To assess the psychometric properties of the consideRATE questions, a measure of serious illness experience.
We recruited people at least 50 years old via paid panels online, with US-Census-based ...quotas. We randomized participants to a patient experience story at two time points. Participants completed a series of measures, including the consideRATE questions. We assessed convergent (Pearson's correlation), discriminative (one-way ANOVA with Tukey's test for multiple comparisons) and divergent (Pearson's correlation) validity. We also assessed intra-rater reliability (intra-class correlation) and responsiveness to change (t-tests).
We included 809 individuals in our analysis. We established convergent validity (r = 0.77; p < 0.001); discriminative validity (bad/neutral stories mean diff=0.4; p < 0.001; neutral/ good stories mean diff=1.3; p < 0.001) and moderate divergent validity (r = 0.57; p < 0.001). We established sensitivity to change in all stories (bad/good mean diff=1.52; p < 0.001; good/bad mean diff= −1.68; p < 0.001; neutral/bad mean diff= −0.57; p < 0.001; good/neutral mean diff= −1.11; p < 0.001; neutral/good mean diff= 1.1; p < 0.001) but one (bad/neutral mean diff= 0.4; p < 0.07). Intra-rater reliability was demonstrated between time points (r = 0.77; p < 0.001).
the consideRATE questions were reliable and valid in a simulated online test.
the consideRATE questions may be a practical way to measure serious illness experience and the effectiveness of interventions to improve it.
•Care of people who are seriously ill needs improvement.•Our measure of serious illness experience is valid and reliable in a simulated online test.•The consideRATE questions may be useful to assess and improve practice and test interventions for people who are seriously ill.
No brief patient-reported experience measure focuses on the most significant concerns of seriously ill individuals.
The objective of the study was to develop the consideRATE questions.
This ...user-centered design study had three phases. We reviewed the literature and consulted stakeholders, including caregivers, clinicians, and researchers, to identify the elements of care most important to patients (Phase 1). We refined items based on cognitive interviews with patients, families, and clinicians (Phase 2). We piloted the measure with patients and families (Phase 3).
Phase 1 resulted in seven questions addressing the following elements: 1) care team attention to patients' physical symptoms, 2) emotional symptoms, 3) environment of care, 4) respect for patients' priorities, 5) communication about future plans, 6) communication about financial and similar affairs, and 7) communication about illness trajectory. Phase 2 participants included eight patients, eight family members, and seven clinicians. We added an open-text comment option. We did not identify any other issues that were important enough to participants to include. Response choices ranged from one (very bad) to four (very good), with a not applicable option (does not apply). Phase 3 involved 15 patients and 16 family members and demonstrated the acceptability of the consideRATE questions. Most reported that the questions were not distressing, disruptive, or confusing. Completion time averaged 2.4 minutes (range 1–5).
Our brief patient-reported serious illness experience measure is based on what matters most to patients, families, and clinicians. It was acceptable to patients and families in a regional sample. It has promise for use in clinical settings.
The isolation and structure elucidation of six new bacterial metabolites spoxazomicin D (2), oxachelins B and C (4, 5), and carboxamides 6–8 and 11 previously reported bacterial metabolites (1, 3, ...9–12a, and 14–18) from Streptomyces sp. RM-14-6 is reported. Structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spectrometry data analysis, along with direct comparison to synthetic standards for 2, 11, and 12a,b. Complete 2D NMR assignments for the known metabolites lenoremycin (9) and lenoremycin sodium salt (10) were also provided for the first time. Comparative analysis also provided the basis for structural revision of several previously reported putative aziridine-containing compounds exemplified by madurastatins A1, B1, C1 (also known as MBJ-0034), and MBJ-0035 as phenol-dihydrooxazoles. Bioactivity analysis including antibacterial, antifungal, cancer cell line cytotoxicity, unfolded protein response (UPR) modulation, and EtOH damage neuroprotection revealed 2 and 5 as potent neuroprotectives and lenoremycin (9) and its sodium salt (10) as potent UPR modulators, highlighting new functions for phenol-oxazolines/salicylates and polyether pharmacophores.
Skillful communication with attention to patient and care partner priorities can help people with serious illnesses. Few patient-facing agenda-setting tools exist to facilitate such communication.
To ...develop a tool to facilitate prioritization of patient and care partner concerns during serious illness visits.
Two family members of seriously ill individuals advised.
We performed a literature review and developed a prototype agenda-setting tool. We modified the tool based on cognitive interviews with patients, families and clinicians. We piloted the tool with patients, care partners and clinicians to gain an initial impression of its perceived value.
Interviews with eight patients, eight care partners and seven clinicians, resulted in refinements to the initial tool, including supplementation with visual cues. In the pilot test, seven clinicians used the tool with 11 patients and 12 family members. Qualitatively, patients and care partners reported the guide helped them consider and assert their priorities. Clinicians reported the tool complemented usual practice. Most participants reported no distress, disruption or confusion.
Patients, care partners and clinicians appreciated centering patient priorities in serious illness visits using the agenda-setting tool. More thorough evaluation is required.
