'Who is going to put their life on the line for a dollar? That's crazy': community perspectives of financial compensation in clinical research.

BACKGROUND: Financial compensation of research participants has been standard practice for centuries, however, there is an ongoing debate among researchers and ethicists regarding the ethical nature of this practice. While these debates develop ethical arguments and theories, they fail to incorporate input from those most affected by financial compensation: potential research participants. METHODS: To identify attitudes surrounding clinical research, participants of a long-standing cohort completed a one-time interview. Open-ended questions stimulated a participant-driven discussion surrounding medical research. Following a grounded theory methodology, 58 semistructured interview transcripts were coded, focusing on attitudes surrounding financial compensation of research participants. RESULTS: Of the interviews coded, the majority of participants identified as Black/African American (n=44) and were women (n=40). Five major themes emerged. In support of financial compensation, participants felt that study participants should be compensated for time, effort and risk. However, participants were concerned that compensation may differentially impact low-income populations and entice them to hide potentially harmful side effects. Participants also mentioned that financial compensation may invalidate study results if participants knowingly provide false information to subvert inclusion/exclusion criteria. CONCLUSION: The emergence of both positive and negative themes reiterates the complicated issue of providing financial compensation for study participation. While compensation as a motivator for research participation raises ethical concerns, participants discussed weighing the benefits with the risks in order to make an informed decision. To avoid paternalistic behaviours, research staff must allow potential research participants to review the available information and make the decision that best reflects their wishes.

Initial Experience With Percutaneous IM Rodding of the Humeri in Children With Osteogenesis Imperfecta.

BACKGROUND: To report a single-center surgical experience treating humeral deformity and fractures in children with osteogenesis imperfecta (OI) using the Fassier-Duval (FD) intramedullary elongating rods. METHODS: A retrospective review was conducted between December 2005 and July 2013 of all OI patients who underwent FD rodding with a minimum of 1-year follow-up. All patients were also being concurrently treated with bisphosphonates. RESULTS: Eighteen patients underwent internal fixation on a total of 35 humeri: 7 males and 11 females with an average age of 49 months. Thirty-five procedures were performed using FD rodding, with 5 utilizing only the male portion. Thirty procedures were primary FD implantation and 5 were revisions. Twelve patients had type III OI and 6 patients type IV OI. Indications for surgery included recurrent fracture, severe bowing deformity, and pain. Osteotomy methods included closed osteoclasis, percutaneous, or open osteotomies. Two patients required transfusions during their hospital stay. At our determined endpoint, 23 humeri (65.7%) had acceptable results with a mean follow-up time of 43 months (SD=27) with no revision. The remaining 12 humeri (34.3%) necessitated revision with a mean time to revision of 35 months (SD=29). Reasons for revision included: migration resulting in pain and functional difficulty (8.6%), migration with bowing (8.6%), and hardware failure secondary to trauma (8.6%). In addition, 2 revisions were required for nonunion (5.7%) and 1 for malunion (2.9%). To our knowledge, all other osteotomies performed during surgery resulted in bony union. CONCLUSIONS: The use of the FD system for correction of humeral deformity demonstrates a reasonable option to improve comfort and function in children with recurrent fractures and deformity secondary to OI. The FD system allows for decreased revision rates and less morbid instrumentation. LEVEL OF EVIDENCE: Level IV-retrospective case series.

Low bone mineral density is a common feature of Zellweger spectrum disorders.

Patients with Zellweger Spectrum Disorders (ZSDs) have impaired peroxisome biogenesis and severe, multisystem disease. Although the neurologic symptoms of ZSD tend to be the most prominent, patients also have hepatic, renal and adrenal impairment. Little is known about bone health in patients with ZSD, particularly those with mild or moderate presentation. We investigated 13 ZSD patients who had strikingly abnormal bone mineral density for age. DXA scans showed mean lumbar and femoral neck Z-scores of -3.2. There were no major differences between ambulatory and nonambulatory patients, and no biochemical abnormalities consistent with rickets or vitamin D deficiency were seen. Cyclic bisphosphonate therapy in one ZSD patient was successfully used to increase in bone mineral density. Although the etiology of bone disease in this condition is unknown, we speculate that altered signaling through the PPARγ pathway or deficient plasmalogens in patients with ZSD disrupts osteogenesis, resulting in poor bone formation and poor mineralization. Further investigation into the pathogenic mechanisms of bone disease in ZSD and the role of peroxisomal metabolism in osteogenesis may yield insights into the pathology of bone disease and suggest novel treatment options.

Development and initial feedback about a human papillomavirus (HPV) vaccine comic book for adolescents.

