INTRODUCTION: Screening for prediabetes and type 2 diabetes may allow earlier detection, diagnosis, and treatment. The US Preventive Services Task Force recommends screening every 3 years for abnormal blood glucose among adults aged 40 to 70 years with overweight or obesity. Using IQVIA Ambulatory Electronic Medical Records, we estimated the proportion of adults aged 40 to 70 years with overweight or obesity who received blood glucose testing within 3 years from baseline in 2016. METHODS: We identified 1,338,509 adults aged 40 to 70 years with overweight or obesity in 2016 and without pre-existing diabetes. We included adults whose records were present in the data set for at least 2 years before their index body mass index (BMI) in 2016 and 3 years after the index BMI (2017-2019), during which we examined the occurrence of blood glucose testing. We calculated the unadjusted and adjusted prevalence of receiving blood glucose testing. RESULTS: The unadjusted prevalence of receiving blood glucose testing was 33.4% when it was defined as having a hemoglobin A(1c) or fasting plasma glucose measure. The unadjusted prevalence was 74.3% when we expanded the definition of testing to include random plasma glucose and unspecified glucose measures. Adults with obesity were more likely to receive the test than those with overweight. Men (vs women) and adults aged 50 to 59 years (vs other age groups) had higher testing rates. CONCLUSION: Our findings could inform clinical and public health promotion efforts to improve screening for blood glucose levels among adults with overweight or obesity.

We examine how a complex transcription network composed of seven “master” regulators and hundreds of target genes evolved over a span of approximately 70 million years. The network controls biofilm formation in several Candida species, a group of fungi that are present in humans both as constituents of the microbiota and as opportunistic pathogens. The ability to form biofilms is crucial for microbial colonization of different host niches, particularly when an implanted medical device is present. We examined and compared the network underlying biofilm formation across four Candida species (C. albicans, C. dubliniensis, C. tropicalis, and C. parapsilosis), all of which form biofilms composed of multiple cell types. To describe the salient features of the network across different species, we employed four approaches: (1) we phenotypically characterized the biofilms formed by these species using a variety of methods; (2) we knocked out — one by one — the master regulators identified in C. albicans in the four species and monitored their effect on biofilm formation; (3) we identified the target genes of 18 master regulator orthologs across the four species by performing ChIP-seq experiments; and (4) we carried out transcriptional profiling across each species during biofilm formation. Additional network information was obtained by analyzing an interspecies hybrid formed between the two most closely related species, C. albicans and C. dubliniensis. We observed two major types of changes that have occurred in the biofilm circuit since the four species last shared a common ancestor. Master regulator “substitutions” occurred over relatively long evolutionary times, resulting in different species having overlapping, but different sets of master regulators of biofilm formation. Second, massive changes in the connections between the master regulators and their target genes occurred over much shorter timescales. Both types of change are crucial to account for the structures of the biofilm networks in extant species. We believe this analysis is the first detailed, empirical description of how a complex transcription network has evolved.Competing Interest StatementThe authors have declared no competing interest.

PURPOSE: To study contemporary trends in the diagnosed prevalence and incidence of age-related eye diseases among Medicare fee-for-service (FFS) beneficiaries. DESIGN: Analysis of Medicare administrative claims data. PARTICIPANTS: Medicare FFS beneficiaries aged 68 and older from 2005-2020. Those included were continuously enrolled in both Part A and Part B for 3 years, including the index year and 2-year lookback period. METHODS: Annual cross-sectional diagnosed prevalence and incidence rates were calculated. Age-standardization was performed using the direct standardization method to account for changes in the age-structure of the study population. Rates stratified by demographics (age, sex, race, and ethnicity) were also calculated. MAIN OUTCOME MEASURES: Annual prevalence and incidence of diagnosed age-related macular degeneration (AMD), diabetic retinopathy (DR) (among those with diabetes), and glaucoma. RESULTS: At baseline, in 2005, 60% of included beneficiaries were female, 20% were aged ≥85, 86% were non-Hispanic White, and one-quarter had diabetes. From 2005-2019, the prevalence of a diagnosis of any of the conditions studied increased from 15.0% (N=3,312,812) to 17.9% (N=3,731,281). Diagnosed incidence decreased over this period from 4.7% (N=917,846) in 2005 to 4.2% in 2019 (N=757,696). The diagnosed prevalence of AMD increased from 6.8% (N=1,504,770) to 9.4% (N=1,965,176); the diagnosed prevalence of any DR among those with diabetes decreased from 9.3% (N= 504,135) to 9.0% (N=532,859), though the diagnosed prevalence of vision-threatening DR increased from 2.0% to 3.4%; and the diagnosed prevalence of any diagnosed glaucoma decreased from 8.8% (N= 1,951,141) to 8.1% (N= 1,692,837). In 2020, the diagnosed prevalence and incidence of all diagnoses decreased. During the study period we detected demographic differences in the prevalence and incidence of diagnosis of each condition. CONCLUSIONS: This study presents updated data on the prevalence and incidence of diagnosed major chronic, age-related eye diseases among Medicare FFS beneficiaries. Compared to older epidemiological estimates, we found that the diagnosed prevalence of each condition studied was higher in more recent years. These findings may inform public health and policy planning and resource allocation to address the eye health of an increasingly older US population.

