Parent-Child Communication Incongruence in Pediatric Healthcare.

Parents play a key role in providing children with health-related information and emotional support. This communication occurs both in their homes and in pediatric healthcare environments, such as hospitals, outpatient clinics, and primary care offices. Often, this occurs within situations entailing heightened stress for both the parent and the child. There is considerable research within the communication literature regarding the nature of both verbal and nonverbal communication, along with the way in which these communication modalities are either similar (i.e., congruent) or dissimilar (i.e., incongruent) to one another. However, less is known about communication congruency/incongruency, specifically in parent-child relationships, or within healthcare environments. In this narrative review, we explore the concept of verbal and nonverbal communication incongruence, specifically within the context of parent-child communication in a pediatric healthcare setting. We present an overview of verbal and nonverbal communication and propose the Communication Incongruence Model to encapsulate how verbal and nonverbal communication streams are used and synthesized by parents and children. We discuss the nature and possible reasons for parental communication incongruence within pediatric settings, along with the consequences of incongruent communication. Finally, we suggest a number of hypotheses derived from the model that can be tested empirically and used to guide future research directions and influence potential clinical applications.

Let Nature Take Its Course: Cultural Adaptation and Pilot Test of Taoist Cognitive Therapy for Chinese American Immigrants With Generalized Anxiety Disorder.

This report describes initial results from a multi-stage project to manualize and adapt an indigenous therapy, Chinese Taoist Cognitive Psychotherapy (CTCP), for dissemination in the United States context. Study aims were to (a) integrate cultural adaptation and implementation science frameworks to manualize and adapt the original intervention and (b) explore the feasibility, acceptability, and effectiveness of the modified intervention, renamed Taoist Cognitive Therapy (TCT), in a sample of Chinese immigrants with generalized anxiety disorder (GAD). Incorporating bottom-up and top-down adaptation approaches, we involved Chinese American clinician stakeholders and experts in Taoist philosophy, cognitive-behavioral therapy, and GAD to help identify cultural and contextual barriers and solutions to enhance treatment acceptability and implementation. Five treatment-seeking Chinese American immigrants (average age = 43.2 years) with a primary diagnosis of GAD completed 14-16 sessions of TCT. Two participants also had secondary diagnoses of major depressive disorder. Changes on primary measures of worry and anxiety were assessed for statistical and clinical significance using reliable change indices (RCIs; Jacobson and Truax, 1991) and comparisons to normative data. In this sample of patients with limited prior exposure to Taoism, results found evidence of feasibility and acceptability of the modified intervention, with strong endorsement of Taoist principles at termination. Statistically and clinically significant improvements in anxiety, worry, psychological inflexibility, and emotional avoidance were found only for the participants without comorbid depression. Results suggest that Taoist principles of acceptance and flexible adaptation to natural laws may be helpful to Chinese immigrants coping with anxiety. However, additional treatment modifications may be required to address the low self-efficacy and fatalism expressed among those with comorbid depression.

Kinetics of maternal pertussis-specific antibodies in infants of mothers vaccinated with tetanus, diphtheria and acellular pertussis (Tdap) during pregnancy.

BACKGROUND: Kinetics of Tdap-induced maternally-derived antibodies in infants are poorly understood. Pre-Tdap era data suggest that maternal pertussis antibodies in infants have a half-life of approximately 5-6 weeks. METHODS: 34 mother-infant pairs had blood collected before maternal Tdap vaccination, 4 weeks later, at delivery (maternal and cord), and at infant ages 3 and 6 weeks from June 2014-March 2015. Immunoglobulin G (IgG) to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbrial proteins (FIM) and pertactin (PRN) was quantified by multiplex luminex assay (IU/ml). Geometric mean concentrations (GMCs) with 95% confidence intervals (C.I.) and half-life of pertussis antibodies were calculated. RESULTS: Tdap was administered to 34 women (mean age 31.1 years) at mean gestation 30.7 weeks (28-32.7). Mean neonatal gestation was 39.1 weeks (36-41.1) and mean birthweight was 3379 g (2580-4584). Four weeks post-Tdap vaccination, maternal pertussis-specific IgG GMCs increased ≥4-fold in 59%, 41%, 29% and 44% of women for PT, FHA, FIM and PRN, respectively, and then waned. The transplacental transport ratio of pertussis antibodies was 1.35 for PT, 1.41 for FHA, 1.31 for FIM and 1.36 for PRN. Between birth and age 6 weeks, infant serum GMC for PT-specific IgG decreased from 55.1 IU/mL (38.6-78.6) to 21.1 IU/ml (14.7-30.2), and the proportion of infants with PT levels ≥10 IU/ml fell from 97% to 67%. Half-life of pertussis-specific IgG in infants in days was 29.4 (95% CI 27.3-31.7) for PT, 29.8 (95% CI 27.7-32.2) for FHA, 31.2 (95% CI 28.9-33.7) for PRN, and 35.8 (95% CI 30.1-44.3) for FIM. CONCLUSION: The half-life of pertussis-specific antibodies in infants induced by maternal Tdap vaccination (29-36 days) is shorter than previously reported. Understanding how the durability of passively-acquired antibodies impacts infant susceptibility to pertussis and response to primary vaccination is critical to refine prevention strategies.

