Feasibility of two levels of protein intake in patients with colorectal cancer: findings from the Protein Recommendation to Increase Muscle (PRIMe) randomized controlled pilot trial.

BACKGROUND: Low muscle mass (MM) predicts unfavorable outcomes in cancer. Protein intake supports muscle health, but oncologic recommendations are not well characterized. The objectives of this study were to evaluate the feasibility of dietary change to attain 1.0 or 2.0 g/kg/day protein diets, and the preliminary potential to halt MM loss and functional decline in patients starting chemotherapy for stage II-IV colorectal cancer. PATIENTS AND METHODS: Patients were randomized to the diets and provided individualized counseling. Assessments at baseline, 6 weeks, and 12 weeks included weighed 3-day food records, appendicular lean soft tissue index (ALSTI) by dual-energy X-ray absorptiometry to estimate MM, and physical function by the Short Physical Performance Battery (SPPB) test. RESULTS: Fifty patients (mean ± standard deviation: age, 57 ± 11 years; body mass index, 27.3 ± 5.6 kg/m2; and protein intake, 1.1 ± 0.4 g/kg/day) were included at baseline. At week 12, protein intake reached 1.6 g/kg/day in the 2.0 g/kg/day group and 1.2 g/kg/day in the 1.0 g/kg/day group (P = 0.012), resulting in a group difference of 0.4 g/kg/day rather than 1.0 g/kg/day. Over one-half (59%) of patients in the 2.0 g/kg/day group maintained or gained MM compared with 44% of patients in the 1.0 g/kg/day group (P = 0.523). Percent change in ALSTI did not differ between groups [2.0 g/kg/day group (mean ± standard deviation): 0.5% ± 4.6%; 1.0 g/kg/day group: -0.4% ± 6.1%; P = 0.619]. No differences in physical function were observed between groups. However, actual protein intake and SPPB were positively associated (ß = 0.37; 95% confidence interval 0.08-0.67; P = 0.014). CONCLUSION: Individualized nutrition counselling positively impacted protein intake. However, 2.0 g/kg/day was not attainable using our approach in this population, and group contamination occurred. Increased protein intake suggested positive effects on MM and physical function, highlighting the potential for nutrition to attenuate MM loss in patients with cancer. Nonetheless, muscle anabolism to any degree is clinically significant and beneficial to patients. Larger trials should explore the statistical significance and clinical relevance of protein interventions.

Randomised controlled trial of analgesia for the management of acute severe pain from traumatic injury: study protocol for the paramedic analgesia comparing ketamine and morphine in trauma (PACKMaN).

BACKGROUND: Prehospital analgesia is often required after traumatic injury, currently morphine is the strongest parenteral analgesia routinely available for use by paramedics in the United Kingdom (UK) when treating patients with severe pain. This protocol describes a multi-centre, randomised, double blinded trial comparing the clinical and cost-effectiveness of ketamine and morphine for severe pain following acute traumatic injury. METHODS: A two arm pragmatic, phase III trial working with two large NHS ambulance services, with an internal pilot. Participants will be randomised in equal numbers to either (1) morphine or (2) ketamine by IV/IO injection. We aim to recruit 446 participants over the age of 16 years old, with a self-reported pain score of 7 or above out of 10. Randomised participants will receive a maximum of 20 mg of morphine, or a maximum of 30 mg of ketamine, to manage their pain. The primary outcome will be the sum of pain intensity difference. Secondary outcomes measure the effectiveness of pain relief and overall patient experience from randomisation to arrival at hospital as well as monitoring the adverse events, resource use and cost-effectiveness outcomes. DISCUSSION: The PACKMAN study is the first UK clinical trial addressing the clinical and cost-effectiveness of ketamine and morphine in treating acute severe pain from traumatic injury treated by NHS paramedics. The findings will inform future clinical practice and provide insights into the effectiveness of ketamine as a prehospital analgesia. TRIAL REGISTRATION: ISRCTN, ISRCTN14124474. Registered 22 October 2020, https://www.isrctn.com/ISRCTN14124474.

Evaluation of short-term multi-component exercise programming on major variables that directly influence fall risk in older women: a pilot study.

