Raymond G. Hoffmann

Measures of postural steadiness: differences between healthy young and elderly adults

Measures of postural steadiness are used to characterize the dynamics of the postural control system associated with maintaining balance during quiet standing. The objective of this study was to evaluate the relative sensitivity of center-of-pressure (COP)-based measures to changes in postural steadiness related to age. A variety of time and frequency domain measures of postural steadiness were compared between a group of twenty healthy young adults (21-35 years) and a group of twenty healthy elderly adults (66-70 years) under both eyes-open and eyes-closed conditions. The measures that identified differences between the eyes-open and eyes-closed conditions in the young adult group were different than those that identified differences between the eye conditions in the elderly adult group. Mean velocity of the COP was the only measure that identified age-related changes in both eye conditions, and differences between eye conditions in both age groups. The results of this study will be useful to researchers and clinicians using COP-based measures to evaluate postural steadiness.

Bone Marrow Transplantation for Chronic Myelogenous Leukemia in Chronic Phase: Increased Risk for Relapse Associated with T-Cell Depletion

Data on 405 patients with chronic myelogenous leukemia who received bone marrow transplants in chronic phase were analyzed for factors predictive of outcome. The 4-year actuarial probability of relapse was 19% (95% confidence interval [CI], 12% to 28%) and of survival, 55%. In multivariate analyses the probability of relapse was higher for recipients of T-cell-depleted bone marrow compared with recipients of non-T-cell-depleted bone marrow (relative risk, 5.4; P less than 0.0001) and for patients who did not develop chronic graft-versus-host disease (95% CI, 50% to 60%) with patients who did (relative risk, 3.1; P less than 0.01). The probability of survival was lower for patients who developed moderate to severe acute graft-versus-host disease than for patients with no or mild acute graft-versus-host disease (relative risk, 3.7; P less than 0.0001), and in patients aged 20 or older than in younger patients (relative risk, 2.6; P less than 0.0002). Duration of disease before transplant was not associated with outcome. Bone marrow transplantation done in the chronic phase of chronic myelogenous leukemia offers some patients prolonged leukemia-free survival. The T-cell-depleted grafts are associated with an increased probability of relapse.

EPIDEMIOLOGIC AND CLINICAL CHARACTERISTICS OF CHILDREN WITH NEWLY DIAGNOSED INFLAMMATORY BOWEL DISEASE IN WISCONSIN: A STATEWIDE POPULATION-BASED STUDY

OBJECTIVE To define epidemiologic and clinical characteristics of newly diagnosed pediatric inflammatory bowel disease (IBD) in a large population-based model. STUDY DESIGN All pediatric gastroenterologists providing care for Wisconsin children voluntarily identified all new cases of IBD during a 2-year period. Demographic and clinical data were sent to a central registry prospectively for analysis. RESULTS The incidence of IBD in Wisconsin children was 7.05 per 100,000, whereas the incidence for Crohns disease was 4.56, more than twice the rate of ulcerative colitis (2.14). An equal IBD incidence occurred among all ethnic groups, and children from sparsely and densely populated counties were equally affected. The majority (89%) of new IBD diagnoses were nonfamilial. CONCLUSIONS This study provides novel, prospective, and comprehensive information on pediatric IBD incidence within the United States. The surprisingly high incidence of pediatric IBD, the predominance of Crohns disease over ulcerative colitis, the low frequency of patients with a family history, the equal distribution of IBD among all racial and ethnic groups, and the lack of a modulatory effect of urbanization on IBD incidence collectively suggest that the clinical spectrum of IBD is still evolving and point to environmental factors contributing to the pathogenesis.

Adiposity, Fat Distribution, and Cardiovascular Risk

STUDY OBJECTIVE To determine the relative importance of adiposity and fat distribution to cardiovascular risk profile. DESIGN A cross-sectional study. SETTING Clinical research center funded by the National Institutes of Health. PATIENTS Convenience sample of 33 healthy premenopausal women with a wide range of body weight who did not have diabetes mellitus, hirsutism and virilism, gynecologic disorder, cardiac disease, or hypertension. Women participating in exercise or dietary programs or taking medication were excluded. All subjects completed the study. INTERVENTIONS Total body fat mass was determined by hydrostatic weighting, and fat distribution was assessed by subscapular skinfold thickness, subscapular-to-triceps skinfold ratio, the waist-to-hip ratio, and computed tomography. Cardiovascular risk was assessed by the serum insulin response during oral glucose stimulation; levels of triglycerides and total cholesterol; high-density lipoprotein cholesterol to total cholesterol concentrations; and systolic and diastolic blood pressures. MEASUREMENTS AND MAIN RESULTS The anthropometric parameters chosen were significantly associated with the cardiovascular risk profile (P less than 0.001). Visceral fat distribution assessed by computed tomography accounted for a significantly greater degree of variance in the cardiovascular risk factors than the total body fat mass (P less than 0.05). The cumulative insulin response was the primary metabolic variable relating the anthropometric indices to cardiovascular risk. CONCLUSIONS Intra-abdominal fat deposition constitutes a greater cardiovascular risk than obesity alone. Hyperinsulinemia may constitute an important component of the increased cardiovascular risk of abdominal obesity.

