IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines.

BACKGROUND: To further explore clinical trial results indicating increasing doses of botulinum toxin A prolong duration of effect, a 2-stage, phase 2, randomized, double-blind study investigated the duration of effect and safety of incobotulinumtoxinA (INCO; Xeomin®, Bocouture®) doses higher than the US Food and Drug Administration-approved 20 units (U) for glabellar frown lines (GFL). The stage 1 primary efficacy and safety results were reported previously. Here, we report the results of the final analysis (stage 1 and 2), including primary and secondary efficacy and safety endpoints. METHODS: A total of 241 subjects with moderate-to-severe GFL were randomized to receive a single treatment with 20 (N=61), 50 (N=60), 75 (N=61), or 100U (N=59) INCO. The primary efficacy endpoint was duration of ≥ 1-point improvement from baseline assessed by investigator at maximum frown on the Facial Wrinkle Scale. RESULTS: The median duration of effect was 175 days for the 20U group (95% CI 142, 185), 185 days for the 50U group (95% CI 182, 205), 210 days for the 75U group (95% CI 182, 217), and 215 days for the 100U group (95% CI 183, 237). The incidence of treatment-related adverse events was low across all doses and there were no treatment-related serious adverse events. CONCLUSIONS: These results demonstrate that all INCO doses were well tolerated, consistent with the known safety profile of 20U, and increasing dose prolongs the duration of effect for GFL. J Drugs Dermatol. 2021;20(10):1052-1060. doi:10.36849/JDD.6377THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines.

BACKGROUND: Recently reported clinical data provides evidence that increasing the dose of botulinum toxin A increases the duration of efficacy. A 2-stage Phase 2, randomized, double-blind study investigated the duration of effect and safety of IncobotulinumtoxinA (INCO; Xeomin®, Bocouture®; Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany) at doses higher than the approved 20 units (U) for glabellar frown lines (GFL). Primary safety and efficacy endpoints of Stage 1 are reported here. METHODS: 151 subjects with moderate-to-severe GFL were randomized 1:2:2 to receive a single treatment with 20U, 50U, or 75U INCO. The primary efficacy endpoint was median duration of at least 1-point improvement from baseline as assessed by investigator at maximum frown on the Facial Wrinkle Scale. RESULTS: The median duration of effect was 185 days for the 50U dose group (95% CI:[182, 205]) and 210 days for the 75U dose group (95% CI:[182, 217]). Duration of effect was significantly longer for 75U vs 50U (P=0.0400) and 20U (P=0.0166) despite the study not being powered for confirmatory statistical significance testing between the dose groups. Duration of effect was also longer for 50U vs 20U, however; statistical significance was not reached (P=0.4349). The incidence of treatment-related adverse events was low across all doses (20U:2[6.7%], 50U:6[10.0%] and 75U:8[13.1%]). CONCLUSIONS: These results demonstrate a dose effect of at least 6 months duration with higher doses in the majority of GFL subjects. All doses were well tolerated and safety was consistent with the known safety profile of 20U INCO for GFL. J Drugs Dermatol. 2020;19(10):985-991. doi:10.36849/JDD.2020.5454.

Oncologists' experiences of discussing complementary and alternative treatment options with their cancer patients. A qualitative analysis.

PURPOSE: The rising use of complementary and alternative medicine (CAM) means oncologists are increasingly asked by patients to discuss CAM treatment options. However, no formal training or established standards are available on the subject. The aim of this paper was to investigate real-world discussions of CAM treatments. In particular, we wanted to learn about the values, norms and defining features that characterise oncologist-patient discussions on CAM. METHODS: Semi-standardised interviews with 17 oncologists were analysed using interpretation pattern analysis combined with thematic analysis. RESULTS: Advice on CAM is seen by oncologists as an important service they provide to their patients, even though their knowledge of the subject is often limited. Many interviewees mentioned an apparent lack of scientific proof, especially when their aim was to warn patients against the use of CAM. Discussions on CAM tend to reflect the idea that CAM belongs 'to another world', and judging by the interviews with oncologists, this notion appears to be shared by patients and oncologists alike. CONCLUSIONS: Oncologists require reliable information on CAM and would profit from training in the communication of CAM treatment options to patients. Knowing scientific data on CAM would also lower barriers stemming from the view that CAM belongs 'to another world'. Under- and postgraduate education programmes should include training on how to respond to requests addressing possible CAM options.

