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Hands-on computing has emerged as an exciting and accessible way to learn about computing and engineering in the physical world for students and makers of all ages. Current end-to-end approaches like Microsoft MakeCode require tethered or battery-powered devices like a micro:bit, limiting usefulness and applicability, as well as abdicating responsibility for teaching sustainable practices. Unfortunately, energy harvesting computing devices are usually only programmable by experts and require significant supporting toolchains and knowledge across multiple engineering and computing disciplines to work effectively. This paper bridges the gap between sustainable computing efforts, the maker movement, and novice-focused programming environments with MakeCode-Iceberg, a set of compiler extensions to Microsoft's open-source MakeCode project. The extensions automatically and invisibly transform user code in any language supported (Blocks, JavaScript, Python)into a version that can safely and correctly execute across intermittent power failures caused by unreliable energy harvesting. Determining where, when, and what to save in a checkpoint on limited energy, time, and hardware budget is challenging. We leverage the unique intermediate representation of the MakeCode source-to-source compiler to design and deploy various checkpointing techniques. Our approach allows us to provide, for the first time, a fully web-based and toolchain-free environment to program intermittent computing devices, making battery-free operation accessible to all. We demonstrate new use cases with multiple energy harvesters, peripherals, and application domains: including a Smart Terrarium, Step Counter, and Combination Lock. MakeCode-Iceberg provides sustainable hands-on computing opportunities to a broad audience of makers and learners, democratizing access to energy harvesting and battery-free embedded systems.

BACKGROUND: Bladder cancer treatments may variably impact health-related quality of life (QOL). OBJECTIVE: To characterize the quality of life of patients with bladder cancer at various time points across the continuum of bladder cancer care from non-muscle-invasive disease to metastatic bladder cancer and develop utility scores to inform cost-effective analyses. METHODS: We performed a cross-sectional survey of bladder cancer patients in the Bladder Cancer Advocacy Network Patient Survey Network. Participants were classified into mutually exclusive health states based upon non-muscle invasive (NMIBC), muscle-invasive (MIBC), or metastatic bladder cancer and completed surveys of generic cancer and bladder cancer-specific quality of life, financial toxicity, and work impairment. We constructed generalized linear mixed models to identify patient, clinical, and treatment factors associated with quality of life over time and derived health state utilities. RESULTS: Among 911 self-identified patients with bladder cancer, overall QOL scores and function domains were worse among those with advanced cancer. Financial toxicity was similar among non-metastatic disease states. Work and activity impairment increased with advancing disease (13%and 12%among non-recurrent NMIBC to 63%and 31%for metastatic disease respectively; p

Background Recurrence of Clostridioides difficile infection (rCDI) is common - up to 35% of patients may recur. RBX2660 is a microbiota restoration therapy to reduce rCDI. Here we report 8 weeks HRQL results using the Clostridioides difficile Health-related Quality-of-Life Questionnaire (Cdiff32), a disease-specific instrument, from PUNCH CD3 (a randomized, double-blinded, placebo-controlled RBX2660 Phase 3 trial, NCT03244644). Methods Cdiff32 includes three domains (physical, mental, and social) and a total score (all range from 0 to 100 [100 best possible]). Changes in Cdiff32 from baseline to week 8 were compared between RBX2660 and placebo (PBO) using unadjusted and adjusted analyses controlling for baseline score, demographic and disease characteristics. Per trial protocol, missing data were imputed via last observation carried forward (LOCF); as-observed data were also analyzed. Patients experiencing recurrence after blinded treatment received open-label RBX2660 per physician discretion; these participants were excluded unless, per LOCF, data were available from the blinded period for week 8 use. Results A total of 206 patients (140 RBX2660, 66 PBO) were included, with similar age (mean±SD) 61.1±16.9 yrs (RBX2660) and 57.3±16.4 yrs (PBO) and baseline Cdiff32 scores. More than half of the patients had multiple comorbidities. Cdiff32 scores improved significantly from baseline to weeks 1, 4, and 8 for both arms, with greater improvements for RBX2660 through week 8 (Figs. 1 & 2). At week 8, statistical differences were found for mental domain (unadjusted: 8.01±3.64; adjusted: 7.07, 95% confidence interval: [0.28, 13.86], both P< 0.05) and total score (adjusted: 6.11, [0.14, 12.08], P< 0.05), all favoring RBX2660. Results were similar for the as-observed analyses, with the adjusted physical domain also statistically favoring RBX2660. Conclusion Most patients in this study reported improved HRQL. Improvements were observed in both arms, but RBX2660-treated patients had more robust and sustained improvements with statistically significant differences in Cdiff32 scores. This study suggests that microbiome restoration therapy might positively affect HRQL; future research may link these improvements directly with microbiota changes. Disclosures Paul Feuerstadt, MD, FACG, AGAF, Ferring/Rebiotix Pharmaceuticals: Advisor/Consultant|Ferring/Rebiotix Pharmaceuticals: Grant/Research Support|Merck and Co: Advisor/Consultant|SERES Therapeutics: Advisor/Consultant|SERES Therapeutics: Grant/Research Support|Takeda Pharmaceuticals: Advisor/Consultant Erik R. Dubberke, MD, MSPH, Abbott: Advisor/Consultant|Ferring: Advisor/Consultant|Ferring: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Seres: Advisor/Consultant|Summit: Advisor/Consultant|Synthetic Biologics: Grant/Research Support Amy Guo, PhD, Ferring Pharmaceuticals: Employee Adam Harvey, PhD, Ferring Pharmaceuticals: Employment Min Yang, MD, PhD, Analysis Group, Inc.: I am an employee of Analysis Group, Inc., which has received consulting fees from Ferring for the conduct of this study. Viviana García-Horton, PhD, Analysis Group, Inc.: Employee of Analysis Group, Inc., which received consulting fees from Ferring for the conduct of this study. Mirko Fillbrunn, PhD, Analysis Group, Inc.: I am an employee of Analysis Group, Inc., which has received consulting fees from Ferring for the conduct of this study. Glenn S. Tillotson, PhD, Ferring Pharmaceuticals: Advisor/Consultant|Paratek Pharmaceuticals: Grant/Research Support|Spero Pharmaceuticals: Advisor/Consultant|Taro Pharmaceuticals: Advisor/Consultant Lindy Bancke, PharmD, Rebiotix, a Ferring Company: Employee Kevin W. Garey, PharmD, MS, Acurx: Grant/Research Support|cidara: Advisor/Consultant|cidara: Grant/Research Support|Paratek: Grant/Research Support|Seres Health: Grant/Research Support|Summit: Grant/Research Support.

