User-Centered Mobile Applications for Stroke Survivors (MAPPS): A Mixed-Methods Study of Patient Preferences.

OBJECTIVE: Investigate stroke survivors' (SS) preferences for a hypothetical mHealth app for post-stroke care and to study the influence of demographic variables on these preferences. DESIGN: Mixed-methods, sequential, observational study. SETTING: Focus groups (phase 1) were conducted to identify SS perceptions and knowledge of mHealth applications (apps). Using grounded theory approach, recurring themes were identified. A multiple-choice questionnaire of 5 desired app features was generated using these themes and mailed to SS (national survey, phase 2). SS' demographics and perceived usefulness (yes/no) for each feature were recorded. In-person usability testing (phase 3) was conducted to identify areas of improvement in user interfaces of existing apps. Summative telephone interviews (phase 4) were conducted for final impressions supplementary to national survey. PARTICIPANTS: SS aged >18 years recruited from study hospital, national stroke association database, stroke support and advocacy groups. Non-English speakers and those unable to communicate were excluded. INTERVENTIONS: None. MAIN OUTCOME MEASURES: (1) Percentage of SS (phase 2) identifying proposed app features to be useful. (2) Influence of age, sex, race, education, and time since stroke on perceived usefulness. RESULTS: Ninety-six SS participated in focus groups. High cost, complexity, and lack of technical support were identified as barriers to adoption of mHealth apps. In the national survey (n=1194), ability to track fitness and diet (84%) and communication (70%) were the most and least useful features, respectively. Perceived usefulness was higher among younger SS (P<.001 to .006) and SS of color (African American and Hispanic) (ORs 1.73-4.41). Simple design and accommodation for neurologic deficits were main recommendations from usability testing. CONCLUSIONS: SS are willing to adopt mHealth apps that are free of cost and provide technical support. Apps for SS should perform multiple tasks and be of simple design. Greater interest for the app's features among SS of color may provide opportunities to address health inequities.

Medical Mobile Applications for Stroke Survivors and Caregivers.

BACKGROUND: Recent studies estimate nearly half of the US population can access mobile medical applications (apps) on their smartphones. The are no systematic data available on apps focused on stroke survivors/caregivers. OBJECTIVE: To identify apps (a) designed for stroke survivors/caregivers, (b) dealing with a modifiable stroke risk factor (SRF), or (c) were developed for other purposes but could potentially be used by stroke survivors/caregivers. METHODS: A systematic review of the medical apps in the US Apple iTunes store was conducted between August 2013 and January 2016 using 18 predefined inclusion/exclusion criteria. SRFs considered were: diabetes, hypertension, smoking, obesity, atrial fibrillation, and dyslipidemia. RESULTS: Out of 30,132 medical apps available, 843 (2.7%) eligible apps were identified. Of these apps, (n = 74, 8.7%) apps were specifically designed for stroke survivors/caregivers use and provided the following services: language/speech therapy (n = 28, 37%), communication with aphasic patients (n = 19, 25%), stroke risk calculation (n = 11, 14%), assistance in spotting an acute stroke (n = 8, 10%), detection of atrial fibrillation (n = 3, 4%), direction to nearby emergency room (n = 3, 4%), physical rehabilitation (n = 3, 4%), direction to the nearest certified stroke center (n = 1, < 2%), and visual attention therapy (n = 1, <2%). 769 apps identified that were developed for purposes other than stroke. Of these, the majority (n = 526, 68%) addressed SRFs. CONCLUSIONS: Over 70 medical apps exist to specifically support stroke survivors/caregivers and primarily targeted language and communication difficulties. Apps encompassing most stroke survivor/caregiver needs could be developed and tested to ensure the issues faced by these populations are being adequately addressed.

Effects of adjunctive lacosamide on mood and quality of life in patients with epilepsy.

