AbstractIntroductionThe development and initial assessment in a clinical setting of a theory-driven, individually tailored educational application (app), MomsTalkShots, focused on increasing uptake ...of maternal and infant vaccines is described. MethodsMomsTalkShots algorithmically tailored videos based on parent needs to deliver an intervention that was specifically responsive to individual vaccine attitudes, beliefs and intentions, demographics, and source credibility. MomsTalkShots was evaluated among 1103 pregnant women recruited from 23 geographically and socio-demographically diverse obstetrician-gynecologist offices in Georgia and Colorado in 2017. Self-reported information needs were assessed pre-and post-videos and participants self-reported factors related to usability and analyzed in 2018. ResultsThe vast majority of women reported MomsTalkShots was helpful (95%), trustworthy (94%), interesting (97%) and clear to understand (99%), none of which varied by demographics or parity. Reported usability was slightly lower among vaccine hesitant women, yet the majority reported MomsTalkShots was helpful (91%), trustworthy (85%), interesting (97%) and clear (99%). The majority of women (72%) who did not have enough vaccine information pre-videos reported enough information post-videos. ConclusionsMomsTalkShots was designed to provide individually tailored vaccine information to pregnant women from a population with varied vaccine intentions, confidence and vaccine concerns. MomsTalkShots was extremely well-received among pregnant women, even among women who were initially vaccine hesitant and did not intend to vaccinate themselves and their infants according to the recommended immunization schedule. Next steps include evaluation to assess impact on vaccine uptake and expansion to adolescent and adult vaccines.
Tangier disease is characterized by low serum high density lipoproteins and a biochemical defect in the cellular efflux of lipids to high density lipoproteins. ABC1, a member of the ATP-binding ...cassette family, recently has been identified as the defective gene in Tangier disease. We report here the organization of the human ABC1 gene and the identification of a mutation in the ABC1 gene from the original Tangier disease kindred. The organization of the human ABC1 gene is similar to that of the mouse ABC1 gene and other related ABC genes. The ABC1 gene contains 49 exons that range in size from 33 to 249 bp and is over 70 kb in length. Sequence analysis of the ABC1 gene revealed that the proband for Tangier disease was homozygous for a deletion of nucleotides 3283 and 3284 (TC) in exon 22. The deletion results in a frameshift mutation and a premature stop codon starting at nucleotide 3375. The product is predicted to encode a nonfunctional protein of 1,084 aa, which is approximately half the size of the full-length ABC1 protein. The loss of a Mn/1 restriction site, which results from the deletion, was used to establish the genotype of the rest of the kindred. In summary, we report on the genomic organization of the human ABC1 gene and identify a frameshift mutation in the ABC1 gene of the index case of Tangier disease. These results will be useful in the future characterization of the structure and function of the ABC1 gene and the analysis of additional ABC1 mutations in patients with Tangier disease.
Abstract Background Men with germline breast cancer 1, early onset ( BRCA1 ) or breast cancer 2, early onset ( BRCA2 ) gene mutations have a higher risk of developing prostate cancer (PCa) than ...noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. Objective To report the first year's screening results for all men at enrolment in the study. Design, setting and participants We recruited men aged 40–69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA >3 ng/ml were offered prostate biopsy. Outcome measurements and statistical analysis PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. Results and limitations We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%—double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups. Conclusions The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease. Patient summary In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment.
ABSTRACTClinical treatment decisions and the survival outcomes of patients with gliomas are directly impacted by accurate tumor classification. New and more reliable prognostic markers are needed to ...better identify the variable duration of survival among histologically defined glioma grades. Microarray expression analysis and immunohistochemistry were used to identify biomarkers associated with gliomas with more aggressive biologic behaviors. The protein expression of IQGAP1 and IGFBP2, when used in conjunction with the World Health Organization grading system, readily identified and defined a subgroup of patients with grade III gliomas whose prognosis was poor. In addition, in patients with glioblastoma multiforme, in whom IQGAP1 and IGFBP2 were absent, long-term survival of more than 3 years was observed. The use of these markers confirmed a nonuniform distribution of survival in those with World Health Organization grade III and IV tumors. Thus, IQGAP1 and IGFBP2 immunostaining supplements current histologic grading by offering additional prognostic and predictive information.
Sustaining increased enrollment and graduation rates of advanced practice registered nursing students during participation in the Graduate Nurse Education demonstration project was paramount. In an ...effort to maintain clinical and academic partnerships, the Graduate Nurse Education collaborative in Arizona surveyed the participating preceptors, developed innovative clinical training models, and offered preceptor advancement courses in addition to the traditional incentives for precepting. This education brief describes the findings of a preceptor incentive survey and the innovative achievements of the academic and clinical partners.
•A 500% increase in student enrollment was seen after the project.•The participating academic partners currently have over 1,800 clinical training sites.•Training in rural telehealth, interprofessional education, and team-based care was provided.
