Sex differences in gray matter, white matter, and regional brain perfusion in young, healthy adults.

Cerebrovascular and neurological diseases exhibit sex-specific patterns in prevalence, severity, and regional specificity, some of which are associated with altered cerebral blood flow (CBF). Females often exhibit higher resting CBF, but understanding the impact of sex per se on CBF is hampered by study variability in age, comorbidities, medications, and control for menstrual cycle or hormone therapies. A majority of studies report whole brain CBF without differentiating between gray and white matter or without assessing regional CBF. Thus fundamental sex differences in regional or whole brain CBF remain unclarified. While controlling for the above confounders, we tested the hypothesis that females will exhibit higher total gray and white matter perfusion as well as regional gray matter perfusion. Adults 18-30 yr old (females = 22 and males = 26) were studied using arterial spin labeling (ASL) magnetic resonance imaging (MRI) scans followed by computational anatomy toolbox (CAT12) analysis in statistical parametric mapping (SPM12) to quantify CBF relative to brain volume. Females displayed 40% higher perfusion globally (females = 62 ± 9 and males = 45 ± 10 mL/100 g/min, P < 0.001), gray matter (females = 75 ± 11 and males = 54 ± 12 mL/100 g/min, P < 0.001), and white matter (females = 44 ± 6 and males = 32 ± 7 mL/100 g/min, P < 0.001). Females exhibited greater perfusion than males in 67 of the 68 regions tested, ranging from 14% to 66% higher. A second MRI approach (4-dimensional flow) focused on large arteries confirmed the sex difference in global CBF. These data indicate strikingly higher basal CBF in females at global, gray, and white matter levels and across dozens of brain regions and offer new clarity into fundamental sex differences in global and regional CBF regulation before aging or pathology.NEW & NOTEWORTHY MRI used to measure cerebral blood flow (CBF) in gray matter, white matter, and 68 regions in healthy men and women. This study demonstrated that CBF is 40% higher in women, the highest sex difference reported, when controlling for numerous important clinical confounders like age, smoking, menstrual cycle, comorbidities, and medications.

An oral glucose tolerance test does not affect cerebral blood flow: role of NOS.

Animal data indicate that insulin triggers a robust nitric oxide synthase (NOS)-mediated dilation in cerebral arteries similar to the peripheral tissue vasodilation observed in healthy adults. Insulin's role in regulating cerebral blood flow (CBF) in humans remains unclear but may be important for understanding the links between insulin resistance, diminished CBF, and poor brain health outcomes. We tested the hypothesis that an oral glucose challenge (oral glucose tolerance test, OGTT), which increases systemic insulin and glucose, would acutely increase CBF in healthy adults due to NOS-mediated vasodilation, and that changes in CBF would be greater in anterior regions where NOS expression or activity may be greater. In a randomized, single-blind approach, 18 young healthy adults (24 ± 5 yr) underwent magnetic resonance imaging (MRI) with a placebo before and after an OGTT (75 g glucose), and 11 of these adults also completed an NG-monomethyl-l-arginine (l-NMMA) visit. Four-dimensional (4-D) flow MRI quantified macrovascular CBF and arterial spin labeling (ASL) quantified microvascular perfusion. Subjects completed baseline imaging with a placebo (or l-NMMA), then consumed an OGTT followed by MRI scans and blood sampling every 10-15 min for 90 min. Contrary to our hypothesis, total CBF (P = 0.17) and global perfusion (P > 0.05) did not change at any time point up to 60 min after the OGTT, and no regional changes were detected. l-NMMA did not mediate any effect of OGTT on CBF. These data suggest that insulin-glucose challenge does not acutely alter CBF in healthy adults.

Randomized controlled trial of a brief cognitive-behavioral strategies intervention for the pain, fatigue, and sleep disturbance symptom cluster in advanced cancer.

