Correlation of effectiveness and tolerability assessments from a pharmacy-based observational study investigating the fixed-dose combination of 400 mg ibuprofen plus 100 mg caffeine for the treatment of acute headache.

Introduction: Observational studies are valuable for investigating correlations between patient-reported treatment outcomes. In this study, we report a secondary analysis of a published pharmacy-based observational (patient-centered "real-world" outcomes) study on experiences reported by patients who treated their headache with an over-the-counter analgesic. Methods: A pharmacy-based exploratory survey was conducted in German community pharmacies. Patients buying a fixed-dose analgesic combination product (400 mg ibuprofen + 100 mg caffeine; IbuCaff) to treat their headache were offered a questionnaire that contained-among others-questions about time to onset of pain relief (OPR), assessment of time to onset of pain relief (AOPR), assessment of efficacy and tolerability, and pain intensity 2 h after intake. A correlation analysis of the data was performed. Moreover, perceived treatment effects compared to other acute headache medications used in the past were collected. Results: The correlation between OPR and AOPR was high (Spearman rank correlation r = 0.594, p < 0.0001). Headache patients assessed the onset of analgesic action within 15 min as "very fast" and within 30 min as "fast". The other readouts were correlated as well [assessment of efficacy and % pain intensity difference (%PID) at 2 h: r = 0.487; OPR/AOPR and %PID at 2 h: r = 0.295/0.318; OPR/AOPR and assessment of tolerability: r = 0.206/0.397; OPR/AOPR and assessment of efficacy: r = 0.406/0.594; assessment of efficacy and assessment of tolerability: r = 0.608; p < 0.0001 for all correlations]. Compared to previous treatments, most patients (>89%) assessed the speed of analgesic action, efficacy, and tolerability of IbuCaff as equal to or better than for the previous treatment. Discussion: Headache patients assessed the onset of analgesia within 15 min as "very fast" and within 30 min as "fast". Efficacy assessments for acute headache medication appear to be highly correlated.

Effects of EPs 7630 on the duration of inability to work in acute bronchitis - a meta-analysis.

Background: Acute bronchitis (AB) has an enormous economic impact through lost working time. We investigated whether treatment with Pelargonium extract EPs 7630 may reduce the time of inability to work. Methods: A meta-analysis of double-blind, randomized, placebo-controlled trials with adult patients suffering from AB was performed. The average number of days of inability to work and the proportion of patients who were still unable to work after one week's treatment were assessed. Results: Four clinical trials with a total of 1,011 evaluable patients who received the marketed dosage of EPs 7630 (n=505) or placebo (n=506) for seven days were included in the meta-analysis. At baseline, 845/1,011 patients (83.6%) were unable to work. In the four trials, the proportion decreased to between 19 and 14% for EPs 7630 and to between 41 and 55% for placebo (meta-analysis risk ratio and 95% confidence interval: 0.35; 0.26-0.45; p<0.001). For the number of sick days, a weighted mean difference of 1.73 days (1.17-2.29 days; p<0.001) favoring EPs 7630 was observed. Conclusions: For adults suffering from AB, this meta-analysis demonstrates that seven days' treatment with Pelargonium sidoides extract EPs 7630 significantly reduces the average number of sick days and significantly increases the proportion of patients who are able to return to work.

[Analgesic use in Germany : Survey of the years 2008 to 2019]. / Schmerzmittelgebrauch in Deutschland : Eine Erhebung über die Jahre 2008 bis 2019.

BACKGROUND: There are previously published data on the per capita use of analgesics in Germany, but only to 2005. In the present analysis, data for the years 2008-2019 were evaluated. The use of prescription and nonprescription analgesics was investigated and possible influencing factors were discussed. MATERIALS AND METHODS: The per capita use of prescription and nonprescription analgesics was determined based on data on prescriptions and cash purchases in pharmacies (IMS Pharmascope®, Wiener Neudorf, Austria). Moreover, an evaluation according to active substances was performed for nonprescription drugs. In addition, pharmaceutical manufacturers' advertising expenditures and changes in distribution channels were analyzed as possible influencing factors. RESULTS: During the observation period 2008-2019, the use of prescription analgesics in Germany increased, while the use of nonprescription analgesics decreased. Single-agent drugs constitute the majority of sales of nonprescription analgesics. The share of combination drugs has decreased in recent years. CONCLUSION: The use of nonprescription analgesics in Germany decreased between 2008 and 2019. The trend as of 1995, which was observed in a previous investigation, is therefore continuing. External factors, such as the increase in advertising expenses or easier access via mail-order pharmacies, do not appear to influence use.

