Physicians' communication skills with patients and legal liability in decided medical malpractice litigation cases in Japan

<p>Abstract</p> <p>Background</p> <p>In medical malpractice litigations in recent years in Japan, it is notable that the growing number of medical litigation cases includes the issue of a doctor's explanation to the patient as a pivotal point. The objective of this study was to identify factors of physicians' communication skills with patients, as related to their legal liability, and differences in doctors' communication skills with patients by the type of medical facility.</p> <p>Methods</p> <p>Decisions of medical malpractice litigation cases between 1988 and 2005 in Japan, the pivotal issue of which was a physician's explanation, were analyzed in the study. The content of each decision was summarized using the study variables (information about the patient, doctor, manner of the doctor's explanation, and subsequent litigation), and a database comprising the content of each decision (<it>N </it>= 100) was constructed. In order to evaluate an association between doctors' communication skills with patients and the outcome of the litigation, the analysis was performed based on the outcome of litigation or the type of medical facility.</p> <p>Results</p> <p>The ratio of acknowledged physician liability by court decision was lower in cases in which the doctor's explanation occurred before treatment or surgery (<it>p </it>= 0.013). The ratio of acknowledged physician liability by court decision was higher in cases of elective or non-urgent treatment (<it>p </it>= 0.046). The ratio of acknowledged physician liability by court decision was higher in clinics than in hospital groups (<it>p </it>= 0.036).</p> <p>Conclusion</p> <p>These findings are beneficial for the prevention of medical disputes and improvement of patient-physician communication.</p

High throughput mutagenesis for identification of residues regulating human prostacyclin (hIP) receptor

The human prostacyclin receptor (hIP receptor) is a seven-transmembrane G protein-coupled receptor (GPCR) that plays a critical role in vascular smooth muscle relaxation and platelet aggregation. hIP receptor dysfunction has been implicated in numerous cardiovascular abnormalities, including myocardial infarction, hypertension, thrombosis and atherosclerosis. Genomic sequencing has discovered several genetic variations in the PTGIR gene coding for hIP receptor, however, its structure-function relationship has not been sufficiently explored. Here we set out to investigate the applicability of high throughput random mutagenesis to study the structure-function relationship of hIP receptor. While chemical mutagenesis was not suitable to generate a mutagenesis library with sufficient coverage, our data demonstrate error-prone PCR (epPCR) mediated mutagenesis as a valuable method for the unbiased screening of residues regulating hIP receptor function and expression. Here we describe the generation and functional characterization of an epPCR derived mutagenesis library compromising >4000 mutants of the hIP receptor. We introduce next generation sequencing as a useful tool to validate the quality of mutagenesis libraries by providing information about the coverage, mutation rate and mutational bias. We identified 18 mutants of the hIP receptor that were expressed at the cell surface, but demonstrated impaired receptor function. A total of 38 non-synonymous mutations were identified within the coding region of the hIP receptor, mapping to 36 distinct residues, including several mutations previously reported to affect the signaling of the hIP receptor. Thus, our data demonstrates epPCR mediated random mutagenesis as a valuable and practical method to study the structurefunction relationship of GPCRs. © 2014 Bill et al

Physicians' explanatory behaviours and legal liability in decided medical malpractice litigation cases in Japan

<p>Abstract</p> <p>Background</p> <p>A physician's duty to provide an adequate explanation to the patient is derived from the doctrine of informed consent and the physician's duty of disclosure. However, findings are extremely limited with respect to physicians' specific explanatory behaviours and what might be regarded as a breach of the physicians' duty to explain in an actual medical setting. This study sought to identify physicians' explanatory behaviours that may be related to the physicians' legal liability.</p> <p>Methods</p> <p>We analysed legal decisions of medical malpractice cases between 1990 and 2009 in which the pivotal issue was the physician's duty to explain (366 cases). To identify factors related to the breach of the physician's duty to explain, an analysis was undertaken based on acknowledged breaches with regard to the physician's duty to explain to the patient according to court decisions. Additionally, to identify predictors of physicians' behaviours in breach of the duty to explain, logistic regression analysis was performed.</p> <p>Results</p> <p>When the physician's explanation was given before treatment or surgery (<it>p </it>= 0.006), when it was relevant or specific (<it>p </it>= 0.000), and when the patient's consent was obtained (<it>p </it>= 0.002), the explanation was less likely to be deemed inadequate or a breach of the physician's duty to explain. Patient factors related to physicians' legally problematic explanations were patient age and gender. One physician factor was related to legally problematic physician explanations, namely the number of physicians involved in the patient's treatment.</p> <p>Conclusion</p> <p>These findings may be useful in improving physician-patient communication in the medical setting.</p

