A New Method for Creating Impact-Induced Intra-Articular Fractures in a Rabbit Model Induces Severe Post-Traumatic Osteoarthritis.

OBJECTIVES: The objective of this work was to develop a model of intra-articular fracture (IAF) in a rabbit and document the speed and severity of degenerative joint changes after fracture fixation. METHODS: With Institutional Animal Care & Use Committee approval, impact-induced IAFs were created in the distal tibia of 16 New Zealand White rabbits. Fractures were fixed with a plate and screws. Pain and function were monitored at regular postoperative intervals with limb loading analysis. Twelve or 26 weeks after fracture, animals were euthanized for histological assessment of cartilage degeneration and micro-computed tomography analysis of bone histomorphometry. RESULTS: Eleven animals successfully completed the study. Maximum foot force in the fractured limb was 41% ± 21% lower than preoperative values ( P = 0.006) 12 weeks after fracture and remained 25% ± 13% lower ( P = 0.081) after 26 weeks. Cortical bone mineral density in micro-computed tomography images was 34% ± 13% lower 12 weeks after fracture ( P < 0.001) and remained (42% ± 8%) lower 26 weeks after fracture ( P < 0.001). Twelve weeks after fracture, Mankin scores of cartilage degeneration were significantly higher in the medial talus ( P = 0.007), lateral talus ( P < 0.001), medial tibia ( P = 0.017), and lateral tibia ( P = 0.002) of the fractured limb compared with the uninjured contralateral limb. Average Mankin scores in the talus increased from 12 to 26 weeks (5.9 ± 0.9 to 9.4 ± 0.4; P < 0.001 lateral; 5.4 ± 1.8 to 7.8 ± 2.0; P = 0.043 medial), indicating substantial and progressive joint degeneration. CONCLUSIONS: The ankle joint of the New Zealand White rabbit provides the smallest available model of impact-induced IAF that can be treated with clinically relevant techniques and replicates key features of healing and degeneration found in human patients.

Pregnancy-Related Deaths by Hispanic Origin, United States, 2009-2018.

Objective: To describe pregnancy-related mortality among Hispanic people by place of origin (country or region of Hispanic ancestry), 2009-2018. Materials and Methods: We conducted a cross-sectional descriptive study of pregnancy-related deaths among Hispanic people, stratified by place of origin (Central or South America, Cuba, Dominican Republic, Mexico, Puerto Rico, Other and Unknown Hispanic), using Pregnancy Mortality Surveillance System data, 2009-2018. We describe distributions of pregnancy-related deaths and pregnancy-related mortality ratios (number of pregnancy-related deaths per 100,000 live births) overall and by place of origin for select demographic and clinical characteristics. Results: For 2009-2018, the overall pregnancy-related mortality ratio among Hispanic people was 11.5 pregnancy-related deaths per 100,000 live births (95% confidence intervals [CI]: 10.8-12.2). In general, pregnancy-related mortality ratios were higher among older age groups (i.e., 35 years and older) and lower among those with higher educational attainment (i.e., college degree or higher). Approximately two in five pregnancy-related deaths among Hispanic people occurred on the day of delivery through 6 days postpartum. Place of origin-specific pregnancy-related mortality ratios ranged from 9.6 (95% CI: 5.8-15.0) among people of Cuban origin to 15.3 (95% CI: 12.4-18.3) among people of Puerto Rican origin. Hemorrhage and infection were the most frequent causes of pregnancy-related deaths overall among Hispanic people. People of Puerto Rican origin had a higher proportion of deaths because of cardiomyopathy. Conclusions: We identified differences in pregnancy-related mortality by place of origin among Hispanic people that can help inform prevention of pregnancy-related deaths.

Development of a Pneumatic-Driven Fiber-Shaped Robot Scaffold for Use as a Complex 3D Dynamic Culture System.

