Effect of cyclic substituents on the anti-cancer activity and DNA interaction of ruthenium(II) bis-phenanthroline dipyridoquinoline.

Introduction: Ruthenium(II) complexes have emerged recently as candidates for anti-cancer therapy, where activity is related to lipohilicity, cellular localization, and specific interactions with biomolecules. Methods: In this work, two novel complexes were synthesized and are reported based on the [Ru(phen)2(dipyrido[3,2-f:2',3'-h]quinoxaline]2+ framework. Results: Compared to the parent complex, annealing of cyclopenteno and cyclohexeno rings to the extended ligand substantially increased cytotoxicity towards a number of cancer cell lines, and induced apoptosis. The complexes localize in the nuclei of cancer cells and co-locate with DAPI on DNA. DNA binding studies show that both complexes bind strongly to DNA and one complex intercalates DNA like the parent, whilst the other appears to have multiple modes of interaction. Discussion: It is likely that the increased lipophilicity of the novel complexes is a key factor for increasing their cytotoxicity, rather than their DNA binding mode.

Organization and Performance of US Health Systems.

Importance: Health systems play a central role in the delivery of health care, but relatively little is known about these organizations and their performance. Objective: To (1) identify and describe health systems in the United States; (2) assess differences between physicians and hospitals in and outside of health systems; and (3) compare quality and cost of care delivered by physicians and hospitals in and outside of health systems. Evidence Review: Health systems were defined as groups of commonly owned or managed entities that included at least 1 general acute care hospital, 10 primary care physicians, and 50 total physicians located within a single hospital referral region. They were identified using Centers for Medicare & Medicaid Services administrative data, Internal Revenue Service filings, Medicare and commercial claims, and other data. Health systems were categorized as academic, public, large for-profit, large nonprofit, or other private systems. Quality of preventive care, chronic disease management, patient experience, low-value care, mortality, hospital readmissions, and spending were assessed for Medicare beneficiaries attributed to system and nonsystem physicians. Prices for physician and hospital services and total spending were assessed in 2018 commercial claims data. Outcomes were adjusted for patient characteristics and geographic area. Findings: A total of 580 health systems were identified and varied greatly in size. Systems accounted for 40% of physicians and 84% of general acute care hospital beds and delivered primary care to 41% of traditional Medicare beneficiaries. Academic and large nonprofit systems accounted for a majority of system physicians (80%) and system hospital beds (64%). System hospitals were larger than nonsystem hospitals (67% vs 23% with >100 beds), as were system physician practices (74% vs 12% with >100 physicians). Performance on measures of preventive care, clinical quality, and patient experience was modestly higher for health system physicians and hospitals than for nonsystem physicians and hospitals. Prices paid to health system physicians and hospitals were significantly higher than prices paid to nonsystem physicians and hospitals (12%-26% higher for physician services, 31% for hospital services). Adjusting for practice size attenuated health systems differences on quality measures, but price differences for small and medium practices remained large. Conclusions and Relevance: In 2018, health system physicians and hospitals delivered a large portion of medical services. Performance on clinical quality and patient experience measures was marginally better in systems but spending and prices were substantially higher. This was especially true for small practices. Small quality differentials combined with large price differentials suggests that health systems have not, on average, realized their potential for better care at equal or lower cost.

A Note on "Sequential Neighborhood Effects" by Hicks et al. (2018).

We revisit a novel causal model published in Demography by Hicks et al. (2018), designed to assess whether exposure to neighborhood disadvantage over time affects children's reading and math skills. Here, we provide corrected and new results. Reconsideration of the model in the original article raised concerns about bias due to exposure-induced confounding (i.e., past exposures directly affecting future exposures) and true state dependence (i.e., past exposures affecting confounders of future exposures). Through simulation, we show that our originally proposed propensity function approach displays modest bias due to exposure-induced confounding but no bias from true state dependence. We suggest a correction based on residualized values and show that this new approach corrects for the observed bias. We contrast this revised method with other causal modeling approaches using simulation. Finally, we reproduce the substantive models from Hicks et al. (2018) using the new residuals-based adjustment procedure. With the correction, our findings are essentially identical to those reported originally. We end with some conclusions regarding approaches to causal modeling.

Wide State-Level Variation In Commercial Health Care Prices Suggests Uneven Impact Of Price Regulation.

