Factors Associated with Poor Quality of Life in a Canadian Cohort of Patients with Inflammatory Bowel Disease: A Cross-sectional Study.

BACKGROUND: Health-related quality of life (QoL) is often adversely affected in patients with inflammatory bowel disease (IBD). We aimed to identify factors associated with poor QoL among Canadian patients with IBD in clinical remission. METHODS: We enrolled patients at a single academic tertiary care center with inactive IBD. All eligible patients completed a series of questionnaires that included questions on demographics, disease activity, anxiety, depression and the presence of irritable bowel syndrome (IBS) symptoms. Stool sample for fecal calprotectin (FC) was also collected to assess for subclinical inflammation. The primary outcome measure was QoL assessed by the short inflammatory bowel disease questionnaire (SIBDQ), with planned subgroup comparisons for fatigue, anxiety, depression and IBS symptoms. RESULTS: Ninety-three patients were eligible for inclusion in this study. The median SIBDQ scores were lower in patients with anxiety (P < 0.001), depression (P = 0.004), IBS symptoms (P < 0.001) and fatigue (P = 0.018). Elevated FC in patients in clinical remission did not impact QoL. These findings were consistent on multivariate linear regression. CONCLUSIONS: Anxiety, depression, fatigue and IBS symptoms are all independently associated with lower QoL in patients with inactive IBD. Clinicians are encouraged to screen for these important factors as they may detrimentally impact QoL in IBD patients even in clinical remission.

The Role of Replication Studies in Theory Building.

At least since Meehl's (in)famous 1978 article, the state of theorizing in psychology has often been lamented. Replication studies have been presented as a way of directly supporting theory development by enabling researchers to more confidently and precisely test and update theoretical claims. In this article I use contemporary work from philosophy of science to make explicit and emphasize just how much theory development is required before "good" replication studies can be carried out and show just how little theoretical payoff even good conceptual replications offer. I suggest that in many areas of psychology aiming at replication is misplaced and that instead replication attempts are better seen as exploratory studies that can be used in the cumulative development of theory and measurement procedures.

Causal manipulation of feed-forward and recurrent processing differentially affects measures of consciousness.

It has been theorized that cortical feed-forward and recurrent neural activity support unconscious and conscious cognitive processes, respectively. Here we causally tested this proposition by applying event-related transcranial magnetic stimulation (TMS) at early and late times relative to visual stimuli, together with a pulse designed to suppress conscious detection. Consistent with pre-registered hypotheses, early TMS affected residual, reportedly 'unseen' capacity. However, conscious perception also appeared critically dependent upon feed-forward processing to a greater extent than the later recurrent phase. Additional exploratory analyses suggested that these early effects dissociated from top-down criterion measures, which were most affected by later TMS. These findings are inconsistent with a simple dichotomy where feed-forward and recurrent processes correspond to unconscious and conscious mechanisms. Instead, different components of awareness may correspond to different phases of cortical dynamics in which initial processing is broadly perceptual whereas later recurrent processing might relate to decision to report.

'Calibrating to scale: a framework for humanitarian health organizations to anticipate, prevent, prepare for and manage climate-related health risks'.

Climate Change is adversely affecting health by increasing human vulnerability and exposure to climate-related stresses. Climate change impacts human health both directly and indirectly, through extreme weather events, changing distribution of health risks, increased risks of undernutrition, population displacement, and greater risks of injuries, disease, and death (Ebi, K., Campbell-Lendrum, D., & Wyns, A. The 1. 5 health report. WHO. 2018). This risk amplification is likely to increase the need for humanitarian support. Recent projections indicate that under a business as usual scenario of sustained greenhouse gas emissions, climate change could double the demand for humanitarian assistance by 2050 (World Health Organization. Operational Framework for building climateresilient health systems. WHO. 2015). Humanitarian assistance is currently not meeting the existing needs, therefore, any additional burden is likely to be highly challenging.Global health advocates, researchers, and policymakers are calling for urgent action on climate change, yet there is little clarity on what that action practically entails for humanitarian organizations. While some humanitarian organizations may consider themselves well designed to respond, climate change as a transversal threat requires the incorporation of a resilience approach to humanitarian action and policy responses.By bringing together authors from two historically disparate fields - climate change and health, and humanitarian assistance - this paper aims to increase the capacity of humanitarian organizations to protect health in an unstable climate by presenting an adapted framework. We adapted the WHO operational framework for climate-resilient health systems for humanitarian organizations and present concrete case studies to demonstrate how the framework can be implemented. Rather than suggest a re-design of humanitarian operations we recommend the application of a climate-lens to humanitarian activities, or what is also referred to as mainstreaming climate and health concerns into policies and programs. The framework serves as a starting point to encourage further dialogue, and to strengthen collaboration within, between, and beyond humanitarian organizations.