The agenda-setting tool may operationalize elements of good serious illness care.
•The experience of serious illness is poor and often misaligned with patient priorities.•Good communication can help improve patient experiences.•With user-centered design, we made an agenda-setting tool so patients and clinicians could set shared discussion priorities.•Called Serious Illness Topics, patients found the agenda-setting tool empowering.•Clinicians found it acceptable and helpful.
TP53,
the gene for the tumor-suppressor protein p53, is the most commonly mutated gene in cancer cells. In this study of head and neck cancer, about half the tumors had a
TP53
mutation. The presence ...of mutations that could disrupt the binding of p53 to a DNA target had the strongest association with decreased survival. The results indicate that a disruptive mutation of
TP53
is an independent risk factor for death among patients with head and neck cancer.
In this study of head and neck cancer, about half the tumors had a
TP53
mutation. The presence of mutations that could disrupt the binding of p53 to a DNA target had the strongest association with decreased survival.
Squamous-cell carcinoma of the head and neck is one of the most common cancers worldwide. More than 45,000 new cases are expected in the United States in 2007.
1
The disease is multifactorial in its pathogenesis and is associated with the use of tobacco
2
,
3
and alcohol
4
,
5
and infection with the human papillomavirus (HPV).
6
,
7
The abrogation of p53 function — through the mutation of its gene,
TP53
8
; the loss of heterozygosity of
TP53
9
; or interaction with viral proteins
10
— is one of the most common molecular alterations in squamous-cell carcinoma of the head and neck.
11
–
13
The . . .
Objectives: A wide variety of intraoperative tests are available in cochlear implantation. However, no consensus exists on which tests constitute the minimum necessary battery. We assembled an ...international panel of clinical experts to develop, refine, and vote upon a set of core consensus statements. Design: A literature review was used to identify intraoperative tests currently used in the field and draft a set of provisional statements. For statement evaluation and refinement, we used a modified Delphi consensus panel structure. Multiple interactive rounds of voting, evaluation, and feedback were conducted to achieve convergence. Results: Twenty-nine provisional statements were included in the original draft. In the first voting round, consensus was reached on 15 statements. Of the 14 statements that did not reach consensus, 12 were revised based on feedback provided by the expert practitioners, and 2 were eliminated. In the second voting round, 10 of the 12 revised statements reached a consensus. The two statements which did not achieve consensus were further revised and subjected to a third voting round. However, both statements failed to achieve consensus in the third round. In addition, during the final revision, one more statement was decided to be deleted due to overlap with another modified statement. Conclusions: A final core set of 24 consensus statements was generated, covering wide areas of intraoperative testing during CI surgery. These statements may provide utility as evidence-based guidelines to improve quality and achieve uniformity of surgical practice.
Qualitative research methods explore and provide deep contextual understanding of real world issues, including people’s beliefs, perspectives, and experiences. Whether through analysis of interviews, ...focus groups, structured observation, or multimedia data, qualitative methods offer unique insights in applied health services research that other approaches cannot deliver. However, many clinicians and researchers hesitate to use these methods, or might not use them effectively, which can leave relevant areas of inquiry inadequately explored. Thematic analysis is one of the most common and flexible methods to examine qualitative data collected in health services research. This article offers practical thematic analysis as a step-by-step approach to qualitative analysis for health services researchers, with a focus on accessibility for patients, care partners, clinicians, and others new to thematic analysis. Along with detailed instructions covering three steps of reading, coding, and theming, the article includes additional novel and practical guidance on how to draft effective codes, conduct a thematic analysis session, and develop meaningful themes. This approach aims to improve consistency and rigor in thematic analysis, while also making this method more accessible for multidisciplinary research teams.
Background
Prior studies demonstrate that ethanol (EtOH) exposure induces the release of intracellular calcium (CA2+) in modulation of γ‐aminobutyric acid‐ergic tone and produces concomitant ...alterations in sigma (σ)‐1 protein expression that may contribute to the development EtOH dependence. However, the influence of CA2+ released from endoplasmic reticulum (ER)‐bound inositol triphosphate (IP3) and σ‐1 receptors in regulating hippocampal function has yet to be delineated.
Methods
Rat hippocampal explants were subjected to chronic intermittent EtOH (CIE) exposure with or without the addition of IP3 inhibitor xestospongin C (0 to 0.5 μM) or σ‐1 receptor antagonist BD‐1047 (0 to 80 μM). Hippocampal viability was assessed via immunohistochemical labeling of neuron‐specific nuclear protein (NeuN)/Fox‐3 in CA1, CA3, and dentate gyrus (DG) subregions.
