Hepatitis B virus reactivation following immunosuppressive therapy: guidelines for prevention and management

It is well known that immunosuppressive drugs or cancer chemotherapy can stimulate replication of hepatitis B virus (HBV) and precipitate severe flares of HBV infection. The risk of this syndrome of 'reactivation hepatitis B' is highest in haematopoietic stem cell or solid organ transplant recipients and in those undergoing chemotherapy for haematological malignancies; however, it has been described following almost any form of immunosuppressive treatment. Fortunately, it can be largely prevented by prophylactic therapy with oral anti-HBV nucleoside/nucleotide analogues. Importantly, chronic HBV infection is usually asymptomatic, and most patients at risk are likely to be unaware that they carry the infection. Thus, the key to avoiding this potentially fatal complication of immunosuppressive treatment is to ensure that all patients at risk of chronic HBV infection are screened for the disease before commencing immunosuppressive treatment or chemotherapy.     

A new multiple dose powder inhaler, (Turbuhaler), compared with a pressurized inhaler in a study of terbutaline in asthmatics

Twelve adult asthmatic patients participated in an open, randomized, cross-over comparison between cumulatively increasing doses of terbutaline sulphate administered via the multiple dose powder inhaler (Turbuhaler) or via a pressurized inhaler. Turbuhaler and the pressurized inhaler showed equipotency both with respect to bronchodilatation and side effects. Both treatments produced a significant increase in pulmonary function measurements, forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). No increase in pulse rate was seen with either treatment but there was an increase in tremor at higher doses with both treatments. Inhalation of beta-agonists via Turbuhaler seems to be an effective way of treating asthma.     

Causative and contributive factors to asthma severity and patterns of medication use in patients seeking specialized asthma care

STUDY OBJECTIVES: (1) To assess the prevalence of specific factors considered causative or contributive to asthma in a population of patients seen in a specialized asthma clinic, and to determine whether any of these factors were associated with more severe disease; and (2) to assess the utilization of inhaled steroids by asthma severity in this population and compare it with published guidelines of the National Heart, Lung, and Blood Institute (NHLBI). DESIGN, SETTING, AND PATIENT POPULATION: We conducted a retrospective chart review of new patients seen in a specialized asthma treatment center over a 2.5-year period and recorded the prevalence of 14 causative or contributive factors, the severity of asthma, and the intensity of treatment with inhaled corticosteroids in each patient. Patients were grouped as mild asthma vs moderate/severe asthma and compared by chi(2) analysis and stepwise logistic regression to determine whether certain factors were associated with more severe asthma. MEASUREMENTS AND RESULTS: The average number of factors recorded was 2.9 +/- 1.8 in the mild group (+/- SD) and 3.5 +/- 1.6 in the moderate/severe asthma group. This difference was statistically significant (p = 0.014). Increasing age, male gender, symptomatic gastroesophageal reflux disease (GERD), and chronic sinusitis were independently associated with more severe asthma. Suboptimal use of inhaled corticosteroids was more common in patients with mild persistent asthma, but suboptimal dosing of inhaled corticosteroids was equally common in mild and moderate/severe asthma. No relationship was found between allergen sensitization combined with exposure to cats, dogs, dust mite, or molds and more severe asthma. CONCLUSIONS: This study confirms earlier studies showing that symptomatic GERD and chronic sinusitis are important comorbid conditions in patients with asthma, both being associated with greater asthma severity. This study further shows that the doses of inhaled corticosteroids used for treatment of asthma fall short of NHLBI guidelines in the majority of patients regardless of asthma severity.     

Dose-ranging study of a new steroid for asthma: mometasone furoate dry powder inhaler.

A new formulation of mometasone furoate (MF) for administration by dry powder inhaler (DPI) was evaluated for the treatment of asthma. A 12-week, double-blind, placebo-controlled dose-ranging study compared the efficacy and safety of three doses of MF DPI (100, 200 and 400 mcg b.i.d) with beclomethasone dipropionate (BDP) 168 mcg b.i.d. administered by metered dose inhaler in 365 adult or adolescent patients being treated with inhaled glucocorticoids. The mean change from baseline to endpoint (last treatment visit) for forced expiratory volume in 1 sec (FEV1) was the primary efficacy variable. Secondary efficacy variables included other objective measures of pulmonary function [forced vital capacity (FVC), forced expiratory flow 25-75% (FEV25-75%.) and peak expiratory flow rate (PEFR)] as well as subjective measures of therapeutic response (patients' daily evaluation of asthma symptoms and physicians' evaluation). At endpoint, all four active treatments were significantly more effective than placebo (P < 0.01) in improving FEV1 (MF DPI 5 to 7%, BDP 3%, placebo -6.6%) and all other measures of pulmonary function (FVC: MF DPI 4 to 5%, BDP 2%, placebo -4.7%; FEF25-75%: MF DPI 6 to 18%, BDP 7.5%, placebo -9.5%; PEFR (AM): MF DPI 5 to 10%, BDP 5.7%, placebo -7%). A consistent trend was observed for better improvement in patients treated with MF DPI 200 mcg b.i.d. than with MF DPI 100 mcg b.i.d., with no apparent additional benefit of MF DPI 400 mcg b.i.d. Results for the MF DPI 100 mcg b.i.d. and BDP 168 mcg b.i.d. treatment groups were similar. Patients' and physicians' subjective evaluations of symptoms found similar improvement in the MF DPI 200 and 400 mcg b.i.d. treatment groups, which were slightly better than that in the MF DPI 100 mcg b.i.d. group. Symptoms tended to worsen in the placebo group. MF DPI was well tolerated at all dose levels and the most frequently reported treatment-related adverse effects were headache, pharyngitis and oral candidiasis. No evidence of HPA-axis suppression was detected in any treatment group. In summary, all doses of MF DPI were well tolerated and significantly improved lung function and MF DPI 400 mcg (200 mcg b.i.d.) was the optimal dose in this study of patients with moderate persistent asthma.     