Cells can sense and respond to different kinds of continuous mechanical strain in the human body. Mechanical stimulation needs to be included within the in vitro culture system to better mimic the existing complexity of in vivo biological systems. Existing commercial dynamic culture systems are generally two-dimensional (2D) which fail to mimic the three-dimensional (3D) native microenvironment. In this study, a pneumatically driven fiber robot has been developed as a platform for 3D dynamic cell culture. The fiber robot can generate tunable contractions upon stimulation. The surface of the fiber robot is formed by a braiding structure, which provides promising surface contact and adequate space for cell culture. An in-house dynamic stimulation using the fiber robot was set up to maintain NIH3T3 cells in a controlled environment. The biocompatibility of the developed dynamic culture systems was analyzed using LIVE/DEAD™ and alamarBlue™ assays. The results showed that the dynamic culture system was able to support cell proliferation with minimal cytotoxicity similar to static cultures. However, we observed a decrease in cell viability in the case of a high strain rate in dynamic cultures. Differences in cell arrangement and proliferation were observed between braided sleeves made of different materials (nylon and ultra-high molecular weight polyethylene). In summary, a simple and cost-effective 3D dynamic culture system has been proposed, which can be easily implemented to study complex biological phenomena in vitro.

Myocarditis in Minnehaha County, South Dakota, 1880-1939.

From 1920 to 1940 in Minnehaha County there was an apparent striking increase in the incidence of fatal myocarditis and chronic myocarditis. Based on an analysis of the interment records of the Mt. Pleasant Cemetery, word frequency studies in two prominent American medical journals and a general review of related medical publications, we explore this increase. We conclude that there was no actual increase in the frequency of inflammatory disorders of the myocardium in Minnehaha County during this period. Rather, it appears that the use of the diagnostic terms was a matter of choice among local physicians that was not supported by contemporaneous clinical and pathophysiologic publications in available journals.

Fatal Accidental Drowning in Minnehaha County, South Dakota, 1880-1939.

Drowning is currently the second leading cause of injury-related death for children 1-4 years of age in the United States and is the leading cause of death worldwide for boys ages 5-14 years. The World Health Organization (WHO) classifies it as a public health threat and advocates for reducing drowning deaths by understanding geographical, cultural, and societal risk factors. To these three we added a fourth: historical studies. To that end, we analyzed accidental causes of death between January 1, 1880, and December 31, 1939, in Minnehaha County, South Dakota, based on interment records from the Mt. Pleasant Cemetery. From these six decades (1880-1939) of data, we classified 217 cases as accidental deaths. Drowning was the leading cause of accidental mortality, accounting for 50 accidental deaths (23%). Drowning deaths were analyzed by the decedents' age and date of death. We discuss specific historical drowning risk factors and hypothesize how they may have affected drowning deaths from 1880-1939 in Minnehaha County.

Drivers of shared decision making in inpatient psychiatry: An exploratory survey of patients' and multi-disciplinary team members' perspectives.

OBJECTIVE: To assess the prevalence and predictors of Shared Decision Making (SDM) in an adult, inpatient psychiatric setting. METHOD: Multi-disciplinary clinician focus groups and patient pre-testing informed the development of a survey on 4 SDM and 11 factors hypothesized to interfere with SDM. The survey was administered to 89 adult inpatients (80% response rate) and their treatment team psychiatrists, nurses, and social workers (n = 338 ratings, 95% response rate). Group differences and predictors were estimated using t and F-tests. RESULTS: Patients' mean SDM score (n = 64, standardized Cronbach alpha = 0.858) was 3.35 ± 1.13 (5 = highest agreement), and correlated with overall satisfaction with care (n = 61, r = 0.399, p = 0.001). Patients' disagreement with clinician's diagnosis (44% of patients) correlated with lower SDM ratings by patients (t = 2.55, df = 62, p = 0.013) and by clinicians (t = 2.99, df = 69, p = 0.004). Psychotic diagnoses were not a significant determining factor for SDM. Overall, clinicians rated SDM more favorably than patients (t = -5.43, df = 63, p < 0.001), with nurses and social workers rating SDM higher than physicians (p < 0.001). CONCLUSIONS: Diagnostic agreement / disagreement is a key predictor of SDM for patients and clinicians, while presence of psychosis is not. SDM was rated higher by clinicians than patients. SDM ratings vary significantly between clinical disciplines.

