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The Department of Energy's (DOE's) nine multipurpose labs may get most of the attention (see main text), but it's the 17 smaller, more focused, and less well-known labs that are [...]

Elephants would seem hard animals to miss, but tracking them back in time hasn't been easy. Paleontologists have zealously followed the fossil trail of elephants and their kin--the ungulates, which [...]

Objectives: A key systematic review (SR) methodology is comprehensive searching. The Drug Effectiveness Review Project (DERP) SRs search US Food and Drug Administration (FDA) documents to identify unpublished evidence. This study evaluates the success of those efforts. Study Design and Setting: We examined DERP reports published since 2003 for the use of FDA preapproval and postmarketing documents. We categorized evidence as (1) unique unpublished studies, (2) supplemental unpublished data, or (3) FDA postmarketing data analysis. Three reviewers independently assigned predetermined impact categories (e.g., qualitative or quantitative usage, fills gaps, confirms findings, and alters conclusions), resolving disagreements through consensus. Results: Among 114 DERP reports, 19% included unpublished studies and/or supplemental data and 10% included postmarketing analyses. From 175 preapproval documents, 14% provided eligible unpublished studies and 4.0% supplemental unpublished data that helped confirm previous findings, identify important harms, and fill gaps in knowledge about understudied subpopulations, outcomes, and comparisons. Report conclusion statements changed in 9 of 33 instances of premarketing documents compared with 4 of 12 postmarketing analyses. Conclusions: The FDA documents can provide important unpublished evidence for SRs, although in a small proportion of cases. Future research should identify attributes that predict which reviews may benefit most from review of FDA documents. [ABSTRACT FROM AUTHOR]

This study extends previous research on motivations for compliance with environmental regulations. It addresses contexts where regulatees have primarily sporadic short term interests, where costs of compliance are modest, and where costs of non-compliance are low. The behavior studied is the movement of firewood for camping, a principal cause for the spread of the emerald ash borer (Agrilus planipennis), one of several invasive species plaguing the eastern United States. Based on a three-wave mail survey that produced 495 usable returns (64% response rate), findings suggest that motivations are influential in these contexts. Calculated motivations exert the greatest influence—especially when related to firewood price and convenience, while normative motivations (civic duty based) exert less influence, as does ability to comply. These findings have important implications, not only for controlling the spread of forest diseases and invasive pests, but also for regulating natural resources in general. They suggest that national, state, and local governments can manage natural resources to encourage user compliance with environmental rules, and develop communication strategies that leverage pro-environment norms. [Copyright &y& Elsevier]

The Drug Effectiveness Review Project was initiated in 2003 in response to dramatic increases in the cost of pharmaceuticals, which lessened the purchasing power of state Medicaid budgets. A collaborative group of state Medicaid agencies and other organizations formed to commission high-quality comparative effectiveness reviews to inform evidence-based decisions about drugs that would be available to Medicaid recipients. The Project is coordinated by the Center for Evidence-based Policy (CEbP) at Oregon Health & Science University (OHSU), and the systematic reviews are undertaken by the Evidence-based Practice Centers (EPCs) at OHSU and at the University of North Carolina. The reviews adhere to high standards for comparative effectiveness reviews. Because the investigators have direct, regular communication with policy-makers, the reports have direct impact on policy and decision-making, unlike many systematic reviews. The Project was an innovator of methods to involve stakeholders and continues to develop its methods in conducting reviews that are highly relevant to policy-makers. The methods used for selecting topics, developing key questions, searching, determining eligibility of studies, assessing study quality, conducting qualitative and quantitative syntheses, rating the strength of evidence, and summarizing findings are described. In addition, our on-going interactions with the policy-makers that use the reports are described. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the time to and key factors associated with decision to update comparative effectiveness of reviews of drugs based on periodic scans of new evidence. Study Design and Setting: Based on periodic scans of new evidence, we analyzed 69 decisions on whether to update for 41 comparative effectiveness reviews conducted for the Drug Effectiveness Review Project. We used the Kaplan–Meier product limit method to estimate mean time to update and generalized estimating equation logistic regression to estimate associations between updating decisions and review topic or characteristics of new evidence. Results: Mean time to update was 24.9 months. Significant predictors of a decision to update were identification of a new drug (odds ratio [OR]: 5.71; 95% confidence interval [CI]: 1.68–19.44) and the number of new relevant trials (OR: 1.06; 95% CI: 1.03–1.10). Compared with nonpsychiatric topics, psychiatric topics were most rapidly developing (mean new relevant citations: 38.4 vs. 8.2; P =0.0127) and were updated at a faster pace (mean survival time: 10.2 vs. 27.5 months; P <0.0001). Conclusion: Using periodic scans of new evidence, updating should be considered yearly for rapidly developing topics and biannually for other topics. [Copyright &y& Elsevier]

