Functional gastrointestinal disorders in children: Effectivity, safety, and tolerability of the herbal preparation STW-5 (Iberogast®) in general practice.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) of the upper and lower digestive system in children and adolescents present with heterogeneous gastrointestinal symptoms and are a common reason for specialist consultations. The herbal medicinal preparation STW-5 has already shown efficacy and safety in clinical studies with more than 7000 adult participants suffering from functional dyspepsia (FD) or irritable bowel syndrome (IBS). Here, we evaluate with a prospective observational study the effectivity and safety of STW-5 in children with FGID under real-life conditions and interpret these data versus the background of controlled clinical studies in a predominantly adult population. METHODS: This prospective observational study included 980 children (age 3-14 years) with FGID. For inclusion, Rome III criteria were recommended to apply. The inclusion of the patients for treatment with STW-5 followed routine clinical practice. Patients were treated for approximately 1 week. The presence and severity of symptoms was documented at the study start and at the end of treatment period utilizing the adapted gastrointestinal symptom score (GIS). Other target parameters included global effectivity and tolerability assessments as well as adverse events. RESULTS: The average patient age was 7.6 ± 2.9 years. Most of the patients were treated for IBS (n = 418; 43 %) or FD (n = 259; 26 %), with a mean baseline GIS of 16.1 ± 8.9. During the treatment period, the GIS decreased 76 % to 3.8 ± 4.2. The decrease in symptoms was similar for different age groups, gender, and indications. Patients with a shorter duration of complaints had a lower GIS at study end (p < 0.0001. The global treatment effect was assessed as good or very good by 87-89 % of patients/parents and physicians. Physicians rated the global tolerability as good or very good for 95 % of the patients. Seven patients (0.7 %) reported adverse events. CONCLUSIONS: The treatment effect of STW-5 in this study was in its range comparable to according data from controlled clinical trials with predominantly adult participants.Thus, supporting robustness of these data generated in an uncontrolled observational setting. The results of this observational study indicate that STW-5 may be an effective and well tolerated treatment option also for children with FGIDs.

Therapeutic Success of Tiotropium/Olodaterol, Measured Using the Clinical COPD Questionnaire (CCQ), in Routine Clinical Practice: A Multinational Non-Interventional Study.

BACKGROUND: The Clinical COPD Questionnaire (CCQ) is a simple patient-reported tool to measure clinical control of chronic obstructive pulmonary disease (COPD). OBJECTIVE: This open-label, single-arm, non-interventional study (NCT03663569) investigated changes in CCQ score during treatment with tiotropium/olodaterol in clinical practice. METHODS: Data were included from consenting COPD patients, enrolled in Bulgaria, Czech Republic, Hungary, Israel, Lithuania, Poland, Romania, Russia, Slovenia, Switzerland and Ukraine, who were receiving a new prescription for tiotropium/olodaterol according to the treating physician in a real-world environment. The primary endpoint was the occurrence of therapeutic success, defined as a 0.4-point decrease in CCQ score after treatment with tiotropium/olodaterol for approximately 6 weeks. RESULTS: Overall, 4819 patients were treated; baseline and Week 6 CCQ scores were available for 4700 patients, mostly classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) B (51.6%) or D (42.7%). After 6 weeks' treatment, 81.4% (95% confidence interval [95% CI] 80.24-82.49) of patients achieved therapeutic success; mean improvement in overall CCQ score was 1.02 points (95% CI 1.00-1.05). Improved CCQ score was seen in 92.2% of patients (95% CI 91.43-92.98), 2.5% had no change and 5.3% showed a worsening. When stratified by prior treatment, the greatest benefit was seen in treatment-naïve patients, with 85.7% achieving therapeutic success, compared with 79.5% of those pretreated with long-acting ß2-agonist (LABA)/inhaled corticosteroid (ICS) and 74.2% of those pretreated with LABA or long-acting muscarinic antagonist (LAMA) monotherapy. Overall, rescue medication decreased by 1.25 puffs/day (95% CI 1.19-1.31) versus baseline. In total, 29 patients (0.6%) reported drug-related adverse events and 7 patients reported serious adverse events (0.15%). CONCLUSION: In 4700 COPD patients, 6 weeks' treatment with tiotropium/olodaterol, as initial treatment or follow-up to LAMA or LABA monotherapy or LABA/ICS, improved CCQ and decreased rescue medication use. The adverse event profile was consistent with the known safety profile of tiotropium/olodaterol.

Analysis of patients with deep vein thrombosis switched from standard therapy to rivaroxaban in the non-interventional XALIA study.

