Euthanasia and assisted suicide in the Netherlands: Clarifying the practice and the nurse's role

Many people believe that euthanasia and assisted suicide are condoned carte blanche in the Netherlands. Not true. Both are formally forbidden by criminal law and can be administered only when certain procedures and criteria have been followed. Below, a look at the policies and practices regarding euthanasia and assisted suicide in The Netherlands and the role of nurses in this area.     

Narrative review: aspirin resistance and its clinical implications

Aspirin is currently the most cost-effective drug for the secondary prevention of cardiovascular disease, but treatment failures are relatively common. Several factors have been linked to these recurrent vascular events in patients prescribed aspirin, including smoking, drug interactions, nonadherence, comorbid conditions, and aspirin resistance. The term aspirin resistance has been used to describe not only an absence of the expected pharmacologic effects of aspirin on platelets but also poor clinical outcomes, such as recurrent vascular events, in patients treated with aspirin. Aspirin resistance is perhaps more precisely understood as the phenomenon of measurable, persisting platelet activation that occurs in patients prescribed a therapeutic dose of aspirin and may underlie an unknown proportion of aspirin treatment failures. Key challenges for future research are to standardize a definition of aspirin resistance and to compare whether different measures of platelet activation, either alone or in combination, independently predict cardiovascular events. These challenges must be met before researchers conduct studies to assess the clinical utility of testing on patient outcomes and cost-effective prescribing.     

Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192

OBJECTIVE: To evaluate CAT-192, a recombinant human antibody that neutralizes transforming growth factor beta1 (TGFbeta1), in the treatment of early-stage diffuse cutaneous systemic sclerosis (dcSSc). METHODS: Patients with SSc duration of <18 months were randomly assigned to the placebo group or to 1 of 3 CAT-192 treatment groups: 10 mg/kg, 5 mg/kg, 0.5 mg/kg. Infusions were given on day 0 and weeks 6, 12, and 18. The primary objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of CAT-192. Secondary outcomes included the modified Rodnan skin thickness score (MRSS), the Scleroderma Health Assessment Questionnaire, assessment of organ-based disease, serum levels of soluble interleukin-2 receptor, collagen propeptides (N propeptide of type I [PINP] and type III collagen), and tissue levels of messenger RNA for procollagens I and III and for TGFbeta1 and TGFbeta2. RESULTS: Forty-five patients were enrolled. There was significant morbidity and mortality, including 1 death in the group receiving 0.5 mg/kg of CAT-192 and 3 deaths in the group receiving 5 mg/kg of CAT-192. There were more adverse events and more serious adverse events in patients receiving CAT-192 than in those receiving placebo, although these events were not more frequent in the high-dose treatment group. The MRSS improved in all groups during the study, but there was no evidence of a treatment effect for CAT-192. Improvement in the MRSS correlated with the disease duration (r = -0.54, P = 0.0008). Changes in the PINP level from baseline correlated with changes in the MRSS (r = 0.37, P = 0.027). CONCLUSION: We report the first evaluation of a systemically administered and repeatedly dosed anti-TGFbeta1 drug. In this pilot study, CAT-192, in doses up to 10 mg/kg, showed no evidence of efficacy. The utility of clinical and biochemical outcome measures and the feasibility of multicenter trials of early dcSSc were confirmed.     

Influence of maternal schistosomiasis on the immunity of adult offspring mice

Schistosoma mansoni infection modulates the immunity to unrelated antigens in the host. In this study, we have investigated the effect of pregnancy and nursing from schistosomotic mother mice on the immune response to ovalbumin (OA), in adult offspring. Then, newborn mice were divided into four groups: animals born from infected mothers (BIM) suckled by non-infected mothers; animals from non-infected mothers suckled by infected mothers (SIM); and two other groups that were mice born and suckled in infected mothers (BSIM) or non-infected (control) mothers. The adult offspring were immunized with OA plus adjuvant. We compared the OA-specific hypersensitivity reactions (HR), antibodies levels (IgG, IgG2a) and the cytokine production in splenocyte cultures. Remarkable interleukin (IL)-10 synthesis was observed in mice BIM; while the anti-OA antibodies levels and immediate HR were impaired. IL-10 neutralization recovered this suppression. Differently, in mice SIM and BSIM there was an enhancement in the anti-OA humoral response and high IL-2 production, however low level of the IL-10 was detected in mice BSIM. In conclusion, schistosomotic pregnancy provides an immunosuppressive potential, IL-10 dependent, which was sustained throughout adult life. Regardless, suckling by infected mothers induces great responsiveness to an unrelated antigen and repairs the inhibitory potential acquired during prenatal stage.     

Problematic Methods in the Assessment of Scholarly Productivity in Clinical PhD Programs

We review the methods in the ranking of clinical psychology doctoral programs provided by Stewart, Roberts, and Roy (2007). Using our own program as an example, we identify several areas of concern (e.g., authorship credits, criteria applied, faculty attrition). The inaccuracies identified for our program ranking, in combination with methodological concerns highlighted by previous commentaries, suggest that the validity of the rankings can be called into question.     

CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis.