Identifying the World Health Organization's fifth moment for hand hygiene: Infection prevention in the operating room.

BACKGROUND: The World Health Organization have designed the fifth of their '5 moments' for hand hygiene to account for microbial transfer from patients to equipment in a narrow area around that patient, known as the patient zone. The study was prompted by emerging local confusion about application of the patient zone in the operating room (OR). AIM/OBJECTIVES: In two phases, we aimed to create a '5 moments' style poster displaying an OR patient zone: phase 1, quantify equipment, in direct contact with the patient and, touched by non-scrubbed staff immediately after touching the patient; and phase 2, categorise equipment identified in phase 1 into patient zone and healthcare zone. An objective is to produce a '5 moments' poster for the OR. METHODS: The first phase used non-participant direct overt observation. In phase 2, phase 1 data were collaboratively assigned to patient zone or healthcare zone. Photography and graphic design were used to produce the OR '5 moments' poster. RESULTS: In 11 full-length surgeries, 20 pieces of equipment were in direct contact with the patient and 57 pieces of equipment were touched. In phase 2, a '5 moments' poster showing an OR patient zone was designed. DISCUSSION: Content of the patient zone was identified and displayed in a novel resource. Having shared understanding of the patient zone has potential to sustain hand hygiene compliance and equipment cleaning in the OR. CONCLUSION: Limitations in methods were balanced by collaboration with frontline staff. The study has been used as a teaching tool in the OR and similar settings.

What works best when implementing a physical activity intervention for teenagers? Reflections from the ACTIVE Project: a qualitative study.

OBJECTIVE: This paper explores what aspects of a multicomponent intervention were deemed strengths and weaknesses by teenagers and the local council when promoting physical activity to young people. DESIGN: Qualitative findings at 12 months from a mixed method randomised control trial. METHODS: Active Children Through Incentive Vouchers-Evaluation (ACTIVE) gave teenagers £20 of activity enabling vouchers every month for a year. Peer mentors were also trained and a support worker worked with teenagers to improve knowledge of what was available. Semistructured focus groups took place at 12 months to assess strengths and weaknesses of the intervention. Eight focus groups (n=64 participants) took place with teenagers and one additional focus group was dedicated to the local council's sport development team (n=8 participants). Thematic analysis was used to analyse the data. RESULTS: Teenagers used the vouchers on three main activities: trampolining, laser tag or the water park. These appeal to both genders, are social, fun and require no prior skill or training. Choice and financial support for teenagers in deprived areas was considered a strength by teenagers and the local council. Teenagers did not engage with a trained peer mentor but the support worker was considered helpful. CONCLUSIONS: The ACTIVE Project's delivery had both strengths and weakness that could be used to underpin future physical activity promotion. Future interventions should focus on improving access to low cost, fun, unstructured and social activities rather than structured organised exercise/sport. The lessons learnt from this project can help bridge the gap between what is promoted to teenagers and what they actually want from activity provision. TRIAL REGISTRATION NUMBER: ISRCTN75594310.

Severe flare as a predictor of poor outcome in ankylosing spondylitis: a cohort study using questionnaire and routine data linkage.

OBJECTIVE: To explore severe flare and constant disease pattern (no periods of remission) in AS as predictors of poor outcomes [impaired function, unemployment/early retirement, work impairment, anti-TNF, surgery, frequent general practitioner (GP) visits, depression and anxiety]. METHODS: Three hundred and forty-eight AS patients completed questionnaires about their experience with disease flares. Questionnaire data were linked to electronic medical records to examine visits to GPs and hospital admission data. Outcomes were stratified in two ways: self-reported experience of severe flare and constant disease pattern using the flare illustration tool. RESULTS: The majority of patients (72%, 208/289) experienced flare pre-diagnosis. Severe flares were reported by 58% (202/348) of participants (self-report); of these, 195 responded about earliest flares and 69% (135/195) of severe flare patients experienced flares pre-diagnosis. Patients who self-reported severe flares had worse function, disease activity, work impairment and symptoms of anxiety and depression, were less likely to be employed and had more GP encounters per year compared with those who never reported severe flares. Participants who reported constant unremitting disease on the flare illustration tool had worse disease activity, impaired function and work impairment and were more likely to smoke compared with those with intermittent disease. Analysis showed a relationship between self-report of severe flare and subsequent depression, impaired function, increased disease activity and work limitations. CONCLUSION: Severe flare is associated with poor outcomes such as work impairment and impaired function. The onset of severe flare early in the disease course may be a risk factor for later poor outcome and this group could benefit from targeted early aggressive treatment to improve prognosis.