Short-range orders (SROs) become more interesting in an intriguing new class of metallic materials – High-Entropy Alloys (HEAs) or Medium-Entropy Alloys (MEAs), that contain multi-principal elements. However, from the atomic level and the compositional viewpoint, observing the SRO in HEAs or MEAs is still very challenging, because it is difficult to distinguish the elements with very closed atomic numbers using electron microscopies. Here we directly observed the SRO in a medium-entropy alloy through deciphering the big data by atomic probe tomography (APT) via a new machine learning method. Using our matching learning method, the nearest neighbors of the detected elements, preferred bonds of each atom, in the APT data can be achieved. Our method offers a new pathway to observe SRO directly not only in those compositionally-complex alloys but also in the traditional dilute alloy systems, which can accelerate the design of advanced materials with favorable SROs for achieving desired properties.

The primary objectives of this study were to propose and validate a procedure for estimating the capacity of midblock bike lanes by taking into account the characteristics of three types of two-whe...

We evaluated the real-world healthcare resource utilization (HRU) and costs among patients with high-grade non-muscle invasive bladder cancer (HG-NMIBC) following Bacillus Calmette-Guerin (BCG) therapy. Patients aged ≥ 65 years diagnosed with HG-NMIBC between 2008 and 2015 who received adequate BCG induction and were identified in the SEER-Medicare database. Those who received intravesical chemotherapy or radical cystectomy within 12 months of the last BCG induction dose, and had ≥ 6 months of data availability after treatment (index date), were included. Annualized HRU and mean medical costs (2020 United States dollars) were estimated and compared between patients with versus without progression. Inverse probability of treatment weighting was used to adjust for differences in baseline characteristics. Of 986 patients diagnosed with HG-NMIBC who met the inclusion criteria, 257 (26.1%) progressed; the mean ages were similar between patients who did and did not progress (77.6 vs. 77.0 years). The overall population had a mean of 0.96 [standard deviation (SD): 1.18] inpatient admissions, 6.47 (11.40) hospitalization days, 1.38 (2.19) emergency department (ED) visits, and 48.03 (44.97) outpatient visits per patient-year during the study period; total annualized costs per patient post-BCG were $39,102 ($44,244). Patients experiencing progression had significantly higher mean numbers of inpatient admissions [1.61 (SD 1.40) vs. 0.72 (0.99)], hospitalization days [11.77 (14.96) vs. 4.59 (9.29)], ED visits [2.34 (2.92) vs. 1.03 (1.76)], and outpatient visits [65.97 (44.72) vs. 41.63 (43.09)] per patient-year compared with patients without progression (all p

Drivers’ take-over intention is important for the design of the automated driving systems and affects the safety of automated driving. This study explored the influence factors on drivers’ take-over intention during conditionally automated driving, examined the correlations among factors through path analysis, and established a take-over intention model. A questionnaire survey was conducted in Hefei, China, and a sample of 277 drivers was obtained. Our study shows that the average take-over intention of those aged under 20 is lower than that of the older age groups. In the positive emotions (PE) scenarios, the take-over intention of aged 31–40 is significantly higher than that of the other age groups. Education and occupation have a significant influence on the take-over intention. The perceived ease of use (PEofU) and perceived usefulness (PU) of automated driving are significantly negatively correlated with drivers’ take-over intention in the road conditions (RC) and climate conditions (CC) scenarios. In addition, through path model analysis, our study shows that trust in the safety of autonomous vehicles (AVs) plays an important role in drivers’ take-over intention. Technology acceptance, risk perception and self-efficacy has indirectly correlated with take-over intention through trust in the safety of AVs. In general, drivers with lower technology acceptance, lower self-efficacy and higher risk perception are less likely to trust automated driving technology and have shown stronger intention to take-over the control of the vehicles.