Human papillomavirus (HPV) vaccination rates do not meet the Healthy People 2020 objective of 80% coverage among adolescent females. We describe the development and initial feedback about an HPV vaccine comic book for young adolescents. The comic book is one component of a multilevel intervention to improve HPV vaccination rates among adolescents. Parents suggested and provided input into the development of a HPV vaccine comic book. Following the development of the comic book, we conducted a pilot study to obtain initial feedback about the comic book among parents (n = 20) and their adolescents ages 9 to 14 (n = 17) recruited from a community-based organization. Parents completed a pre-post test including items addressing HPV knowledge, HPV vaccine attitudes, and about the content of the comic book. Adolescents completed a brief interview after reading the comic book. After reading the comic book, HPV knowledge improved (2.7 to 4.6 correct answers on a 0-5 scale; p < 0.01) and more positive attitudes toward HPV vaccination (p < 0.05) were reported among parents. Parents confirmed that the comic book's content was acceptable and adolescents liked the story, found it easy to read, and thought the comic book was a good way to learn about being healthy. Parents provided valuable information in the development of a theoretically-based comic book and the comic book appears to be an acceptable format for providing HPV vaccine information to adolescents. Future research will include the comic book in an intervention study to improve HPV vaccination rates.

Process Evaluation of a Policy, Systems, and Environmental Change Intervention in an Urban School District.

OBJECTIVE: To conduct a comprehensive process evaluation of a policy, systems, and environmental (PSE) change intervention. DESIGN: Quasi-experimental, mixed methods. SETTING: Low-income urban school district. PARTICIPANTS: Fifth-grade students in 4 schools assigned to 2 intervention and 2 comparison schools (intervention, n = 142; comparison, n = 170). INTERVENTION: Both groups received a nutrition curriculum delivered by classroom teachers. Intervention schools also received 10 PSE lessons taught by paraprofessional educators. MAIN OUTCOME MEASURES: Quantitative data were obtained from fidelity and observation checklists, grading rubrics and self-reported student surveys. Focus group and interviews provided qualitative data. Quantitative measures included assessments of PSE and fruit and vegetable knowledge, as well as assessment of times fruits and vegetables (FV) were consumed yesterday. ANALYSES: Qualitative data were analyzed using inductive content analysis. Quantitative data were analyzed using repeated measures analysis of variance and analysis of co-variance. RESULTS: Fidelity, dose, reach, and acceptance of PSE intervention were high; students felt more empowered, although PSE lessons were considered lengthy and complicated. Intervention PSE and FV knowledge scores were significantly higher than comparison scores (F37.56, P < .001; and F3.94, P < .05, respectively). However, issues in communication were identified between school staff and researchers. CONCLUSIONS AND IMPLICATIONS: Policy, systems, and environmental classroom interventions commented on the differences between quantitative and qualitative assessments, and this suggests the need for more sensitive quantitative assessments. Future research should look at long-term outcomes as this study only looked at short-term outcomes.

Echocardiographic phenotype in osteogenesis imperfecta varies with disease severity.

BACKGROUND AND OBJECTIVES: Our purpose was to investigate cardiovascular abnormalities in children with osteogenesis imperfecta (OI). METHODS: Two hundred children (100 OI, 100 matched volunteers) were prospectively studied. Aortic and left ventricular (LV) measurements were performed using transthoracic echocardiography. Patients were typed according to modified phenotypical Sillence classification as published in the Nosology and Classification of Genetic Skeletal disorders: 2015 Revision. RESULTS: Patients (age 9.6±4.1 years, body surface area 1.08±0.47 m2) consisted of OI types: 1 (n=44), 3/4 (n=54), 4 (n=1) and 15 (n=1). The 95% CIs for Z-score of aortic annulus, sinus, sinotubular junction and ascending aorta for OI were 0.43 to 0.73, 0.56 to 0.94, 0.28 to 0.70 and 0.78 to 1.24, respectively. In type 1, sinus, sinotubular junction and ascending aorta diameters were 2.29 cm, 1.81 cm and 2.05 cm, respectively, which did not differ compared with controls. The LV dimensions were larger in type 1. In type 3/4, aortic dimensions were larger than controls at all levels: annulus (1.61 vs 1.50 cm, p<0.001), sinus (2.19 vs 2.05 cm, p=0.001), sinotubular junction (1.77 vs 1.64 cm, p<0.001) and ascending aorta (1.98 vs 1.82 cm, p<0.001), but LV dimensions were normal. CONCLUSIONS: Cardiovascular effects are identifiable in childhood even in mild forms of OI. Aortic dilation was the predominant finding, while valvular abnormalities were infrequent. Patients with more severe skeletal pathology (types 3/4) have more significant findings. Aortic and LV dilation in type 1 vs type 3/4 appears to differ based on the biochemical mechanism of disease.

Interaction between non-psychotropic cannabinoids in marihuana: effect of cannabigerol (CBG) on the anti-nausea or anti-emetic effects of cannabidiol (CBD) in rats and shrews.