Falls are linked to gait and balance inconsistencies influenced by a combination of variables including muscle strength and power. Multicomponent athlete training models that incorporate high-intensity challenging activities have been shown to significantly improve strength, power, and balance. This study evaluated the efficacy of a short-term multi-component dynamic training program on strength, power, and balance in older women. Seventeen women participated in 8-weeks of specialized exercise training. Significant changes were observed in all performance variables from baseline. Results suggest short-term, high intensity multi-component programming can be used safely and effectively to improve major variables that influence falls in older women.

Invasive Paget's Disease of the Breast: Rash or Recurrence?

Paget's disease of the breast is rare among breast cancers. Secondary Paget's disease of the breast presenting as local recurrence is even rarer, with limited published information on the overall prevalence. In this report, we present a case of secondary Paget's disease of the breast presenting as a pruritic rash and skin changes with normal imaging. This patient's case was unique as her presentation involved invasive Paget's disease of the breast presenting as a local recurrence, with a diffuse rash covering the entirety of the right breast including the nipple-areolar complex, pathology examination showing dermal invasion, and a 20-year time interval between her initial treatment and presentation at our institution. Furthermore, diagnostic mammogram and breast MRI revealed no underlying suspicious findings within the breast tissue. In this case, the patient benefitted from mastectomy with removal of the affected skin, resulting in a clear margin and clinically favorable outcome. The patient did well postoperatively, did not receive any systemic adjuvant treatment, and is now under surveillance. Currently, there is insufficient data on the incidence of diffuse Paget's disease of the breast with dermal invasion. It is important to recognize this atypical presentation to ensure timely diagnosis and treatment of affected patients.

Patients and Partners in Research: Patient and Caregiver Perceptions of Research Engagement and the Role of Their Psychosocial States in Participation.

Multiple sclerosis (MS) is one of the most common, nontraumatic, disabling diseases diagnosed in adults. Self-empowered patients and families are valued members of the MS research team. The objective of this study was to explore patient and family perceptions of the influence of psychosocial state on their willingness to be research partners. Researchers conducted 5 focus groups with MS patients and family from the Upper Midwest Chapter of the National Multiple Sclerosis Society. The researchers asked questions addressing psychosocial factors influencing ability and willingness to work with MS researchers as partners. Relevant themes were identified including comfort level of individuals in formulating research questions, comfort level engaging in research, understanding of the meaning of research and self-perception about skills, research training, and knowledge needs. The findings of this study support the role of MS patients' perspectives about MS, their understanding of the science of MS, and role of their psychosocial states as all these factors were patient identified as being key to their ability to be active, engaged and willing research participants.

Celebrity Suicide.

Background: Increased suicides following media coverage of celebrities' suicide deaths have been documented in several countries. Recommendations for Reporting on Suicide were published to provide guidance for media professionals when covering suicide. Research indicates guidelines have been poorly followed. Aim: We aimed to determine whether the recommendations were similarly observed when studying two online news organizations' coverage of a celebrity's suicide. Method: In the 3 days following a high-profile celebrity's death, two US cable networks' news websites were studied to compare how the death was reported. Online articles were reviewed using a coding rubric organized by six themes and 21 coding categories. Results: Between the two organizations, 34 articles were published. Regarding the recommendations, neither source followed all of the recommendations, as measured in this study. Source A fared better in providing help-seeking information. Limitations: Only two news organizations were studied for a 3-day period. Online videos, print articles, and social media were excluded. Conclusion: The suicide of a celebrity received repetitive media coverage with little emphasis on prevention or help-seeking. The recommendations were not consistently followed by the two news websites included in this review.

"Girl, just pray ": Factors That Influence Breast and Cervical Cancer Screening Among Black Women in Rochester, MN.

