Clinical outcome and atherothrombogenic risk profile after prolonged wash-out following long-term treatment with high doses of n-3 PUFAs in patients with an acute myocardial infarction

BACKGROUND: Sustained effects following withdrawal of n-3 PUFAs are unknown. METHODS: Clinical outcome [cardiac death, resuscitation, recurrent myocardial infarction (MI) or unstable angina pectoris] was assessed after prolonged wash-out following randomised treatment with high-dosed n-3 PUFAs or corn oil for 12-24 months in 300 acute MI patients. Atherothrombogenic risk markers, serum glucose and markers of lipid peroxidation and inflammation were evaluated in 89 out of the 100 last included patients. RESULTS: After a total median observation period of 45 (range 0-53) months no intergroup difference in prognosis was observed for any of the cardiac events. Favourable effects on serum triglycerides and HDL-cholesterol by n-3 PUFAs were lost after washout, but triglycerides decreased in the corn oil as compared to the n-3 group, P < 0.001. The decline in total cholesterol after withdrawal was similar in both groups. No intergroup difference in the change in thiobarbituric acid-malondialdehyde, a marker of lipid peroxidation, ultrasensitive C-reactive protein, homocysteine, glucose or blood platelets was noted at sustained follow-up. CONCLUSION: Clinical outcome was similar in both patient groups, and the atherothrombogenic risk improvement by n-3 PUFAs was lost after prolonged wash-out. Withdrawal did not affect homocysteine, glucose or markers of lipid peroxidation or inflammation.     

Community-based health insurance in low-income countries: a systematic review of the evidence

Health policy makers are faced with competing alternatives, and for systems of health care financing. The choice of financing method should mobilize resources for health care and provide financial protection. This review systematically assesses the evidence of the extent to which community-based health insurance is a viable option for low-income countries in mobilizing resources and providing financial protection. The review contributes to the literature on health financing by extending and qualifying existing knowledge. Overall, the evidence base is limited in scope and questionable in quality. There is strong evidence that community-based health insurance provides some financial protection by reducing out-of-pocket spending. There is evidence of moderate strength that such schemes improve cost-recovery. There is weak or no evidence that schemes have an effect on the quality of care or the efficiency with which care is produced. In absolute terms, the effects are small and schemes serve only a limited section of the population. The main policy implication of the review is that these types of community financing arrangements are, at best, complementary to other more effective systems of health financing. To improve reliability and validity of the evidence base, analysts should agree on a more coherent set of outcome indicators and a more consistent assessment of these indicators. Policy makers need to be better informed as to both the costs and the benefits of implementing various financing options. The current evidence base on community-based health insurance is mute on this point.     

Revitalising the Metropolit 1953 Danish male birth cohort: background, aims and design

Recent research indicates that factors operating during childhood are related to adult health. Thus, longitudinal studies with information on subsequent phases may be key to understanding later health outcomes. The main objective of this paper is to describe the history and design of a Danish birth cohort, and its revitalisation. In 1965, information from birth certificates for 11 591 of a total of 12 270 males born in 1953 in the Metropolitan area of Copenhagen, Denmark were traced. These boys were the study population of a sociological investigation conducted with the aim of describing social mobility. At age 12 years, 9537 of these cohort members completed a questionnaire in school, which included cognitive measures and information on social aspirations and leisure time activities. In 1966 educational performance tests were administered for these boys and, in 1968, mothers of 2890 cohort members were interviewed regarding family social backgrounds. With the establishment of the Civil Registration System (CRS) in 1968, it was possible to identify 11 532 cohort members. In 2002 we began the process of revitalising this study with the aim of investigating the influence of early life factors on later health. We succeeded in ascertaining the vital status of all subjects in the CRS. This showed that 863 subjects had died between 1968 and 2002. Linkages to the Register of Causes of Death, the National Hospital Register, Psychiatric Central Register and Danish Cancer Registry have been completed. In total, 7969 cohort members had been hospitalised for any somatic illness and, according to the Psychiatric Central Register, 1382 men had been admitted to a psychiatric hospital or ward. In the Cancer Registry we found 363 of our study participants. Analyses exploring the influence of social conditions in early life, birth dimensions, and childhood cognition on adult health experience are at various stages of completion. A questionnaire-based postal follow-up survey is planned. Thus, the Metropolit study provides an important opportunity to examine the processes by which factors that operate over the life course influence adult health.     