County-Level Associations Between Pregnancy-Related Mortality Ratios and Contextual Sociospatial Indicators.

OBJECTIVE: To characterize county-level differences in pregnancy-related mortality as a function of sociospatial indicators. METHODS: We conducted a cross-sectional multilevel analysis of all pregnancy-related deaths and all live births with available ZIP code or county data in the Pregnancy Mortality Surveillance System during 2011-2016 for non-Hispanic Black, Hispanic (all races), and non-Hispanic White women aged 15-44 years. The exposures included 31 conceptually-grounded, county-specific sociospatial indicators that were collected from publicly available data sources and categorized into domains of demographic; general, reproductive, and behavioral health; social capital and support; and socioeconomic contexts. We calculated the absolute difference of county-level pregnancy-related mortality ratios (deaths per 100,000 live births) per 1-unit increase in the median absolute difference between women living in counties with higher compared with lower levels of each sociospatial indicator overall and stratified by race and ethnicity. RESULTS: Pregnancy-related mortality varied across counties and by race and ethnicity. Many sociospatial indicators were associated with county-specific pregnancy-related mortality ratios independent of maternal age, population size, and Census region. Across domains, the most harmful indicators were percentage of low-birth-weight births (absolute ratio difference [RD] 6.44; 95% CI 5.36-7.51), percentage of unemployed adults (RD 4.98; 95% CI 3.91-6.05), and food insecurity (RD 4.92; 95% CI 4.14-5.70). The most protective indicators were higher median household income (RD -2.76; 95% CI -3.28 to -2.24), percentage of college-educated adults (RD -2.28; 95% CI -2.81 to -1.75), and percentage of owner-occupied households (RD -1.66; 95% CI -2.29 to -1.03). The magnitude of these associations varied by race and ethnicity. CONCLUSION: This analysis identified sociospatial indicators of pregnancy-related mortality and showed an association between pregnancy-related deaths and place of residence overall and stratified by race and ethnicity. Understanding county-level context associated with pregnancy-related mortality may be an important step towards building public health evidence to inform action to reduce pregnancy-related mortality at local levels.

Intra-Articular Adeno-Associated Virus-Mediated Proteoglycan 4 Gene Therapy for Preventing Posttraumatic Osteoarthritis.

Lubricin, a glycoprotein encoded by the proteoglycan 4 (PRG4) gene, is an essential boundary lubricant that reduces friction between articular cartilage surfaces. The loss of lubricin subsequent to joint injury plays a role in the pathogenesis of posttraumatic osteoarthritis. In this study, we describe the development and evaluation of an adeno-associated virus (AAV)-based PRG4 gene therapy intended to restore lubricin in injured joints. The green fluorescent protein (GFP) gene was inserted the PRG4 gene to facilitate tracing the distribution of the transgene product (AAV-PRG4-GFP) in vivo. Transduction efficiency of AAV-PRG4-GFP was evaluated in joint cells, and the conditioned medium containing secreted PRG4-GFP was used for shear loading/friction and viability tests. In vivo transduction of joint tissues following intra-articular injection of AAV-PRG4-GFP was confirmed in the mouse stifle joint in a surgical model of destabilization of the medial meniscus (DMM), and chondroprotective activity was tested in a rabbit anterior cruciate ligament transection (ACLT) model. In vitro studies showed that PRG4-GFP has lubricin-like cartilage-binding and antifriction properties. Significant cytoprotective effects were seen when cartilage was soaked in PRG4-GFP before cyclic shear loading (n = 3). Polymerase chain reaction and confocal microscopy confirmed the presence of PRG4-GFP DNA and protein, respectively, in a mouse DMM (n = 3 per group). In the rabbit ACLT model, AAV-PRG4-GFP gene therapy enhanced lubricin expression (p = 0.001 vs. AAV-GFP: n = 7-14) and protected the cartilage from degeneration (p = 0.014 vs. AAV-GFP: n = 9-10) when treatments were administered immediately postoperation, but efficacy was lost when treatment was delayed for 2 weeks. AAV-PRG4-GFP gene therapy protected cartilage from degeneration in a rabbit ACLT model; however, data from the ACLT model suggest that early intervention is essential for efficacy.