Risk factors for acute graft‐versus‐host disease

Summary. Acute graft‐versus‐host disease (GvHD) is an important complication of bone marrow transplantation in humans. Risk factors are imprecisely defined and controversial. We analysed data from 2036 recipients of HLA‐identical sibling transplants for leukaemia or aplastic anaemia to identify risk factors for GvHD. Analyses indicate that grading of GvHD can be reproducibly divided into absent or mild versus moderate to severe; 2‐year actuarial probability was 54% (95% confidence interval 52–56%) for absent or mild and 46% (44–48%) for moderate to severe. Factors predictive of development of moderate to severe GvHD include donor/recipient sex‐match (female→male greater than others, relative risk 2.0, P<0.001). This risk was markedly increased if female donors for male recipients were previously pregnant or transfused (relative risk 2.9, P<0.0001). Older patients were at increased risk of GvHD (relative risk 1.6, P<0.001), but the age gradient was modest, even the youngest patients had a substantial risk of GvHD and, if parous or transfused female→male transplants were excluded, age was not a significant risk factor. Cyclosporine or methotrexate were equally effective at preventing GvHD and were superior to no prophylaxis (relative risk 2.3, P<0.01). These data should be useful in estimating the risk of acute GvHD in an individual patient and in designing clinical trials to investigate methods to modify or prevent GvHD.

Multiple Neuronal Networks Mediate Sustained Attention

Sustained attention deficits occur in several neuropsychiatric disorders. However, the underlying neurobiological mechanisms are still incompletely understood. To that end, functional MRI was used to investigate the neural substrates of sustained attention (vigilance) using the rapid visual information processing (RVIP) task in 25 healthy volunteers. In order to better understand the neural networks underlying attentional abilities, brain regions where task-induced activation correlated with task performance were identified. Performance of the RVIP task activated a network of frontal, parietal, occipital, thalamic, and cerebellar regions. Deactivation during task performance was seen in the anterior and posterior cingulate, insula, and the left temporal and parahippocampal gyrus. Good task performance, as defined by better detection of target stimuli, was correlated with enhanced activation in predominantly right fronto-parietal regions and with decreased activation in predominantly left temporo-limbic and cingulate areas. Factor analysis revealed that these performance-correlated regions were grouped into two separate networks comprised of positively activated and negatively activated intercorrelated regions. Poor performers failed to significantly activate or deactivate these networks, whereas good performers either activated the positive or deactivated the negative network, or did both. The fact that both increased activation of task-specific areas and increased deactivation of task-irrelevant areas mediate cognitive functions underlying good RVIP task performance suggests two independent circuits, presumably reflecting different cognitive strategies, can be recruited to perform this vigilance task.

Minimal hepatic encephalopathy is associated with motor vehicle crashes: the reality beyond the driving test.

Patients with minimal hepatic encephalopathy (MHE) have impaired driving skills, but association of MHE with motor vehicle crashes is unclear. Standard psychometric tests (SPT) or inhibitory control test (ICT) can be used to diagnose MHE. The aim was to determine the association of MHE with crashes and traffic violations over the preceding year and on 1‐year follow‐up. Patients with cirrhosis were diagnosed with MHE by ICT (MHEICT) and SPT (MHESPT). Self and department‐of‐transportation (DOT)‐reports were used to determine crashes and violations over the preceding year. Agreement between self and DOT‐reports was analyzed. Patients then underwent 1‐year follow‐up for crash/violation occurrence. Crashes in those with/without MHEICT and MHESPT were compared. 167 patients with cirrhosis had DOT‐reports, of which 120 also had self‐reports. A significantly higher proportion of MHEICT patients with cirrhosis experienced crashes in the preceding year compared to those without MHE by self‐report (17% vs 0.0%, P = 0.0004) and DOT‐reports (17% vs 3%, P = 0.004, relative risk: 5.77). SPT did not differentiate between those with/without crashes. A significantly higher proportion of patients with crashes had MHEICT compared to MHESPT, both self‐reported (100% vs 50%, P = 0.03) and DOT‐reported (89% vs 44%, P = 0.01). There was excellent agreement between self and DOT‐reports for crashes and violations (Kappa 0.90 and 0.80). 109 patients were followed prospectively. MHEICT patients had a significantly higher future crashes/violations compared to those without (22% vs 7%, P = 0.03) but MHESPT did not. MHEICT (Odds ratio: 4.51) and prior year crash/violation (Odds ratio: 2.96) were significantly associated with future crash/violation occurrence. Conclusion: Patients with cirrhosis and MHEICT have a significantly higher crash rate over the preceding year and on prospective follow‐up compared to patients without MHE. ICT, but not SPT performance is significantly associated with prior and future crashes and violations. There was an excellent agreement between self‐ and DOT‐reports. (HEPATOLOGY 2009.)