A trial of metaproterenol by metered-dose inhaler and two spacers in preschool asthmatics

Because most young children have difficulty in coordination for correct use of metered-dose inhalers (MDI), a trial of two spacer devices attached to MDIs was performed. In 13 children with asthma, aged 2-5 years old, a collapsible bag (Inspir-Ease) and a tube spacer (Aerochamber) were tested in a double-blind crossover trial with metaproterenol (1,300 micrograms). Respiratory resistance was measured by the forced oscillation method. Thirty minutes after metaproterenol administration there was a significant decrease in resistance with both spacers, while no significant change occurred after placebo administration. There was no difference in degree of bronchodilation between the two spacers. It is concluded that metaproterenol can be safely and effectively administered to preschool asthmatics by an MDI with spacer devices.     

Near-fatal asthma in South Australia:descriptive features and medication use

Background: Self-reported prior morbidity levels and medication use among survivors of a near-fatal asthma attack (NFA) were studied.
Aims: To identify deficiencies in asthma management and opportunities for intervention.
Methods: A hundred and twenty-seven consecutive patients aged 15 years or more presenting with a NFA to accident and emergency departments of teaching hospitals were interviewed.
Results: High levels of morbidity due to asthma were reported. Most cases (79%) reported symptoms occurring at least weekly in the three months before their NFA. A mean of 20.8 days was reportedly lost from work, school or other usual daily activity in the 12 months before these events. Regular use of beta agonist as nebuliser solution was reported by 27% of cases, increasing to 34.5% in response to increased symptoms, while 41% reported use of nebulised beta agonist in response to the NFA event. Less than half of all cases (46%) reported using an inhaled corticosteroid on a regular basis. Oral corticosteroids were used by 33% of cases at times of increased symptoms in the preceding 12 months. However, only 7% of cases reported initiating or increasing oral corticosteroids at the time of the NFA.
Conclusions: Despite high levels of prior asthma morbidity, regular preventive inhaled corticosteroid use was not widespread in this series of NFA asthmatics. By comparison, over-reliance on regular beta agonist medication was common. Oral corticosteroids were rarely commenced in response to the NFA.     

Lipid management in cardiovascular disease prevention guidelines: strategies and tactics for implementation

Despite the widespread dissemination of clinical practice guidelines on the prevention and treatment of cardiovascular disease (CVD), CVD causes one third of deaths worldwide and almost half of all deaths in the developed world. It is therefore likely that, although some aspects of CVD management have improved, there is still a significant shortfall between what is known about CVD prevention and what is put into action. Twenty-one experts in the field of CVD from around the world attended a focus panel meeting in Marlow-on-Thames, UK (see acknowledgements for a list of meeting participants). These experts were invited to discuss practical strategies and tactics for overcoming barriers to the implementation of guidelines on CVD prevention, and lipid management in particular. This article reviews and updates the key topics presented during the course of the meeting, captures the essence of the group discussions, and summarizes the meeting outcomes. The participants concluded that initial efforts to implement CVD prevention guidelines more effectively are best directed at high-risk patients who have already been identified. Once current patients achieve their targets, more attention can be paid to finding untreated patients at risk. Recommendations from the expert panel included: Harmonize guidelines; focus on common areas of consensus rather than state-of-the-art science. Remove the boundary between primary and secondary prevention and focus on level of overall risk. Help policy makers understand the different components of CVD. Include professional societies from different specialties in guideline development and implementation, to increase ownership and decrease fragmentation of guideline committees.     

Patients' and providers' perceptions of asthma and asthma care: a qualitative study

Background: Differences in patients' and providers' perceptions of asthma and asthma care can create barriers to successful treatment. The primary goal of this qualitative study was to further explore patient and provider perceptions of asthma and asthma care as part of a larger Asthma Comparative Effectiveness Study. Methods: Focus groups held every 6 months for 3 years were designed to have a mix of both patients and providers allowing for unique understanding around asthma care. Results: The discussion centered on goal setting, asthma action plans and prevention strategies for asthma exacerbations. Three overarching themes, with a variety of subthemes, emerged as the main findings of this study. The three main themes were Cost/Economic Barriers/Process, Self-Governance/Adherence and Education. Conclusions: These themes indicated a strong need for patient educational interventions around asthma as well as education for providers around cost, insurance coverage and patient-centered communication. Specifically, education on learning to use inhalers properly, avoiding triggers and understanding the importance of a controller medication will benefit patients in the long-term management of asthma.     