Abortion Surveillance - United States, 2019.

PROBLEM/CONDITION: CDC conducts abortion surveillance to document the number and characteristics of women obtaining legal induced abortions and number of abortion-related deaths in the United States. PERIOD COVERED: 2019. DESCRIPTION OF SYSTEM: Each year, CDC requests abortion data from the central health agencies for 50 states, the District of Columbia, and New York City. For 2019, 49 reporting areas voluntarily provided aggregate abortion data to CDC. Of these, 48 reporting areas provided data each year during 2010-2019. Census and natality data were used to calculate abortion rates (number of abortions per 1,000 women aged 15-44 years) and ratios (number of abortions per 1,000 live births), respectively. Abortion-related deaths from 2018 were assessed as part of CDC's Pregnancy Mortality Surveillance System (PMSS). RESULTS: A total of 629,898 abortions for 2019 were reported to CDC from 49 reporting areas. Among 48 reporting areas with data each year during 2010-2019, in 2019, a total of 625,346 abortions were reported, the abortion rate was 11.4 abortions per 1,000 women aged 15-44 years, and the abortion ratio was 195 abortions per 1,000 live births. From 2018 to 2019, the total number of abortions increased 2% (from 614,820 total abortions), the abortion rate increased 0.9% (from 11.3 abortions per 1,000 women aged 15-44 years), and the abortion ratio increased 3% (from 189 abortions per 1,000 live births). From 2010 to 2019, the total number of reported abortions, abortion rate, and abortion ratio decreased 18% (from 762,755), 21% (from 14.4 abortions per 1,000 women aged 15-44 years), and 13% (from 225 abortions per 1,000 live births), respectively. In 2019, women in their 20s accounted for more than half of abortions (56.9%). Women aged 20-24 and 25-29 years accounted for the highest percentages of abortions (27.6% and 29.3%, respectively) and had the highest abortion rates (19.0 and 18.6 abortions per 1,000 women aged 20-24 and 25-29 years, respectively). By contrast, adolescents aged <15 years and women aged ≥40 years accounted for the lowest percentages of abortions (0.2% and 3.7%, respectively) and had the lowest abortion rates (0.4 and 2.7 abortions per 1,000 women aged <15 and ≥40 years, respectively). However, abortion ratios in 2019 were highest among adolescents (aged ≤19 years) and lowest among women aged 25-39 years. Abortion rates decreased from 2010 to 2019 for all women, regardless of age. The decrease in abortion rate was highest among adolescents compared with any other age group. From 2018 to 2019, abortion rates decreased or did not change among women aged ≤24 years; however, the abortion rate increased among those aged ≥25 years. Abortion ratios also decreased or did not change from 2010 to 2019 for all age groups, except adolescents aged <15 years. The decrease in abortion ratio was highest among women aged ≥40 years compared with any other age group. From 2018 to 2019, abortion ratios increased for all age groups, except adolescents aged <15 years. In 2019, 79.3% of abortions were performed at ≤9 weeks' gestation, and nearly all (92.7%) were performed at ≤13 weeks' gestation. During 2010-2019, the percentage of abortions performed at >13 weeks' gestation remained consistently low (≤9.0%). In 2019, the highest proportion of abortions were performed by surgical abortion at ≤13 weeks' gestation (49.0%), followed by early medical abortion at ≤9 weeks' gestation (42.3%), surgical abortion at >13 weeks' gestation (7.2%), and medical abortion at >9 weeks' gestation (1.4%); all other methods were uncommon (<0.1%). Among those that were eligible (≤9 weeks' gestation), 53.7% of abortions were early medical abortions. In 2018, the most recent year for which PMSS data were reviewed for pregnancy-related deaths, two women died as a result of complications from legal induced abortion. INTERPRETATION: Among the 48 areas that reported data continuously during 2010-2019, overall decreases were observed during 2010-2019 in the total number, rate, and ratio of reported abortions; however, from 2018 to 2019, 1%-3% increases were observed across all measures. PUBLIC HEALTH ACTION: Abortion surveillance can be used to help evaluate programs aimed at promoting equitable access to patient-centered quality contraceptive services in the United States to reduce unintended pregnancies.