IMPORTANCE: The coronavirus 2019 (COVID-19) pandemic abruptly impacted health care service delivery and utilization. However, the impact on older adults with diabetes in the United States is unclear. OBJECTIVE: To estimate changes in health care utilization among older adults with diabetes during the initial 2 years of the COVID-19 pandemic compared to the 2 years before, and to examine the variation in utilization changes by demographic and socioeconomic characteristics. DESIGN SETTING AND PARTICIPANTS: In this study, we analyzed changes in utilization, measured by the average use of health care services per 1,000 persons with diabetes, using medical claims for Medicare fee-for-service beneficiaries aged 67 years and above. Utilization changes by setting (acute inpatient, emergency room [ER], hospital outpatient, physician office, and ambulatory surgery center [ASC]) and by media (telehealth and in-person) were examined for 22 months of the pandemic (03/2020-12/2021) compared with pre-pandemic period (03/2018-12/2019). We also estimated utilization changes by beneficiaries' age group, sex, race/ethnicity, and residential urbanicity. RESULTS: The study sample consisted of approximately 6 million beneficiaries with diabetes each month. In the first 2 years of the pandemic, the average use of health care services by setting was 5-17% lower than the pre-pandemic level for all types of services. Phase 1 (03/2020-05/2020) had the largest decrease in utilization: physician office visits changed by -51.2% (95% CI, -55.0% to -47.5%), ASC procedures by -45.1% (95% CI, -49.8% to -40.4%), ER visits by -36.9% (95% CI, -39.0% to -34.7%), acute inpatient stays by -31.5% (95% CI, -33.6% to -29.3%), and hospital outpatient visits by -27% (95% CI, -29.3% to -24.8%). The reduction in utilization varied by sociodemographic subgroup. During the pandemic, the use of telehealth visits increased by 511.1% (95% CI, 502.2% to 520.0%) compared to the pre-pandemic period. The increase was smaller among rural residents. CONCLUSIONS AND RELEVANCE: Medicare beneficiaries with diabetes experienced a reduction in the use of health care services during the COVID-19 pandemic, some of which persisted through two years into the pandemic. Telehealth visits increased, but not enough to overcome decreases in in-person visits. Understanding these patterns may help to optimize the use of health care resources for diabetes management in the post-pandemic era and during future emergencies.

Seoul virus (SEOV) is an emerging global health threat that can cause hemorrhagic fever with renal syndrome (HFRS), which results in case fatality rates of ∼2%. There are no approved treatments for SEOV infections. We developed a cell-based assay system to identify potential antiviral compounds for SEOV and generated additional assays to characterize the mode of action of any promising antivirals. To test if candidate antivirals targeted SEOV glycoprotein-mediated entry, we developed a recombinant reporter vesicular stomatitis virus expressing SEOV glycoproteins. To facilitate the identification of candidate antiviral compounds targeting viral transcription/replication, we successfully generated the first reported minigenome system for SEOV. This SEOV minigenome (SEOV-MG) screening assay will also serve as a prototype assay for discovery of small molecules inhibiting replication of other hantaviruses, including Andes and Sin Nombre viruses. Ours is a proof-of-concept study in which we tested several compounds previously reported to have activity against other negative-strand RNA viruses using our newly developed hantavirus antiviral screening systems. These systems can be used under lower biocontainment conditions than those needed for infectious viruses, and identified several compounds with robust anti-SEOV activity. Our findings have important implications for the development of anti-hantavirus therapeutics.

OBJECTIVE: To estimate medical costs associated with 17 diabetes complications and treatment procedures among Medicare beneficiaries aged ≥65 years with type 1 diabetes. RESEARCH DESIGN AND METHODS: With use of the 2006-2017 100% Medicare claims database for beneficiaries enrolled in fee-for-service plans and Part D, we estimated the annual cost of 17 diabetes complications and treatment procedures. Type 1 diabetes and its complications and procedures were identified using ICD-9/ICD-10, procedure, and diagnosis-related group codes. Individuals with type 1 diabetes were followed from the year when their diabetes was initially identified in Medicare (2006-2015) until death, discontinuing plan coverage, or 31 December 2017. Fixed-effects regression was used to estimate costs in the complication occurrence year and subsequent years. The cost proportion of a complication was equal to the total cost of the complication, calculated by multiplying prevalence by the per-person cost divided by the total cost for all complications. All costs were standardized to 2017 U.S. dollars. RESULTS: Our study included 114,879 people with type 1 diabetes with lengths of follow-up from 3 to 10 years. The costliest complications per person were kidney failure treated by transplant ($77,809 in the occurrence year and $13,556 in subsequent years), kidney failure treated by dialysis ($56,469 and $41,429), and neuropathy treated by lower-extremity amputation ($40,698 and $7,380). Sixteen percent of the total medical cost for diabetes complications was for treating congestive heart failure. CONCLUSIONS: Costs of diabetes complications were large and varied by complications. Our results can assist in cost-effectiveness analysis of treatments and interventions for preventing or delaying diabetes complications in Medicare beneficiaries aged ≥65 years with type 1 diabetes.

