Cryolipolysis of the Arms and Inner Thighs Shows Similar Treatment Outcomes in Chinese Individuals Compared to White Individuals Treated in a Prior Study: The XinCOOL Study.

Background: Studies of predominantly White participants show that cryolipolysis reduces subcutaneous fat in the arms and inner thighs, but none have specifically tested for similar outcomes in participants of Chinese descent. Objectives: This study assessed the safety and effectiveness of cryolipolysis treatment for noninvasive subcutaneous fat reduction of arms and inner thighs in participants of Chinese descent to assess equivalence to results seen in a prior study of White participants. Methods: Replicating a similar study design, participants of first- or second-generation Chinese descent underwent cryolipolysis treatment of arms and/or inner thighs. Effectiveness was assessed using pretreatment and posttreatment photographic review by blinded, independent experts, investigator-assessed caliper measurements, and participant satisfaction 12 weeks posttreatment. Safety was assessed throughout. Results: Among 50 enrolled participants, 48 completed the study. The majority of participants (97.9%) were female, with a mean age of 36.0 years and mean BMI of 24.16 kg/m2 (range 19.3-29.9 kg/m2). Overall, 76.4% and 70.0% of pretreatment photographs of arms and pairs of inner thighs, respectively, were correctly identified by at least 2 of 3 reviewers. The mean reduction from baseline in caliper-measured fat thickness was 6.5 mm for arms and 6.6 mm for inner thighs, and the majority of participants (>60%) were satisfied with the treatment. No adverse events were reported. Conclusions: Cryolipolysis is a well-tolerated, effective means of noninvasive fat reduction of arms and inner thighs in participants of Chinese descent. The results from this study show similar effectiveness and safety in Chinese participants compared with White participants treated in a prior study.

OnabotulinumtoxinA Reduces Health Resource Utilization in Chronic Migraine: PREDICT Study.

BACKGROUND: PREDICT was a Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA treatment for chronic migraine (CM). We descriptively assess health resource utilization, work productivity, and acute medication use. METHODS: OnabotulinumtoxinA (155-195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Participants completed a 4-item health resource utilization questionnaire and 6-item Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Acute medication use was recorded in daily headache diaries. Treatment-emergent adverse events were recorded throughout the study. RESULTS: A total of 197 participants were enrolled, and 184 received ≥1 treatment with onabotulinumtoxinA and were included in the analysis. Between baseline and the final visit, there were decreases in the percentage of participants who reported headache-related healthcare professional visit(s) (96.2% to 76.8%) and those who received headache-related diagnostic testing (37.5% to 9.9%). Reductions from baseline were also observed in the mean number of headache-related visits to an emergency room/urgent care clinic (2.5 to 1.4) and median headache-related hospital admissions (4.0 to 1.0). OnabotulinumtoxinA improved work productivity and reduced the mean (standard deviation) number of hours missed from work over a 7-day period (6.1 [9.7] to 3.0 [6.8]). Mean (standard deviation) acute medication use decreased from baseline (15.2 [7.6] to 9.1 [6.5] days). No new safety signals were identified. CONCLUSIONS: Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA treatment for CM in the Canadian population reduces health resource utilization and acute medication use and improves workplace productivity, supporting the long-term benefits of using onabotulinumtoxinA for CM.

OnabotulinumtoxinA Improves Quality of Life in Chronic Migraine: The PREDICT Study.

BACKGROUND: The PREDICT study assessed real-world, long-term health-related quality of life in adults with chronic migraine (CM) receiving onabotulinumtoxinA. METHODS: Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA for CM. OnabotulinumtoxinA (155-195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Primary endpoint: mean change in Migraine-Specific Quality of Life Questionnaire (MSQ) at treatment 4 (Tx4) versus baseline. Secondary endpoints: mean change in MSQ at final visit versus baseline, and headache days. RESULTS: 184 participants (average age 45 years; 84.8% female; 94.6% Caucasian) received ≥1 onabotulinumtoxinA treatment; 150 participants completed 4 treatments (1 year) and 123 completed all 7 treatment cycles (2 years). Mean (SD) onabotulinumtoxinA dose per treatment cycle was 171 (18) U and treatment interval was 13.2 (1.8) weeks. Baseline mean (SD) 20.9 (6.7) headache days/month decreased (Tx1: -3.5 [6.3]; Tx4: -6.5 [6.6]; p < 0.0001 versus baseline). Mean (SD) increased from baseline in MSQ at Tx4 (restrictive: 21.5 [24.3], preventive: 19.5 [24.7], emotional: 22.9 [32.9]) and the final visit (restrictive: 21.3 [23.0], preventive: 19.2 [23.7], emotional: 27.4 [30.7]), exceeding minimal important differences (all p < 0.0001). Seventy-seven (41.8%) participants reported 168 treatment-emergent adverse events (TEAEs); 38 TEAEs (12.0%) were considered treatment-related. Four (2.2%) participants reported six serious TEAEs; none were considered treatment-related. No new safety signals were identified. CONCLUSIONS: Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA for CM in Canada improved MSQ scores and reduced headache frequency and severity, adding to the body of evidence on the long-term safety and effectiveness of onabotulinumtoxinA for CM.

