Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial.

BACKGROUND: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF. METHODS: BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488). FINDINGS: Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference -0·5%, 95% CI -1·8 to 0·9; p=0·48). INTERPRETATION: Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation. FUNDING: Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter.

Masking the Bioactivity of Hydroxamic Acids by Coordination to Cobalt: Towards Bioreductive Anticancer Agents.

The clinical use of many potent anticancer agents is limited by their non-selective toxicity to healthy tissue. One of these examples is vorinostat (SAHA), a pan histone deacetylase inhibitor, which shows high cytotoxicity with limited discrimination for cancerous over healthy cells. In an attempt to improve tumor selectivity, we exploited the properties of cobalt(III) as a redox-active metal center through stabilization with cyclen and cyclam tetraazamacrocycles, masking the anticancer activity of SAHA and other hydroxamic acid derivatives to allow for the complex to reach the hypoxic microenvironment of the tumor. Biological assays demonstrated the desired low in vitro anticancer activity of the complexes, suggesting effective masking of the activity of SAHA. Once in the tumor, the bioactive moiety may be released through the reduction of the CoIII center. Investigations revealed high long-term stability of the complexes, with cyclic voltammetry and chemical reduction experiments supporting the design hypothesis of SAHA release through the reduction of the CoIII prodrug. The results highlight the potential for further developing this complex class as novel anticancer agents by masking the high cytotoxicity of a given drug, however, the cellular uptake needs to be improved.

Consensus pregnancy-related criteria for suicide and unintentional overdoses using a Delphi process.

Suicide and unintentional overdose are leading manners of preventable death during and within a year of pregnancy. Recently, the Utah Maternal Mortality Review Committee (MMRC) developed 10 criteria to guide pregnancy-related classification of these deaths. Our objective was to (1) evaluate if consensus could be reached across experts in maternal mortality review when applying criteria to the determination of pregnancy-relatedness in mock MMRC case evaluation and (2) assess how additional case information shifted participants' determination of pregnancy-relatedness in these mock cases. We used a modified Delphi process to evaluate criteria for pregnancy-related suicides and unintentional overdose. The study team developed base case scenarios to reflect the 10 proposed criteria. Base scenarios varied in timing of death (prenatal or delivery, early postpartum (<6 months), late postpartum (6-12 months)) and level of additional information available (e.g., informant interviews, social media posts). Consensus in favor of a criterion was met when ≥75% of participants identified a case as pregnancy-related in at least 1 scenario. Fifty-eight participants, representing 48 MMRCs, reviewed scenarios. Of 10 proposed criteria, 8 reached consensus. Overall, participants classified 19.4% of base case scenarios as pregnancy-related, which increased to 56.8% with additional information. Pregnancy-related classification changed across timing of death and with availability of additional information (prenatal or delivery 27.7% versus 84.6%; early postpartum 30.0% versus 58.3%; late postpartum 0.0% versus 25.0%, respectively). We identified consensus supporting the application of 8 standardized criteria in MMRC determinations of pregnancy-relatedness among suicide and unintentional overdose deaths.

Kidney transplantation in people living with human immunodeficiency virus: An overview of the Australian experience.

Kidney transplantation in people living with HIV (PLWHIV) is occurring with increasing frequency. Limited international data suggest comparable patient and graft survival in kidney transplant recipients with and without HIV. All PLWHIV aged ≥18 years who received a kidney transplant between 2000 and 2020 were identified by retrospective data initially extracted from Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), with additional HIV-specific clinical data extracted from linked local health-care records. Twenty-five PLWHIV and kidney failure received their first kidney transplant in Australia between January 2000 and December 2020. Majority were male (85%), with median age 54 years (interquartile range, IQR 43-57). Focal segmental glomerulosclerosis was the most common primary kidney disease (20%), followed by polycystic kidney disease (16%). 80% of patients underwent induction with basiliximab and none with anti-thymocyte globulin (ATG). Participants were followed for median time of 3.5 years (IQR 2.0-6.5). Acute rejection occurred in 24% of patients. Two patients lost their allografts and three died. Virological escape occurred in 28% of patients, with a maximum viral load of 190 copies/mL. In conclusion, kidney transplantation in PLWHIV in Australia is occurring with increasing frequency. Acute rejection is more common than in Australia's general transplant population, but this does not appear to be associated with higher rates of graft failure or mortality out to four years.

