ABSTRACT
Aims Marketing that promotes mixing caffeinated ‘energy’ drinks with alcoholic beverages (e.g. Red Bull with vodka) targets young drinkers and conveys the expectation that caffeine will ...offset the sedating effects of alcohol and enhance alertness. Such beliefs could result in unwarranted risk taking (e.g. driving while intoxicated). The aim of this study was to assess the acute effects of caffeinated versus non‐caffeinated alcoholic beverages on a simulated driving task and attention/reaction time.
Design We conducted a 2 × 2 between‐groups randomized trial in which participants were randomized to one of four conditions: beer and non‐alcoholic beer, with and without caffeine added. Caffeine was added in the same proportion as found in a commercially available caffeinated beer (69 mg/12 oz of beer at 4.8% alc. by vol).
Participants Participants were 127 non‐dependent, heavy episodic, young adult drinkers (age 21–30) who were college students or recent graduates. The target breath alcohol level was 0.12 g%.
Measures Driving performance was assessed with a driving simulator; sustained attention/reaction with the Psychomotor Vigilance Task (PVT).
Findings Across the driving and attention/reaction time we found main effects for alcohol, with alcohol significantly impairing driving and sustained attention/reaction time, with mainly large statistical effects; however, the addition of caffeine had no main or interaction effects on performance.
Conclusion The addition of caffeine to alcohol does not appear to enhance driving or sustained attention/reaction time performance relative to alcohol alone.
Health technology assessment organizations evaluate medical therapies and technologies to help inform coverage and reimbursement decisions for payers around the globe. Even as they establish strict ...review processes, these organizations--and the reimbursement authorities that use their assessments--have sometimes handled cancer interventions with special care. We found that some countries have created separate health technology assessment pathways for cancer treatment, while others have eased access to cancer treatments through end-of-life or disease-severity exceptions within health technology assessment policies. In the United States, although no separate evaluation pathways exist for cancer, cancer drugs receive special status by virtue of unique Medicare rules covering off-label indications. Worldwide, we demonstrate that health technology assessment organizations are struggling with cancer's "exceptionalism."
Photodegradation has been recognized as a significant driver of plant litter decomposition in drylands. Another potential driver is the thermal emission of trace gases that occurs in the absence of ...solar radiation and microbial activity. Most field assessments documenting photodegradation have employed filters that absorb solar radiation, along with transparent filter controls; faster litter decay under transparent filters is taken as evidence of photodegradation. However, the temperature of litter under transparent filters is often higher, and its faster decay might conceivably stem from greater thermal emission, rather than photodegradation. If true, the growing consensus that photodegradation is a significant driver of litter decay needs rethinking. We assessed the contribution of thermal emission of CO2 and CH4 to the C loss of 12 litter types over a 34‐month photodegradation study in the Sonoran Desert by quantifying thermal emission responses and using field litter temperatures to estimate emissions. Emission of both gases from litter increased exponentially with temperature. Emission of CO2 was much greater than CH4, but their rates were strongly correlated. Concentrations of surface waxes and dissolved organic C in litter were strong predictors of emission of both gases. Emission declined from dried green leaves to naturally senesced litter, and as litter decayed. Diurnal litter temperature averaged 39.8°C under transparent filters over the field experiment and averaged 1.7°C higher than that of litter under filters that absorbed UV through blue solar wavelengths. Through all mechanisms, litter lost an average of 77.8% of its original C under transparent filters and 60.8% under filters that absorbed UV through blue wavelengths. However, thermal emission of these gases accounted for only 0.8% of the original C in litter under transparent filters and 1.0% under filters that absorbed UV through blue wavelengths, corresponding to only 1.2% and 2.0% of the total C lost from litter. While litter temperatures were higher under transparent filters, thermal emission losses from this litter were lower because emission from this litter declined faster with decay. We conclude that thermal abiotic emission was a minor C loss pathway and that photodegradation was responsible for the faster decay of litter in sunlight.
Abstract Episode-based payment, commonly referred to as bundled payment, has emerged as a key component of U.S. health care payment reform. Bundled payments are appealing as they share the financial ...risk of treating patients between payers and providers, encouraging the delivery of cost-effective care. A closely watched example is the U.S. End Stage Renal Disease (ESRD) Prospective Payment System, known as the ‘expanded ESRD bundle.’ In this paper we consider the expanded ESRD bundle 2 years after its implementation. First, we discuss emerging lessons, including how implementation has changed dialysis care with respect to the use of erythropoietin stimulating agents, how implementation has led to an increase in the use of home-based peritoneal dialysis, and how it may have contributed to the market consolidation of dialysis providers. Second, we use the expanded ESRD bundle to illustrate the importance of accounting for stakeholder input and staging policy implementation. Third, we highlight the need to consider system-wide consequences of implementing bundled payment policies. Fourth, we suggest how bundled payments may create research opportunities. Bundled payment policies offer opportunities and challenges. Their success will be determined not only by impacts on cost containment, but also to the extent they encourage high quality care.