OBJECTIVE: Patients receiving treatment for advanced cancer suffer significant symptom burden, including co-occurring pain, fatigue, and sleep disturbance. There is limited evidence for effective interventions targeting this common symptom cluster. METHODS: A randomized controlled trial of a brief cognitive-behavioral strategies (CBS) intervention was conducted. A sample of 164 patients with advanced cancer receiving chemotherapy practiced imagery, relaxation, and distraction exercises or listened to cancer education recordings (attention-control) to manage co-occurring pain, fatigue, and sleep disturbance over a 9-week period. Symptom cluster severity, distress, and interference with daily life were measured at baseline and 3, 6, and 9 weeks. We also evaluated the moderating influence of imaging ability and number of concurrent symptoms, and mediating effects of changes in stress, anxiety, outcome expectancy, and perceived control over symptoms. RESULTS: Compared with the cancer education condition, participants receiving the CBS intervention reported less symptom cluster distress at week 6 (M = 1.82 vs 2.15 on a 0-4 scale, P < .05). No other group differences were statistically significant. The number of concurrent symptoms moderated the intervention effect on symptom cluster interference. Changes in stress, outcome expectancy, and perceived control mediated the extent of intervention effects on symptom outcomes, primarily at weeks 6 and 9. CONCLUSIONS: The brief CBS intervention had limited effects in this trial. However, findings regarding potential mediators affirm hypothesized mechanisms and provide insight into ways to strengthen future interventions to reduce the suffering associated with co-occurring pain, fatigue, and sleep disturbance.

Reduced basal macrovascular and microvascular cerebral blood flow in young adults with metabolic syndrome: potential mechanisms.

Ninety-million Americans suffer metabolic syndrome (MetSyn), increasing the risk of diabetes and poor brain outcomes, including neuropathology linked to lower cerebral blood flow (CBF), predominantly in anterior regions. We tested the hypothesis that total and regional CBF is lower in MetSyn more so in the anterior brain and explored three potential mechanisms. Thirty-four controls (25 ± 5 yr) and 19 MetSyn (30 ± 9 yr), with no history of cardiovascular disease/medications, underwent four-dimensional flow magnetic resonance imaging (MRI) to quantify macrovascular CBF, whereas arterial spin labeling quantified brain perfusion in a subset (n = 38/53). Contributions of cyclooxygenase (COX; n = 14), nitric oxide synthase (NOS, n = 17), or endothelin receptor A signaling (n = 13) were tested with indomethacin, NG-monomethyl-L-arginine (L-NMMA), and Ambrisentan, respectively. Total CBF was 20 ± 16% lower in MetSyn (725 ± 116 vs. 582 ± 119 mL/min, P < 0.001). Anterior and posterior brain regions were 17 ± 18% and 30 ± 24% lower in MetSyn; reductions were not different between regions (P = 0.112). Global perfusion was 16 ± 14% lower in MetSyn (44 ± 7 vs. 36 ± 5 mL/100 g/min, P = 0.002) and regionally in frontal, occipital, parietal, and temporal lobes (range 15-22%). The decrease in CBF with L-NMMA (P = 0.004) was not different between groups (P = 0.244, n = 14, 3), and Ambrisentan had no effect on either group (P = 0.165, n = 9, 4). Interestingly, indomethacin reduced CBF more in Controls in the anterior brain (P = 0.041), but CBF decrease in posterior was not different between groups (P = 0.151, n = 8, 6). These data indicate that adults with MetSyn exhibit substantially reduced brain perfusion without regional differences. Moreover, this reduction is not due to loss of NOS or gain of ET-1 signaling but rather a loss of COX vasodilation.NEW & NOTEWORTHY We tested the impact of insulin resistance (IR) on resting cerebral blood flow (CBF) in adults with metabolic syndrome (MetSyn). Using MRI and research pharmaceuticals to study the role of NOS, ET-1, or COX signaling, we found that adults with MetSyn exhibit substantially lower CBF that is not explained by changes in NOS or ET-1 signaling. Interestingly, adults with MetSyn show a loss of COX-mediated vasodilation in the anterior but not posterior circulation.

Revisiting patient-related barriers to cancer pain management in the context of the US opioid crisis.