Recommended medication prescribing hierarchies for adult attention-deficit hyperactivity disorder (ADHD) vary between different guideline committees. Few trials directly compare competing ADHD medications in adults and provide little insight for clinicians making treatment choices. The objective of this study was to assess comparative benefits and harms of competing medications for adult ADHD using indirect comparison meta-analysis. Eligible studies were English-language publications of randomized controlled trials comparing ADHD drugs to placebo. Data sources were electronic bibliographic databases, Drugs@FDA, manufacturer data, and reference lists. Two reviewers independently abstracted data on design, internal validity, population, and results. Benefits and harms were compared between drug types using indirect comparison meta-regression (ratio of relative risks). Twenty-two placebo-controlled trials were included ( n = 2,203). Relative benefit of clinical response for shorter-acting stimulants, primarily immediate release methylphenidate, was 3.26 times greater than for patients taking longer-acting stimulants (95% CI 2.03, 5.22) and 2.24 times greater than for patients taking longer-acting forms of bupropion (95% CI 1.23, 4.08). Immediate release methylphenidate is also the only drug shown to reduce ADHD symptoms in adults with substance abuse disorders. Neither non-stimulants nor longer-acting stimulants reduced adverse effects compared to shorter-acting stimulants. Key gaps in evidence were academic, occupational, social functioning, cardiovascular toxicity, and longer-term outcomes, influences of ADHD subtype and/or comorbidities, and misuse/diversion of the drugs. Current best evidence supports using immediate release methylphenidate as first-line treatment for most adults with ADHD. [ABSTRACT FROM AUTHOR]

The Institute of Medicine identifies evidence-based practice (EBP) as a core competency for health care providers. Barriers to EBP among non-physician providers include lack of knowledge, lack of time, and lack of organizational support/ awareness. EBP is supported at the institutional level through a central Nursing Research and Evidence-Based Practice Council, as a component of the professional advancement Model and as a requirement of the nurse residency program. As a way to invigorate EBP in the Cancer Center: a committee is formed, under the guidance of the central council, to provide support and guidance to Oncology EBP. The purpose of this project is to describe the committee's mission and goals, its early achievements, and its effect on EBP culture, as evidenced by scholarly work from the Cancer Center. Interventions included recruiting interdisciplinary staff interested in EBP for patients with cancer, creating a charter with a mission; activities, membership, reporting, and delegation of authorities. Monthly meetings with agendas and minutes are held to facilitate EBP projects, review scholarly work, create and provide EBP education, provide organizational support for EBP, and practice EBP together. The committee started in August of 2020, has 23 members, with an average of 15 members attending each meeting. The committee reviewed and approved eleven posters at the hospital's Clinical Practice Summit in 2021. The Cancer Center submitted 65% more posters than in 2019representing an increase in scholarly work within the department. Education was also developed and disseminated to the staff. There was one session on literature search strategies and PICO question development. A second education topic demonstrated literature and guideline resources available to oncology staff and subsequently, the committee created an oncology-specific search portal highlighting important oncology-related journals and links to evidence-based national and international guidelines. The committee is currently working on an EBP project. The committee continues to provide organizational support, staff education, expert reviews of scholarly work, and a place to learn EBP as a group. This methodology can be repeated in other organizations to improve oncology nursing competency and culture for EBP. [ABSTRACT FROM AUTHOR]

The potential clinical and financial advantages of providing neurorehabilitation directly in patients' homes and communities have recently been discussed. However, the specific characteristics and outcomes of a coordinated, interdisciplinary, home-based programme does not currently exist in the rehabilitation literature. The present paper presents patient demographics, type and intensity of services provided, satisfaction measures, and clinical outcomes for 77 brain injured individuals in an attempt to begin to define and evaluate this new level of care. Additionally, the challenges of conducting homebased rehabilitation, and needs for further research are discussed. [ABSTRACT FROM AUTHOR]

Examines the role of the A3 adenosine receptor on the activation of chlorine ion channels of nonpigmented (NPE) ciliary epithelial cells. Description of human DPE cells; Effects of selective A3-receptor antagonists on adenosine-stimulated isotonic shrinkage of NPE cells; Description of rabbit iris-ciliary body.

Application of voltage pulses of 10 mV for periods of 9 sec across toad urinary bladder elicits a rapid deflection in transepithelial current. Frequently, the current decays back towards its baseline value during the course of the polarizing pulse. This transient phenomenon can be induced, or its magnitude increased, by raising the mucosal or serosal Na concentration. The transient can be abolished by sufficiently hyperpolarizing the tissue (rendering serosa positive to mucosa), by inhibiting transcellular Na transport with amiloride or ouabain, and by increasing the serosal K concentration. Vasopressin increases net Na movement across toad bladder but does not elicit these transients. It is proposed as a working hypothesis for further study that the transient behavior characterized in this study reflects: (1) the partition of Na between the apical plasma membrane and contiguous fluid layers, (2) the partition of K between the basolateral plasma membrane and adjacent submucosal fluid layer, and (3) the negative feedback interaction between intracellular Na activity and Na permeability of the apical plasma membrane of the transporting cells. [ABSTRACT FROM AUTHOR]

A theory of the cell volume is presented with emphasis on the swelling effect of high concentrations of KCl and other chloride salts. In this theory a particular cell volume represents a state of balance between the tendency of the cell water to build deeper layers of polarized water and the restraining forces exerted by the salt linkages and H-bonds. Taking into account also the different structure-breaking effects of different salts, theoretical curves can be constructed which describe the complex multiple peak-plateau of swelling curve observed in frog muscle in response to increasing concentrations of different chloride salts. [ABSTRACT FROM AUTHOR]

