Use of cystatin C to inform metformin eligibility among adult veterans with diabetes.

AimsRecommendations for metformin use are dependent on eGFR category: eGFR >45 ml/min/1.73 m2 - "first-line agent"; eGFR 30-44 - "use with caution"; eGFR<30 - "do not use". Misclassification of metformin eligibility by creatinine-based MDRD GFR estimates (eGFRcr) may contribute to its misuse. We investigated the impact of cystatin c estimates of GFR (eGFRcys) on metformin eligibility.MethodsIn a consecutive cohort of 550 Veterans with diabetes, metformin use and eligibility were assessed by eGFR category, using eGFRcr and eGFRcys. Discrepancy in eligibility was defined as cases where eGFRcr and eGFRcys categories (<30, 30-44, 45-60, and >60 ml/min/1.73 m2) differed with an absolute difference in eGFR of >5 ml/min/1.73 m2. We modeled predictors of metformin use and eGFR category discrepancy with multivariable relative risk regression and multinomial logistic regression.ResultsSubjects were 95% male, median age 68, and racially diverse (45% White, 22% Black, 11% Asian, 22% unknown). Metformin use decreased with severity of eGFRcr category, from 63% in eGFRcr >60 to 3% in eGFRcr <30. eGFRcys reclassified 20% of Veterans into different eGFR categories. Factors associated with a more severe eGFRcys category compared to eGFRcr were older age (aOR = 2.21 per decade, 1.44-1.82), higher BMI (aOR = 1.04 per kg/m2, 1.01-1.08) and albuminuria >30 mg/g (aOR = 1.81, 1.20-2.73).ConclusionsMetformin use is low among Veterans with CKD. eGFRcys may serve as a confirmatory estimate of kidney function to allow safe use of metformin among patients with CKD, particularly among older individuals and those with albuminuria

Healthy People/Healthy Economy: A Five-Year Review and Five Priorities for the Future

The first Report Card (2011) identified a dozen priorities for decisive action to improve health in Massachusetts. The need to act was summed up in the title of our first report, The Boston Paradox, published in 2007. As we saw it, Massachusetts had "plenty of health care, but not enough health." The Commonwealth ranked high on many measures of health status and health care compared to the rest of the United States. But it was not immune to risks such as rising rates of overweight, obesity and diabetes that threatened to increase the burden of illness on many families, to drive up health-care costs that were already too high, and to sap the economic vitality of the state.So how have we done? Clear signs have emerged that rates of growth in overweight and obesity in the Massachusetts population at large have stayed flat over the last two to three years. Similarly, overweight and obesity have leveled off among youth in several high-risk communities aided by the Commonwealth's Mass in Motion program. We have seen a widespread effort to promote a "culture of health."A real culture of health requires investment of real dollars in priorities that shape our lifelong health. Here there have been encouraging signs as well.In 2011 we documented a "mismatch": increased health care spending by the Commonwealth came at the expense of investment in crucial long-term determinants of health such as education and public health programs. Since then, the Commonwealth's spending on health care and other health-related priorities has come closer into balance.But it is far too early to give ourselves good grades. First, it remains to be seen whether the unhealthy weight gain in Massachusetts has stopped for good. After all, America's obesity crisis has been more than 30 years in the making. In Massachusetts, rates of overweight, obesity and related conditions such as diabetes remain at historically high levels. Disparities in rates and resulting health risks among African-American and Latino residents remain stubbornly high. There is an especially urgent need for addressing what can be termed "ZIP-code disparities," or huge differences in health between affluent communities and low-income, high-risk urban neighborhoods throughout the state.And while Massachusetts adults are among the nation's healthiest, the state's youth consistently fall in the middle of the pack for risks such as overweight and obesity, with especially troubling numbers for the youngest children. These facts do not bode well for our economic future.It likewise remains to be seen whether the Commonwealth's tentative steps toward a better balance can be sustained in state expenditures on both health care and the determinants of health. The growth in health-care spending in Massachusetts has slowed in the last two to three years, but experts are divided on whether this trend will continue. Meanwhile, recent budget increases for public health and other health-related programs have not come close to making up for cuts in real inflation-adjusted spending suffered over the last 15 years.And so as Governor Baker, the Legislature and community leaders reset the state's agenda, we offer one overarching goal and five specific recommendations for further action. The Commonwealth's overarching goal should be to make steady progress toward a culture of health. To make this a reality, Massachusetts officials need to fully embrace the "health in all policies" approach that many experts and health-care leaders see as essential if we are to improve health, avoid unnecessary spending, and sustain our economic vitality. Nearly every government action, from capital planning and construction to the design or reform of programs, represents an opportunity to contribute to better health for all residents