The Relationship Between Regional Growth in Neonatal Intensive Care Capacity and Perinatal Risk.

BACKGROUND: The supply of US neonatal intensive care unit (NICU) beds and neonatologists is known to vary markedly across regions, but there have been no investigation of patterns of recent growth (1991-2017) in NICUs in relation to newborn need. OBJECTIVE: The objective of this study was to test the hypothesis that greater growth in NICU capacity occurred in neonatal intensive care regions with higher perinatal risk. RESEARCH DESIGN: A longitudinal ecological analysis with neonatal intensive care regions (n=246) as the units of analysis. Associations were tested using linear regression. SUBJECTS: All US live births ≥400 g in 1991 (n=4,103,528) and 2017 (n=3,849,644). MEASURES: Primary measures of risk were the proportions of low-birth weight and very low-birth weight newborns and mothers who were Black or had low educational attainment. RESULTS: Over 26 years, the numbers of NICU beds and neonatologists per live birth increased 42% and 200%, respectively, with marked variation in growth across regions (interquartile range: 0.3-4.1, beds; neonatologists, 0.4-1.0 per 1000 live births). A weak association of capacity with perinatal risk in 1991 was absent in 2017. There was no meaningful (ie, clinical or policy relevant) association between regional changes in capacity and regions with higher perinatal risk or lower capacity in 1991; higher increases in perinatal risk were not associated with higher capacity growth. CONCLUSION: The lack of association between newborn medical needs and the supply of NICU resources raises questions about the current effectiveness of newborn care at a population level.

Azimuthal invariance to looming stimuli in the Drosophila giant fiber escape circuit.

Spatially invariant feature detection is a property of many visual systems that rely on visual information provided by two eyes. However, how information across both eyes is integrated for invariant feature detection is not fully understood. Here, we investigated spatial invariance of looming responses in descending neurons (DNs) of Drosophila melanogaster. We found that multiple looming responsive DNs integrate looming information across both eyes, even though their dendrites are restricted to a single visual hemisphere. One DN, the giant fiber (GF), responds invariantly to looming stimuli across tested azimuthal locations. We confirmed visual information propagates to the GF from the contralateral eye, through an unidentified pathway, and demonstrated that the absence of this pathway alters GF responses to looming stimuli presented to the ipsilateral eye. Our data highlight a role for bilateral visual integration in generating consistent, looming-evoked escape responses that are robust across different stimulus locations and parameters.

Regional Differences in Procedural Care of Hemorrhoid Management in Medicare Patients; Unwarranted Variation in Clinical Practice for a Medical-First Problem.

INTRODUCTION: Hemorrhoid disease is very common problem in the Medicare population. Prior work has shown significant variation in county-level practices of hemorrhoidectomy; however, regional variation of rubber band ligation (RBL) has yet to be assessed. This is important as many different practitioners from different specialties can perform this procedure repeatedly in an office-based setting. We aim to evaluate the variation of RBL and hemorrhoidectomy over a 7-y period. METHODS: Using Medicare part B claims data, we identified all beneficiaries >65 y seen for hemorrhoid disease between 2006 and 2013. Current Procedural Terminology (CPT) codes were used to identify all events for hemorrhoidectomy (46083, 46250, 46255, 46257, 46260, and 46261) or RBL (46221) by hospital referral region (HRR). We determined HRR-level rates of hemorrhoidectomy and RBL per 1000 beneficiaries adjusted for age, sex, and race. We calculated annual coefficients of variation (SD × 100/mean) for hemorrhoidectomy and RBL. RESULTS: 1.2 to 1.3 million fee-for-service Medicare beneficiaries were seen annually for evaluation of hemorrhoid disease. Mean-adjusted annual rates for hemorrhoidectomy by HRRs varied from 4.34 to 63.03 per 1000 beneficiaries. Mean-adjusted rates of RBL by HRRs varied from 7.06 to 163 per 1000 beneficiaries. Annual procedural coefficients of variation over the study period were 41-48 (high) for hemorrhoidectomy and 69-74 (very high) for RBL. CONCLUSIONS: While continued high variation exists for hemorrhoidectomy, there is very high variation for RBL between HRRs in treating hemorrhoid disease among Medicare beneficiaries. There are substantial Medicare expenditures in this high-volume population that are likely unwarranted.