Combination antifungal therapy is widely used but not well understood. We analyzed the spectrophotometric readings from a multicenter study conducted by the New York State Department of Health to further characterize the in vitro interactions of the major classes of antifungal agents against Candida spp. Loewe additivity-based fractional inhibitory concentration index (FICi) analysis and Bliss independence-based response surface (BIRS) analysis were used to analyze two-drug inter- and intraclass combinations of triazoles (AZO) (voriconazole, posaconazole), echinocandins (ECH) (caspofungin, micafungin, anidulafungin), and a polyene (amphotericin B) against Candida albicans, C. parapsilosis, and C. glabrata. Although mean FIC indices did not differ statistically significantly from the additivity range of 0.5−4, indicating no significant pharmacodynamic interactions for all of the strain−combinations tested, BIRS analysis showed that significant pharmacodynamic interactions with the sum of percentages of interactions determined with this analysis were strongly associated with the FIC indices (Χ2 646, p < 0.0001). Using a narrower additivity range of 1−2 FIC index analysis, statistically significant pharmacodynamic interactions were also found with FICi and were in agreement with those found with BIRS analysis. All ECH+AB combinations were found to be synergistic against all Candida strains except C. glabrata. For the AZO+AB combinations, synergy was found mostly with the POS+AB combination. All AZO+ECH combinations except POS+CAS were synergistic against all Candida strains although with variable magnitude; significant antagonism was found for the POS+MIF combination against C. albicans. The AZO+AZO combination was additive for all strains except for a C. parapsilosis strain for which antagonism was also observed. The ECH+ECH combinations were synergistic for all Candida strains except C. glabrata for which they were additive; no antagonism was found.

OBJECTIVE: To estimate medical costs associated with 17 major diabetes-related complications and treatment procedures among Medicare beneficiaries aged ≥65 years with type 2 diabetes. RESEARCH DESIGN AND METHODS: Claims data from 100% of Medicare beneficiaries enrolled in fee-for-service plans from 2006 to 2017 were analyzed. Records with type 2 diabetes and complications were identified using ICD-9, ICD-10, and diagnosis-related group codes. The index year was the year when a person was first identified as having diabetes with an inpatient claim or an outpatient claim plus another inpatient/outpatient claim in the 2 years following the first claim in Medicare. Included individuals were followed from index years until death, discontinuation of plan coverage, or 31 December 2017. Fixed-effects regression was used to estimate the cost in years when the complication event occurred and in subsequent years. The total cost for each complication was calculated for 2017 by multiplying the complication prevalence by the cost estimate. All costs were standardized to 2017 U.S. dollars. RESULTS: Our study included 10,982,900 beneficiaries with type 2 diabetes. Follow-up ranged from 3 to 10 years. The three costliest complications were kidney failure treated by transplant (occurring year $79,045, subsequent years $17,303), kidney failure treated by dialysis ($54,394, $38,670), and lower-extremity amputation ($38,982, $8,084). Congestive heart failure accounted for the largest share (18%) of total complication costs. CONCLUSIONS: Costs associated with diabetes complications were substantial. Our cost estimates provide essential information needed for conducting economic evaluation of treatment and programs to prevent and delay diabetes complications in Medicare beneficiaries.

INTRODUCTION: Geographic disparities in diabetes burden exist throughout the United States (US), with many risk factors for diabetes clustering at a community or neighborhood level. We hypothesized that the likelihood of new onset type 2 diabetes (T2D) would differ by community type in three large study samples covering the US. RESEARCH DESIGN AND METHODS: We evaluated the likelihood of new onset T2D by a census tract-level measure of community type, a modification of RUCA designations (higher density urban, lower density urban, suburban/small town, and rural) in three longitudinal US study samples (REGARDS [REasons for Geographic and Racial Differences in Stroke] cohort, VADR [Veterans Affairs Diabetes Risk] cohort, Geisinger electronic health records) representing the CDC Diabetes LEAD (Location, Environmental Attributes, and Disparities) Network. RESULTS: In the REGARDS sample, residing in higher density urban community types was associated with the lowest odds of new onset T2D (OR [95% CI]: 0.80 [0.66, 0.97]) compared to rural community types; in the Geisinger sample, residing in higher density urban community types was associated with the highest odds of new onset T2D (OR [95% CI]: 1.20 [1.06, 1.35]) compared to rural community types. In the VADR sample, suburban/small town community types had the lowest hazard ratios of new onset T2D (HR [95% CI]: 0.99 [0.98, 1.00]). However, in a regional stratified analysis of the VADR sample, the likelihood of new onset T2D was consistent with findings in the REGARDS and Geisinger samples, with highest likelihood of T2D in the rural South and in the higher density urban communities of the Northeast and West regions; likelihood of T2D did not differ by community type in the Midwest. CONCLUSIONS: The likelihood of new onset T2D by community type varied by region of the US. In the South, the likelihood of new onset T2D was higher among those residing in rural communities.