A Multicenter Noninferiority Study Comparing Safety and Effectiveness of Hyaluronic Acid Fillers for Correction of Nasolabial Folds in Chinese Subjects.

Hyaluronic acid fillers are the preferred choice for minimally invasive facial volume restoration. In this study, a split-face design was used to compare the effectiveness and safety results of Belotero Balance Lidocaine (BEL) and Restylane (RES, control) to investigate whether BEL is noninferior compared with RES in nasolabial fold (NLF) correction. Methods: This was a prospective, controlled clinical study in Chinese subjects. Subjects with symmetrical moderate NLFs according to the Wrinkle Severity Rating Scale were randomized to receive BEL in one NLF and RES in the other. The primary objective was to investigate whether BEL is noninferior compared with RES after being injected mid-dermally in moderate NLFs after 6 months. Secondary objectives included responses at other visits and pain sensation. Treatment-emergent adverse events (TEAEs) were assessed. Results: A total of 220 subjects were enrolled. The Wrinkle Severity Rating Scale response rates at month 6 were 62.9% for BEL versus 64.9% for RES, demonstrating noninferiority. The secondary endpoints supported this. Significantly reduced pain scores were observed for BEL versus RES. For both products, injection site nodule and bruising were the most frequent treatment-emergent adverse events at the injection site. All treatment-related treatment-emergent adverse events were mild. Conclusions: The study showed that BEL is effective and well tolerated for correction of moderate NLFs in Chinese subjects. Noninferiority of BEL was demonstrated compared with RES, and regardless of applied pain treatment, a further reduction in injection pain was observed in BEL.

IncobotulinumtoxinA for Glabellar Frown Lines in Chinese Subjects: A Randomized, Double-blind, Active-Controlled Phase-3 Study.

This study evaluated the efficacy and safety of IncobotulinumtoxinA 20 U for treatment of glabellar frown lines in Chinese subjects. Methods: This was a prospective, randomized, double-blind, active-controlled, phase-3 study conducted in China. Subjects with moderate to severe glabellar frown lines at maximum frown were randomized to receive IncobotulinumtoxinA (N = 336) or OnabotulinumtoxinA (N = 167). Results: For the primary efficacy endpoint at day 30, response rates at maximum frown (score "none" or "mild") on the Merz Aesthetic Scales Glabella Lines - Dynamic were comparable between IncobotulinumtoxinA (92.5%) and OnabotulinumtoxinA (95.1%) per investigator's live rating. Noninferiority of IncobotulinumtoxinA versus OnabotulinumtoxinA was successfully demonstrated, as the two-sided 95% confidence interval of -0.97% to 0.43% for the difference in Merz Aesthetic Scales-based response rates (-0.27%) lay completely above the predefined noninferiority margin of -15%. For the secondary efficacy endpoints assessed at day 30, Merz Aesthetic Scales-based response rates (score "none" or "mild") at maximum frown were similarly comparable between both groups per subject (>85%) and independent review panel (>96%) rating. Per Global Impression of Change Scales, greater than 80% of subjects and greater than 90% of investigators in both groups rated treatment results as at least "much improved" at day 30 compared with baseline. Safety profiles were consistent between groups; IncobotulinumtoxinA was well tolerated, and no new safety concerns were identified in Chinese subjects. Conclusion: IncobotulinumtoxinA 20 U is safe and effective for treatment of moderate to severe glabellar frown lines at maximum frown in Chinese subjects and is noninferior to OnabotulinumtoxinA 20 U.

Long-term Safety and Effectiveness of Hyaluronic Acid Fillers Correcting Nasolabial Folds in Chinese Patients.