Prices charged for health care services in the commercial insurance market are high and vary widely within and between market areas. As a result, prices have been the focus of much policy debate. We extended the literature on commercial prices by examining state-level price variation in the commercial market, relative to Medicare, for a broader set of states and a wider set of services than had been examined. We assessed the potential impact on provider revenue of setting commercial prices at Medicare rates. Consistent with the existing literature, we found that average commercial prices for inpatient and outpatient facility services were about double Medicare fees, while commercial prices for professional services were about 60 percent higher. Finally, average hospital revenue would fall about 35 percent if commercial prices were limited to Medicare rates, but this would vary widely by state. If Medicaid rates were also increased to match Medicare rates, hospital revenue would likely fall by about 30 percent. Given the potentially large impact, policies to address the market failures that lead to high and variable prices in the commercial insurance sector are needed, but they should be structured to avoid the large disruptions that could occur if there were a very rapid transition to Medicare rates in the commercial market.

What are the potential savings from steering patients to lower-priced providers? a static analysis.

OBJECTIVES: Healthcare payers are increasingly using price transparency and benefit design to encourage patients to choose lower-priced providers. We quantify potential savings from shifting patients to lower-priced providers. If there is limited price variation or if higher-priced providers command little market share, savings could be minimal. STUDY DESIGN: Using 2013-2014 commercial claims for 697,381 enrollees in California, we characterized within-market price variation and the relationship between providers' market shares and relative prices for 3 nonemergent, shoppable outpatient services: laboratory tests, imaging services, and durable medical equipment (DME). In a stylized policy simulation that holds provider price and utilization constant, we computed potential savings if patients who visited providers with prices above the median price shifted to the median-priced provider in their geographic market for the same service. METHODS: Observational analyses. RESULTS: Of the service categories examined, laboratory tests had greatest within-market price variation (median coefficient of variation of 100% vs 87% for imaging services and 43% for DME). Roughly half of services (53%, 47%, and 54% for laboratory tests, imaging services, and DME, respectively) were billed by providers with prices above their market median. Shifting these patients to the median-priced provider in their markets could save 42%, 45%, and 15% of spending on laboratory tests, imaging services, and DME, respectively, together representing savings of 11% of total outpatient spending and 7% of the sum of inpatient and outpatient spending. CONCLUSIONS: Steering patients from higher- to lower-priced providers within geographic markets in targeted service categories could generate substantial healthcare savings.

Prices for physician services in Medicare Advantage versus traditional Medicare.

OBJECTIVES: To compare the prices paid to physicians by employer-sponsored Medicare Advantage (MA) plans with those paid by traditional Medicare (TM) and to determine whether the relationship between MA and TM prices is affected by the generosity of MA benchmarks. STUDY DESIGN: Descriptive analysis of medical claims data from the 2014-2015 MarketScan Medicare Claims Database. METHODS: We focus on claims for low-complexity office visits with an established patient (Current Procedural Terminology [CPT] code 99213) and electrocardiograms (CPT code 93000). For a given service, we identify the prices paid by MA plans and by TM in a metropolitan statistical area (MSA), which is our definition of a market. We then construct an MA-to-TM price ratio for each MSA and report the median price ratio. In a subanalysis, we disaggregate the result for office visits by MA benchmark generosity. RESULTS: For both services, the estimated median price ratio is close to 1.00. We also find that even as MA benchmarks (relative to local fee-for-service spending) increase, the median price ratio for office visits remains close to 1.00. CONCLUSIONS: After analyzing claims for common physician services, we find that employer-sponsored MA plans pay prices that are similar to TM rates. This holds even as the generosity of MA plan payment changes. Similarity between MA and TM prices appears to be stable over time, despite recent policy changes. Our findings emphasize the important role that TM plays in the MA market and that TM payment changes could have a spillover effect on MA prices and spending.

Sequential Neighborhood Effects: The Effect of Long-Term Exposure to Concentrated Disadvantage on Children's Reading and Math Test Scores.