PURPOSE: Two common variant alleles of the cytochrome CYP2C9 (CYP2C9*2 and CYP2C9*3) lead to reduced warfarin metabolism in vitro and in vivo. The study objective was to examine the strength and quality of existing evidence about CYP2C9 gene variants and clinical outcomes in warfarin-treated patients. METHODS: The study was a systematic review and meta-analysis. Multiple electronic databases were searched, references identified from bibliographies were sought, and experts and authors of primary studies were also contacted. Strict review inclusion criteria were determined. Three reviewers independently extracted data using prepiloted proformas. RESULTS: In all, 11 studies meeting review inclusion criteria were identified (3029 patients). Nine were included in the meta-analyses (2775 patients). Random effects meta-analyses were performed; statistical heterogeneity and inconsistency was assessed. Twenty percent of patients studied carry a variant allele: CYP2C9*2 12.2% (9.7%-15.0%) and CYP2C9*3, 7.9% (6.5%-9.7%). Mean difference in daily warfarin dose: for CYP2C9*2, the reduction was 0.85 mg (0.60-1.11 mg), a 17% reduction. For CYP2C9*3, the reduction was 1.92 mg (1.37-2.47 mg), a 37% reduction. For CYP2C9*2 or *3, the reduction was 1.47 mg (1.24-1.71 mg), a 27% reduction. The relative bleeding risk for CYP2C9*2 was 1.91 (1.16-3.17) and for CYP2C9*3 1.77 (1.07-2.91). For either variant, the relative risk was 2.26 (1.36-3.75). CONCLUSIONS: Patients with CYP2C9*2 and CYP2C9*3 alleles have lower mean daily warfarin doses and a greater risk of bleeding. Testing for gene variants could potentially alter clinical management in patients commencing warfarin. Evidence for the clinical utility and cost-effectiveness of genotyping is needed before routine testing can be recommended.     

Three-year durability of dual-nucleoside versus triple-nucleoside therapy in a Thai population with HIV infection

We compared the long-term immunologic and virologic efficacy of the dual- and triple-nucleoside therapy for HIV infection. This was a retrospective analysis of 2 randomized clinical trials in antiretroviral-naive patients. In the dual-nucleoside group, 15 started with didanosine (ddI) monotherapy and then added stavudine (d4T) after 24 weeks, 63 started with various doses of d4T and ddI, and 53 started with zidovudine (ZDV) and lamivudine (3TC). In the triple-nucleoside group, 53 started with ZDV, 3TC, and ddI. After 48 weeks, patients who were not failing were randomized to immediate (before treatment failure) versus delayed (at the time of virologic failure) switching from ddI and d4T to ZDV and 3TC or vice versa and from ZDV, 3TC, and ddI to d4T, 3TC, and abacavir (ABC). Failure was defined as a plasma HIV-1 RNA level>or=1 log10 above nadir or >or=10,000 copies/mL when nadir was <500 copies/mL. Patients failing therapy before week 48 received the new treatment as in the immediate switching group. Hydroxyurea was added to the last treatment regimen if patients failed after week 96. CD4 count and plasma HIV-1 RNA level (branched DNA assay with a cutoff point of 50 copies/mL) at week 144 were analyzed by intention to treat. Compared with the dual-nucleoside group, the triple-nucleoside group had a higher proportion of patients with <50 copies/mL at 144 weeks (60% vs. 18%; P<0.001), higher median CD4 count (388 cells/microL vs. 346 cells/microL; P=0.018), and longer duration of response, defined as the time from onset of viral suppression (<500 copies/mL) to the time of treatment failure (the first of 2 consecutive HIV-1 RNA measurements >500 copies/mL never followed by 2 consecutive visits showing suppressible viremia to <500 copies/mL) or discontinuation from the study (144 weeks vs. 104 weeks; P=0.002). Multivariate regression analyses showed that significant predictors for treatment success, defined as a plasma viral load <50 copies/mL at week 144, were asymptomatic clinical status at enrollment, a baseline plasma viral load 相似文献   

Management of CMV infection and disease in transplant patients. 27-29 February 2004

The International Herpes Management Forum (IHMF) has published guidelines for the diagnosis and management of cytomegalovirus (CMV) infection and disease in solid organ (SOT) and haematopoietic stem cell transplant (HSCT) recipients. These recommendations have been updated to include, among others: (1) use of whole blood for the polymerase chain reaction (PCR) diagnosis of CMV infection; (2) CMV load measurements for prognostication and for monitoring response to anti-CMV therapy; (3) valganciclovir prophylaxis in CMV donor-positive/recipientnegative (D+/R-) SOT patients for prevention of CMV disease; (4) oral ganciclovir prophylaxis, in preference to aciclovir, to reduce incidence of CMV disease in SOT patients; (5) pre-emptive therapy with oral ganciclovir to reduce incidence of CMV disease and viraemia in liver transplant patients; (6) valaciclovir prophylaxis, in preference to high-dose oral aciclovir, to prevent CMV infection in allogeneic HSCT patients; and (7) foscarnet as an alternative to intravenous ganciclovir for pre-emptive treatment of CMV infection in allogeneic HSCT patients. New developments in the field requiring further research were highlighted, including: optimal frequency of CMV monitoring in CMV D+/R- SOT patients; optimal duration of prophylaxis for the prevention of late CMV disease; need for an acceptable viral threshold for initiation of pre-emptive therapy; and assessment of the clinical efficacy of valganciclovir for the treatment of CMV disease and as pre-emptive therapy in SOT and HSCT patients. This article presents supporting evidence for these recommendations and statements.     

<Emphasis Type="Italic">TCF7L2</Emphasis>variant genotypes and type 2 diabetes risk in Brazil: significant association,but not a significant tool for risk stratification in the general population

Background  

Genetic polymorphisms of the TCF7L2 gene are strongly associated with large increments in type 2 diabetes risk in different populations worldwide. In this study, we aimed to confirm the effect of the TCF7L2 polymorphism rs7903146 on diabetes risk in a Brazilian population and to assess the use of this genetic marker in improving diabetes risk prediction in the general population.