Background: Soft-tissue fillers, specifically hyaluronic acid fillers, can reduce many signs of aging by treating the associated loss of subcutaneous fat and midfacial contour deficiencies. The objective of this study was to investigate whether the effectiveness and safety of Belotero Volume Lidocaine (BVL) compared with Restylane (RES, control) is noninferior in the treatment of severe nasolabial folds (NLFs) in Chinese patients. Methods: This was a prospective, randomized, controlled, split-face clinical study. Overall, 220 Chinese patients of both sexes with symmetrical NLFs of severe intensity (grade 4) on the Wrinkle Severity Rating Scale (WSRS) were treated with both fillers. Treatment outcomes were assessed by the WSRS, and other scales, at multiple time points up to 18 months postinjection. The co-primary effectiveness outcomes were based on the blinded evaluator ratings of NLFs according to the WSRS scale after 6 and 12 months. Adverse events were assessed during the whole study and patients' pain sensation at three time points after injection. Results: Noninferiority of BVL versus control based on the WSRS was demonstrated at month 6 and month 12. Response rates were slightly higher for BVL than control at all time points, and BVL had a sustained effect until month 18. Pain sensation scores were significantly lower for BVL compared with control. The incidence rates of treatment-related AEs were low and very similar for both treatments. Conclusions: This study demonstrates that BVL is a safe, long-lasting, and effective treatment to correct severe NLFs in Chinese patients while being noninferior to the control device.

Smokers' expectations toward the engagement of their general practitioner in discussing lifestyle behaviors.

Barriers associated with the sparse engagement of general practitioners (GPs) in lifestyle counseling are well investigated. The aim of the study was (a) to explore to what extent smoking patients want to discuss about lifestyle; and (b) to investigate whether patient characteristics might influence the expectations to discuss smoking, alcohol, nutrition, or physical activity. Data were collected during the 24-month follow-up of a smoking cessation efficacy study. Participants were 1,029 patients. More than half of the patients expected that their GP should address smoking, alcohol, and nutrition in a proactive way. Patients who preferred to address the issue of smoking, alcohol, nutrition, and physical activity only for themselves were more likely to be female. Older patients were more likely to reject a discussion concerning these three lifestyle habits in general. Regarding smoking and alcohol, higher age predicted a lower readiness to use an extra appointment. There are some reservations among several patient groups to accept a GP-initiated offer for a discussion about lifestyle habits. Therefore, the improvement of skills and a high sensitivity to address lifestyle habits conveniently can have a large effect on public health.

Residual Renal Function and Effect of Low-Sodium Solution on Blood Pressure in Peritoneal Dialysis Patients.

Background:Residual renal function (RRF) affects sodium and fluid balance. The aim of this analysis was to examine the impact of RRF on the effect of a sodium-reduced peritoneal dialysis fluid (PDF) on blood pressure (BP).Methods:This is a post-hoc analysis of a prospective, randomized, controlled double-blind clinical trial with 82 patients on continuous ambulatory PD (CAPD) treated with a low-sodium (125 mmol/L Na) or a standard-sodium (134 mmol/L Na) PDF. Subgroups according to glomerular filtration rate (GFR) at baseline (≤ / > 6 mL/min/1.73 m2) were analyzed for BP and antihypertensive medication.Results:In the low-GFR group on low-sodium PDF (N = 26), systolic BP was reduced from 152 ± 24 mmHg at baseline to 137 ± 21 mmHg at week 12, diastolic BP from 90 ± 16 mmHg to 83 ± 11 mmHg. In the low-GFR group on standard-sodium PDF and in the high-GFR group on both PDF types, only minor changes were observed. For the low-GFR subgroup, the confounder-adjusted mean study group difference in systolic BP at week 12 between low-sodium and standard-sodium PDF was -16.9 (95% confidence interval [CI] -27.2 to -6.6) mmHg, for diastolic BP, it was -7.0 (95% CI -12.6 to -1.4) mmHg. In both GFR subgroups, more patients had a reduced daily dose of antihypertensive medication and fewer patients an increased daily dose in the low-sodium compared with the standard-sodium group at week 12.Conclusions:The reduction of BP with a sodium-reduced PDF seems to be more effective in patients with no or low RRF than in patients with residual capacity of renal sodium and fluid control.

Effects of high-volume online mixed-hemodiafiltration on anemia management in dialysis patients.