Patritumab with Cetuximab plus Platinum-Containing Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: An Open-Label, Phase Ib Study.

Purpose Patritumab plus cetuximab with platinum as first-line therapy for patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) was evaluated for safety and to determine the recommended phase II combination dose.Patients and methods Patients aged ≥18 years with confirmed R/M SCCHN received intravenous patritumab (18 mg/kg loading dose; 9 mg/kg maintenance dose every 3 weeks) + cetuximab (400 mg/m 2 loading dose; 250 mg/m 2 maintenance dose weekly) + cisplatin (100 mg/m 2 every 3 weeks) or carboplatin (AUC of 5) for six cycles or until toxicity, disease progression, or withdrawal. Primary endpoints were dose-limiting toxicities [DLT; grade ≥3 (21-day observation period)] and treatment-emergent adverse events (TEAE). Pharmacokinetics, human antihuman antibodies (HAHA), tumor response, progression-free survival (PFS), and overall survival (OS) were assessed.Results Fifteen patients completed a median (range) of 8.7 (2.0-20.7) patritumab cycles. No DLTs were reported. Serious adverse events were reported in 9 patients (patritumab-related n = 4). TEAEs ( N = 15 patients) led to patritumab interruption in 7 patients. Patritumab-related dose reductions were reported in 1 patient. Patritumab (18 mg/kg) pharmacokinetics ( N = 15) showed mean (SD) AUC 0-21d of 2,619 (560) μg/day/mL and maximum concentration of 499.9 (90.4) μg/mL. All patients were HAHA-negative at study end (single, transient low titer in 1 patient). Tumor response rate (complete plus partial response; N = 15) was 47%. Median (95% confidence interval) PFS and OS ( N = 15) were 7.9 (3.7-9.7) and 13.5 (6.6-17.5) months, respectively.Conclusions Patritumab (18 mg/kg loading dose, 9 mg/kg maintenance dose) plus cetuximab/platinum was tolerable, active in SCCHN, and selected as the phase II dose regimen

The state of the art: immune-mediated mechanisms of monoclonal antibodies in cancer therapy

A number of antibody products have now become accepted as effective anti-cancer therapies. Despite being mainly designed to act by inhibiting functional tumour antigens, there is increasing evidence that Fc-mediated engagement of the immune system is an important contributor to the efficacy of several of these therapies. The optimisation of this engagement offers the potential not only to augment efficacy against existing targets, but also to exploit non-functional tumour antigens. Antibodies that achieve efficacy wholly or predominantly through Fc-mediated mechanisms, represent rich opportunities for future therapeutics in oncology. This mini review summarises some of the key challenges, which need to be addressed to select the most effective molecules. These include the identification of optimal antibody characteristics and improvement of the drug discovery process, in particular, the relevance and predictive power of existing in vitro and in vivo screening methods. Advances in our understanding of tumour immunobiology and successful application of technologies designed to enhance immune system engagement will further aid this process

Comparative SNP and Haplotype Analysis Reveals a Higher Genetic Diversity and Rapider LD Decay in Tropical than Temperate Germplasm in Maize