ABSTRACT: Patient fear of addiction is a well-documented barrier to the use of analgesic medications for cancer pain control. Over the past 2 decades in the United States, an "opioid crisis" has arisen, accompanied by risk messages delivered through news outlets, public health education, and patient-provider communication. The purpose of this study was to determine if patient-related barriers to cancer pain management-specifically, fears of addiction-and related pain outcomes (pain severity, pain interference with daily life, and adequacy of pain management) have worsened over the last 20 years. A sample of 157 outpatients with active recurrent or active metastatic cancer completed the Barriers Questionnaire-II (BQ-II) and measures of pain and analgesic use. We identified 7 comparison studies published between 2002 and 2020 that reported patient-related barriers using the BQ-II. Significant linear relationships were found between later year of publication and greater fear of addiction (harmful effect subscale score, B = 0.0350, R2 = 0.0347, F1,637 = 23.19, P < 0.0001) and between year of publication and more pain management barriers overall (total BQ-II score, B = 0.039, R2 = 0.065, F1,923 = 73.79, P < 0.0001). Relationships between BQ-II scores (harmful effect and total) and pain outcomes did not change over time. Despite worsening in patient-related barriers, the proportion of patients with adequate vs inadequate analgesic use did not differ over time. Notably, 40% of participants reported inadequate analgesic use, a statistic that has not improved in 20 years. Additional research is necessary to clarify factors contributing to changing beliefs. Findings indicate a continuing need for clinical and possibly system/policy-level interventions to support adequate cancer pain management.

Testing mediation in nursing research: beyond Baron and Kenny.

BACKGROUND: R. M. Baron and D. A. Kenny (1986) defined mediation and described how to perform statistical tests of mediation hypotheses. Their approach to testing mediation has been used extensively in the nursing literature. However, many statisticians have identified problems with the Baron and Kenny approach. PURPOSE: The aim of this paper is to critically evaluate alternative approaches to testing mediation. APPROACH: The Baron and Kenny approach and its shortcomings are briefly reviewed. A critical analysis of 17 alternate methods in three categories is then presented: (a)causal steps, (b) difference in coefficients, and (c) product of coefficients. The evaluation focuses on Type I error rate control, power, ease of computation, and versatility of use. RESULTS: Of the methods that control Type I error rate adequately, the joint significance test of [alpha] and [beta], the asymmetric distribution of products test, and the test of the products using the percentile bootstrap method are the most powerful tests of mediation. Of these three, the joint significance test of [alpha] and [beta] is superior due to its computational ease and versatility of use. DISCUSSION: Knowledge development in nursing will benefit from continued research testing mediation models. Nurse researchers could move beyond the Baron and Kenny approach to utilize more robust tests of mediation.

Simpson's paradox and experimental research.

BACKGROUND: Experimental research in nursing has increased considerably in recent years. To improve the quality of such research, it is critical to reduce threats to internal validity. One threat that has received inadequate attention in the nursing literature is Simpson's paradox--a case of extreme confounding that can lead to erroneous conclusions about the effects of an experimental intervention. In fact, it can lead to a conclusion about an intervention effect that is the opposite of the correct inference. APPROACH: The aims of this study were to describe Simpson's paradox, provide a hypothetical example, and discuss approaches to avoiding the paradox. RESULTS: The paradox is due to the combination of an overlooked confounding variable and a disproportionate allocation of that variable among experimental groups. Different designs and analysis approaches that can be used to avoid the paradox are presented. DISCUSSION: Simpson's paradox can be avoided by selecting an appropriate experimental design and analysis that incorporates the confounding variable in such a way as to obtain unconfounded estimates of treatment effects, thus more accurately answering the research question.

A randomized trial of a representational intervention to decrease cancer pain (RIDcancerPain).

OBJECTIVE: Based on theories regarding cognitive representations of illness and processes of conceptual change, a representational intervention to decrease cancer pain (RIDcancerPain) was developed and its efficacy tested. DESIGN: A two-group RCT (RIDcancerPain versus control) with outcome and mediating variables assessed at baseline (T1) and 1 and 2 months later (T2 and T3). Subjects were 176 adults with pain related to metastatic cancer. MAIN OUTCOME MEASURES: Outcome variables were two pain severity measures (BPI and TPQM), pain interference with life, and overall quality of life. Mediating variables were attitudinal barriers to pain management and coping (medication use). RESULTS: One hundred and fifty subjects completed the study. Subjects in RIDcancerPain (T1-T2 and T1-T3) showed greater decreases in Barrier scores than those in control. Subjects in RIDcancerPain (T1-T3) showed greater decreases in pain severity than those in control. Change in Barriers scores mediated the effect of RIDcancerPain on pain severity. CONCLUSION: RIDcancerPain was efficacious with respect to some outcomes. Further work is needed to strengthen it.