Abstract
Photodegradation has been recognized as a significant driver of plant litter decomposition in drylands. Another potential driver is the thermal emission of trace gases that occurs in the ...absence of solar radiation and microbial activity. Most field assessments documenting photodegradation have employed filters that absorb solar radiation, along with transparent filter controls; faster litter decay under transparent filters is taken as evidence of photodegradation. However, the temperature of litter under transparent filters is often higher, and its faster decay might conceivably stem from greater thermal emission, rather than photodegradation. If true, the growing consensus that photodegradation is a significant driver of litter decay needs rethinking. We assessed the contribution of thermal emission of
CO
2
and
CH
4
to the C loss of 12 litter types over a 34‐month photodegradation study in the Sonoran Desert by quantifying thermal emission responses and using field litter temperatures to estimate emissions. Emission of both gases from litter increased exponentially with temperature. Emission of
CO
2
was much greater than
CH
4
, but their rates were strongly correlated. Concentrations of surface waxes and dissolved organic C in litter were strong predictors of emission of both gases. Emission declined from dried green leaves to naturally senesced litter, and as litter decayed. Diurnal litter temperature averaged 39.8°C under transparent filters over the field experiment and averaged 1.7°C higher than that of litter under filters that absorbed
UV
through blue solar wavelengths. Through all mechanisms, litter lost an average of 77.8% of its original C under transparent filters and 60.8% under filters that absorbed
UV
through blue wavelengths. However, thermal emission of these gases accounted for only 0.8% of the original C in litter under transparent filters and 1.0% under filters that absorbed
UV
through blue wavelengths, corresponding to only 1.2% and 2.0% of the total C lost from litter. While litter temperatures were higher under transparent filters, thermal emission losses from this litter were lower because emission from this litter declined faster with decay. We conclude that thermal abiotic emission was a minor C loss pathway and that photodegradation was responsible for the faster decay of litter in sunlight.
Abstract Objective To investigate Food and Drug Administration (FDA) regulatory actions against drug companies' health economic promotions from 2002 through 2011 to understand how frequently and in ...what circumstances the agency has considered such promotions false or misleading. Methods We reviewed all warning letters and notices of violation (“untitled letters”) issued by the FDA's Division of Drug Marketing, Advertising and Communications (DDMAC) to pharmaceutical companies from January 2002 through December 2011. We analyzed letters containing a violation related to “health economic promotion,” defined according to one of several categories (e.g., implied claims of cost savings due to work productivity or economic claims containing unsupported statements about effectiveness or safety). We also collected information on factors such as the indication and type of media involved and whether the letter referenced Section 114 of the Food and Drug Administration Modernization Act. Results Of 291 DDMAC letters sent to pharmaceutical companies during the study period, 35 (12%) cited a health economic violation. The most common type of violation cited was an implied claim of cost savings due to work productivity or functioning (found in 20 letters) and economic claims containing unsubstantiated comparative claims of effectiveness, safety, or interchangeability (7 letters). The violations covered various indications, mostly commonly psychiatric disorders (6 letters) and pain (6 letters). No DDMAC letter pertained to Food and Drug Administration Modernization Act Section 114. Conclusion The FDA has cited inappropriate health economic promotions in roughly 12% of the letters issued by the DDMAC. The letters highlight drug companies' interest in promoting the value of their products and the FDA's concerns in certain cases about the lack of supporting evidence.
Nursing programs are challenged to prepare future nurses to provide care and affect determinants of health for individuals and populations. This article advances a pedagogical model for clinical ...education that builds concepts related to both population-level care and direct care in the community through a contextual learning approach. Because the conceptual pillars and hybrid constructivist approach allow for conceptual learning consistency across experiences, the model expands programmatic capacity to use diverse community clinical sites that accept only small numbers of students. The concept-based and hybrid constructivist learning approach is expected to contribute to the development of broad intellectual skills and lifelong learning. The pillar concepts include determinants of health and nursing care of population aggregates; direct care, based on evidence and best practices; appreciation of lived experience of health and illness; public health nursing roles and relationship to ethical and professional formation; and multidisciplinary collaboration.
Objective: To investigate Food and Drug Administration (FDA) regulatory actions against drug companies' health economic promotions from 2002 through 2011 to understand how frequently and in what ...circumstances the agency has considered such promotions false or misleading. Methods: We reviewed all warning letters and notices of violation ("untitled letters") issued by the FDA's Division of Drug Marketing, Advertising and Communications (DDMAC) to pharmaceutical companies from January 2002 through December 2011. We analyzed letters containing a violation related to "health economic promotion," defined according to one of several categories (e.g., implied claims of cost savings due to work productivity or economic claims containing unsupported statements about effectiveness or safety). We also collected information on factors such as the indication and type of media involved and whether the letter referenced Section 114 of the Food and Drug Administration Modernization Act. Results: Of 291 DDMAC letters sent to pharmaceutical companies during the study period, 35 (12%) cited a health economic violation. The most common type of violation cited was an implied claim of cost savings due to work productivity or functioning (found in 20 letters) and economic claims containing unsubstantiated comparative claims of effectiveness, safety, or interchangeability (7 letters). The violations covered various indications, mostly commonly psychiatric disorders (6 letters) and pain (6 letters). No DDMAC letter pertained to Food and Drug Administration Modernization Act Section 114. Conclusion: The FDA has cited inappropriate health economic promotions in roughly 12% of the letters issued by the DDMAC. The letters highlight drug companies' interest in promoting the value of their products and the FDA's concerns in certain cases about the lack of supporting evidence. Adapted from the source document.