IMPORTANCE: While diabetes prevalence among US adults has increased in recent decades, few studies document trends in diabetes-related eye disease. OBJECTIVE: To examine 10-year trends (2009-2018) in annual prevalence of Medicare beneficiaries with diabetes with a diagnosis of diabetic macular edema (DME) or vision-threatening diabetic retinopathy (VTDR) and trends in treatment. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study using Centers for Medicare & Medicaid Services research identifiable files, data for patients 65 years and older were analyzed from claims. Beneficiaries were continuously enrolled in Medicare Part B fee-for-service (FFS) insurance for the calendar year and had a diagnosis of diabetes on 1 or more inpatient claims or 2 or more outpatient claims during the calendar year or a 1-year look-back period. MAIN OUTCOMES AND MEASURES: Using diagnosis and procedure codes, annual prevalence was determined for beneficiaries with 1 or more claims for (1) any DME, (2) either DME or VTDR, and (3) anti-vascular endothelial growth factor (VEGF) injections, laser photocoagulation, or vitrectomy, stratified by any DME, VTDR with DME, and VTDR without DME. Racial and ethnic disparities in diagnosis and treatment are presented for 2018. RESULTS: In 2018, 6 960 823 beneficiaries (27.4%) had diabetes; half were aged 65 to 74 years (49.7%), half (52.7%) were women, and 75.7% were non-Hispanic White. From 2009 to 2018, there was an increase in the annual prevalence of beneficiaries with diabetes who had 1 or more claims for any DME (1.0% to 3.3%) and DME/VTDR (2.8% to 4.3%). Annual prevalence of anti-VEGF increased, particularly among patients with any DME (15.7% to 35.2%) or VTDR with DME (20.2% to 47.6%). Annual prevalence of laser photocoagulation decreased among those with any DME (45.5% to 12.5%), VTDR with DME (54.0% to 20.3%), and VTDR without DME (22.5% to 5.8%). Among all 3 groups, prevalence of vitrectomy in 2018 was less than half that in 2009. Prevalence of any DME and DME/VTDR was highest among Hispanic beneficiaries (5.0% and 7.0%, respectively) and Black beneficiaries (4.5% and 6.2%, respectively) and lowest among non-Hispanic White beneficiaries (3.0% and 3.8%, respectively). Among those with DME/VTDR, anti-VEGF was most prevalent among non-Hispanic White beneficiaries (30.3%). CONCLUSIONS AND RELEVANCE: From 2009 to 2018, prevalence of DME or VTDR increased among Medicare Part B FFS beneficiaries alongside an increase in anti-VEGF treatment and a decline in laser photocoagulation and vitrectomy.

BACKGROUND: Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes. METHODS: In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR). FINDINGS: In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources. INTERPRETATION: All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

We examine how a complex transcription network composed of seven 'master' regulators and hundreds of target genes evolved over a span of approximately 70 million years. The network controls biofilm formation in several Candida species, a group of fungi that are present in humans both as constituents of the microbiota and as opportunistic pathogens. Using a variety of approaches, we observed two major types of changes that have occurred in the biofilm network since the four extant species we examined last shared a common ancestor. Master regulator 'substitutions' occurred over relatively long evolutionary times, resulting in different species having overlapping, but different sets of master regulators of biofilm formation. Second, massive changes in the connections between the master regulators and their target genes occurred over much shorter timescales. We believe this analysis is the first detailed, empirical description of how a complex transcription network has evolved.

Estimates based on the National Inpatient Sample (NIS) showed that diabetes-related nontraumatic lower- extremity amputation (NLEA) rates declined among hospitalized patients between 2000 and 2009, followed by an increasing NLEA rate between 2009 and 2015 (1). The increase was largely observed in young and middle-aged adults (1). However, the NIS dataset includes only inpatient admissions; minor amputation surgeries that were performed in ambulatory settings were not included in these estimates. In addition, NIS data are event-based, and multiple amputations in the same person are considered as a new event each time. In the current study, we used the IBM MarketScan Commercial Database to examine NLEA occurring in inpatient and outpatient settings among privately insured adults 18–64 years of age with diabetes.

BACKGROUND: Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time. METHODS: In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995-2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time. FINDINGS: Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from -1·1% to -10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions. INTERPRETATION: The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Andes virus (ANDV) and Sin Nombre virus (SNV), highly pathogenic hantaviruses, cause hantavirus pulmonary syndrome in the Americas. Currently no therapeutics are approved for use against these infections. Griffithsin (GRFT) is a high-mannose oligosaccharide-binding lectin currently being evaluated in phase I clinical trials as a topical microbicide for the prevention of human immunodeficiency virus (HIV-1) infection (ClinicalTrials.gov Identifiers: NCT04032717, NCT02875119) and has shown broad-spectrum in vivo activity against other viruses, including severe acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, and Nipah virus. In this study, we evaluated the in vitro antiviral activity of GRFT and its synthetic trimeric tandemer 3mGRFT against ANDV and SNV. Our results demonstrate that GRFT is a potent inhibitor of ANDV infection. GRFT inhibited entry of pseudo-particles typed with ANDV envelope glycoprotein into host cells, suggesting that it inhibits viral envelope protein function during entry. 3mGRFT is more potent than GRFT against ANDV and SNV infection. Our results warrant the testing of GRFT and 3mGRFT against ANDV infection in animal models.

OBJECTIVE: Diabetes is a leading cause of nontraumatic lower-extremity amputation (NLEA) in the U.S. After a period of decline, some national U.S. data have shown that diabetes-related NLEAs have recently increased, particularly among young and middle-aged adults. However, the trend for older adults is less clear. RESEARCH DESIGN AND METHODS: To examine NLEA trends among older adults with diabetes (≥67 years), we used 100% Medicare claims for beneficiaries enrolled in Parts A and B, also known as fee for service (FFS). NLEA was defined as the highest-level amputation per patient per calendar year. Annual NLEA rates were estimated from 2000 to 2017 and stratified by age-group, sex, race/ethnicity, NLEA level (toe, foot, below-the-knee amputation [BKA], above-the-knee amputation [AKA]), and state. All rates were age and sex standardized to the 2000 Medicare population. Trends over time were assessed using Joinpoint regression and annual percent change (APC) reported. RESULTS: NLEA rates (per 1,000 people with diabetes) decreased by half from 8.5 in 2000 to 4.4 in 2009 (APC -7.9, P < 0.001). However, from 2009 onward, NLEA rates increased to 4.8 (APC 1.2, P < 0.01). Trends were similar across most age, sex, and race/ethnic groups, but absolute rates were highest in the oldest age-groups, blacks, and men. By NLEA type, overall increases were driven by increases in rates of toe and foot NLEAs, while BKA and AKA continued to decline. The majority of U.S. states showed recent increases in NLEA, similar to national estimates. CONCLUSIONS: This study of the U.S. Medicare FFS population shows that recent increases in diabetes-related NLEAs are also occurring in older populations but at a less severe rate than among younger adults (<65 years) in the general population. Preventive foot care has been shown to reduce rates of NLEA among adults with diabetes, and the findings of the study suggest that those with diabetes-across the age spectrum-could benefit from increased attention to this strategy.