Improvement in Quality of Life with OnabotulinumtoxinA for Cervical Dystonia: POSTURe.

INTRODUCTION: Symptoms of cervical dystonia (CD) can vary in severity and cause significant pain. OnabotulinumtoxinA is an approved treatment for CD. This study assessed health-related quality of life (HRQoL) in patients with CD who received multiple onabotulinumtoxinA treatments. METHODS: This prospective, observational standard-of-care study was conducted at multiple neurology centers in Québec, Canada. Patients reported the health impact of CD using the Cervical Dystonia Impact Profile (CDIP)-58, before and after up to eight onabotulinumtoxinA treatments. Other measures included the Cervical Dystonia Severity Rating Scale by physician, employment status using the Work Productivity Questionnaire and pain using the Pain Numeric Rating Scale (PNRS). Adverse events (AEs) were recorded. RESULTS: Sixty-two patients were enrolled (safety population, n = 61; modified efficacy population, n = 58). Participants were mostly females who were employed; most (79.3%) had torticollis. In all, 21/62 patients (33.9%) discontinued the study. At the final visit, there was a statistically significant (p < 0.001) improvement in all eight CDIP-58 subscales, particularly head and neck symptoms (-31.0) and psychosocial functioning (-28.2). Employment increased from baseline (55%) to the end of the study (64%), and there was improvement in work productivity. There was a significant (p < 0.0001) reduction in pain measured by the PNRS, from -0.5 post-treatment 1 to -2.4 at end of study. AEs (neck pain, muscular weakness, dysphagia, nausea) were consistent with onabotulinumtoxinA use. CONCLUSION: These real-world data indicate that after repeated, long-term use, onabotulinumtoxinA continues to be a safe and effective treatment for CD, improving HRQoL and work productivity.

Long-term Safety and Dosing of OnabotulinumtoxinA: A Prospective, Observational Study.

BACKGROUND: Although therapeutic treatments are intended to help alleviate symptoms associated with disease, safety must be carefully considered and monitored to confirm continued positive benefit/risk balance. The objective of MOBILITY was to study the long-term safety of onabotulinumtoxinA for treatment of various therapeutic indications. METHODS: A prospective, multicenter, observational, Phase IV Canadian study in patients treated with onabotulinumtoxinA for a therapeutic indication. Dosing was determined by the participating physician. Adverse events (AEs) were recorded throughout the study. RESULTS: Patients (n = 1372) with adult focal spasticity, blepharospasm, cerebral palsy, cervical dystonia, hemifacial spasm, hyperhidrosis, or "other" diagnoses were enrolled into the safety cohort. Eighty-three patients (6%) reported 209 AEs; 44 AEs in 24 patients (2%) were considered treatment-related AEs. Seventy-two serious AEs were reported by 38 patients (3%); 10 serious AEs in 5 patients (0.4%) were considered treatment related. Most commonly reported treatment-related AEs were muscular weakness (n = 7/44) and dysphagia (n = 6/44). CONCLUSIONS: In patients with follow-up for up to six treatments with onabotulinumtoxinA, treatment-related AEs were reported in <2% of the safety population over the course of nearly 5 years. Our findings from MOBILITY provide further evidence that onabotulinumtoxinA treatment is safe for long-term use across a variety of therapeutic indications.