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.

Abortion Surveillance - United States, 2018.

PROBLEM/CONDITION: CDC conducts abortion surveillance to document the number and characteristics of women obtaining legal induced abortions and number of abortion-related deaths in the United States. PERIOD COVERED: 2018. DESCRIPTION OF SYSTEM: Each year, CDC requests abortion data from the central health agencies for 50 states, the District of Columbia, and New York City. For 2018, 49 reporting areas voluntarily provided aggregate abortion data to CDC. Of these, 48 reporting areas provided data each year during 2009-2018. Census and natality data were used to calculate abortion rates (number of abortions per 1,000 women aged 15-44 years) and ratios (number of abortions per 1,000 live births), respectively. Abortion-related deaths from 2017 were assessed as part of CDC's Pregnancy Mortality Surveillance System (PMSS). RESULTS: A total of 619,591 abortions for 2018 were reported to CDC from 49 reporting areas. Among 48 reporting areas with data each year during 2009-2018, in 2018, a total of 614,820 abortions were reported, the abortion rate was 11.3 abortions per 1,000 women aged 15-44 years, and the abortion ratio was 189 abortions per 1,000 live births. From 2017 to 2018, the total number of abortions and abortion rate increased 1% (from 609,095 total abortions and from 11.2 abortions per 1,000 women aged 15-44 years, respectively), and the abortion ratio increased 2% (from 185 abortions per 1,000 live births). From 2009 to 2018, the total number of reported abortions, abortion rate, and abortion ratio decreased 22% (from 786,621), 24% (from 14.9 abortions per 1,000 women aged 15-44 years), and 16% (from 224 abortions per 1,000 live births), respectively. In 2018, women in their 20s accounted for more than half of abortions (57.7%). In 2018 and during 2009-2018, women aged 20-24 and 25-29 years accounted for the highest percentages of abortions; in 2018, they accounted for 28.3% and 29.4% of abortions, respectively, and had the highest abortion rates (19.1 and 18.5 per 1,000 women aged 20-24 and 25-29 years, respectively). By contrast, adolescents aged <15 years and women aged ≥40 years accounted for the lowest percentages of abortions (0.2% and 3.6%, respectively) and had the lowest abortion rates (0.4 and 2.6 per 1,000 women aged <15 and ≥40 years, respectively). However, abortion ratios in 2018 and throughout 2009-2018 were highest among adolescents (aged ≤19 years) and lowest among women aged 25-39 years. Abortion rates decreased from 2009 to 2018 for all women, regardless of age. The decrease in abortion rate was highest among adolescents compared with women in any other age group. From 2009 to 2013, the abortion rates decreased for all age groups and from 2014 to 2018, the abortion rates decreased for all age groups, except for women aged 30-34 years and those aged ≥40 years. In addition, from 2017 to 2018, abortion rates did not change or decreased among women aged ≤24 and ≥40 years; however, the abortion rate increased among women aged 25-39 years. Abortion ratios also decreased from 2009 to 2018 among all women, except adolescents aged <15 years. The decrease in abortion ratio was highest among women aged ≥40 years compared with women in any other age group. The abortion ratio decreased for all age groups from 2009 to 2013; however, from 2014 to 2018, abortion ratios only decreased for women aged ≥35 years. From 2017 to 2018, abortion ratios increased for all age groups, except women aged ≥40 years. In 2018, approximately three fourths (77.7%) of abortions were performed at ≤9 weeks' gestation, and nearly all (92.2%) were performed at ≤13 weeks' gestation. In 2018, and during 2009-2018, the percentage of abortions performed at >13 weeks' gestation remained consistently low (≤9.0%). In 2018, the highest proportion of abortions were performed by surgical abortion at ≤13 weeks' gestation (52.1%), followed by early medical abortion at ≤9 weeks' gestation (38.6%), surgical abortion at >13 weeks' gestation (7.8%), and medical abortion at >9 weeks' gestation (1.4%); all other methods were uncommon (<0.1%). Among those that were eligible (≤9 weeks' gestation), 50.0% of abortions were early medical abortions. In 2017, the most recent year for which PMSS data were reviewed for pregnancy-related deaths, two women were identified to have died as a result of complications from legal induced abortion. INTERPRETATION: Among the 48 areas that reported data continuously during 2009-2018, decreases were observed during 2009-2017 in the total number, rate, and ratio of reported abortions, and these decreases resulted in historic lows for this period for all three measures. These decreases were followed by 1%-2% increases across all measures from 2017 to 2018. PUBLIC HEALTH ACTION: The data in this report can help program planners and policymakers identify groups of women with the highest rates of abortion. Unintended pregnancy is a major contributor to induced abortion. Increasing access to and use of effective contraception can reduce unintended pregnancies and further reduce the number of abortions performed in the United States.