Drug use and HIV risk in Trinidad and Tobago: qualitative study

Crack use is an important risk factor for HIV infection because of its association with unsafe sexual practices. We investigated factors promoting the initiation of crack cocaine use; the sexual behaviour of crack users; and their rehabilitation care seeking behaviour in Trinidad and Tobago. We conducted 40 in-depth interviews with drug users. Respondents frequently reported a history of parental desertion, alcohol abuse, and physical abuse within the family. They perceived peer pressure and drug use in the family as important factors promoting first drug use. Exchanging sex for drugs was common, and practising oral sex was considered safe. Female drug users rarely seek rehabilitative care because of stigmatization and lack of care for their children. In Trinidad, attitudes towards drugs in society and families need to be changed. Campaigns promoting safer sex should emphasize the risk of oral sex. Rehabilitation facilities caring for female drug users should offer child care.     

Understanding clinicians' attitudes toward a mobile health strategy to childhood asthma management: A qualitative study

Objectives: Mobile technology for childhood asthma can provide real-time data to enhance care. What real-time adherence information clinicians want, how they may use it, and if the data meet their clinical needs have not been fully explored. Our goal was to determine whether pediatric primary care and pulmonary clinicians believe if a sensor-based mobile intervention is useful in caring for patients with asthma. Methods: We recruited participants from 3 urban, primary care and 1 pulmonary practice from July to September 2015 in Hartford, CT. Forty-one participated in four focus groups, which included a demonstration of the technology. Participants were probed with open-ended questions on the type, frequency, and format of inter-visit patient information they found useful. Results: 41 participants (mean age 49 (±13.7) years) were board-certified clinicians (41% MDs and 20% mid-level practitioners), practiced medicine on an average of 19 (±14) years, were primarily white (59%) and women (78%). Clinicians wanted 1) adherence to prescribed inhaler therapy and 2) data on inhaler technique. Clinicians wanted it at the time of a scheduled clinic visit but also wanted inter-visit alerts for excessive use of rescue therapy. Pulmonologists liked the mobile spirometer's provision of inter-visit lung function data; pediatricians did not share this view. Concerns with data accuracy were raised due to families who shared inhalers, access to smartphones, and protection of health information. Conclusions: Overall, clinicians view an asthma mobile health technology as enhancing the patient-centered medical home. Pediatric primary care clinicians and pulmonologists want different information from a mobile app.     

Effectiveness of a multi-level asthma intervention in increasing controller medication use: a randomized control trial

Introduction: Poor self-management by families is an important factor in explaining high rates of asthma morbidity in Puerto Rico, and for this reason we previously tested a family intervention called CALMA that was found effective in improving most asthma outcomes, but not effective in increasing the use of controller medications. CALMA-plus was developed to address this issue by adding to CALMA, components of provider training and screening for asthma in clinics. Methods: Study participants were selected from claims Medicaid data in San Juan, Puerto Rico. After screening, 404 children in eight clinics were selected after forming pairs of clinics and randomizing the clinics) to CALMA-only or CALMA-plus. Results: For all three primary outcomes at 12 months, the mean differences between treatment arms were small but in the predicted direction. However, after adjusting for clinic variation, the study failed to demonstrate that the CALMA-plus intervention was more efficacious than the CALMA-only intervention for increasing controller medication use, or decreasing asthma symptoms. Both groups had lower rates of asthma symptoms and service utilization, consistent with previous results of the CALMA-only intervention. Conclusions: Compliance of providers with the intervention and training, small number of clinics available and the multiple barriers experienced by providers for medicating may have been related to the lack of difference observed between the groups. Future interventions should respond to the limitations of the present study design and provide more resources to providers that will increase provider participation in training and implementation of the intervention.     

Gender and age risks for hoarseness and dysphonia with use of a dry powder fluticasone propionate inhaler in asthma.

Dry powder inhalers (DPIs) of fluticasone propionate (FP) are the most commonly prescribed inhaled glucocorticosteroid (ICS) devices in Japan because of their ease of use. FP has the strongest anti-inflammatory effects in vitro among ICS, and it has few systemic adverse effects because of its <1% oral bioavailability. However, local adverse effects, especially hoarseness or dysphonia (hoarseness/dysphonia), appear to be frequent. We investigated hoarseness/dysphonia in 313 patients with bronchial asthma who were using or had used the FP-DPI. Overall, 20.4% of FP-DPI users complained of hoarseness/dysphonia, with women and elderly patients complaining of it more frequently; 35.8% of female FP-DPI users > or =65 years of age complained of hoarseness/dysphonia. The prevalence of hoarseness/dysphonia was dose dependent in patients <65 years old but not in patients > or =65 years of age. Inspiratory flow rates adjusted by resistance of the DPIs were not related to the prevalence of hoarseness/dysphonia. In patients using ICS, especially in women and the elderly patients, who develop hoarseness/dysphonia, it is important to select the most suitable device so that patients can continue ICS therapy comfortably.