Background: Exposure to toxic metals (TMs) such as lead can cause lifelong neurodevelopmental impairment and other adverse outcomes. TMs enter drinking water from human activity, geogenic contamination, and corrosion of water system components. Several studies report TM contamination in piped systems and private wells in high-income countries (HICs). However, few robust studies report on TM contamination in low- and middle-income countries (LMICs). Objectives: We characterized the occurrence and investigated sources of TM contamination in 261 rural water systems in three West African LMICs to inform prevention and management. Methods: Water samples were collected from 261 community water systems (handpumps and public taps) across rural Ghana, Mali, and Niger. Scrapings were collected from accessible components of a subset of these systems using a drill with acid-washed diamond-tipped bits. Samples were analyzed by inductively coupled plasma (ICP) mass spectrometry or ICP optical emission spectroscopy. Results: Of the TMs studied, lead most frequently occurred at levels of concern in sampled water system components and water samples. Lead mass fractions exceeded International Plumbing Code (IPC) recommended limits (0.25% wt/wt) for components in 82% (107/130) of systems tested; brass components proved most problematic, with 72% (26/36) exceeding IPC limits. Presence of a brass component in a water system increased expected lead concentrations in drinking-water samples by 3.8 times. Overall, lead exceeded World Health Organization (WHO) guideline values in 9% (24/261) of drinking-water samples across countries; these results are broadly comparable to results observed in many HICs. Results did not vary significantly by geography or system type. Discussion: Ensuring use of lead-free (

Healthcare provider (HCP) satisfaction is important for staff retention and effective health service delivery. Inadequate resources, understaffing, and ineffective organizational structure may reduce HCP satisfaction in low- and middle-income countries (LMICs). Some qualitative studies have described links between environmental conditions and job satisfaction in HCPs; however, few studies have explored this link using survey data. This study explores associations between HCP satisfaction and water, sanitation, and hygiene (WaSH) infrastructure, cleanliness, and infection prevention and control (IPC) practices in rural healthcare facilities (HCFs) in LMICs. This study analyzes 2002 HCFs in rural areas of 14 LMICs. Generalized linear mixed-effects logistic regression models were used to analyze the association between HCP satisfaction, WaSH infrastructure, and cleanliness and IPC practices. Most respondents reported that they were unsatisfied with water (65%), sanitation (68%), and hygiene infrastructure (54%) at their HCF. Insufficient supply and poor quality of WaSH resources were the most commonly reported reasons for provider dissatisfaction. Respondents were less likely to report dissatisfaction with cleanliness and IPC practices (36%). Dissatisfaction with cleanliness and IPC were most reported because patients and staff did not wash their hands at the correct times or with proper materials, or because the facility was not clean. Several characteristics of the WaSH environment were significantly associated with provider satisfaction at their HCFs, including acceptable water quality, readily available supply of water (on premises and improved), accessible supply of WaSH infrastructure to people with reduced mobility, accessible supplies of sanitation and hygiene materials, and sufficient training and budgeting for WaSH or IPC needs. Our results suggest that the provision of on premises, improved water service accessible to people with reduced mobility, interventions that prioritize the acceptability of sanitation facilities within the local context, and the provision of hygienic materials are key interventions to improve HCP satisfaction. Dedicated funding and oversight should be established at the HCF level to ensure access to consumable hygiene and IPC products and maintenance of WASH infrastructure. Improvements to WaSH in HCF may improve HCP satisfaction and ultimately patient outcomes.

Safe and sufficient water, sanitation, and hygiene (WaSH) prevent the spread of disease in health-care facilities (HCFs). Little research has been conducted on WaSH in HCF in sub-Saharan Africa. We carried out a cross-sectional study of WaSH in 1,318 randomly selected rural HCF (hospitals, health centers, health posts, and clinics) in regions throughout Ethiopia, Kenya, Mozambique, Rwanda, Uganda, and Zambia. Methods included questionnaires with head doctors and nurses to document WaSH access, continuity, quality, quantity and reliability, and analysis of drinking water samples for Escherichia coli. We found that fewer than 50% of rural HCFs had access to improved water sources on premises, improved sanitation, and consistent access to water and soap for handwashing (Ethiopia [7%), Kenya [30%], Mozambique [29%], Rwanda [50%], Uganda [30%], and Zambia [21%]). Adequate hand hygiene reduces disease transmission and health-care-acquired infections, but fewer than 25% of HCF in each country reported that a combination of water, soap, and hand-drying materials were always available. Our research points to a lack of basic WaSH services in rural HCFs in regions of sub-Saharan Africa, which poses a threat to the health of patients and health-care workers in these settings.