Benchmarking the effectiveness of psychotherapy treatment for adult depression in a managed care environment: a preliminary study.

This preliminary study evaluated the effectiveness of psychotherapy treatment for adult clinical depression provided in a natural setting by benchmarking the clinical outcomes in a managed care environment against effect size estimates observed in published clinical trials. Overall results suggest that effect size estimates of effectiveness in a managed care context were comparable to effect size estimates of efficacy observed in clinical trials. Relative to the 1-tailed 95th-percentile critical effect size estimates, effectiveness of treatment provided in this setting was observed to be between 80% (patients with comorbidity and without antidepressants) and 112% (patients without comorbidity concurrently on antidepressants) as compared to the benchmarks. Because the nature of the treatments delivered in the managed care environment were unknown, it was not possible to make conclusions about treatments. However, while replications are warranted, concerns that psychotherapy delivered in a naturalistic setting is inferior to treatments delivered in clinical trials appear unjustified.

Evaluation of the Symptom Representation Questionnaire (SRQ) for assessing cancer-related symptoms.

Multidimensional, multisymptom approaches to cancer symptom assessment and management have been emphasized across health disciplines. However, each dimension that is assessed significantly increases patient/subject burden. Efficient, reliable, and valid assessment of the critical dimensions of patients' most salient symptoms is important in clinical and research settings. The Symptom Representation Questionnaire (SRQ), derived from information processing theory, assesses critical cognitive and emotional factors that are known to influence coping and outcomes. The SRQ was developed and evaluated in a three-phase process: (1) item selection, modification, and review by theoretical and clinical experts; (2) pilot evaluation of feasibility and psychometric properties; and (3) large sample psychometric evaluation. In Phase 3, members (n=713) of the National Ovarian Cancer Coalition participated via mailed surveys. Internal consistency was good for all subscales (alpha=0.63-0.88). The internal structure of the SRQ was theoretically consistent except that emotional representation, identity, and consequence items all loaded onto a single factor. Between-group comparisons supported construct validity: Representations differed between long-term survivors and women with active disease. Finally, there were significant correlations between SRQ subscales and Symptom Interference and Life Satisfaction. The SRQ appears to be a psychometrically sound instrument for assessing representations of cancer-related symptoms. This instrument could play an essential role in advancing knowledge of the relationships among representations of symptoms, symptom management processes, and symptom-related outcomes. It could also be used in intervention research when changes in symptom representations are hypothesized to mediate changes in outcomes as a result of psychoeducational interventions.

Oncology nurses' use of nondrug pain interventions in practice.

Cancer pain management guidelines recommend nondrug interventions as adjuvants to analgesic medications. Although physicians typically are responsible for pharmacologic pain treatments, oncology staff nurses, who spend considerable time with patients, are largely responsible for identifying and implementing nondrug pain treatments. Oncology nurses' use of nondrug interventions, however, has not been well studied. The purpose of this study was to describe oncology nurses' use of four nondrug interventions (music, guided imagery, relaxation, distraction) and to identify factors that influence their use in practice. A national sample of 724 oncology staff nurses completed a mailed survey regarding use of the nondrug interventions in practice, beliefs about the interventions, and demographic characteristics. The percentages of nurses who reported administering the strategies in practice at least sometimes were 54% for music, 40% for guided imagery, 82% for relaxation, and 80% for distraction. Use of each nondrug intervention was predicted by a composite score on beliefs about effectiveness of the intervention (e.g., perceived benefit; P<0.025) and a composite score on beliefs about support for carrying out the intervention (e.g., time; P<0.025). In addition, use of guided imagery was predicted by a composite score on beliefs about characteristics of patients who may benefit from the intervention (e.g., cognitive ability; P<0.05). Some nurse demographic, professional preparation, and practice environment characteristics also predicted use of individual nondrug interventions. Efforts to improve application of nondrug interventions should focus on innovative educational strategies, problem solving to secure support, and development and testing of new delivery methods that require less time from busy staff nurses.