Effects of Pelargonium sidoides extract EPs 7630 on acute cough and quality of life - a meta-analysis of randomized, placebo-controlled trials.

Background: Cough is a leading symptom of viral acute respiratory infections such as acute bronchitis (AB) and the common cold (CC), which can be debilitating and may persist for several weeks. We investigated whether treatment with Pelargonium extract EPs 7630 may reduce cough and improve disease-related quality of life (QoL). Methods: We performed a meta-analysis of randomized, placebo-controlled trials investigating the efficacy of EPs 7630 in AB or CC. Efficacy analyses included change from baseline in a cough intensity score, remission of cough, and disease-associated impairments of QoL. Results: Data of 2,195 participants from 11 trials (3 in children/adolescents with AB, 3 in adults with AB, 5 in adults with CC) were eligible. In children/adolescents with AB, 79.6% of participants treated with EPs 7630 and 41% treated with placebo showed a reduction in the intensity of cough by at least 50% of baseline values at day 7 [meta-analysis rate/risk ratio (RR), EPs 7630 / placebo: 1.86 (95% CI: 1.34; 2.95)], and 18.0% vs 5.5% presented with complete remission of cough [RR: 2.91 (95% CI: 1.26; 6.72)]. In adults with AB, 88.7% of participants in the EPs 7630 group and 47.6% in the placebo group showed a ≥50% response for cough intensity [RR: 2.13 (95% CI: 1.37; 3.31)], while 26.0% vs 6.3% did not cough any more at day 7 [RR: 5.00 [95% CI: 3.10; 8.07)]. Cough scale results were supported by significant improvements over placebo in the pursuit of normal daily activities and other QoL measures. In CC, 56.8% of participants treated with EPs 7630 and 38.8% treated with placebo showed a ≥50% cough intensity reduction [RR: 1.40 (95% CI: 1.19; 1.65)] at day 5, while 26.1% versus 18.4% showed complete remission of cough for EPs 7630 and placebo, respectively [RR: 1.40 (95% CI: 1.06; 1.84)]. CCassociated pain/discomfort and impairment of usual activities were no longer present in 41.5% and 48.8% of participants treated with EPs 7630 compared to less than 40% of patients in the placebo group. Conclusions: The results show that EPs 7630 reduces the burden and leads to earlier remission of cough. Advantages for EPs 7630 were also reflected in self-rated measures of disease-associated QoL. Of note, patients treated with the herbal product felt able to resume their usual daily activities sooner.

Aspirin, paracetamol (acetaminophen) and caffeine for the treatment of acute migraine attacks: A systemic review and meta-analysis of randomized placebo-controlled trials.

BACKGROUND AND PURPOSE: Many migraine patients rely on over-the-counter analgesics for the treatment of migraine attacks. Fixed-dose combinations of aspirin, paracetamol and caffeine (APC) have been used for treating migraine in many countries for a long time. We performed a meta-analysis for the comparison of APC versus placebo, which has not been done to date. METHODS: Randomized, blinded, placebo-controlled, parallel-group studies using APC to treat a migraine attack were included in a meta-analysis. We calculated the rate ratio (RRs) associated with APC versus placebo. RESULTS: Seven studies were included, with 3306 participants (2147 treated with APC and 1159 treated with placebo). For the primary efficacy outcome, being pain-free at 2 h, APC was superior to placebo (19.6% vs. 9.0%, RR 2.2, 95% confidence interval [CI] 1.4-3.3). For the co-primary efficacy outcome, pain relief at 2 h, APC was superior to placebo (54.3% vs. 31.2%, RR 1.7, 95% CI 1.6-1.9). Adverse events were more frequent in the APC than the placebo groups (10.9% vs. 7.8%, RR 1.7, 95% CI 1.3-2.2). CONCLUSIONS: Results showed that APC is superior to placebo in the treatment of acute migraine attacks. Efficacy, measured by pain-free response and pain relief at 2 h, was clinically relevant.