Medication nonadherence is common in the treatment of serious mental illness (SMI) and leads to poor outcomes. The digital medicine system (DMS) objectively measures adherence with oral aripiprazole ...in near-real time, allowing recognition of adherence issues. This pilot study evaluated the functionality of an integrated call center in optimizing the use of the DMS.
An 8-week, open-label, single-arm trial at four US sites enrolled adults with bipolar I disorder, major depressive disorder, and schizophrenia on stable oral aripiprazole doses and willing to use the DMS (oral aripiprazole + ingestible event marker IEM, IEM-detecting skin patch, and software application). Integrated call-center functionality was assessed based on numbers and types of calls. Ingestion adherence with prescribed treatment (aripiprazole + IEM) during good patch wear and proportion of time with good patch wear (days with ≥80% patch data or detected IEM) were also assessed.
All enrolled patients (n=49) used the DMS and were included in analyses; disease duration overall approached 10 years. For a duration of 8 weeks, 136 calls were made by patients, and a comparable 160 calls were made to patients, demonstrating interactive communication. The mean (SD) number of calls made by patients was 2.8 (3.5). Approximately half of the inbound calls made by patients occurred during the first 2 weeks and were software application- or patch-related. Mean ingestion adherence was 88.6%, and corresponding good patch wear occurred on 80.1% of study days.
In this pilot study, the integrated call center facilitated DMS implementation in patients with SMI on stable doses of oral aripiprazole. In clinical practice, the call center and the DMS will facilitate objective measurement of adherence and potentially improve rates of adherence in patients with SMI.
Student-teacher relationships are critical to ensuring successful transitions to high school, but programs focused on building strong relationships have been concentrated at younger school levels. ...Therefore, the purpose of this study was to gather feedback from ninth grade students, teachers/staff, and administrators regarding an existing student-teacher relationship intervention, Establish-Maintain-Restore (EMR), to inform a “scaling-out” adaptation of EMR for high schools. Data were collected from 7 administrators, 8 teachers/staff, and 10 ninth-grade students from diverse ethnic/ racial backgrounds. Participants quantitatively rated the acceptability and effectiveness of EMR strategy for the high school context and then described their rationale for their ratings in focus groups. ANOVAs were used to examine differences in appropriateness and effectiveness of EMR strategies across participant groups. We then used content analysis to explore identified problems and recommendations regarding discrepant strategies. We discuss implications for relationships at the high school level and for scaling-out interventions to novel developmental contexts.
Translocation of TMPRSS2 to the ERG gene, found in a high proportion of human prostate cancer, results in overexpression of the 3′- ERG sequences joined to the 5′- TMPRSS2 promoter. The studies ...presented here were designed to test the ability of expression analysis on GeneChip Human Exon 1.0 ST arrays to detect 5′- TMPRSS2-ERG -3′ hybrid transcripts encoded by this translocation. Monitoring the relative expression of each ERG exon revealed altered transcription of the ERG gene in 15 of a series of 27 prostate cancer samples. In all cases, exons 4 to 11 exhibited enhanced expression compared with exons 2 and 3. This pattern of expression indicated that the most abundant hybrid transcripts involve fusions to ERG exon 4, and RT-PCR analyses confirmed the joining of TMPRSS2 exon 1 to ERG exon 4 in all 15 cases. The exon expression patterns also indicated that TMPRSS2-ERG fusion transcripts commonly contain deletion of ERG exon 8. Analysis of gene-level data from the arrays allowed the identification of genes whose expression levels significantly correlated with the presence of the translocation. These studies demonstrate that expression analyses using exon arrays represent a valuable approach for detecting ETS gene translocation in prostate cancer, in parallel with analyses of gene expression profiles.
Abstract The increased chemosensitivity of oligodendroglial tumours has been associated with loss of heterozygosity (LOH) of the p arm of chromosome 1 and the q arm of chromosome 19 (LOH 1p/19q). ...Other clinical and molecular factors have also been identified as being prognostic and predictive of treatment outcome. We reviewed 105 patients with oligodendroglioma treated at a single centre over 20 years. Median survival in oligodendroglioma patients with LOH 1p/19q was significantly longer (10.9 vs . 2.0 years). In the anaplastic oligodendroglioma group, univariate analysis demonstrated decreased patient age, presentation with seizures, use of adjuvant chemotherapy and LOH 1p/19q as predictors of improved survival. Multivariate analysis confirmed LOH 1p/19q as a significant predictor of improved survival (hazard ratio, 3.4; p = 0.015). Median survival in patients with anaplastic oligodendroglioma with LOH 1p/19q was 15.4 years vs . 1.2 years for those without LOH 1p/19q. This study confirms the utility of LOH 1p/19q as a prognostic marker in oligodendroglioma.
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