Effects of a communication training for oncologists on early addressing palliative and end-of-life care in advanced cancer care (PALLI-COM): a randomized, controlled trial.

INTRODUCTION: In advanced cancer care, early communication about palliative care (PC) and end-of-life (EoL)-related issues is recommended, but is often impeded by physicians' communication insecurities. We investigated the effect of a newly developed compact communication skills training 'PALLI-COM' on oncologists' competencies to early address PC/EoL-related issues. MATERIALS AND METHODS: We conducted a randomized, controlled trial (RCT) with an intervention group (IG; 2 × 90 min training) and a wait list control group (CG) at five sites. At two assessment points, participating oncologists led videotaped medical consultations with simulated patients (SPs) via a privacy compliant video conference platform. SPs were represented by trained actors. The taped conversations were rated for primary outcome (communication skills assessed by adapted COM-ON-checklist and COM-ON-coaching rating scales) by raters blinded for study group. Secondary outcomes included oncologists' self-reported communication skills (Self-Efficacy in Palliative Care Scale, Thanatophobia-Scale, Communication about End of Life Survey, study-specific items) as well as external rating of the SPs. Univariate analyses of covariance with baseline adjustment were used to analyze intervention effects. RESULTS: A total of 141 oncologists [age: mean (standard deviation) = 32.7 (6.3) years, 60% female (nIG = 73, nCG = 68)] participated. Following intervention, the IG showed significantly more improvement in four out of five assessed communication skills: 'reacting to emotions and showing empathy', 'pointing out opportunities and giving hope', 'addressing the EoL' and 'explaining the concept of PC'. IG participants also improved more than CG participants in almost all secondary outcomes assessed by participants and SPs: oncologists' self-efficacy, attitudes towards caring for terminally ill patients, communication strategies and confidence in dealing with PC/EoL-related issues as well as communication quality from the SPs' perspective. CONCLUSION: Findings indicate that the compact communication skills training PALLI-COM increases oncologists' competencies in early addressing PC/EoL-related issues from different perspectives. Implementation in routine oncology residency might improve advanced cancer care by strengthening these communication skills.

Comparison of unmet health care needs in children with intellectual disability, autism spectrum disorder and both disorders combined.

BACKGROUND: The purpose of this study was to assess the unmet health care needs of children with intellectual disability (ID) compared with children with autism spectrum disorder (ASD) and whether access to health insurance coverage is a contributing factor. Children with ID may be masked in the health care system due to increased diagnosis and awareness of ASD. The needs, unmet needs and insurance coverage of children with ID alone, ASD alone, and co-occurring ID and ASD were assessed in this study. METHODS: The 2016 to 2019 United States' Census Bureau National Survey of Children's Health was used to determine differences in unmet needs, care not received and health insurance coverage during the past year for children with ID and/or ASD. Adjusted odds ratios and 95% confidence intervals for care not received were determined controlling for sex, insurance, race, age and parents' highest education level. RESULTS: Children with ID were nearly four times more likely not to receive needed medical care as children with ASD. Results were similar for unmet hearing and mental health care. Children with both ID and ASD were more likely to have unmet health care but less likely to have unmet medical care compared with children with ASD alone. There were no significant differences for unmet dental or vision care. Children with ID were 3.58 (95% confidence interval: 1.6-8.0) times more likely to have inconsistent health insurance compared with children with ASD. CONCLUSIONS: Children with ID alone are more likely to have unmet medical, hearing and mental health care needs than children with ASD alone. Children with co-occurring ID and ASD have a large amount of general unmet health care needs but less unmet medical needs. Children with ID are less likely to have consistent health insurance than children with ASD. This hinders the ability of children with ID to receive quality care. Further research is needed to determine if the diagnosis of ASD in children in the United States is negatively affecting children with ID alone.

Protein tyrosine phosphatase non-receptor type 22 gene variants at position 1858 are associated with type 1 and type 2 diabetes in Estonian population.

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is considered an important regulator of T-cell activation. Polymorphisms within the PTPN22 gene have been suggested to confer susceptibility to autoimmune endocrine disorders. To evaluate the impact of a functional variation in the PTPN22 gene in type 1 (T1D) and type 2 diabetes (T2D), the PTPN22 C1858T single nucleotide polymorphism (SNP) was studied in the population of Estonian origin, including 170 T1D patients, 244 T2D patients and 230 controls. Using two methods for PTPN22 C1858T detection in parallel, we found that not only T1D but also T2D is associated with the PTPN22 1858T allele. The role of PTPN22 gene in the pathogenesis of T2D is yet unclear and needs further investigation.

Androgen receptor gene haplotype is associated with male infertility.