A lifestyle intervention during pregnancy to reduce obesity in early childhood: the study protocol of ADEBAR - a randomized controlled trial.

BACKGROUND: The prevalence of obesity in childhood is increasing worldwide and may be affected by genetic factors and the lifestyle (exercise, nutrition behavior) of expectant parents. Lifestyle factors affect adipokines, namely leptin, resistin, and adiponectin as well as cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), which are involved in the regulation of maternal metabolic homeostasis, glucose metabolism, and the development of insulin resistance, metabolic syndrome, gestational diabetes mellitus, and hypertension. However, studies focusing on the effect of exercise or a combination of parental exercise and nutrition on the above-mentioned markers in newborns (venous cord blood) and especially on the long-term development of infants' weight gain are lacking. The study will investigate the effects of a multimodal intervention (regular exercise, diet) on parental and childhood adipocytokines (leptin, resistin, adiponectin, TNF-α, IL-6, BDNF). The effect of a lifestyle-related change in "fetal environmental conditions" on the long-term weight development of the child up to the age of two will also be assessed. METHODS/DESIGN: A randomized multi-center controlled trial will be conducted in Germany, comparing supervised aerobic and resistance training 2x/week (13th to 36th weeks of gestation) and nutritional counseling (6th to 36th weeks of gestation) during pregnancy with usual care. Thirty women (pre-pregnancy Body Mass Index ≥25 kg/m2, 6th-10th week of gestation) will be included in each group. Maternal anthropometric and physical measurements as well as blood sampling will occur at the 6th-10th, 13th-14th, 21st-24th, and 36th week of gestation, at delivery as well as 8 weeks and 24 months postpartum. Neonatal measurements and umbilical blood sampling will be performed at birth. Maternal and infants' weight development will be assessed every 6 months till 24 months postpartum. A difference in childhood BMI of 1 kg/m2 at the age of two years between both groups will be assumed. A power size of 80% using a significance level of 0.05 and an effect size of 1.0 is presumed. DISCUSSION: A better understanding of how lifestyle-related changes in the fetal environment might influence infants' outcome after two years of life could have a profound impact on the prevention and development of infants' obesity. TRIAL REGISTRATION: The trial is registered at the German Clinical Trial Register (DRKS00007702); Registered on 10th of August 2016; retrospectively registered https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00007702.

Cognitive behavioral therapy in adolescents with early-onset psychosis: a randomized controlled pilot study.

Cognitive behavioral therapy for psychosis (CBT) is an effective treatment in adult patients with schizophrenia. However, no randomized controlled and blinded trial in adolescents with early-onset psychosis (EOP) has been conducted. Therefore, the present pilot study explores the acceptance, tolerability, feasibility, and safety of a modified CBT in adolescents with EOP. Twenty-five adolescents with EOP were randomized to either 9 months (20 sessions) of CBT + treatment as usual (TAU) or TAU alone. The primary endpoint was the PANSS-positive subscale (P1-7). Secondary endpoints included psychopathology, global functioning, and quality of life (QoL). Acceptance, tolerability, feasibility, and safety were assessed. Blinded assessments took place by the end of the treatment (9 months) and at 24-month follow-up. Despite improvements in both groups and lack of statistical significance between CBT + TAU and TAU regarding the primary endpoint, we observed between-group effect sizes of at least d = 0.39 in favor of CBT + TAU at post-treatment for delusions, negative symptoms, functioning and QoL after the intervention and effect sizes of at least d = 0.35 after 24 months. CBT in EOP was highly acceptable (73.5% agreed to randomization), well-tolerated (83.1% attendance rate, no drop-outs), and safe (one serious adverse event (SAE) in CBT + TAU in comparison with six SAEs in TAU). These findings suggest that CBT adapted to the needs of adolescents with EOP is a promising approach regarding negative symptoms, functioning, and QoL. CBT is a safe and tolerable treatment. However, due to the small sample size and the pilot character of the study, these conclusions are limited, and should be tested in a larger, adequately powered randomized controlled trial.