Importance: Individuals with prediabetes are at increased risk of developing type 2 diabetes, chronic kidney disease, and cardiovascular disease. The incidence and prevalence of type 2 diabetes in the US adolescent population have increased in the last decade. Therefore, it is important to monitor the prevalence of prediabetes and varying levels of glucose tolerance to assess the future risk of type 2 diabetes in the youngest segment of the population. Objective: To examine the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and increased glycated hemoglobin A1c (HbA1c) levels in US adolescents (aged 12-18 years) and young adults (aged 19-34 years) without diabetes. Design, Setting, and Participants: This cross-sectional analyses of the 2005-2016 National Health and Nutrition Examination Survey assessed a population-based sample of adolescents and young adults who were not pregnant, did not have diabetes, and had measured fasting plasma glucose, 2-hour plasma glucose after a 75-g oral glucose tolerance test, and HbA1c levels. Analysis began in April 2017. Main Outcomes and Measures: Impaired fasting glucose was defined as fasting plasma glucose of 100 mg/dL to less than 126 mg/dL, IGT as 2-hour plasma glucose of 140 mg/dL to less than 200 mg/dL, and increased HbA1c level as HbA1c level between 5.7% and 6.4%. The prevalence of IFG, isolated IFG, IGT, isolated IGT, increased HbA1c level, isolated increased HbA1c level, and prediabetes (defined as having IFG, IGT, or increased HbA1c level) were estimated. Fasting insulin levels and cardiometabolic risk factors across glycemic abnormality phenotypes were also compared. Obesity was defined as having age- and sex-specific body mass index (calculated as weight in kilograms divided by height in meters squared) in the 95th percentile or higher in adolescents or 30 or higher in young adults. Results: Of 5786 individuals, 2606 (45%) were adolescents and 3180 (55%) were young adults. Of adolescents, 50.6% (95% CI, 47.6%-53.6%) were boys, and 50.6% (95% CI, 48.8%-52.4%) of young adults were men. Among adolescents, the prevalence of prediabetes was 18.0% (95% CI, 16.0%-20.1%) and among young adults was 24.0% (95% CI, 22.0%-26.1%). Impaired fasting glucose constituted the largest proportion of prediabetes, with prevalence of 11.1% (95% CI, 9.5%-13.0%) in adolescents and 15.8% (95% CI, 14.0%-17.9%) in young adults. In multivariable logistic models including age, sex, race/ethnicity, and body mass index, the predictive marginal prevalence of prediabetes was significantly higher in male than in female individuals (22.5% [95% CI, 19.5%-25.4%] vs 13.4% [95% CI, 10.8%-16.5%] in adolescents and 29.1% [95% CI, 26.4%-32.1%] vs 18.8% [95% CI, 16.5%-21.3%] in young adults). Prediabetes prevalence was significantly higher in individuals with obesity than in those with normal weight (25.7% [95% CI, 20.0%-32.4%] vs 16.4% [95% CI, 14.3%-18.7%] in adolescents and 36.9% [95% CI, 32.9%-41.1%] vs 16.6% [95% CI, 14.2%-19.4%] in young adults). Compared with persons with normal glucose tolerance, adolescents and young adults with prediabetes had significantly higher non-high-density lipoprotein cholesterol levels, systolic blood pressure, central adiposity, and lower insulin sensitivity (P < .05 for all). Conclusions and Relevance: In the United States, about 1 of 5 adolescents and 1 of 4 young adults have prediabetes. The adjusted prevalence of prediabetes is higher in male individuals and in people with obesity. Adolescents and young adults with prediabetes also present an unfavorable cardiometabolic risk profile, putting them both at increased risk of type 2 diabetes and cardiovascular diseases.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

Diabetes affects approximately 12% of the U.S. adult population and approximately 25% of adults aged >/=65 years. From 2009 to 2017, there was no significant change in diabetes prevalence overall or among persons aged 65-79 years (1). However, these estimates were based on survey data with <5,000 older adults. Medicare administrative data sets, which contain claims for millions of older adults, afford an opportunity to explore both trends over time and heterogeneity within an older population. Previous studies have shown that claims data can be used to identify persons with diagnosed diabetes (2). This study estimated annual prevalence and incidence of diabetes during 2001-2015 using Medicare claims data for beneficiaries aged >/=68 years and found that prevalence plateaued after 2012 and incidence decreased after 2006. In 2015 (the most recent year estimated) prevalence was 31.6%, and incidence was 3.0%. Medicare claims can serve as an important source of data for diabetes surveillance for the older population, which can inform prevention and treatment strategies.