The Role of Inflammation in the Pain, Fatigue, and Sleep Disturbance Symptom Cluster in Advanced Cancer.

CONTEXT: Symptom researchers have proposed a model of inflammatory cytokine activity and dysregulation in cancer to explain co-occurring symptoms including pain, fatigue, and sleep disturbance. OBJECTIVES: We tested the hypothesis that psychological stress accentuates inflammation and that stress and inflammation contribute to one's experience of the pain, fatigue, and sleep disturbance symptom cluster (symptom cluster severity, symptom cluster distress) and its impact (symptom cluster interference with daily life, quality of life). METHODS: We used baseline data from a symptom cluster management trial. Adult participants (N = 158) receiving chemotherapy for advanced cancer reported pain, fatigue, and sleep disturbance on enrollment. Before intervention, participants completed measures of demographics, perceived stress, symptom cluster severity, symptom cluster distress, symptom cluster interference with daily life, and quality of life and provided a blood sample for four inflammatory biomarkers (interleukin-1ß, interleukin-6, tumor necrosis factor-α, and C-reactive protein). RESULTS: Stress was not directly related to any inflammatory biomarker. Stress and tumor necrosis factor-α were positively related to symptom cluster distress, although not symptom cluster severity. Tumor necrosis factor-α was indirectly related to symptom cluster interference with daily life, through its effect on symptom cluster distress. Stress was positively associated with symptom cluster interference with daily life and inversely with quality of life. Stress also had indirect effects on symptom cluster interference with daily life, through its effect on symptom cluster distress. CONCLUSION: The proposed inflammatory model of symptoms was partially supported. Investigators should test interventions that target stress as a contributing factor in co-occurring pain, fatigue, and sleep disturbance and explore other factors that may influence inflammatory biomarker levels within the context of an advanced cancer diagnosis and treatment.

Benchmarks for psychotherapy efficacy in adult major depression.

This study estimates pretreatment-posttreatment effect size benchmarks for the treatment of major depression in adults that may be useful in evaluating psychotherapy effectiveness in clinical practice. Treatment efficacy benchmarks for major depression were derived for 3 different types of outcome measures: the Hamilton Rating Scale for Depression (M. A. Hamilton, 1960, 1967), the Beck Depression Inventory (A. T. Beck, 1978; A. T. Beck & R. A. Steer, 1987), and an aggregation of low reactivity-low specificity measures. These benchmarks were further refined for 3 conditions: treatment completers, intent-to-treat samples, and natural history (wait-list) conditions. The study confirmed significant effects of outcome measure reactivity and specificity on the pretreatment-posttreatment effect sizes. The authors provide practical guidance in using these benchmarks to assess treatment effectiveness in clinical settings.

The effectiveness of the Pain Resource Nurse Program to improve pain management in the hospital setting: A cluster randomized controlled trial.