Prior research has suggested that children living in a disadvantaged neighborhood have lower achievement test scores, but these studies typically have not estimated causal effects that account for neighborhood choice. Recent studies used propensity score methods to account for the endogeneity of neighborhood exposures, comparing disadvantaged and nondisadvantaged neighborhoods. We develop an alternative propensity function approach in which cumulative neighborhood effects are modeled as a continuous treatment variable. This approach offers several advantages. We use our approach to examine the cumulative effects of neighborhood disadvantage on reading and math test scores in Los Angeles. Our substantive results indicate that recency of exposure to disadvantaged neighborhoods may be more important than average exposure for children's test scores. We conclude that studies of child development should consider both average cumulative neighborhood exposure and the timing of this exposure.

Offering A Price Transparency Tool Did Not Reduce Overall Spending Among California Public Employees And Retirees.

Insurers, employers, and states increasingly encourage price transparency so that patients can compare health care prices across providers. However, the evidence on whether price transparency tools encourage patients to receive lower-cost care and reduce overall spending remains limited and mixed. We examined the experience of a large insured population that was offered a price transparency tool, focusing on a set of "shoppable" services (lab tests, office visits, and advanced imaging services). Overall, offering the tool was not associated with lower shoppable services spending. Only 12 percent of employees who were offered the tool used it in the first fifteen months after it was introduced, and use of the tool was not associated with lower prices for lab tests or office visits. The average price paid for imaging services preceded by a price search was 14 percent lower than that paid for imaging services not preceded by a price search. However, only 1 percent of those who received advanced imaging conducted a price search. Simply offering a price transparency tool is not sufficient to meaningfully decrease health care prices or spending.

Who Uses a Price Transparency Tool? Implications for Increasing Consumer Engagement.

Despite the recent proliferation of price transparency tools, consumer use and awareness of these tools is low. Better strategies to increase the use of price transparency tools are needed. To inform such efforts, we studied who is most likely to use a price transparency tool. We conducted a cross-sectional study of use of the Truven Treatment Cost Calculator among employees at 2 large companies for the 12 months following the introduction of the tool in 2011-2012. We examined frequency of sign-ons and used multivariate logistic regression to identify which demographic and health care factors were associated with greater use of the tool. Among the 70 408 families offered the tool, 7885 (11%) used it at least once and 854 (1%) used it at least 3 times in the study period. Greater use of the tool was associated with younger age, living in a higher income community, and having a higher deductible. Families with moderate annual out-of-pocket medical spending ($1000-$2779) were also more likely to use the tool. Consistent with prior work, we find use of this price transparency tool is low and not sustained over time. Employers and payers need to pursue strategies to increase interest in and engagement with health care price information, particularly among consumers with higher medical spending.

THE DELINKING OF SEX AND MARRIAGE: PATHWAYS TO FERTILITY AMONG YOUNG FILIPINO WOMEN.

Partnership and fertility patterns of young Filipinos have changed dramatically from previous generations, with a widening gap between sexual initiation and marriage, and concurrent increases in teenage pregnancy and unwanted fertility. Further understanding of young adults' social contexts and partnership patterns are needed to inform reproductive health programmes and policies affecting young Filipinos. Multivariate Poisson regression models were conducted with longitudinal and inter-generational data from the Cebu Longitudinal Health and Nutrition Survey (1998-2009) to examine the predictors of young women's fertility. Age at first sex, and number and duration of partnerships each independently and significantly predicted women's fertility by 2009 after controlling for contextual influences. Young women with more conservative attitudes towards dating, sex and marriage, and who perceived their mothers to have more conservative attitudes, had higher fertility than their peers, as did young women with mothers who reported more adolescent sexual behaviours. In contrast, fertility was lower among daughters who had higher levels of communication with their mothers. Given high levels of unintended fertility and teenage pregnancy in the Philippines, the findings indicate that the interval between sexual initiation and first and subsequent partnerships may be ideal intervention points for reproductive health services for young Filipinos.

Association Between Availability of a Price Transparency Tool and Outpatient Spending.