The purpose of the current study was to evaluate the importance of androgen receptor (AR) gene haplotypes and polymorphic CAG/GGN microsatellites in the aetiology of male infertility. We genotyped six haplotype-tagging single nucleotide polymorphisms and CAG/GGN microsatellites of the AR gene in 112 infertile and 212 control Estonian men. A total of 13 AR haplotypes (HAP1-13) were identified, among which HAP4 was found to confer increased risk for male infertility (OR = 5.15, 95% CI = 1.75-15.15, p = 0.003). However, infertile patients and controls had similar lengths and distributions of both AR CAG (mean +/- SD number of repeats 21.1 +/- 2.5 vs. 21.2 +/- 2.3, respectively) and GGN (mean +/- SD number of repeats 22.5 +/- 1.5 vs. 22.4 +/- 1.9, respectively) repeats. In addition, HAP2 was associated with more CAG repeats (r = 1.17, p = 0.033) and HAP3 with fewer CAG repeats (r = -2.93, p < 0.001) than the major haplotype HAP1. HAP3 and HAP4 were associated with more GGN repeats (r = 1.35, p = 0.001 and r = 1.36, p = 0.002, respectively) than HAP1. In conclusion, our results implicated the AR-HAP4 gene haplotype in increased risk for male infertility, while no association was found between AR CAG/GGN microsatellites and impaired spermatogenesis.

Insulin VNTR I/III genotype is associated with autoantibodies against glutamic acid decarboxylase in newly diagnosed type 1 diabetes.

BACKGROUND: In type 1 diabetes (T1D), the influence of age at diagnosis and of the IDDM1 and IDDM2 genetic susceptibility loci on the profile of beta-cell autoantibodies has been demonstrated. We studied these associations in a group of 92 patients (children, adolescents and adults, aged 2-62 years) with newly diagnosed T1D. METHODS: The prevalence of the HLA-DQB1*02 and *0302 alleles and of the classes of variable number of tandem repeats (VNTR) of the insulin gene (INS), and of beta-cell autoantibodies (GADA, IA-2A, ICA and IAA) was determined. Statistical analysis was performed using linear and logistic regression models. RESULTS: The presence of IAA, IA-2A and ICA, but not of GADA, was negatively associated with age at diagnosis. Younger patients were more likely to have multiple autoantibodies. There was a tendency of a higher prevalence of IAA in patients with the HLA-DQB1*02/0302 genotype or with the DQB1*0302 allele compared to patients lacking these markers. As a novel observation, the INS VNTR I/III genotype was significantly associated with the presence of GADA (OR = 4.79; p = 0.018). CONCLUSION: The association between the INS VNTR I/III genotype and GADA may suggest that in patients with T1D lacking the INS VNTR I/I genotype, the effect of other susceptibility factors prevails, which promotes the development of autoimmunity to beta-cell antigens other than insulin.

Insulin gene VNTR, CTLA-4 +49A/G and HLA-DQB1 alleles distinguish latent autoimmune diabetes in adults from type 1 diabetes and from type 2 diabetes group.

Recent research has underlined the need to explore pathogenic, genetic and clinical spectrum of adult onset autoimmune diabetes, also known as latent autoimmune diabetes in adults (LADA). We aimed to investigate whether genetic factors that are associated with type 1 diabetes (T1D) susceptibility, namely HLA-DQB1 alleles, cytotoxic T-lymphocyte antigen 4 gene (CTLA-4) and insulin gene (INS) polymorphisms, are also associated with an atypical subset of patients diagnosed with type 2 diabetes (T2D). The case-control study included 70 T1D, 305 T2D and 252 nondiabetic controls. The T2D group was divided into atypical T2D (LADA, n = 61) or typical T2D (n = 244) subgroups based on the presence of at least one pancreas-specific antibody. Our data suggested that HLA-DQB1 alleles of all three risk classes, INS variable number of tandem repeat (VNTR) I/I and CTLA-4 +49 GG or AG genotypes, were independent risk factors for developing LADA and could be used as a diagnostic tool to discriminate between LADA and T2D. Additionally, there was an increased association between LADA and CTLA-4 diabetes-susceptibility genotypes and decreased association with INS VNTR and high-risk HLA-DQB1 alleles, compared with T1D. Our study suggested the need for further investigation into the genetic background and functional genomics of LADA in comparison with T1D and T2D.

The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint.

