Can Smartphone Notifications Help With Gout Management? A Feasibility Study.

OBJECTIVE: This feasibility study aimed to assess the acceptability of using smartphone notifications to modify the medication beliefs of people with gout. We evaluated the feasibility and acceptability of a smartphone application using the Technology Acceptance Model. We explored adherence rate differences and outcomes between the intervention and control groups. METHODS: Fifty-two patients with gout who were prescribed allopurinol were randomly assigned to either active control (n = 24) or intervention group (n = 28). Over 3 months, both groups used the study app on their smartphones. The active control group received notifications about general health advice, whereas the intervention group received adherence-targeted notifications. The feasibility and acceptability of the smartphone app was measured through semistructured interviews. Adherence rate was assessed through serum urate levels and missed doses at 3 timepoints: baseline, 3 months (post intervention), and 6 months (follow-up). RESULTS: The smartphone app demonstrated high feasibility, with strong participant retention and compliance. The participants expressed high levels of satisfaction with the app's user-friendliness and content, highlighting its acceptability. Both groups showed a significant reduction in missed doses over time (P < 0.05), but no significant differences in serum urate levels were found between the groups. Patients who received adherence-targeted notifications reported finding it more convenient to take allopurinol and expressed higher overall treatment satisfaction throughout the study. CONCLUSION: Adherence-targeted notifications have the potential to be an effective and scalable approach to supporting medication adherence in patients with gout. Further research is needed with larger samples to refine the components of the intervention and explore its optimal implementation.

A content analysis of medication adherence material in patient educational resources about gout.

Objective: This study aimed to investigate how medication adherence is addressed in online gout resources in six countries. We investigated how often adherence was referred to, the strategies suggested to improve patient adherence, and the types of nonadherence that were targeted. We also examined the readability of the adherence material. Methods: A content analysis was conducted on 151 online gout resources from medical and health organisations in six predominantly English-speaking countries. Two reviewers coded the content of the websites into categories (kappa 0.80). The analysis involved coding the resources for reasons for nonadherence, and adherence-promoting strategies. Flesch-Kincaid Reading Ease scores and word count were also computed. Results: Out of 151 websites examined, 77 websites discussed medication adherence (51%), with intentional nonadherence being more prevalent than unintentional nonadherence. 67 websites targeted different types of nonadherence, including drug-specific concerns (50%), misconceptions of gout curability and the necessity of medication (16%), forgetfulness (16%), and other practical challenges (5%). Strategies to promote adherence were found in one-third of the websites, with medication education being the most prevalent strategy (17%), followed by healthcare provider engagement (13%) and memory aid strategies (6%). On average, about 11% of the words (89.27, SD = 76.35) in the entire document were focused on adherence. Difficult reading comprehension was found in one-fifth of adherence-related websites. Conclusion: Findings reveal limited medication adherence coverage and narrow strategies in online gout resources. Improved adherence portrayal is needed for effective gout management through comprehensive strategies and clear, understandable information.

Why Do Patients With Gout Not Take Allopurinol?

OBJECTIVE: The objectives of this study were to examine the reasons patients give for nonadherence to allopurinol and to examine differences in intentional nonadherence for patients who did and did not achieve serum urate (SU) levels at treatment target. METHODS: Sixty-nine men with gout attending rheumatology clinics, all prescribed allopurinol for ≥ 6 months, completed the Intentional Non-Adherence Scale (INAS). Differences in the types of intentional nonadherence were analyzed between those who did and did not achieve SU at treatment target (< 0.36 mmol/L, 6 mg/dL). RESULTS: The most frequently endorsed reasons for not taking their urate-lowering therapies (ULT) were because participants wanted to lead a normal life (23%) or think of themselves as a healthy person again (20%). Patients also reported not taking allopurinol as a way of testing if they really needed it (22%). Participants with SU above target endorsed significantly more INAS items as reasons for not taking their medication, had more medicine-related concerns, and were more likely to give Testing treatment as a reason for nonadherence. Participants who were younger, single, and non-New Zealand European also endorsed more reasons for not taking their allopurinol. CONCLUSION: The major reasons behind the patient's decision not to take allopurinol relate to the desire to lead a normal life and the strategy of testing the treatment to see if they could reduce the dose without getting symptoms. These results provide some potentially modifiable targets for adherence interventions and some recommendations to clinicians about how to reframe ULT for patients in order to improve adherence.

