Changing preferences for information and participation in the last phase of life: a longitudinal study among newly diagnosed advanced lung cancer patients.

PURPOSE: The objective is to explore changes over time in the information and participation preferences of newly diagnosed stage IIIb/IV non-small-cell lung cancer patients. METHODS: Patients were recruited by physicians in 13 hospitals and interviewed every 2 months until the fourth and every 4 months until the sixth interview. RESULTS: Sixty-seven patients were interviewed three times. Over a period of 4 months from diagnosis, half of patients changed their information preferences for palliative care and end-of-life decisions with a possible or certain life-shortening effect (ELDs, e.g., non-treatment decisions) in both directions, from not wanting to wanting the information, but also--and as much--from wanting to no longer wanting it. The latter were more likely to be in a better physical condition. Preferences for participation in medical decision making also changed: 50% to 78%, depending on the type of decision (general, treatment, transfer or ELD), changed their preference towards wanting more or less participation. Pain seemed to be a trigger for patients wanting more involvement, which contrasts with studies suggesting that patients who are more ill tend to give up more control. CONCLUSIONS: Doctors should regularly ask their advanced lung cancer patients how much information and participation they want because preferences do change in unexpected ways.

[Life with Locked-In syndrome]. / Quelle vie après le Locked-In syndrome?

The Locked-In Syndrome (LIS) is classically caused by an anterior pontine vascular lesion and characterized by quadriplegia and anarthria with preserved consciousness and intellectual functioning. We here review the definition, etiologies, diagnosis and prognosis of LIS patients and briefly discuss the few studies on their quality of life and the challenging end-of-life decisions that can be encountered. Some clinicians may consider that LIS is worse than being in a vegetative or in a minimally conscious state. However, preliminary data from chronic LIS survivors show a surprisingly preserved self-scored quality of life and requests of treatment withdrawal or euthanasia, though not absent, are infrequent.

In vitro assessment of cytotoxic agents in murine cancers: comparison between antiproliferative and antimetabolic assays.

Different methods were compared for the in vitro evaluation of the therapeutic effects of the antineoplastic agents doxorubicin, cisplatin, fluorouracil, and vinblastine sulfate in a model system of murine tumor cell lines consisting of L1210 leukemia, P815 mast cell leukemia, and B16 melanoma. Excellent correlations were found with the in vivo effects with the use of a soft agar clonogenic assay, irrespective of the method of growth assessment (i.e., visual colony counting or incorporation of tritiated thymidine in proliferating colonies). Drug effects on the proliferation of tumor cell lines in liquid medium frequently led to an overestimation or underestimation of the actual in vivo effects. Direct incorporation of the radiolabeled precursors thymidine, uridine, and leucine after pretreatment with drugs always led to the prediction of resistance and was therefore considered unreliable.

The Belgian PCB and dioxin incident of January-June 1999: exposure data and potential impact on health.

In January 1999, 500 tons of feed contaminated with approximately 50 kg of polychlorinated biphenyls (PCBs) and 1 g of dioxins were distributed to animal farms in Belgium, and to a lesser extent in the Netherlands, France, and Germany. This study was based on 20,491 samples collected in the database of the Belgian federal ministries from animal feed, cattle, pork, poultry, eggs, milk, and various fat-containing food items analyzed for their PCB and/or dioxin content. Dioxin measurements showed a clear predominance of polychlorinated dibenzofuran over polychlorinated dibenzodioxin congeners, a dioxin/PCB ratio of approximately 1:50,000 and a PCB fingerprint resembling that of an Aroclor mixture, thus confirming contamination by transformer oil rather than by other environmental sources. In this case the PCBs contribute significantly more to toxic equivalents (TEQ) than dioxins. The respective means +/- SDs and the maximum concentrations of dioxin (expressed in TEQ) and PCB observed per gram of fat in contaminated food were 170.3 +/- 487.7 pg, 2613.4 pg, 240.7 +/- 2036.9 ng, and 51059.0 ng in chicken; 1.9 +/- 0.8 pg, 4.3 pg, 34.2 +/- 30.5 ng, and 314.0 ng in milk; and 32.0 +/- 104.4 pg, 713.3 pg, 392.7 +/- 2883.5 ng, and 46000.0 ng in eggs. Assuming that as a consequence of this incident between 10 and 15 kg PCBs and from 200 to 300 mg dioxins were ingested by 10 million Belgians, the mean intake per kilogram of body weight is calculated to maximally 25,000 ng PCBs and 500 pg international TEQ dioxins. Estimates of the total number of cancers resulting from this incident range between 40 and 8,000. Neurotoxic and behavioral effects in neonates are also to be expected but cannot be quantified. Because food items differed widely (more than 50-fold) in the ratio of PCBs to dioxins, other significant sources of contamination and a high background contamination are likely to contribute substantially to the exposure of the Belgian population.