Dosage et sécurité à long terme de l'onabotulinumtoxinA : une étude prospective et observationnelle. Contexte : Bien que les traitements thérapeutiques soient destinés à soulager les symptômes associés à une maladie, il importe d'examiner avec grand soin leur sécurité et d'en assurer un suivi afin de maintenir un rapport bénéfice/risque qui soit positif. L'objectif de MOBILITY a donc été d'étudier la sécurité à long terme de l'onabotulinumtoxinA dans le traitement de plusieurs indications thérapeutiques. Méthodes : Nous avons ainsi fait appel à une étude canadienne prospective et observationnelle menée dans plusieurs centres de santé. Dans cette étude de phase IV, des patients ont été traités avec l'onabotulinumtoxinA en vertu d'indications thérapeutiques. Ce sont des médecins participants qui en avaient déterminé le dosage. De plus, tout événement indésirable a été noté en cours d'étude. Résultats : Au total 1372 patients ont été inclus dans cette cohorte (n = 1372). Ces patients étaient atteints des troubles suivants : spasticité focale chez l'adulte, blépharospasme, infirmité motrice cérébrale, dystonie cervicale, spasmes hémifaciaux, hyperhidrose, etc. On a signalé chez 83 patients, soit 6 % d'entre eux, des événements indésirables. On a aussi estimé que 44 événements indésirables ayant affecté 24 patients (2 %) étaient reliés au traitement proprement dit. Ajoutons que 38 patients (3 %) ont signalé avoir été victimes d'événements indésirables et que 10 événements indésirables ont été reliés au traitement chez 5 patients (0,4 %). Enfin, les événements indésirables les plus communément signalés ont été la faiblesse musculaire (n = 7/44) et la dysphagie (n = 6/44). Conclusions : Dans le cas de patients ayant bénéficié de six traitements ou moins avec l'onabotulinumtoxinA, des événements indésirables ont été signalés chez < 2 % d'entre eux au cours des presque cinq prochaines années. Tirés de MOBILITY, nos résultats apportent une preuve additionnelle que les traitements avec l'onabotulinumtoxinA sont à long terme sécuritaires dans le cas de nombreuses indications thérapeutiques.

Reoperation Rate After Primary Augmentation With Smooth, Textured, High Fill, Cohesive, Round Breast Implants (RANBI-I Study).

BACKGROUND: Reoperation after primary breast augmentation remains an important clinical issue. OBJECTIVE: The authors sought to evaluate incidence and causes of reoperation in patients who underwent primary augmentation. METHODS: This retrospective, noninterventional study conducted at 16 Canadian sites reviewed medical records and patient-completed questionnaires of women who underwent primary breast augmentation with smooth or textured Natrelle Inspira implants containing TruForm 1 or TruForm 2 gel. Patients were aged ≥22 years, received implants via inframammary fold incision, and returned for follow-up at 2 to 4 years. RESULTS: A total of 319 women received Inspira implants (smooth TruForm 2, n = 205; textured TruForm 2, n = 99; smooth or textured TruForm 1, n = 15). At follow-up, 30 women (9.4%) had undergone reoperation, including 19 (9.3%) in the smooth TruForm 2 subgroup and 9 (9.1%) in the textured TruForm 2 subgroup. The mean time to reoperation was 1.2 years; the risk rate for reoperation was 9.9% at 3 years. The most common reasons for reoperation were implant malposition (36.7%), capsular contracture (33.3%), and the patient's request for a change in implant size or style (20.0%). Most women were very or somewhat satisfied with the initial surgery (89.3% overall; 90.7% smooth TruForm 2; 86.9% textured TruForm 2). Thirty-four women (10.7%) reported adverse events, including 20 (9.8%) in the smooth TruForm 2 subgroup and 14 (14.1%) in the textured TruForm 2 subgroup. CONCLUSIONS: This analysis suggests that Natrelle Inspira TruForm 2 implants are safe when used in primary breast augmentation, resulting in low reoperation rates that are consistent with those for other breast implants.

Real-World, Long-Term Quality of Life Following Therapeutic OnabotulinumtoxinA Treatment.