Results
Exposure to CIE produced consistent and significant decreases of NeuN/Fox‐3 in each primary cell layer of the hippocampal formation. Co‐exposure to xestospongin reversed these effects in the CA1 subregion and significantly attenuated these effects in the CA3 and DG regions. Xestospongin application also significantly increased NeuN/Fox‐3 immunofluorescence in EtOH‐naïve hippocampi. Co‐exposure to 20 μM BD‐1047 also reversed the loss of NeuN/Fox‐3 during CIE exposure in each hippocampal cell layer, whereas exposure to 80 μM BD‐1047 did not alter NeuN/Fox‐3 in EtOH‐treated hippocampi. By contrast, 80 μM BD‐1047 application significantly increased NeuN/Fox‐3 immunofluorescence in EtOH‐naïve hippocampi in each subregion.
Conclusions
These data suggest that EtOH stimulates ER IP3 and σ‐1 receptors to promote hippocampal loss of NeuN/Fox‐3 during CIE.
These findings suggest that, while exposed to ethanol, endoplasmic reticulum (ER)‐bound inositol triphosphate (IP3) and sigma (σ)‐1 receptors work cooperatively to promote mobilization of calcium from intracellular stores into the cytosol. This is demonstrated by the ability of xestospongin C and BD 1047, respectively, to reverse ethanol‐associated changes promoting withdrawal effects. This calcium mobilization contributes to neuroadaptions to prolonged ethanol exposure that promote a well‐characterized glutamatergic receptor‐mediated ethanol withdrawal‐induced excitotoxic cascade in the hippocampus.
A devastating feature of drug dependence is the susceptibility of relapse (40-60%) after stretches of abstinence. In both animal and human research, it has been demonstrated that cues (e.g., levers, ...paraphernalia) associated with drug reward can instigate renewed drug taking. Research has shown animals that attend to a cue that predicts reward more than the location of reward delivery when the cue is present (sign trackers) have an increase in corticosterone (CORT), a primary stress hormone when compared with animals that do not sign track. This interaction of sign tracking and CORT implicate CORT's effects as a possible pharmacological target for cue-induced relapse behaviors. PT150 is a novel glucocorticoid receptor antagonist that reduces the effects of CORT. Previous research has shown that oral administration of 40 mg/kg PT150 reduced sign tracking. To better understand dose-dependent effects and to control for more accurate doses, the current experiment hypothesized that PT150 (20/40/60 mg/kg) given by subcutaneous (SC) injection to male quail would reduce sign tracking to a keylight conditional stimulus that predicts a grain unconditioned stimulus dose dependently. Results showed that SC injection of 20 mg/kg PT150 reduced sign tracking, but 40 or 60 mg/kg did not. The main findings from the current study are that the glucocorticoid receptor antagonist PT150 reduces sign tracking behavior dose dependently, and SC administration may provide better bioavailability compared with our previous study that used an oral route of administration. The current findings support previous literature by suggesting that the glucocorticoid receptor may be a potential pharmacological target for reducing relapse-like behaviors.
Public Health Significance
The main findings from the current study are that the glucocorticoid receptor antagonist PT150 dose dependently reduces sign tracking. Because persistent sign tracking behavior is associated with drug relapse, the ability to reduce it may contribute to drug addiction treatment. Potential pharmacological treatments that alter the glucocorticoid stress system may be of significance for drug addiction research.
•Levels of EtOH and nicotine intake during co-use were pharmacologically relevant.•Increasing the fixed ratio (FR) requirement for nicotine increases EtOH intake during co-use.•Naltrexone decreased ...EtOH and water intake, but not nicotine intake during co-use.•Varenicline and r-bPiDI decreased active and inactive lever pressing for nicotine.
Background Although pharmacotherapies are available for alcohol (EtOH) or tobacco use disorders individually, it may be possible to develop a single pharmacotherapy to treat heavy drinking tobacco smokers by capitalizing on the commonalities in their mechanisms of action.
Methods Female alcohol-preferring (P) rats were trained for EtOH drinking and nicotine self-administration in two phases: (1) EtOH alone (0 vs. 15% EtOH, 2-bottle choice) and (2) concomitant access, during which EtOH access continued with access to nicotine (0.03 mg/kg/infusion, i.v.) using a 2-lever choice procedure (active vs. inactive lever) in which the fixed ratio (FR) requirement was gradually increased to FR30. When stable co-use was obtained, rats were pretreated with varying doses of naltrexone, varenicline, or r-bPiDI, an α6β2* subtype-selective nicotinic acetylcholine receptor antagonist shown previously to reduce nicotine self-administration.
Results While EtOH intake was initially suppressed in phase 2 (co-use), pharmacologically relevant intake for both substances was achieved by raising the “price” of nicotine to FR30. In phase 2, naltrexone decreased EtOH and water consumption but not nicotine intake; in contrast, naltrexone in phase 1 (EtOH only) did not significantly alter EtOH intake. Varenicline and r-bPiDI in phase 2 both decreased nicotine self-administration and inactive lever pressing, but neither altered EtOH or water consumption.
Conclusions These results indicate that increasing the “price” of nicotine increases EtOH intake during co-use. Additionally, the efficacy of naltrexone, varenicline, and r-bPiDI was specific to either EtOH or nicotine, with no efficacy for co-use. Nevertheless, future studies on combining these treatments may reveal synergistic efficacy.
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