IMPORTANCE: There is increasing interest in using price transparency tools to decrease health care spending. OBJECTIVE: To measure the association between offering a health care price transparency tool and outpatient spending. DESIGN, SETTING, AND PARTICIPANTS: Two large employers represented in multiple market areas across the United States offered an online health care price transparency tool to their employees. One introduced it on April 1, 2011, and the other on January 1, 2012. The tool provided users information about what they would pay out of pocket for services from different physicians, hospitals, or other clinical sites. Using a matched difference-in-differences design, outpatient spending among employees offered the tool (n=148,655) was compared with that among employees from other companies not offered the tool (n=295,983) in the year before and after it was introduced. EXPOSURE: Availability of a price transparency tool. MAIN OUTCOMES AND MEASURES: Annual outpatient spending, outpatient out-of-pocket spending, use rates of the tool. RESULTS: Mean outpatient spending among employees offered the tool was $2021 in the year before the tool was introduced and $2233 in the year after. In comparison, among controls, mean outpatient spending changed from $1985 to $2138. After adjusting for demographic and health characteristics, being offered the tool was associated with a mean $59 (95% CI, $25-$93) increase in outpatient spending. Mean outpatient out-of-pocket spending among those offered the tool was $507 in the year before introduction of the tool and $555 in the year after. Among the comparison group, mean outpatient out-of-pocket spending changed from $490 to $520. Being offered the price transparency tool was associated with a mean $18 (95% CI, $12-$25) increase in out-of-pocket spending after adjusting for relevant factors. In the first 12 months, 10% of employees who were offered the tool used it at least once. CONCLUSIONS AND RELEVANCE: Among employees at 2 large companies, offering a price transparency tool was not associated with lower health care spending. The tool was used by only a small percentage of eligible employees.

Association of Financial Integration Between Physicians and Hospitals With Commercial Health Care Prices.

IMPORTANCE: Financial integration between physicians and hospitals may help health care provider organizations meet the challenges of new payment models but also may enhance the bargaining power of provider organizations, leading to higher prices and spending in commercial health care markets. OBJECTIVE: To assess the association between recent increases in physician-hospital integration and changes in spending and prices for outpatient and inpatient services. DESIGN, SETTING, AND PARTICIPANTS: Using regression analysis, we estimated the relationship between changes in physician-hospital integration from January 1, 2008, through December 31, 2012, in 240 metropolitan statistical areas (MSAs) and concurrent changes in spending. Adjustments were made for patient, plan, and market characteristics, including physician, hospital, and insurer market concentration. The study population included a cohort of 7,391,335 nonelderly enrollees in preferred-provider organizations or point-of-service plans included in the Truven Health MarketScan Commercial Database during the study period. Data were analyzed from December 1, 2013, through July 13, 2015. EXPOSURE: Physician-hospital integration, measured using Medicare claims data as the share of physicians in an MSA who bill for outpatient services with a place-of-service code indicating employment or practice ownership by a hospital. MAIN OUTCOMES AND MEASURES: Annual inpatient and outpatient spending per enrollee and associated use of health care services, with utilization measured by price-standardized spending (the sum of annual service counts multiplied by the national mean of allowed charges for the service). RESULTS: Among the 240 MSAs, physician-hospital integration increased from 2008 to 2012 by a mean of 3.3 percentage points, with considerable variation in increases across MSAs (interquartile range, 0.8-5.2 percentage points). For our study sample of 7,391,335 nonelderly enrollees, an increase in physician-hospital integration equivalent to the 75th percentile of changes experienced by MSAs was associated with a mean increase of $75 (95% CI, $38-$113) per enrollee in annual outpatient spending (P < .001) from 2008 to 2012, a 3.1% increase relative to mean outpatient spending in 2012 ($2407 [95% CI, $2400-$2414] per enrollee). This increase in outpatient spending was driven almost entirely by price increases because associated changes in utilization were minimal (corresponding change in price-standardized spending, $14 [95% CI, -$13 to $41] per enrollee; P = .32). Changes in physician-hospital integration were not associated with significant changes in inpatient spending ($22 [95% CI, -$1 to $46] per enrollee; P = .06) or utilization ($10 [95% CI, -$12 to $31] per enrollee; P = .37). CONCLUSIONS AND RELEVANCE: Financial integration between physicians and hospitals has been associated with higher commercial prices and spending for outpatient care.

Maternal health care seeking by rural Tibetan women: characteristics of women delivering at a newly-constructed birth center in western China.

