Background
In 2008, bevacizumab received accelerated Food and Drug Administration (FDA) approval for use in human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). ...Based on the pre-clinical and preliminary clinical activity of the trastuzumab and bevacizumab combination, ECOG-ACRIN E1105 trial was developed to determine if the addition of bevacizumab to a chemotherapy and trastuzumab combination for first-line therapy would improve progression-free survival (PFS) in patients with HER2-positive MBC.
Findings
96 patients were randomized to receive standard first-line chemotherapy and trastuzumab with or without bevacizumab between November 2007 and October 2009, and 93 began protocol therapy. Induction therapy was given for 24 weeks, followed by maintenance trastuzumab with or without bevacizumab. 60% (56/93) began carboplatin and 74% (69/93) completed 6 cycles of induction therapy. Primary endpoint was PFS. Median PFS was 11.1 and 13.8 months for placebo and bevacizumab arms, respectively (hazard ratio HR 95%, Confidence Interval Cl for bevacizumab vs. placebo: 0.73 0.43–1.23, p = 0.24), and at a median follow-up of 70.7 months, median survival was 49.1 and 63 months (HR 95% Cl for OS: 1.09 0.61–1.97, p = 0.75). The most common toxicities across both arms were neutropenia and hypertension, with left ventricular systolic dysfunction, fatigue, and sensory neuropathy reported more frequently with bevacizumab.
Conclusions
In this trial, the addition of bevacizumab did not improve outcomes in patients with metastatic HER2-positive breast cancer. Although the trial was underpowered due to smaller than anticipated sample size, these findings corroborated other clinical trials during this time.
Clinical Trial Information: NCT00520975
Background
The comparative effectiveness study (ClinicalTrials.gov, NCT03016403) assessed the effects of a stepped‐care intervention versus usual care on mental health outcomes, including anxiety, ...depression, coping self‐efficacy, emotional distress (anxiety and depression combined), health‐related quality of life (HRQoL), and perceived stress among underserved patients (i.e., low‐income, uninsured, underinsured) with lung cancer (LC) and head‐and‐neck cancer (HNC).
Methods
In a randomized controlled trial, we investigated if 147 patients who received the stepped‐care intervention had better mental health outcomes compared to 139 patients who received usual care. Using an intent‐to‐treat approach, we analyzed outcomes with linear mixed models.
Results
For the primary outcomes estimated mean differences (denoted by “Δ”), depression (Δ = 1.75, 95% CI = 0.52, 2.98, p = 0.01) and coping self‐efficacy (Δ = −15.24, 95% CI = −26.12, −4.36, p = 0.01) were better for patients who received the intervention compared to patients who received usual care, but anxiety outcomes were not different. For secondary outcomes, emotional distress (Δ = 1.97, 95% CI: 0.68, 3.54, p =< 0.01) and HRQoL (Δ = −4.16 95% CI: −7.45, −0.87, p = 0.01) were better for patients who received the intervention compared to usual care patients, while perceived stress was not different across groups.
Conclusions
The stepped‐care intervention influenced depression and coping self‐efficacy, important outcomes for patients with acute illnesses like LC and HNC. Although differences in emotional distress met the minimally important differences (MID) previously reported, depression and HRQoL were not above the MID threshold. Our study is among a few to report differences in mental health outcomes for underserved LC and HNC patients after receiving a psychological intervention.
ClinicalTrials.gov identifier
NCT03016403.
To describe patient desire and reasons for specialist referrals in a gatekeeper-model managed care plan.
Cross-sectional prospective study.
We developed a patient questionnaire to gather demographic ...data and to gauge patients' desire for specialist referral and their reasons for seeking such referral. The survey was administered at 2 sites--an ambulatory care facility of a university hospital and an internal medicine clinic in a suburban ambulatory care site. Patients asked to complete the questionnaire at the university hospital site were enrolled in a gatekeeper-model managed care plan (called CU Gold); those seen at the internal medicine clinic were enrolled in a group-model health maintenance organization. Patients were asked to complete the 1-page questionnaire in the waiting room before being seen by their primary care physician.