BACKGROUND: Black women in Minnesota and beyond have a greater burden of death due to some cancers than their White counterparts. Delayed screening and treatment may explain these disparate statistics. The purpose of this study was to work in collaboration with a local Black faith-based organization to gain an updated understanding of Black women's knowledge, attitudes, and behaviors related to breast and cervical cancer, and determine to what extent known factors persist as barriers to accessing cancer screening among Black women in Rochester, MN. We also sought to identify unique barriers for Black women residing in a particularly health resource rich community. METHODS: Using a community-based participatory research approach, two academic institutes worked in collaboration with a local Black faith-based organization to conduct focus groups. Focus groups were utilized to identify factors that may limit Black women's access to cancer screening and health care. RESULTS: Forty-five eligible participants attended one of eight focus group sessions. All participants self-identified as Black women and most were born in the United States. Content analysis of participant responses suggested that Black women's health-seeking behaviors related to breast and cervical cancer screening continue to be very much influenced by known factors that serve as barriers to screening services. Four primary themes pertaining to these influential factors emerged from participants' focus group discussions: 1) knowledge of cancer, risk factors, and screening options; and 2) socioeconomic factors, 3) psycho-social factors, including lack of trust of doctors specifically involved in clinical research, and 4) cultural factors, including reliance on religious practice in place of medical intervention. CONCLUSION: Black women face real and perceived barriers to cancer screening even where health resources are abundant. Results reiterate an on going need for culturally appropriate interventions to improve Black women's breast and cervical cancer screening participation by minimizing barriers and engaging entire communities - including Black women, religious leaders, and health care providers.

Quality of Life and Mental Health in Older Adults with Obesity and Frailty: Associations with a Weight Loss Intervention.

OBJECTIVE: To examine the bi-directional associations of a weight loss intervention with quality of life and mental health in obese older adults with functional limitations. DESIGN: Combined-group analyses of secondary variables from the MEASUR-UP randomized controlled trial. SETTING: Academic medical center. PARTICIPANTS: Obese community-dwelling men and women (N = 67; age ≥60; BMI ≥30) with functional limitations (Short Physical Performance Battery [SPPB] score of 4-10 out of 12). INTERVENTION: Six-month reduced calorie diet at two protein levels. MEASUREMENTS: Weight, height, body composition, physical function, medical history, and mental health and quality of life assessments (Center for Epidemiologic Studies Depression Scale [CES-D]; Profile of Mood States [POMS], Pittsburgh Sleep Quality Index [PSQI]; Perceived Stress Scale [PSS]; Satisfaction with Life Scale [SWLS]; and Short Form Health Survey [SF-36]) were acquired at 0, 3 and 6 months. RESULTS: Physical composite quality of life (SF-36) improved significantly at 3 months (ß = 6.29, t2,48 = 2.60, p = 0.012) and 6 months (ß = 10.03, t2,48 = 4.83, p < 0.001), as did several domains of physical quality of life. Baseline depression symptoms (CES-D and POMS) were found to predict lower amounts of weight loss; higher baseline sleep latency (PSQI) and anger (POMS) predicted less improvement in physical function (SPPB). CONCLUSION: The significant bi-directional associations found between a weight loss intervention and mental health/quality of life, including substantial improvements in physical quality of life with obesity treatment, indicate the importance of considering mental health and quality of life as part of any weight loss intervention for older adults.

Lobular Carcinoma in Situ: A 29-Year Longitudinal Experience Evaluating Clinicopathologic Features and Breast Cancer Risk.

PURPOSE: The increased breast cancer risk conferred by a diagnosis of lobular carcinoma in situ (LCIS) is poorly understood. Here, we review our 29-year longitudinal experience with LCIS to evaluate factors associated with breast cancer risk. PATIENTS AND METHODS: Patients participating in surveillance after an LCIS diagnosis are observed in a prospectively maintained database. Comparisons were made among women choosing surveillance, with or without chemoprevention, and those undergoing bilateral prophylactic mastectomies between 1980 and 2009. RESULTS: One thousand sixty patients with LCIS without concurrent breast cancer were identified. Median age at LCIS diagnosis was 50 years (range, 27 to 83 years). Fifty-six patients (5%) underwent bilateral prophylactic mastectomy; 1,004 chose surveillance with (n = 173) or without (n = 831) chemoprevention. At a median follow-up of 81 months (range, 6 to 368 months), 150 patients developed 168 breast cancers (63% ipsilateral, 25% contralateral, 12% bilateral), with no dominant histology (ductal carcinoma in situ, 35%; infiltrating ductal carcinoma, 29%; infiltrating lobular carcinoma, 27%; other, 9%). Breast cancer incidence was significantly reduced in women taking chemoprevention (10-year cumulative risk: 7% with chemoprevention; 21% with no chemoprevention; P < .001). In multivariable analysis, chemoprevention was the only clinical factor associated with breast cancer risk (hazard ratio, 0.27; 95% CI, 0.15 to 0.50). In a subgroup nested case-control analysis, volume of disease, which was defined as the ratio of slides with LCIS to total number of slides reviewed, was also associated with breast cancer development (P = .008). CONCLUSION: We observed a 2% annual incidence of breast cancer among women with LCIS. Common clinical factors used for risk prediction, including age and family history, were not associated with breast cancer risk. The lower breast cancer incidence in women opting for chemoprevention highlights the potential for risk reduction in this population.

