The Ethics of Promoting Living Kidney Donation Using Nonargumentative Influence: Applications, Concerns, and Future Directions.

Recommendations from the 2014 Consensus Conference on Best Practices in Living Kidney Donation reflect increasing attention to overcoming barriers to donation as a means of expanding access to living donor kidney transplantation. "High priority" initiatives include empowering transplant candidates and their loved ones in their search for a living kidney donor. Transplant programs are assuming an unprecedented role as facilitators of patients' solicitation for donors, and nonprofits are promoting living kidney donation (LKD) in the community. New strategies to promote LKD incorporate "nonargumentative" forms of influence (i.e. approaches to shaping behavior that do not attempt to persuade through reason) such as appeals to emotion, messenger effects and social norms. These approaches have raised ethical concerns in other settings but have received little attention in the transplantation literature despite their increasing relevance. Previous work on using nonargumentative influence to shape patient behavior has highlighted implications for (1) the relationship between influencer and influenced and (2) patient autonomy. We argue that using nonargumentative influence to promote LKD is a promising strategy that can be compatible with ethical standards. We also outline potential concerns and solutions to be implemented in practice.

Donor Hemodynamics as a Predictor of Outcomes After Kidney Transplantation From Donors After Cardiac Death.

Donation after cardiac death is an important source of transplantable organs, but evidence suggests donor warm ischemia contributes to inferior outcomes. Attempts to predict recipient outcome using donor hemodynamic measurements have not yielded statistically significant results. We evaluated novel measures of donor hemodynamics as predictors of delayed graft function and graft failure in a cohort of 1050 kidneys from 566 donors. Hemodynamics were described using regression line slopes, areas under the curve, and time beyond thresholds for systolic blood pressure, oxygen saturation, and shock index (heart rate divided by systolic blood pressure). A logistic generalized estimation equation model showed that area under the curve for systolic blood pressure was predictive of delayed graft function (above median: odds ratio 1.42, 95% confidence interval [CI] 1.06-1.90). Multivariable Cox regression demonstrated that slope of oxygen saturation during the first 10 minutes after extubation was associated with graft failure (below median: hazard ratio 1.30, 95% CI 1.03-1.64), with 5-year graft survival of 70.0% (95%CI 64.5%-74.8%) for donors above the median versus 61.4% (95%CI 55.5%-66.7%) for those below the median. Among older donors, increased shock index slope was associated with increased hazard of graft failure. Validation of these findings is necessary to determine the utility of characterizing donor warm ischemia to predict recipient outcome.

What are the harms of refusing to allow living kidney donation? An expanded view of risks and benefits.

Recent Organ Procurement and Transplantation Network policies relating to living kidney donation (LKD)warrant renewed attention to the ethics of transplantation from living donors. These policies focus on risks related to potential donor evaluation, informed consent and follow-up. The ethical basis of living donation is a favorable risk/benefit ratio for the donor, but regulations and research have given less attention to the benefits of donation. Relatedly, the transplant field has also failed to consider potential harms from denying patients the opportunity to donate. These harms may be substantial in the setting of directed kidney donation to a spouse/partner, sibling or child.We argue that complete assessment of donor risks and benefits demands consideration of not only the risks and benefits of donation, but also those of refusing a donor. In contrast to the ever-expanding literature on risks of donation, there are no data describing outcomes for individuals who were turned down as kidney donors. We consider factors contributing to this omission in the transplant literature, argue that current regulations may perpetuate a narrow understanding of relevant risks and benefits in LKD, and identify areas for improvement in research and clinical practice.

WUS and STM-based reporter genes for studying meristem development in poplar.