Correctional health care and Australian prisoners as recipients of kidney transplants: Legal and ethical issues.

AIM: This research aims to examine the legal and ethical issues surrounding Australia prisoners as potential kidney transplant recipients. METHODS: Examination of relevant statutory and common law including human rights law, state and territory corrections legislation and negligence law. Ethical principles considered, particularly in regards to practical and logistical considerations including adequate delivery of transplantation medical care and implications on the broader organ donation program. Approaches in the United States of America and United Kingdom are compared with the Australian approach. RESULTS: Prisoners are more likely than non-incarcerated individuals to have chronic medical conditions. For most people with kidney failure, kidney transplantation improves both quality of life and life expectancy compared with dialysis therapy. Prisoners have a right to access reasonable medical care under state-based corrections legislation, which is underpinned by human rights law and ethical principles, primarily beneficence, transparency and justice. The right of prisoners to receive reasonable medical care likely extends to ensuring prisoners with kidney failure are considered for kidney transplantation and waitlisted if medically appropriate. Social factors and logistical factors can be relevant when considering eligibility for transplantation as they can relate to a person's ability to comply with medical therapy. Additionally, organ allocation decisions can be emotive, and a decision to offer a kidney transplant to a prisoner may generate significant negative publicity. CONCLUSION: Prisoners with kidney failure should be considered for kidney transplantation. Logistical barriers, such as guard availability, should be addressed by state departments responsible for prisoner health.

Unwarranted geographic variation in paediatric health care in the United States and Norway.

AIM: We present the four US and Norwegian paediatric and neonatal health atlases and discuss the concept and causes of unwarranted geographic variation in paediatric health care. METHODS: The four atlases analyse data from both publicly owned health registers, registers of insurance claims and quality registers. Healthcare utilisation is counted per recipient in predefined hospital service areas, adjusted for relevant confounders and presented as extremal ratios between the highest and lowest rate. RESULTS: The atlases describe geographic variation in rates for primary health care, hospital admissions, outpatient visits, treatment procedures and diagnostic testing. A difference in extremal ratios from 2 to 4 between health service areas are common, and for some procedures extremal ratios is even higher. CONCLUSION: Variation in healthcare utilisation of the magnitude described in these four atlases cannot be explained by differences in population morbidity or patient preferences and are therefore characterised as unwarranted variation. Individual provider preferences or supply of resources such as hospital beds may explain the observed variation.

Examining the Ratio of Obstetric Beds to Births, 2000-2019.

The number of U.S. births has been declining. There is also concern about rural obstetric units closing. To better understand the relationship between births and obstetric beds during 2000-2019, we examined changes over time in births, birth hospital distributions (i.e., hospital birth volume, ownership, and urban-rural designation), and the ratio of births to obstetric beds. We analyzed American Hospital Association Annual Survey data from 2000 to 2019. We included U.S. hospitals with at least 25 reported births during the year and at least 1 reported obstetric bed. We categorized birth volume to identify and describe hospitals with maternity services using seven categories. We calculated ratios of number of births to number of obstetric beds overall, by annual birth volume category, by three categories of hospital ownership, and by six urban-rural categories. The ratio of births to obstetric beds, which may represent need for maternity services, has stayed relatively consistent at 65 over the past two decades, despite the decline in births and changes in birth hospital distributions. The ratios were smallest in hospitals with < 250 annual births and largest in hospitals with ≥ 7000 annual births. The largest ratios of births to obstetric beds were in large metro areas and the smallest ratios were in noncore areas. At a societal level, the reduction in obstetric beds corresponds with the drop in the U.S. birth rate. However, consistency in the overall ratio can mask important differences that we could not discern, such as the impact of closures on distances to closest maternity care.

Neonatal Intensive Care Utilization and Postdischarge Newborn Outcomes: A Population-based Study of Texas Medicaid Insured Infants.