INTRODUCTION: XALIA assessed the safety and effectiveness of rivaroxaban for deep vein thrombosis (DVT) treatment in routine clinical practice. This substudy describes the clinical characteristics and outcomes of 'early switchers' - patients who received heparin or fondaparinux for >2-14days and/or a vitamin K antagonist (VKA) for 1-14days before switching to rivaroxaban. MATERIALS AND METHODS: Patients with DVT (latterly with concomitant pulmonary embolism) received rivaroxaban or standard anticoagulation (initial treatment with heparin or fondaparinux, usually overlapping with and followed by a VKA). Patients administered rivaroxaban alone, or heparin or fondaparinux for ≤48h pre-enrollment were included in the rivaroxaban cohort. Therapy type, dose, and duration were at the physician's discretion. Primary outcomes were major bleeding, recurrent venous thromboembolism (VTE), and all-cause mortality. RESULTS: In 368 early switchers, recurrence or bleeding risk factors were more prevalent versus the rivaroxaban cohort, including creatinine clearance<50mL/min (6.5% vs. 3.9%), previous major bleeding (4.6% vs. 1.4%), active cancer (8.2% vs. 5.6%), and concomitant pulmonary embolism (20.9% vs. 8.4%). Crude incidence rates were numerically higher versus the rivaroxaban cohort for major bleeding (1.4% vs. 0.7%), recurrent VTE (2.2% vs. 1.4%), and all-cause mortality (0.8% vs. 0.5%). CONCLUSIONS: Patients who switched to rivaroxaban early in the treatment process had a higher frequency of risk factors for bleeding and recurrent VTE than patients treated with rivaroxaban; reflected by the higher risk of adverse events in that group during follow-up.

[Improvement of Stress Resistance and Quality of Life of Adults with Nervous Restlessness after Treatment with a Passion Flower Dry Extract].

BACKGROUND: The passion flower dried ethanolic extract investigated in this non-interventional study has well-documented calmative effects and good tolerability. We investigated the effects of this extract on the stress resistance (resilience) and quality of life (QoL) of patients suffering from nervous restlessness. The addiction potential of the drug and the course of symptoms were also evaluated. METHODS: Adult patients aged ≤ 95 years with the diagnosis 'nervous restlessness' were treated for 12 weeks with a dried ethanolic extract of passion flower (Passiflora incarnata L.). Standardized questionnaires were used to evaluate the resilience (RS-13), QoL (EQ-5D including EQ-VAS), and the addiction potential (BDEPQ). RESULTS: After 12 weeks of treatment, significant (p < 0.001) improvements were measured in the patients' resilience (RS-13: from 52.1 to 67.7 points) and QoL (EQ-VAS: from 47.9 to 75.0 points). Also, the mean BDEPQ score was significantly (p < 0.001) reduced (from 23.0 to 19.3 points). The mean values of all accompanying symptoms (inner restlessness, sleep disturbance, exhaustion, fear, lack of concentration, transpiration, nausea, trembling, and palpitation) improved significantly (p < 0.001). Tolerability of treatment was rated as 'very good' or 'good' by the majority of the patients. Three cases of mild adverse events (tiredness) were reported. CONCLUSION: The passion flower extract investigated in the present study appears to be effective in improving resilience and QoL in patients suffering from nervous restlessness and is well tolerated.

Safety and compliance of a complex homeopathic drug (Contramutan N Saft) in the treatment of acute respiratory tract infections: A large observational (non-interventional) study in children and adults focussing on homeopathy specific adverse reactions versus adverse drug reactions.

BACKGROUND: This non-interventional study was performed to generate data on safety and treatment effects of a complex homeopathic drug (Contramutan N Saft). PATIENTS AND METHODS: 1050 outpatients suffering from common cold were treated with the medication for 8days. The study was conducted in 64 outpatient practices of medical doctors trained in CAM. Tolerability, compliance and the treatment effects were assessed by the physicians and by patient diaries. Adverse events were collected and assessed with specific attention to homeopathic aggravation and proving symptoms. Each adverse effect was additionally evaluated by an advisory board of experts. RESULTS: The physicians detected 60 adverse events from 46 patients (4.4%). Adverse drug reactions occurred in 14 patients (1.3%). Six patients showed proving symptoms (0.57%) and only one homeopathic aggravation (0.1%) appeared. The rate of compliance was 84% in average for all groups and the global assessment of the treatment effects attributed to "good" and "very good" in 84.9% of all patients. CONCLUSIONS: The homeopathic complex drug was shown to be safe and effective for children and adults likewise. Adverse reactions specifically related to homeopathic principles are very rare. All observed events recovered quickly and were of mild to moderate intensity.

Safety and effect on reported symptoms of depigmented polymerized allergen immunotherapy: a retrospective study of 2927 paediatric patients.