Understanding of genetic diversity and linkage disequilibrium (LD) decay in diverse maize germplasm is fundamentally important for maize improvement. A total of 287 tropical and 160 temperate inbred lines were genotyped with 1943 single nucleotide polymorphism (SNP) markers of high quality and compared for genetic diversity and LD decay using the SNPs and their haplotypes developed from genic and intergenic regions. Intronic SNPs revealed a substantial higher variation than exonic SNPs. The big window size haplotypes (3-SNP slide-window covering 2160 kb on average) revealed much higher genetic diversity than the 10 kb-window and gene-window haplotypes. The polymorphic information content values revealed by the haplotypes (0.436–0.566) were generally much higher than individual SNPs (0.247–0.259). Cluster analysis classified the 447 maize lines into two major groups, corresponding to temperate and tropical types. The level of genetic diversity and subpopulation structure were associated with the germplasm origin and post-domestication selection. Compared to temperate lines, the tropical lines had a much higher level of genetic diversity with no significant subpopulation structure identified. Significant variation in LD decay distance (2–100 kb) was found across the genome, chromosomal regions and germplasm groups. The average of LD decay distance (10–100 kb) in the temperate germplasm was two to ten times larger than that in the tropical germplasm (5–10 kb). In conclusion, tropical maize not only host high genetic diversity that can be exploited for future plant breeding, but also show rapid LD decay that provides more opportunity for selection

Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

BACKGROUND: It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. METHODS: To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. RESULTS: Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. CONCLUSIONS: Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones

Evaluation of in-stent restenosis in the APPROACH trial (assessment on the prevention of progression by Rosiglitazone on atherosclerosis in diabetes patients with cardiovascular history)

To determine (1) the medium-term effect of rosiglitazone and glipizide on intra-stent neointima hyperplasia, (2) restenosis pattern as assessed by intra-vascular ultrasound (IVUS) and quantitative coronary angiography (QCA) in patients with T2DM and coronary artery disease. A total of 462 patients with T2DM were randomized to rosiglitazone or glipizide for up to 18 months in the APPROACH trial, and had evaluable baseline and follow-up IVUS examinations. There was no significant difference in the size of plaque behind stent between the rosiglitazone and glipizide groups at 18 months among those treated with a bare metal stent (−5.6 mm3 vs. 1.9 mm3; P = 0.61) or with a drug-eluting stent (12.1 mm3 vs. 5.5 mm3; P = 0.09). Similarly, there was no significant difference in percentage intimal hyperplasia volume between the rosiglitazone and glipizide groups at 18 months among those treated with a bare metal stent (24.1% vs. 19.8%; P = 0.38) or with a drug-eluting stent (9.8% vs. 8.3%; P = 0.57). QCA data (intra-stent late loss, intra-stent diameter stenosis or binary restenosis) were not different between the rosiglitazone and glipizide groups. This study suggests that both rosiglitazone and glipizide have a similar effect on neointimal growth at medium term follow-up, a finding that warrants investigation in dedicated randomized trials

Clonal mutations in primary human glial tumors: evidence in support of the mutator hypothesis

<p>Abstract</p> <p>Background</p> <p>A verifiable consequence of the mutator hypothesis is that even low grade neoplasms would accumulate a large number of mutations that do not influence the tumor phenotype (clonal mutations). In this study, we have attempted to quantify the number of clonal mutations in primary human gliomas of astrocytic cell origin. These alterations were identified in tumor tissue, microscopically confirmed to have over 70% neoplastic cells.</p> <p>Methods</p> <p>Random Amplified Polymorphic DNA (RAPD) analysis was performed using a set of fifteen 10-mer primers of arbitrary but definite sequences in 17 WHO grade II astrocytomas (low grade diffuse astrocytoma or DA) and 16 WHO grade IV astrocytomas (Glioblastoma Multiforme or GBM). The RAPD profile of the tumor tissue was compared with that of the leucocyte DNA of the same patient and alteration(s) scored. A quantitative estimate of the overall genomic changes in these tumors was obtained by 2 different modes of calculation.</p> <p>Results</p> <p>The overall change in the tumors was estimated to be 4.24% in DA and 2.29% in GBM by one method and 11.96% and 6.03% in DA and GBM respectively by the other. The difference between high and lower grade tumors was statistically significant by both methods.</p> <p>Conclusion</p> <p>This study demonstrates the presence of extensive clonal mutations in gliomas, more in lower grade. This is consistent with our earlier work demonstrating that technique like RAPD analysis, unbiased for locus, is able to demonstrate more intra-tumor genetic heterogeneity in lower grade gliomas compared to higher grade. The results support the mutator hypothesis proposed by Loeb.</p