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Abstract: Alcohol abuse coincides with a wide variety of clinical, sociological and psychological features and symptoms. Gastrointestinal symptoms are also very common in alcoholics, but the reason is unclear. We aimed to determine the prevalence of alexithymia in alcoholics and furthermore if gastrointestinal symptoms were associated with alexithymia. Out of the 84 alcoholics who completed the alexithymia questionnaire (Toronto Alexithymia Scale, TAS20) and the standard gastrointestinal symptoms questionnaire, 92% reported gastrointestinal symptoms and 54% were alexithymic. Alcoholics above age 43 had more difficulty describing feelings (odds ratio=4.1, confidence interval=1.5–11.4). Almost all measured gastrointestinal symptoms in alcoholics were associated with scores on an alexithymia questionnaire. [Copyright &y& Elsevier]

We examined the prevalence of vitamin B12 deficiency and its association with medication use and characteristics, including infection with Helicobacter pylori (H. pylori), in 255 patients hospitalized for cardiovascular disease. In almost half of the study population, vitamin B12 deficiency was found; patients using acetylsalicylic acid were more frequently vitamin B12 deficient in comparison to nonusers (p = 0.02). Fifty-one percent of the patients were infected with H. pylori, and fewer infected patients were vitamin B12 deficient. [Copyright &y& Elsevier]

Abstract: Context: Upper gastrointestinal cancer is associated with a poor prognosis. The multidimensional problems of incurable patients require close monitoring and frequent support, which cannot sufficiently be provided during conventional one to two month follow-up visits to the outpatient clinic. Objectives: To compare nurse-led follow-up at home with conventional medical follow-up in the outpatient clinic for patients with incurable primary or recurrent esophageal, pancreatic, or hepatobiliary cancer. Methods: Patients were randomized to nurse-led follow-up at home or conventional medical follow-up in the outpatient clinic. Outcome parameters were quality of life (QoL), patient satisfaction, and health care consumption, measured by different questionnaires at one and a half and four months after randomization. As well, cost analyses were done for both follow-up strategies in the first four months. Results: In total, 138 patients were randomized, of which 66 (48%) were evaluable. At baseline, both groups were similar with respect to clinical and sociodemographic characteristics and health-related QoL. Patients in the nurse-led follow-up group were significantly more satisfied with the visits, whereas QoL and health care consumption within the first four months were comparable between the two groups. Nurse-led follow-up was less expensive than conventional medical follow-up. However, the total costs for the first four months of follow-up in this study were higher in the nurse-led follow-up group because of a higher frequency of visits. Conclusion: The results suggest that conventional medical follow-up is interchangeable with nurse-led follow-up. A cost utility study is necessary to determine the preferred frequency and duration of the home visits. [Copyright &y& Elsevier]

Elevated total plasma homocysteine is an established risk factor for cardiovascular disease. Experimental evidence suggests that non–protein-bound free homocysteine is particularly hazardous to the vascular endothelium. This study evaluates the predictive role of free plasma homocysteine levels on cardiovascular endpoints in patients with acute coronary syndrome (ACS). In a cohort of 379 hospitalized patients with a diagnosis of myocardial infarction or unstable angina pectoris, total and free plasma homocysteine levels were measured by high performance liquid chromatography. The patients were followed for a median 2.7 years. The primary endpoint was a composite of cardiovascular death, myocardial infarction and stroke during follow-up. Stepwise Cox regression was used for multivariate analysis. Primary outcome events occurred in 82 patients (22%) with a median time to event of 6 months. The unadjusted hazard ratio for a free homocysteine level >4.11 μmol/L was 2.16 (95% confidence intervals [CI] 1.36 to 3.42) compared with the 4 lower quintiles. After adjusting for the covariates the hazard ratio was 2.25 (95% CI 1.41 to 3.58, p = 0.01). Compared with the lower 4 quintiles, patients with a total homocysteine level >22.4 μmol/L had a 2.09-fold higher risk (95% CI 1.31 to 3.35) for an event during follow-up. Adjusted for age, discharge diagnosis, serum creatinine, history of atherothrombotic events, and diabetes mellitus, the adjusted hazard ratio was 1.37 (95% CI 0.83 to 2.25, p = 0.22). In conclusion, plasma free homocysteine levels >4.11 μmol/L are a significant and independent risk factor for recurrent cardiovascular events in patients hospitalized for ACS, although total plasma homocysteine levels have no predictive value. [Copyright &y& Elsevier]