Treatment of signs and symptoms of the common cold using EPs 7630 - results of a meta-analysis.

The efficacy of Pelargonium sidoides preparation EPs 7630 in the common cold (CC) was assessed by performing meta-analyses of randomized, double-blind, placebo-controlled trials. Mean differences (MD) and risk ratios (RR) with their 95% confidence intervals (CI) were computed. Five trials with a total of 833 patients were included. All trials had a treatment period of ten days with visits at days 3, 5, and 10 after baseline and used a ten-symptom Cold Intensity Score (CIS) as the primary outcome. Significant differences favoring EPs 7630 were observed for total CIS reduction (day 5: MD = -2·30; 95%CI = -4·12,-0·49; day 10: MD = -1·16; 95%CI = -2·22,-0·10), proportion of patients with substantial improvement (day 5: RR = 1·73; day 10: RR = 1·06) and complete remission (day 5: RR = 2·52; day 10: RR = 2·13). Subjects treated with EPs 7630 missed fewer days at work, used less paracetamol and had an improved sleep quality. No serious adverse reactions to EPs 7630 were reported. The results support the efficacy of EPs 7630 in adults with CC.

Treatment with EPs 7630, a Pelargonium Sidoides Root Extract, Is Effective and Safe in Patients with the Common Cold: Results From a Randomized, Double Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: EPs 7630 was shown to be effective and safe in the treatment of acute respiratory tract infections such as acute bronchitis, acute rhinosinusitis, and acute tonsillopharyngitis. A clinical trial was conducted to investigate its efficacy and safety in the common cold. METHODS: In this multicenter, randomized, double-blind phase 3 clinical trial, 105 adults suffering from common cold symptoms were randomized to a thrice-daily administration of either 1 film-coated tablet containing 40 mg EPs 7630 or matched placebo for a treatment period of 10 days. The primary outcome measure was the sum of differences in the cold intensity score (CIS) from day 1 to day 5, defined as the Sum of the Symptom Intensity Differences (SSID), indicating the degree of symptom improvement in the course of 5 days of treatment. Among the secondary outcomes were clinical cure defined as (a) complete resolution of all cold symptoms (CIS = 0 points) or (b) complete resolution of all or all but one cold symptom, treatment outcome, satisfaction with treatment, and safety parameters. RESULTS: On day 5, the mean (±SD) SSID was significantly higher in the EPs 7630 group compared with the placebo group (12.5 ± 4.4 points versus 8.8 ± 6.8 points). Moreover, 55% of patients in the EPs 7630 group rated the treatment outcome as at least "major improvement" compared with 15% of patients in the placebo group. On day 10, 45% of patients of the EPs 7630 group and 12% of patients of the placebo group had reached 0 points on the CIS (=clinical cure, definition a), whereas all or all but one symptom (clinical cure, definition b) had completely resolved in 74% (EPs 7630) and 25% of patients (placebo), respectively. Satisfaction with treatment was higher in the EPs 7630 than in the placebo group (75% vs 37%) (P values ≤ .0002). During the clinical trial, adverse events occurred in 5 patients (9.4%) in the EPs 7630 and in 7 (13.5%) in the placebo group. All adverse events were of mild intensity, with the exception of 3 events in the placebo group, which were classified as moderate. CONCLUSIONS: Treatment with EPs 7630 was shown to be superior to placebo in patients with the common cold indicating faster reduction of symptom intensity and distinctly more pronounced effects achieved by administration of the investigational drug in patients suffering from the common cold. Results extend previous findings on efficacy, safety, and tolerability of this active substance.

Faster recovery and reduced paracetamol use - a meta-analysis of EPs 7630 in children with acute respiratory tract infections.

