Perceived adherence to prescribed treatment in juvenile idiopathic arthritis over a one‐year period

Objective

To document perceived adherence to treatment (taking medications and performing exercises) in patients with juvenile idiopathic arthritis (JIA) over a 1‐year period and to identify related factors.

Methods

We surveyed parents of patients with JIA at the Montreal Children's Hospital and British Columbia's Children's Hospital in Vancouver. Parents were asked to respond to a series of questionnaires every 3 months over a 12‐month period. Perceived adherence was evaluated on a 100‐mm visual analog scale (VAS) in the Parent Adherence Report Questionnaire (PARQ). Parental coping, distress, child function, disease severity and duration, perceived helpfulness of treatment, problems encountered, and sociodemographic data were also assessed.

Results

The mean age of our sample of 175 children was 10.2 years; mean age at diagnosis was 6.1 years and mean disease duration was 4.1 years. Perceived adherence to medications was consistently high, with average adherence at baseline, 3, 6, 9, and 12 months being 86.1, 91.7, 90.4, 92.0, and 88.8, respectively, on the PARQ VAS. Perceived adherence to exercise was lower but remained steady, with corresponding means of 54.5, 64.1, 61.2, 63.0, and 54.3, respectively. Using generalized estimating equation analysis, factors associated with higher perceived adherence to medications included perceived helpfulness of medications and lower disease severity; those associated with higher perceived adherence to exercise were younger age of the child, child involvement in responsibility for treatment, and higher perceived helpfulness of the treatment.

Conclusion

Belief in helpfulness of treatment is associated with higher parental perceived adherence to treatment.     

Prospects for a Vaccine for Clostridium difficile

Clostridium difficile diarrhoea and colitis is a new disease that is attributable to broad spectrum antibiotic therapy. During the past 2 decades C. difficile has become one of the most common nosocomial pathogens in the developed world. As changing demographics create an increasingly elderly population and the use of broad spectrum antimicrobials continues to expand, C. difficile is likely to become increasingly problematic. Disease caused by this organism is caused by the inflammatory actions of its 2 toxins, A and B, on the intestinal mucosa. Human antibody responses to these toxins are common in the general population and in patients with C. difficile-associated disease. There is substantial, albeit inconclusive, evidence to indicate that antitoxin antibodies provide protection against severe, prolonged or recurrent C. difficile diarrhoea. Immunity induced by oral or parenteral passive administration of antibody is protective in animal models of C. difficile infection. In humans, intravenous passive immunisation with pooled human immunoglobulin has been successful in the treatment of recurrent and severe C. difficile colitis. Human trials of oral passive immunotherapy with bovine immunoglobulin therapy are in progress. Formalin-inactivated culture filtrate from toxigenic C. difficile, as well as purified and inactivated toxins, have been used to successfully immunise animals. Similar preparations are under investigation as possible human vaccines. Antibiotic therapy is effective in treating most individual patients with C. difficile diarrhoea, but has proven ineffective in reducing the overall incidence of nosocomial infection. Active immunisation is probably the most promising approach to long term control of this difficult iatrogenic disease.     

Clostridium difficile vaccine and serum immunoglobulin G antibody response to toxin A

There is a strong association between serum antibody responses to toxin A and protection against Clostridium difficile diarrhea. A parenteral C. difficile toxoid vaccine induced very-high-level responses to anti-toxin A immunoglobulin G (IgG) in the sera of healthy volunteers. After vaccination, the concentrations of anti-toxin A IgG in the sera of all 30 recipients exceeded the concentrations that were associated with protection in previous clinical studies. Furthermore, the median concentration of serum anti-toxin A IgG in the test group was 50-fold higher than the previous threshold. These findings support the feasibility of using a vaccine to protect high-risk individuals against C. difficile-associated diarrhea and colitis.     

Absence of Toxemia in Clostridioides difficile Infection: Results from Ultrasensitive Toxin Assay of Serum

Digestive Diseases and Sciences - Clostridioides difficile infection (CDI) is caused by Toxins A and B, secreted from pathogenic strains of C. difficle. This infection can vary greatly in symptom...     

Distinct conformations of the protein complex p97-Ufd1-Npl4 revealed by electron cryomicroscopy

p97 is a key regulator of numerous cellular pathways and associates with ubiquitin-binding adaptors to remodel ubiquitin-modified substrate proteins. How adaptor binding to p97 is coordinated and how adaptors contribute to substrate remodeling is unclear. Here we present the 3D electron cryomicroscopy reconstructions of the major Ufd1-Npl4 adaptor in complex with p97. Our reconstructions show that p97-Ufd1-Npl4 is highly dynamic and that Ufd1-Npl4 assumes distinct positions relative to the p97 ring upon addition of nucleotide. Our results suggest a model for substrate remodeling by p97 and also explains how p97-Ufd1-Npl4 could form other complexes in a hierarchical model of p97-cofactor assembly.     