A systematic review of the effects of advance care planning facilitators training programs.

BACKGROUND: Advance care planning (ACP) is the process of ongoing communication among patients, family and health care professionals regarding what plans for future care are preferred in the event that patients become unable to make their own decisions. Clinicians play an important role in ACP as both initiators and decision coaches. However, lack of training for clinicians has frequently been reported as the reason for low involvement in ACP discussions - hence the present review evaluates the effectiveness of ACP training programs for healthcare professionals to guide the development of novel training programs for them in the future. METHODS: A literature search for intervention studies was conducted independently by two reviewers in July 2018. Participants included all healthcare professionals working with adult patients suffering from terminal illness. The primary outcomes were the professionals' knowledge of and attitudes towards ACP, and self-perceived competence in ACP conversations. The Effective Public Health Practice Project appraisal tool was used to examine the quality of the studies included. RESULTS: A total of 4025 articles were identified, and ten eligible articles, covering 1081 participants, were included in the review. However, there is a lack of high quality randomized controlled trials of providing ACP training for nurses working in non-palliative care hospital settings. The overall quality of the intervention studies was moderate. All the studies included used instructional sessions in their interventions, while some contained group discussion, role-play and the use of advanced technology. The training programs increased the knowledge, attitudes towards shared decision-making, perceived communication skills, confidence, comfort and experiences concerned with discussing end-of-life (EOL) issues. Patient advocacy, job satisfaction and perceived level of adequate training for EOL care were improved. The use of 'decision aids' was rated as acceptable and clinically useful. CONCLUSIONS: Training for healthcare professionals in ACP has positive effects on their knowledge, attitude and skills. The use of decision aids and advanced technology, instructional sessions with role play, training content focused on ACP communication skills and the needs and experience of patient in the ACP process, and a values-based ACP process are all those factors that made the ACP training programs effective.

Cost-effectiveness of a transitional home-based palliative care program for patients with end-stage heart failure.

BACKGROUND: Studies have shown positive clinical outcomes of specialist palliative care for end-stage heart failure patients, but cost-effectiveness evaluation is lacking. AIM: To examine the cost-effectiveness of a transitional home-based palliative care program for patients with end-stage heart failure patients as compared to the customary palliative care service. DESIGN: A cost-effectiveness analysis was conducted alongside a randomized controlled trial (Trial number: NCT02086305). The costs included pre-program training, intervention, and hospital use. Quality of life was measured using SF-6D. SETTING/PARTICIPANTS: The study took place in three hospitals in Hong Kong. The inclusion criteria were meeting clinical indicators for end-stage heart failure patients including clinician-judged last year of life, discharged to home within the service area, and palliative care referral accepted. A total of 84 subjects (study = 43, control = 41) were recruited. RESULTS: When the study group was compared to the control group, the net incremental quality-adjusted life years gain was 0.0012 (28 days)/0.0077 (84 days) and the net incremental costs per case was -HK$7935 (28 days)/-HK$26,084 (84 days). The probability of being cost-effective was 85% (28 days)/100% (84 days) based on the cost-effectiveness thresholds recommended both by National Institute for Health and Clinical Excellence (£20,000/quality-adjusted life years) and World Health Organization (Hong Kong gross domestic product/capita in 2015, HK$328117). CONCLUSION: Results suggest that a transitional home-based palliative care program is more cost-effective than customary palliative care service. Limitations of the study include small sample size, study confined to one city, clinic consultation costs, and societal costs including patient costs and unpaid care-giving costs were not included.