Case-control study of student-perpetrated physical violence against educators.

PURPOSE: Although prior research focused primarily on student-on-student school violence, educators are also at risk. This study was designed to identify risk factors for assaults against educators. METHODS: Kindergarten-grade 12 educators (n = 26,000), randomly selected from a state license database, were screened for eligibility (6,469, eligible) by mailed questionnaire. Phase 1 (12-month recall) identified eligible assault cases (n = 372) and controls (n = 1,116), June 2004 to December 2005; phase 2 (case-control study; response, 78%) enabled identification of exposures through 1-month recall before student-perpetrated assaults (cases) and randomly selected months (controls). Directed acyclic graphs enabled confounder selection for multivariable logistic regression analyses; reweighting adjusted for potential biases. RESULTS: Risks (odds ratios, 95% confidence intervals) increased for working in: Special Education (5.84; 4.07-8.39) and School Social Work (7.18; 2.72-18.91); kindergarten to second grade (1.81; 1.18-2.77); urban (1.95; 1.38-2.76) schools; schools with less than 50 (8.40; 3.12-22.63), 50-200 (3.67; 1.84-7.34), 201-500 (2.09; 1.32-3.29), and 501-1000 (1.94; 1.25-3.01) students versus more than 1000; schools with inadequate resources always/frequently (1.62; 1.05-2.48) versus infrequently/never; inadequate building safety always/frequently (4.48; 2.54-7.90) versus infrequently/never; and environments with physical barriers (1.50; 1.07-2.10). Risks decreased with routine locker searches (0.49; 0.29-0.85) and accessible exits (0.36; 0.17-0.74). CONCLUSIONS: Identification of assault risk factors provides a basis for further investigation and interventions.

Types of urethral catheter for reducing symptomatic urinary tract infections in hospitalised adults requiring short-term catheterisation: multicentre randomised controlled trial and economic evaluation of antimicrobial- and antiseptic-impregnated urethral catheters (the CATHETER trial).