We examined the effects of adjunctive lacosamide (LCM) on mood and quality of life (QOL) in adult patients with partial-onset seizures in a prospective, controlled, single-blind study. Patients in whom LCM was added to their AED regimen for clinical indications comprised the LCM group (n=18), while the control group (n=32) comprised patients on ≥2 AEDs with anticipated stable dosing for the duration of the study. Profile of Mood States (POMS) and QOLIE-89 were used to assess mood and QOL at enrollment and 12-16weeks later. Adherence to LCM was measured electronically with the Medication Event Monitoring System (MEMS) and using a self-report measure. There were no significant between-group differences in age, AED load, side-effects (A-B Neurotoxicity Scale), MoCA mental status, or seizure-related factors. LCM adherence (measured by MEMS) was 70.7%. There was a significant decrease in negative mood states in the LCM group (estimated marginal mean at baseline=49.4, at follow-up=29.7; p=0.02), after controlling for seizure freedom. Based on previously reported benchmarks, clinically significant change on the POMS occurred in 7 (38%) LCM patients. The effect of LCM on the overall QOL was not significant (p=0.078). Correlation between POMS Total Mood Distress and Emotional-Wellbeing on the QOLIE-89 was significant (r=-0.783; p=0.01). These results suggest that LCM may have a favorable impact on mood.

Renal Medullary Carcinoma with an Aggressive Clinical Course: A Case Report and Review of the Literature.

Renal medullary carcinoma (RMC) is a rare, yet aggressive malignancy of the kidney that is found predominantly in young patients with African descent and sickle cell hemoglobinopathies and most specifically sickle cell trait. Due to its aggressive nature, most cases have metastasis or local invasion at the time of diagnosis. Prognosis is extremely poor with survival less than 1 year after diagnosis. Here we present a case of metastatic RMC in a 29-year-old African female. Despite chemotherapy with cisplatin, gemcitabine, and paclitaxel, and initial shrinkage of the tumor, the patient died 5 months after diagnosis.

Role of HER2 status in the treatment for brain metastases arising from breast cancer with stereotactic radiosurgery.

HER2-positive breast cancer is a known risk factor for CNS metastases, and the use of trastuzumab in the adjuvant setting does not prevent brain metastases. The purpose of this study is to compare outcomes in HER2-positive and HER2-negative intracranial disease treated with stereotactic radiosurgery (SRS). Among 57 breast cancer patients with brain metastases, 28 patients were HER2-positive. All patients were treated with SRS as their first treatment modality for CNS metastases. The median dose was 20 Gy (range 12-20 Gy). Statistical analysis was performed using the Kaplan-Meier method and χ (2) test. With a median follow-up of 11.0 months, the median time to progression in the HER2-positive group compared with the HER2-negative group was 7 versus 11 months (p = 0.080), respectively. Salvage therapy was performed in 50 % of HER2-positive patients compared with 21 % of HER2-negative patients (p = 0.02). The median OS for the HER2-positive group compared with the HER2-negative group was 22 versus 12 months (p = 0.053). Stereotactic radiosurgery results in excellent local control in the treatment for breast cancer brain metastases. Compared with HER2-negative disease, HER2-positive disease appears to show higher rates of intracranial relapse despite better overall survival rates. This data suggests that we need effective adjuvant therapy to prevent and treat brain metastases in HER2-positive patients.

Involved field radiation therapy after surgical resection of solitary brain metastases--mature results.

BACKGROUND: Whole brain radiation therapy (WBRT) reduces local recurrence in patients after surgical resection of brain metastases without improving overall survival. Involved field radiation therapy (IFRT) has been used at our center to avoid delayed neurotoxicity associated with WBRT in well-selected patients with surgically resected single brain metastases. The purpose of this study was to evaluate the long-term outcomes of these patients. METHODS: Thirty-three consecutive patients with single brain metastases from a known primary tumor were treated with gross total resection followed by IFRT between 2006 and 2011. The postoperative surgical bed was treated to 40.05 Gy in 15 fractions of 2.67 Gy with conformal radiation therapy. Patients received serial MRIs and neurological exams in follow-up. Surgery, WBRT, or stereotactic radiosurgery was performed as salvage treatment when necessary. RESULTS: The median follow-up was 16 months (range: 2-65 months). Local control, distant brain recurrence-free survival, and overall survival at 12 and 24 months were 90.3% and 85.8%, 60.7% and 51.4%, and 65.6% and 61.5%, respectively. Overall, 5 (15%) patients developed recurrence at the resection cavity, and 13 (39%) patients experienced recurrence at a new intracranial site. Two patients received WBRT, 8 stereotactic radiosurgery, 2 surgery, and 2 both chemotherapy and IFRT as salvage. Four patients died from CNS disease progression. CONCLUSION: For patients with newly diagnosed single brain metastases treated with surgical resection, postoperative IFRT to the resection cavity achieves reasonable rates of local control and is an excellent alternative to WBRT.