Protease inhibitor combination therapies and perceptions of gay men regarding AIDS severity and the need to maintain safer sex.

Background:Advances in the treatment of HIV disease with protease inhibitor combination therapies have been widely documented in the media. Objectives:To investigate perceptions concerning the severity of HIV/AIDS and the need to maintain safer sex practices in the light of recent HIV treatment advances. Methods:A survey eliciting demographic characteristics, HIV serostatus and treatment information, and HIV/AIDS severity and safer sex perceptions was administered to a community sample of 379 homo-/bisexual men who reported awareness of combination therapy regimens. Results:Ten per cent of all respondents agreed or strongly agreed with the statement that ‘AIDS is now very nearly cured’ and 13% felt that the threat of AIDS is less serious than in the past. HIV-positive men were more likely to perceive AIDS as a less serious threat or as very nearly cured. Overall, 8% of men in the sample indicated that they practice safer sex less often since new AIDS treatments came along; 18% of HIV-positive men on combination therapy regimens said they practice safer sex less frequently since treatments have advanced. Regardless of serostatus, nearly 20% of men indicated they would stop practicing safer sex if an AIDS cure was announced. Conclusion:It is essential to integrate behavior change counseling into HIV treatment programs and to temper optimism concerning treatment advances with recognition that the threat of HIV/AIDS remains great.

Probiotic Yogurt for the Treatment of Minimal Hepatic Encephalopathy

OBJECTIVES:Minimal hepatic encephalopathy (MHE), the preclinical stage of overt hepatic encephalopathy (OHE), is a significant condition affecting up to 60% of cirrhotics. All MHE therapies modify gut microflora, but consensus regarding MHE treatment and long-term adherence studies is lacking. The aim was to determine the effect of probiotic supplementation in the form of a food item, probiotic yogurt, on MHE reversal and adherence.METHODS:Nonalcoholic MHE cirrhotics (defined by a standard psychometric battery) were randomized with unblinded allocation to receive probiotic yogurt (with proven culture stability) or no treatment (no Rx) for 60 days in a 2:1 ratio. Quality of life (short form [SF]-36), adherence, venous ammonia, model of end-stage liver disease (MELD) scores, and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6) were also measured. Outcomes were MHE reversal using blinded scoring, OHE development, and adherence.RESULTS:Twenty-five patients (17 yogurt, 8 no Rx; 84% Child class A) were enrolled. A significantly higher percentage of yogurt patients reversed MHE compared to no Rx patients (71% vs 0%, P= 0.003, intention-to-treat). Yogurt patients demonstrated a significant improvement in number connection test-A (NCT-A), block design test (BDT), and digit symbol test (DST) compared to baseline/no Rx group. Twenty-five percent of no Rx versus 0% of yogurt patients developed OHE during the trial. Eighty-eight percent of yogurt patients were adherent. No adverse effects or change in covariates were observed. All patients who completed the yogurt arm were agreeable to continue yogurt for 6 months if needed.CONCLUSIONS:This trial demonstrated a significant rate of MHE reversal and excellent adherence in cirrhotics after probiotic yogurt supplementation with potential for long-term adherence.

Relation between appropriateness of primary therapy for earlystage breast carcinoma and increased use of breast-conserving surgery

BACKGROUND Breast-conserving surgery is a more complex treatment than mastectomy, because a separate incision is needed for axillary lymph-node dissection, and postoperative radiotherapy is necessary. We postulated that adoption of this therapy into clinical practice might have led to discrepancies between the care recommended and that received. METHODS We used records of the US national Surveillance, Epidemiology, and End Results tumour registry to study 144,759 women aged 30 years and older who underwent surgery for early-stage breast cancer between 1983 and 1995. We calculated the proportion undergoing at least the minimum appropriate primary treatment (defined, in accordance with the recommendations of a National Institutes of Health Consensus Conference in 1990, as total mastectomy with axillary node dissection or breast-conserving surgery with axillary node dissection and radiotherapy) during each 3-month period. FINDINGS The proportion of women receiving appropriate primary therapy fell from 88% in 1983-89 to 78% by the end of 1995. This decline was observed in all subgroups of age, race, stage, and population density. Of all women in the cohort, the proportion undergoing an inappropriate form of mastectomy remained stable at about 2.7% throughout the study period. The proportion undergoing an inappropriate form of breast-conserving surgery (omission of radiotherapy, axillary node dissection, or both) increased from 10% in 1989 to 19% at the end of 1995. INTERPRETATION Although most women undergo appropriate care, the appropriateness of care for early-stage breast cancer in the USA declined from 1990 to 1995. Because the proportion of all women who were treated by breast-conserving surgery increased, and because this approach was more likely than was mastectomy to be applied inappropriately, the proportion of all women having inappropriate care increased.