Cost-Effectiveness Analysis of Trastuzumab Deruxtecan Versus Trastuzumab Emtansine for Patients With Human Epidermal Growth Factor Receptor 2 Positive Metastatic Breast Cancer in the United States.

OBJECTIVES: To assess the cost-effectiveness of trastuzumab deruxtecan compared with trastuzumab emtansine as second-line therapy for patients with human epidermal growth factor receptor 2 positive metastatic breast cancer from a US healthcare sector perspective. METHODS: A 3-state partitioned survival model was developed to estimate the cost-effectiveness of trastuzumab deruxtecan compared with trastuzumab emtansine. For both treatments, modeled patients were administered treatment intravenously every 3 weeks indefinitely or until disease progression. Transition parameters were principally derived from the updated DESTINY-Breast03 phase III randomized clinical trial. Costs include drug costs extracted from Centers for Medicare and Medicaid Services average sales price and administrative, adverse event, and third-line therapy costs derived from published literature, measured in 2022 US dollars. Health utilities for health states and disutilities for adverse events were sourced from published literature. Effects were measured in quality-adjusted life years (QALYs). We conducted both probabilistic sensitivity analysis and comprehensive scenario analysis to test model assumptions and robustness, while utilizing a lifetime horizon. RESULTS: In our base-case analysis, total costs for trastuzumab deruxtecan were $1 266 945, compared with $820 082 for trastuzumab emtansine. Total QALYs for trastuzumab deruxtecan were 5.09, compared with 3.15 for trastuzumab emtansine. The base-case incremental cost-effectiveness ratio was $230 285/QALY. Probabilistic sensitivity analysis indicated that trastuzumab deruxtecan had an 11.1% probability of being cost-effective at a $100 000 per QALY willingness-to-pay threshold. CONCLUSIONS: Despite the higher efficacy of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 positive metastatic breast cancer, our findings raise concern regarding its value at current prices.

Trends in Telerehabilitation Utilization in the United States 2020-2021.

OBJECTIVE: To examine telerehabilitation utilization in the United States (US) during the first 2 years of the pandemic. DESIGN: We performed a retrospective analysis of outpatient insurance claims from the IBM MarketScan Commercial Claims and Encounters Database to identify the number and proportion of patients using telerehabilitation from 2020 to 2021. Telerehabilitation was identified based on the presence of specific code modifiers and place of service. SETTING: Retrospective claims analysis. PARTICIPANTS: Individuals living in the United States with employer-sponsored insurance plans using outpatient physical or occupational therapy (PT/OT) (N=2,007,524). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Number and proportion of outpatient PT/OT visits completed via telerehabilitation. RESULTS: We identified 21,026,608 PT/OT visits among 2,007,524 patients. Overall, 49,974 (2.5%) patients received ≥1 telerehabilitation visit during the specified timeframe. We observed trends in utilization over time, with utilization peaking in April 2020 when 10.9% of all PT/OT visits were conducted by telerehabilitation. We also observed geographic trends with lower rates of utilization identified in rural areas. State-by-state utilization rates ranged from 10.4% (California) to 0.3% (Wyoming). CONCLUSION: Telerehabilitation may be underutilized as a means of improving access to PT/OT, especially in rural areas of the country. Further research is needed to examine contributing factors to low observed utilization rates, such as provider and patient perceptions of telerehabilitation.

Surface boulder banding indicates Martian debris-covered glaciers formed over multiple glaciations.

Glacial landforms, including lobate debris aprons, are a global water ice reservoir on Mars preserving ice from past periods when high orbital obliquity permitted nonpolar ice accumulation. Numerous studies have noted morphological similarities between lobate debris aprons and terrestrial debris-covered glaciers, an interpretation supported by radar observations. On Earth and Mars, these landforms consist of a core of flowing ice covered by a rocky lag. Terrestrial debris-covered glaciers advance in response to climate forcing driven by obliquity-paced changes to ice mass balance. However, on Mars, it is not known whether glacial landforms emplaced over the past 300 to 800 formed during a single, long deposition event or during multiple glaciations. Here, we show that boulders atop 45 lobate debris aprons exhibit no evidence of monotonic comminution but are clustered into bands that become more numerous with increasing latitude, debris apron length, and pole-facing flow orientation. Boulder bands are prominent at glacier headwalls, consistent with debris accumulation during the current Martian interglacial. Terrestrial glacier boulder bands occur near flow discontinuities caused by obliquity-driven hiatuses in ice accumulation, forming internal debris layers. By analogy, we suggest that Martian lobate debris aprons experienced multiple cycles of ice deposition, followed by ice destabilization in the accumulation zone, leading to boulder-dominated lenses and subsequent ice deposition and continued flow. Correlation between latitude and boulder clustering suggests that ice mass-balance works across global scales on Mars. Lobate debris aprons may preserve ice spanning multiple glacial/interglacial cycles, extending Mars climate records back hundreds of millions of years.