We describe the development of a reporter system for monitoring meristem initiation in poplar using promoters of poplar homologs to the meristem-active regulatory genes WUSCHEL (WUS) and SHOOTMERISTEMLESS (STM). When ~3 kb of the 5' flanking regions of close homologs were used to drive expression of the GUSPlus gene, 50-60% of the transgenic events showed expression in apical and axillary meristems. However, expression was also common in other organs, including in leaf veins (40 and 46% of WUS and STM transgenic events, respectively) and hydathodes (56% of WUS transgenic events). Histochemical GUS staining of explants during callogenesis and shoot regeneration using in vitro stems as explants showed that expression was detectable prior to visible shoot development, starting 3-15 days after explants were placed onto callus inducing medium. A minority of WUS and STM events also showed expression in the cambium, phloem, or xylem of regenerated, greenhouse grown plants undergoing secondary growth. Based on microarray gene expression data, a paralog of poplar WUS was detectably up-regulated during shoot initiation, but the other paralog was not. Both paralogs of poplar STM were down-regulated threefold to sixfold during early callus initiation. We identified 15-35 copies of cytokinin response regulator binding motifs (ARR1AT) and one copy of the auxin response element (AuxRE) in both promoters. Several of the events recovered may be useful for studying the process of primary and secondary meristem development, including treatments intended to stimulate meristem development to promote clonal propagation and genetic transformation.

Reproducibility of bronchodilator response for a reservoir dry powder inhaler following routine clinical use.

The performance of dry powder inhaler (DPI) devices, particularly reservoir DPIs, may be influenced by environmental conditions. This study compared the bronchodilator efficacy and in vitro aerosol characteristics of salbutamol, delivered via a novel reservoir DPI (Clickhaler) and a conventional pressurized metered-dose inhaler (MDI) before and after use of the DPI in clinical practice. Following a screening visit, patients received cumulative doses of salbutamol (100, 200, and 400 microg) via DPI or MDI on separate days in a double-blind, crossover design before and after a 4-week period, during which the DPI was used as the patients' first-line bronchodilator. Lung function responses (forced expiratory volume in 1 sec [FEV1], forced vital capacity [FVC], and peak expiratory flow [PEF]) to salbutamol delivered by DPI and MDI and in vitro aerosol characteristics were not significantly different before and after the period of DPI patient use. DPI performance, assessed in vivo and in vitro, is maintained following an extended period of patient use.

General practice spirometry in North Staffordshire.

Spirometry is suggested, in North American and European guidelines, to be the most important measurement of lung function for the management of patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to determine attitudes to and utilization of spirometry in general practices within North Staffordshire. All 95 practices in North Staffordshire were surveyed by telephone, using a standard proforma. Eighty-four practices (48 fundholding) containing 224 general practitioners (GPs) and serving 472,420 patients, agreed to take part. The survey was completed by practice nurses on 63 occasions, GPs on 14 and practice managers on seven. Eighteen practices possessed a spirometer, although eight did not use it. The measurements were performed by doctors in five of the practices, nurses in two and by both in three. Only two users had received formal training in the performance and interpretation of spirometry. Of the three practices using pneumotachograph spirometers, none knew how often the machine should be calibrated. Spirometry was used by five practices for diagnosis (although only four used it to determine forced expiratory volume in one second (FEV1)), three for monitoring and only one for bronchodilator reversibility testing. Although 44 (52%) practices thought that, ideally, spirometry should be available in the practice, only 10 of the 18 who had spirometers were currently providing this facility. Furthermore, the poor training puts into question the validity of some of the results obtained. Open access to hospital spirometry is one method of addressing these problems, and 73 (87%) practices, including 16 who already owned a spirometer, said that they would use such a service.

Pulmonary toxicity of cardiac drugs.

Pulmonary damage caused by the undesired effects of cardiac drugs is being increasingly recognized. With the symptoms of breathlessness, wheeze, cough and hemoptysis common to both cardiac and respiratory diseases, an adverse pulmonary reaction to a cardiac drug may be mistakenly attributed to deterioration of cardiac status. This is especially true if the onset of symptoms are subacute or chronic. The pulmonary side effects of cardiac drugs are varied and may actually mimic the disease being treated. It is essential that the clinician remain highly suspicious that new and unexplained pulmonary symptoms and signs may be drug-related. Most of the side effects are reversible with early drug cessation and subsequent challenge should be avoided if possible.

Compliance with oral corticosteroids during steroid trials in chronic airways obstruction.