When symptoms become side effects: Development of the side effect attribution scale (SEAS).

OBJECTIVES: Symptom misattribution is a central process in the nocebo effect but it is not accurately assessed in current side effect measures. We have developed a new measure, the Side Effect Attribution Scale (SEAS), which examines the degree to which people believe their symptoms are treatment side effects. METHODS: The SEAS was tested in three New Zealand studies: a vaccination sample (n = 225), patients with gout or rheumatoid arthritis (n = 102), and patients switching to a generic medicine (n = 69). The internal reliability of the scale was examined using Cronbach's alpha. To assess validity, the Side Effect Attribution Total Score and Side Effect Attribution Binary Score were related to a number of psychological measures associated with side effect reporting. RESULTS: The scale showed good internal reliability across the three studies, with Cronbach alphas ranging from 0.840 to 0.943. Analysis of the effect sizes showed that the Attribution Total Score was generally more strongly associated with nocebo responding than Attribution Binary Score. Participants had greater Side Effect Attribution Total Scores if they had higher expectations for vaccination side effects (r = 0.18, p = .028), more worry about future vaccine effects (r = 0.16, p = .046), a higher perceived sensitivity to medicines (r = 0.50, p < .001), greater anxiety (r = 0.25, p = .016), greater intentional non-adherence (r = 0.30, p = .003), greater medicine information seeking (r = 0.26, p = .010), lower trust in pharmaceutical agencies (r = -0.29, p = .026), and lower medicine efficacy beliefs (r = -0.46, p < .001). CONCLUSIONS: The SEAS provides a more nuanced assessment of symptom attribution beliefs. It appears to be more sensitive measure than just a side effect total, as it is associated with a greater number of relevant psychological variables. Future research should examine the scale in other populations and settings.

Levels of cytokine in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation.

This study was designed to analyze cytokine levels in bronchoalveolar lavage (BAL) fluid of patients with pulmonary fibrosis (PF) and was performed at a University hospital. Nineteen veterans had mustard gas-induced PF, and 19 normal veterans were used as a control group. Chest roentgenograms, pulmonary function tests (PFTs), the percentage diffusing capacity of carbon monoxide (D(LCO)), high-resolution CT scans of the chest, and analyses of BAL fluids for five cytokines interleukin-8 (IL-8), IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-12, and the growth factors transforming growth factor-beta (TGF-beta), insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF) were performed in all cases. A transbronchial lung biopsy was done in all patients. There were significant differences in cytokine (IL-8, IL-1beta, IL-6, TNF-alpha, IL-12) levels of BAL fluid between patients with PF and healthy controls. TGF-beta, EGF, and IGF-1 levels were also significantly increased in patients with PF compared with controls. A significant negative correlation was observed between the percentage of D(LCO) and IL-8 levels in BAL fluid in patients with PF (r = -0.47, p = 0.04). A significant negative correlation was also seen between the percentage of D(LCO) and TGF-beta (r = 0.53, p = 0.02) in these patients. Except for the percentage and the absolute number of the BAL fluid neutrophils (r = 0.70, p = 0.001 and r = -0.62, p = 0.005, respectively), no correlation was found between D(LCO)% and the other BAL cells. Of all measured cytokines and growth factors, only IL-8 and TGF-beta showed a significant correlation with the degree of fibrosis (p = 0.004, p = 0.04). The increased levels of cytokines and growth factors in the BAL fluid suggest the possible causative mechanism in the lung in sulfur mustard gas-induced PF by recruitment of neutrophils and eosinophils into the lung.

Increased in CD8 T lymphocytes in the BAL fluid of patients with sulfur mustard gas-induced pulmonary fibrosis.