OBJECTIVE: To test the hypothesis that newborn infants cared for in hospitals with greater utilization of neonatal intensive care experienced fewer postdischarge adverse events. STUDY DESIGN: We developed 3 retrospective population-based cohorts of Texas Medicaid insured singletons born in 2010-2014 (very low birth weight [VLBW n = 11 139], late preterm [n = 57 509], and non-preterm [n = 664 447]) who received care in higher volume hospitals with level III/IV neonatal intensive care units (NICUs). Measures of NICU care were hospital-level risk adjusted NICU admission rates, special care days (days of nonroutine care) per infant, and the percent of intensive (highest billable care code) special care days. The units of analysis were hospitals (n = 80) and the primary outcome was an adverse event, (defined as admission, emergency department visit, or death) within 30 days postdischarge. RESULTS: Higher use of NICU care at a hospital level was not associated with lower postdischarge 30-day adverse event. Infants cared for in hospitals with above vs below median special care day rates experienced slightly higher postdischarge adverse event per 100 infants (VLBW: 14.01 [95% CI 12.74-15.27] vs 11.84 [10.52-13.16], P < .05; late preterm: 7.33 [6.68-7.97] vs 6.28 [5.87-6.69], P < .01; non-preterm: 4.47 [4.17-4.76] vs 3.97 [3.75-4.18], P < .01). Weak positive associations (Pearson correlations of 0.31-0.37, P < .01) were observed for adverse event with special care days; in no instance was a negative association observed between NICU utilization and adverse event. CONCLUSION: Higher utilization of NICU care was not associated with lower rates of short-term events suggesting that there may be opportunities to safely decrease admission rates and length of NICU stays.

Epidemiology of Surgical Procedures, Anesthesia, and Imaging Studies by Gestational Age during the First Year of Life in Medicaid-Insured Infants.

OBJECTIVES: To evaluate the rate of surgical procedures, anesthetic use, and imaging studies by prematurity status for the first year of life we analyzed data for Texas Medicaid-insured newborns. STUDY DESIGN: We developed a retrospective population-based live birth cohort of newborn infants insured by Texas Medicaid in 2010-2014 with 4 subcohorts: extremely premature, very premature, moderate/late premature, and term. RESULTS: In 1 102 958 infants, surgical procedures per 100 infants were 135.9 for extremely premature, 35.4 for very premature, 15.5 for moderate/late premature, and 6.5 for term. Anesthetic use was 62.0 for extremely premature, 20.8 for very premature, 11.1 for moderate/late premature, and 5.6 for the term subcohort. The most common procedures in the extremely premature were neurosurgery, intubations, and procedures that facilitated caloric intake (gastrostomy tubes and fundoplications). The annual rates for the first year of life for chest radiograph ranged from 15.0 per year for the extremely premature cohort to 0.6 for term infants and for magnetic resonance imaging (MRI) from 0.3 to 0.01. MRI was the most common imaging study with anesthesia support in all maturity levels. MRIs were done in extremely premature without anesthesia in over 90% and in term infants in 57.2%. CONCLUSIONS: Surgical procedures, anesthetic use, and imaging studies in infants are common and more frequent with higher a degree of prematurity while the use of anesthesia is lower in more premature newborns. These findings can provide direction for outcome studies of surgery and anesthesia exposure.

Transplant Options for Patients With Diabetes and Advanced Kidney Disease: A Review.

Optimal glycemic control in kidney transplant recipients with diabetes is associated with improved morbidity and better patient and allograft survival. Transplant options for patients with diabetes requiring insulin therapy and chronic kidney disease who are suitable candidates for kidney transplantation should include consideration of ß-cell replacement therapy: pancreas or islet transplantation. International variation related to national regulatory policies exists in offering one or both options to suitable candidates and is further affected by pancreas/islet allocation policies and transplant waiting list dynamics. The selection of appropriate candidates depends on patient age, coexistent morbidities, the timing of referral to the transplant center (predialysis versus on dialysis) and availability of living kidney donors. Therefore, early referral (estimated glomerular filtration rate < 30 mL/min/1.73 m2) is of the utmost importance to ensure adequate time for informed decision making and thorough pretransplant evaluation. Obesity, cardiovascular disease, peripheral vascular disease, smoking, and frailty are some of the conditions that need to be addressed before acceptance on the transplant list, and ideally before dialysis becoming imminent. This review offers insights into selection of pancreas/islet transplant candidates by transplant centers and an update on posttransplant outcomes, which may have practice implications for referring nephrologists.

Urban-rural differences in pregnancy-related deaths, United States, 2011-2016.