AIMS/HYPOTHESIS: Cancer-related death is higher among people with vs without diabetes. However, it is not known if this excess risk has changed over time or what types of cancer may be driving these changes. METHODS: To estimate rates of site-specific cancer mortality in adults with vs without self-reported diagnosed diabetes, we used data from adults aged >/=18 years at the time of the interview who participated in the 1985-2012 National Health Interview Survey. Participants' data were linked to the National Death Index by the National Center for Health Statistics to determine vital status and cause of death through to the end of 2015. Cancer deaths were classified according to underlying cause of death. Death rates for five time periods (1988-1994, 1995-1999, 2000-2004, 2005-2009, 2010-2015) were estimated using discrete Poisson regression models adjusted for age, sex and race/ethnicity with p for linear trend reported (ptrend). Site-specific cancer mortality rates were stratified by diabetes status and period, and total cancer mortality rates were additionally stratified by sex, race/ethnicity, education and BMI status. RESULTS: Among adults with diabetes, age-adjusted cancer mortality rates (per 10,000 person-years) declined 25.5% from 39.1 (95% CI 30.1, 50.8) in 1988-1994 to 29.7 (26.6, 33.1) in 2010-2015, ptrend < 0.001. Among adults without diabetes, rates declined 25.2% from 30.9 (28.6, 33.4) in 1988-1994 to 23.2 (22.1, 24.2) in 2010-2015, ptrend < 0.01. Adults with diabetes remained approximately 30% more likely to die from cancer than people without diabetes, and this excess risk did not improve over time. In adults with diabetes, cancer mortality rates did not decline in some population subgroups (including black people, people with lower levels of education and obese people), and the excess risk increased for obese adults with vs without diabetes. Declines in total cancer mortality rates in adults with diabetes appear to be driven by large relative declines in cancers of the pancreas (55%) and breast (65%), while for lung cancer, declines are modest (7%). CONCLUSIONS/INTERPRETATION: Declines in cancer mortality rates were observed in adults with and without diabetes. However, adults with diabetes continue to be more likely to die from cancer than people without diabetes. This study highlights the continued need for greater cancer risk-factor mitigation, especially in adults with diabetes.

In January 2018, a woman admitted to a Delaware hospital tested positive for New World hantavirus immunoglobulin M (IgM) and immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA). Subsequent testing by CDC’s Viral Special Pathogens Branch detected New World hantavirus by nested reverse transcription–polymerase chain reaction (RT-PCR) and Andes virus by nucleic acid sequencing. This case represents the first confirmed importation of Andes virus infection into the United States; two imported cases have also been reported in Switzerland (1). Before her illness, the patient had traveled to the Andes region of Argentina and Chile from December 20, 2017, to January 3, 2018. She stayed in cabins and youth hostels in reportedly poor condition. No rodent exposures were reported. After returning to the United States on January 10, she developed fever, malaise, and myalgias on January 14. On January 17, while ill, she traveled on two commercial domestic flights. She was hospitalized during January 20–25 in Delaware and discharged to her home after clinical recovery.

Unlike superficial fungal infections of the skin and nails, which are the most common fungal diseases in humans, invasive fungal infections carry high morbidity and mortality, particularly those associated with biofilm formation on indwelling medical devices. Therapeutic management of these complex diseases is often complicated by the rise in resistance to the commonly used antifungal agents. Therefore, the availability of accurate susceptibility testing methods for determining antifungal resistance, as well as discovery of novel antifungal and antibiofilm agents, are key priorities in medical mycology research. To direct advancements in this field, here we present an overview of the methods currently available for determining (i) the susceptibility or resistance of fungal isolates or biofilms to antifungal or antibiofilm compounds and compound combinations; (ii) the in vivo efficacy of antifungal and antibiofilm compounds and compound combinations; and (iii) the in vitro and in vivo performance of anti-infective coatings and materials to prevent fungal biofilm-based infections.

Background: Candida auris is an emerging, nosocomial multidrug-resistant threat with high treatment failure rate and mortality. The optimal antifungal agent to use and susceptibility breakpoints are based on limited clinical data. Methods: Nine clinical C. auris strains were used. MICs were determined by CLSI standards. Drug treatment studies consisted of: fluconazole (FLC) dose range 0.78–200 mg/kg/12 h, micafungin (MFG) dose range 0.3125–80 mg/kg/24 h, or amphotericin B deoxycholate (AMB) dose range 0.0.78–20 mg/kg/24 hours. Plasma PK was previously determined in the murine model for all three drugs. A 96 h neutropenic murine model of invasive candidiasis (IC) was used for all studies. The Emax Hill equation was used to model the dose–response data to PK/PD index AUC/MIC (FLC and MFG) and Cmax/MIC (AMB). The static and 1 log kill doses (when achieved) and the associated PK/PD targets (AUC/MIC or Cmax/MIC) were determined and compared with previous murine IC studies with C. albicans, C. glabrata, and C. parapsilosis. Results: MIC range: FLC 2–256 mg/l, MFG 0.125–4 mg/l, and AMB 0.38–6 mg/l. Dose-dependent activity was observed with all three drugs. Net stasis was achieved against seven strains for FLC, eight strains for MFG, and eight strains for AMB. However, MFG performed significantly better than comparators for cidal endpoints. A 1 log kill endpoint was achieved in eight strains for MFG, whereas this endpoint was only achieved in one strain for FLC and three strains for AMB. PK/PD analyses demonstrated a strong relationship between AUC/MIC and treatment outcome for FLC (R2 0.61) and MFG (R2 0.77); and Cmax/MIC and treatment outcome for AMB (R2 0.64). The median static dose and 1 log kill dose (MFG only) and associated AUC/MIC or Cmax/MIC values are shown (Table).Stasis1 log killDrugDose (mg/kg/24 hours)AUC/MIC or [Cmax/MIC]Dose (mg/kg/24 hours)AUC/MICFLC10726.3MFG1.2553.73.36130AMB3.86[0.87] Conclusion: MFG was the most potent drug over the dose range achieving up to 2 log kill against eight of nine strains. PK/PD targets for C. auris against FLC and AMB were similar to other Candida species; however, MFG targets were ≥20-fold lower than C. albicans, C. glabrata, and C. parapsilosis. Using the median stasis targets and human PK for each drug, resistance thresholds could be 16 mg/l for FLC, 2–4 mg/l for MFG, and 1–2 mg/l for AMB. Disclosures: All authors: No reported disclosures.