Marital history from age 15 to 40 years and subsequent 10-year mortality: a longitudinal study of Danish males born in 1953

BACKGROUND: The aims of the present study are to analyse the association between marital status at age 24, 29, 34, and 39 years and subsequent mortality in a cohort of men born in 1953 (sensitive period); to study the impact of number of years married, number of years divorced/widowed, and number of marital break-ups on mortality (cumulative effect), and to examine whether these effects were independent of marital status at age 39 (proximity effect). METHODS: Prospective birth cohort study with follow-up of mortality from 1992 to 2002. Participants were 10891 men born within the metropolitan area of Copenhagen, Denmark. Marital status in 1992 as well as start and termination of all previous marital status events from 1968 to 1992 were retrieved from the Danish Civil Registration System. MAIN OUTCOME MEASURES: Were hazard ratios (HR) for all-cause mortality from age 40 to 49 years. RESULTS: We found a strong protective effect of being married compared with never being married or divorced/widowed at every age. The association increased in strength with increasing age. Number of years divorced was associated with increased mortality risk in a dose-dependent manner at age 34 and 39 years. One or more marital break-ups was associated with higher mortality, whereas increasing number of years married was associated with lower mortality. Inclusion of current marital status attenuated the strength of the associations but most of them remained statistically significant. CONCLUSIONS: Marital status and cumulated marital periods, especially cumulated periods divorced/widowed are strong independent predictors of mortality among younger males.     

Dihydrexidine--the first full dopamine D1 receptor agonist

The functional role of dopamine D(1) receptors is still controversial. One reason for this controversy is that for a long time the only available agonists for in vivo characterization of dopamine D(1) receptors were benzazepines. Among them was the prototype dopamine D(1) receptor partial agonist, SKF 38393. The lack of a selective and fully efficacious dopamine D(1) receptor agonist hampered basic research on dopamine D(1) receptors and left the potential clinical utility of dopamine D(1) receptor agonists elusive. The research situation improved when the first potent full dopamine D(1) receptor agonist dihydrexidine, a phenanthridine, was introduced in the late 1980s. In contrast to SKF 38393, dihydrexidine was shown to stimulate cyclic AMP synthesis just as well or better than dopamine, and potently displaced [(3)H]SCH 23390 from rat and monkey striatal membranes. Also, dihydrexidine was the first dopamine D(1) receptor agonist that had potent antiparkinsonian activity in a primate model of Parkinson's disease. This finding suggested clinical utility for dopamine D(1) receptor agonists in Parkinson's disease and that this utility might be critically dependent on the intrinsic efficacy of the drug. Clinical utility for dopamine D(1) receptor agonists in other central nervous disorders might also be dependent on the intrinsic efficacy of the drug. However, even though studies with dihydrexidine as a pharmacological tool have pointed to the clinical use for dopamine D(1) receptor agonists, dihydrexidine's unfavorable pharmacokinetic profile and various adverse effects are likely to restrict or even preclude its use in humans. This review article provides an updated overview of the pharmacology of dihydrexidine and discusses possible clinical utility of dopamine D(1) receptor agonists in various central nervous system disorders.     

Cognitive deficits in long-term survivors of childhood brain tumors: Identification of predictive factors

BACKGROUND: To describe cognitive function and to evaluate the association between potentially predictive factors and cognitive outcome in an unselected population of survivors of childhood brain tumors. PROCEDURE: We studied a consecutive sample of 133 patients (76 had received radiotherapy (RT)) who had a brain tumor diagnosed before the age of 15 years and were treated during the period January 1970 through February 1997 in the Eastern part of Denmark. Biologic effective dose of irradiation (BED) was assessed in 71 patients. One hundred twenty-seven patients were able to cooperate to WISC-R and WAIS-R. Multiple regression models were constructed to evaluate relationships between possible risk factors and cognitive outcome. RESULTS AND CONCLUSIONS: The mean intelligence (IQ) scores were substantially lower than the expected means of the general population. Younger age at diagnosis, tumor site in cerebral hemisphere, hydrocephalus treated with shunt, and treatment with RT were found to be significant predictors of lower cognitive functions. RT was the most important risk factor for impaired intellectual outcome. The mean observed full scale IQ was 97.1 (SD = 14.3) for the non-irradiated patients and 78.8 (SD = 14.3) for the irradiated patients (adjusted P < 0.001). Verbal IQ, but not performance and full scale IQ, had a significant negative correlation to BED to the tumor site (P < 0.05). These results can be used to identify subgroups of children who are at increased risk for cognitive deficits allowing early and goal-directed intervention.     

