Randomized clinical trials are important in both clinical and academic stroke communities with increasing numbers of new design concepts emerging. One of the “less traditional” designs that have gained increasing interest in the last decade is non-inferiority trials. Whilst the concept might appear straightforward, the design and interpretation of non-inferiority trials can be challenging. In this review, we will use exemplars from clinical trials in the stroke field to provide an overview of the advantages and limitations of non-inferiority trials and how they should be interpreted in stroke research.

Randomized clinical trials are important in both clinical and academic stroke communities with increasing numbers of new design concepts emerging. One of the “less traditional” designs that have gained increasing interest in the last decade is non-inferiority trials. Whilst the concept might appear straightforward, the design and interpretation of non-inferiority trials can be challenging. In this review, we will use exemplars from clinical trials in the stroke field to provide an overview of the advantages and limitations of non-inferiority trials and how they should be interpreted in stroke research.

Purpose: Urgency urinary incontinence (UUI) is a common finding in patients with a history of stroke or cerebrovascular accident (CVA). UUI is associated with impaired quality of life as well as increased morbidity, mortality, and need for institutionalization. Medical therapy is often limited by side effects and/or cost prohibitiveness. As a result, third-line therapy is often implemented. The objective is to determine the efficacy of sacral neuromodulation (SNM) and onabotulinum toxin (BTX) in the management of post-CVA UUI. Methods: Retrospective analysis was performed to identify patients with post-CVA UUI who underwent SNM or BTX at a large academic medical center. The primary outcome was patient symptom response to third-line therapy. Treatment response was determined using the global response assessment scale. Patients reporting >50% improvement were categorized as having significant response. Secondary endpoints were proportion of patients achieving total dry and duration of therapy for those achieving significant response. Results: One hundred seventy-seven patients were identified (95 BTX, 82 SNM). Patients in the BTX group were older (71.9 years vs. 67.4 years, P=0.02) with otherwise similar demographics. Rate of symptom improvement to >50% of baseline was similar between the groups (66% of BTX, 61% of SNM, P=0.46) as was rate of patients experiencing total dryness (24% of BTX, 16% of SNM, P=0.17). Among patients achieving significant improvement there was no difference in continuation of therapy between the BTX and SNM groups. Younger age was identified as a predictor of >50% symptom improvement (odds ratio, 0.96; P=0.04) and treatment discontinuation (hazard ratio, 0.97; P=0.04) in SNM. Most common adverse events were urinary tract infection in BTX (11%) and pain in SNM (4%). Conclusions BTX and SNM show roughly equal efficacy in the management of post-CVA UUI with nearly two-thirds of patients achieving significant benefit.

Randomized clinical trials are important in both clinical and academic stroke communities with increasing numbers of new design concepts emerging. One of the “less traditional” designs that have gained increasing interest in the last decade is non-inferiority trials. Whilst the concept might appear straightforward, the design and interpretation of non-inferiority trials can be challenging. In this review, we will use exemplars from clinical trials in the stroke field to provide an overview of the advantages and limitations of non-inferiority trials and how they should be interpreted in stroke research.

Purpose: Urgency urinary incontinence (UUI) is a common finding in patients with a history of stroke or cerebrovascular accident (CVA). UUI is associated with impaired quality of life as well as increased morbidity, mortality, and need for institutionalization. Medical therapy is often limited by side effects and/or cost prohibitiveness. As a result, third-line therapy is often implemented. The objective is to determine the efficacy of sacral neuromodulation (SNM) and onabotulinum toxin (BTX) in the management of post-CVA UUI. Methods: Retrospective analysis was performed to identify patients with post-CVA UUI who underwent SNM or BTX at a large academic medical center. The primary outcome was patient symptom response to third-line therapy. Treatment response was determined using the global response assessment scale. Patients reporting >50% improvement were categorized as having significant response. Secondary endpoints were proportion of patients achieving total dry and duration of therapy for those achieving significant response. Results: One hundred seventy-seven patients were identified (95 BTX, 82 SNM). Patients in the BTX group were older (71.9 years vs. 67.4 years, P=0.02) with otherwise similar demographics. Rate of symptom improvement to >50% of baseline was similar between the groups (66% of BTX, 61% of SNM, P=0.46) as was rate of patients experiencing total dryness (24% of BTX, 16% of SNM, P=0.17). Among patients achieving significant improvement there was no difference in continuation of therapy between the BTX and SNM groups. Younger age was identified as a predictor of >50% symptom improvement (odds ratio, 0.96; P=0.04) and treatment discontinuation (hazard ratio, 0.97; P=0.04) in SNM. Most common adverse events were urinary tract infection in BTX (11%) and pain in SNM (4%). Conclusions BTX and SNM show roughly equal efficacy in the management of post-CVA UUI with nearly two-thirds of patients achieving significant benefit.