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a major preventable cause of harm for patients in hospital and incurs significant costs for health-care providers such as the UK NHS. Many preventative strategies and measures have been introduced to minimise CAUTI risk, including the use of antimicrobial catheters. However, there is considerable uncertainty regarding their usefulness in terms of reducing symptomatic CAUTI, and whether or not they are cost-effective. OBJECTIVES: Do antimicrobial catheters reduce the rate of symptomatic urinary tract infection (UTI) during short-term hospital use and is their use cost-effective for the UK NHS? DESIGN: A pragmatic multicentre UK randomised controlled trial comparing three catheters as they would be used in the UK NHS: antimicrobial-impregnated (nitrofurazone) and antiseptic-coated (silver alloy) catheters with the standard polytetrafluoroethylene (PTFE)-coated catheters. Economic evaluation used a decision model populated with data from the trial. Sensitivity analysis was used to explore uncertainty. SETTING: Relevant clinical departments in 24 NHS hospitals throughout the UK. PARTICIPANTS: Adults requiring temporary urethral catheterisation for a period of between 1 and 14 days as part of their care, predominantly as a result of elective surgery. INTERVENTIONS: Eligible participants were randomised 1 : 1 : 1 to one of three types of urethral catheter in order to make the following pragmatic comparisons: nitrofurazone-impregnated silicone catheter compared with standard PTFE-coated latex catheter; and silver alloy-coated hydrogel latex catheter compared with standard PTFE-coated latex catheter. MAIN OUTCOME MEASURES: The primary outcome for clinical effectiveness was the incidence of UTI at any time up to 6 weeks post randomisation. This was defined as any symptom reported during catheterisation, up to 3 days or 1 or 2 weeks post catheter removal or 6 weeks post randomisation combined with a prescription of antibiotics, at any of these times, for presumed symptomatic UTI. The primary economic outcome was incremental cost per quality-adjusted life-year (QALY). Health-care costs were estimated from NHS sources with QALYs calculated from participant completion of the European Quality of Life-5 Dimensions (EQ-5D). RESULTS: Outcome analyses encompassed 6394 (90%) of 7102 participants randomised. The rate of symptomatic UTI within 6 weeks of randomisation was 10.6% in the nitrofurazone group (n = 2153; -2.1% absolute risk difference), 12.5% in the silver alloy group (n = 2097; -0.1% absolute risk difference) and 12.6% in the PTFE group (n = 2144). The effect size {odds ratio (OR) [97.5% confidence interval (CI)]} was 0.82 (97.5% CI 0.66 to 1.01) for nitrofurazone (p = 0.037) and 0.99 (97.5% CI 0.81 to 1.22) for silver alloy (p = 0.92) catheters. The nitrofurazone catheters were more likely to cause discomfort during use and on removal. The primary economic analysis suggested that nitrofurazone-impregnated catheters would be, on average, the least costly (> £7 less than PTFE) and most effective option at current NHS prices. There was a 73% chance that nitrofurazone would be cost saving and an 84% chance that the incremental cost per QALY would be < £30,000. At the trial price (£6.46), silver alloy catheters were very unlikely to be cost-effective. These results were unchanged in sensitivity analyses, although when the length of stay cost was excluded the incremental cost per QALY for nitrofurazone against PTFE was £28,602. CONCLUSIONS: The trial estimate of clinical effectiveness for nitrofurazone-impregnated catheters was less than the pre-specified minimum absolute risk difference that we considered important (-3.3%), and the surrounding CI included zero, indicating that any reduction in catheter-associated UTI was uncertain. Economic analysis, although associated with uncertainty, suggested that nitrofurazone-impregnated catheters may be cost-effective for the NHS. The trial ruled out the possibility that silver alloy-coated catheters might reach the pre-set degree of clinical effectiveness and that their use was unlikely to be cost-effective. These findings should be considered by patients, clinicians and health-care policy-makers to determine whether or not a change in practice is worthwhile. Future research should be aimed at determining the minimum clinically important difference in terms of CAUTI prevention in comparative trials, and to identify reliable methods which can detect the impact of the intervention on quality of life and other drivers of cost, when the intervention is a subsidiary part of overall treatment plans.

Violence against educators: a population-based study.

OBJECTIVE: Identify the magnitude and risk factors for occupational physical assault (PA) and nonphysical violence (NPV) against Minnesota educators. METHODS: Among 26,000 randomly selected licensed kindergarten to grade 12 educators, 6469 eligible educators reported whether they experienced PA or NPV during the prior year. Multiple logistic regression models were based on directed acyclic graphs. RESULTS: Respective PA and NPV annual rates per 100 educators were 8.3 and 38.4. Work changes resulted among PA (13% to 20%) and NPV (22%) victims. Risks increased for master's prepared or education specialists who worked in public alternative schools and special education. Risks decreased for those working for more than 20 years, part time, and in private schools. Physical assault risk decreased when teaching grades 3 to 12 (vs kindergarten to grade 2), but NPV risk increased. CONCLUSION: Targeted efforts on specific violence risk and protective factors are essential to improve educators' work environments.

School resources, resource allocation, and risk of physical assault against Minnesota educators.