Skins from the frog Rana pipiens pipiens were studied under short-circuited conditions during the course of removing and replacing potassium in the inner bathing media in 14 experiments. The intracellular potential ( V), fractional resistance ( FR), short-circuit current ( I) and total tissue conductance ( g) were constantly monitored during impalements of the epithelial cells. The mean value (± se) for V was −79 (±3) mV under baseline conditions. Removal of potassium from the inner bathing solution transiently stimulated the short-circuit current and hyperpolarized the basolateral membrane; with sufficiently long incubations, the basolateral membrane was eventually depolarized. Restoration of potassium to the inner solution within 43 min after initiating the perfusion with K-free solution depolarized the basolateral membrane. However, restoration of potassium after at least 11/2 hr of incubation hyperpolarized the membrane. Ouabain consistently depolarized the basolateral membrane, even after extended periods of potassium depletion as long as 320 min. In the presence of ouabain, restoration of potassium depolarized the basolateral membrane. The data provide further evidence for the concept that the Na−K exchange pump of frog skin is rheogenic. Furthermore, the results suggest that the pump continues to be active even during prolonged periods of potassium depletion, reaccumulating potassium which has leaked out of the epithelial cells. [ABSTRACT FROM AUTHOR]

Background: Systematic reviews (SRs) depend on comprehensive searches for evidence to provide balanced, accurate results. Requesting published and unpublished studies from pharmaceutical manufacturers has been proposed as a method to engage industry stakeholders and potentially reduce reporting bias. The Drug Effectiveness Review Project (DERP) has been requesting such evidence since 2003; the purpose of this study was to retrospectively evaluate the type and impact of the evidence received. Methods: Data from "dossiers" submitted by pharmaceutical manufacturers for a set of 40 SRs conducted for DERP from July 2006 to June 2015 were retrospectively evaluated. Characteristics of data submitted in dossiers, including numbers, types, and characteristics of studies submitted and then included in DERP SRs, were abstracted. Time trends, study quality, publication status, and whether the submission represented a unique study or supplemental data to a published study were assessed. The impact of this evidence on SR conclusions was assessed using dual review. Differences were resolved through a consensus. Results: Over 9 years, 160 dossiers were received, relating to 40 DERP SRs. Out of 7360 studies/datasets submitted, 2.2% (160) were included in a SR. The ratio of submitted-to-included increased over time. Most were unique studies (23% were supplemental data sets), and almost 42% of the studies were unpublished. The majority of the studies were rated fair quality, with 7.3% rated good and 14% rated poor quality by the original SR authors. Considering all literature search sources, 7.2% of all studies included in the 40 SRs came from a dossier, and 16% of dossier studies were included in a meta-analysis. The dossier studies resulted in changes to conclusions in 42% of the SRs. Out of 46 unpublished unique studies included in a SR, 25 (54%) influenced the conclusions in favor of the manufacturers drug, 8% favored a competitor drug, and 40% favored neither. In 92% of cases favoring the manufacturer's drug, the dossier study was the only evidence for that drug in a specific population or outcome. Conclusions: In SRs conducted for DERP, few studies submitted by pharmaceutical manufacturers were ultimately included in a SR. The included data helped to reduce reporting and publication bias by filling important gaps and in some cases led to altered conclusions. [ABSTRACT FROM AUTHOR]

Background: Managing acute pain in patients with opioid use disorder (OUD) on medication (methadone, buprenorphine, or naltrexone) can be complicated by patients' higher baseline pain sensitivity and need for higher opioid doses to achieve pain relief. This review aims to evaluate the benefits and harms of acute pain management strategies for patients taking OUD medications and whether strategies vary by OUD medication type or cause of acute pain. Methods: We systematically searched multiple bibliographic sources until April 2020. One reviewer used prespecified criteria to assess articles for inclusion, extract data, rate study quality, and grade our confidence in the body of evidence, all with second reviewer checking. Results: We identified 12 observational studies—3 with control groups and 9 without. Two of the studies with control groups suggest that continuing buprenorphine and methadone in OUD patients after surgery may reduce the need for additional opioids and that ineffective pain management in patients taking methadone can result in disengagement in care. A third controlled study found that patients taking OUD medications may need higher doses of additional opioids for pain control, but provided insufficient detail to apply results to clinic practice. The only case study examining naltrexone reported that postoperative pain was managed using tramadol. We have low confidence in these findings as no studies directly addressed our question by comparing pain management strategies and few provided adequate descriptions of the dosage, timing, or rationale for clinical decisions. Discussion: We lack rigorous evidence on acute pain management in patients taking medication for OUD; however, evidence supports the practice of continuing methadone or buprenorphine for most patients during acute pain episodes. Well-described, prospective studies of adjuvant pain management strategies when OUD medications are continued would add to the existing literature base. Studies on nonopioid treatments are also needed for patients taking naltrexone. Protocol Registration: PROSPERO; CRD42019132924 [ABSTRACT FROM AUTHOR]