Promoting medication adherence among patients with bipolar disorder: a multicenter randomized controlled trial of a multifaceted intervention.

BACKGROUND: The present research aimed to investigate the efficacy of a multifaceted intervention that included motivational interviewing (MI) and psychoeducation in improving medication adherence (MA) among patients with bipolar disorder (BD). METHOD: A multicenter, cluster randomized, observer-blind, controlled, parallel-group trial was conducted in ten academic centers in Iran. Patients with BD were randomly assigned to the experimental group (EXP; n = 136) or the usual care group (UC; n = 134). The EXP group received five sessions of MI and psychoeducation together with their family members. The primary outcome measure was changes in scores on the Medication Adherence Rating Scale from baseline to 6 months post-intervention. Other outcome measures included serum levels of mood stabilizers, clinical symptoms, quality of life, as well as measures of intention, beliefs about medicine, perceived behavioral control, automaticity, action and coping planning, and adverse reactions. RESULTS: Medication adherence improved over time in both groups, but patients in the EXP group improved more (baseline score: 6.03; score at the sixth month: 9.55) than patients in the UC group (baseline score: 6.17; score at the sixth month: 6.67). In addition, patients in the EXP group showed greater improvement than patients in the UC group in almost all secondary outcomes 6 months following the intervention. CONCLUSIONS: Multifaceted interventions that include motivational-interviewing and psychoeducation can significantly improve MA and clinical and functional outcomes in patients with BD. TRIAL REGISTRATION NUMBER: The trial was registered with theClinicalTrials.gov database (NCT02241863) https://clinicaltrials.gov/ct2/show/NCT02241863.

Innovative strategies to improve diabetes outcomes in disadvantaged populations.

Diabetes disproportionately affects disadvantaged populations. Eighty percent of deaths directly caused by diabetes occurred in low- and middle-income countries. In high-income countries, there are marked disparities in diabetes control among racial/ethnic minorities and those with low socio-economic status. Innovative, effective and cost-effective strategies are needed to improve diabetes outcomes in these populations. Technological advances, peer educators and community health workers have expanded methodologies to reach, educate and monitor individuals with diabetes. In the present manuscript we review the outcomes of these strategies, and describe the barriers to and facilitators of these approaches for improving diabetes outcomes.

Transferrin receptor expression in serum exosomes as a marker of regenerative anaemia in the horse.

REASONS FOR PERFORMING STUDY: Evaluation of erythrocyte regeneration in horses is challenging, as they do not release reticulocytes into the peripheral blood. This study investigated transferrin receptor 1 (TfR1) expression in exosomes as a noninvasive method of characterising the regenerative response in anaemic horses. OBJECTIVES: To quantify TfR1 in ultraprecipitate of serum in horses before and after phlebotomy-induced anaemia, and to identify exosomes as the source of TfR1. The hypothesis was that serum exosomal TfR1 expression would increase during a regenerative response. STUDY DESIGN: Experimental model of anaemia. METHODS: Six horses were phlebotomised to achieve a 25% decrease in packed cell volume. Transferrin receptor 1 quantity in exosomes was determined by western blot and relative densitometry before and after phlebotomy. The size and density of the TfR1-associated particles were confirmed by transmission electron microscopy and density gradient centrifugation, respectively. RESULTS: Regenerative anaemia was confirmed by decreased packed cell volumes and decreased myeloid:erythroid ratios in the bone marrow. In all 6 horses, TfR1 expression increased between Days 7 and 10. Mean TfR1 levels peaked on Day 10 and at 3-fold higher than levels on Day 0. Appropriately sized particles were evident on transmission electron microscopy and sucrose density gradient fractions expected to contain exosomes also contained TfR1. CONCLUSIONS: These data indicate that TfR1 expression in serum exosomes may provide a marker for regeneration in anaemic horses.

Long-term evaluation of mesenchymal stem cell therapy in a feline model of chronic allergic asthma.

BACKGROUND: Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodelling in murine models of acutely induced asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic feline asthma model. OBJECTIVE: To document effects of allogeneic, adipose-derived MSCs on airway inflammation, AHR, and remodelling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental feline allergic asthma. METHODS: Cats with chronic, experimentally induced asthma received six intravenous infusions of MSCs (0.36-2.5 × 10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for 1 year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia, pulmonary mechanics and clinical scoring to assess AHR, and thoracic computed tomographic (CT) scans to assess structural changes (airway remodelling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. RESULTS: There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA P = 0.0311; BWT P = 0.0489). No differences were noted between groups in the immunologic assays. CONCLUSIONS AND CLINICAL RELEVANCE: When administered after development of chronic allergic feline asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodelling by month 8, although the effect was not sustained at month 12. Further study of MSC therapy including repeated MSC administration is warranted to assess impact on remodelling in chronic asthma.

