The neuronal noradrenaline transporter, anxiety and cardiovascular disease

Panic disorder can serve as a clinical model for testing whether mental stress can cause heart disease. Potential neural mechanisms of cardiac risk are the sympathetic activation during panic attacks, continuing release of adrenaline as a co-transmitter in the cardiac sympathetic nerves, and impairment of noradrenaline neuronal reuptake, augmenting sympathetic neural respnses.

The phenotype of impaired neuronal reuptake of noradrenaline: an epigenetic mechanism? We suspect that this phenotype, in sensitizing people to heart symptom development, is a cause of panic disorder, and by magnifying the sympathetic neural signal in the heart, underlies increased cardiac risk. No loss of function mutations of the coding region of the norepinephrine transporter (NET) are evident, but we do detect hypermethylation of CpG islands in the NET gene promoter region. Chromatin immunoprecipitation methodology demonstrates binding of the inhibitory transcription factor, MeCP2, to promoter region DNA in panic disorder patients.

Cardiovascular illnesses co-morbid with panic disorder. Panic disorder commonly coexists with essential hypertension and the postural tachycardia syndrome. In both of these cardiovascular disorders the impaired neuronal noradrenaline reuptake phenotype is also present and, as with panic disorder, is associated with NET gene promoter region DNA hypermethylation. An epigenetic ‘co-morbidity’ perhaps underlies the clinical concordance.

Brain neurotransmitters. Using internal jugular venous sampling, in the absence of a panic attack we find normal norepinephrine turnover, but based on measurements of the overflow of the serotonin metabolite, 5HIAA, a marked increase (six to sevenfold) in brain serotonin turnover in patients with panic disorder. This appears to represent the underlying neurotransmitter substrate for the disorder. Whether this brain serotonergic activation is a prime mover, or consequential on other primary causes of panic disorder, including cardiac sensitization by faulty neuronal noradrenaline reuptake leading to cardiac symptoms and the enhanced vigilance which accompanies them, is unclear at present.

The effects of playing violent video games on adolescents : should parents be quaking in their boots?

Debate regarding the psychological and behavioural effects of playing violent video games has recently led to claims that violent video games increase aggression effects in adolescents, and that this issue has now been settled. However, other researchers have found either no detrimental effects from game playing or even positive (cathartic) effects. In this research we demonstrate that these different conclusions are not mutually exclusive and can be explained by the method of assessment and analytic techniques utilised. We had adolescents play a violent video game (Quake II) and took measurements of anger both before, during and after game play. The results demonstrated that some people increase, some decrease and the majority show no change in anger ratings. Unlike past research, we also demonstrate that these changes are mediated by the player's feelings immediately prior to game play and a labile temperament - one predisposed to aggression - and that these variables predict people's reactions with an average 73% concordance rate.

Estimating individual glomerular volume in the human kidney : clinical perspectives

Background. Measurement of individual glomerular volumes (IGV) has allowed the identification of drivers of glomerular hypertrophy in subjects without overt renal pathology. This study aims to highlight the relevance of IGV measurements with possible clinical implications and determine how many profiles must be measured in order to achieve stable size distribution estimates.

Methods. We re-analysed 2250 IGV estimates obtained using the disector/Cavalieri method in 41 African and 34 Caucasian Americans. Pooled IGV analysis of mean and variance was conducted. Monte-Carlo (Jackknife) simulations determined the effect of the number of sampled glomeruli on mean IGV. Lin’s concordance coefficient (RC), coefficient of variation (CV) and coefficient of error (CE) measured reliability.

Results. IGV mean and variance increased with overweight and hypertensive status. Superficial glomeruli were significantly smaller than juxtamedullary glomeruli in all subjects (P < 0.01), by race (P < 0.05) and in obese individuals (P < 0.01). Subjects with multiple chronic kidney disease (CKD) comorbidities showed significant increases in IGV mean and variability. Overall, mean IGV was particularly reliable with nine or more sampled glomeruli (RC > 0.95, <5% difference in CV and CE). These observations were not affected by a reduced sample size and did not disrupt the inverse linear correlation between mean IGV and estimated total glomerular number.

Conclusions. Multiple comorbidities for CKD are associated with increased IGV mean and variance within subjects, including overweight, obesity and hypertension. Zonal selection and the number of sampled glomeruli do not represent drawbacks for future longitudinal biopsy-based studies of glomerular size and distribution.

The effect of different doses of an arginine-containing supplement on the healing of pressure ulcers

Objective: To investigate if a lower dose of arginine in the form of an oral nutritional supplement can show similar benefit in the healing rate of pressure ulcers compared with the current evidence for 9g of arginine.