BACKGROUND: The US pregnancy-related mortality ratio has not improved over the past decade and includes striking disparities by race and ethnicity and by state. Understanding differences in pregnancy-related mortality across and within urban and rural areas can guide the development of interventions for preventing future pregnancy-related deaths. OBJECTIVE: We sought to compare pregnancy-related mortality across and within urban and rural counties by race and ethnicity and age. STUDY DESIGN: We conducted a descriptive analysis of 3747 pregnancy-related deaths during 2011-2016 (the most recent available data) with available zone improvement plan code or county data in the Pregnancy Mortality Surveillance System, among Hispanic and non-Hispanic White, Black, American Indian or Alaska Native, and Asian or Pacific Islander women aged 15 to 44 years. We aggregated data by US county and grouped counties per the National Center for Health Statistics Urban-Rural Classification Scheme for Counties. We used R statistical software, epitools, to calculate the pregnancy-related mortality ratio (number of pregnancy-related deaths per 100,000 live births) for each urban-rural grouping, obtain 95% confidence intervals, and perform exact tests of ratio comparisons using the Poisson distribution. RESULTS: Of the total 3747 pregnancy-related deaths analyzed, 52% occurred in large metro counties, and 7% occurred in noncore (rural) counties. Large metro counties had the lowest pregnancy-related mortality ratio (14.8; 95% confidence interval, 14.2-15.5), whereas noncore counties had the highest (24.1; 95% confidence interval, 21.4-27.1), including race and ethnicity and age groups. Pregnancy-related mortality ratio age disparities increased with rurality. Women aged 25 to 34 years and 35 to 44 years living in noncore counties had pregnancy-related mortality ratios 1.5 and 3 times higher, respectively, than women of the same age groups in large metro counties. Within each urban-rural category, pregnancy-related mortality ratios were higher among non-Hispanic Black women than non-Hispanic White women. Non-Hispanic American Indian or Alaska Native pregnancy-related mortality ratios in small metro, micropolitan, and noncore counties were 2 to 3 times that of non-Hispanic White women in the same areas. CONCLUSION: Although more than half of pregnancy-related deaths occurred in large metro counties, the pregnancy-related mortality ratio rose with increasing rurality. Disparities existed in urban-rural categories, including by age group and race and ethnicity. Geographic location is an important context for initiatives to prevent future deaths and eliminate disparities. Further research is needed to better understand reasons for the observed urban-rural differences and to guide a multifactorial response to reduce pregnancy-related deaths.

Effect of Delays in Maternal Access to Healthcare on Neonatal Mortality in Sierra Leone: A Social Autopsy Case-Control Study at a Child Health and Mortality Prevention Surveillance (CHAMPS) Site.

INTRODUCTION: In low-resource settings, a social autopsy tool has been proposed to measure the effect of delays in access to healthcare on deaths, complementing verbal autopsy questionnaires routinely used to determine cause of death. This study estimates the contribution of various delays in maternal healthcare to subsequent neonatal mortality using a social autopsy case-control design. METHODS: This study was conducted at the Child Health and Mortality Prevention Surveillance (CHAMPS) Sierra Leone site (Makeni City and surrounding rural areas). Cases were neonatal deaths in the catchment area, and controls were sex- and area-matched living neonates. Odds ratios for maternal barriers to care and neonatal death were estimated, and stratified models examined this association by neonatal age and medical complications. RESULTS: Of 53 neonatal deaths, 26.4% of mothers experienced at least one delay during pregnancy or delivery compared to 46.9% of mothers of stillbirths and 18.6% of control mothers. The most commonly reported delay among neonatal deaths was receiving care at the facility (18.9%). Experiencing any barrier was weakly associated (OR 1.68, CI 0.77, 3.67) and a delay in receiving care at the facility was strongly associated (OR 19.15, CI 3.90, 94.19) with neonatal death. DISCUSSION: Delays in healthcare are associated with neonatal death, particularly delays experienced at the healthcare facility. Heterogeneity exists in the prevalence of specific delays, which has implications for local public health policy. The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Pregnant? Validity of the pregnancy checkbox on death certificates in four states, and characteristics associated with pregnancy checkbox errors.