Starting to develop self-help for social anxiety associated with vitiligo: using clinical significance to measure the potential effectiveness of enhanced psychological self-help.

BACKGROUND: Vitiligo can be associated with high levels of distress, yet there are currently no self-help interventions available. OBJECTIVES: To describe the initial development of a psychosocial self-help intervention designed to reduce social anxiety associated with vitiligo. Also to examine whether including a planning exercise, aimed at increasing use of the intervention (termed implementation intentions), has the potential to achieve a clinically significant reduction in distress. METHODS: Participants (n = 75) were randomized to one of three groups: cognitive behavioural self-help (CBSH), CBSH augmented with implementation intentions (CBSH+), or no intervention. Participants were assessed at baseline and after 8 weeks on measures of social anxiety, anxiety and depression, and appearance-related concern. The two intervention groups also completed a questionnaire evaluating their use of, and satisfaction with, the intervention. RESULTS: High levels of social anxiety and concern over appearance were reported. Twenty-four per cent of participants in the CBSH+ group experienced clinically significant change on the measure of social anxiety compared with 8% in the CBSH group and 0% in the control group. In addition, 58% of the control group deteriorated during the study period. There were no significant differences between the conditions on the other outcome measures. Participants reported that the self-help leaflets were helpful. CONCLUSIONS: The findings demonstrate that augmented CBSH provides a relatively simple and accessible intervention that can result in a clinically significant reduction in social anxiety. The augmented intervention has potential and might be further developed and evaluated in subsequent trials.

A meta-analysis of the effectiveness of psychological interventions for adults with skin conditions.

Skin conditions can be associated with heightened levels of psychological morbidity, suggesting the need for psychological interventions. A number of specific interventions (such as habit reversal) have been developed. However, to date, there has not been a systematic review of the effectiveness of psychological interventions. We sought to systematically evaluate the effectiveness of psychological interventions designed to improve the severity of and adjustment to skin conditions in adults. Database, archival and citation searches were conducted. Studies were included if participants were allocated to either a psychological intervention (excluding educational interventions and complementary therapies) or a comparison condition, and if they measured outcomes relevant to the skin condition. Twenty-two studies met these inclusion criteria. Effect sizes for each intervention were computed and we also coded a number of potential moderators of intervention efficacy. Psychological interventions were found to have a medium-sized effect on skin conditions (g = 0·54). The type of skin condition, age of sample, nature of the intervention, time interval between the end of the intervention and follow-up, and type of outcome measure all moderated the effect of interventions on outcomes. For example, interventions had a medium effect on the severity of the condition (g = 0·40) and psychosocial outcomes (g = 0·53), and a medium-to-large effect on itch/scratch reactions (g = 0·67). Psychological interventions are beneficial for people with skin conditions. However, more research is needed to extend the variety and focus of the psychological interventions that are available. Studies are also needed to explore the longer-term benefits of such interventions.

Thrombophlebitis of the great saphenous vein--recommendations for treatment.

OBJECTIVES: The purpose of this study was to evaluate the incidence of great saphenous vein (GSV) thrombosis in symptomatic patients and its possible relationship to complications usually attributed to deep venous thrombosis (DVT). METHODS: To quantitate the frequency of GSV thrombosis and evaluate its possible morbidity, we reviewed all the venous studies, both inpatient and outpatient, at a Level I Trauma Center over one year. The charts of all patients who had a thrombus in the GSV, either alone or in combination with a DVT, were examined. RESULTS: A total of 2646 lower extremity venous scans were done in the year studied. In this group, there were 388 (14.5%) positive studies for a DVT. There were 36 (9.3%) patients in this group who had a DVT of the lower extremity and a thrombus in the GSV. In the total group, there were 30 patients (1.1%) with a superficial thrombophlebitis of the GSV alone. In these patients, 22 (73%) either showed cephalad progression of the thrombus, symptoms of shortness of breath, a mobile tip in the thrombus or extension of the thrombus into the common femoral vein. Five patients (16.6%), after failing medical therapy (heparin, bed rest and antibiotics), underwent surgical treatment. CONCLUSIONS: Thrombophlebitis of the GSV, although not very common, needs to be carefully followed with a repeat duplex scan to determine if there is propagation of the thrombus. This study shows that thrombophlebitis of the GSV can cause many of the complications attributed to deep venous thrombi and, therefore, must be thoroughly evaluated, followed, and, if necessary, treated.

Mechanism of site-selective DNA nicking by the hydrodioxyl (perhydroxyl) radical.