BACKGROUND: OnabotulinumtoxinA is an efficacious treatment option for patients with various conditions. Although studies have reported on the efficacy of onabotulinumtoxinA, quality of life (QoL) data are limited. This study evaluated QoL in patients treated with onabotulinumtoxinA across various therapeutic indications. METHODS: MDs on BOTOX Utility (MOBILITY) was a prospective, multicenter, observational Canadian study in patients initiating (naïve) or receiving ongoing (maintenance) onabotulinumtoxinA treatment. Health utility was the primary outcome measure and was obtained from the Short Form-12 Health Survey using the Short Form-6D at baseline, week 4 posttreatment, and up to five subsequent treatment visits. The safety cohort included patients who received ≥1 onabotulinumtoxinA treatment. RESULTS: The efficacy cohort included 1062 patients; the majority were Caucasian, female, and on maintenance onabotulinumtoxinA treatment. Adult focal spasticity (n=398), blepharospasm (n=81), cerebral palsy (n=22), cervical dystonia (n=234), hemifacial spasm (n=116), and hyperhidrosis (n=211) patients were included. Baseline health utility was generally higher in maintenance versus naïve patients; however, naïve patients showed the greatest improvements over time. Health utility was generally maintained or trended toward improvement across all cohorts, including maintenance patients who had been treated for up to 22 years before study entry. Eighteen of 1222 patients (2%) in the safety cohort reported 28 treatment-related adverse events; eight were serious in four patients. CONCLUSION: MOBILITY is the largest prospective study to date to provide QoL data over a variety of therapeutic indications following treatment with onabotulinumtoxinA. Although the QoL burden varies by disease, data suggest that long-term treatment may help improve or maintain QoL over time.

Efficacy and Safety of OnabotulinumtoxinA Treatment of Forehead Lines: A Multicenter, Randomized, Dose-Ranging Controlled Trial.

BACKGROUND: Various onabotulinumtoxinA doses are effective in treating forehead lines (FHL), with a trend toward lower doses. OBJECTIVE: To evaluate efficacy and safety of onabotulinumtoxinA dose-ranging treatment of FHL when the frontalis area and glabellar complex are treated together. MATERIALS AND METHODS: Adults with moderate-to-severe FHL received onabotulinumtoxinA 40 U (FHL, 20 U; glabellar lines [GL], 20 U), 30 U (FHL, 10 U; GL, 20 U), or placebo. Response was assessed at weeks 1, 2, day 30, and monthly to day 180. Coprimary efficacy end points were investigator- and subject-assessed Facial Wrinkle Scale scores of none or mild (day 30). Patient-reported outcomes, onset/duration of effect, and adverse events (AEs) were evaluated. RESULTS: Responder rates (investigator/subject, respectively) were 40-U group, 91.2%/89.5%; 30-U group, 86.4%/81.4%; placebo, 1.7%/5.1%. OnabotulinumtoxinA resulted in significantly greater responder rates than placebo (p < .001). Adverse events were mild to moderate and similar between groups (most common AEs: nasopharyngitis [4.6%] and headache [4.0%]). CONCLUSION: Treatment of FHL with onabotulinumtoxinA 40 and 30 U (in frontalis and glabellar complex muscles) was tolerable, effective, and sustained. Both doses significantly reduced FHL severity; however, the 40-U dose demonstrated a trend toward greater sustained benefit and longer duration of effect versus the 30-U dose, with similar AE rates.

An observational study of bimatoprost 0.01% in patients on prior intraocular pressure-lowering therapy: the Canadian Lumigan(®) RC Early Analysis Review (CLEAR) trial.

PURPOSE: To evaluate the ocular hyperemia and intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.01% in subjects with elevated IOP due to primary open-angle glaucoma (POAG) or ocular hypertension (OHT) in a real-world clinical setting. SUBJECTS AND METHODS: This open-label, 12-week, observational study was conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline, week 6, and week 12 using a standardized photographic 5-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes the subgroup of 268 subjects who had been previously treated with latanoprost 0.005%, bimatoprost 0.03%, travoprost 0.004%, and travoprost 0.004% with SofZia™ or nonselective beta-adrenergic receptor blockers prior to the study. RESULTS: After 12 weeks of treatment with 0.01% bimatoprost, ocular hyperemia was graded as none-to-mild hyperemia (grades 0, +0.5, or +1) for 94.1% of subjects and as moderate-to-severe hyperemia (grades +2 or +3) for 5.9%. No statistically significant shifts in ocular hyperemia ratings were observed at week 12 for any of the prior IOP-lowering therapies except bimatoprost 0.03%, in which 20.8% of subjects experienced an improvement. The mean percentage change from baseline IOP at week 12 following the switch to bimatoprost 0.01% monotherapy ranged from -2.3%±17.3% to -26.3%±12.4%. Furthermore, the decreased mean percentage change from baseline IOP was statistically significant across all prior IOP-lowering medications, except for bimatoprost 0.03% at the 6- and 12-week visits and travoprost 0.004% at the 6-week visit. CONCLUSION: This observational study demonstrates that bimatoprost 0.01% was well tolerated among POAG and OHT subjects who switched from prior IOP-lowering medication. Furthermore, a switch in ocular hypertensive treatment to bimatoprost 0.01% was associated with an additional 10%-15% reduction in IOP.