Antiangiogenic therapy in the management of brain tumors: a clinical overview.

Central to the process of brain tumor development is angiogenesis, which involves a host of molecules and receptors. In recent years, antiangiogenic therapies have been developed and tested for their effectiveness against these tumors. Among them are inhibitors against vascular endothelial growth factor and its receptors, as well as inhibitors targeting the platelet-derived growth factor family, integrins, and histone deacetylase. While many have been shown to be effective with limited toxicity, some tumors are able to adopt escape mechanisms. Further research is needed in the development of effective multi-targeted agents to reduce these effects.

Change in pattern of relapse after antiangiogenic therapy in high-grade glioma.

PURPOSE: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. METHODS AND MATERIALS: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. RESULTS: At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R(2) = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). CONCLUSION: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials.

A clinical trial of bevacizumab, temozolomide, and radiation for newly diagnosed glioblastoma.

OBJECT: The presence of angiogenesis is a hallmark of glioblastoma (GBM). Vascular endothelial growth factor (VEGF), which drives angiogenesis, provides an additional target for conventional therapy. The authors conducted a prospective clinical trial to test the effectiveness of bevacizumab, an inhibitor of VEGF, in newly diagnosed GBM. METHODS: From 2006 through 2010, 51 eligible patients with newly diagnosed GBM were treated with involved-field radiation therapy and concomitant temozolomide (75 mg/m(2) daily for 42 days) along with bevacizumab (10 mg/kg every 2 weeks), starting 29 days after surgery. This was followed by 6 cycles of adjuvant temozolomide therapy (150 mg/m(2) on Days 1-7 of a 28-day cycle) with bevacizumab administered at 10 mg/kg on Days 8 and 22 of each 28-day cycle. RESULTS: The 6- and 12-month progression-free survival (PFS) rates were 85.1% and 51%, respectively. The 12- and 24-month overall survival (OS) rates were 85.1% and 42.5%, respectively. Grade III/IV toxicities were noted in 10 patients (19.6%). No treatment-related deaths were observed. Asymptomatic intracranial bleeding was noted in 5 patients. CONCLUSIONS: The addition of bevacizumab to conventional therapy in newly diagnosed GBM appears to improve both PFS and OS in patients with newly diagnosed GBM, with acceptable morbidity. A shift toward diffuse relapse was noted in a significant number of patients. Ongoing Phase III clinical trials will show the true benefit of this antiangiogenic approach.

Invasion is not an independent prognostic factor in high-grade glioma.

PURPOSE: The role of invasion as a prognostic factor in high-grade gliomas (HGG) remains controversial. An apparent increase in invasiveness following anti-angiogenic therapy makes this question clinically relevant. The goal of this study is to assess survival differences in patients with newly diagnosed HGG who present with diffuse invasive disease compared to those who did not, but went on to develop diffuse invasive disease following bevacizumab therapy. MATERIALS AND METHODS: Twenty-three patients presented as newly diagnosed diffuse invasive HGG. All patients underwent surgical resection with radiation therapy and temozolomide for one year. Progression-free survival (PFS) and overall survival (OS) were compared to a control of 58 patients with focal high-grade glioma who received similar therapy, but that included bevacizumab at 10 mg/kg given every two weeks. RESULTS: The patient characteristics were similar in each group. The median PFS and OS for invasive HGG patients were 6 and 13 months and for the focal HGG patients, 11 and 24 months, respectively (P=0.092 and P=0.071). In the subgroup of invasive HGG that showed significant angiogenesis, the median PFS and OS were 3 and 9 months, respectively. 56% of the focal HGG patients recurred as diffuse invasive relapse. For patients with focal HGG who recurred as invasive disease, the median PFS and OS were 9 and 21 months respectively. CONCLUSIONS: Presence of diffuse invasive disease not accompanied by angiogenesis either prior to therapy or subsequent to anti-angiogenic therapy does not seem to have prognostic significance. However, invasion accompanied by angiogenesis in newly diagnosed HGG may confer a poor prognosis.