Among the 860 CU Gold patients who met the inclusion criteria during the 3-month study period (September to December 1997), 112 (13%) reported a definite desire to see a specialist and 274 (32%) indicated a possible desire to see a specialist at the time of their primary care visit. Compared with the CU Gold patients, significantly fewer patients in the health maintenance organization indicated a definite desire to see a specialist (3% versus 13%), but a similar percentage expressed a possible desire to see a specialist (30% versus 32%). The difference in definite desire for referral between the 2 groups could not be explained by patient or primary care physician characteristics. The principal health concerns for which patients sought referral were musculoskeletal, genitourinary or gynecologic, or dermatologic problems. Need for reassurance (cited by 67% of patients), seeing a specialist before (56%), and believing the primary care physician lacked expertise (49%) were the primary reasons patients sought referral. Seventy-four percent of patients referred by their primary care provider and 54% of those not referred agreed it was a good idea to see their primary care physician first before seeing a specialist.
Patients have a significant desire for specialist referral, driven by their need for reassurance, previous specialist referral, and belief that their primary care physician does not have the requisite expertise. Patients' expectations for referral varied significantly, depending on the healthcare system (academic primary care clinic or health maintenance organization) in which they were enrolled.
Objective. To measure synovial fluid (SF) levels of interleukin‐1 receptor antagonist (IL‐1ra) and to determine the capacity of SF neutrophils (PMN) to synthesize and release IL‐1ra.
Methods. A ...sensitive and specific enzyme‐linked immunosorbent assay was used to measure SF IL‐1ra protein concentrations and IL‐1ra production by isolated SF PMN.
Results. SF IL‐1ra levels were elevated in 13 of 16 samples from patients with rheumatoid arthritis (RA) (mean 17.1 ng/ml), in 6 of 18 samples from patients with infectious or inflammatory, non‐RA arthropathies (mean 10.6 ng/ml), and in none of 11 noninflammatory SF samples. SF IL‐1ra levels correlated with SF PMN concentrations (r = 0.680, P < 0.00001). Isolated SF PMN contained preexisting IL‐1ra protein in the absence of messenger RNA (mRNA). In addition, both lipopolysaccharide and granulocyte‐macrophage colonystimulating factor induced modest increases in IL‐1ra mRNA by cultured SF PMN.
Conclusion. IL‐1ra levels are increased in >80% of RA SF samples. SF PMN produce IL‐1ra, possibly contributing to the levels of IL‐1ra present within the SF.
An examination of relevant ideas from linguistic, structuralist, and semiotic theories leads to a concept of style as theoretical construct of the competency in symbolic functioning presupposed by a ...given work or group of works. Style is viewed as only partially systematic in a structuralist sense, and along with sub-systems (s-codes in Umberto Eco's semiotic theory) styles have increasingly freer levels of 'codes'. Style is also viewed as a historical construct, and an examination of disciplines which differ significantly in their theoretical approaches leads to the placing of style studies as semiotically conceived in a position between the scientific and the speculative. Style is thus central to the explanation of music; within a model of style the theorist may incorporate the findings (often merely descriptive) of scientific or mathematical approaches as affordances but not determinants of style explanation. A hierarchical (vs. atomistic or holistic) conception of levels of (semiotic) cognitive organization allows for organization that may well go beyond the constraints implied by lower-level atomistic or Gestalt perceptual theories. Emergence due to increasingly connotational codes leads to harder-to-reconstruct levels of interpretation, which may be multiple. For that reason, the methodological focus for style reconstruction is what Nelson Goodman calls 'literal exemplification,' which can be considered a kind of 'meaningful syntax,' rather than 'metaphorical exemplification' (expression), which deals with increasingly more elusive interpretative levels. Several methodological dialectics (checks and balances) are proposed to aid in the reconstruction of, and pragmatic postulation of styles. These include history/theory, style/strategy of the individual work, system/usage, and growth/change. A discussion of usage versus system leads to the relationships between (temporal) implication and function, and a critical look at concepts of prolongation. Style change is distinguished from growth (for theoretical purposes) by the degree of (hierarchical) reformulation of (levels or) constraints required. Implications of the proposed model of style for the theories of Schenker, Meyer, Narmour, Rosen, Jackendoff and Lerdahl, and Keiler are investigated. Appendices include a brief sketch of concepts of style in music and illustrations of method with respect to different musical problems.