While the clinical benefits of dalfampridine extended-release (D-ER) have been established in patients with multiple sclerosis (MS) through multiple clinical trials, there is limited real-world data on D-ER use, in particular the persistent use of D-ER, and associated acute care resource utilization and costs.To examine the real-world association of D-ER use and inpatient admissions and costs among patients with MS.This study was a retrospective observational claims analysis of the MarketScan database (April 2009-March 2014). Eligible patients consisted of adult enrollees aged 18-64 years who had (a) 12 months of continuous private plan enrollment preceding (baseline) and following (follow-up) the first D-ER claim; (b) ≥ 2 MS diagnosis codes with ≥ 1 during the baseline period; (c) ≥ 2 consecutive D-ER claims; and (d) no alternate gait-impairing etiologies during the baseline and follow-up periods. Patients were separated into 2 D-ER cohorts in the main analysis: persistent (≥ 360 days of D-ER supply) and nonpersistent (360 days of supply) users. Sensitivity analyses were conducted, examining additional breakdowns of days of supply within the nonpersistent cohort. Inpatient admissions (all-cause and MS-related) and health care expenditures were calculated and compared between the cohorts during follow-up using Wilcoxon rank-sum and chi-square tests. Regression models were conducted, controlling for age, sex, MS relapses, comorbidities, disease-modifying therapy use, and other baseline factors, including inpatient admissions and costs.Of 1,598 eligible patients, 719 (45.0%) were persistent D-ER users, and 879 (55.0%) were nonpersistent D-ER users. The 2 cohorts had similar demographic and clinical characteristics, with mean (SD) ages of 51.0 (8.4) and 50.6 (8.6) years and were 71.3% and 66.6% female, respectively. Compared with nonpersistent D-ER use, persistent D-ER use was associated with lower odds of all-cause inpatient admissions (OR = 0.58, P = 0.010) and MS-related inpatient admissions (OR = 0.50, P = 0.004). Persistent use was also associated with lower inpatient expenditures for all-cause admissions ($669 vs. $1,515, P = 0.002) and MS-related admissions ($388 vs. $891, P = 0.008).Persistent D-ER use was associated with significantly lower rates of all-cause and MS-related inpatient admissions and costs.Funding for this research and medical writing assistance was provided by Acorda Therapeutics. The study sponsor was involved in all stages of the study research and manuscript preparation. Guo and Niyazov were employees of Acorda Therapeutics at the time of this study and may own stock/stock options. Wu, Macaulay, Terasawa, and Schmerold are employees of Analysis Group, which received consultancy fees from Acorda Therapeutics for this project. Krieger was a consultant for Acorda Therapeutics for this project and has the following additional financial interests to report: consulting/advisory board work with Bayer, Biogen, EMD Serono, Novartis, Genentech, Genzyme, and Teva. Study concept and design were contributed by Guo, Niyazov, Macaulay, and Wu. Macaulay, Terasawa, Schmerold, and Wu helped prepare the data, and data interpretation was performed by Krieger, Guo, Niyazov, and Macaulay, along with Terasawa and Wu. The manuscript was written by Terasawa and Schmerold, along with Macaulay, and revised by all the authors. A portion of the current research was presented in poster format at the 2106 American Academy of Neurology Annual Meeting, which took place in Vancouver, BC, Canada, on April 15-21, 2016.

Adequate environmental conditions, comprising sufficient environmental hygiene items (e.g. gloves, soap, and disinfectant), adequate infrastructure (e.g. sanitation facilities, water supply), a clean environment, and hygienic behaviors in healthcare facilities (HCFs) are necessary for safe care in maternity wards. Few data are available describing environmental conditions in maternity wards in rural areas of low- and middle-income countries (LMICs). We collected data on these conditions from 1547 HCFs with maternity wards in 14 countries (Ethiopia, Ghana, Honduras, India, Kenya, Malawi, Mali, Mozambique, Niger, Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe). We described patterns and availability of essential environmental conditions, and a regression model was developed to explore predictive factors. 73% of HCFs offering maternal and neonatal health (MNH) services did not meet the guidelines for the World Health Organization ‘six cleans’ (clean perineum, clean bed surface, clean hands, clean blade, clean cord tie, and clean towels to wrap the baby and mother). The items with the lowest availability were clean towels (40%). In a multivariable logistic regression model, HCFs that provided maternity services were more likely to have all ‘six cleans’ available if they: had at least an improved water source; had an infection prevention and control (IPC) protocol; had a budget considered sufficient that included funding for water, sanitation, hygiene, and IPC; and emphasized the importance of IPC within the nearby community. Our results demonstrate substantial differences between countries in the availability of environmental hygiene items, facility cleanliness, and quality of environmental health infrastructure in HCF maternity wards. There are several low-cost, high-impact, context-relevant opportunities to enhance essential environmental conditions that would improve the quality of neonatal and maternal care in maternity wards in HCFs in LMICs.

Improving access to water, sanitation, and hygiene (WaSH) and menstrual hygiene management (MHM) in schools is important to achieve Sustainable Development Goals (SDGs) 3 and 6. Inadequate WaSH and MHM in schools adversely affect student health and educational performance, as well as teacher satisfaction. However, there is little evidence describing factors associated with WaSH services and MHM in schools. We conducted 2690 surveys and collected 1946 water samples at randomly selected schools in rural areas of 14 low- and middle-income countries (LMICs). We developed multilevel mixed-effects logistic regression models to identify factors associated with basic water services, water quality, basic sanitation facilities, basic handwashing facilities, and availability of MHM materials. We found that 51% of schools had at least a basic, on-premises water service. Twenty-eight percent of schools had at least basic sanitation services, 12% had at least a basic handwashing facility, and 26% had MHM materials available. Four percent of schools had all basic WaSH services. Half (52%) of schools had drinking water compliant with the WHO guideline value for E. coli. In regression models, we found that schools that did not share their water point with a community, had a parent-teacher association that supported WaSH, or had support from an external WaSH program were more likely to have access to basic, continuous, on-premises water service versus worse access. Schools with an on-premises water point, water available on the day of survey, a health club, or handwashing stations near toilets were more likely to have a basic sanitation service versus a lower service. Schools with limited or basic sanitation, health clubs, an MHM curriculum, a designated MHM focal person, or school funds for WaSH were more likely to have MHM materials. We conclude that improved institutional management and external support, accountability mechanisms, and enhanced training and hygiene curriculum will support sustained WaSH service delivery in schools in LMICs.