Patient perspectives of managing fatigue in Ankylosing Spondylitis, and views on potential interventions: a qualitative study.

BACKGROUND: Fatigue is a major component of living with ankylosing spondylitis (AS), though it has been largely over-looked, and currently there are no specific agreed management strategies. METHODS: This qualitative exploratory study involved participants who are members of an existing population-based ankylosing spondylitis (PAS) cohort. Participants residing in South West Wales were invited to participate in a focus group to discuss; (1) effects of fatigue, (2) self-management strategies and (3) potential future interventions. The focus groups were audio-recorded and the transcripts were analysed using thematic analysis. RESULTS: Participants consisted of 3 males/4 females (group 1) and 4 males/3 females (group 2), aged between 35 and 73 years (mean age 53 years). Three main themes were identified: (1) The effects of fatigue were multi-dimensional with participants expressing feelings of being 'drained' (physical), 'upset' (emotional) and experiencing 'low-mood' (psychological); (2) The most commonly reported self-management strategy for fatigue was a balanced combination of activity (exercise) and rest. Medication was reluctantly taken due to side-effects and worries over dependency; (3) Participants expressed a preference for psychological therapies rather than pharmacological for managing fatigue. Information on Mindfulness-Based Stress Reduction (MBSR) was received with interest, with recommendations for delivery in a group format with the option of distance-based delivery for people who were not able to attend a group course. CONCLUSIONS: Patients frequently try and manage their fatigue without any formal guidance or support. Our research indicates there is a need for future research to focus on psychological interventions to address the multi-faceted aspects of fatigue in AS.

Treatment-, patient-, and disease-related factors and the emergence of adverse events with tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

Four breakpoint cluster region (BCR)-ABL1 tyrosine kinase inhibitors (TKIs) are currently available for the treatment of chronic myeloid leukemia (CML): imatinib, nilotinib, dasatinib, and bosutinib. Choosing the most appropriate TKI requires clinicians to consider a host of patient-, disease-, and treatment-related factors, not the least of which include the safety profiles of the agents. This review discusses the potential impact of treatment-, patient-, and disease-related characteristics on the emergence of adverse events during TKI therapy, with a focus on the underlying mechanisms believed to be responsible for a number of important adverse events associated with these agents and what implications they may have for treatment choice, particularly in the setting of first-line treatment. A literature search of the PubMed database was conducted to identify articles that described the molecular mechanisms of BCR-ABL1-mediated leukemic transformation, the efficacy and safety of imatinib, nilotinib, dasatinib, and bosutinib in patients with CML, the kinase-binding spectrum of each TKI, and evidence suggesting a link between the TKI-binding profile and adverse events. The pattern of adverse events associated with each agent is important when selecting treatment with a TKI. Clinical studies suggest that imatinib, nilotinib, dasatinib, and bosutinib have differing safety profiles, which are in part attributable to the specificity and selectivity of each agent. Although much basic research must be conducted to further illuminate the mechanisms responsible for TKI-related adverse events, on- and off-target effects are believed to be at least partly responsible for cardiovascular toxicity, myelosuppression, fluid retention, gastrointestinal toxicity, and dermatologic toxicity. Increased understanding of the factors that affect TKI-associated adverse events and long-term safety data will enable a more informed approach to the selection of therapy best suited to the individual needs of patients with CML.

Fatigue in ankylosing spondylitis: treatment should focus on pain management.