RATIONALE: The interaction between two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), which have been reported to act as a 5-hydroxytryptamine 1A (5-HT(1A)) agonist and antagonist, respectively, was evaluated. OBJECTIVE: To evaluate the potential of CBG to reverse the anti-nausea, anti-emetic effects of CBD. MATERIALS AND METHODS: In experiment 1, rats were pre-treated with CBG (0.0, 1, 5, and 10 mg/kg, ip), 15 min prior to being treated with CBD (experiment 1a: VEH or 5 mg/kg, ip) or 8-OH-DPAT (experiment 1b: VEH or 0.01 mg/kg, ip). Thirty minutes later, all rats received a pairing of 0.1% saccharin solution and LiCl (20 ml/kg of 0.15 M, ip). Seventy-two hours later, the rats received a drug-free taste reactivity test with saccharin to evaluate the effects of the treatments on the establishment of conditioned gaping reactions (a model of nausea). As well, conditioned saccharin avoidance was measured. In experiment 2, Suncus murinus were injected with CBG (5 mg/kg, ip) or VEH 15 min prior to CBD (5 mg/kg) or VEH and 30 min later were injected with LiCl (60 ml/kg of 0.15 M, i.p.), and the number of vomiting episodes were measured. RESULTS: CBD (5 mg/kg) suppressed conditioned gaping in rats and vomiting in shrews, which were reversed by pre-treatment with all doses of CBG. CBG also prevented the anti-nausea effects of 8-OH-DPAT. CONCLUSIONS: Interactions between moderate doses of CBG and CBD may oppose one another at the 5-HT(1A) receptor in the regulation of nausea and vomiting.

Infant crying and sleeping in London, Copenhagen and when parents adopt a "proximal" form of care.

OBJECTIVE: Western parents are given conflicting advice about whether to introduce a "scheduled" approach to infant care or to follow their infants' demands. Attempts to address this issue using randomized, controlled trials have been unsuccessful. This comparative study collected evidence about methods of parenting and associated infant crying and sleeping in 2 communities with substantially different approaches to infant care (London, United Kingdom, and Copenhagen, Denmark) and in a "proximal care" group, where parents planned to hold their infants > or =80% of the time between 8 am and 8 pm, breastfeed frequently, and respond rapidly to infant cries. METHODS: Validated behavior diaries were used to measure parental behavior and infant crying and night waking longitudinally at 8 to 14 days, 5 to 6 weeks, and 10 to 14 weeks of age. Feeding and sleeping practices were measured by questionnaire. RESULTS: Proximal care parents held infants for 15 to 16 hours per 24 hours and coslept with them through the night more often than other groups. London parents had 50% less physical contact with their infants than proximal care parents, including less contact when the infants were crying and when awake and settled. London parents also abandoned breastfeeding earlier than other groups. Copenhagen parents fell in between the other groups in measures of contact and care. These differences in caregiving were associated with substantial differences in several aspects of infant crying and settled behavior at night. London infants cried 50% more overall than infants in both other groups at 2 and 5 weeks of age. However, bouts of unsoothable crying occurred in all 3 of the groups, and the groups did not differ in unsoothable bouts or in colicky crying at 5 weeks of age. Proximal care infants woke and cried at night most often at 12 weeks. Compared with proximal care infants, Copenhagen infants cried as little per 24 hours, but woke and cried at night less often at 12 weeks of age. CONCLUSIONS: "Infant-demand" care and conventional Western care, as practiced by London parents, are associated with different benefits and costs. As used by proximal care and Copenhagen parents, infant demand parenting is associated with less overall crying per 24 hours. However, the proximal form of infant-demand parenting is associated with more frequent night waking and crying at 12 weeks of age. Copenhagen infants cry as little per 24 hours as proximal care infants but are settled at night like London infants at 12 weeks of age. Colicky crying bouts at 5 weeks of age are unaffected by care. The findings have implications for public health care policy. First, they add to evidence that bouts of unsoothable crying, which are common in early infancy, are not much affected by variations in parenting, providing reassurance that this aspect of infant crying is not parents' fault. Second, the findings provide information that professionals can give to parents to help them to make choices about infant care. Third, the findings support some experts' concerns that many English parents are adopting methods of care that lead to increased crying in their infants. There is a need for informed debate among professionals, policy makers, and parents about the social and cultural bases for the marked differences between London and Copenhagen parents' approach to care.

A map of WW domain family interactions.

WW domains are protein modules that bind proline-rich ligands. WW domain-ligand complexes are of importance as they have been implicated in several human diseases such as muscular dystrophy, cancer, hypertension, Alzheimer's, and Huntington's diseases. We report the results of a protein array aimed at mapping all the human WW domain protein-protein interactions. Our biochemical approach integrates parallel synthesis of peptides, protein expression, and high-throughput screening methodology combined with tools of bioinformatics. The results suggest that the majority of the bioinformatically predicted WW peptide ligands and most WW domains are functional, and that only about 10% of the measured domain-ligand interactions are positive. The analysis of the WW domain protein arrays also underscores the importance of the amino acid residues surrounding the WW ligand core motifs for specific binding to WW domains. In addition, the methodology presented here allows for the rapid elucidation of WW domain-ligand interactions with multiple applications including prediction of exact WW ligand binding sites, which can be applied to the mapping of other protein signaling domain families. Such information can be applied to the generation of protein interaction networks and identification of potential drug targets. To our knowledge, this report describes the first protein-protein interaction map of a domain in the human proteome.