Diagnosis and Treatment Patterns of Chronic Thromboembolic Pulmonary Hypertension in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia: A Registry Study.

BACKGROUND: Patients with chronic thromboembolic pulmonary hypertension (CTEPH) in countries with limited resources have, to date, been poorly represented in registries. OBJECTIVE: This work assesses the epidemiology, diagnosis, hemodynamic and functional parameters, and treatment of CTEPH in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia. METHODS: A prospective, cohort, phase IV, observational registry with 3-year follow-up (n = 212) in patients aged ≥ 18 years diagnosed with CTEPH was created. Clinical, hemodynamic, and functional parameters were obtained at an initial visit, follow-up visits, and a final visit at the end of 3 years' observation or end of follow-up. Data were recorded on electronic case report forms. Parameters evaluated included 6-minute walking distance (6MWD), use of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), pulmonary hypertension (PH)-targeted therapy, and survival. All statistical analyses were exploratory and descriptive, and were performed in the overall population. RESULTS: The most common symptoms were typical of those expected for CTEPH. Almost 90% of patients underwent right heart catheterization at diagnosis or initial study visit. In total, 66 patients (31%) underwent PEA before the initial visit; 95 patients (45%) were considered operable, 115 (54%) were inoperable, and two (1%) had no operability data. Only 26 patients (12%) had been assessed for BPA at their initial visit. PH-targeted therapy was documented at diagnosis for 77 patients (36%), most commonly a phosphodiesterase type 5 inhibitor (23%). Use of PH-targeted therapy increased to 142 patients (67%) at the initial visit, remaining similar after 3 years. Use of riociguat increased from 6% of patients at diagnosis to 38% at 3 years. Between baseline and end of observation, results for patients with paired data showed an increase in 6MWD. Survival at the end of observation was 88%. CONCLUSIONS: These data highlight the current diagnosis and management of CTEPH in the participating countries. They show that early CTEPH diagnosis remains challenging, and use of off-label PH-targeted therapy is common. CLINICALTRIALS: gov: NCT02637050; registered December 2015.

Assessment of Medication Adherence Using a Medical App Among Patients With Multiple Sclerosis Treated With Interferon Beta-1b: Pilot Digital Observational Study (PROmyBETAapp).

BACKGROUND: Accurate measurement of medication adherence using classical observational studies typically depends on patient self-reporting and is often costly and slow. In contrast, digital observational studies that collect data directly from the patient may pose minimal burden to patients while facilitating accurate, timely, and cost-efficient collection of real-world data. In Germany, ~80% of patients with multiple sclerosis (MS) treated with interferon beta 1b (Betaferon) use an electronic autoinjector (BETACONNECT), which automatically records every injection. Patients may also choose to use a medical app (myBETAapp) to document injection data and their well-being (using a "wellness tracker" feature). OBJECTIVE: The goal of this pilot study was to establish a digital study process that allows the collection of medication usage data and to assess medication usage among patients with MS treated with interferon beta-1b who use myBETAapp. METHODS: The PROmyBETAapp digital observational study was a mixed prospective and retrospective, noninterventional, cohort study conducted among users of myBETAapp in Germany (as of December 2017: registered accounts N=1334; actively used accounts N=522). Between September and December 2017, users received two invitations on their app asking them to participate. Interested patients were provided detailed information and completed an electronic consent process. Data from consenting patients' devices were collected retrospectively starting from the first day of usage if historical data were available in the database and collected prospectively following consent attainment. In total, 6 months of data on medication usage behavior were collected along with 3 months of wellness tracker data. Descriptive statistics were used to analyze persistence, compliance, and adherence to therapy. RESULTS: Of the 1334 registered accounts, 96 patients (7.2%) provided informed consent to participate in the study. Of these, one patient withdrew consent later. For another patient, injection data could not be recorded during the study period. Follow-up of the remaining 94 patients ended in May 2018. The mean age of participants was 46.6 years, and 50 (53%) were female. Over the 6-month study period, persistence with myBETAapp usage was 96% (90/94), mean compliance was 94% of injections completed, and adherence (persistence and ≥80% compliance) was 89% (84/94). There was no apparent difference between male and female participants and no trend across age groups. The wellness tracker was used by 21% of participants (20/94), with a mean of 3.1 entries per user. CONCLUSIONS: This study provides important information on medication usage among patients with MS treated with interferon beta-1b and on consenting behavior of patients in digital studies. In future studies, this approach may allow patients' feedback to be rapidly implemented in existing digital solutions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03134573; https://clinicaltrials.gov/ct2/show/NCT03134573.

