Mathematical modelling in risk/exposure assessment of tobacco related lung cancer

The existence of a dose-related increase of lung cancer riskin cigarette smokers has been indisputably established. Thisfinding, however, is not confirmed at low doses (< 5 cigarettes/day),there still being a lack of epidemiological data. The use ofmathematical models of carcinogenesis to extrapolate from higherdoses allows estimation of the risk for very light smokers.The present study has been designed to compare a set of mathematicalmodels, i.e. one-hit, two-stage, multi-stage, logit, probit,and Weibull, in extrapolating relative risks at low doses fromthe data of nine large cohort studies on cigarette smokers reportedin the IARC Scientific Monograph on tobacco smoking. All modelsevaluated, apart from the one-hit, achieved a good fit, withthe proportion of explained variance ranging between 61% and67%. The relative risk estimates for passive smokers from themost updated epidemiological studies were taken into accountto evaluate, on the basis of these models, the correspondingexposure in terms of ‘cigarette equivalent’ smoked.These values ranged from 0.21 to 0.43 cigarettes/day for thetwo-stage and multistage model, while probit, logit and Weibullmodels, yielded estimates one or even two orders of magnitudelower. The authors emphasize the substantial agreement betweenthe estimates of ‘cigarette equivalent9 based on the applicationof two-stage and multi-stage models to the epidemiological evidenceon the effect of passive smoking and to the data based on thecomparison of tobacco metabolites in active and passive smokers.     

Drinking History Is Related to Persistent Blood Pressure Dysregulation in Postwithdrawal Alcoholics

We have previously demonstrated that alcoholics with transitory (< 72 hr) elevations in blood pressure (BP) during withdrawal continue to show residual cardiovascular dysregulation up to 4 weeks of abstinence. The present study replicates and extends these findings. Alcoholic inpatients were divided into three subgroups ( ns = 14) based on BP during the first 72 hr of withdrawal: transitory hypertensives (tHTs; BP > 160/95 mm Hg), transitory borderline hypertensives (tBHs; 140/90 BP < 160/95), and normotensives (NTs; all BPs < 140/90). All patients had normal resting pressures after 72 hr of withdrawal. At 3–4 weeks postadmission, the alcoholics and 14 nonalcoholic controls (CONTs) were tested at rest and during a 5-min handgrip task. The tHTs showed an exaggerated systolic and diastolic BP response to handgrip compared with NTs and CONTs, with tBHs intermediate ( ps < 0.05). Drinking history showed the tHTs had the highest reported level of alcohol consumption and severity of withdrawal symptoms ( ps < 0.05). Regression analyses indicated that consumption of hard liquor was the variable most predictive of admission BPs; further, parental history of hypertension potentiated this relationship for systolic BP. Age and consumption of nicotine and caffeine were not significant predictors of admission BP. The results suggest a persistent cardiovascular dysregulation in alcoholics showing transient hypertensive withdrawal BPs. These alcoholics may be at increased risk for future alcohol-related cardiovascular disorder.     

Initial lithium augmentation improves the antidepressant effects of standard TCA treatment in non-resistant depressed patients

The hypothesis was tested that an initial lithium-tricyclic antidepressant (TCA) combination has a better antidepressant effect than standard TCA treatment in non-refractory depression at the beginning of an episode. Twenty bipolar melancholic type depressed inpatients under lithium-TCA treatment were compared with 20 patients with the same diagnosis and TCA-placebo treatment for 5 weeks under double-blind conditions. All patients were male. Initial lithium-TCA treatment reduced depressive symptoms significantly more than antidepressant treatment with TCA and placebo after 5 weeks, but not in weeks 1 or 2. It can be concluded that lithium augmentation of TCA treatment should be started even at the beginning of antidepressant TCA treatment to provide a better treatment response in those patients who will profit from long-term lithium prophylaxis, e.g. bipolar patients with melancholic type depression.     

Dopamine transporters, D2 receptors, and glucose metabolism in corticobasal degeneration.

Alterations in presynaptic and postsynaptic dopaminergic system and cerebral glucose metabolism in corticobasal degeneration (CBD) were assessed to evaluate the potential usefulness of different imaging methods for CBD. (123)I-FP-CIT/(123)I-beta-CIT SPECT and (123)I-IBZM SPECT as well as (18)F-FDG PET were performed in eight CBD patients. Decreased presynaptic dopamine transporter binding was found in all CBD patients while D2 receptor binding was reduced in only one patient. (18)F-FDG PET displayed a contralateral hypometabolism in cortical and subcortical areas in seven out of eight patients. Our results demonstrate that glucose metabolism and DAT are reduced, while D2 receptors may be frequently preserved in CBD.     

Prognostic value of pharmacological stress echocardiography in diabetic and nondiabetic patients with known or suspected coronary artery disease.