Bevacizumab in the treatment of high-grade gliomas: an overview.

Angiogenesis is a process that is integral to the pathogenesis of high-grade gliomas. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor has emerged as an important therapeutic agent. Data from clinical trials in both recurrent and newly-diagnosed gliomas have shown improved radiological responses and quality of life with acceptable morbidity. However, an improvement in overall survival has not yet been seen and there are concerns on possible change in the pattern of relapse following therapy. Several unanswered questions remain including the dose, timing and sequencing that warrant further research.

Prospective neuraxis MRI surveillance reveals a high risk of leptomeningeal dissemination in diffuse intrinsic pontine glioma.

Prognosis of diffuse intrinsic pontine gliomas (DIPGs) remains poor. Failure has been predominantly local, with leptomeningeal dissemination (LD) occurring in 4-33% of patients in pre-MRI era series. Routine craniospinal imaging after initial treatment may reveal other relapse patterns relapse. Sixteen consecutive pediatric patients with DIPG treated between 2006 and 2009 were retrospectively reviewed. Treatment regimens, recurrence patterns, survival, and pathologic diagnosis were recorded. Fourteen patients received involved-field radiotherapy to 54 Gy, and two patients received craniospinal irradiation for LD at presentation. Neuraxis MRI was performed at diagnosis and at 4 month intervals following radiotherapy. Fifteen patients have had progression of disease (median progression-free survival 5.0 ± 1.2 months), and 13 patients have died (median survival 9.0 ± 1.4 months). Local failure occurred in 12 patients (75%). LD occurred in nine patients (56%). LD was present at diagnosis in three patients, after initial staging and treatment in six patients, and during autopsy in two patients. Median overall survival was 12.0 ± 3.3 months without LD and 8.0 ± 2.1 months with LD (P = 0.059, log rank test). Median progression-free survival was 9.5 ± 3.9 months without LD and 3.0 ± 2.1 months with LD (P = 0.012, log rank test). The high incidence of LD probably reflects liberal use of spine MRI surveillance. All patients should undergo routine craniospinal imaging at diagnosis and follow-up. Central nervous system prophylaxis should be considered in future clinical trials.

Bevacizumab in recurrent high-grade pediatric gliomas.

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise in treating recurrent adult high-grade glioma (HGG). However, there is very little data on recurrent or progressive pediatric HGG treated with bevacizumab. We report the results of a single institution experience using bevacizumab and irinotecan in children who relapsed or progressed following standard therapy. Twelve pediatric patients with recurrent or progressive HGG received bevacizumab at 10 mg/kg every 2 weeks with irinotecan at 125 mg/m(2). Magnetic resonance imaging (MRI) was performed prior to therapy and every 8 weeks subsequently. Ten patients had supratentorial HGG; 2 had DIPG. Radiological responses were defined according to MacDonald's criteria. Progression-free survival (PFS), overall survival (OS), and toxicities were analyzed. Ten (83.3%) patients tolerated bevacizumab without serious toxicity. Therapy was discontinued in 1 patient because of anaphylaxis. Another patient developed grade III delayed wound healing and deep vein thrombosis. Two patients (16.7%) experienced a partial response after the first MRI. No complete radiographic responses were seen. Stable disease was noted in 4 (33.3%) patients. The median PFS and OS were 2.25 and 6.25 months, respectively. A diffuse invasive recurrence pattern was noted in 5 (45.5%) patients. Treatment tolerance, toxicity, and recurrence profiles were comparable to adult HGG patients treated with bevacizumab. However, the radiological response rate, response duration, and survival appeared inferior in pediatric patients. Genetic differences in pediatric gliomas might account for this difference.