Exposure to toxic metals and metalloids (TMs) such as arsenic and lead at levels of concern is associated with lifelong adverse health consequences. As exposure to TMs from paint, leaded gasoline, canned foods, and other consumer products has decreased in recent decades, the relative contribution of drinking water to environmental TM exposure and associated disease burdens has increased. We conducted a rapid review from June to September 2019 to synthesize information on the sources of TM contamination in small rural drinking water systems and solutions to TM contamination from these sources, with an emphasis on actionable evidence applicable to small rural drinking water systems worldwide. We reviewed publications from five databases (ProQuest, PubMed, Web of Science, Embase, and Global Health Library) as well as grey literature from expert groups including WHO, IWA, and others; findings from 61 eligible review publications were synthesized. Identified sources of TMs in included studies were natural occurrence (geogenic), catchment pollution, and corrosion of water distribution system materials. The review found general support for preventive over corrective actions. This review informs a useful planning and management framework for preventing and mitigating TM exposure from drinking water based on water supply characteristics, identified contamination sources, and other context-specific variables.

e17026 Background: Management of non-muscle-invasive bladder cancer (NMIBC) when BCG fails engages complex decision-making that incorporates consideration of radical cystectomy (RC) and several intravesical options. We sought to characterize trends in practice variation and health outcomes for patients receiving intravesical therapy and radical cystectomy for presumption of recurrent or progressive high-risk NMIBC that has failed BCG. Methods: We identified patients with high-risk NMIBC from SEER-Medicare diagnosed from 2004-2015 who completed a full dose of BCG treatment. We evaluated receipt of intravesical therapy after BCG fails based on a code for a transurethral resection of bladder tumor (TURBT) within 6 months of BCG treatment followed by a switch to a different intravesical agent, systemic therapy, or radical cystectomy. We constructed risk estimates for disease-specific survival and subsequent need for radical cystectomy and using the Kaplan-Meier method and multivariate Cox proportional-hazards models adjusted for competing risks of death and patient clinical/demographic factors. Results: Among high-risk NMIBC patients who received BCG in their first year of diagnosis (n = 14,369), 9.7% (n = 1,273) went on to receive intravesical therapy, 4.2% (n = 607) proceeded directly to cystectomy, 15.8% (n = 2,272) underwent re-induction with BCG, 7.0% (n = 1,009) initiated systemic chemotherapy and 4.4% died without receiving treatment after BCG. Median follow-up after the post-BCG recurrence was 29 months (IQR 42, 14-56). Those receiving intravesical therapy after BCG fails were older, had more comorbidities, resided in rural areas, and had higher proportion of clinical Ta cancers (p < 0.05 for all) compared with immediate RC patients. Intravesical agents after BCG fails are listed in the Figure. Among those undergoing intravesical therapy, 12.9% (n = 478) eventually underwent RC a median 13 months (IQR 20, 7-27) after treatment post-BCG (2-year cystectomy free survival 89.4% [95% CI 88.3-90.5%]). Actuarial 2-year and 5-year bladder cancer-specific survival was 84.0% (95% CI 82.3-85.7%) and 71.0% (95% CI 68.3-73.7%), respectively, after intravesical treatment post-BCG. Conclusions: The heterogeneity in treatments used for NMIBC that fails BCG indicates potential provider uncertainty in the management of this challenging clinical situation. The paucity of effective bladder-sparing therapies, which is reflected in a high 2-year risk of RC and bladder cancer-specific death, highlights the urgent need for new therapies in this patient population.

Travellers’ environmental awareness can affect their mode choices. The primary objective of this study is to identify the effect of electric bicycle (e-bike) users’ environmental awareness on their mode choice when the use of e-bikes is prohibited in urban areas in China. The data were collected via a questionnaire survey administered at ten locations in Nanjing, China. Using mixed multinomial logit (MMNL) models, we examined the relationship between the e-bike users’ mode choice and their environmental awareness, combined with socioeconomic and demographic characteristics and trip attributes. The results show that the level of environmental awareness, gender, age, education, income, the ownership of car and conventional bike, and trip distance affect e-bike users’ choices significantly. Those with a high level of environmental awareness are more likely to choose zero-emission transport modes. A stratified analysis reveals that the effect of environmental awareness is associated with their original transport mode choice prior to their use of the e-bike. With a high level of environmental awareness, original car users tend to opt for moderate- or zero-emission modes; original bus and metro users incline to choose a zero-emission mode or their original mode; and few original cyclists and walkers favour moderate- or high-emission modes. The results of the current study provide transport authorities with insights to establish sustainable urban transportation management policies and strategies to increase the share of zero- and low-emission transport modes.

453 Background: For patients with high-grade (HG) non-muscle invasive bladder cancer (NMIBC) who recur after Bacillus Calmette-Guérin (BCG) therapy, treatment options other than radical cystectomy have been limited. This study examined real-world utilization and outcomes of current bladder preservation therapies (BPT) after BCG treatment. Methods: We analyzed the SEER-Medicare database and identified patients diagnosed with HG NMIBC between 2008 and 2015 who received at least one BCG induction course (defined as ≥5 weekly instillations). Use of BPT within six months of the last consecutive BCG instillation was identified and included BCG + interferon alpha, docetaxel, doxorubicin, epirubicin, gemcitabine, mitomycin C, nab-paclitaxel, thiotepa, valrubicin, or their combinations. Progression was identified as initiation of treatment for muscle-invasive bladder cancer, radical cystectomy, or presence of metastases. Time to progression (TTP) was defined as time from BPT initiation to progression event. Progression-free survival (PFS) was assessed from BPT initiation and defined as the absence of progression or death due to bladder cancer. TTP and PFS were assessed using Kaplan-Meier analysis. Results: A total of 7,074 patients were diagnosed with HG NMIBC and received ≥ 5 BCG weekly induction instillations. Of these, 8.8% (620 patients) initiated BPT. The most commonly used agents were mitomycin C (66.0%), followed by BCG + interferon alpha (22.9%), valrubicin (4.0%), doxorubicin (2.9%), and gemcitabine (2.1%). Disease progression occurred in 18.7% of patients within 1 year of treatment initiation (40.5% due to metastases), 36.4% within 3 years (50.0% due to metastases), and 45.4% within 5 years (50.2% due to metastases). The rate of PFS was 80.9%, 61.8%, and 52.3% at 1, 3, and 5 years, respectively. Conclusions: High rates of metastatic disease are noted in HG NMIBC following available BPT treatments after failure of BCG therapy. A high unmet need remains for novel bladder-sparing therapies to improve outcomes in this difficult-to-treat population.