OBJECTIVE: In an attempt to understand better the potential role of the T cell in the pathogenesis of pulmonary fibrosis (PF) due to sulfur mustard gas inhalation, this study was designed to analyze bronchoalveolar lavage (BAL) lymphocyte subsets and to determine the ratio of CD4 to CD8 lymphocytes in BAL fluid. SETTING: University hospital. PATIENTS: Twenty-one veterans with mustard gas-induced pulmonary fibrosis and 20 normal veterans as control group. INTERVENTION: Chest roentgenograms, pulmonary function tests (PFTs), tests for carbon monoxide diffusing capacity of the lung (DLCO), high-resolution CT scans of the chest, BAL via fiberoptic bronchoscopy, analyses of BAL fluids for cellular and Flow-cytometric analysis of the phenotype of bronchoalveolar cells were performed in all cases. A transbronchial lung biopsy was done in all patients following BAL. RESULTS: Neutrophilic alveolitis was the predominant feature. Neutrophils (P<0.0001) and eosinophils (P=0.0006) were the predominant cell types in the BAL fluid of patients with PF. CD8 lymphocytes expressed as percentage or absolute number were significantly higher in patients with PF than in healthy controls (22.96+/-7.48% vs. 14.16+/-7.73%, respectively; P=0.0006; and 2.28+/-0.84 vs. 1.10+/-0.55 x 10(3) cells/ml, respectively; P<0.0001). The CD4/CD8 ratio was significantly lower in patients with PF than in healthy controls (0.73+/-0.25 vs. 1.58+/-0.67; P<0.0001). Except for the percentage and the absolute number of the BAL fluid neutrophils (r=0.70, P=0.001: r=-0.62, P=0.005; respectively), no correlation was found between DLCO% and the other BAL cells. A significant negative correlation was observed between the percentage of DLCO and both the percentage and the absolute number of CD8 lymphocytes in BAL fluid in patients with PF (r=-0.81, P=0.0003; r=-0.61, P=0.006; respectively). A significant correlation was also seen between the percentage of DLCO and the CD4/CD8 ratio (r=-0.60, P=0.006) in our patients. CONCLUSION: CD8 T cells in BAL fluid were significantly elevated in patients with pulmonary fibrosis. Patients with higher grades of pulmonary fibrosis expressed as percentage of DLCO, revealed higher percentages and the absolute number of CD8 T cells and a lower CD4/CD8 ratio.

Relationship between airway reactivity induced by methacholine or ultrasonically nebulized distilled cold water and BAL fluid cellular constituents in patients with sulfur mustard gas-induced asthma.

The objective of this article was to evaluate the relationship between the bronchial reactivity to methacholine and distilled cold water and inflammatory bronchial alveolar lavage (BAL) cells in mustard gas-induced asthma. This was a randomized, crossover clinical study set in a university hospital. The patients were 17 veterans with mustard gas-induced asthma and 17 normal veterans as a control group. Inhalation challenges with ultrasonically nebulized distilled water and methacholine and BAL via bronchoscopy and were performed in all patients and subjects. All patients did sustain a 20% fall in FEV(1) after methacholine, whereas two of them did not with distilled cold water. The patients were sensitive to distilled cold water with a median PD20 of 8.44 +/- 6.55 mL and sensitive to methacholine with the median PC20 of 4.88 +/- 4.22 mg/mL. Significant correlation was found between PC20 of methacholine and PD20 of distilled cold water (r = -0.74, p = 0.005). The proportion of BAL macrophages was significantly lower in patients with asthma than in the control group (p = 0.001). The proportions of lymphocytes and neutrophils were similar in the two groups. The percentage of eosinophils was higher in BAL fluid from the asthmatics compared with that in BAL fluid from the control group (p < 0.001). The percentage of the BAL eosinophils significantly correlated with both PC20 of methacholine (r = - 0.58, p = 0.01) and PD20 of distilled cold water (r = -0.81, p = 0.002). No relationship between PC20 of methacholine or PD20 of distilled cold water was found for other inflammatory BAL cells. This study showed that in patients with mustard gas-induced asthma, the degree of airway responsiveness to both methacholine and distilled water was associated with the percentage of BAL eosinophils.

Increased granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) levels in BAL fluid from patients with sulfur mustard gas-induced pulmonary fibrosis.

The objective of this article was to show the role of cytokines in the pathogenesis of pulmonary fibrosis due to sulfur mustard gas inhalation. Eighteen veterans with mustard gas-induced pulmonary fibrosis and 18 normal patients were used as controls. Bronchoalveolar larvage (BAL) and analyses of BAL fluids for cellular and cytokine levels were performed. There was a significant difference in granulocyte colony stimulating factor (G-CSF) level in the BAL fluid of patients and the controls (p < 0.0001). Granulocyte-macrophage colony stimulating pulmonary fibrosis (GM-CSF) BAL levels were significantly increased in patients with pulmonary fibrosis (PF) in comparison with controls (p < 0.0001). Patients with PF have highly significant increases in IL-8 level compared to controls (87.94 +/- 59.63 vs. 8.66 +/- 6.97 g/mL(1); p < 0.0001) as well. IL-8 and G-CSF levels in BAL fluid correlate only with the percentage and the absolute number of neutrophils of the BAL fluid in patients with PF (p = 0.02/p = 0.01; p = 0.01/p = 0.01; respectively). A significant correlation was found between GM-CSF BAL fluid level and the percentage and the absolute number of the BAL fluid eosinophils (p = 0.04 and p = 0.03). Neutrophils alveolitis, the presence of eosinophils, and higher concentrations of interleukin-8, G-CSF, and GM-CSF in BAL fluid are associated with the development of fibrosis in sulfur mustard victims.