Minimal-change nephropathy and malignant thymoma.

A 56-year-old man had fever, precordial pain, and a mediastinal mass. The mass disappeared two months later and the patient remained asymptomatic for 2 1/2 years. At that time a full-blown nephrotic syndrome developed, with minimal-change glomerulopathy. The chest x-ray film showed the reappearance of a giant mediastinal mass. On biopsy of the mass, malignant thymoma was diagnosed. Association between minimal-change disease and Hodgkin's disease is well known, while the association with malignant thymoma has not been previously reported. The relationship between malignant thymoma and minimal-change disease is discussed, and a possible pathogenic mechanism involving cell-mediated immunity is proposed.

Similia similibus obscurantur: the pharmacological clinical activity bias I. A prototype model to correct a disease-drug interaction leading to misestimations of drug-attributable side effects.

Drugs have side effects that manifest as signs or symptoms which are sometimes undistinguishable from signs or symptoms of active disease. The conventional approximation of the rate of side effects of drugs is by subtracting the rate of signs and symptoms in the placebo group from that in the drug group. This measures net side effects and is adequate in studies with healthy volunteers, in which no interaction between drug and disease exists. For ethical and practical reasons, however, volunteer studies cannot be large and the frequency of non-rare side effects must be estimated in large-scale clinical trials. In the latter, biasing drug disease interactions may occur. We report on such a hitherto undescribed interaction: the pharmacological clinical activity bias. If one is interested in estimating not the net, but the direct or intrinsic, ie, drug-attributable side effects, the conventional approximation is biased whenever, in clinical trials, both of two conditions apply. The first is that the variable on the scale of which a sign or symptom is recorded as a putative side effect, is also in the absence of drug affected by uncontrolled disease. The second is that the drug has pharmacological clinical activity (A) on that sign or symptom, thus reducing the contribution of disease (D) to what is measured. In this case the drug affects the variable under study both directly, through its intrinsic side effect, and indirectly, through its clinical activity, and the rate of attributable side effects differs from the rate of net side effects as calculated by the conventional approximation. We present a simple deterministic model, which assumes that disease remains stable if untreated, additivity of the relative contributions of drug, placebo and disease to the total rate of the sign or symptom, and no other interaction between intrinsic properties of the drug and active disease than pharmacological clinical activity. This theoretical model quantifies the bias as DO(Ad-Ap), in which DO is the baseline frequency of the sign or symptom in the studied patients, and Ad and Ap are the intrinsic clinical activities of drug and placebo, respectively, on the sign or symptom under study. The model confirms that the conventional approximation of drug side effects is unbiased only in healthy volunteers or with drugs devoid of clinical activity. Without correction by such a model, any clinical activity of the drug or manifestation of active disease will cause the conventional approximation of side effects to be biased. This may manifest as artifacts such as attribution of a side effect when there is none, and as under- or overestimation, pseudotachyphylaxis, or pseudo-delayedness of attributable side effects.

[Evaluation of the quality of life during treatment]. / Evaluation de la qualité de la vie en cours de traitement.