A retrospective comparison was undertaken to determine if the risks of undergoing surgery for nonvariceal upper gastrointestinal hemorrhage had changed between 1972 and 1982. In 1982, patients were ...on the average 9 years older, there was a significant decrease in bleeding from duodenal ulcers compared with 1972 data, gastric ulcer rates remained unchanged, and diffuse gastritis occurred more frequently in 1982. Mortality and morbidity rates showed no significant differences; however, the patient population did change with the emergence of older patients, in whom bleeding developed after hospitalization for other reasons. These patients comprised 30 percent of the 1982 study population. If further improvements in surgical treatment of upper gastrointestinal hemorrhage are to occur, these patients must be identified and aggressively managed.
National-level summaries of crop production and nutrient use efficiency, important for international comparisons, only partially elucidate agricultural dynamics within a country. Agricultural ...production and associated environmental impacts in large countries vary significantly because of regional differences in crops, climate, resource use and production practices. Here, we review patterns of regional crop production, nitrogen use efficiency (NUE), and major inputs of nitrogen to US crops over 1987–2012, based on the Farm Resource Regions developed by the Economic Research Service (USDA-ERS). Across the US, NUE generally decreased over time over the period studied, mainly due to increased use in mineral N fertilizer above crop N requirements. The Heartland region dominates production of major crops and thus tends to drive national patterns, showing linear response of crop production to nitrogen inputs broadly consistent with an earlier analysis of global patterns of country-scale data by Lassaletta et al. (2014). Most other regions show similar responses, but the Eastern Uplands region shows a negative response to nitrogen inputs, and the Southern Seaboard shows no significant relationship. The regional differences appear as two branches in the response of aggregate production to N inputs on a cropland area basis, but not on a total area basis, suggesting that the type of scaling used is critical under changing cropland area. Nitrogen use efficiency (NUE) is positively associated with fertilizer as a percentage of N inputs in four regions, and all regions considered together. NUE is positively associated with crop N fixation in all regions except Northern Great Plains. It is negatively associated with manure (livestock excretion); in the US, manure is still treated largely as a waste to be managed rather than a nutrient resource. This significant regional variation in patterns of crop production and NUE vs N inputs, has implications for environmental quality and food security.
Display omitted
•NUE decreased in a majority of regions in the US from the decade 1987–97 to 2002–12.•Cropland area generally decreased & mineral fertilizer increased over the same period.•Response of crop production to nitrogen inputs varies regionally across the country.•Patterns differ depending upon whether cropland area or total area scaling is used in each region.
A Telerobotic System for Transnasal Surgery Burgner, Jessica; Rucker, D. Caleb; Gilbert, Hunter B. ...
IEEE/ASME transactions on mechatronics,
06/2014, Letnik:
19, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Mechanics-based models of concentric tube continuum robots have recently achieved a level of sophistication that makes it possible to begin to apply these robots to a variety of real-world clinical ...scenarios. Endonasal skull base surgery is one such application, where their small diameter and tentacle-like dexterity are particularly advantageous. In this paper, we provide the medical motivation for an endonasal surgical robot featuring concentric tube manipulators, and describe our model-based design and teleoperation methods, as well as a complete system incorporating image guidance. Experimental demonstrations using a laparoscopic training task, a cadaver reachability study, and a phantom tumor resection experiment illustrate that both novice and expert users can effectively teleoperate the system, and that skull base surgeons can use the robot to achieve their objectives in a realistic surgical scenario.
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