Validity of mobile electronic data capture in clinical studies: a pilot study in a pediatric population.

BACKGROUND: Clinical studies in children are necessary yet conducting multiple visits at study centers remains challenging. The success of "care-at-home" initiatives and remote clinical trials suggests their potential to facilitate conduct of pediatric studies. This pilot aimed to study the feasibility of remotely collecting valid (i.e. complete and correct) saliva samples and clinical data utilizing mobile technology. METHODS: Single-center, prospective pilot study in children undergoing elective tonsillectomy at the University of Basel Children's Hospital. Data on pain scores and concomitant medication and saliva samples were collected by caregivers on two to four inpatient study days and on three consecutive study days at home. A tailored mobile application developed for this study supported data collection. The primary endpoint was the proportion of complete and correct caregiver-collected data (pain scale) and saliva samples in the at-home setting. Secondary endpoints included the proportion of complete and correct saliva samples in the inpatient setting, subjective feasibility for caregivers, and study cost. RESULTS: A total number of 23 children were included in the study of which 17 children, median age 6.0 years (IQR 5.0, 7.4), completed the study. During the at-home phase, 71.9% [CI = 64.4, 78.6] of all caregiver-collected pain assessments and 53.9% [CI = 44.2, 63.4] of all saliva samples were complete and correct. Overall, 64.7% [CI = 58.7, 70.4] of all data collected by caregivers at home was complete and correct. The predominant reason for incorrectness of data was adherence to the timing of predefined patient actions. Participating caregivers reported high levels of satisfaction and willingness to participate in similar trials in the future. Study costs for a potential sample size of 100 patients were calculated to be 20% lower for the at-home than for a traditional in-patient study setting. CONCLUSIONS: Mobile device supported studies conducted at home may provide a cost-effective approach to facilitate conduct of clinical studies in children. Given findings in this pilot study, data collection at home may focus on electronic data capture rather than biological sampling

Reporting randomised clinical trials of analgesics after traumatic or orthopaedic surgery is inadequate: a systematic review

Background Several randomised clinical trials (RCTs) of analgesics in postoperative pain after traumatic or orthopaedic surgery (TOS) have been published, but no studies have assessed the quality of these reports. We aimed to examine the quality of reporting RCTs on analgesics for postoperative pain after TOS. Methods Reports of RCTs assessing analgesics in postoperative pain after TOS were systematically searched from electronic databases. The quality of reports was assessed using the CONSORT checklist (scoring range from 0 to 22). The quality was considered poor when scoring was 12 or lesser. The publication year and the impact factor of journals were recorded. Results A total of 92 reports of RCTs were identified and 69 (75%) scored 12 or lesser in CONSORT checklist (range 5-17). The mean (SD) CONSORT score of all reports was 10.6 (2.7). Missing CONSORT items included primary and secondary outcome measures (11%), the specific objectives and hypothesis definition (12%), the sample size calculation (12%), the dates defining the periods of recruitment (12%), the discussion of external validity of findings (14%), the allocation sequence generation (24%), and the interpretation of potential bias or imprecision of results (25%). There was a little improvement in CONSORT scores over time (r = 0.62; p < 0.001) and with impact factor of journals (r = 0.30; p < 0.001). Conclusion Quality of reporting RCTs on analgesics after TOS is poor. Reporting of those RCTs should be improved according to methodological standard checklists in the next years

The use of a bayesian hierarchy to develop and validate a co-morbidity score to predict mortality for linked primary and secondary care data from the NHS in England

Background: We have assessed whether the linkage between routine primary and secondary care records provided an opportunity to develop an improved population based co-morbidity score with the combined information on co-morbidities from both health care settings. Methods: We extracted all people older than 20 years at the start of 2005 within the linkage between the Hospital Episodes Statistics, Clinical Practice Research Datalink, and Office for National Statistics death register in England. A random 50% sample was used to identify relevant diagnostic codes using a Bayesian hierarchy to share information between similar Read and ICD 10 code groupings. Internal validation of the score was performed in the remaining 50% and discrimination was assessed using Harrell’s C statistic. Comparisons were made over time, age, and consultation rate with the Charlson and Elixhauser indexes. Results: 657,264 people were followed up from the 1st January 2005. 98 groupings of codes were derived from the Bayesian hierarchy, and 37 had an adjusted weighting of greater than zero in the Cox proportional hazards model. 11 of these groupings had a different weighting dependent on whether they were coded from hospital or primary care. The C statistic reduced from 0.88 (95% confidence interval 0.88–0.88) in the first year of follow up, to 0.85 (0.85–0.85) including all 5 years. When we stratified the linked score by consultation rate the association with mortality remained consistent, but there was a significant interaction with age, with improved discrimination and fit in those under 50 years old (C=0.85, 0.83–0.87) compared to the Charlson (C=0.79, 0.77–0.82) or Elixhauser index (C=0.81, 0.79–0.83). Conclusions: The use of linked population based primary and secondary care data developed a co-morbidity score that had improved discrimination, particularly in younger age groups, and had a greater effect when adjusting for co-morbidity than existing scores

Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer

<p>Abstract</p> <p>Background</p> <p>The cytochrome P450 (CYP) enzymes 2C19, 2D6, and 3A5 are responsible for converting the selective estrogen receptor modulator (SERM), tamoxifen to its active metabolites 4-hydroxy-tamoxifen (4OHtam) and 4-hydroxy-<it>N</it>-demethyltamoxifen (4OHNDtam, endoxifen). Inter-individual variations of the activity of these enzymes due to polymorphisms may be predictors of outcome of breast cancer patients during tamoxifen treatment. Since tamoxifen and estrogens are both partly metabolized by these enzymes we hypothesize that a correlation between serum tamoxifen and estrogen levels exists, which in turn may interact with tamoxifen on treatment outcome. Here we examined relationships between the serum levels of tamoxifen, estrogens, follicle-stimulating hormone (FSH), and also determined the genotypes of CYP2C19, 2D6, 3A5, and SULT1A1 in 90 postmenopausal breast cancer patients.</p> <p>Methods</p> <p>Tamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Estrogen and FSH levels were determined using a sensitive radio- and chemiluminescent immunoassay, respectively.</p> <p>Results</p> <p>We observed significant correlations between the serum concentrations of tamoxifen, <it>N</it>-dedimethyltamoxifen, and tamoxifen-<it>N</it>-oxide and estrogens (p < 0.05). The genotype predicted CYP2C19 activity influenced the levels of both tamoxifen metabolites and E1.</p> <p>Conclusions</p> <p>We have shown an association between tamoxifen and its metabolites and estrogen serum levels. An impact of CYP2C19 predicted activity on tamoxifen, as well as estrogen kinetics may partly explain the observed association between tamoxifen and its metabolites and estrogen serum levels. Since the role of estrogen levels during tamoxifen therapy is still a matter of debate further prospective studies to examine the effect of tamoxifen and estrogen kinetics on treatment outcome are warranted.</p

Bioprocessing strategies to enhance the challenging isolation of neuro-regenerative cells from olfactory mucosa

Olfactory ensheathing cells (OECs) are a promising potential cell therapy to aid regeneration. However, there are significant challenges in isolating and characterizing them. In the current study, we have explored methods to enhance the recovery of cells expressing OEC marker p75NTR from rat mucosa. With the addition of a 24-hour differential adhesion step, the expression of p75NTR was significantly increased to 73 ± 5% and 46 ± 18% on PDL and laminin matrices respectively. Additionally, the introduction of neurotrophic factor NT-3 and the decrease in serum concentration to 2% FBS resulted in enrichment of OECs, with p75NTR at nearly 100% (100 ± 0% and 98 ± 2% on PDL and laminin respectively), and candidate fibroblast marker Thy1.1 decreased to zero. Culturing OECs at physiologically relevant oxygen tension (2–8%) had a negative impact on p75NTR expression and overall cell survival. Regarding cell potency, co-culture of OECs with NG108-15 neurons resulted in more neuronal growth and potential migration at atmospheric oxygen. Moreover, OECs behaved similarly to a Schwann cell line positive control. In conclusion, this work identified key bioprocessing fundamentals that will underpin future development of OEC-based cell therapies for potential use in spinal cord injury repair. However, there is still much work to do to create optimized isolation methods

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Roles of glial cells in synapse development

Brain function relies on communication among neurons via highly specialized contacts, the synapses, and synaptic dysfunction lies at the heart of age-, disease-, and injury-induced defects of the nervous system. For these reasons, the formation—and repair—of synaptic connections is a major focus of neuroscience research. In this review, I summarize recent evidence that synapse development is not a cell-autonomous process and that its distinct phases depend on assistance from the so-called glial cells. The results supporting this view concern synapses in the central nervous system as well as neuromuscular junctions and originate from experimental models ranging from cell cultures to living flies, worms, and mice. Peeking at the future, I will highlight recent technical advances that are likely to revolutionize our views on synapse–glia interactions in the developing, adult and diseased brain