BACKGROUND: Anemia is a major comorbidity of patients with end-stage renal disease and poses an enormous economic burden to health-care systems. High dose erythropoiesis-stimulating agents (ESAs) have been associated with unfavorable clinical outcomes. We explored whether mixed-dilution hemodiafiltration (Mixed-HDF), based on its innovative substitution modality, may improve anemia outcomes compared to the traditional post-dilution hemodiafiltration (Post-HDF). METHODS: We included 174 adult prevalent dialysis patients (87 on Mixed-HDF, 87 on Post-HDF) treated in 24 NephroCare dialysis centers between January 2010 and August 2016 into this retrospective cohort study. All patients were dialyzed three times per week and had fistula/graft as vascular access. Patients were matched at baseline and followed over a one-year period. The courses of hemoglobin levels (Hb) and monthly ESA consumption were compared between the two groups with linear mixed models. RESULTS: Mean baseline Hb was 11.9±1.3 and 11.8±1.1g/dl in patients on Mixed- and Post-HDF, respectively. While Hb remained stable in patients on Mixed-HDF, it decreased slightly in patients on Post-HDF (at month 12: 11.8±1.2 vs 11.1±1.2g/dl). This tendency was confirmed by our linear mixed model (p = 0.0514 for treatment x time interaction). Baseline median ESA consumption was 6000 [Q1:0;Q3:16000] IU/4 weeks in both groups. Throughout the observation period ESA doses tended to be lower in the Mixed-HDF group (4000 [Q1:0;Q3:16000] vs 8000 [Q1:0;Q3:20000] IU/4 weeks at month 12; p = 0.0791 for treatment x time interaction). Sensitivity analyses, adjusting for differences not covered by matching at baseline, strengthened our results (Hb: p = 0.0124; ESA: p = 0.0687). CONCLUSIONS: Results of our explorative study suggest that patients on Mixed-HDF may have clinical benefits in terms of anemia management. This may also have a beneficial economic impact. Future studies are needed to confirm our hypothesis-generating results and to provide additional evidence on the potential beneficial effects of Mixed-HDF.

Information and Training Needs Regarding Complementary and Alternative Medicine: A Cross-sectional Study of Cancer Care Providers in Germany.

BACKGROUND: Among cancer care providers (CCPs), lack of knowledge constitutes an important barrier to the discussion of complementary and alternative medicine (CAM) use with patients. This study assessed CCPs' needs and preferences regarding CAM information and training (I&T). METHODS: An online survey was completed by 209 general practitioners, 437 medical specialists, 159 oncology nurses and medical assistants, and 244 psychologists and social workers engaged in cancer care. Latent class analysis (LCA) was used to identify subgroups of individuals with distinct preference patterns regarding I&T content. RESULTS: CCPs prefer CAM I&T to be provided as lectures, information platforms on the internet, workshops, and e-mail newsletters. Concerning subject matters, many CCPs considered CAM therapy options for the treatment of a variety of cancer disease- and therapy-related symptoms to be very important (75%-72% of the sample); the same applies to an "overview of different CAM therapies" (74%). LCA identified 5 latent classes (LCs) of CCPs. All of them attached considerable importance to "medical indication," "potential side effects," and "tips for usage." LCs differed, however, in terms of overall importance ratings, the perceived importance of "patients' reasons" for using specific CAM therapies, "case examples," and "scientific evidence." Notably, the 5 LCs were clearly present in all 4 occupational groups. CONCLUSIONS: CAM I&T should provide CCPs with an overview of different CAM therapies and show how CAM might help in treating symptoms cancer patients frequently demonstrate (eg, fatigue). Moreover, I&T programs should be flexible and take into account that individual information needs vary even within the same occupational group.

[WINHO quality indicators for outpatient oncology care in Germany]. / WINHO-Qualitätsindikatoren für die ambulante onkologische Versorgung in Deutschland.

The aim of the WINHO indicators project is to describe and enhance the quality of outpatient oncology care in Germany with indicators. This paper deals with the development of a set of evidence- and consensus-based meaningful indicators to assess the quality of outpatient oncology care in Germany. These indicators are intended to be applied in assessments of quality of patient care in oncology practices, in quality reports and in peer-to-peer benchmarking. A set of 272 already existing indicators was identified through internet and literature searches. After redundancy reduction and addition of newly developed indicators for areas of ambulatory oncology care that were not yet covered, a preliminary set of 67 indicators was established. The further development of the indicator set was based on a modified version of the two-step RAND/UCLA expert evaluation method, which has been internationally established for developing quality indicator sets. The indicators were modified after the first round of ratings. After completing and assessing the second round of ratings, a set of 46 homogeneously positively rated quality indicators is now available for outpatient oncology care in Germany.