Many healthcare facilities (HCFs) in rural areas of low- and middle-income countries (LMICs) lack safe, sufficient water supplies. We sought to understand which factors affect water quality in rural HCF in LMICs. In Ethiopia, Ghana, Honduras, India, Kenya, Malawi, Mali, Mozambique, Niger, Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe, doctors and nurses were interviewed at over 2000 outpatient HCFs about their water source, staff training, and management practices. Water samples were also tested for contamination with E. coli. We generated descriptive analyses and logistic regressions. Overall, 52% of surveyed HCFs used at least a basic water service, 23% used a limited water service, and 25% had no water service as defined by the WHO/UNICEF Joint Monitoring Programme. Use of an improved water source type (OR ≈ 1.4–1.7), treatment of water (OR = 1.26), management by a person with medical training (OR ≈ 3.4–8.9), and presence of a protocol for operations and management (OR = 1.29) were associated with safer water. These results suggest that in addition to addressing water source, storage, and treatment, stakeholders should also target organizational factors in order to improve water quality in HCFs.

Background Dalfampridine extended-release tablets (dalfampridine-ER; in Europe, prolonged-release fampridine, and elsewhere, fampridine modified or fampridine sustained release), 10 mg twice daily, are available for the treatment of improvement of walking in patients with multiple sclerosis, as demonstrated by an increase in walking speed. On-drug patient perspectives and experiences are valuable to understand and manage this patient population. Objective The objective of this study was to examine perspectives and experiences of patients receiving dalfampridine-ER in a real-world setting. Methods Step Together, an ongoing program that captures real-world patient experience with dalfampridine-ER treatment, consists of a survey administered at baseline (before dalfampridine-ER initiation) and at 30 (first follow-up) and 60 days (second follow-up) after initiation. The survey includes modified versions of the 12-item Multiple Sclerosis Walking Scale (mMSWS-12) and the Sheehan Disability Scale (mSDS) to assess walking ability and functional impairment, respectively. Results As of September 2013, 2,248 patients participated in the baseline survey and 522 completed both follow-up surveys (completers). Among the completers, improvements in walking ability and function relative to baseline were significant at both follow-ups as measured by mMSWS-12 and mSDS scores, respectively. Notably, 69–74 % of completers at both follow-ups had improved mMSWS-12 scores, with scores greater than the range considered to be minimally clinically significant. Patients who completed the program expressed satisfaction with overall dalfampridine-ER treatment, and 69 % indicated that the survey would help them communicate better with their healthcare providers. Conclusion Results highlight the utility of patient-reported outcomes in the assessment of patient perspective and experience, providing a useful supplement to traditional objective measures used in clinical studies. Electronic supplementary material The online version of this article (doi:10.1007/s40271-014-0102-z) contains supplementary material, which is available to authorized users.

Hair follicles: Secret to prevent scars? Although some animals easily regenerate limbs and heal broken flesh, mammals are generally not so gifted. Wounding can leave scars, which are characterized by a lack of hair follicles and cutaneous fat. Plikus et al. now show that hair follicles in both mice and humans can convert myofibroblasts, the predominant dermal cell in a wound, into adipocytes (see the Perspective by Chan and Longaker). The hair follicles activated the bone morphogenetic protein (BMP) signaling pathway and adipocyte transcription factors in the myofibroblast. Thus, it may be possible to reduce scar formation after wounding by adding BMP. Science , this issue p. 748 ; see also p. 693

e16012 Background: 75–85% of bladder cancer patients present with non-muscle invasive disease (NMIBC). While transurethral resection of bladder tumors (TURBT) is the initial standard treatment for visible lesions, there is variation in the utilization of adjuvant intravesical treatments in the real world. This study aims to assess current treatment patterns in privately insured NMIBC patients. Methods: Bladder cancer patients were identified from Truven MarketScan Commercial and Medicare Supplemental databases using ICD-9/ICD-10 codes. In the absence of tumor staging information, patients were considered to have NMIBC based on diagnosis of CIS or an algorithm centered on the use of TURBT, intravesical treatments and absence of immediate progression to muscle invasive disease. Patients were included in the final cohort if they had one year of continuous insurance coverage prior to index diagnosis, and were without any bladder cancer treatment during this period. Results: 18,683 patients met the eligibility criteria and had a median follow-up of 23 months; the mean age was 68.6 years and 75% were male. The median time from diagnosis to TURBT was 8 days. 54% of the cohort had an intravesical treatment (35% specifically with Bacillus Calmette–Guérin (BCG), with median time from TURBT of 69 days). 77% of BCG-treated patients received 5 or more administrations during induction. However, only 22% of patients received maintenance BCG after induction. 16% of the total cohort developed a recurrence or progression during the available follow-up; five percent underwent a cystectomy, while seven percent were diagnosed with metastatic disease. Only 4% of patients with 5 or more BCG administrations during induction met the definition for being BCG-unresponsive; this is influenced by the low adherence to BCG maintenance protocol. Conclusions: Only a third of NMIBC patients are given intravesical BCG treatment. Adherence to BCG maintenance protocols is suboptimal. Rates of cystectomy/ exenteration are low, suggesting patients’ preference of bladder preservation and the unmet need for new bladder-sparing alternatives.