Comparison of bronchial responsiveness to ultrasonically nebulized distilled water (UNDW), methacholine, and ultrasonically nebulized distilled cold water (UDCW) in patients with sulfur mustard gas-induced asthma.

OBJECTIVE: To evaluate bronchial challenges using three different stimuli as screening tools for bronchial hyper-responsiveness in sulfur mustard gas-induced asthma. DESIGN: Randomized, cross-over clinical study. SETTING: University hospital. PATIENTS: Eighteen veterans with mustard gas-induced asthma and 18 normal veterans as the control group. INTERVENTION: Pulmonary function tests and inhalation challenges with ultrasonically nebulized distilled water (UNDW), methacholine, and ultrasonically nebulized cold water (UNDCW) were performed on all patients and subjects. RESULTS: Six mustard gas-induced asthmatic veterans did not respond to a 20% in FEV(1) after distilled water (13.3%), and two of them (11.11%) did not respond with distilled cold water; all responded with methacholine. Only one healthy subject developed a PC20 FEV(1) after methacholine but did not with both distilled water and distilled cold water challenges. The asthmatic patients were sensitive to distilled water with a median PD20 of 7.24 +/- 3.83 ml (range 2.54 ml to 15.83 ml), and sensitive to cold water with a median PD20 of 6.42 +/- 6.24 ml (range 1.92 ml to 25.15 ml). The median PC20 methacholine was 1.90 +/- 1.88 mg/ml (range 0.14 mg/ml to 6.20 mg/ml). In patients with a positive response to the distilled water challenge test, no significant correlation was found between PC20 of methacholine and PD20 of distilled water (Rho = -0.34, p = 0.25), whereas in patients whose responses to distilled cold water (DCW) were positive, PD20 of distilled cold water (DCW) correlated well with PC20 of methacholine (Rho = -0.69, p = 0.006). CONCLUSION: Overall, the methacholine challenge test is the best method to distinguish these asthmatic patients from normal subjects in this study. When compared to the methacholine challenge, although the airway response to ultrasonically nebulized distilled cold water test was somewhat less sensitive, it may be used as a simple, fast, inexpensive, and relatively reliable method to predict the absence of asthma in sulfur mustard gas-induced asthma.

Relationship between eosinophilia and levels of chemokines (CCL5 and CCL11) and IL-5 in bronchoalveolar lavage fluid of patients with mustard gas-induced pulmonary fibrosis.

OBJECTIVE: Therefore, this study was designed to analyze the bronchoalveolar lavage (BAL) fluid concentrations of interleukin-5 (IL-5), normal T cell expressed and presumably secreted (RANTES; CCL5), and eotaxin (CCL11) and also to examine the relationship between the percentage and absolute number of the BAL eosinophils and these measured chemokines in patients with sulfur mustard (SM) gas-induced pulmonary fibrosis (PF). PATIENTS: Included in this study were fifteen veterans with mustard gas-induced PF and 14 normal veterans as control group. INTERVENTION: Pulmonary function tests (PFTs), tests for D (LCO), computed tomography (CT) scans of the chest, analyses of BAL fluids for RANTES (CCL5), eotaxin (CCL11), and IL-5 were performed in all cases. RESULTS: Eosinophilic alveolitis was the predominant feature (p < 0.0001). There were significant differences in CCL5, CCL11, and IL-5 levels of BAL fluid between patients with PF and controls (p < 0.0001, p < 0.0001, and p = 0.001, respectively). The concentrations of CCL5 and CCL11 showed positive correlations with percentage (r = 0.57 and p = 0.03, r = 0.52 and p = 0.04, respectively) and absolute counts (r = 0.54 and p = 0.04, r = 0.53 and p = 0.04, respectively) of BAL eosinophils. There were significant positive correlations between the concentrations of IL-5 and the proportion and total cell number of eosinophils in BAL (r = 0.67 and p = 0.01; r = 0.59 and p = 0.02, respectively) too. CONCLUSION: A significant correlation between BAL CCL5, CCL11, and IL-5 levels and eosinophils in patients with pulmonary fibrosis caused by SM gas inhalation has been demonstrated, suggesting that these C-C chemokines and IL-5 contribute to the recruitment of eosinophils cells in the lung in these victims.