BACKGROUND: Maternal mortality rates in the United States appear to be increasing. One potential reason may be increased identification of maternal deaths after the addition of a pregnancy checkbox to the death certificate. In 2016, 4 state health departments (Georgia, Louisiana, Michigan, and Ohio) implemented a pregnancy checkbox quality assurance pilot, with technical assistance provided by the Centers for Disease Control and Prevention. The pilot aimed to improve accuracy of the pregnancy checkbox on death certificates and resultant state maternal mortality estimates. OBJECTIVE: To estimate the validity of the pregnancy checkbox on the death certificate, and to describe characteristics associated with errors using 2016 data from a 4-state quality assurance pilot. MATERIALS AND METHODS: Potential pregnancy-associated deaths were identified by linking death certificates with birth or fetal death certificates from within 1 year preceding death or by pregnancy checkbox status. Death certificates that indicated that the decedent was pregnant within 1 year of death via the pregnancy checkbox, but that did not link to a birth or fetal death certificate, were referred for active follow-up to confirm pregnancy status by either death certifier confirmation or medical record review. Descriptive statistics and 95% confidence intervals were used to examine the distributions of demographic characteristics by pregnancy confirmation category (confirmed pregnant, confirmed not pregnant, and unable to confirm). We compared the proportion confirmed pregnant and confirmed not pregnant within age, race/ethnicity, pregnancy checkbox category, and certifier type categories using a Wald test of proportions. Binomial and Poisson regression models were used to estimate prevalence ratios for having an incorrect pregnancy checkbox (false positive, false negative) by age group, race/ethnicity, pregnancy checkbox category, and certifier type. RESULTS: Among 467 potential pregnancy-associated deaths, 335 (72%) were confirmed pregnant via linkage to a birth or fetal death certificate, certifier confirmation, or review of medical records. A total of 97 women (21%) were confirmed not pregnant (false positives) and 35 (7%) were unable to be confirmed. Women confirmed pregnant were significantly younger than women confirmed not pregnant (P < .001). Deaths certified by coroners and medical examiners were more likely to be confirmed pregnant than confirmed not pregnant (P = .04). The association between decedent age category and false-positive status followed a dose-response relationship (P < .001), with increasing prevalence ratios for each increase in age category. Death certificates of non-Hispanic black women were more likely to be false positive, compared with non-Hispanic white women (prevalence ratio, 1.41; 95% confidence interval, 1.01, 1.96). The sensitivity of the pregnancy checkbox among these 4 states in 2016 was 62% and the positive predictive value was 68%. CONCLUSION: We provide a multi-state analysis of the validity of the pregnancy checkbox and highlight a need for more accurate reporting of pregnancy status on death certificates. States and other jurisdictions may increase the accuracy of their data used to calculate maternal mortality rates by implementing quality assurance processes.

Geographical variation in palliative cancer care in a tax-based healthcare system: drug reimbursement in Denmark.

BACKGROUND: In Denmark, a tax-based universal healthcare setting, drug reimbursement for terminal illness (DRTI) should be equally accessible for all terminally ill patients. Examining DRTI status by regions provides new knowledge on inequality in palliative care provision and associated factors. This study aims to investigate geographical variation in DRTI among terminally ill cancer patients. METHODS: We linked socioeconomic and medical data from 135 819 Danish cancer decedents in the period 2007-15 to regional healthcare characteristics. We analyzed associations between region of residence and DRTI. Prevalence ratios (PR) for DRTI were estimated using generalized linear models adjusted for patient factors (age, gender, comorbidity and socioeconomic profile) and multilevel models adjusted for both patient factors and regional healthcare capacity (patients per general practitioner, numbers of hospital and hospice beds). RESULTS: DRTI allocation differed substantially across Danish regions. Healthcare capacity was associated with DRTI with a higher probability of DRTI among patients living in regions with high compared with low hospice bed supply (PR 1.13, 95% CI 1.10-1.17). Also, the fully adjusted PR of DRTI was 0.94 (95% CI 0.91-0.96) when comparing high with low number of hospital beds. When controlled for both patient and regional healthcare characteristics, the PR for DRTI was 1.17 (95% CI 1.14-1.21) for patients living in the Central Denmark Region compared with the Capital Region. CONCLUSION: DRTI status varied across regions in Denmark. The variation was associated with the distribution of healthcare resources. These findings highlight difficulties in ensuring equal access to palliative care even in a universal healthcare system.