The spindle assembly checkpoint (SAC) guards against chromosomal mis-segregation and the emergence of aneuploidy. SAC in higher eukaryotes includes at least 10 proteins including MAD1-3, BUB1-3, and Msp1. A long-standing observation has been that rodent cells are more tolerant of microtubule toxins than primate cells indicating that SAC function is more relaxed in the former than the latter. Here, we report on an unexpected functional difference between the rodent and human MAD1 component of the respective SAC. Ectopic expression of human MAD1 in mouse and hamster cells corrected a relaxed SAC to a more stringent form. Our findings posit MAD1 as a species-specific determinant which influences the stringency of cellular response to microtubule depolymerization and spindle damage.

Type 1 diabetes is insulin -2221 MspI and CTLA-4 +49 A/G polymorphism dependent.

BACKGROUND: Several studies have demonstrated an association of type 1 diabetes with specific alleles of HLA class II molecules, as with polymorphisms of insulin gene region. The aim of our study was to evaluate the interaction of insulin -2221 MspI polymorphism to type 1 diabetes susceptibility in connection with autoimmunity associated gene--CTLA-4 polymorphism. MATERIALS AND METHODS: Insulin -2221 MspI C/T and CTLA-4 +49 A/G polymorphisms were detected by restriction fragment-length polymorphism analysis or oligonucleotide hybridization in type 1 (n = 69), type 2 diabetes (n = 301) patients and 158 healthy controls. Regression model adjusted for age, gender and gene polymorphisms was studied. RESULTS: C-allele of insulin -2221 MspI and G-allele of +49 CTLA-4 were significant risk factors for type 1 diabetes (crude OR 3.53 and 1.59, respectively) and this impact increased in the homozygous form of both alleles. The regression model supported the idea of insulin CC and CTLA-4 GG genotypes for an independent and clearly significant risk for developing type 1 diabetes. We could not detect any significant correlation between investigated polymorphisms and type 2 diabetes. CONCLUSIONS: There exists a significant association between the C-allele of -2221 MspI in the insulin gene and type 1 diabetes. The CTLA-4 G-allele is also positively correlated with type 1 diabetes. According to the regression model the investigated gene polymorphisms are independent risk factors for development of type 1 diabetes in the Estonian population. We propose that -2221 MspI is a good marker for evaluation of risk of insulin gene haplotype in type 1 diabetes patients.

Evaluation of the culture of safety: survey of clinicians and managers in an academic medical center.

BACKGROUND: Despite the emphasis on patient safety in health care, few organizations have evaluated the extent to which safety is a strategic priority or their culture supports patient safety. In response to the Institute of Medicine's report and to an organizational commitment to patient safety, we conducted a systematic assessment of safety at the Johns Hopkins Hospital (JHH) and, from this, developed a strategic plan to improve safety. The specific aims of this study were to evaluate the extent to which the culture supports patient safety at JHH and the extent to which safety is a strategic priority. METHODS: During July and August 2001 we implemented two surveys in disparate populations to assess patient safety. The Safety Climate Scale (SCS) was administered to a sample of physicians, nurses, pharmacists, and other ICU staff. SCS assesses perceptions of a strong and proactive organizational commitment to patient safety. The second survey instrument, called Strategies for Leadership (SLS), evaluated the extent to which safety was a strategic priority for the organization. This survey was administered to clinical and administrative leaders. RESULTS: We received 395 completed SCS surveys from 82% of the departments and 86% of the nursing units. Staff perceived that supervisors had a greater commitment to safety than senior leaders. Nurses had higher scores than physicians for perceptions of safety. Twenty three completed SLS surveys were received from 77% of the JHH Patient Safety Committee members and 50% of the JHH Management Committee members. Management Committee responses were more positive than Patient Safety Committee, indicating that management perceived safety efforts to be further developed. Strategic planning received the lowest scores from both committees. CONCLUSIONS: We believe this is one of the first large scale efforts to measure institutional culture of safety and then design improvements in health care. The survey results suggest that strategic planning of patient safety needs enhancement. Several efforts to improve our culture of safety were initiated based on these results, which should lead to measurable improvements in patient safety.

Tax-dependent stimulation of G1 phase-specific cyclin-dependent kinases and increased expression of signal transduction genes characterize HTLV type 1-transformed T cells.