Effects of a transitional palliative care model on patients with end-stage heart failure: a randomised controlled trial.

OBJECTIVE: To examine the effects of home-based transitional palliative care for patients with end-stage heart failure (ESHF) after hospital discharge. METHODS: This was a randomised controlled trial conducted in three hospitals in Hong Kong. The recruited subjects were patients with ESHF who had been discharged home from hospitals and referred for palliative service, and who met the specified inclusion criteria. The interventions consisted of weekly home visits/telephone calls in the first 4 weeks then monthly follow-up, provided by a nurse case manager supported by a multidisciplinary team. The primary outcome measures were any readmission and count of readmissions within 4 and 12 weeks after index discharge, compared using χ(2) tests and Poisson regression, respectively. Secondarily, change in symptoms over time between control and intervention groups were evaluated using generalised estimating equation analyses of data collected using the Edmonton Symptom Assessment Scale (ESAS). RESULTS: The intervention group (n=43) had a significantly lower readmission rate than the control group (n=41) at 12 weeks (intervention 33.6% vs control 61.0% χ(2)=6.8, p=0.009). The mean number (SE) of readmissions for the intervention and control groups was, respectively, 0.42 (0.10) and 1.10 (0.16) and the difference was significant (p=0.001). The relative risk (CI) for 12-week readmissions for the intervention group was 0.55 (0.35 to 0.88). There was no significant difference in readmissions between groups at 4 weeks. However, when compared with the control group, the intervention group experienced significantly higher clinical improvement in depression (45.9% vs 16.1%, p<0.05), dyspnoea (62.2% vs 29.0%, p<0.05) and total ESAS score (73.0% vs 41.4%, p<0.05) at 4 weeks. There were significant differences between groups in changes over time in quality of life (QOL) measured by McGill QOL (p<0.05) and chronic HF (p<0.01) questionnaires. CONCLUSIONS: This study provides evidence of the effectiveness of a postdischarge transitional care palliative programme in reducing readmissions and improving symptom control among patients with ESHF. TRIAL REGISTRATION NUMBER: HKCTR-1562; Results.

Knowledge and attitiudes of pregnant women and their providers towards recommendations for immunization during pregnancy.

OBJECTIVES: Tetanus, diphtheria and acellular pertussis (Tdap) and influenza vaccination is recommended during each pregnancy but uptake is suboptimal. We evaluated knowledge and acceptance of vaccination recommendations among pregnant women. METHODS: Prospective, convenience survey of pregnant women presenting for antenatal care at the Pavilion for Women, Texas Children's Hospital, Houston, and their healthcare providers. RESULTS: 796 of 825 (96.5%) of women and 63 of 87 (72.4%) providers completed surveys. Mean age of pregnant women was 30.2 (18-45) years. Self-identified race/ethnicity was 45% white, 26% Hispanic, 13% black, 12% Asian and 4% other. Most women had college degrees (84%) and private health insurance (83%). Mean gestation was 28.5 weeks with 4.8%, 37.8% and 57.4%, in the 1st, 2nd and 3rd trimesters, respectively. Women used various sources for pregnancy information (personal contacts, providers, print, audiovisual and online media) but 89.1% cited a provider as their most trusted source, predominantly (85.8%) their physician. 668 (84%) knew vaccines are recommended during pregnancy, specifically influenza (77%) and Tdap (61%) vaccines. 659 (83%) were willing to receive vaccines if recommended by their physician. Factors impacting vaccination decisions included safety for baby, safety for mother and sufficient information, scoring 4.7, 4.5 and 4.2, respectively, on a 5-point scale; less important were additional visit time (2.6), cost (1.9) or needle phobia (1). Women surveyed in the 3rd trimester showed greater acceptance than those earlier in gestation (87% vs 78%; P0.003). Maternal education, ethnicity, insurance, multiple gestation or history of serious illness in a prior infant did not affect willingness to receive vaccines. CONCLUSIONS: Pregnant women are willing to accept vaccination in pregnancy if recommended by their physician and if sufficient discussion of safety and rationale occurs. Strong physician recommendation, as reported for pediatric vaccination, is essential to optimizing uptake of vaccines during pregnancy.