Neonatal Intensive Care Variation in Medicaid-Insured Newborns: A Population-Based Study.

OBJECTIVE: To assess the contribution of maternal and newborn characteristics to variation in neonatal intensive care use across regions and hospitals. STUDY DESIGN: This was a retrospective population-based live birth cohort of newborn infants insured by Texas Medicaid in 2010-2014 with 2 subcohorts: very low birth weight (VLBW) singletons and late preterm singletons. Crude and risk-adjusted neonatal intensive care unit (NICU) admission rates, intensive and intermediate special care days, and imaging procedures were calculated across Neonatal Intensive Care Regions (n = 21) and hospitals (n = 100). Total Medicaid payments were calculated. RESULTS: Overall, 11.5% of live born, 91.7% of VLBW, and 37.6% of infants born late preterm were admitted to a NICU, receiving an average of 2 days, 58 days, and 5 days of special care with payments per newborn inpatient episode of $5231, $128 075, and $10 837, respectively. There was little variation across regions and hospitals in VLBW NICU admissions but marked variation for NICU admissions in late preterm newborn infants and for special care days and imaging rates in all cohorts. The variation decreased slightly after health risk adjustment. There was moderate substitution of intermediate for intensive care days across hospitals (Pearson r VLBW -0.63 P < .001; late preterm newborn -0.53 P < .001). CONCLUSIONS: Across all risk groups, the variation in NICU use was poorly explained by differences in newborn illness levels and is likely to indicate varying practice styles. Although the "right" rates are uncertain, it is unlikely that all of these use patterns represent effective and efficient care.

Role of Prices, Utilization, and Health in Explaining Texas Medicaid Newborn Care Spending Variation.

BACKGROUND: Newborn care is one of the most frequent types of hospitalization and Medicaid covers over 50% of all births nationwide. However, little is known about regional variation in Medicaid newborn care spending and its drivers. OBJECTIVES: To measure the contribution of market-level prices, utilization, and health risk on regional variation in spending among newborn Medicaid population in Texas. RESEARCH DESIGN AND METHODS: The study used 2014 Texas Medicaid newborn claims and encounters linked to birth and death certificate data. Newborn care spending was defined as Medicaid payments per newborn hospital stay, including hospital transfers, from birth through discharge home or death. Spending was further categorized into inpatient facility and related professional spending. Variation in spending across neonatal intensive care regions was decomposed into price and utilization, accounting for input price and health risk differences. RESULTS: Newborn care spending across Texas regions varied significantly (coefficient of variation, 0.31), with most of the variation attributed to spending on inpatient facility services (91%). Both price (41%) and utilization (27%) played a role in explaining this variation, after adjusting for health status (29%) and input price (4%). Though most regions with the highest spending indexes had high price and utilization indexes, some had high spending driven mostly by high prices and others by high utilization. CONCLUSIONS: Significant regional variations in price, utilization, and health status exist in Medicaid newborn care across Texas in 2014. Disentangling the effect of each driver is important to address spending variation and improve efficiency in newborn care.

Changing the conversation: applying a health equity framework to maternal mortality reviews.

The risk of maternal death in the United States is higher than peer nations and is rising and varies dramatically by the race and place of residence of the woman. Critical efforts to reduce maternal mortality include patient risk stratification and system-level quality improvement efforts targeting specific aspects of clinical care. These efforts are important for addressing the causes of an individual's risk, but research to date suggests that individual risk factors alone do not adequately explain between-group disparities in pregnancy-related death by race, ethnicity, or geography. The holistic review and multidisciplinary makeup of maternal mortality review committees make them well positioned to fill knowledge gaps about the drivers of racial and geographic inequity in maternal death. However, committees may lack the conceptual framework, contextual data, and evidence base needed to identify community-based contributing factors to death and, when appropriate, to make recommendations for future action. By incorporating a multileveled, theory-grounded framework for causes of health inequity, along with indicators of the community vital signs, the social and community context in which women live, work, and seek health care, maternal mortality review committees may identify novel underlying factors at the community level that enhance understanding of racial and geographic inequity in maternal mortality. By considering evidence-informed community and regional resources and policies for addressing these factors, novel prevention recommendations, including recommendations that extend outside the realm of the formal health care system, may emerge.