Patient Satisfaction and Clinical Outcomes with Budesonide plus Formoterol Spiromax for Asthma and Chronic Obstructive Pulmonary Disease: A Real-World, Observational Trial.

BACKGROUND: The fixed-dose combination of budesonide/formoterol (B/F) has been available in the Spiromax® dry powder inhaler since 2014. OBJECTIVES: To assess patient satisfaction, inhaler use errors, and disease control in patients with asthma or chronic obstructive pulmonary disease (COPD) treated with B/F Spiromax. METHODS: This non-interventional, prospective, 12-week study enrolled consecutive asthma or COPD patients who had recently begun treatment with B/F Spiromax or were switched from another inhaled corticosteroid/long-acting ß2-agonist combination to B/F Spiromax in routine clinical practice. Patients recruited from 243 specialist respiratory clinics or general practices in Germany were assessed for patient satisfaction (Satisfaction with Inhalers and Preference questionnaire), inhaler application errors (modified Easy Low Instruction over Time checklist), disease control, and safety. RESULTS: The population included 3,943 patients: asthma n = 2,707 (68.7%); COPD n = 1,236 (31.3%). At baseline, 60.1% of patients were "satisfied" or "very satisfied" with their previous inhaler, and this increased to 88.8% at week 12 of B/F Spiromax use. Overall, 62.1% of pre-treated patients preferred B/F Spiromax to their old inhaler. The frequency of any handling error observed with B/F Spiromax at week 12 was lower than at baseline (11.9 vs. 25.5% of patients, respectively). After 12 weeks, 77.4% were assessed as having improved (minimally, much, or very much) overall health status versus baseline. Guideline-defined disease severity (as rated by physicians) and patient-reported symptom severity improved during the study in both asthma and COPD patients. B/F Spiromax was well tolerated. CONCLUSION: B/F Spiromax was associated with high patient satisfaction, low device handling error rate, and improvements in clinical outcomes in real-world clinical practice.

An open prospective pilot study of a herbal combination "Relief" as a supportive dietetic measure during alcohol withdrawal.

OBJECTIVE: A herbal combination (saffron extract, passion flower herb extract, cocoa seed extract, radish extract and black cumin extract) called "Relief" was designed as a supportive therapy of alcohol withdrawal syndrome (AWS). This combination was based on the scientific evidence of each constituent effect on AWS-like symptoms. In addition, our preclinical studies have shown the effectiveness of Relief on AWS detoxification. The rationale of the study was to document whether the oral intake of the designed content of Relief could have a positive effect on the course of alcohol detoxification by reducing some of the AWS in hospitalized patients. METHODS: This pilot study was performed as non-interventional, open, single-armed, prospective on 32 hospitalized patients entered for detoxification of alcohol withdrawal syndrome. Each patient received daily three capsules of Relief for 15 days, and AWS parameters were monitored, in addition to serum liver enzymes and quality of life which was evaluated using the Befindlichkeits-Skala (Bf-SR) scaling system. RESULTS: Relief administration significantly reduced the percentage of patients with hyperhidrosis (r=0.815, p<0.001), reduced serum liver enzymes by ~50-80% (p<0.05), and increased normalization of appetite (r=0.777, p<0.001). Besides, before the treatment began the Bf-SR scale was 28.3±4.3, which was typical for neurological syndromes such as depression or insomnia, and during Relief administration the Bf-SR scale significantly dropped to 15.6±2.4 (p<0.001). As for the safety, four, but not serious, adverse events were observed; two of them may be product related. Finally, 84.4% of patients' assessed Relief treatment as good to excellent and 87.5% of the patients declared an interest in reusing Relief for the next detoxification period. CONCLUSIONS: Despite the limitations of the present study, the findings showed the potential of Relief for the improvement of the clinical situation of patients with symptoms of alcohol withdrawal and therefore, justify a full-scale well-controlled study design to be implemented.

Comparative evaluation of patients' and physicians' satisfaction with interferon beta-1b therapy.