BACKGROUND: Increasing skilled birth attendance at delivery is key to reducing maternal mortality, particularly among marginalized populations. Despite China's successful rollout of a national policy to promote facility deliveries, challenges remain among rural and ethnic minority populations. In response, a Tibetan Birth and Training Center (TBTC) was constructed in 2010 to provide high-quality obstetric care in a home-like environment to a predominantly Tibetan population in Tso-ngon (Qinghai) province in western China to improve maternal care in the region. This study examines if and how first users of the TBTC differ from women in the broader community, and how this information may inform subsequent maternal health care interventions in this area. METHODS: Trained, Tibetan interviewers administered a face-to-face, quantitative questionnaire to two groups of married, Tibetan women: women who had delivered at the TBTC between June 2011-June 2012 (n = 114) and a non-equivalent comparison group of women from the same communities who had delivered in the last two years, but not at the TBTC (n = 108). Chi-squared and ANOVA tests were conducted to detect differences between the samples. RESULTS: There were no significant differences between the samples in education or income; however, women from the TBTC sample were significantly younger (25.55 vs. 28.16 years; p < 0.001) and had fewer children (1.54 vs. 1.70; p = 0.05). Items measuring maternity health care-seeking and perceived importance of health facility amenities indicated minimal differences between the samples. However, as compared to the community sample, the TBTC sample had a greater proportion of women who reported having the final say regarding where to deliver (26% vs. 14%; p = 0.02) and having a friend or family member who delivered at home (50% vs. 28%; p < 0.001). CONCLUSIONS: Findings did not support the hypothesis that the TBTC attracts lower-income, less-educated women. Minimal differences in women's characteristics and perceptions regarding delivery care between the two samples suggest that the TBTC is serving a broad cross-section of women. Differences between the samples with respect to delivery care decision-making and desire for skilled birth care underscore areas that may be further explored and supported in subsequent efforts to promote facility delivery in this population, and similar populations, of women.

Tibetan women's perspectives and satisfaction with delivery care in a rural birth center.

OBJECTIVE: To identify sociodemographic characteristics and factors involved in Tibetan women's decisions to deliver at the Tibetan Birth and Training Center (TBTC) in rural western China. METHODS: In the present mixed-methods study, a random sample of married women who delivered at the TBTC between June 2011 and June 2012 were surveyed. Additionally, four focus group discussions were conducted among married women living in the TBTC catchment area. Descriptive analyses were conducted, and dominant themes were identified. RESULTS: In focus group discussions, women (n=33) reported that improved roads and transportation meant that access to health facilities was easier than in the past. Although some of the 114 survey participants voiced negative perceptions of healthcare facilities and providers, 99 (86.8%) indicated that they chose to deliver at the TBTC because they preferred to have a doctor present. Most women (75 [65.8%]) said their mother/mother-in-law made the final decision about delivery location. Women valued logistic and cultural aspects of the TBTC, and 108 (94.7%) said that they would recommend the TBTC to a friend. CONCLUSION: Study participants preferred delivery care that combines safety and comfort. The findings highlight avenues for further promotion of facility delivery among populations with lower rates of skilled deliveries.

Gendered differences in the predictors of sexual initiation among young adults in Cebu, Philippines.

PURPOSE: Social environment and family context exert substantial influence on adolescent sexual behaviors. These influences are especially important to examine in countries undergoing rapid demographic and social change. This study employs unique, intergenerational and longitudinal data (1998-2009) to examine the effects of parental, peer, and household influences on sexual initiation among young adults in Cebu, Philippines. METHODS: Intergenerational and longitudinal cohort data from the 1998 Cebu Longitudinal Health and Nutrition Survey (CLHNS) are analyzed to examine the effects of household, peer, family, and young adults' sexual attitudes on age at first sex by 2009 among young men and women. Gender-stratified Cox proportional hazards models and Cox regression models are used to model time to first sex. RESULTS: Household, family, peer, and individual characteristics have disparate influences on sexual initiation among Filipino boys and girls. Boys' sexual initiation was positively associated with urbanicity, household wealth, and the presence of a family member working abroad, whereas for girls, these variables had no significant effects. Unique effects were also found for girls-mother's education was negatively associated, and girls' number of siblings was positively associated, with higher hazards of sex. Additionally, the effects of some variables on the occurrence of first sex differed across time, indicating that boys and girls may be differentially influenced by contextual characteristics across adolescence. CONCLUSIONS: Amid substantial sociodemographic changes and persistence of traditional gender norms, this study highlights the importance of examining the unique influences and intersections of gender and context on sexual initiation in the Philippines.