Tetanus and diphtheria toxoids and acellular pertussis vaccine uptake during pregnancy in a metropolitan tertiary care center.

OBJECTIVES: Tetanus, diphtheria and acellular pertussis (Tdap) vaccine is recommended during each pregnancy, but national uptake is poor. We assessed Tdap uptake in a tertiary referral hospital served by university-affiliated and private obstetrical offices. METHODS: Review of women delivering at Texas Children's Hospital Pavilion for Women, Houston, Texas, during April 2013-June 2014. RESULTS: 6577 deliveries occurred during the study period. Mean maternal age was 29.8 years (range 13-49); race/ethnicity was 43.6% White, 27% Hispanic, 21% Black, 7.1% Asian, and 1.3% other. 252 were multiple gestations; 229 sets of twins, 21 triplets and 2 quadruplets. 3678 (56%) women received Tdap during pregnancy, 249 (3.8%) postpartum and 100 (1.5%) received Tdap pre-conception only. Tdap uptake during pregnancy increased from 36% in April 2013 to a sustained uptake of greater than 61% since November 2013, with increases noted coincidental with presentations highlighting Tdap maternal immunization recommendations at faculty and staff meetings, and the release of the ACOG "toolkit". When antenatal Tdap vaccine was administered, mean gestation at receipt of Tdap was 31.4 weeks and 95% of vaccinated women received Tdap at the recommended gestation interval of 27-36 weeks, 71.6% during the 28-32 week window believed optimal for placental transport and 98.5% at least 7 days before delivery. Of 19 women with two pregnancies during the study period, four (21%) had Tdap during both. Black women were less likely to receive antenatal Tdap than women of other race/ethnicity (41% versus 60%; P<0.001). CONCLUSIONS: Sustained antenatal Tdap uptake rates exceeding 61% were achieved after strategies to increase awareness of recommendations were introduced and 95% of women were immunized at a gestation optimal for efficient maternal antibody placental transport. Further increases in uptake will require system changes such as best practice alerts in electronic medical records.

Cyclin D1 is a direct target of JAG1-mediated Notch signaling in breast cancer.

The Notch ligand, JAG1 is associated with breast cancer recurrence. Herein, we report on a genomics approach to elucidate mechanisms downstream of JAG1 that promote breast cancer growth. In a survey of 46 breast cancer cell lines, we found that triple negative (TN; basal and mesenchymal ER-, PR-, and Her2-negative) lines express JAG1 at significantly higher levels than do HER2(+) or luminal (ER(+)) Her2(-) cell lines. In contrast to the luminal lines tested (T47D and MCF7), TN breast cancer cell lines (HCC1143 and MDA MB231) display high-level JAG1 expression and growth inhibition with RNA interference-induced JAG1 down-regulation. We used microarray profiling of TN tumor cells transfected with JAG1 siRNA to identify JAG1-regulated genes (P or=1.5). Among JAG1-regulated genes identified, cyclin D1 was found to be a direct target of NOTCH1 and NOTCH3. We show that JAG1 down-regulation reduces direct binding of Notch to the cyclin D1 promoter, reduced cyclin D1 expression and inhibition of cell cycle progression through the cyclin D1-dependant G1/S checkpoint. Furthermore, we show that cyclin D1 and JAG1 expression correlate in TN breast cancer expression datasets. These data suggest a model whereby JAG1 promotes cyclin D1-mediated proliferation of TN breast cancers.

Design and analysis of quantitative differential proteomics investigations using LC-MS technology.