To investigate the relation between schools' resource levels (i.e., annual per student expenditures), school resource allocations, and physical assault (PA) against Minnesota's educators, a study was conducted from the two-phase Minnesota Educators' Study (MES) that incorporated school-level fiscal and demographic data from the Minnesota Department of Education (MDE). The MES examined a randomly selected cohort of employed, state-licensed kindergarten through grade 12 educators. From mailed questionnaires, response rates for both Phase I (comprehensive data collection on violent events) and Phase II (case-control) were 84%. Cases experienced a work-related PA event in the previous 12 months; controls reported no assaults. Based on the school in which they worked the most time and available MDE school-level data, together with MES questionnaire data, analyses were conducted on 238 cases and 640 controls. Multivariate analyses, using directed acyclic graphs to guide selection of confounders, suggested that increased spending (i.e. resources) was associated with decreased risk of PA. Analyses further suggested that the highest quartiles of resource allocations, compared with the lowest quartiles (referents), were associated with decreased risks of PA for: district level administration; regular instruction; special education; student activities and athletics; and pupil support services expenditures. Associations between increased resource allocations to student activities expenditures and decreased risks of PA were the strongest. For example, an allocation greater than 5% of the total annual per student expenditure to student activities programming (referent, less than 0.04%) was associated with a decreased risk of PA (OR=0.30, 95% CI: 0.12, 0.77). Results suggested that allocations of school resources (i.e., expenditures) to key program areas such as student athletics and extracurricular activities may reduce risk of work-related PA against educators. Research to further explore the nature of the relations between disparities in school resources and spending, resource allocations, and PA will be important to the continued development of relevant prevention strategies.

Characterization of a CNS penetrant, selective M1 muscarinic receptor agonist, 77-LH-28-1.

BACKGROUND AND PURPOSE: M1 muscarinic ACh receptors (mAChRs) represent an attractive drug target for the treatment of cognitive deficits associated with diseases such as Alzheimer's disease and schizophrenia. However, the discovery of subtype-selective mAChR agonists has been hampered by the high degree of conservation of the orthosteric ACh-binding site among mAChR subtypes. The advent of functional screening assays has enabled the identification of agonists such as AC-42 (4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine), which bind to an allosteric site and selectively activate the M(1) mAChR subtype. However, studies with this compound have been limited to recombinantly expressed mAChRs. EXPERIMENTAL APPROACH: In this study, we have compared the pharmacological profile of AC-42 and a close structural analogue, 77-LH-28-1 (1-[3-(4-butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone) at human recombinant, and rat native, mAChRs by calcium mobilization, inositol phosphate accumulation and both in vitro and in vivo electrophysiology. KEY RESULTS: Calcium mobilization and inositol phosphate accumulation assays revealed that both AC-42 and 77-LH-28-1 display high selectivity to activate the M1 mAChR over other mAChR subtypes. Furthermore, 77-LH-28-1, but not AC-42, acted as an agonist at rat hippocampal M1 receptors, as demonstrated by its ability to increase cell firing and initiate gamma frequency network oscillations. Finally, 77-LH-28-1 stimulated cell firing in the rat hippocampus in vivo following subcutaneous administration. CONCLUSIONS AND IMPLICATIONS: These data suggest that 77-LH-28-1 is a potent, selective, bioavailable and brain-penetrant agonist at the M1 mAChR and therefore that it represents a better tool than AC-42, with which to study the pharmacology of the M1 mAChR.

Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement.

RATIONALE: Orexins A and B have recently been discovered and shown to be derived from preproorexin, primarily expressed in the rat hypothalamus. Orexin-A has been ascribed a number of in vivo functions in the rat after intracerebroventricular (ICV) administration, including hyperphagia, neuroendocrine modulation and, most recently, evidence for a behavioural response characterised by an increase in grooming. OBJECTIVES: Here, we have investigated the orexin-receptor subtypes involved in the grooming response to orexin-A (3 microg, ICV) in the rat. METHODS: Male rats, habituated to clear Perspex behavioural observation boxes, were pretreated with antagonists with mixed selectivity for OX1, OX2, 5-HT2B and 5-HT2C receptor subtypes prior to the administration of orexin-A and the intense grooming response elicited by this peptide assessed. RESULTS: Pretreatment of rats with a mixed OX1/5-HT2B/2C receptor antagonist 1-(4-methylsulfanylphenyl)-3-quinolin-4-ylurea (SB-284422), revealed a significant, but incomplete, blockade of orexin-A-induced grooming. Despite the low potency of orexin-A at 5-HT2B and 5-HT2C receptors in vitro (pKi<5), studies were undertaken to determine whether downstream 5-HT2B or 5-HT2C receptors mediate in the grooming-elicited by orexin-A. Whilst the selective 5-HT2B receptor antagonist, SB-215505 (3 mg/kg, PO, 5-HT2B, pKi=8.58; OX1, pKB < 5.15) failed to effect orexin-A-induced grooming, the selective 5-HT2C receptor antagonist, SB-242084 (1 mg/kg, IP, 5-HT2C, pKi = 8.95; OX1, pKB < 5.1) potently antagonised the grooming response to this peptide. This suggested that the partial blockade of orexin-A-induced grooming obtained with SB-284422 might be attributable to its 5-HT2C and/or OX1 receptor blocking activity. However, complete blockade of orexin-A-induced grooming by the subsequently identified selective OX1 receptor antagonist 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea hydrochloride, SB-334867-A (OX1, pKB = 7.4; OX2, pKB = 5.7), devoid of appreciable affinity for either 5-HT2B (pKi < 5.3) or 5-HT2C (pKi < 5.4) receptors, provides the first definitive evidence that a central behavioural effect of orexin-A (grooming) is mediated by OX1 receptors. CONCLUSIONS: This data suggests that orexin-A indirectly activates 5-HT2C receptors downstream from OX1 receptors to elicit grooming in the rat. The use of SB-334867-A in vivo will enable the role of OX,1 receptors within the rat central nervous system to be further characterised.