This study investigated the treatment patterns and outcomes for US veteran patients with chronic myeloid leukemia-chronic phase (CML-CP) initiated on imatinib (IM).Patients (age≥18 years) with at least one CML diagnosis (International Classification of Diseases, Ninth Edition Clinical Modification: 205.1x) during the period January 1, 2000, to June 30, 2011, and initiated on IM as first-line therapy were identified in the VISN 16 data warehouse (N=137). Accelerated and blastic phases (AP/BP) were identified on the basis of WHO classification using complete blood count (CBC) data. Rates of IM dose adjustment, discontinuation, and switching to another drug therapy were estimated. Time to discontinuation, progression to AP/BP, and survival were assessed using Kaplan-Meier analysis (KM).During follow-up, 19.0% of patients had at least one dose increase; of these, 19.2% switched to another therapy. Dose reductions occurred in 25.6% of patients. Among patients who discontinued IM (n=74; 54.0%), whereas 16.2% switched to other therapies, 27.0% neither restarted IM nor switched to other therapies. KM showed that 25.6% and 42.4% of patients discontinued IM treatment by year 1 and 2, and 8.1% and 16.0% demonstrated disease progression by year 1 and 2, respectively. Among patients who experienced disease progression (n=28), 32.1% continued IM postprogression, 32.1% discontinued IM before progression, 28.6% discontinued IM postprogression without switching, and 7.1% switched to other therapies postprogression. The mortality rates were 3.0% and 9.5% after IM initiation, and 21.7% and 42.7% after disease progression by year 1 and 2, respectively.In this veteran population, a substantial number of IM-treated patients, including those with disease progression, either discontinued or interrupted IM use without switching to other therapies.

This study was conducted to evaluate the treatment outcomes associated with common second-line targeted therapies given after first-line sunitinib for metastatic renal cell carcinoma (mRCC). The sample comprised patients with mRCC (n = 257) who were receiving second-line everolimus, sorafenib, or temsirolimus between April 1, 2008, and February 29, 2011, after first-line sunitinib treatment. The patients were followed-up from the start of second-line treatment until treatment failure (defined as advancement to a third-line therapy or to mortality) or the last observation in the medical and pharmacy databases. Treatment failure was observed in 38.5% (n = 99) of cases: 20.2% of patients (n = 52) advanced a line of treatment; and 18.3% of patients (n = 47) died. Kaplan-Meier analysis indicated a statistical difference in time to treatment failure among the 3 second-line targeted therapies (log-rank test, P = .045). The estimated 1-year cumulative probabilities of treatment failure were 49.9% for everolimus, 68.4% for sorafenib, and 71.4% for temsirolimus. In a multivariate Cox proportional hazards model, a higher adjusted risk of treatment failure vs. everolimus was observed for both temsirolimus (hazard ratio [HR] 2.05 [95% CI, 1.26-3.35]; P = .004) and sorafenib (HR 1.77 [95% CI, 1.02-3.07]; P = .043). The results of this real-world data analysis suggest that the risk of second-line treatment failure after first-line sunitinib was significantly higher with temsirolimus and sorafenib compared with everolimus.

Amy Guo,1 Michael Grabner,2 Swetha Rao Palli,2 Jessica Elder,1 Matthew Sidovar,1 Peter Aupperle,1 Stephen Krieger31Acorda Therapeutics Inc., Ardsley, New York, NY, USA; 2HealthCore Inc., Wilmington, DE, USA; 3Corinne Goldsmith Dickinson Center for MS, Icahn School of Medicine at Mount Sinai, New York, NY, USA Background: Although previous studies have demonstrated the clinical benefits of dalfampridine extended release (D-ER) tablets in patients with multiple sclerosis (MS), there are limited real-world data on D-ER utilization and associated outcomes in patients with MS. Purpose: The objective of this study was to evaluate treatment patterns, budget impact, and health care resource utilization (HRU) associated with D-ER use in a real-world setting. Methods: A retrospective claims database analysis was conducted using the HealthCore Integrated Research DatabaseSM. Adherence (measured by medication possession ratio, or [MPR]) and persistence (measured by days between initial D-ER claim and discontinuation or end of follow-up) were evaluated over 1-year follow-up. Budget impact was calculated as cost per member per month (PMPM) over the available follow-up period. D-ER and control cohorts were propensity-score matched on baseline demographics, comorbidities, and MS-related resource utilization to compare walking-impairment-related HRU over follow-up. Results: Of the 2,138 MS patients identified, 1,200 were not treated with D-ER (control) and 938 were treated with D-ER. Patients were aged 51 years on average and 74% female. Approximately 82.6% of D-ER patients were adherent (MPR >80%). The estimated budget impact range of D-ER was $0.014–$0.026 PMPM. Propensity-score-matched D-ER and controls yielded 479 patients in each cohort. Postmatching comparison showed that the D-ER cohort was associated with fewer physician (21.5% vs 62.4%, P