OBJECTIVES: Fatigue is an important symptom associated with ankylosing spondylitis (AS). This study examines patients' perspectives and clinical associations of fatigue to help inform potential strategies to alleviate fatigue in AS. METHODS: A mixed methods approach was taken to examine fatigue in a cohort of people with AS. Fatigue levels were evaluated from 3 consecutive monthly questionnaires. Open-ended questions on fatigue were analyzed using thematic analysis and logistic regression was used to examine quantitative data. In addition, fatigue levels were examined before and after treatment with anti-tumor necrosis factor (TNF) compared to nontreated controls. RESULTS: Three hundred forty-eight of 385 participants completed a fatigue questionnaire. Fatigue was reported to have significant physical, social, and psychological effects. A third of the participants reported that there was nothing they could do to reduce their fatigue, whereas other participants reported that medication, exercise, and resting helped. The main factor associated with fatigue was pain [ß-coefficient: 0.74 (95% CI: 0.66 to 0.81)], whereas depression was much less strongly associated. However, these factors only explained 40% of the variation in fatigue levels. Starting anti-TNF therapy reduced fatigue and pain levels compared to the period of time before taking anti-TNF [difference: 14.4 (95% CI: 5.3 to 23.5) on a scale of 0-100] and this reduction was not seen in controls over the same period. CONCLUSIONS: Fatigue is not strongly associated with anxiety, motivation, and depression; instead the factor most associated with fatigue is pain. This suggests that in addition to treatments to reduce disease activity, strategies for alleviating fatigue in AS should focus on pain management techniques and actively treating inflammation.

The information needs of people living with ankylosing spondylitis: a questionnaire survey.

BACKGROUND: Today, health care is patient-centred with patients more involved in medical decision making and taking an active role in managing their disease. It is important that patients are appropriately informed about their condition and that their health care needs are met. We examine the information utilisation, sources and needs of people with ankylosing spondylitis (AS). METHODS: Participants in an existing AS cohort study were asked to complete a postal or online questionnaire containing closed and open-ended questions, regarding their information access and needs. Participants were stratified by age and descriptive statistics were performed using STATA 11, while thematic analysis was performed on open-ended question narratives. Qualitative data was handled in Microsoft Access and explored for emerging themes and patterns of experiences. RESULTS: Despite 73% of respondents having internet access, only 49% used the internet to access information regarding AS. Even then, this was only infrequently. Only 50% of respondents reported accessing written information about AS, which was obtained mainly in specialist clinics. Women were more likely than men to access information (63% (women) 46% (men)) regardless of the source, while younger patients were more likely to use online sources. The main source of non-written information was the rheumatologist. Overall, the respondents felt there was sufficient information available, but there was a perception that the tone was often too negative. The majority (95%) of people would like to receive a regular newsletter about AS, containing positive practical and local information. Suggestions were also made for more information about AS to be made available to non-specialist medical professionals and the general public. CONCLUSIONS: There appears to be sufficient information available for people with AS in the UK and this is mostly accessed by younger AS patients. Many patients, particularly men, choose not to access AS information and concerns were raised about its negative tone. Patients still rely on written and verbal information from their specialists. Future initiatives should focus on the delivery of more positive information, targeting younger participants in particular and increasing the awareness in the general population and wider non-specialist medical community.

Assessing health-related quality of life in patients with inflammatory bowel disease in Zhejiang, China.

AIMS: The aim of this study was to assess health-related quality of life in patients with inflammatory bowel disease in Zhejiang, Mainland China. BACKGROUND: The incidence of inflammatory bowel disease in China is believed to be low but has been increasing in the past decade. The quality of life of Chinese patients with inflammatory bowel disease is unknown. DESIGN: A cross-sectional study. METHODS: The study was conducted in 92 patients with inflammatory bowel disease in Zhejiang, China, 52 with ulcerative colitis and 40 with Crohn's disease. Health-related quality of life was measured by the Chinese version of the Inflammatory Bowel Disease Questionnaire and Short Form-36, respectively. Disease activity was assessed by the Walmsley and Harvey-Bradshaw simple indices for ulcerative colitis and Crohn's disease, respectively. Demographic and clinical variables were also recorded. Short Form-36 data from the study sample were compared with a reference population of 1688 Chinese people residing in Hangzhou, Zhejiang, China. RESULTS: No significant health-related quality of life differences were found between patients with ulcerative colitis and Crohn's disease (p > 0.05). Pooled data showed that inflammatory bowel disease patients with active disease had significantly lower scores for all eight dimensions of Short Form-36 compared to those in remission (p < 0.01); those with active disease scored significantly lower than population norms in all dimensions of Short Form-36 except mental health (p < 0.05); whereas those in remission scored significantly lower than population norms in role physical (p < 0.01) and general health dimensions (p < 0.05). The regression analyses identified only disease activity index and employment status to explain variations in health-related quality of life (p < 0.01). CONCLUSIONS: Inflammatory bowel disease similarly impairs health-related quality of life in patients with both ulcerative colitis and Crohn's disease. RELEVANCE TO CLINICAL PRACTICE: The results suggest that any interventions that produce a stable clinical remission, whether medical or surgical, allowing patients to return to their usual work position can decrease the disease impact on their daily lives.