A Multi-Functional Implant Induces Bone Formation in a Diabetic Model.

Patients with diabetes mellitus (DM) have defective healing of bone fractures. It was previously shown that nonviral gene delivery of plasmid DNA (pDNA) that independently encodes bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2), acts synergistically to promote bone regeneration in a DM animal model. Additionally, both insulin (INS) and the hormonally active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2 D3 ) (VD3) have independently been shown to play key roles in regulating bone fracture healing in DM patients. However, these individual therapies fail to adequately stimulate bone regeneration, illustrating a need for novel treatment of bone fractures in diabetic patients. Here, the ability of local delivery of INS and VD3 along with BMP-2 and FGF-2 genes is investigated to promote bone formation ectopically in Type-2 diabetic rats. A composite consisting of VD3 and INS is developed that contains poly(lactic-co-glycolic acid) microparticles (MPs) embedded in a fibrin gel surrounded by a collagen matrix that is permeated with polyethylenimine (PEI)-(pBMP-2+pFGF-2) nanoplexes. Using a submuscular osteoinduction model, it is demonstrated that local delivery of INS, VD3, and PEI-(pBMP-2+pFGF-2) significantly improves bone generation compared to other treatments, thusimplicating this approach as a method to promote bone regeneration in DM patients with bone fractures.

Using Supervised Learning Methods to Develop a List of Prescription Medications of Greatest Concern during Pregnancy.

INTRODUCTION: Women and healthcare providers lack adequate information on medication safety during pregnancy. While resources describing fetal risk are available, information is provided in multiple locations, often with subjective assessments of available data. We developed a list of medications of greatest concern during pregnancy to help healthcare providers counsel reproductive-aged and pregnant women. METHODS: Prescription drug labels submitted to the U.S. Food and Drug Administration with information in the Teratogen Information System (TERIS) and/or Drugs in Pregnancy and Lactation by Briggs & Freeman were included (N = 1,186 medications; 766 from three data sources, 420 from two). We used two supervised learning methods ('support vector machine' and 'sentiment analysis') to create prediction models based on narrative descriptions of fetal risk. Two models were created per data source. Our final list included medications categorized as 'high' risk in at least four of six models (if three data sources) or three of four models (if two data sources). RESULTS: We classified 80 prescription medications as being of greatest concern during pregnancy; over half were antineoplastic agents (n = 24), angiotensin converting enzyme inhibitors (n = 10), angiotensin II receptor antagonists (n = 8), and anticonvulsants (n = 7). DISCUSSION: This evidence-based list could be a useful tool for healthcare providers counseling reproductive-aged and pregnant women about medication use during pregnancy. However, providers and patients may find it helpful to weigh the risks and benefits of any pharmacologic treatment for both pregnant women and the fetus when managing medical conditions before and during pregnancy.