Relationship between eosinophilia and levels of chemokines (CCL5 and CCL11) and IL-5 in bronchoalveolar lavage fluid of patients with mustard gas-induced pulmonary fibrosis.

OBJECTIVE: Therefore, this study was designed to analyze the bronchoalveolar lavage (BAL) fluid concentrations of IL-5, RANTES (CCL5) and eotaxin (CCL11) and also to examine the relationship between the percentage and absolute number of the BAL eosinophils and these measured chemokines in patients with sulfur mustard (SM) gas-induced pulmonary fibrosis (PF). PATIENTS: Fifteen veterans with mustard gas-induced PF and 14 normal veterans as control group. INTERVENTION: Pulmonary function tests, tests for D(LCO), computed tomography scans of the chest, analyses of BAL fluids for RANTES (CCL5), eotaxin (CCL11), and IL-5 were performed in all cases. RESULTS: Eosinophilic alveolitis was the predominant feature (p < 0.0001). There were significant differences in CCL5, CCL11, and IL-5 levels of BAL fluid between patients with PF and controls (p < 0.0001, p < 0.0001, and p = 0.001, respectively). The concentrations of CCL5 and CCL11 showed positive correlations with percentage (r = 0.57 and p = 0.03; r = 0.52 and p = 0.04, respectively) and absolute counts (r = 0.54 and p = 0.04, r = 0.53 and p = 0.04, respectively) of BAL eosinophils. There were significant positive correlations between the concentrations of IL-5 and the proportion and total cell number of eosinophils in BAL (r = 0.67 and p = 0.01; r = 0.59 and p = 0.02, respectively) too. CONCLUSION: A significant correlation between BAL CCL5, CCL11, and IL-5 levels and eosinophils in patients with pulmonary fibrosis due to SM gas inhalation has been demonstrated, suggesting that these C-C chemokines and IL-5 contribute to the recruitment of eosinophils cells in the lung in these victims.

CD4/CD8 ratio and cytokine levels of the BAL fluid in patients with bronchiectasis caused by sulfur mustard gas inhalation.

OBJECTIVE: To analyze cytokine levels in BAL fluid of patients with bronchiectasis due to mustard gas inhalation. PATIENTS: 29 victims with mustard gas-induced bronchiectasis and 25 normal veterans as control group. INTERVENTION: PFTs,, high-resolution CT scans of the chest, analyses of BAL fluids for five cytokines (IL-8, IL-1beta, IL-6, TNF-alpha, IL-12) and analyses of BAL fluids for cellular and flow-cytometric analysis of the phenotype of bronchoalveolar cells were performed in all cases. RESULTS: CD4 lymphocytes expressed as percentage or absolute number were significantly higher in patients with bronchiectasis than in controls (32.17 +/- 16.00 vs 23.40 +/- 6.97%, respectively; p = 0.01; and 3.31 +/- 2.03 vs 1.88 +/- 0.83 x 10(3) cells/ml, respectively; p = 0.001). The CD4/CD8 ratio was significantly higher in patients with bronchiectasis than in controls (3.08 +/- 2.05 vs 1.68 +/- 0.78; p = 0.002). There were significant differences in cytokine (IL-8, IL-1beta, IL-6, TNF-alpha, IL-12) levels of BAL fluid between patients with bronchiectasis and healthy controls.A significant correlation was observed between the HRCT scores and both the percentage and the absolute number of CD4 lymphocytes in BAL fluid in patients with bronchiectasis (r = -0.49, p = 0.009; r = -0.50, p = 0.008; respectively). HRCT scores showed a significant correlation with CD4/CD8 ratios (r = 0.54, p = 0.004) too. Of measured BAL cytokines, only IL-8 (r = -0.52, p = 0.005) and TNF-aalpha (r = 0.44, p = 0.01) showed significant correlations with the HRCT scores. CONCLUSION: The increased levels of cytokines CD4 lymphocytes in the BAL fluid suggest the possible causative mechanism in the lung in sulfur mustard gas-induced bronchiectasis by the recruitment of neutrophils into the lung.