Probable amlodipine-induced angioedema.

OBJECTIVE: To report a case of angioedema likely associated with amlodipine administration in a patient with a right thalamic hemorrhagic stroke. CASE SUMMARY: A 50-year-old female experienced angioedema during hospitalization for a right thalamic hemorrhagic stroke. She had no past history of angioedema and all of her medications were assessed for risk of angioedema. After careful evaluation, case reports linking calcium channel blockers (CCBs) and angioedema led to further examination of amlodipine as a cause. Amlodipine therapy had been initiated 24 hours prior to the development of angioedema, which then resolved 72 hours after discontinuation of the drug. In total, the patient experienced oropharyngeal swelling for 10 days. DISCUSSION: In determining a cause for the patient's angioedema we eliminated genetic, allergic, physically induced, thyroid autoimmune disease-associated, and medication-induced causes. Three case reports describing 7 patients have linked the CCBs verapamil, diltiazem, and nifedipine with angioedema. The onset and resolution of symptoms in our patient were very similar to those seen in other case reports. Application of the Naranjo probability scale found a probable link between amlodipine and angioedema. CONCLUSIONS: Although few reports of CCB-induced angioedema exist, to our knowledge, this is the first reported case to suggest a link between angioedema and amlodipine therapy. Clinicians should consider amlodipine as a potential cause of angioedema.

Signal detection theory, the exclusion failure paradigm and weak consciousness--evidence for the access/phenomenal distinction?

Block [Block, N. (2005). Two neural correlates of consciousness. Trends in Cognitive Science, 9, 46-52] and Snodgrass (2006) claim that a signal detection theory (SDT) analysis of qualitative difference paradigms, in particular the exclusion failure paradigm, reveals cases of phenomenal consciousness without access consciousness. This claim is unwarranted on several grounds. First, partial cognitive access rather than a total lack of cognitive access can account for exclusion failure results. Second, Snodgrass's Objective Threshold/Strategic (OT/S) model of perception relies on a problematic 'enable' approach to perception that denies the possibility of intentional control of unconscious perception and any effect of following different task instructions on the presence/absence of phenomenal consciousness. Many of Block's purported examples of phenomenal consciousness without cognitive access also rely on this problematic approach. Third, qualitative difference paradigms may index only a subset of access consciousness. Thus, qualitative difference paradigms like exclusion failure cannot be used to isolate phenomenal consciousness, any attempt to do so still faces serious methodological problems.

Water sources accessed by arid zone riparian trees in highly saline environments, Australia.

The flow regimes of arid zone rivers are often highly variable, and shallow groundwater in the alluvial aquifers can be very saline, thus constraining the availability and quality of the major water sources available to riparian trees-soil water, shallow groundwater and stream water. We have identified water sources and strategies used by riparian trees in more highly saline and arid conditions than previously studied for riparian trees of arid zone rivers. Our research focused on the riparian species Eucalyptus coolabah, one of the major riparian trees of ephemeral arid zone rivers in Australia. The water sources available to this riparian tree were examined using delta(18)O isotope data from xylem, soil water, groundwater and surface water. Additionally, soil chloride and matric potential data were used to infer zones of water availability for root uptake. Despite the saline conditions, the trees used a mixture of soil water and groundwater sources, but they did not use surface water directly. The study identified three strategies used to cope with typically high groundwater and soil water salinities. Firstly, the trees preferentially grow in zones of most frequent flushing by infiltrating streamflow, such as the bank-tops of channels. Secondly, the trees limit water use by having low transpiration rates. Thirdly, the trees are able to extract water at very low osmotic potentials, with water uptake continuing at chloride concentrations of at least 20,000-30,000 mg L(-1).

Voltage-gated potassium channel modulation of neurotoxic activity in human immunodeficiency virus type-1(HIV-1)-infected macrophages.

Macrophages play an important role in brain immune and inflammatory responses. They are also critical cells in mediating the pathology of neurodegenerative disorders such as HIV-associated dementia. This is largely through their capacity to secrete a variety of bioactive molecules such as cytokines, leading to neuronal dysfunction and/or death. Accumulating evidence indicates that voltage-gated potassium (Kv) channels play a pivotal role in the modulation of macrophage proliferation, activation, and secretion. Blockade of Kv channels by specific antagonists decreases macrophage cytokine production and ameliorates macrophage-associated neuronal injury. These results suggest that Kv channels might become a potential target for the development of new therapeutic strategies for chronic inflammatory diseases.