Bone marrow (BM) metastasis of breast cancer (BC) can recur even decades after initial diagnosis and treatment, implying the long-term survival of disseminated cancer cells in a dormant state. Here ...we investigated the role of microRNAs (miRNA) transmitted from BM stroma to BC cells via gap junctions and exosomes in tumor cell quiescence. MDA-MB-231 and T47D BC cells arrest in G(0) phase of the cell cycle when cocultured with BM stroma. Analyses of miRNA expression profiles identified numerous miRNAs implicated in cell proliferation including miR-127, -197, -222, and -223 targeting CXCL12. Subsequently, we showed that these CXCL12-specific miRNAs are transported from BM stroma to BC cells via gap junctions, leading to reduced CXCL12 levels and decreased proliferation. Stroma-derived exosomes containing miRNAs also contributed to BC cell quiescence, although to a lesser degree than miRNAs transmitted via gap junctions. This study shows that the transfer of miRNAs from BM stroma to BC cells might play a role in the dormancy of BM metastases.
Local cancer relapse risk after breast conservation surgery followed by radiotherapy has fallen sharply in many countries, and is influenced by patient age and clinicopathological factors. We ...hypothesise that partial-breast radiotherapy restricted to the vicinity of the original tumour in women at lower than average risk of local relapse will improve the balance of beneficial versus adverse effects compared with whole-breast radiotherapy.
IMPORT LOW is a multicentre, randomised, controlled, phase 3, non-inferiority trial done in 30 radiotherapy centres in the UK. Women aged 50 years or older who had undergone breast-conserving surgery for unifocal invasive ductal adenocarcinoma of grade 1–3, with a tumour size of 3 cm or less (pT1–2), none to three positive axillary nodes (pN0–1), and minimum microscopic margins of non-cancerous tissue of 2 mm or more, were recruited. Patients were randomly assigned (1:1:1) to receive 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast radiotherapy and 40 Gy to the partial breast (reduced-dose group), or 40 Gy to the partial breast only (partial-breast group) in 15 daily treatment fractions. Computer-generated random permuted blocks (mixed sizes of six and nine) were used to assign patients to groups, stratifying patients by radiotherapy treatment centre. Patients and clinicians were not masked to treatment allocation. Field-in-field intensity-modulated radiotherapy was delivered using standard tangential beams that were simply reduced in length for the partial-breast group. The primary endpoint was ipsilateral local relapse (80% power to exclude a 2·5% increase non-inferiority margin at 5 years for each experimental group; non-inferiority was shown if the upper limit of the two-sided 95% CI for the local relapse hazard ratio HR was less than 2·03), analysed by intention to treat. Safety analyses were done in all patients for whom data was available (ie, a modified intention-to-treat population). This study is registered in the ISRCTN registry, number ISRCTN12852634.
Between May 3, 2007, and Oct 5, 2010, 2018 women were recruited. Two women withdrew consent for use of their data in the analysis. 674 patients were analysed in the whole-breast radiotherapy (control) group, 673 in the reduced-dose group, and 669 in the partial-breast group. Median follow-up was 72·2 months (IQR 61·7–83·2), and 5-year estimates of local relapse cumulative incidence were 1·1% (95% CI 0·5–2·3) of patients in the control group, 0·2% (0·02–1·2) in the reduced-dose group, and 0·5% (0·2–1·4) in the partial-breast group. Estimated 5-year absolute differences in local relapse compared with the control group were −0·73% (−0·99 to 0·22) for the reduced-dose and −0·38% (−0·84 to 0·90) for the partial-breast groups. Non-inferiority can be claimed for both reduced-dose and partial-breast radiotherapy, and was confirmed by the test against the critical HR being more than 2·03 (p=0·003 for the reduced-dose group and p=0·016 for the partial-breast group, compared with the whole-breast radiotherapy group). Photographic, patient, and clinical assessments recorded similar adverse effects after reduced-dose or partial-breast radiotherapy, including two patient domains achieving statistically significantly lower adverse effects (change in breast appearance p=0·007 for partial-breast and breast harder or firmer p=0·002 for reduced-dose and p<0·0001 for partial-breast) compared with whole-breast radiotherapy.
We showed non-inferiority of partial-breast and reduced-dose radiotherapy compared with the standard whole-breast radiotherapy in terms of local relapse in a cohort of patients with early breast cancer, and equivalent or fewer late normal-tissue adverse effects were seen. This simple radiotherapy technique is implementable in radiotherapy centres worldwide.
Cancer Research UK.
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