Developing and Validating Service Innovation Readiness

Services have emerged as major economic activities in Taiwan in recent years, since more than 70% of GDP in Taiwan is generated by service sectors. Nevertheless, knowledge of service innovation remained under-explored. To address this research gap, this study proposed the concept of “Service Innovation Readiness” based on expert interviews of five service industries (Department Stores and Retail, Financial, Biotechnology and Medicine, Tourism, and Information Services) and a review of existing literature. Given this, we propose a multi-dimensional construct of Service Innovation Readiness (SIR) consisting of five factors: Strategic Investment, Risk Tolerance, Innovative Champion, IT Experience, and Inter-Organizational Collaboration. To validate the framework of SIR, a survey was conducted in the five service sectors and the final sample consisted of 312 valid cases. The results grant support to the framework, showing that SIR is a multi-dimensional construct. The positive relationship between SIR and service performance provides further evidence to support the predictive validity of the construct measurement. Conclusion and implications are included

Step by Step to Fairness: Attributing Societal Bias in Task-oriented Dialogue Systems

Recent works have shown considerable improvements in task-oriented dialogue (TOD) systems by utilizing pretrained large language models (LLMs) in an end-to-end manner. However, the biased behavior of each component in a TOD system and the error propagation issue in the end-to-end framework can lead to seriously biased TOD responses. Existing works of fairness only focus on the total bias of a system. In this paper, we propose a diagnosis method to attribute bias to each component of a TOD system. With the proposed attribution method, we can gain a deeper understanding of the sources of bias. Additionally, researchers can mitigate biased model behavior at a more granular level. We conduct experiments to attribute the TOD system's bias toward three demographic axes: gender, age, and race. Experimental results show that the bias of a TOD system usually comes from the response generation model

Japanese Encephalitis in Small-Scale Pig Farming in Rural Cambodia: Pig Seroprevalence and Farmer Awareness

Japanese encephalitis (JE) is endemic in Cambodia, but circulation of JE virus (JEV) among domestic pigs has previously only been studied in the southern part of the country. The main purpose of this study was to determine the seroprevalence of JEV antibodies in smallholder pigs held in rural areas of Kampong Thom, Preah Vihear, Ratanakiri, and Stung Treng provinces, northeastern Cambodia. Another purpose was to identify possible associations between serologic status and other factors, such as reproductive disorders, and to investigate the farmers' knowledge of mosquito-borne diseases and use of preventive measures. In October 2019, 139 households were visited throughout the study area, and 242 pigs were sampled for blood. The sera were analysed with ELISA for JEV antibodies. Household representatives were interviewed, and data were recorded for each sampled pig. The apparent seroprevalence was 89.1% in pigs between 3 and 6 months of age, and 100% in pigs over 6 months of age. In total, 93.0% of the pigs tested positive. Province appeared to be the only factor significantly associated with serologic status (p < 0.001). Almost all (97.8%) respondents knew that mosquitos could transmit diseases, and 70.5% had heard of JE. However, only one respondent knew that JEV is transmitted to people through mosquito bites. Very few respondents knew that pigs can become infected with JEV, and no one knew that mosquitos transmit the virus. All families used some sort of mosquito protection for themselves, but only 15.1% protected their pigs from mosquito bites. The children were vaccinated against JE in 93 households, while adults only were vaccinated in eight households. The results suggest that JEV transmission is intense in northeastern Cambodia, and that people's knowledge about the transmission route of JEV and the role of pigs in the transmission cycle is low. Fortunately, people are well aware of mosquito-borne diseases in general and use mosquito protection, and many children are vaccinated against JE. Nonetheless, it is important that national vaccination is continued, and that people-especially in rural areas where pigs are commonly kept-are educated on the ecology and transmission of JEV

Fosmidomycin Decreases Membrane Hopanoids and Potentiates the Effects of Colistin on Burkholderia multivorans Clinical Isolates

Burkholderia cepacia complex (Bcc) pulmonary infections in people living with cystic fibrosis (CF) are difficult to treat because of the extreme intrinsic resistance of most isolates to a broad range of antimicrobials. Fosmidomycin is an antibacterial and antiparasitic agent that disrupts the isoprenoid biosynthesis pathway, a precursor to hopanoid biosynthesis. Hopanoids are involved in membrane stability and contribute to polymyxin resistance in Bcc bacteria. Checkerboard MIC assays determined that although isolates of the Bcc species B. multivorans were highly resistant to treatment with fosmidomycin or colistin (polymyxin E), antimicrobial synergy was observed in certain isolates when the antimicrobials were used in combination. Treatment with fosmidomycin decreased the MIC of colistin for isolates as much as 64-fold to as low as 8 μg/ml, a concentration achievable with colistin inhalation therapy. A liquid chromatography-tandem mass spectrometry technique was developed for the accurate quantitative determination of underivatized hopanoids in total lipid extracts, and bacteriohopanetetrol cyclitol ether (BHT-CE) was found to be the dominant hopanoid made by B. multivorans. The amount of BHT-CE made was significantly reduced upon fosmidomycin treatment of the bacteria. Uptake assays with 1-N-phenylnaphthylamine were used to determine that dual treatment with fosmidomycin and colistin increases membrane permeability, while binding assays with boron-dipyrromethene-conjugated polymyxin B illustrated that the addition of fosmidomycin had no impact on polymyxin binding. This work indicates that pharmacological suppression of membrane hopanoids with fosmidomycin treatment can increase the susceptibility of certain clinical B. multivorans isolates to colistin, an agent currently in use to treat pulmonary infections in CF patients