BACKGROUND: Due to the preventive nature of disease-modifying therapies for multiple sclerosis, treatment success particularly depends on adherence to therapeutic regimens and patients' perception of treatment efficacy. The latter is strongly influenced by the confidence in the involved health care professionals and the relationship to the treating physician. METHODS: In this report, we considered physicians' and patients' evaluation of satisfaction with interferon beta-1b treatment efficacy for assessing the congruence in ratings. Data were queried in a study conducted between 2009 and 2013. RESULTS: After 6 months of therapy, > 80 % of the patients and physicians (N = 445) showed high degrees of satisfaction regarding interferon beta-1b treatment, with only few physicians and patients (≤2.0 %) rating "not satisfied". The proportion of patients rating with the same category as their physicians was similar after 6 months (47 % congruence) and at the 24 months/study end visit (49 %). Discrepancies between ratings were observed with respect to study end: for patients with premature study end, more patients and physicians rated being not satisfied with the therapy, accompanied by a considerably lower congruence of 33 % compared to 54 % for patients receiving the therapy for at least 2 years and completing the study regularly. CONCLUSIONS: Regular communication between physicians and patients about their perception of therapy might improve alignment of treatment evaluation and could result in increased therapy persistence. In addition, patients' willingness to perform a long-term therapy - even in the absence of disease symptoms - might be promoted by repeated exchange between health care providers and patients with regard to realistic treatment expectations. TRIAL REGISTRATION: ClinicalTrials.gov NCT00902135 (registered May 13, 2009).

Adherence to Long-Term Interferon Beta-1b Injection Therapy in Patients with Multiple Sclerosis Using an Electronic Diary.

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system requiring long-term treatment, which is often hampered by non-adherence to self-applicable therapies, provoking continued disease activity and health care system burdens. This study assessed the influence of a personal digital assistant (PDA) with diary function (n = 339 patients) on persistence and adherence to an interferon beta treatment regimen in comparison to a paper patient diary (n = 330 patients). METHODS: Patients who recently started with subcutaneous injections of interferon beta-1b were recruited in this prospective, non-interventional, national cohort study for an observational period of 2 years after successful completion of the initial dose escalation. RESULTS: Therapy persistence as assessed by the drop-out rate within 104 weeks was about 50% in both study cohorts. In male patients, the drop-out rate was 10% lower when using a PDA compared to the non-PDA group. Use of a PDA with an injection reminder function increased adherence to the injection schedule (every other day) by a mean of 24.5 injections over 24 months in comparison to use of a PDA without injection reminder function. CONCLUSION: Persistence in this study was in the published range of observational MS studies. Furthermore, in male patients continuation of therapy might be positively influenced by use of a PDA, and both female and male patients might benefit from an integrated reminder function. In conclusion, electronic diaries reminding patients of upcoming injections can promote an improved adherence to MS therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00902135. FUNDING: Bayer Vital GmbH.

Evaluation of an electronic diary for improvement of adherence to interferon beta-1b in patients with multiple sclerosis: design and baseline results of an observational cohort study.

BACKGROUND: Multiple sclerosis is a chronic, incurable, demyelinating disease that requires long-term treatment. Rates of non-adherence to prescribed therapy of up to 50% have been reported for chronic diseases. Strategies to improve treatment adherence are therefore of the utmost importance. This study will evaluate the effect of using electronic and paper diaries on treatment adherence to interferon beta-1b in patients with a first clinical isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS). Here we report on the study design and results of baseline assessments. METHODS: Patients were recruited into a prospective national multicenter cohort study for an observational period of 2 years. At the start of the study, patients opted to use a digital (DiD) or paper diary (PD) to document self-administered injections of interferon beta-1b. Adherence to treatment will be assessed on the dropout rate at the end of the observation period and on the regularity of injections every other day at 6-month intervals. Patient-related health outcomes will also be evaluated. RESULTS: 700 patients with a mean age of 38.3 (SD 10.3) years and a mean duration of disease since diagnosis of 3.6 (SD 5.9) years were enrolled. 383 patients opted for the digital diary, 192 of which included an injection reminder. Significantly more male than female patients opted for the DiD. Only gender was identified as a factor influencing the decision for DiD or PD. Based on rating scales, a significantly higher proportion of women had depressive comorbidities at baseline. CONCLUSIONS: Demographic characteristics of the two cohorts were similar at baseline. More women chose a paper diary, and more had depression at baseline. These imbalances will be addressed in the analysis of the study as possible confounders influencing long-term treatment adherence in the digital and paper diary cohorts.