Purpose: Urgency urinary incontinence (UUI) is a common finding in patients with a history of stroke or cerebrovascular accident (CVA). UUI is associated with impaired quality of life as well as increased morbidity, mortality, and need for institutionalization. Medical therapy is often limited by side effects and/or cost prohibitiveness. As a result, third-line therapy is often implemented. The objective is to determine the efficacy of sacral neuromodulation (SNM) and onabotulinum toxin (BTX) in the management of post-CVA UUI. Methods: Retrospective analysis was performed to identify patients with post-CVA UUI who underwent SNM or BTX at a large academic medical center. The primary outcome was patient symptom response to third-line therapy. Treatment response was determined using the global response assessment scale. Patients reporting >50% improvement were categorized as having significant response. Secondary endpoints were proportion of patients achieving total dry and duration of therapy for those achieving significant response. Results: One hundred seventy-seven patients were identified (95 BTX, 82 SNM). Patients in the BTX group were older (71.9 years vs. 67.4 years, P=0.02) with otherwise similar demographics. Rate of symptom improvement to >50% of baseline was similar between the groups (66% of BTX, 61% of SNM, P=0.46) as was rate of patients experiencing total dryness (24% of BTX, 16% of SNM, P=0.17). Among patients achieving significant improvement there was no difference in continuation of therapy between the BTX and SNM groups. Younger age was identified as a predictor of >50% symptom improvement (odds ratio, 0.96; P=0.04) and treatment discontinuation (hazard ratio, 0.97; P=0.04) in SNM. Most common adverse events were urinary tract infection in BTX (11%) and pain in SNM (4%). Conclusions BTX and SNM show roughly equal efficacy in the management of post-CVA UUI with nearly two-thirds of patients achieving significant benefit.

Objective: Cambodia is one of seven countries globally that met Millennium Development Goal 5A: reduction of maternal deaths by at least 75% between 1990 and 2015. To support improving maternal care, the Maternal Death Audit (MDA) was instituted in 2004. This report highlights changes in maternal health services and MDA implementation in Cambodia between 2010 and 2017. Methods: International experts and the national MDA Committee assessed all case abstracts, investigation questionnaires and audit meeting minutes covering all maternal deaths reported in Cambodia in 2010 and 2017 for quality of classification, data, care and recommendations. They convened provincial MDA committees to conduct similar assessments and develop evidence-informed recommended actions. Results: In 2010 and 2017, 176 and 59 maternal death cases were reported, respectively. Cases were more likely in 2017 than in 2010 to have antenatal care (90.0% vs 68.2%, P = 0.004), give birth in a facility (81.6% vs 55.3%, P = 0.01) and receive a prophylactic uterotonic (95.7% vs 73%, P < 0.05) for postpartum haemorrhage (PPH) and magnesium sulfate (66% vs 37%, P = 0.18) for pre-eclampsia/eclampsia. However, additional interventions and improved timeliness of referral with equipped and competent staff were identified as critical. Data quality prevented classifying one-fourth of cases during both periods. MDA recommendation quality improved from 2.8% in 2011 to 42% in 2018. Discussion: Improvements in maternal care are reflected in the increased antenatal care, facility births and better PPH and preeclampsia-eclampsia management. However, additional care management improvements are highlighted. The MDA reporting needs improved data completeness and more specific recommendations to address causes of death.

Purpose: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). Materials and Methods: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. Results: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). Conclusion GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Tremor is an involuntary and repetitive swinging movement of limb, which can be regarded as a periodic disturbance in tremor suppression system based on functional electrical stimulation (FES). Therefore, using repetitive controller to adjust the level and timing of FES applied to the corresponding muscles, so as to generate the muscle torque opposite to the tremor motion, is a feasible means of tremor suppression. At present, most repetitive control systems based on FES assume that tremor is a fixed single frequency signal, but in fact, tremor may be a multi-frequency signal and the tremor frequency also varies with time. In this paper, the tremor data of intention tremor patients are analyzed from the perspective of frequency, and an adaptive repetitive controller with internal model switching is proposed to suppress tremor signals with different frequencies. Simulation and experimental results show that the proposed adaptive repetitive controller based on parallel multiple internal models and series high-order internal model switching can suppress tremor by up to 84.98% on average, which is a significant improvement compared to the traditional single internal model repetitive controller and filter based feedback controller. Therefore, the adaptive repetitive control method based on FES proposed in this paper can effectively address the issue of wrist intention tremor in patients, and can offer valuable technical support for the rehabilitation of patients with subsequent motor dysfunction.
Humans ; Wrist ; Tremor/therapy* ; Movement ; Computer Simulation ; Electric Stimulation