The relationship of daily mood and stressful events to symptoms in juvenile rheumatic disease.

OBJECTIVES: The purpose of this study was 3-fold: 1) to assess the feasibility of a daily diary for use with children with juvenile rheumatic disease (JRD), 2) to describe daily variation in mood, stressful events, and symptoms in children with JRD, and 3) to examine the extent to which daily mood and daily stressful events predict daily symptoms in children with JRD. METHODS: Twelve children with JRD completed a daily booklet for 7 days. The daily booklet included measures of daily mood, daily stressful events, daily symptoms, and daily function. The children also completed a visual analog scale for pain and the Children's Depression Inventory. RESULTS: Subjects showed good compliance with scheduled completion and return of the daily diaries. Results indicated that children with JRD showed variability in daily mood, frequency of daily stressful events, and daily symptoms across days. Multilevel fixed effects models showed that more negative daily mood and more daily stressful events significantly predicted increased reports of fatigue, stiffness, and cutting back on daily activities. Negative daily mood also correlated with increases in daily reported pain. CONCLUSIONS: These results indicate that daily diary research is both feasible and potentially informative in children with JRD. Our data emphasize the need for further investigation into the role of daily mood and daily stressful events on disease course in JRD.

Latency to paroxetine-induced anxiolysis in the rat is reduced by co-administration of the 5-HT(1A) receptor antagonist WAY100635.

We report here the use of rat high-light social interaction to model the temporal anxiolytic/antidepressant effects of SSRIs seen in the clinic. Compared to vehicle controls, 21, but not 14, days of paroxetine treatment (3 mg kg(-1), p.o., daily) produced a marked increase in rat social interaction (Vehicle=71.3+/-7.3 s; Paroxetine=116.7+/-14.7 s; P<0.01) with no concurrent effect on locomotor activity, consistent with anxiolysis. To assess whether concurrent 5-HT(1A) receptor blockade reduces the time to onset of anxiolysis seen with paroxetine alone (21 days), rats were implanted with osmotic minipumps to continuously infuse the 5-HT(1A) receptor antagonist WAY100635 (1 mg kg(-1) day(-1), s.c., 7 days) alone or in combination with paroxetine (3 mg kg(-1), p.o., daily, 7 days), prior to anxiety testing. Paroxetine (Veh/Par=61.9+/-7.9 s) or WAY100635 (WAY/Veh=71.6+/-4.7 s) alone, had no effect on social interaction time compared to vehicle treated controls (Veh/Veh=76.4+/-4.9 s), whilst coadministration of WAY100635 with paroxetine, produced a marked elevation in social interaction (WAY/Par=149.3+/-16.8 s; P<0.01) relative to all other groups with no concurrent change in locomotor activity. In contrast, acute administration of WAY100635 (0.03 mg kg(-1), s.c.) with paroxetine (3 mg kg(-1), p.o.) did not alter any behavioural measure, suggesting that the anxiolysis induced by the combination after 7 days is attributable to a CNS adaptive response. This data demonstrates that coadministration of a 5-HT(1A) receptor antagonist with paroxetine markedly reduces the latency to anxiolysis, in the rat. This study supports the use of the rat social interaction test to further delineate adaptive changes in the CNS responsible for the anxiolytic/antidepressant action of SSRIs seen in humans.