Increased training of general practitioners in Ireland may increase the frequency of exercise counselling in patients with chronic illness: A cross-sectional study

Background: Recent systematic reviews have established that brief interventions in primary care are effective and economic at promoting physical activity. Lack of training has previously been identified as a barrier to lifestyle counselling in Ireland.

Objectives: This study evaluates frequency of exercise counselling (EC), in patients with six chronic illnesses (type 2 diabetes mellitus, stable coronary heart disease, hypertension, depression, obesity, osteoarthritis) and healthy adults, by general practitioners (GPs) in the mid-west of Ireland, as well as, whether training in EC influences the frequency of EC.

Methods: A questionnaire survey of GPs based in the mid-west of Ireland was conducted during February and March 2012. The questionnaire was distributed to 39 GPs at two continuing medical education meetings and posted to 120 other GPs in the area. The questionnaire assessed the frequency of EC, use of written advice and frequency of recommending resistance exercise in the above patient groups. It also assessed training in EC.

Results: 64% of GPs responded (n = 102). Frequency of EC varied among the chronic illnesses evaluated. Use of written advice and advice on resistance exercise in EC was low. Only 17% of GPs had previous training in EC. If available, 94% of GPs would use guidelines to prescribe exercise in chronic illness. The association of previous training in EC with frequency of EC was variable, with significantly higher counselling rates found in T2DM, obesity and healthy adults.

Conclusion: Improved training of GPs and development of guidelines may increase the frequency of EC in Ireland.     

A systematic review and meta-analysis of the ethnic density effect in psychotic disorders

Purpose

A number of studies have found an ethnic density effect in psychotic disorders, where the incidence for ethnic minorities increases as the neighbourhood proportional ethnic composition decreases [Morgan and Hutchinson, Psychol Med 40:705–709, (2010); Singh, Psychol Med 39:1402–1403, (2009); Schofield et al., Psychol Med 41:1263–1269, (2010)]. However, there is a mixed picture with some studies reporting no effect [Schofield et al., Psychol Med 41:1263–1269, (2010)]. This review aimed to establish the existence of the effect by answering the review question: is there an ethnic density dose effect in the prevalence of psychotic disorders?

Methods

A systematic review and meta-analysis was conducted by two independent reviewers using PsychINFO, Web of Science and PubMed databases. Studies were measured against eligibility criteria and then pooled with any discrepancies discussed between reviewers. Studies were then assessed for quality using a standardised quality assessment.

Results

In total, eight studies were included. A meta-analysis was conducted which found that the incidence of psychotic disorders was higher in low ethnic density areas than high ethnic density areas. A narrative synthesis reflected the complexity when results were broken down by individual ethnic groups where some ethnic groups had inverse or no associations with ethnic density. The synthesis also analysed methodological differences between studies.

Conclusions

The review reports evidence of an overall ethnic density dose effect for ethnic minorities, but with more mixed results for individual ethnic groups. The possible mechanisms behind this effect are explored, including exposure to racism, social capital and social cohesion hypotheses. The wide-ranging implications of the review are discussed along with recommendations for future research to continue to inform public health policy.     

Gastrointestinal stromal tumors: insights from a new familial GIST kindred with unusual genetic and pathologic features

Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder. We report the second family to date with a germline point mutation in exon 17 of the KIT gene that leads to substitution of aspartic acid at position 820 with tyrosine (D820Y). One or more GISTs was documented in three generations of this kindred, and there was associated hyperplasia of the interstitial cells of Cajal (ICC). One affected family member complained of dysphagia and another suffered small intestinal diverticulosis with perforation, which may represent additional consequences of ICC hyperplasia. Diffuse and nodular ICC hyperplasia associated with the latter family member's small intestinal diverticulosis is illustrated, providing supportive functional and morphologic evidence for the ICC being the cell of origin of GISTs. Skin hyperpigmentation was not observed. Analysis of a 17-cm malignant GIST in the index patient revealed that it was hemi/homozygous for the germline D820Y mutation, indicating loss of the remaining wild-type KIT allele with tumor progression. Two smaller lesions from this patient were heterozygous for the mutation. This phenomenon has been observed in up to 8% of sporadic malignant GISTs but has not been documented in familial disease.     

Assisting death or letting die? Withdrawing treatment at the patients' request

Withdrawing ventilation from patients who are incapable of consent because they lack mental capacity is an uncomplicated decision at common law. This decision is less clear when the patient's capacity is in doubt, because of the great difficulty in identification of the exact boundary between capacity and incapacity. An additional difficulty arises in cases where a patients capacity is questionable and they refuse treatment. This paper uses the recent case of B v. an NHS Hospital Trust [2002] to explore the dilemmas that face nurses in the acute sector when they are involved in the care of a patient who appears to have made a competent request to have treatment withdrawn, knowing that this will lead directly to death.