Tamoxifen (TAM) has been prescribed for decades and aromatase inhibitors (AIs) have been used since the early 2000s in preventing subsequent breast cancer. However, outside of clinical trials, the effectiveness of AIs is not established. We examined the long-term risk of subsequent breast cancer among survivors treated with TAM and AIs in a large health plan. The study included 22,850 survivors, diagnosed with initial breast cancer (stages 0-IV) from 1996 to 2006, and followed 13 years maximum. We compared the risk of subsequent breast cancer in those who used TAM and/or AIs versus nonusers (the reference group). Hazard ratios (HR) adjusted for patient, tumor, treatment, and health-care characteristics were estimated using Cox models with time-dependent drug use status. Women who used TAM/AIs had a large reduction in risk of subsequent breast cancer compared with nonusers. While confidence intervals (CI) for all hormone treatment groups overlapped, women with high adherence (medication possession ratio ≥80%) who used AIs exclusively and had positive ER or PR receptor status had the greatest risk reduction (HR = 0.34, 95% CI: 0.28-0.41), followed by those who switched from TAM to AIs (HR = 0.39, 95% CI: 0.30-0.49), and those who used TAM exclusively (HR = 0.42, 95% CI: 0.36-0.47). Women with high adherence had the greatest risk reduction in subsequent breast cancer, but the results were not substantially different from women who took the drugs less regularly. Compared with nonusers, the reduction in subsequent breast cancer risk ranged from 58% to 66% across the hormone treatment groups and degree of adherence.

Summary What is known and Objective: Patients with sickle-cell disease (SCD) receiving chronic transfusions of red blood cells are at risk of developing serious adverse effects. Iron chelation therapy (ICT) helps eliminate iron overload by binding with plasma iron to form a non-toxic conjugate that can be safely excreted from the body. Two iron chelating agents are currently available in the United States: Deferoxamine (DFO) is an injectable formulation, and deferasirox (Exjade®) is an oral suspension. This study compared the frequency of hospitalizations, persistence and compliance of patients with SCD from Medicaid programmes treated with DFO vs. deferasirox. Methods: Health care claims from Medicaid Florida (1998–2007), Missouri (1993–2008) and New Jersey (1996–2008) were analysed. Patients with continuous enrolment for ≥6 months prior to ICT initiation and ≥1 SCD diagnosis were included in the analysis. Patients were divided into four cohorts: patients treated with DFO (any-DFO group) and patients treated with deferasirox (any-deferasirox group); the latter was further divided into patients initiated on DFO and then switched to deferasirox (deferasirox switchers), and patients treated with deferasirox-only (deferasirox-only group). Frequency of hospitalization for crisis conditions related to SCD as well as length of stay pre- and post-ICT treatment initiation were assessed. Persistence was defined as time to drug discontinuation with ≥1 Rx gap, using Kaplan–Meier approach. Compliance was estimated using a medication possession ratio (MPR) based on the drug exposure approach. Adjusted analyses of persistence and compliance were also conducted. Results: A total of 217 (mean age: 19·4 years, 39·2 men), 275 (20·1 years, 41·5% men), 105 (19·4 years, 42·9% men) and 166 (20·4 years, 41·6% men) patients were included in the any-DFO, any-deferasirox, deferasirox switchers and deferasirox-only groups, respectively. After ICT initiation, the any-deferasirox and deferasirox-only groups experienced a statistically significant reduction in the frequency of hospitalizations relative to pretreatment [any-deferasirox: from 0·09 to 0·06 hospitalizations per patient per month (pmpm), P = 0·0105; deferasirox-only: from 0·11 to 0·07 hospitalizations pmpm, P = 0·0188], whereas it remained stable in the any-DFO group at 0·08 hospitalizations pmpm (P = 0·9483). The Kaplan–Meier rates of medication persistence assessed at 6 and 12 months of follow-up were significantly lower for DFO patients (6 months: 0·34, 12 months: 0·21) as compared to all deferasirox (0·51, 0·29, P = 0·0002), deferasirox switchers (0·56, 0·37, P = 0·0002) and deferasirox-only (0·47, 0·24, P = 0·0176) patients. Similarly, compliance to treatment was significantly lower for patients treated with DFO (mean MPR: 0·64) compared with any-deferasirox (0·78, P

To examine the effect of timely zoledronic acid (ZA) treatment on clinical outcomes and health care utilization in patients with bone-metastatic prostate cancer. Patients with prostate cancer and bone metastasis were identified in a Veterans Affairs database (01/2002-09/2009). Eligible patients had no documented skeletal-related events (SREs) before the index date (that is, the first bone metastasis diagnosis date). Patients who received early ZA treatment, defined as having a ZA infusion after the index date and before any recorded SREs, were matched 1:1 on propensity score to patients not treated with bisphosphonates (BPs). Risks of SREs, hospitalization and death during the 6-month post-index period were compared between matched cohorts using Kaplan-Meier analyses. Baseline characteristics were well balanced between the matched cohorts (n = 73 per group). 6-month SRE-free survival and hospitalization-free survival were higher in patients receiving timely ZA than patients without BP treatment (91.7 versus 71.5%, P0.01; 80.5 versus 66.3%, P = 0.05, respectively). 6-month mortality risk was significantly lower in patients treated with ZA versus those without BP treatment (4.3 versus 13.8%, P = 0.04). Timely ZA intervention in bone-metastatic prostate cancer patients was associated with significant reductions in 6-month risks of SREs, hospitalization and mortality, as compared with no BP treatment.