Identifying factors that predict worse constipation symptoms in palliative care patients: A secondary analysis

© Copyright 2017, Mary Ann Liebert, Inc. 2017. Objective: The aim of this work was to investigate whether variables identified as likely to impact the experience of constipation in other clinical settings similarly affected the experiences of constipated palliative care patients. Background: The majority of palliative care patients with cancer are likely to be bothered by constipation symptoms at some point in their disease trajectory. Despite this, it remains unclear as to which factors predict more severe problems. Methods: This study was conducted in a sample of 94 constipated palliative care patients who were asked to voluntarily complete a series of questions regarding their demographic and other characteristics, including whether they had chronic constipation symptoms, that is, constipation symptoms for 12 months. Other variables included age, body mass index, sex, performance status, and regular opioids and their doses. At the same time, they were asked to complete the Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires. Results: Descriptive statistics summarized baseline data. Unadjusted associations between the selected variables on PAC-SYM were examined by using bi-variate analyses. Significant variables identified on bi-variate analyses were included in a multivariate analysis. The final results identified that only the chronicity of constipation symptoms predicted more severe symptoms. This relationship persisted when this single variable was retained in the final model, illustrating that PAC-SYM scores are 0.41 higher in patients with chronic constipation compared with those without it (p = 0.02). In contrast, regular opioid use was not identified as a significant factor (p = 0.56). Discussion: This study suggests that the factor most likely to predict worse constipation symptoms was the duration that people had experienced problems. Further, those who perceived their constipation symptoms to be more severe had a poorer quality of life. More work is required to better define constipation risk factors and ways to best modify a patient's experiences

'Everyday memory' impairments in autism spectrum disorders

‘Everyday memory’ is conceptualised as memory within the context of day-to-day life and, despite its functional relevance, has been little studied in individuals with autism spectrum disorders (ASDs). In the first study of its kind, 94 adolescents with an ASD and 55 without an ASD completed measures of everyday memory from the Rivermead Behavioural Memory Test (RBMT) and a standard word recall task (Children’s Auditory Verbal Learning Test-2: CAVLT-2). The ASD group showed significant impairments on the RBMT, including in prospective memory, alongside impaired performance on the CAVLT-2. Social and communication ability was significantly associated with prospective remembering in an everyday memory context but not with the CAVLT-2. The complex nature of everyday memory and its relevance to ASD is discussed

The clinical overlap between functional dyspepsia and irritable bowel syndrome based on Rome III criteria

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies suggest considerable overlap between functional dyspepsia (FD) and irritable bowel syndrome (IBS). To date, no surveys have been performed to investigate the clinical overlap between these two disorders using Rome III criteria. Our aim was to investigate the prevalence and risk factors for the overlap of FD and IBS based on Rome III criteria in a large clinical sample.</p> <p>Methods</p> <p>Consecutive patients at the general gastroenterology outpatient clinic were requested to complete a self-report questionnaire. FD and IBS were defined by Rome III criteria.</p> <p>Results</p> <p>Questionnaires were returned by 3014 patients (52.8% female, 89% response rate). FD-IBS overlap was observed in 5.0% of the patients, while 15.2% and 10.9% of the patients were classified as FD alone and IBS alone, respectively. Compared with non-IBS patients, the odds ratio of having FD among IBS patients was 2.09 (95% CI: 1.68–2.59). Patients with FD-IBS overlap had higher severity scores for the postprandial fullness symptom (2.35 ± 1.49 vs. 1.72 ± 1.59, P < 0.001) and overall FD symptom (6.65 ± 2.88 vs. 5.82 ± 2.76, P = 0.002) than those with FD alone. The only independent risk factor for FD-IBS overlap vs. FD alone was the presence of postprandial fullness symptom (OR 2.67, 95% CI: 1.34–5.31).</p> <p>Conclusion</p> <p>Clinical overlap of FD and IBS according to Rome III criteria is very common. One risk factor for FD-IBS overlap is the presence of postprandial fullness symptom. This study provides clues for future pathophysiological studies of FD and IBS.</p

A 6-week, multicentre, randomised, double-blind, double-dummy, active-controlled, clinical safety study of lumiracoxib and rofecoxib in osteoarthritis patients

<p>Abstract</p> <p>Background</p> <p>Lumiracoxib is a selective cyclooxygenase-2 inhibitor effective in the treatment of osteoarthritis (OA) with a superior gastrointestinal (GI) safety profile as compared to traditional non-steroidal anti-inflammatory drugs (NSAIDs, ibuprofen and naproxen). This safety study compared the GI tolerability, the blood pressure (BP) profile and the incidence of oedema with lumiracoxib and rofecoxib in the treatment of OA. Rofecoxib was withdrawn worldwide due to an associated increased risk of CV events and lumiracoxib has been withdrawn from Australia, Canada, Europe and a few other countries following reports of suspected adverse liver reactions.</p> <p>Methods</p> <p>This randomised, double-blind study enrolled 309 patients (aged greater than or equal to 50 years) with primary OA across 51 centres in Europe. Patients were randomly allocated to receive either lumiracoxib 400 mg od (four times the recommended dose in OA) (<it>n </it>= 154) or rofecoxib 25 mg od (<it>n </it>= 155). The study was conducted for 6 weeks and assessments were performed at Weeks 3 and 6. The primary safety measures were the incidence of predefined GI adverse events (AEs) and peripheral oedema. The secondary safety measures included effect of treatment on the mean sitting systolic and diastolic blood pressure (msSBP and msDBP). Tolerability of lumiracoxib 400 mg was assessed by the incidence of AEs.</p> <p>Results</p> <p>Lumiracoxib and rofecoxib displayed similar GI safety profiles with no statistically significant difference in predefined GI AEs between the two groups (43.5% <it>vs</it>. 37.4%, respectively). The incidence and severity of individual predefined GI AEs was comparable between the two groups. The incidence of peripheral oedema was low and identical in both the groups (<it>n </it>= 9, 5.8%). Only one patient in the lumiracoxib group and three patients in the rofecoxib group had a moderate or severe event. At Week 6 there was a significantly lower msSBP and msDBP in the lumiracoxib group compared to the rofecoxib group (<it>p </it>< 0.05). A similar percentage of patients in both groups showed an improvement in target joint pain and disease activity. The tolerability profile was similar in both the treatment groups.</p> <p>Conclusion</p> <p>Lumiracoxib 400 mg od (four times the recommended dose in OA) provided a comparable GI safety profile to rofecoxib 25 mg od (therapeutic dose). However, lumiracoxib was associated with a significantly better BP profile as compared to rofecoxib.</p> <p>Trial registration number -</p> <p>NCT00637949</p