Despite the 2009 implementation of a tobacco tax increase in Thailand, smoking rates remained unchanged between 2009 and 2011. Prior evidence has linked cigarette tax increases to compensatory behaviours aimed at lowering the cost of smoking, such as switching to lower-priced cigarette brands. Using data from 2009 and 2011 Global Adult Tobacco Surveys in Thailand, we estimated unadjusted changes in cigarette prices paid, cigarette affordability, and consumption of cigarettes in three price categories classified as upper-, middle-, and lower-priced brand tiers (or price tertiles). We used ordered logit regression to analyse the correlates of price-tier choice and to estimate the change in price-tier consumption adjusted for demographic and region characteristics. Between 2009 and 2011, real cigarette prices increased, but the affordability of cigarettes remained unchanged overall. There was a significant reduction in the consumption of cigarette brands in the top price-tier overall, accompanied by increases in the consumption of brands in the bottom and middle price-tiers, depending on the region. Adjusted estimates from the logit models indicate that, on average, the proportion of smokers selecting brands from upper- and middle price-tiers decreased while consumption of lower price-tier brands increased during the study period. The estimated shifts in consumption from more expensive to less expensive cigarette brands and the overall lack of change in cigarette affordability in Thailand between 2009 and 2011 are both factors that may have contributed to the observed lack of change in smoking rates after the 2009 tax increase.

Andes virus (ANDV) is the major cause of hantavirus pulmonary syndrome (HPS) in South America. Despite a high fatality rate (up to 40%), no vaccines or antiviral therapies are approved to treat ANDV infection. To understand the role of endocytic pathways in ANDV infection, we used 3 complementary approaches to identify cellular factors required for ANDV entry into human lung microvascular endothelial cells. We screened an siRNA library targeting 140 genes involved in membrane trafficking, and identified 55 genes required for ANDV infection. These genes control the major endocytic pathways, endosomal transport, cell signaling, and cytoskeleton rearrangement. We then used infectious ANDV and retroviral pseudovirions to further characterize the possible involvement of 9 of these genes in the early steps of ANDV entry. In addition, we used markers of cellular endocytosis along with chemical inhibitors of known endocytic pathways to show that ANDV uses multiple routes of entry to infect target cells. These entry mechanisms are mainly clathrin-, dynamin-, and cholesterol-dependent, but can also occur via a clathrin-independent manner.

BACKGROUND: Invasive candidiasis (IC) is a common cause of mortality in solid organ transplant recipients (OTRs), but knowledge of epidemiology in this population is limited. METHOD: The present analysis describes data from 15 US centers that prospectively identified IC from nearly 17,000 OTRs. Analyses were undertaken to determine predictors of infection and mortality. RESULTS: A total of 639 cases of IC were identified. The most common species was Candida albicans (46.3%), followed by Candida glabrata (24.4%) and Candida parapsilosis (8.1%). In 68 cases >1 species was identified. The most common infection site was bloodstream (44%), followed by intra-abdominal (14%). The most frequently affected allograft groups were liver (41.1%) and kidney (35.3%). All-cause mortality at 90 days was 26.5% for all species and was highest for Candida tropicalis (44%) and C. parapsilosis (35.2%). Non-white race and female gender were more commonly associated with non-albicans species. A high rate of breakthrough IC was seen in patients receiving antifungal prophylaxis (39%). Factors associated with mortality include organ dysfunction, lung transplant, and treatment with a polyene antifungal. The only modifiable factor identified was choice of antifungal drug class based upon infecting Candida species. CONCLUSION: These data highlight the common and distinct features of IC in OTRs. This article is protected by copyright. All rights reserved.

Anticipating how epidemics will spread across landscapes requires understanding host dispersal events that are notoriously difficult to measure. Here, we contrast host and virus genetic signatures to resolve the spatiotemporal dynamics underlying geographic expansions of vampire bat rabies virus (VBRV) in Peru. Phylogenetic analysis revealed recent viral spread between populations that, according to extreme geographic structure in maternally inherited host mitochondrial DNA, appeared completely isolated. In contrast, greater population connectivity in biparentally inherited nuclear microsatellites explained the historical limits of invasions, suggesting that dispersing male bats spread VBRV between genetically isolated female populations. Host nuclear DNA further indicated unanticipated gene flow through the Andes mountains connecting the VBRV-free Pacific coast to the VBRV-endemic Amazon rainforest. By combining Bayesian phylogeography with landscape resistance models, we projected invasion routes through northern Peru that were validated by real-time livestock rabies mortality data. The first outbreaks of VBRV on the Pacific coast of South America could occur by June 2020, which would have serious implications for agriculture, wildlife conservation, and human health. Our results show that combining host and pathogen genetic data can identify sex biases in pathogen spatial spread, which may be a widespread but underappreciated phenomenon, and demonstrate that genetic forecasting can aid preparedness for impending viral invasions.