OBJECTIVE: Fever is a very common adaptive immune response in acute respiratory tract disorders during infancy. Antipyretic / analgesic drugs such as paracetamol (acetaminophen) are widely used to improve the comfort of the child but may cause medically unneeded antipyresis and rare but potentially serious side effects. We assess whether treatment with Pelargonium sidoides extract EPs 7630 reduces the administration of paracetamol in children with acute tonsillopharyngitis (ATP) or acute bronchitis (AB). DESIGN: Meta-analysis of randomised, placebo-controlled clinical trials. METHODS: We searched clinical trial registries (ISRCTN, ClinicalTrials.gov ) and medical literature (MEDLINE, EMBASE), for randomised, placebo-controlled trials investigating the administration of EPs 7630 to children with ATP or AB and reporting the co-administration of paracetamol. Based on the individual participant data of the eligible trials, study populations were characterized according to sex and age, and meta-analyses were performed for cumulative paracetamol use and ability to attend school at treatment end. RESULTS: Six trials including a total of 523 children aged 6-10 years (EPs 7630: 265; placebo: 258) and suffering from non-ß-hemolytic streptococcal ATP (3 trials) or from AB (3 trials) were identified and eligible. Children received EPs 7630 or placebo for 6 (ATP) or 7 days (AB). Compared to placebo, EPs 7630 reduced the cumulative dose of paracetamol in 5 out of the 6 trials, by an average of 244 mg (Hedges' g; - 0.28; 95% confidence interval: [- 0.53; - 0.02]; p < 0.03). At treatment end, 30.2% (EPs 7630) and 74.4% (placebo) of the children were still unable to attend school (risk ratio: 0.43; 95% confidence interval: [0.29; 0.65]; p < 0.001). CONCLUSIONS: In children aged 6-10 years with AB or ATP, EPs 7630 alleviated the symptom burden and accelerated recovery. Although EPs 7630 has no known antipyretic effect, concomitant use of paracetamol was reduced.

EPs 7630 is effective and safe in children under 6 years with acute respiratory tract infections: clinical studies revisited.

OBJECTIVE: Pelargonium sidoides preparation EPs 7630 has been proven safe and effective in acute respiratory tract infections (aRTIs), but data for young children have not been presented separately. This study reviewed clinical studies and presents an overview of known and newly analyzed data from children <6 years. METHODS: MEDLINE and EMBASE were searched for interventional and non-interventional studies which investigated the effects of EPs 7630 in aRTIs and included children <6 years of age. Sub-group analyses for this age range were performed for symptom scales, global efficacy or effectiveness assessments, and safety outcomes. RESULTS: Seven studies with 1067 children <6 years exposed to EPs 7630 were identified. Efficacy of EPs 7630 was significantly superior to placebo in reducing symptom intensity and time until complete recovery in two randomized, double-blind trials in patients with acute bronchitis (AB). Similar symptom time courses were observed in two non-comparative observational studies in AB. One non-comparative, open-label study was identified in acute tonsillopharyngitis (ATP), and one in acute rhinosinusitis (ARS). In both indications, nearly all children showed complete recovery or major symptom improvements during the treatment period, with changes that were similar to those observed in controlled trials investigating older patient populations. The results were supported by an additional observational study including children with various diagnoses of aRTIs. EPs 7630 was safe and well-tolerated. CONCLUSIONS: EPs 7630 is efficacious in children <6 years suffering from AB. The analyses also support the effectiveness of the product in ATP and in ARS. No safety concerns were identified.

Efficacy and Tolerability of High-dose Pelargonium Extract in Patients With the Common Cold.