Hospitalizations and Deaths Associated with EVALI.

BACKGROUND: As of January 7, 2020, a total of 2558 hospitalized patients with nonfatal cases and 60 patients with fatal cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) had been reported to the Centers for Disease Control and Prevention (CDC). METHODS: In a national study, we compared the characteristics of patients with fatal cases of EVALI with those of patients with nonfatal cases to improve the ability of clinicians to identify patients at increased risk for death from the condition. Health departments reported cases of EVALI to the CDC and included, when available, data from medical-record abstractions and patient interviews. Analyses included all the patients with fatal or nonfatal cases of EVALI that were reported to the CDC as of January 7, 2020. We also present three case reports of patients who died from EVALI to illustrate the clinical characteristics common among such patients. RESULTS: Most of the patients with fatal or nonfatal cases of EVALI were male (32 of 60 [53%] and 1666 of 2498 [67%], respectively). The proportion of patients with fatal or nonfatal cases was higher among those who were non-Hispanic white (39 of 49 [80%] and 1104 of 1818 [61%], respectively) than among those in other race or ethnic groups. The proportion of patients with fatal cases was higher among those 35 years of age or older (44 of 60 [73%]) than among those younger than 35 years, but the proportion with nonfatal cases was lower among those 35 years of age or older (551 of 2514 [22%]). Among the patients who had an available medical history, a higher proportion of those with fatal cases than those with nonfatal cases had a history of asthma (13 of 57 [23%] vs. 102 of 1297 [8%]), cardiac disease (26 of 55 [47%] vs. 115 of 1169 [10%]), or a mental health condition (32 of 49 [65%] vs. 575 of 1398 [41%]). A total of 26 of 50 patients (52%) with fatal cases had obesity. Half the patients with fatal cases (25 of 54 [46%]) were seen in an outpatient setting before hospitalization or death. CONCLUSIONS: Chronic conditions, including cardiac and respiratory diseases and mental health conditions, were common among hospitalized patients with EVALI.

Sulfasalazine Resolves Joint Stiffness in a Rabbit Model of Arthrofibrosis.

Joint stiffness due to fibrosis/capsule contracture is a seriously disabling complication of articular injury that surgical interventions often fail to completely resolve. Fibrosis/contracture is associated with the abnormal persistence of myofibroblasts, which over-produce and contract collagen matrices. We hypothesized that intra-articular therapy with drugs targeting myofibroblast survival (sulfasalazine), or collagen production (ß-aminopropionitrile and cis-hydroxyproline), would reduce joint stiffness in a rabbit model of fibrosis/contracture. Drugs were encapsulated in poly[lactic-co-glycolic] acid pellets and implanted in joints after fibrosis/contracture induction. Capsule α-smooth muscle actin (α-SMA) expression and intimal thickness were evaluated by immunohistochemistry and histomorphometry, respectively. Joint stiffness was quantified by flexion-extension testing. Drawer tests were employed to determine if the drugs induced cruciate ligament laxity. Joint capsule fibroblasts were tested in vitro for contractile activity and α-SMA expression. Stiffness in immobilized joints treated with blank pellets (control) was significantly higher than in non-immobilized, untreated joints (normal) (p = 0.0008), and higher than in immobilized joints treated with sulfasalazine (p = 0.0065). None of the drugs caused significant cruciate ligament laxity. Intimal thickness was significantly lower than control in the normal and sulfasalazine-treated groups (p = 0.010 and 0.025, respectively). Contractile activity in the cells from controls was significantly increased versus normal (p = 0.001). Sulfasalazine and ß-aminopropionitrile significantly inhibited this effect (p = 0.005 and 0.0006, respectively). α-SMA expression was significantly higher in control versus normal (p = 0.0021) and versus sulfasalazine (p = 0.0007). These findings support the conclusion that sulfasalazine reduced stiffness by clearing myofibroblasts from fibrotic joints. Statement of clinical significance: The results provide proof-of-concept that established joint stiffness can be resolved non-surgically. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:629-638, 2020.