Adoption, reach and effectiveness of computer-based, practitioner delivered and combined smoking interventions in general medical practices: a three-arm cluster randomized trial.

BACKGROUND: Brief advice for smoking patients has not been sufficiently integrated in routine care. Computer-based interventions emerged as a time saving option that might help to exhaust the potential population impact of the general practice setting. METHOD: 151 practices were randomly assigned to one of three intervention programs consisting in the delivery of: (1) brief advice by the practitioner; (2) individually tailored computer-generated letters; or (3) a combination of both interventions. We assessed three dimensions of population impact: (1) adoption, i.e., the rate of practices participating in the program; (2) reach, measured as the number of interventions provided within 7 months; (3) effectiveness, measured as smoking abstinence at 12-months follow-up. RESULTS: Among the practices, 70% adopted the program with no significant differences across study groups. Treatment was provided to 3086 adult smokers. Negative binomial regression analysis revealed that the number of interventions provided was higher in practices allocated to the tailored letter and combination intervention groups by 215% (p<.01) and 127% (p=.02), respectively, compared to the brief advice intervention group. Among the patients who received the combination of both intervention, the odds of point abstinence from smoking was increased by 65% (p=.02) and 32% (p=.01) compared to the brief advice and tailored letters intervention respectively. Comparing the number of abstinent patients at follow-up revealed that the tailored letter and combination interventions were superior to the brief advice intervention. CONCLUSIONS: Computer-based interventions alone or in addition to conventional practitioner-delivered advice can foster the participation of general medical practices in tobacco control.

Workplace smoking restrictions: smoking behavior and the intention to change among continuing smokers.

OBJECTIVES: In this study, the association between three levels of workplace smoking restrictions and smoking behavior and variables related to the intention to quit among continuing smokers was examined. METHODS: Adult smokers were recruited from consecutive patients attending a random sample of 34 general medical practices from a pre-defined, north-eastern German region. Self-reported data were gathered in the waiting room by questionnaire. Cross-sectional data of 1,012 employees were analyzed using ordered logistic regression analyses. RESULTS: Among the sample, 12% reported a smoke-free workplace, 51% had partial, and 37% no smoking restrictions. Daily cigarette consumption was lower when there were higher levels of restriction. No association was found between smoking restrictions and previous attempts to quit, nicotine dependence, or indicators of adjusted inhalation to compensate for the lower number of cigarettes (e.g. puffs per cigarette, darker coloring of filter). Smoking restrictions were positively associated with single psychological measures related to the intention to quit. CONCLUSION: Employees who continue to smoke may benefit from workplace smoking restrictions in terms of reduced, active smoke exposure and psychological effects increasing their readiness to quit.

Effects of practitioner-delivered brief counseling and computer-generated tailored letters on cigarettes per day among smokers who do not quit--a quasi-randomized controlled trial.

BACKGROUND: It is still unclear how brief counseling for smoking cessation, combined with proactive recruitment of participants, impacts on those smokers not reaching the primary treatment goal of tobacco abstinence. Thus, within a quasi-randomized controlled trial, we examined the effects of (1) practitioner-delivered brief advice and (2) computer-generated tailored letters on cigarettes per day (CPD) among participants not succeeding in quitting. METHODS: A total of 34 general practices (participation rate 87%) were randomly selected in a German region. Within these practices, 1499 daily smoking patients aged 18-70 years (participation rate 80%) agreed to participate in a smoking cessation intervention trial. Allocation to study condition was based on time of practice attendance. Latent growth analyses were performed on the subsample of 1334 (89%) smokers who did not reach 6-month prolonged abstinence within the 2-year follow-up period. CPD was assessed at baseline and at 6-, 12-, 18-, and 24-month follow-ups. RESULTS: Both interventions led to small but significant reductions in CPD, and they did not differ in efficacy. Treatment effects occurred within the first 6 months and could be sustained by the continuing smokers until the 24-month follow-up. CONCLUSIONS: Present results complement earlier findings of increased abstinence rates in the total sample. It can be concluded that, even if applied to unselected samples of smokers, from which only a minority initially intends to change, both brief counseling strategies are able to significantly decrease tobacco consumption. They hence appear to provide a means to reducing tobacco-related disease among general medical practice patients.