Background: Pragmatic randomised controlled trials are often used in primary care to evaluate the effect of a treatment strategy. In these trials it is difficult to achieve both high internal validity and high generalisability. This article will discuss several methodological challenges in designing and conducting a pragmatic primary care based randomised controlled trial, based on our experiences in the DIAMOND-study and will discuss the rationale behind the choices we made. From the successes as well as the problems we experienced the quality of future pragmatic trials may benefit. Discussion: The first challenge concerned choosing the clinically most relevant interventions to compare and enable blinded comparison, since two interventions had very different appearances. By adding treatment steps to one treatment arm and adding placebo to both treatment arms both internal and external validity were optimized. Nevertheless, although blinding is essential for a high internal validity, it should be warily considered in a pragmatic trial because it decreases external validity. Choosing and recruiting a representative selection of participants was the second challenge. We succeeded in retrieving a representative relatively large patient sample by carefully choosing (few) inclusion and exclusion criteria, by random selection, by paying much attention to participant recruitment and taking the participant's reasons to participate into account. Good and regular contact with the GPs and patients was to our opinion essential. The third challenge was to choose the primary outcome, which needed to reflect effectiveness of the treatment in every day practice. We also designed our protocol to follow every day practice as much as possible, although standardized treatment is usually preferred in trials. The aim of this was our fourth challenge: to limit the number of protocol deviations and increase external validity. Summary: It is challenging to design and conduct a pragmatic trial. Thanks to thorough preparation, we were able to collect highly valid data. To our opinion, a critical deliberation of where on the pragmatic - explanatory spectrum you want your trial to be on forehand, in combination with consulting publications especially on patient recruitment procedures, has been helpful in conducting a successful trial. [ABSTRACT FROM AUTHOR]

Aims: Alcohol misuse is now regarded as an important risk factor for development of chronic pancreatitis (CP). However, not every alcohol misuser develops CP and it therefore might be suggested that susceptibility could be further influenced by inter-individual variations in the activities of alcohol-metabolizing enzymes. Several genetic polymorphisms that may affect the activities of alcohol-metabolizing enzymes have been described. Therefore we determined whether polymorphisms in the genes for alcohol dehydrogenase 3 (ADH3) or cytochrome P450 2E1 (CYP2E1) predispose to the development of CP. Methods: DNA samples were obtained from 142 adult CP patients with hereditary (n = 21), alcoholic (n = 82) or idiopathic (n = 39) CP. DNA from 128 healthy controls and from 93 alcoholic controls was analysed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms in ADH3 and CYP2E1 were determined by PCR, followed by restriction-fragment-length-polymorphism analyses in all subjects. Results: The frequencies of ADH3 and CYP2E1 c1c2 genotypes did not differ between CP patients and alcoholic and healthy controls. However, a trend for a higher frequency of the CYP2E1 intron 6 D allele was demonstrated in patients with alcohol-induced CP, compared to that of healthy controls (OR = 3.03, 95%CI = 1.0-9.1) or alcoholic controls (OR = 2.76, 95%CI = 0.9-8.7). Conclusions: These data suggest that the presence of the CYP2E1 intron 6 DD genotype might confer a higher risk of alcoholic CP. [ABSTRACT FROM AUTHOR]

The aim of this work was to study abstinence rates and withdrawal effects of rapid detoxification of opioid-dependents under general anesthesia (RD-GA) compared to standard methadone tapering (SMT) using a prospective clinical trial with a follow-up of 3 months, as a preliminary study at the Novadic addiction centre in St Oedenrode and St Joseph Hospital in Veghel, the Netherlands. Thirty opioid-dependent patients took part. Outcome measures included urine toxicology screening for opiates to determine abstinence and presence of objective and subjective opioid withdrawal distress symptoms. Statistically significant differences in abstinence rate between RD-GA and SMT were present after one (RD-GA 100% vs. SMT 40%, p< 0.01) and 2 months (RD-GA 93% vs. SMT 33%, p <0.01). After 3 months the difference in abstinence was still substantial, but no longer statistically significant (RD-GA 67% vs. SMT 33%, p= 0.14). Objective and subjective withdrawal symptoms showed largely identical outcomes and were equally low in the two groups for those who remained in the study. There was a considerably higher percentage of abstinence in the RD-GA group after 1, 2 and 3 months of follow-up accompanied by relatively mild withdrawal symptoms of shorter duration. However, if one completes SMT the data suggest a greater chance of staying clean in the long term than those completing RD-GA. [ABSTRACT FROM AUTHOR]

Offers letters to the editor on a variety of medical topics as of December 5, 2001. Brain injury resulting from falls among elderly persons; Perceptions of graduating residents of their preparedness for practice; Physical activity counseling in primary care; Meningococcal disease in college students; Use of meta-analysis to answer clinical questions; Politics and medicare; More.

Examines the importance of magnetic resonance imaging and mammography to women with breast cancer in the Netherlands. Risk of breast cancer carriers; Detection of cancer; Use of multivariate analysis.

Familial atypical multiple mole melanoma (FAMMM) syndrome is a hereditary syndrome characterized by multiple dysplastic nevi and melanoma. Patients with FAMMM may have a heterozygous, inactivating, pathogenic germline variant in the CDKN2A gene, especially the NM_000077.4: c.225_243del19 (p.p75fs) variant, also known as p16 -Leiden variant. Patients with this variant are at high risk for developing melanomas and pancreatic cancer due to somatic inactivation of the wild-type CDKN2A allele. The combination of an inactivating germline CDKN2A mutation and somatic inactivation of the wild-type CDKN2A allele in the same cell results in tumor formation. It has been suggested that carriers of a germline CDKN2A mutation are also at increased risk for several other cancer types, including esophageal cancer. Here, we describe two unrelated patients with the p16 -Leiden variant who developed esophageal squamous cell cancer. Evidence of loss of the wild-type CDKN2A allele was obtained in the tumor tissue of both patients indicating biallelic inactivation of p16 in the tumor cells. These results suggest that these patients developed esophageal squamous cell cancer in the context of FAMMM syndrome. [ABSTRACT FROM AUTHOR]