Method: Twenty-three inpatients with category II, III or IV pressure ulcers were randomised to receive daily, for 3 weeks, the standard hospital diet plus 4.5 or 9g arginine in the form of a commercial supplement. Pressure ulcer size and severity was measured weekly (by PUSH tool; pressure ulcer scale for healing; 0= completely healed, 17= greatest severity). Nutritional status was determined by Subjective Global Assessment.

Results: There were no significant differences in patients’ age, gender, BMI, haemoglobin levels, albumin levels and diagnosis of diabetes between treatment groups. There was a significant decrease in pressure ulcer severity over time (p < 0.001), with no evidence of a difference in healing rate between the two arginine dosages (p=0.991). Based on expected healing time, patients in both treatment groups were estimated to achieve an almost 2-fold improvement compared with the historical control group. Patients categorised as malnourished showed clinically significant impaired healing rates compared with wellnourished patients (p=0.057), although this was unaffected by arginine dosage (p=0.727).

Conclusion: Similar clinical benefits in healing of pressure ulcers can be achieved with a lower dosage of arginine, which can translate into improved concordance and significant cost-savings for both the health-care facilities and for patients.

Relationship between Clinical Macular Changes and Retinal Function in Age-Related Macular Degeneration

Purpose

A five-gene hedgehog signature developed as a patient preselection tool for hedgehog inhibitor therapy in medulloblastoma

Purpose: 

Depression and suicidal behavior in adolescents : a multi-informant and multi-methods approach to diagnostic classification

Informant discrepancies have been reported between parent and adolescent measures of depressive disorders and suicidality. We aimed to examine the concordance between adolescent and parent ratings of depressive disorder using both clinical interview and questionnaire measures and assess multi-informant and multi-method approaches to classification.

A critical ethnography of communication processes involving the management of oral chemotherapeutic agents by patients with a primary diagnosis of colorectal cancer: study protocol.

AIM: To describe the protocol used to examine the processes of communication between health professionals, patients and informal carers during the management of oral chemotherapeutic medicines to identify factors that promote or inhibit medicine concordance. BACKGROUND: Ideally communication practices about oral medicines should incorporate shared decision-making, two-way dialogue and an equality of role between practitioner and patient. While there is evidence that healthcare professionals are adopting these concordant elements in general practice there are still some patients who have a passive role during consultations. Considering oral chemotherapeutic medications, there is a paucity of research about communication practices which is surprising given the high risk of toxicity associated with chemotherapy. DESIGN: A critical ethnographic design will be used, incorporating non-participant observations, individual semi-structured and focus-group interviews as several collecting methods. METHODS: Observations will be carried out on the interactions between healthcare professionals (physicians, nurses and pharmacists) and patients in the outpatient departments where prescriptions are explained and supplied and on follow-up consultations where treatment regimens are monitored. Interviews will be conducted with patients and their informal carers. Focus-groups will be carried out with healthcare professionals at the conclusion of the study. These several will be analysed using thematic analysis. This research is funded by the Department for Employment and Learning in Northern Ireland (Awarded February 2012). DISCUSSION: Dissemination of these findings will contribute to the understanding of issues involved when communicating with people about oral chemotherapy. It is anticipated that findings will inform education, practice and policy.

Fuel stores of juvenile waders on autumn migration in high arctic Canada

Little is known about the fuel stores that arctic-breeding waders put on before departure from the breeding grounds. During a ship-based expedition to arctic Canada, we caught waders at seven, mainly coastal sites, with-in 68°-76°N and 139°-67°W, from 28 July to 31 August 1999. More than two hundred waders of twelve species were trapped, mainly White-rumped Calidris fuscicollis, Semipalmated C. pusilla, Baird's C. bairdii and Buff-breasted Sandpipers Tryngites subruficollis. The vast majority of the birds were juveniles. Body masses and visual fat stores were low, close to the lowest values found anywhere during the non-breeding season for the different species. The relatively fattest birds were Buff-breasted Sandpipers, but they were still far from their maximum body mass on spring migration. We conclude that juvenile arctic waders depart from their natal areas with only small fuel stores, which is in concordance with a time-minimising migration strategy.