Human T cell leukemia virus protein induces T cells to permanent IL-2-dependent growth. These cells occasionally convert to factor independence. The viral oncoprotein Tax acts as an essential growth factor of transformed lymphocytes and stimulates the cell cycle in the G(1) phase. In T cells and fibroblasts Tax enhances the activity of the cyclin-dependent kinases (CDK) CDK4 and CDK6. These kinases, which require binding to cyclin D isotypes for their activity, control the G(1) phase. Coimmunoprecipitation from these cells revealed that Tax associates with cyclin D3/CDK6, suggesting a direct activation of this kinase. The CDK stimulation may account in part for the mitogenic Tax effect, which causes IL-2-dependent T cell growth by Tax. To address the conversion to IL-2-independent proliferation and to identify overexpressed genes, which contribute to the transformed growth, the gene expression patterns of HTLV-1-transformed T cells were compared with that of peripheral blood lymphocytes. Potentially overexpressed cDNAs were cloned, sequenced, and used to determine the RNA expression. Genes found to be up-regulated are involved in signal transduction (STAT5a, cyclin G(1), c-fgr, hPGT) and also glycoprotein synthesis (LDLC, ribophorin). Many of these are also activated during T cell activation and implicated in the regulation of growth and apoptosis. The transcription factor STAT5a, which is involved in IL-2 signaling, was strongly up-regulated only in IL-2-independent cells, thus suggesting that it contributes to factor-independent growth. Thus, the differentially expressed genes could cooperate with the Tax-induced cell cycle stimulation in the maintenance of IL-2-dependent and IL-2-independent growth of HTLV-transformed lymphocytes.

The accuracy of substituted judgments in patients with terminal diagnoses.

BACKGROUND: Patients' loved ones often make end-of-life treatment decisions, but the accuracy of their substituted judgments and the factors associated with accuracy are poorly understood. OBJECTIVE: To assess the accuracy of judgments made by surrogate decision makers; ascertain the beliefs, practices, and clinical and sociodemographic factors associated with accuracy of surrogates' decisions; assess the preferences of patients for life-sustaining treatments; and compare differences in accuracy across diagnoses. DESIGN: Cross-sectional paired interviews. SETTING: Outpatient practices of three university hospitals. PATIENTS: 250 patients with terminal diagnoses of congestive heart failure, AIDS, amyotrophic lateral sclerosis, lung cancer, and chronic obstructive pulmonary disease (50 patient-surrogate pairs in each group) and 50 general medical patients and their surrogates. MEASUREMENTS: The accuracy of surrogate predictions was measured by using scales based on 10 potential treatments in each of three hypothetical clinical scenarios. RESULTS: Preferences varied according to mode of treatment and scenario. On average, surrogates made correct predictions in 66% of instances. Accuracy was better for the permanent coma scenario than for the scenarios of severe dementia or coma with a small chance of recovery (P < 0.001). In a binary logit model, the accuracy of substituted judgments was positively associated with the patient having spoken with the surrogate about end-of-life issues (odds ratio [OR], 1.9 [95% CI, 1.6 to 2.3]), the patient having private insurance (OR, 1.4 [CI, 1.1 to 1.7]), the surrogate's level of education (OR, 1.5 [CI, 1.2 to 1.9]), and the patient's level of education (OR, 1.7 [CI, 1.4 to 2.2]). Accuracy was negatively associated with the patient's belief that he or she would live longer than 10 years (OR, 0.6 [CI, 0.5 to 0.7]), surrogate experience with life-sustaining treatment (OR, 0.4 [CI, 0.3 to 0.5]), surrogate participation in religious services (OR, 0.67 [CI, 0.50 to 0.91]), and a diagnosis of heart failure (OR, 0.6 [CI, 0.5 to 0.8]). Age, ethnicity, marital status, religion, and advance directives were not associated with accuracy. CONCLUSIONS: The accuracy of substituted judgments is associated with multiple clinically apparent patient and surrogate factors. This information can help clinicians identify conditions under which substituted judgments are likely to be accurate or inaccurate and can help target populations for education designed to improve the accuracy of surrogate decision making.

Brefeldin A affects synthesis and integrity of a eukaryotic flagellum.

Eukaryotic flagella and cilia are highly dynamic organelles. In green algae like Chlamydomonas reinhardtii, flagella absorption and resynthesis is a normal process during the vegetative cell cycle. Rapid regeneration also occurs after stress-induced shedding of flagella. Ca2+ ions, protein synthesis, and a kinase activity are the main factors known to affect resynthesis. Recently, we have detected that certain small G proteins (Ypt/Rab) and a GTPase regulator (GDP dissociation inhibitor), known as regulatory elements of intracellular vesicle transport, are present in flagellar membranes of green algae, raising the possibility that the organelle's synthesis and/or integrity depends on functional membrane traffic. In this study, we examined the effect of brefeldin A (BFA), an inhibitor of intracellular membrane flow and Golgi function in animal and plant cells, on flagella regeneration in the colonial green alga Gonium pectorale. We show that low BFA concentrations (< 1 microgram/ml) inhibit flagella out-growth, while higher amounts cause dose-dependent deflagellation and cell death. Our findings provide experimental evidence for a direct connection between intracellular transport and eukaryotic flagella synthesis.