Context • The common cold (CC) is usually caused by a viral infection. Antibiotics are often prescribed unnecessarily for it, although no evidence exists for any benefit in the CC. Effective alternatives are needed. Objective • The study intended to evaluate the efficacy of 7630, a proprietary extract of Pelargonium sidoides, the active ingredient in umckaloabo, compared with a placebo for the treatment of the CC. Design • This was a prospective, double-blind, parallel-group, placebo-controlled, phase 3 clinical trial (RCT), with an adaptive group-sequential design with 2 parts, both of which were 2-arm trials. The first used a standard dose (SD) of 3 × 30 drops per day of the active medication and the second used a high dose (HD) of 3 × 60 drops per day of the active medication, against 3 × 30 drops per day and 3 × 60 drops per day of a placebo, respectively. Setting • The study took place in 8 outpatient departments affiliated with hospitals. Participants • For the entire study, 207 adults with predefined cold symptoms that had been present for 24 to 48 h prior were included in the study, with 103 participating in the SD part and 104 participating in the HD part. Intervention • In the HD part, as covered in this article, the intervention group received treatment with 3 × 60 drops per day of the active medication and the control group received a placebo (control group), for a maximum period of 10 d. Outcome Measures • The primary outcome measure was the sum of differences in the cold intensity score (CIS) from day 1 to day 3 and from day 1 to day 5, defined as the sum of the symptom intensity differences (SSID). The criteria for the secondary outcome, efficacy, were (1) diverse response criteria according to the total CIS; (2) changes in individual CIS symptoms; (3) changes in further cold-relevant symptoms; (4) ability to work; (5) activity level; (6) general well-being; (7) health-related quality of life-the EuroQol questionnaire with 5 dimensions (EQ-5D), including the visual analogue scale EQ-VAS; (8) time until onset of treatment effect; (9) treatment outcome; and (10) satisfaction with treatment. Results • From baseline to day 5, the mean CIS decreased by 11.2 ± 4.8 points for the 7630 group and 6.3 ± 4.7 points for the control group. The mean SSID was 16.0 ± 7.6 points for the control group (P < .0001). After 10 d, 90.4% of the group receiving the active medication and 21.2% of the control group were clinically cured (P < .0001). In the treatment group, participants' inability to work was significantly lower, with a mean duration of 6.4 ± 1.6 d vs 8.3 ± 2.1 d for the control group (P < .0001), and treatment outcome-complete recovery or major improvement-was significantly better at day 5 for the active treatment group compared with the control group (P < .0001). Mild-to-moderate adverse events-all nonserious-occurred in 15.4% of those receiving active treatment vs in 5.8% for the control group. Conclusions • The active medication is an effective, well tolerated, and safe treatment for the CC. It significantly reduces the severity of symptoms and shortens the duration of the disease.

Dose-finding study of carbamylated monomeric allergoid tablets in grass-allergic rhinoconjunctivitis patients.

AIM: To determine the optimal effective and safe dose of sublingual immunotherapy tablets containing carbamylated monomeric allergoids in patients with grass pollen-induced allergic rhinoconjunctivitis. METHODS: In this prospective, randomized, double-blind, active-controlled, multicenter, Phase II study, four different daily doses were applied preseasonally for 12 weeks. RESULTS: Of 158 randomized adults, 155 subjects (safety population) received 300 units of allergy (UA)/day (n = 36), 600 UA/day (n = 43), 1000 UA/day (n = 39), or 2000 UA/day (n = 37). After treatment, 54.3, 47.6, 59.0 and 51.4% of patients, respectively, ceased to react to the highest allergen concentration in a conjunctival provocation test. Furthermore, the response threshold improved in 70.4, 62.9, 76.7 and 66.7% of patients, respectively. No serious adverse events occurred. CONCLUSION: This study found 1000 UA/day to be the optimal effective and safe dose.

Randomized, investigator-blinded, controlled clinical study with lice shampoo (Licener®) versus dimethicone (Jacutin® Pedicul Fluid) for the treatment of infestations with head lice.