BACKGROUND: The Pain Resource Nurse program is a widely disseminated, evidence-based, nursing staff development program, designed to improve pain management in hospitals. The program has shown promising results, but has never been tested with a rigorous research design. OBJECTIVES: Our objective was to test the effectiveness of the Pain Resource Nurse program. Hypothesized outcomes included improvements in nurses' knowledge, attitudes, and assessment practices, and in patients' participation in decision-making, adequacy of pain management, pain severity, time spent in severe pain, pain interference, and satisfaction. DESIGN: Cluster randomized controlled trial. SETTING: A 650-bed university hospital in Iceland Participants: The sample consisted of a) patients ≥18 years of age, native speaking, hospitalized for at least 24h, alert and able to participate; and b) registered nurses who worked on the participating units. METHODS: Twenty three surgical and medical inpatient units were randomly assigned to the Pain Resource Nurse program (n=12) or to wait list control (n=11). The American Pain Society Outcome Questionnaire and the Knowledge and Attitudes Survey were used to collect data from patients and nurses respectively. Baseline data (T1) for patients were collected simultaneously on all units, followed by data collection from nurses. Then randomization took place, and the Pain Resource Nurse program was instituted. Ten months later, follow up (T2) data were collected, after which the nurses on the control group units received the Pain Resource Nurse program. RESULTS: At baseline, data were collected from 305 of the 396 eligible patients and at follow up from 326 of the 392 eligible patients, a 77% and 83% response rate respectively. At baseline, 232 of 479 eligible nurses responded and at follow-up 176 of the eligible 451 nurses responded, a 49% and 39% response rate, respectively. A nested mixed model analysis of covariance revealed that the intervention was successful in changing pain assessment practices, with pain assessment using standardized measures increasing from 13% to 25% in the intervention group while decreasing from 21% to 16% in the control group. None of the other hypothesized improvements were found. CONCLUSIONS: The Pain Resource Nurse program was successful in improving nurses' use of standardized measures for pain assessment. No effects were found on patient outcomes; pain was both prevalent and severe at both time points. Only minimal improvements were noted in response to this evidence-based staff development program. Changes in pain management practices remain a challenge in clinical settings.

Patient-related barriers to pain management: the Icelandic Barriers Questionnaire II.

The Barriers Questionnaire-II (BQ-II) is used to evaluate eight attitudinal barriers to cancer pain management. The purpose of this study was to evaluate the psychometric properties of the Icelandic BQ-II (IBQ-II). Icelandic adults (n=244) completed the IBQ-II, the Brief-Pain-Inventory, and demographic questions. Half the responders were male (52%), and 42.8% had pain on the day of data collection. Participants had a mean (SD) age of 34.73 (11.78) years and education of 15.08 (3.69) years. Factor analysis of the IBQ-II supported three factors. The alpha was 0.90. The mean (SD) IBQ-II total score was 2.32 (0.78), on a scale of 0 to 5, with higher scores indicating stronger barriers. IBQ-II total scores were inversely related to education (r=-0.21; P<0.01), and positively related to least pain (r=0.24; P<0.05), average pain (r=0.23; P<0.05), and pain interference with life activities (r=0.22; P<0.05) for those who had pain. There is support for reliability, validity, and feasibility of the IBQ-II.

Nursing and psychological treatments.

Presents a comment on "Psychological Treatments" by D. H. Barlow. In his article, Barlow pointed to the need "to solidify the identification of psychology as a health care profession" by changing the terminology of practice in the health care context from psychotherapy to psychological treatments and suggested that the only persons qualified to carry out such interventions are doctoral-level psychologists. Unfortunately, there was no discussion of the health care professionals who already provide psychological treatments in health care settings and their contribution to the evidence base supporting such treatment. The authors find several aspects of the article to be problematic. Overall, the authors feel that suggesting that psychology should claim treatment of psychological disorders and psychological components of physical disorders in health care settings as exclusively its own domain ignores the research and clinical contributions of others.

Size and consistency of problem-solving consultation outcomes: an empirical analysis.

In this study, we analyzed extant data to evaluate the variability and magnitude of students' behavior change outcomes (academic, social, and behavioral) produced by consultants through problem-solving consultation with teachers. Research questions were twofold: (a) Do consultants produce consistent and sizeable positive student outcomes across their cases as measured through direct and frequent assessment? and (b) What proportion of variability in student outcomes is attributable to consultants? Analyses of extant data collected from problem-solving consultation outcome studies that used single-case, time-series AB designs with multiple participants were analyzed. Four such studies ultimately met the inclusion criteria for the extant data, comprising 124 consultants who worked with 302 school teachers regarding 453 individual students. Consultants constituted the independent variable, while the primary dependent variable was a descriptive effect size based on student behavior change as measured by (a) curriculum-based measures, (b) permanent products, or (c) direct observations. Primary analyses involved visual and statistical evaluation of effect size magnitude and variability observed within and between consultants and studies. Given the nested nature of the data, multilevel analyses were used to assess consultant effects on student outcomes. Results suggest that consultants consistently produced positive effect sizes on average across their cases, but outcomes varied between consultants. Findings also indicated that consultants, teachers, and the corresponding studies accounted for a significant proportion of variability in student outcomes. This investigation advances the use of multilevel and integrative data analyses to evaluate consultation outcomes and extends research on problem-solving consultation, consultant effects, and meta-analysis of case study AB designs. Practical implications for evaluating consultation service delivery in school settings are also discussed.