BACKGROUND: Allergen immunotherapy (AIT) is effective treatment for allergic diseases, and subcutaneous use of depigmented polymerized extracts may allow rapid up-dosing and safe therapy. To date, there is little information on their safety and clinical effects for children and adolescents with allergic disease. METHODS: We performed a retrospective survey of patient notes of 2927 children and adolescents across 136 centres who had received subcutaneous AIT (SCIT) with depigmented polymerized extracts to pollen or mite allergens for at least 1 yr to collect documentation on safety and clinical symptoms. RESULTS: 16.3% percent of patients had local reactions, of these 148 were larger than 12 cm in diameter. Systemic reactions were documented in 1.6% of children and in 0.8% of adolescents. There were no documented cases of anaphylactic shock. There were significant reductions in the frequency of patients with recorded nasal symptoms over time of treatment. Moreover, the prescribing rate of rescue medication was reduced over the course of SCIT. CONCLUSION: These 'real-life' data from a large retrospective analysis including 2927 children and adolescents with pollen- and/or mite-induced allergic rhinoconjunctivitis with/or without allergic asthma indicate that AIT with depigmented polymerized extracts is well tolerated, and they are compatible with clinical response.

Efficacy of acarbose in different geographical regions of the world: analysis of a real-life database.

BACKGROUND: Alpha-glucosidase inhibitors are recommended in some international guidelines as first-line, second-line and third-line treatment options but are not used worldwide due to perceived greater effectiveness in Asians than Caucasians. METHODS: Data from ten post-marketing non-interventional studies using acarbose, the most widely used alpha-glucosidase inhibitor, from 21 countries, provinces and country groups were pooled. Effects on glycated hemoglobin (HbA1c ) were analysed for four major ethnicity/region groups (European Caucasians and Asians from East, Southeast and South Asia) to identify differences in the response to acarbose. RESULTS: The safety and efficacy populations included 67 682 and 62 905 patients, respectively. Mean HbA1c in the total population decreased by 1.12 ± 1.31% at the 3-month visit from 8.4% at baseline (p < 0.0001). Reductions in HbA1c , fasting plasma glucose and post-prandial plasma glucose were greater in patients with higher baseline values. Acarbose was well tolerated, with few episodes of hypoglycemia (0.03%) and gastrointestinal adverse events (2.76%). Data from 30 730 Caucasians from Europe and Asians from three major regions of Asia with non-missing gender/age information and baseline/3-month HbA1c data were analysed by multivariable analyses of covariance. After adjustment for relevant baseline confounding factors, Southeast and East Asians had slightly better responses to acarbose than South Asians and European Caucasians; however, the differences were small. CONCLUSIONS: Acarbose was effective in both European Caucasians and Asians; however, after adjustment for baseline confounding factors, significant small differences in response favoured Southeast and East Asians.

Management of severe chronic pain with tapentadol prolonged release - long-term data from pain specialists.

BACKGROUND AND OBJECTIVE: Clinical trials have documented the efficacy and good tolerability of tapentadol prolonged released (PR) for severe chronic pain. This study investigated routine long-term administration by pain specialists. METHODS: The effectiveness analysis included prospective data collected over a 3 month period (cohort I, n = 1457, mean age 61.2 ± 13 years) and over a 12 month period (cohort II, n = 588, 60.1 ± 13.2 years) regarding previous and concomitant analgesic treatment, tapentadol dosage, pain intensity, sleep and quality of life parameters, and tolerability. RESULTS: Most patients (>77%) had suffered from severe chronic pain for ≥2 years with low back pain the main pain diagnosis (82%); 91% had already received analgesic long-term treatment prior to initiation of tapentadol therapy (42% of those received strong opioids). After 3 month tapentadol treatment, cohort I had experienced a mean pain reduction of 2.4 points (from 6.8 ± 1.6 at baseline) and improvements of 2.1 points in quality of sleep (from 5.8 ± 2.5) and quality of life (from 6.5 ± 2; all p ≤ 0.001). The 12 month tapentadol treatment (cohort II) reduced the mean pain intensity by 3.2 points from 6.7 ± 1.6 at baseline (NRS-11; p ≤ 0.001); 57% of the patients experienced clinically relevant pain relief of ≥50%. At end of observation, 92% attained either their intended pain reduction and/or an additional individual treatment target, both predefined at start of tapentadol therapy. This was accompanied by a significant reduction in pain-related impairments in daily activities and an improvement in quality of life (all p ≤ 0.001). Most frequent side-effects were nausea (6.3% of patients) and dizziness (3.8%) for cohort I, and nausea (1.5%) and constipation (1.2%) for cohort II. CONCLUSION: Tapentadol PR is effective and well tolerated and can be considered an alternative to classical strong opioids in long-term chronic pain therapy. LIMITATIONS: The study lacks a control group; assessment under routine practice conditions, however, reflects daily practice clinical management conditions.