabetes and patients whose eyes had thicker tumors, tumors close to or beneath the FAZ, tumor-associated retinal detachment, or tumors that were not dome shaped were those most likely to have a poor visual acuity outcome within 3 years after I(125) brachytherapy.

Quality of life in patients with choroidal melanoma: a pilot study.

PURPOSE: To assess the internal consistency of a short, widely-used health-related quality of life instrument in patients with choroidal melanoma, its appropriateness for use in a large clinical trial in patients with that disease, and the feasibility of various methods of instrument administration. METHODS: The SF-36 was administered to 31 choroidal melanoma patients identified from two ocular oncology practices. Fifteen patients were interviewed by telephone, 4 were interviewed in person at the clinic, and 12 patients completed the instrument themselves while at the clinic. RESULTS: Twenty-three patients had already been treated for choroidal melanoma; 20 patients were treated with some form of radiation. The remaining 8 patients had not yet been treated. Metastasis had not been diagnosed in any of the patients. Patient age ranged from 37 to 85 years with a median of 59 years; 55% of the patients were female. The in-person and telephone interviews performed better than self-administered interviews in terms of missing items due to non-response (0% vs. 3.2%). The overall SF-36 health profile for the choroidal melanoma patients was similar in shape to that expected for a general U.S. population sample with the same age and gender distribution, although the choroidal melanoma patients averaged 4 to 11 points higher, indicating better health-related quality of life, for all scales except the role functioning-emotional scale. CONCLUSIONS: The results supported the internal consistency of the SF-36 in this population. Interviewer administration of the SF-36 either in-person or by telephone was acceptable to the patients and provided more complete data.

Ethnic variation in the incidence of stomach cancer in Illinois, 1986-1988.

Wide ethnic and geographic variation in stomach cancer incidence has been reported in Eastern and Western countries. Stomach cancer is reported to be the most common malignant neoplasm in Asia, specifically, China, Japan, and Korea. In contrast, stomach cancer incidence in the United States among Caucasians is low and among blacks, moderate to low. Only one other study has directly compared the rates of stomach cancer in the three ethnic groups (i.e., white, African American, and immigrant Korean) living in the same region. The authors extend their investigation by comparing the incidence rate of stomach cancer among the same three ethnic groups in the state of illinois from 1986 to 1988. In this study, the incidence of stomach cancer was observed to be lowest in whites, intermediate in African Americans, and highest in immigrant Koreans. The overall 3-year cumulative incidence rate from 1986 to 1988 was 62.6/100,000 (95% confidence interval (CI) 38.6-86.7), 28.2/100,000 (95% CI 25.7-31), and 22.5/100,000 (95% CI 21.5-23.5) for immigrant Koreans, African Americans, and whites, respectively. The 3-year age-adjusted cumulative incidence rate for immigrant Koreans (172/100,000) was approximately four-and eightfold higher than for African Americans (41/100,000) and whites (21/100,000). The incidence of stomach cancer increased as a function of age in both sexes. Although a higher rate was observed in males than in females, these rates were four-and eightfold higher in African Americans and immigrant Koreans, when compared with their white counterparts in both sexes. Despite a substantial reduction of stomach cancer incidence in the United States and other Western countries, it remains the most frequent malignancy in native and immigrant Koreans. The high rate of stomach cancer in immigrant Koreans compared with African Americans and white populations residing in Illinois indicates either a drastically disproportionate undercount of immigrant Koreans in the 1990 census or a profound genetic-environmental interaction.

Ascertainment corrected rates: applications of capture-recapture methods.

Accurate rates, though fundamental to epidemiology, are often very difficult to obtain. Incidence, prevalence, and mortality rates have traditionally been established through either passive reporting surveillance systems, through active surveillance systems, or by a combination of the two methods. Typically, when researchers employ these approaches they do not formally evaluate or correct for the degree of underascertainment. Undercount of cases is a potent determinant of rates which we cannot continue to ignore. We believe all rates should be adjusted for underascertainment in order to achieve a truer picture of the risk and risk factors of disease. Here, we present a procedure to ascertainment correct rates based upon well established capture-recapture methods.

Insulin-dependent diabetes mellitus, physical activity, and death.

The beneficial effect of physical activity in the general population is well known, but, to the authors' knowledge, has not been reported for persons with insulin-dependent diabetes mellitus. In a cohort of 548 diabetes patients followed as part of the Pittsburgh Insulin-dependent Diabetes Mellitus Morbidity and Mortality Study, physical activity was ascertained by survey in 1981, and mortality was ascertained through January 1, 1988. Cases were also compared with non-diabetic sibling controls. Activity level among cases varied inversely with the occurrence of diabetic complications. Overall activity level was inversely related to mortality risk. Sedentary males (< 1,000 kcal/week) were three times more likely to die than active males (> 2,000 kcal/week). A similar, but statistically nonsignificant, relation was seen in females. Cox proportional hazards analysis controlling for potential confounders (age, body mass index, insulin dose, reported diabetes complications, cigarette smoking, and current alcohol drinking) similarly revealed that activity level was inversely associated with mortality risk. Comparison of cases with non-diabetic sibling controls identified similar activity levels for the two groups. The results suggest that activity is not detrimental with regard to mortality, and may in fact provide a beneficial effect in terms of longevity in diabetes patients.

Insulin-dependent diabetes mellitus mortality. The risk of cigarette smoking.

The relation between cigarette smoking and mortality was examined prospectively in a population of adult insulin-dependent diabetes mellitus (IDDM) patients. In 1981, information on smoking history and other health and lifestyle factors was obtained by questionnaire from 93% of the 723 patients included in the Children's Hospital of Pittsburgh IDDM registry who were diagnosed between 1950 and 1964. Vital status as of January 1, 1988 was ascertained for 98% of the 548 patients who participated in the baseline survey and were alive as of January 1, 1982. Fifty-four cases died during the 6-year follow-up (32 male, 22 female). Proportional hazards analysis revealed that heavy smoking was a significant independent predictor of all-cause mortality among females but not males. The excess mortality in female diabetics was explained primarily by a marked excess risk of coronary heart disease mortality in smokers. These data strongly suggest that cigarette smoking, especially among diabetic females, should be avoided in order to improve longevity.