Preserved Microvascular Endothelial Function in Young, Obese Adults with Functional Loss of Nitric Oxide Signaling.

Data indicate endothelium-dependent dilation (EDD) may be preserved in the skeletal muscle microcirculation of young, obese adults. Preserved EDD might be mediated by compensatory mechanisms, impeding insight into preclinical vascular dysfunction. We aimed to determine the functional roles of nitric oxide synthase (NOS) and cyclooxygenase (COX) toward EDD in younger obese adults. We first hypothesized EDD would be preserved in young, obese adults. Further, we hypothesized a reduced contribution of NOS in young, obese adults would be replaced by increased COX signaling. Microvascular EDD was assessed with Doppler ultrasound and brachial artery infusion of acetylcholine (ACh) in younger (27 ± 1 year) obese (n = 29) and lean (n = 46) humans. Individual and combined contributions of NOS and COX were examined with intra-arterial infusions of l-NMMA and ketorolac, respectively. Vasodilation was quantified as an increase in forearm vascular conductance (ΔFVC). Arterial endothelial cell biopsies were analyzed for protein expression of endothelial nitric oxide synthase (eNOS). ΔFVC to ACh was similar between groups. After l-NMMA, ΔFVC to ACh was greater in obese adults (p < 0.05). There were no group differences in ΔFVC to ACh with ketorolac. With combined NOS-COX inhibition, ΔFVC was greater in obese adults at the intermediate dose of ACh. Surprisingly, arterial endothelial cell eNOS and phosphorylated eNOS were similar between groups. Younger obese adults exhibit preserved EDD and eNOS expression despite functional dissociation of NOS-mediated vasodilation and similar COX signaling. Compensatory NOS- and COX-independent vasodilatory mechanisms conceal reduced NOS contributions in otherwise healthy obese adults early in life, which may contribute to vascular dysfunction.

Patient-related barriers to pain management: the Barriers Questionnaire II (BQ-II).

Patients' beliefs can act as barriers to optimal management of cancer pain. The Barriers Questionnaire (BQ) is a tool used to evaluate such barriers. Here, the BQ has been revised to reflect changes in pain management practices, resulting in the Barriers Questionnaire-II (BQ-II), a 27-item, self report instrument. This paper presents the results from two studies where the psychometric properties of the BQ-II were evaluated. In the first study, the responses of 27 nurses trained in pain management were compared to responses of a convenience sample of 12 patients with cancer. The results indicated that patients with cancer had higher mean scores on the BQ-II than did nurses trained in pain management. In the second study, a convenience sample of 172 patients with cancer responded to the BQ-II and a set of pain and quality of life (QOL) measures. A factor analysis supported four factors. Factor one, physiological effects, consists of 12 items addressing the beliefs that side effects of analgesics are inevitable and unmanageable, concerns about tolerance, and concerns about not being able to monitor changes in one's body when taking strong pain medications. Factor two, Fatalism, consists of three items addressing fatalistic beliefs about cancer pain and its management. Factor three, Communication, consists of six items addressing the concern that reports of pain distract the physician from treating the underlying disease, and the belief that 'good' patients do not complain of pain. The fourth and final factor, harmful effects, consists of six items addressing fear of becoming addicted to pain medication and the belief that pain medications harm the immune system. The BQ-II total had an internal consistency of 0.89, and alpha for the subscales ranged from 0.75 to 0.85. Mean (SD) scores on the total scale was 1.52 (0.73). BQ-II scores were related to measures of pain intensity and duration, mood, and QOL. Patients who used adequate analgesics for their levels of pain had lower scores on the BQ-II than did patients who used inadequate analgesics. The BQ-II is a reliable and valid measure of patient-related barriers to cancer pain management.