OBJECTIVES: We sought to compare the prognostic value of pharmacological stress echocardiography (SE) in diabetic and nondiabetic patients with known or suspected coronary artery disease. BACKGROUND: Although SE is a useful tool for risk stratification of patients with diabetes, it has not been established whether it retains the same prognostic information in diabetic patients compared with nondiabetic patients. METHODS: A total of 5,456 patients (749 diabetics) undergoing dipyridamole (n = 3,306) or dobutamine (n = 2,150) SE were prospectively followed up for the occurrence of hard events (death and/or nonfatal myocardial infarction). RESULTS: During a median time of 31 months, 411 deaths and 236 infarctions occurred. There were 132 events in diabetic patients and 515 in nondiabetic patients (18% vs. 11%, respectively; p < 0.0001). Moreover, 1,607 (29%) patients underwent coronary revascularization and were censored. Ischemia at SE, resting wall motion score index, and age were independent predictors of death and hard events in both diabetic and nondiabetic patients. Compared with a normal test, ischemia and scar test patterns were associated to significantly lower age-corrected five-year hard event-free survival in diabetic as well as nondiabetic patients. However, a normal test was associated with a greater than two-fold annual event rate in diabetic patients as compared with nondiabetics who were either younger (2.6% vs. 1.0%) or older (5.5% vs. 2.2%) than 65 years of age. CONCLUSIONS: Stress echocardiography is equally effective in risk stratifying diabetic and nondiabetic patients independently of age. However, the normal test result predicts a less favorable outcome in diabetic than in nondiabetic patients.     

Initial steps taken by nine primary care practices to implement alcohol screening guidelines with hypertensive patients: the AA-TRIP project.

Many medical conditions are caused or exacerbated by heavy drinking, necessitating alcohol screening and discussion in primary care practices. This is particularly true of hypertension, the most common primary diagnosis in the United States, which has been linked to the regular consumption of 3 or more standard alcoholic beverages a day. The Accelerating Alcohol Screening-Translating Research into Practice (AA-TRIP) project was designed to improve detection and management of alcohol problems in primary care patients with hypertension. Medical providers are being trained using the Practice Partner Research Network's- Translating Research into Practice (PPRNet-TRIP) quality improvement model. This includes a multi-method intervention (electronic medical records, on-site academic detailing, practice feedback reports and annual network meetings) to help practices increase adherence to clinical guidelines. Qualitative analyses of initial steps taken by nine primary care practices toward the routine implementation of alcohol screening guidelines are presented. Organizational factors and provider and patient characteristics all influenced the method and consistency of alcohol screening and intervention. Perceived time constraints, patient sensitivity to questions about alcohol, and possible stigma associated with a diagnosis of alcoholism were also relevant barriers requiring problem solving.     

Helicobacter pylori and luminal gastric pH

The relationships between gastric pH and Helicobacter pylori infection were studied in 37 consecutive subjects affected with nonulcer dyspepsia. Each underwent esophagogastroduodenoscopy with multiple gastric biopsies for both H. pylori and histologic assessment, and 24-hr antral pH monitoring. H. pylori was harbored by 59.5% of the subjects with whole gastric spread of infection in all but one patient. Histologic gastritis was shown in 70.3% of the subjects. H. pylori was strongly associated with gastritis, both antral nonatrophic and multifocal atrophic. The ranges of 24-hr pH values were 1.3-6.9 in the H. pylori-positive and 1.2-6.8 in the H. pylori-negative group. Differences in pH values between the two groups were not significant. Moreover, the mean percent time duration of pH above 2, 4, and 6 did not significantly differ between the two groups. Therefore, this study has shown that chronic H. pylori infection is not related to luminal gastric pH.     

Mediation as a new technique for resolving disputes in the mental health system

In the mental health service system, disputes take on various forms and exist in both clinical practice and management. Existing policy and administrative practice has favored a combination of medical and judicial/legal models to handle conflicts among consumers, mental health professionals, and others. The authors propose the addition of mediation as a third form of resolving issues, explicate some of the differences between mediation and current methods of resolving conflicts, and suggest benefits of using mediation.Noel Mazade is Executive Director, National Association of State Mental Health Program Directors Research Institute and a practicing mediator. Andrea Blanch is Director of Community Support Programs for the New York Office of Mental Health in Albany, NY.The views presented in this article are those of the authors only. Endorsement by the authors' organizational affiliations is not implied nor should it be inferred.     

Plasma beta-endorphin, free fatty acids and blood lipid changes in type 2 (non-insulin dependent) diabetic patients

A lipolytic activity for beta-endorphin (beta EP) has been recently suggested both in vitro and in vivo. In our study we evaluated the relationship between beta EP and blood lipid pattern in Type 2 (non-insulin dependent) diabetic patients. Plasma beta EP, together with plasma beta-lipotropin (beta LPH), ACTH, cortisol and plasma insulin (IRI), was measured by RIA after silicic acid plasma extraction and Sephedex G-75 column chromatography. Although reduced beta EP (7.12 +/- 3.8 fmol/ml) and increased beta LPH (9.3 +/- 3.7 fmol/ml) levels were found in diabetic patients, compared to controls (8.53 +/- 3.3 fmol/ml, p less than 0.05 and 8.34 +/- 2.6 fmol/ml, p less than 0.05, respectively), higher plasma beta EP concentrations were demonstrated in hyperlipidemic diabetic patients (10.3 +/- 3.9 fmol/ml) than in patients with normal blood lipid pattern (4.85 +/- 1.45 fmol/ml, p less than 0.001). Several positive correlations between beta EP, plasma free fatty acids (r = 0.75, p less than 0.001), triglycerides (r = 0.84, p less than 0.001) and VLDL (r = 0.80, p less than 0.001) were found in our patients independently of overweight, hypoglycemic treatment, plasma IRI levels and of the degree of metabolic control. A higher prevalence of micro- and macrovascular complications was demonstrated in hyperlipidemic than in normolipidemic patients. Blood lipid disorders might therefore be associated with increased plasma beta EP levels in Type 2 diabetes.