BACKGROUND: Corticosteroid trials are an important part of the assessment of patients with chronic airways obstruction, but false negative results will occur if the treatment is not taken. To determine compliance low dose phenobarbitone has been used as a marker. METHODS: Thirty six patients referred to a chest clinic for assessment of their airways obstruction were studied. They were instructed to take eight capsules (each containing 5 mg prednisolone and 0.5 mg phenobarbitone) per day for two weeks. The response was assessed by home peak flow monitoring and clinic spirometric tests. Plasma phenobarbitone levels were measured after the trial to enable calculation of the dose to plasma concentration ratio (level to dose ratio, LDR) and the result was compared with the reference range for fully compliant individuals. RESULTS: Five patients defaulted from follow up, 23 had LDR values within the expected range, and eight had low LDR values consistent with poor compliance. The nine patients with steroid responsive disease (> 20% improvement in peak flow or spirometric parameters) all had LDR values in the expected range. CONCLUSION: Excluding those who defaulted whose compliance must be questionable, eight (26%) patients did not fully comply with the steroid trial. Not all patients who fail to respond to a two week home steroid trial have a steroid "unresponsive" disease.

Low incidence of red cell and HLA antibody formation by bone marrow transplant patients.

BACKGROUND: Bone marrow transplant (BMT) patients, although immunosuppressed, are at risk for the development of red cell (RBC) and HLA antibodies, and they often are given filtered blood in an effort to prevent the latter complication. This study attempts to determine the rate of formation and the specificity of both RBC and HLA alloantibodies in this patient population. STUDY DESIGN AND METHODS: BMT patients (148 received autologous marrow; 45 received allogeneic marrow) from an 18-month period, including patients with leukemia (57 patients), lymphoma (54), breast cancer (68), myeloma (8), myelodysplastic syndrome (5), and aplastic anemia (1), were studied to determine the rate of alloantibody formation to RBC and HLA antigens. A total of 2,410 RBC antibody screens were performed. The patients received 3,921 packed RBCs and 5,915 single-donor platelet units; all were irradiated and administered via white cell-reduction filters. RESULTS: Seven (3.6%) of 193 patients had RBC antibodies upon hospital admission. Four (2.1%) of 193 developed RBC antibodies during the course of BMT: 3 patients had one RBC antibody and 1 patient had two RBC antibodies. RBC antibodies included anti-E (n = 2), anti-M (n = 1), anti-Jkb (n = 1), and anti-Lu14 (n = 1). Thus, 98 percent of patients (189/193) did not develop new (182/186) or additional (7/7) RBC antibodies during BMT. BMT patients were also screened weekly for HLA antibody formation (60-cell panel). Upon admission, 170 (85%) patients were negative. Of these, 8 (4.7%) developed persistent HLA antibodies (mean panel-reactive antibody score, 33 +/- 29%) and 9 (5.3%) were variably positive. Thus, in our setting and population, RBC antibody formation was 0.1 percent per unit transfused, and the HLA alloimmunization rate was 5 to 10 percent. CONCLUSION: As RBC antibody screens are done every Monday, Wednesday, and Friday on this BMT service and as RBC antibody formation is low in these patients, screening for unexpected antibodies might be possible on a more infrequent basis. Also, the rate of HLA alloimmunization in this population receiving filtered blood components is low.

Childhood cancer in Britain: the National Registry of Childhood Tumours and incidence rates 1978-1987.

The National Registry of Childhood Tumours contains population-based data on childhood cancers diagnosed throughout Great Britain from 1962 onwards. This paper describes the methodology of the Registry, presents incidence rates for 1978-1987 and describes other uses of the data. Total age-standardised annual incidence was 118.3 per million. The most frequent diagnostic groups were leukaemias (age-standardised rate 39.8), brain and spinal tumours (27.0), lymphomas (11.1), sympathetic nervous system tumours (8.3), kidney tumours (7.7) and soft-tissue sarcomas (7.5). Incidence rates were similar to those reported from other Western industrialised countries. The data are also used for a wide range of epidemiological and other studies. These include analyses of geographical variations in incidence, trends in survival, health of long-term survivors and their offspring and the genetics of childhood cancer. Information is frequently provided for clinicians and research workers, and series of specific types of cancer are compiled for further study. The Registry depends for the completeness and accuracy of its data on a wide range of organisations and individuals, and it is essential that this cooperation continues if the Registry is to be maintained.