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.

Assessing the Burden of Neonatal Abstinence Syndrome: Validation of ICD-9-CM Data, Florida, 2010-2011.

CONTEXT: On October 1, 2015, the United States transitioned from using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to ICD-10-CM. Continuing to monitor the burden of neonatal abstinence syndrome (NAS) after the transition presently requires use of data dependent on ICD-9-CM coding to enable trend analyses. Little has been published on the validation of using ICD-9-CM codes to identify NAS cases. OBJECTIVE: To assess the validity of hospital discharge data (HDD) from selected Florida hospitals for passive NAS surveillance, based on ICD-9-CM codes, which are used to quantify baseline prevalence of NAS. DESIGN: We reviewed infant and maternal data for all births at 3 Florida hospitals from 2010 to 2011. Potential NAS cases included infants with ICD-9-CM discharge codes 779.5 and/or 760.72 in linked administrative data (ie, HDD linked to vital records) or in unlinked HDD and infants identified through review of neonatal intensive care unit admission logs or inpatient pharmacy records. Confirmed infant cases met 3 clinician-proposed criteria. Sensitivity and positive predictive value were calculated to assess validity for the 2 ICD-9-CM codes, individually and combined. RESULTS: Of 157 confirmed cases, 134 with 779.5 and/or 760.72 codes were captured in linked HDD (sensitivity = 85.4%) and 151 in unlinked HDD (sensitivity = 96.2%). Positive predictive value was 74.9% for linked HDD and 75.5% for unlinked HDD. For either HDD types, the single 779.5 code had the highest positive predictive value (86%), lowest number of false positives, and good to excellent sensitivity. CONCLUSIONS: Passive surveillance using ICD-9-CM code 779.5 in either linked or unlinked HDD identified NAS cases with reasonable validity. Our work supports the use of ICD-9-CM code 779.5 to assess the baseline prevalence of NAS through 2015.

Update: Characteristics of Patients in a National Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injuries - United States, October 2019.

CDC, the Food and Drug Administration, state and local health departments, and other public health and clinical stakeholders are investigating a national outbreak of electronic-cigarette (e-cigarette), or vaping, product use-associated lung injury (EVALI) (1). As of October 22, 2019, 49 states, the District of Columbia (DC), and the U.S. Virgin Islands have reported 1,604 cases of EVALI to CDC, including 34 (2.1%) EVALI-associated deaths in 24 states. Based on data collected as of October 15, 2019, this report updates data on patient characteristics and substances used in e-cigarette, or vaping, products (2) and describes characteristics of EVALI-associated deaths. The median age of EVALI patients who survived was 23 years, and the median age of EVALI patients who died was 45 years. Among 867 (54%) EVALI patients with available data on use of specific e-cigarette, or vaping, products in the 3 months preceding symptom onset, 86% reported any use of tetrahydrocannabinol (THC)-containing products, 64% reported any use of nicotine-containing products, and 52% reported use of both. Exclusive use of THC-containing products was reported by 34% of patients and exclusive use of nicotine-containing products by 11%, and for 2% of patients, no use of either THC- or nicotine-containing products was reported. Among 19 EVALI patients who died and for whom substance use data were available, 84% reported any use of THC-containing products, including 63% who reported exclusive use of THC-containing products; 37% reported any use of nicotine-containing products, including 16% who reported exclusive use of nicotine-containing products. To date, no single compound or ingredient used in e-cigarette, or vaping, products has emerged as the cause of EVALI, and there might be more than one cause. Because most patients reported using THC-containing products before symptom onset, CDC recommends that persons should not use e-cigarette, or vaping, products that contain THC. In addition, because the specific compound or ingredient causing lung injury is not yet known, and while the investigation continues, persons should consider refraining from the use of all e-cigarette, or vaping, products.