The relationship of arthritis self-efficacy to daily pain, daily mood, and daily pain coping in rheumatoid arthritis patients.

There is an increasing awareness in the medical community that psychosocial variables such as beliefs in self-efficacy are important determinants of treatment outcome. However, before measures of self-efficacy are widely incorporated into clinical practice, there needs to be a better understanding of how they relate to daily pain, mood and coping. In the present study 128 rheumatoid arthritis patients completed diaries for 30 days in which they provided daily ratings of joint pain, negative and positive mood, the use of pain coping strategies, and coping efficacy. The patients then participated in an evaluation session during which measures of self-efficacy (the Arthritis Self Efficacy Scale (ASES)), demographic variables, and medical status were collected. A series of hierarchical regression analyses was conducted to determine the degree to which self-efficacy measures collected at the time of the evaluation session were related to daily diary measures collected during the 30 preceding days. The results revealed that self-efficacy was significantly related to daily ratings of pain, mood, coping and coping efficacy. Interestingly, the findings regarding self-efficacy were obtained even after taking into account the effects of important demographic and medical status variables. Taken together, these results suggest that self-efficacy ratings collected from arthritis patients at the time of an evaluation session may well be related to recent experiences of daily pain and mood, as well as the daily use and perceived effectiveness of pain coping strategies.

The effect of application of aquaphor on skin condition, fluid requirements, and bacterial colonization in very low birth weight infants.

OBJECTIVE: To determine the effects of repeated application of an occlusive ointment on the skin of very low birth weight infants. STUDY DESIGN: Nineteen neonates of 26 to 30 weeks gestational age were randomly assigned to receive topical Aquaphor ointment twice daily for 2 weeks or to receive standard skin care. Skin quality, fluid requirements, and skin bacterial colonization counts were assessed. RESULTS: Infants treated with Aquaphor had significantly improved skin condition scores versus controls (p = 0.002). Aquaphor improved skin scores over time (p = 0.012) in treated infants, whereas skin scores of untreated infants worsened before eventually healing. There were no significant differences in total fluid requirements, urine output, serum sodium concentrations, skin bacterial counts, fungal counts, or colonization patterns between treated and control infants in either gestational age cohort. CONCLUSION: Aquaphor ointment, used during the first two postnatal weeks, improved skin condition in infants of 26 to 30 weeks' gestation without changing skin bacterial flora. We speculate that improved skin condition may limit transepidermal water loss and decrease portals of entry for pathogens, thereby potentially decreasing fluid and electrolyte imbalances and sepsis in very low birth weight infants.

Changes in cognitive coping skills and social support during cognitive behavioral stress management intervention and distress outcomes in symptomatic human immunodeficiency virus (HIV)-seropositive gay men.

OBJECTIVE: We have previously reported decreases in dysphoria, anxiety, and total mood disturbance in symptomatic HIV seropositive gay men after a 10-week cognitive behavioral stress management (CBSM) group intervention. This structured intervention was designed a) to increase cognitive and behavioral coping skills related to managing the distress of symptomatic HIV, and b) to increase social support among group members. Here we examine the relative contribution of changes in coping skills and social support during the intervention period to reductions in dysphoria, anxiety, and distress-related symptoms in this sample. METHODS: Participants were randomized to a 10-week CBSM group intervention or to a wait-list control condition. Coping, social supports, and mood were measured before and after the intervention period. RESULTS: Members of the CBSM group (N = 22) showed significant improvement in cognitive coping strategies involving positive reframing and acceptance, and in social supports involving attachment, alliances, and guidance at the end of the 10-week CBSM program compared with controls (N = 18) who showed decrements in these coping abilities and no changes in social support. Improved cognitive coping, specifically acceptance of the HIV infection, was strongly related to lower dysphoria, anxiety, and total mood disturbance in both conditions. Changes in social support and in cognitive coping skills seem to mediate the effects of the experimental condition on the changes in distress noted during the intervention. CONCLUSIONS: These results suggest that cognitive coping and social support factors can be modified by psychosocial interventions and may be important determinants of the changes in psychological well-being and quality of life during symptomatic HIV infection that can be achieved through this form of intervention.