Biomedical advances to further the quality of life (QL) of cancer patients must nowadays be complemented by psycho-social evaluation and intervention. The challenge is to quantify the qualitative and to objectivate the subjective. To evaluate QL during treatment of individual patients, open interviews are unsurpassed. However, to measure QL of patient groups, questionnaires are necessary. Some examples from the QL literature illustrate the main drawbacks of questionnaires: lack of sensitivity, specificity, and iterative applicability. To circumvent these problems, it is suggested to add a global self-assessment of QL to questionnaires. Such an instrument, Anamnestic Comparative Self-Assessment is briefly described.

[A comparative study of the euthanasia laws of Belgium and the Netherlands]. / Similitudes et différences entre les lois belge et néérlandaise relatives à l'euthanasie.

Recently, laws on euthanasia have been adopted in the Netherlands and Belgium. In both countries the legality of euthanasia is conditioned by adherence to strict conditions and by confirmation after a notification procedure. Although both laws are rather similar, the Belgian law is more fastidious on the requirements of prudent practice. The Belgian law does and the Dutch law does not distinguish between terminal conditions and non-terminal or slowly evolutive chronic conditions. In Belgium, the law only applies to adults, whereas in the Netherlands, minors over 12 years of age may under certain conditions receive euthanasia. However, the Belgian National Medical Disciplinary Board has recently mitigated differences by drafting guidelines which reflect a broad interpretation of the law. A major difference between the two countries is that in the Dutch society the norm setting on euthanasia developed more through jurisprudence and endorsement by the Medical Association than through legislation. We anticipate that the implementation of the new law and the notification procedure may be more difficult in Belgium than in the Netherlands. In order to promote the quality of the euthanasia practice, the euthanasia notification procedure in the Netherlands is followed by systematic feedback to the physicians. The strict anonymity of the Belgian notification procedure will be broken only when the control commission finds some anomaly or deficiency in the declaration. Therefore, unless the Evaluation and Control Commission makes ample use of its prerogative to contact the physician, the Belgian physicians may be less supported by the notification procedure to improve their knowledge and skills in euthanasia.

Pereira's attack on legalizing euthanasia or assisted suicide: smoke and mirrors.

OBJECTIVE: To review the empirical claims made in: Pereira J. Legalizing euthanasia or assisted suicide: the illusion of safeguards and controls. Curr Oncol 2011;18:e38-45. DESIGN: We collected all of the empirical claims made by Jose Pereira in "Legalizing euthanasia or assisted suicide: the illusion of safeguards and controls." We then collected all reference sources provided for those claims. We compared the claims with the sources (where sources were provided) and evaluated the level of support, if any, the sources provide for the claims. We also reviewed other available literature to assess the veracity of the empirical claims made in the paper. We then wrote the present paper using examples from the review. RESULTS: Pereira makes a number of factual statements without providing any sources. Pereira also makes a number of factual statements with sources, where the sources do not, in fact, provide support for the statements he made. Pereira also makes a number of false statements about the law and practice in jurisdictions that have legalized euthanasia or assisted suicide. CONCLUSIONS: Pereira's conclusions are not supported by the evidence he provided. His paper should not be given any credence in the public policy debate about the legal status of assisted suicide and euthanasia in Canada and around the world.

DNA synthesis and proliferation of human lymphocytes in vitro. II. Characterization of the DNA newly synthesized after phytohemagglutinin stimulation.

DNA newly synthesized by phytohemagglutinin-(PHA) stimulated human lymphocytes has been analyzed for the possibility that all DNA synthesis may not represent premitotic genome duplication. Equilibrium density gradient characterization of bromodeoxyuridine-(BUdR) substituted DNA demonstrates semi-conservative DNA replication, without evidence for repair synthesis. Experiments to detect selective replication (amplification) of a portion of the DNA involved measurement of reassociation kinetics as well as measurement of the kinetics of BUdR appearance in prelabeled DNA. The presence of large quantities of amplified DNA has been excluded, although amplification cannot be ruled out completely by these techniques. Finally, the kinetics of DNA release from dead lymphocytes is characterized, and factors tending to reduce the complexity of released, labeled DNA are identified.