INTRODUCTION: In 2008, Turkey became one of 26 countries with a complete ban on all forms of direct and indirect tobacco marketing. We assessed the level of exposure to anti- and pro-cigarette advertising and to cigarette promotions and sponsorships among various demographic groups in Turkey. METHODS: We used the data from the Global Adult Tobacco Survey (GATS), conducted in November 2008 in Turkey. The data consist of answers to GATS questions by 9030 respondents from a nationally representative, multistage probability sample of adults 15 years of age or older. To find differences in exposure to the advertising by sex, age, education level and smoking status, we analyzed responses to GATS questions about cigarette advertisements and anti-cigarette smoking information in various forms and through various advertising channels, during the 30 days before the survey, using bivariate analysis. RESULTS: Overall, 13.3% of respondents aged 15 years or older noticed some type of cigarette marketing during the 30 days before the survey: 7.1% saw advertisements, 5.3% saw promotions and 3.3% saw sports sponsorships. Men were more likely than women to have seen cigarette promotions (7.8% versus 3.0%) and sports sponsorships (5.3% versus 1.4%). Respondents aged 15-24 years were more likely than those aged 25 years or older to have seen cigarette advertisements (10.2% versus 6.2%), promotions (8.7% versus 4.4%) and sponsorships (6.6% versus 2.3%), respectively. Respondents were most likely to have seen cigarette advertisements on television (3.4%) or in shops (2.7%). In addition, 2.8% of respondents reported seeing a clothing item with a brand name or logo, 2.5% reported that they received free samples of cigarettes and 0.3% received gifts along with the purchase of cigarettes. Almost 9 of 10 survey respondents (88.8%) reported having noticed some anti-cigarette information during the 30 days before the survey. Most anti-cigarette information was seen on television (85.5%). The anti-cigarette information was seen by slightly more cigarette smokers (91.6%) than nonsmokers (87.6%). Persons with less than a primary education were less likely to notice anti-cigarette information than those with a higher level of education, in all examined media channels. CONCLUSIONS: Our findings showed a low prevalence of noticing cigarette marketing, which indicates high compliance with the Turkish law banning such marketing. GATS data provide an in-depth understanding of the level of exposure to pro- and anti-cigarette information in 2008 and they are of practical assistance to those who implement policies to reduce the demand for tobacco. The challenge now is to maintain rigorous enforcement. To do so requires ongoing surveillance to produce data on the effectiveness of the enforcement efforts.

INTRODUCTION: We assessed the differences in exposure to secondhand smoke (SHS) among adults at home, in indoor workplaces, and in various public places in the Philippines across various socio-demographic groups. METHODS: Data from the Global Adult Tobacco Survey conducted in 2009 in the Philippines were used. The data consist of survey answers from 9705 respondents from a nationally representative, multistage probability sample of adults aged 15 years or older. We considered that respondents were exposed to SHS if during the previous 30 days they reported that they lived in a home, worked in a building, or visited a public place where people smoked. The public places included in our analysis were indoor workplaces, public transportation vehicles, restaurants, government buildings or offices, and healthcare facilities. The differences in various socioeconomic and demographic groups' exposure to SHS in these places were also examined. RESULTS: Of respondents who reported working indoors, 36.8% were exposed to SHS. Men (43.3% [95% CI 39.7-46.9]) were more likely than women (28.8% [95% CI 25.4-32.4]) to be exposed to SHS (p < 0.001). Of those working in sites where smoking was not allowed, 13.9% were exposed to SHS, whereas 66.5% were exposed where smoking is allowed in some enclosed areas, and 90.7% were exposed where smoking is allowed everywhere. During the 30 days preceding the survey, more than 50% of those who took public transportation were exposed to SHS; exposure for those who visited public buildings was 33.6% in restaurants, 25.5% in government buildings or offices, and 7.6% in healthcare facilities. CONCLUSION: Despite a national law passed and several local government ordinances that have promulgated smoke-free workplaces, schools, government offices, and healthcare facilities, our findings show that a large proportion of adults were exposed to SHS at work and in public places, which offers opportunities to strengthen and improve enforcement of the smoke-free initiatives and ordinances in the Philippines.

In 2008, the Centers for Disease Control and Prevention (CDC) and the World Health Organization developed the Global Adult Tobacco Survey (GATS), an instrument to monitor global tobacco use and measure indicators of tobacco control. GATS, a nationally representative household survey of persons aged 15 years or older, was conducted for the first time during 2008-2010 in 14 low- and middle-income countries. In each country, GATS used a standard core questionnaire, sample design, and procedures for data collection and management and, as needed, added country-specific questions that were reviewed and approved by international experts. The core questionnaire included questions about various characteristics of the respondents, their tobacco use (smoking and smokeless), and a wide range of tobacco-related topics (cessation; secondhand smoke; economics; media; and knowledge, attitudes, and perceptions). In each country, a multistage cluster sample design was used, with households selected proportionate to the size of the population. Households were chosen randomly within a primary or secondary sampling unit, and one respondent was selected at random from each household to participate in the survey. Interviewers administered the survey in the country's local language(s) using handheld electronic data collection devices. Interviews were conducted privately, and same-sex interviewers were used in countries where mixed-sex interviews would be culturally inappropriate. All 14 countries completed the survey during 2008-2010. In each country, the ministry of health was the lead coordinating agency for GATS, and the survey was implemented by national statistical organizations or surveillance institutes. This article describes the background and rationale for GATS and includes a comprehensive description of the survey methods and protocol.