An observational study of bimatoprost 0.01% in treatment-naïve patients with primary open angle glaucoma or ocular hypertension: the CLEAR trial.

BACKGROUND: This study was designed to evaluate the occurrence and severity of ocular hyperemia in subjects with elevated intraocular pressure (IOP) due to primary open angle glaucoma (POAG) or ocular hypertension (OHT) following treatment with bimatoprost 0.01% in a real-world clinical setting. METHODS: This was an open-label, observational study conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% topically as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline and weeks 6 and 12 using a photographic five-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes only the subgroup of 522 subjects who were naïve to IOP-lowering medication prior to the study. RESULTS: After 12 weeks of treatment with bimatoprost 0.01%, hyperemia was graded as none-to-mild (grades 0, +0.5, or +1) for 93.3% of subjects and as moderate-to-severe (grades +2 or +3) for 6.7%. At weeks 6 and 12, most subjects (93.2% and 93.5%) had no change in hyperemia grade from baseline. IOP was reduced by 7.4 mmHg (29.8%) at week 6 and 7.7 mmHg (30.9%) at week 12 from baseline. CONCLUSION: This real-world, observational study found that bimatoprost 0.01% instilled once daily reduced IOP by a mean of 30% from baseline without moderate or severe ocular hyperemia in 93% of treatment-naïve subjects with POAG or OHT.

Causes for treatment delays in dystonia and hemifacial spasm: a Canadian survey.

BACKGROUND: Dystonia must be accurately diagnosed so that treatment can be administered promptly. However, dystonia is a complex disorder, with variable presentation, which can delay diagnosis. METHODS: Data were gathered by questionnaire from 866 patients with dystonia or hemifacial spasm (HFS) treated in 14 movement disorders centres in Canada injecting botulinum toxin, to better understand the path to diagnosis, wait times and obstacles to treatment. RESULTS: Most participants were female (64.1%), mean age was 58 years, and patients consulted an average of 3.2 physicians before receiving a dystonia or HFS diagnosis. Many patients (34%) received other diagnoses before referral to a movement disorders clinic, most commonly "stress" (42.7%). A variety of treatments were often received without a diagnosis. The mean lag time between symptom onset and diagnosis was 5.4 years. After the decision to use botulinum toxin, patients waited a mean of 3.1 months before treatment. The most common diagnoses were cervical dystonia (51.6% of patients), HFS (20.0%) and blepharospasm (9.8%). CONCLUSIONS: Survey results show that diagnosis of dystonias or of HFS, and therefore, access to treatment, is delayed. An educational program for primary care physicians may be helpful to decrease the time to diagnosis and referral to a specialist centre for treatment.

Validation of internal controls for gene expression analysis in the intestine of rats infected with Hymenolepis diminuta.

The non-invasive parasitic cestode Hymenolepis diminuta induces hypertrophy, hyperplasia and other changes in cell activity in the intestine of rats which are indicated in the expression of mRNA. We have investigated various house-keeping genes (GAPDH, beta-actin, 18S and HPRT) and other internal controls (total RNA/unit biomass, total RNA/unit length of intestine) to validate gene expression in the rat intestine after cestode infection and drug-induced neuromodulation. Variation in GAPDH, beta-actin, 18S and HPRT expression was observed in rat jejunal tissue according to treatment. Total RNA/unit length of intestine was found to be the most suitable internal control for normalizing target gene mRNA expression in both infected and/or drug-induced rat intestine. This normalization method may be applied to studies of gene expression levels in intestinal tissue where hypertrophy, hyperplasia, rapid growth and cell differentiation generally occur.