Liquid chromatography-mass spectrometry (LC-MS)-based proteomics is becoming an increasingly important tool in characterizing the abundance of proteins in biological samples of various types and across conditions. Effects of disease or drug treatments on protein abundance are of particular interest for the characterization of biological processes and the identification of biomarkers. Although state-of-the-art instrumentation is available to make high-quality measurements and commercially available software is available to process the data, the complexity of the technology and data presents challenges for bioinformaticians and statisticians. Here, we describe a pipeline for the analysis of quantitative LC-MS data. Key components of this pipeline include experimental design (sample pooling, blocking, and randomization) as well as deconvolution and alignment of mass chromatograms to generate a matrix of molecular abundance profiles. An important challenge in LC-MS-based quantitation is to be able to accurately identify and assign abundance measurements to members of protein families. To address this issue, we implement a novel statistical method for inferring the relative abundance of related members of protein families from tryptic peptide intensities. This pipeline has been used to analyze quantitative LC-MS data from multiple biomarker discovery projects. We illustrate our pipeline here with examples from two of these studies, and show that the pipeline constitutes a complete workable framework for LC-MS-based differential quantitation. Supplementary material is available at http://iec01.mie.utoronto.ca/~thodoros/Bukhman/.

Synthesis and characterization of a hemoglobin-ribavirin conjugate for targeted drug delivery.

A novel conjugate of human hemoglobin (Hb) and the nucleoside analogue ribavirin (RBV) was synthesized to demonstrate the utility of Hb as a biocompatible drug carrier for improved drug delivery in the treatment of liver disease. RBV is used in combination with interferon for the treatment of hepatitis C, but its side effects can result in dose limitation or discontinuation of treatment. Targeted delivery of RBV may help to prevent or minimize its toxicity. The hemoglobin-ribavirin conjugate (Hb-RBV) was designed to release bioactive drug upon endocytosis by cells and tissues involved in extracellular Hb catabolism and clearance. Ribavirin-5'-monophosphate (RBV-P) was prepared from RBV and activated as the 5'-monophosphorimidazolide (RBV-P-Im) for reaction with carbonmonoxyhemoglobin to yield Hb-RBV consisting of multiple RBV drugs covalently attached as physiologically labile phosphoramidates via their 5'-hydroxyl groups. A molar drug ratio of six to eight RBV molecules per Hb tetramer was obtained with near complete haptoglobin (Hp) binding of the drug modified Hb maintained. The conjugate complex (Hp-Hb-RBV) was selectively taken up in vitro by cells that express the hemoglobin-haptoglobin receptor, CD163. Recovered ribavirin enzymatically cleaved from Hb-RBV showed equipotent antiproliferative activity compared to control unconjugated RBV against human HepG2 and mouse AML12 liver cell lines. Based upon the reported high level of Hb uptake in the liver, Hb-RBV may be useful in the treatment of certain liver diseases, as well as inflammatory disorders associated with CD163-positive macrophages.

Targeted delivery of ribavirin improves outcome of murine viral fulminant hepatitis via enhanced anti-viral activity.

Side effects of interferon-ribavirin combination therapy limit the sustained viral response achievable in hepatitis C virus (HCV) patients. Coupling ribavirin to macromolecular carriers that target the drug to the liver would reduce systemic complications. The aim of this study was to evaluate the efficacy of a hemoglobin-ribavirin conjugate (HRC 203) in murine hepatitis virus strain 3 (MHV-3) induced viral hepatitis. HRC 203 had greater anti-viral activity on both isolated hepatocytes and macrophages, whereas both ribavirin and HRC 203 inhibited production of the pro-inflammatory cytokines interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) by macrophages. In vivo, untreated MHV-3-infected mice all developed clinical and biochemical signs of acute viral hepatitis and died by day 4 post infection. Livers recovered from untreated infected mice showed greater than 90% necrosis. In contrast, survival was enhanced in both ribavirin- and HRC 203-treated mice with a marked reduction in biochemical [ALT(max) 964 +/- 128 IU/L (ribavirin); 848 +/- 212 IU/L (HRC 203)] and histological evidence of hepatic necrosis (<10% in ribavirin/HRC 203 vs. 90% in untreated controls). Clinically, HRC 203-treated mice behaved normally, in contrast to ribavirin-treated mice, which developed lethargy and abnormal fur texture. In conclusion, targeted delivery of ribavirin to the liver alters the course of MHV-3 infection as demonstrated by prolonged survival, improved behavior, and reduced signs of histologically evident disease, as well as inhibition of viral replication and production of inflammatory cytokines in vitro.