Quantifying adenovirus-neutralizing antibodies by luciferase transgene detection: addressing preexisting immunity to vaccine and gene therapy vectors

The presence of various levels of anti-adenovirus serotype 5 (Ad5)-neutralizing antibodies in humans is thought to contribute to the inconsistent clinical results obtained so far in diverse gene transfer and vaccination studies and might preclude universal dosing with recombinant Ad5. Prescreening of individuals eligible for Ad5 or alternative serotype treatment and subsequently tailoring the vector dose might aid in ensuring the consistency of clinical parameters. For this purpose, a qualified Ad neutralization assay is required. Here we have tested the different protocols used to date to determine anti-Ad neutralizing activity. Based on simplicity, speed, high throughput, sensitivity, and robustness, we propose a qualified assay in which Ad neutralization is monitored by luciferase reporter gene expression.     

Anticipatory adjustments in the unloading task: is an efference copy necessary for learning?

In the unloading task, a weight is held in the palm of one hand. When an external agent removes the weight, an upward perturbation of the loaded hand is observed. However, when a person removes the weight by lifting it with their own hand, the perturbation is attenuated due to an anticipatory adjustment of the flexor muscles in the load-bearing arm. An experiment was conducted to examine conditions under which this anticipatory response could be learned. Using a virtual reality system with force-feedback robotic arms, normal subjects performed the unloading task under one of four learning conditions: (a) the participant initiated the unloading by pressing a button, (b) the unloading was cued by a brief visual stimulus, (c) the unloading was performed by a virtual "hand" that moved smoothly towards the object, and (d) the unloading followed three rhythmic force-pulses applied to the finger of the participant. After extended practice (192 trials) we found a significant reduction of the upward perturbation only in the button pressing condition. Control conditions indicated that the acquired response was due to an anticipatory feedforward response rather than due to a change in tonic state such as an increase in arm stiffness. These results indicate that a voluntary action is necessary to acquire an anticipatory adjustment in the unloading task. Electronic Publication     

The effect of centralization of primary surgery on survival in ovarian cancer patients

OBJECTIVE: To examine the effect of centralized surgery on overall survival in patients with ovarian cancer and, in particular, patients with advanced disease (stage III/IV). METHODS: In a historical prospective study design, patients referred from community hospitals to a teaching hospital for primary surgery during the 2-year period, 1995-1997, were included as cases. For each referred case, two controls, matched for International Federation of Gynecology and Obstetrics (FIGO) stage and age, were selected among patients who had had primary surgery at the referral hospitals (nonteaching) in the years, 1992-1995. Kaplan-Meier survival curves were computed and tested statistically by the log rank test. Cox proportional hazard model was applied for estimation of prognostic factors of survival. RESULTS: There was no difference in postoperative mortality for stage I/II patients by level of care (community hospitals versus teaching hospital). However, for advanced stage disease (III + IV), the controls had significantly shorter crude survival than patients who had been operated on at the teaching hospital (5-year survival: 4% versus 26%; median survival: 12 months versus 21 months) (P=.01). Multivariable analyses showed that completed chemotherapy and size of residual tumor after primary surgery were independent prognostic factors of survival. Patients optimally operated on at the teaching hospital had significantly lower risk of death compared with all other groups, independently of chemotherapy. This indicates that the extent of cytoreductive surgery and the overall management undertaken in the teaching hospital are significant predictors of improved survival. CONCLUSION: Centralization of primary ovarian cancer surgery in one health region in Norway has improved survival for patients with advanced disease. Patients with apparent advanced ovarian cancer should be referred to a subspecialty unit for primary surgery, and every effort should be made to attain as complete cytoreduction as possible.     

Maternal characteristics and lifestyle factors and the risk of delivering high birth weight infants

OBJECTIVE: To identify factors associated with an increased risk of giving birth to infants weighing more than 4000 g and to study whether changes in these factors over time can explain the increasing proportion of high birth weight infants over the last decade. METHODS: Our analyses included 24,093 pregnancies of nondiabetic women with information on potential risk factors for high birth weight: maternal prepregnancy weight, height, age, parity, smoking habits, alcohol and caffeine intake, marital status, educational level, gestational age, and infant gender. Information was obtained from questionnaires completed during pregnancy and birth registration forms at the Department of Obstetrics and Gynaecology, Aarhus University Hospital, Aarhus, Denmark, from 1990 to 1999. RESULTS: We found a statistically significantly increased risk of giving birth to infants weighing more than 4000 g for women with high prepregnancy weight and height, parity greater than 2, gestational age greater than 42 weeks, and male infant gender and for nonsmokers. Women with a low caffeine intake or 10 or more years of education were also at statistically significantly higher risk. The variation found in birth weight over the past 10-year period was explained by changes in maternal prepregnancy weight, height, smoking habits, educational level, and caffeine intake over the same period. CONCLUSION: Risk factors associated with a higher proportion of high birth weight infants may be clinically significant and have an impact on public health. High birth weight increases the risk of adverse outcomes of delivery as well as the risk of childhood morbidity.