This validation quantifies strengths and weaknesses of actigraphy as a tool measuring sleep in clinical and population studies. Overall, the participant-specific accuracy is relatively high, and for most participants, above 80%. We validate this finding across multiple nights and a variety of adults across much of the young to midlife years, in both men and women, in those with and without insomnia, and in 77 participants. We conclude that actigraphy is overall a useful and valid means for estimating total sleep time and wakefulness after sleep onset in field and workplace studies, with some limitations in specificity.
Although in vitro models have been a cornerstone of anti-cancer drug development, their direct applicability to clinical cancer research has been uncertain. Using a state-of-the-art Taqman-based quantitative RT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of six cancer types, in established cancer cell lines (grown in monolayer, 3D scaffold, or in xenograft) and clinical samples, either containing >75% tumor cells or microdissected. The MDR transcriptome was determined a priori based on an extensive curation of the literature published during the last three decades, which led to the enumeration of 380 genes. No correlation was found between clinical samples and established cancer cell lines. As expected, we found up-regulation of genes that would facilitate survival across all cultured cancer cell lines evaluated. More troubling, however, were data showing that all of the cell lines, grown either in vitro or in vivo, bear more resemblance to each other, regardless of the tissue of origin, than to the clinical samples they are supposed to model. Although cultured cells can be used to study many aspects of cancer biology and response of cells to drugs, this study emphasizes the necessity for new in vitro cancer models and the use of primary tumor models in which gene expression can be manipulated and small molecules tested in a setting that more closely mimics the in vivo cancer microenvironment so as to avoid radical changes in gene expression profiles brought on by extended periods of cell culture.
BACKGROUND: Long-term efficacy of opioids for noncancer pain is unproven, but risks argue for cautious prescribing. Few data suggest how long or how much opioid can be prescribed for opioid-naïve patients without inadvertently promoting long-term use. OBJECTIVE: To examine the association between initial opioid prescribing patterns and likelihood of long-term use among opioid-naïve patients. DESIGN: Retrospective cohort study; data from Oregon resident prescriptions linked to death certificates and hospital discharges. PARTICIPANTS: Patients filling opioid prescriptions between October 1, 2012, and September 30, 2013, with no opioid fills for the previous 365 days. Subgroup analyses examined patients under age 45 who did not die in the follow-up year, excluding most cancer or palliative care patients. MAIN MEASURES: Exposure: Numbers of prescription fills and cumulative morphine milligram equivalents (MMEs) dispensed during 30 days following opioid initiation (Binitiation month^). Outcome: Proportion of patients with six or more opioid fills during the subsequent year (Blong-term users^). KEY RESULTS: There were 536,767 opioid-naïve patients who filled an opioid prescription. Of these, 26,785 (5.0 %) became long-term users. Numbers of fills and cumulative MMEs during the initiation month were associated with long-term use. Among patients under age 45 using short-acting opioids who did not die in the follow-up year, the adjusted odds ratio (OR) for long-term use among those receiving two fills versus one was 2.25 (95 % CI: 2.17, 2.33). Compared to those who received < 120 total MMEs, those who received between 400 and 799 had an OR of 2.96 (95 % CI: 2.81, 3.11). Patients initiating with long-acting opioids had a higher risk of long-term use than those initiating with short-acting drugs.CONCLUSIONS: Early opioid prescribing patterns are associated with long-term use. While patient characteristics are important, clinicians have greater control over initial prescribing. Our findings may help minimize the risk of inadvertently initiating long-term opioid use.
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