Measles vaccination in humanitarian emergencies: a review of recent practice

<p>Abstract</p> <p>Background</p> <p>The health needs of children and adolescents in humanitarian emergencies are critical to the success of relief efforts and reduction in mortality. Measles has been one of the major causes of child deaths in humanitarian emergencies and further contributes to mortality by exacerbating malnutrition and vitamin A deficiency. Here, we review measles vaccination activities in humanitarian emergencies as documented in published literature. Our main interest was to review the available evidence focusing on the target age range for mass vaccination campaigns either in response to a humanitarian emergency or in response to an outbreak of measles in a humanitarian context to determine whether the current guidance required revision based on recent experience.</p> <p>Methods</p> <p>We searched the published literature for articles published from January 1, 1998 to January 1, 2010 reporting on measles in emergencies. As definitions and concepts of emergencies vary and have changed over time, we chose to consider any context where an application for either a Consolidated Appeals Process or a Flash Appeal to the UN Central Emergency Revolving Fund (CERF) occurred during the period examined. We included publications from countries irrespective of their progress in measles control as humanitarian emergencies may occur in any of these contexts and as such, guidance applies irrespective of measles control goals.</p> <p>Results</p> <p>Of the few well-documented epidemic descriptions in humanitarian emergencies, the age range of cases is not limited to under 5 year olds. Combining all data, both from preventive and outbreak response interventions, about 59% of cases in reports with sufficient data reviewed here remain in children under 5, 18% in 5-15 and 2% above 15 years. In instances where interventions targeted a reduced age range, several reports concluded that the age range should have been extended to 15 years, given that a significant proportion of cases occurred beyond 5 years of age.</p> <p>Conclusions</p> <p>Measles outbreaks continue to occur in humanitarian emergencies due to low levels of pre-existing population immunity. According to available published information, cases continue to occur in children over age 5. Preventing cases in older age groups may prevent younger children from becoming infected and reduce mortality in both younger and older age groups.</p

Characterizing Ligand-Gated Ion Channel Receptors with Genetically Encoded Ca++ Sensors

We present a cell based system and experimental approach to characterize agonist and antagonist selectivity for ligand-gated ion channels (LGIC) by developing sensor cells stably expressing a Ca2+ permeable LGIC and a genetically encoded Förster (or fluorescence) resonance energy transfer (FRET)-based calcium sensor. In particular, we describe separate lines with human α7 and human α4β2 nicotinic acetylcholine receptors, mouse 5-HT3A serotonin receptors and a chimera of human α7/mouse 5-HT3A receptors. Complete concentration-response curves for agonists and Schild plots of antagonists were generated from these sensors and the results validate known pharmacology of the receptors tested. Concentration-response relations can be generated from either the initial rate or maximal amplitudes of FRET-signal. Although assaying at a medium throughput level, this pharmacological fluorescence detection technique employs a clonal line for stability and has versatility for screening laboratory generated congeners as agonists or antagonists on multiple subtypes of ligand-gated ion channels. The clonal sensor lines are also compatible with in vivo usage to measure indirectly receptor activation by endogenous neurotransmitters

Purinergic Receptor Stimulation Reduces Cytotoxic Edema and Brain Infarcts in Mouse Induced by Photothrombosis by Energizing Glial Mitochondria

Treatments to improve the neurological outcome of edema and cerebral ischemic stroke are severely limited. Here, we present the first in vivo single cell images of cortical mouse astrocytes documenting the impact of single vessel photothrombosis on cytotoxic edema and cerebral infarcts. The volume of astrocytes expressing green fluorescent protein (GFP) increased by over 600% within 3 hours of ischemia. The subsequent growth of cerebral infarcts was easily followed as the loss of GFP fluorescence as astrocytes lysed. Cytotoxic edema and the magnitude of ischemic lesions were significantly reduced by treatment with the purinergic ligand 2-methylthioladenosine 5′ diphosphate (2-MeSADP), an agonist with high specificity for the purinergic receptor type 1 isoform (P2Y1R). At 24 hours, cytotoxic edema in astrocytes was still apparent at the penumbra and preceded the cell lysis that defined the infarct. Delayed 2MeSADP treatment, 24 hours after the initial thrombosis, also significantly reduced cytotoxic edema and the continued growth of the brain infarction. Pharmacological and genetic evidence are presented indicating that 2MeSADP protection is mediated by enhanced astrocyte mitochondrial metabolism via increased inositol trisphosphate (IP3)-dependent Ca2+ release. We suggest that mitochondria play a critical role in astrocyte energy metabolism in the penumbra of ischemic lesions, where low ATP levels are widely accepted to be responsible for cytotoxic edema. Enhancement of this energy source could have similar protective benefits for a wide range of brain injuries