The present clinical trial was conducted to obtain additional data for the safety and efficacy of a head lice shampoo that is free of silicone compared with an anti-head lice product containing dimethicone. Both products act by a physical mode of action. This randomized, investigator-blinded, controlled clinical study was conducted between July and November 2016 in households of two villages (Abou Rawash and Shandalat) in Egypt. Children older than 2 years with an active head lice infestation were treated with either a shampoo-based head lice treatment containing neem extract (Licener®) or dimethicone (Jacutin® Pedicul Fluid) on day 1 and additionally on day 9. Assessment for living lice by combing was conducted before and 1-2 h after treatment and on days 5 and 13. The main objective was to demonstrate a cure rate of the test product of at least 85% after a single application (day 5 and 9). Secondary objectives were to scrutinize patient safety and satisfaction as well as cure rates on day 13 after two treatments and the evaluation of ovicidal and licicidal efficacies of the products. Sixty-one children in the test-group (Licener®) and 58 children in the reference group (Jacutin® Pedicul Fluid) were included in this study. The test product and the reference product were very well tolerated. Both products exceeded the objective of cure rates of over 85% after single treatment (test group 60/60 = 100%; 95% CI = 94.04-100.00%; reference group 54/57 = 94.74%; 95% CI = 85.38-98.90%; p = 0.112; CI by Clopper-Pearson) and after two treatments (test group 58/58 = 100%; 95% CI = 93.84-100.00%; reference group 52/54 = 96.30%; 95% CI = 87.25-99.55%; p = 0.230) with higher cure rates and non-inferiority for the test product. The combined success rate shows significant superiority of the test product against the reference product (test group 58/58 = 100%; 95% CI = 93.84-100.00%; reference group 49/54 = 90.7%; 95% CI = 79.70-96.92%; p = 0.024). The test product showed higher ovicidal efficacy than the reference product. Thus, the present study demonstrates that a single treatment with a head lice product like Licener® can be sufficient to eliminate a head lice infestation.

Comparison of central and local serial CT assessments of metastatic renal cell carcinoma patients in a clinical phase IIB study.

Background Clinical oncological studies attempt to improve precision of data by central radiological assessments. However, it is unclear, to which extent local and central assessments diverge. Purpose To quantify inter-reader variability and the deviation of local from central radiological assessments of computed tomography (CT) scans. Material and Methods This was a sub-study of a randomized clinical phase IIb trial in metastatic renal cell carcinoma (RCC), comparing first-line sorafenib with interferon-alpha-2a (IFN-α-2a). It analyzed agreements of local with central RECIST CT assessments by Cohen's kappa (κ), symmetry tests, deviations in waterfall plots, Bland-Altman plots, and parametric survival analyses. Results The concordance between local and central radiologic review was quantified by κ = 0.53. While local assessment yielded progressive disease (PD) in 18.6%, central assessment classified 22.5% of patient time points as PD exhibiting only a partial overlap with the 18.6% The tumor shrinkage rates in waterfall plots were 68.1% in local and 55.8% in central review (57.8% and 59% by Reader 1 and Reader 2). Bland-Altman plots identified a systematic shift of tumor change rates by -7.5% in local compared to central assessments, that may reflect a systematic tendency of more favorable results in local assessments. The discordance between local and central review was reflected by a time to progression (TTP) hazard ratio (HR) of 1.73 ( P = 0.0003). Conclusion These data suggest that central radiologic review may reduce technical measurement variability in clinical trials, which should be scrutinized in future studies compared to a volumetric reference.

Feasibility and acceptance of exercise recommendations (10,000 steps a day) within routine German health check (Check-Up 35/GOÄ29)-study protocol.

BACKGROUND: Benefits of exercise to prevent non-communicable diseases are well-documented. Limited data exists to promote physical activity in healthy but sedentary and/or overweight people. Brief interventions within routine German health checks may be an effective way to reach these patients. METHODS/DESIGN: The quasi-experimental, multi-center prospective feasibility study is designed for general practices in Cologne (intervention group) and Düsseldorf (control group), up to 20 per region. Eight to 10 inactive and/or overweight patients per practice will be recruited for a total of 300. General practitioners and at least one of their nurses for the intervention group will be trained in motivational interviewing and familiarized with low-threshold recommendations for exercise (activities of daily life (ADL), target of 10,000 steps/day) and additional tools (pedometers, activity diaries). Participants in the control group will only receive general advice (150 min of exercise/week). The primary aims are to evaluate the feasibility of this intervention and to determine whether it is possible to reach a mean increase of 1000 steps/day in the target group within 6 months. Secondary objectives focus on the number of patients who reach a target of 10,000 steps/day and their improvements in quality of life and decrease in body mass index, waist circumference, and blood pressure. DISCUSSION: The study will assess whether it is feasible to run brief interventions within the GP setting can promote an active lifestyle in overweight and/or inactive patients.

Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease: Prospective 5 Years of Follow-Up and Apolipoprotein(a) Characterization.

OBJECTIVE: Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical correlations of apolipoprotein(a) (apo(a)) by analyzing genotypes and phenotypes. APPROACH AND RESULTS: This prospective observational multicenter study included 170 patients with Lp(a)-HLP and progressive cardiovascular disease (48.9 years median age at diagnosis) despite other cardiovascular risk factors, including low-density lipoprotein cholesterol had maximally been treated (mean baseline low-density lipoprotein cholesterol: measured, 2.56 mmol/L [98.9 mg/dL] and corrected, 1.72 mmol/L [66.3 mg/dL]). Patients were prospectively investigated during a 5-year period about annual incidence rates of cardiovascular events. In addition, apo(a) isoforms and polymorphisms at the apo(a) gene (LPA) were characterized. One hundred fifty-four patients (90.6%) completed 5 years of follow-up. Mean Lp(a) concentration before commencing regular LA was 108.1 mg/dL. This was reduced by a single LA treatment by 68.1% on average. Significant decline of the mean annual cardiovascular event rate was observed from 0.58±0.53 2 years before regular LA to 0.11±0.15 thereafter (P<0.0001); 95.3% of patients expressed at least 1 small apo(a) isoform. Small apo(a) isoform (35.2%) carrying phenotypes were not tagged by single-nucleotide polymorphisms rs10455872 or rs3798220. CONCLUSIONS: Results of 5 years of prospective follow-up confirm that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP. Patients clinically selected by progressive cardiovascular disease were characterized by a highly frequent expression of small apo(a) isoforms. Only Lp(a) concentration seemed to comprehensively reflect Lp(a)-associated cardiovascular risk, however.

Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis.

OBJECTIVE: To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). DESIGN: This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. OUTCOME MEASURES: Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. RESULTS: 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. CONCLUSIONS: NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators.

First-line therapy for non-transplant eligible patients with multiple myeloma: direct and adjusted indirect comparison of treatment regimens on the existing market in Germany.

OBJECTIVES: The purpose of this study was to compare approved first-line therapies for patients with multiple myeloma. METHODS: A systematic literature search for phase III randomized controlled trials (RCTs) comparing first-line chemotherapies approved in Germany and recommended by guidelines at the time of study design was conducted. Random-effects meta-analysis (MA) was used for direct and the Bucher method for adjusted indirect treatment comparison. RESULTS: One RCT comparing melphalan and prednisone plus bortezomib (VMP) vs. melphalan and prednisone (MP) and six RCTs comparing MP plus thalidomide (MPT) vs. MP were analysed. For MPT vs. MP, an individual patient data (IPD) MA was used for sensitivity analyses. VMP and MPT were superior to MP regarding efficacy endpoints (VMP vs. MP, overall survival (OS): hazard ratio (HR) 0.70, 95 % confidence interval (CI) 0.57-0.86; progression-free survival (PFS): HR 0.56, 0.39-0.79; complete response (CR), risk-ratio (RR) for non-response: 0.70, 0.65-0.75; MPT vs. MP, OS: HR 0.83, 0.66-1.03; PFS: HR 0.67, 0.56-0.81; CR, RR for non-response 0.92, 0.88-0.95); but had a higher risk of developing any grade 3-4 adverse events (AEs) (VMP vs. MP: RR 1.13, 1.06-1.20; MPT vs. MP: RR 2.06, 1.43-2.98). The indirect comparison of VMP vs. MPT via MP showed a statistically not significant advantage for VMP regarding survival outcomes (OS: HR 0.85, 0.63-1.14; PFS: HR 0.83, 0.56-1.23) and a significant advantage regarding CR (RR for non-response 0.76, 0.70-0.83) and AEs (RR 0.55, 0.38-0.80). Treatment comparisons using results of IPD MA yielded similar effect sizes. CONCLUSIONS: VMP and MPT seem more effective than MP, VMP was superior to MPT regarding response criteria and AEs. Our results may best be confirmed by a head-to-head trial of VMP vs. MPT.