In previous studies, the ability of the hydrodioxyl (perhydroxyl) radical [HOO., the conjugate acid of superoxide (O2.-] to "nick" DNA under biomimetic conditions was demonstrated, and a sequence selectivity was observed. A background level of nonspecific nicking also was noted. This paper provides support for 5'-hydrogen atom abstraction from the deoxyribose ring as the initial event in the sequence-selective nicking by 02.-/HOO.. Two experiments support the proposed mechanism. First, using a defined sequence 5'-32P-labeled restriction fragment as the DNA substrate, only free (unalkylated) 3'-phosphate is produced at the site of nicking. Second, using poly (dA).poly (T) as the substrate, furfural is formed in the reaction from deoxyribose ring breakdown. Both results are consistent with 5'-hydrogen atom abstraction for initiation of the site-selective nicking. Hydrogen atom abstraction at other sites of the deoxyribose ring and/or base oxidation and loss followed by strand scission likely are responsible for the nonspecific nicking. The 5'-abstraction mechanism contrasts to those elicited by other 02-derived and metal-associated oxidants, which may provide a biomarker for the reactivity of HOO. in vivo.

Controlled exposures of young asthmatics to mixed oxidant gases and acid aerosol.

To help assess short-term respiratory responses to summertime air pollution, we exposed 24 asthmatic volunteers aged 11-18 in a chamber to respirable acid aerosol (mass median aerodynamic diameter 0.66 micron) plus 0.3 ppm nitrogen dioxide (NO2) plus 0.2 ppm ozone (O3). The aerosol contained available hydrogen ions (H-) at an average concentration of 2.6 mumol/m-, equivalent to 127 micrograms/m3 sulfuric acid (H2SO4); some H+ probably was in NH4HSO4 rather than H2SO4. The volunteers were exposed separately to O3/NO2 without acid and to clean air. Exposures lasted 90 min, including three 15-min exercise sessions with ventilation averaging 32 L/min, at 21 degrees C and 50% relative humidity. Asthma medications were withheld before and during exposures. Subjects gargled lemonade to minimize acid neutralization by oral ammonia (NH3). Exercise-induced bronchospasm was evident in all exposures. Differences in group mean lung function response among H2SO4/O3/NO2, O3/NO2, and clean-air exposures were not statistically significant. Individuals' measured oral NH3 concentrations or estimated inhaled doses of H2SO4 did not significantly predict their lung function changes. A few subjects showed unfavorable function changes during pollutant exposures, which might be chance occurrences or might indicate the existence of an acid-pollution-susceptible subgroup among young asthmatic subjects.

Time-activity patterns and diurnal variation of respiratory status in a panel of asthmatics: implications for short-term air pollution effects.

To understand the short-term health risks to people from air pollution exposure, we investigated time-activity patterns and temporal variation of the respiratory status in 49 asthmatic Los Angeles area residents 18-50 years old. During the summer (May-September) and winter (November-March), subjects measured their lung function two to four times daily at home for one week periods, and every hour recorded their symptoms, medication, and activity hourly in diaries. Almost all subjects recorded heart rates (HR), which were converted to ventilation rate (VR) estimates using individual laboratory exercise data. Most subjects' lung function and symptoms varied diurnally, and were worst in early morning. For subjects with clinically mild asthma, diurnal forced expired volume in 1 sec (FEV1) changes averaged 7%, versus 12% in those with moderate symptoms, and 18% in severely asthmatic subjects. Lung function was similar in summer and winter, but symptoms and medication use decreased in winter. In the aggregate, subjects reported spending 75% of waking hours indoors at self-rated slow activity and 11% in vehicles. HR records usually corroborated reports of medium or fast activity. Mean estimated VR at slow, medium, and fast activity was 19, 37, and 61 L/min for men, and 16, 24, and 32 L/min for women. Outdoor fast activity, representing the greatest vulnerability to outdoor pollution, occupied approximately 0.2% of waking hours (2 min/day on average); outdoor medium activity occupied about 2% of waking hours (19 min/day on average). Estimated cumulative ventilation was higher than that of previous healthy panels because of asthmatics' higher VR at slow activity. If these activity patterns are typical, asthmatics may be especially vulnerable to pollutants with effects dependent on cumulative inhaled dose. Effects dependent on high inhaled dose rates over a short period, e.g., sulfur dioxide effects, would be unlikely, except perhaps for uncommonly active individuals in uncommonly polluted areas.

Regrowth of Pseudomonas aeruginosa and other bacteria after the bactericidal action of carbenicillin and other beta-lactam antibiotics.

Exposure of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus to bactericidal concentrations of beta-lactam antibiotics in broth culture resulted in a decrease in viability over the first 6--8 hr, followed by regrowth which was not due to the selection of resistant variants or loss of antibiotic potency. During incubation, bacteria adhered to the surface of the culture vessel and multiplied despite the presence of bactericidal concentrations of antibiotic in the medium. It is concluded that the phenomenon of "regrowth" results from such adhesion and the subsequent dispersal of some of these cells into the culture medium. The significance of these findings is discussed in relation to the treatment of infection, the determination of minimal bactericidal concentrations, and the phenomena of tolerance and persisters.