The factors influencing the decision making of operative treatment for proximal humeral fractures

Background:
The factors influencing the decision making of operative treatment for fractures of the proximal humerus are debated. We hypothesized that there is no difference in treatment recommendations between surgeons shown radiographs alone and those shown radiographs and patient information. Secondarily, we addressed (1) factors associated with a recommendation for operative treatment, (2) factors associated with recommendation for arthroplasty, (3) concordance with the recommendations of the treating surgeons, and (4) factors affecting the inter-rater reliability of treatment recommendations.
Methods: A total of 238 surgeons of the Science of Variation Group rated 40 radiographs of patients with proximal humerus fractures. Participants were randomized to receive information about the patient and mechanism of injury. The response variables included the choice of treatment (operative vs nonoperative) and the percentage of matches with the actual treatment.
Results: Participants who received patient information recommended operative treatment less than those who received no information. The patient information that had the greatest influence on treatment recommendations included age (55%) and fracture me chanism (32%). The only other factor associated with a recommendation for operative treatment was region of practice. There was no significant difference between participants who were and were not provided with information regarding agreement with the actual treatment (operative vs nonoperative) provided by the treating surgeon.
Conclusion: Patient information - older age in particular - is associated with a higher likelihood of recommending nonoperative treatment than radiographs alone. Clinical information did not improve agreement of the Science of Variation Group with the actual treatment or the generally poor interobserver agreement on treatment recommendations

Development and interrater reliability of the UK Mental Health Triage Scale

Mental health triage scales are clinical tools used at point of entry to specialist mental health service to provide a systematic way of categorizing the urgency of clinical presentations, and determining an appropriate service response and an optimal timeframe for intervention. The aim of the present study was to test the interrater reliability of a mental health triage scale developed for use in UK mental health triage and crisis services. An interrater reliability study was undertaken. Triage clinicians from England and Wales (n = 66) used the UK Mental Health Triage Scale (UK MHTS) to rate the urgency of 21 validated mental health triage scenarios derived from real occasions of triage. Interrater reliability was calculated using Kendall's coefficient of concordance (w) and intraclass correlation coefficient (ICC) statistics. The average ICC was 0.997 (95% confidence interval (CI): 0.996-0.999 (F (20, 1300) = 394.762, P < 0.001). The single measure ICC was 0.856 (95% CI: 0.776-0.926 (F (20, 1300) = 394.762, P < 0.001). The overall Kendall's w was 0.88 (P < 0.001). The UK MHTS shows substantial levels of interrater reliability. Reliable mental health triage scales employed within effective mental health triage systems offer possibilities for not only improved patient outcomes and experiences, but also for efficient use of finite specialist mental health services.

Reproducibility of the online food4me food-frequency questionnaire for estimating dietary intakes across Europe

BACKGROUND: Accurate dietary assessment is key to understanding nutrition-related outcomes and is essential for estimating dietary change in nutrition-based interventions. OBJECTIVE: The objective of this study was to assess the pan-European reproducibility of the Food4Me food-frequency questionnaire (FFQ) in assessing the habitual diet of adults. METHODS: Participants from the Food4Me study, a 6-mo, Internet-based, randomized controlled trial of personalized nutrition conducted in the United Kingdom, Ireland, Spain, Netherlands, Germany, Greece, and Poland, were included. Screening and baseline data (both collected before commencement of the intervention) were used in the present analyses, and participants were included only if they completed FFQs at screening and at baseline within a 1-mo timeframe before the commencement of the intervention. Sociodemographic (e.g., sex and country) and lifestyle [e.g., body mass index (BMI, in kg/m(2)) and physical activity] characteristics were collected. Linear regression, correlation coefficients, concordance (percentage) in quartile classification, and Bland-Altman plots for daily intakes were used to assess reproducibility. RESULTS: In total, 567 participants (59% female), with a mean ± SD age of 38.7 ± 13.4 y and BMI of 25.4 ± 4.8, completed both FFQs within 1 mo (mean ± SD: 19.2 ± 6.2 d). Exact plus adjacent classification of total energy intake in participants was highest in Ireland (94%) and lowest in Poland (81%). Spearman correlation coefficients (ρ) in total energy intake between FFQs ranged from 0.50 for obese participants to 0.68 and 0.60 in normal-weight and overweight participants, respectively. Bland-Altman plots showed a mean difference between FFQs of 210 kcal/d, with the agreement deteriorating as energy intakes increased. There was little variation in reproducibility of total energy intakes between sex and age groups. CONCLUSIONS: The online Food4Me FFQ was shown to be reproducible across 7 European countries when administered within a 1-mo period to a large number of participants. The results support the utility of the online Food4Me FFQ as a reproducible tool across multiple European populations. This trial was registered at clinicaltrials.gov as NCT01530139.

How reliable is internet-based self-reported identity, socio-demographic and obesity measures in European adults?

In e-health intervention studies, there are concerns about the reliability of internet-based, self-reported (SR) data and about the potential for identity fraud. This study introduced and tested a novel procedure for assessing the validity of internet-based, SR identity and validated anthropometric and demographic data via measurements performed face-to-face in a validation study (VS). Participants (n = 140) from seven European countries, participating in the Food4Me intervention study which aimed to test the efficacy of personalised nutrition approaches delivered via the internet, were invited to take part in the VS. Participants visited a research centre in each country within 2 weeks of providing SR data via the internet. Participants received detailed instructions on how to perform each measurement. Individual's identity was checked visually and by repeated collection and analysis of buccal cell DNA for 33 genetic variants. Validation of identity using genomic information showed perfect concordance between SR and VS. Similar results were found for demographic data (age and sex verification). We observed strong intra-class correlation coefficients between SR and VS for anthropometric data (height 0.990, weight 0.994 and BMI 0.983). However, internet-based SR weight was under-reported (Δ -0.70 kg [-3.6 to 2.1], p < 0.0001) and, therefore, BMI was lower for SR data (Δ -0.29 kg m(-2) [-1.5 to 1.0], p < 0.0001). BMI classification was correct in 93 % of cases. We demonstrate the utility of genotype information for detection of possible identity fraud in e-health studies and confirm the reliability of internet-based, SR anthropometric and demographic data collected in the Food4Me study. TRIAL REGISTRATION: NCT01530139 ( http://clinicaltrials.gov/show/NCT01530139 ).

Effective self-management strategies for bipolar disorder: a community-engaged Delphi consensus consultation study

BACKGROUND: Self-management represents an important complement to psychosocial treatments for bipolar disorder (BD), but research is limited. Specifically, little is known about self-management approaches for elevated mood states; this study investigated self-management strategies for: (1) maintaining balance in mood, and (2) stopping progression into hypomania/mania. METHODS: To identify the common components of BD self-management, Delphi Consensus Consultation methods were combined with a Community-Based Participatory Research (CBPR) approach across five study phases: (1) Qualitative dataset content analysis; (2) Academic/grey literature reviews; (3) Content analysis; (4) Two Delphi rounds (rating strategies on a 5-point Likert scale, Very Unhelpful-Very Helpful), and; (5) Quantitative analysis and interpretation. Participants were people with BD and healthcare providers. RESULTS: Phases 1 and 2 identified 262 and 3940 candidate strategies, respectively; 3709 were discarded as duplicates/unintelligible. The remaining 493 were assessed via Delphi methods in Phase 4: 101 people with BD and 52 healthcare providers participated in Round 1; 83 of the BD panel (82%) and 43 of the healthcare provider panel (83%) participated in Round 2-exploratory factor analysis (EFA) was conducted on Round 2 results. LIMITATIONS: EFA was underpowered and sample was not ethnically diverse, limiting generalizability. DISCUSSION: High concordance was observed in ratings of strategy effectiveness between the two panels. Future research could usefully investigate the provisional discovery here of underlying factors which link individual strategies. For example, 'maintaining hope' underpinned strategies for maintaining balance, and 'decreasing use of stimulants' underpinned strategies to interrupt hypo/manic ascent. There is merit in combining CBPR and Delphi methods.

Comparison of medication policies to guide nursing practice across seven Victorian health services

Objectives The objective of this paper is to review and compare the content of medication management policies across seven Australian health services located in the state of Victoria. Methods The medication management policies for health professionals involved in administering medications were obtained from seven health services under one jurisdiction. Analysis focused on policy content, including the health service requirements and regulations governing practice. Results and Conclusions The policies of the seven health services contained standard information about staff authorisation, controlled medications and poisons, labelling injections and infusions, patient self-administration, documentation and managing medication errors. However, policy related to individual health professional responsibilities, single- and double-checking medications, telephone orders and expected staff competencies varied across the seven health services. Some inconsistencies in health professionals' responsibilities among medication management policies were identified. What is known about the topic? Medication errors are recognised as the single most preventable cause of patient harm in hospitals and occur most frequently during administration. Medication management is a complex process involving several management and treatment decisions. Policies are developed to assist health professionals to safely manage medications and standardise practice; however, co-occurring activities and interruptions increase the risk of medication errors. What does this paper add? In the present policy analysis, we identified some variation in the content of medication management policies across seven Victorian health services. Policies varied in relation to medications that require single- and double-checking, as well as by whom, nurse-initiated medications, administration rights, telephone orders and competencies required to check medications. What are the implications for practitioners? Variation in medication management policies across organisations is highlighted and raises concerns regarding consistency in governance and practice related to medication management. Lack of practice standardisation has previously been implicated in medication errors. Lack of intrajurisdictional concordance should be addressed to increase consistency. Inconsistency in expectations between healthcare services may lead to confusion about expectations among health professionals moving from one healthcare service to another, and possibly lead to increased risk of medication errors.