Estimated Savings From Using Added Therapeutic Benefit and Therapeutic Reference Pricing in United States Medicare Drug Price Negotiations.

OBJECTIVES: US Medicare will begin negotiating prices for top-selling drugs in 2023. This study describes and estimates potential savings from a therapeutic reference pricing approach, linking comparative effectiveness with the costs of existing therapeutic alternatives, that Medicare could use to adjust the starting point for price negotiations. METHODS: First, we identified target drugs likely to be selected for Medicare negotiation. Second, we identified comparative effectiveness ratings for target drugs based on French Haute Autorité de Santé reports. For target drugs with minor or no added benefit, we identified therapeutic alternatives based on the French reports and US clinical guidelines. For each target drug with minor or no added benefit, we computed the difference between spending based on the drug's estimated statutory ceiling price and spending based on the weighted average cost of therapeutic alternatives or the lowest cost therapeutic alternative. Finally, we calculated potential annual savings from using a starting point in negotiations based on costs of therapeutic alternatives. RESULTS: Potential drug-level savings to Medicare from using a starting point in negotiations based on average spending across therapeutic alternatives, compared with using the statutory ceiling price alone, ranged from $186 541 340 to $2 173 441 197. Potential savings from using a starting point based on the lowest cost alternative ranged from $199 872 163 to $3 605 904 765. CONCLUSIONS: Although we do not expect Medicare to rely on French comparative effectiveness assessments, this study demonstrates the potential for additional savings when using comparative effectiveness and costs of therapeutic alternatives to inform the starting price for negotiations.

STAT3 Gain-of-Function Mutations Underlie Deficiency in Human Nonclassical CD16+ Monocytes and CD141+ Dendritic Cells.

Genetic analysis of human inborn errors of immunity has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. The STAT family of transcription factors orchestrate hematopoietic cell differentiation. Patients with de novo activating mutations of STAT3 present with multiorgan autoimmunity, lymphoproliferation, and recurrent infections. We conducted a detailed characterization of the blood monocyte and dendritic cell (DC) subsets in patients with gain-of-function (GOF) mutations across the gene. We found a selective deficiency in circulating nonclassical CD16+ and intermediate CD16+CD14+ monocytes and a significant increase in the percentage of classical CD14+ monocytes. This suggests a role for STAT3 in the transition of classical CD14+ monocytes into the CD16+ nonclassical subset. Developmentally, ex vivo-isolated STAT3GOF CD14+ monocytes fail to differentiate into CD1a+ monocyte-derived DCs. Moreover, patients with STAT3GOF mutations display reduced circulating CD34+ hematopoietic progenitors and frequency of myeloid DCs. Specifically, we observed a reduction in the CD141+ DC population, with no difference in the frequencies of CD1c+ and plasmacytoid DCs. CD34+ hematopoietic progenitor cells from patients were found to differentiate into CD1c+ DCs, but failed to differentiate into CD141+ DCs indicating an intrinsic role for STAT3 in this process. STAT3GOF-differentiated DCs produced lower amounts of CCL22 than healthy DCs, which could further explain some of the patient pathological phenotypes. Thus, our findings provide evidence that, in humans, STAT3 serves to regulate development and differentiation of nonclassical CD16+ monocytes and a subset of myeloid DCs.

Gastrointestinal bleeding in children with familial dysautonomia: a case-control study.

OBJECTIVE: Familial dysautonomia (FD) is a rare inherited autosomal recessive disorder with abnormal somatosensory, enteric, and afferent autonomic neurons. We aimed to define the incidence of gastrointestinal bleeding and its associated risk factors in patients with FD. METHODS: In this retrospective case-control study, we identified all episodes of gastrointestinal bleeding in patients with FD, occurring over four decades (January 1980-December 2017), using the New York University FD registry. RESULTS: We identified 104 episodes of gastrointestinal bleeding occurring in 60 patients with FD. The estimated incidence rate of gastrointestinal bleeds in the FD population rate was 4.20 episodes per 1000 person-years. We compared the 60 cases with 94 age-matched controls. Bleeding in the upper gastrointestinal tract from gastric and duodenal ulcers occurred most frequently (64 bleeds, 75.6%). Patients were more likely to have a gastrostomy (G)-tube and a Nissen fundoplication [odds ratio (OR) 3.73, 95% confidence interval (CI) 1.303-13.565] than controls. The mean time from G-tube placement to first gastrointestinal bleed was 7.01 years. The mean time from Nissen fundoplication to bleed was 7.01 years. Cases and controls had similar frequency of intake of nonsteroidal antiinflammatory drugs (NSAID) and selective serotonin reuptake inhibitors (SSRI). CONCLUSION: The incidence of gastrointestinal bleeding in the pediatric FD population was estimated to be 4.20 per 1000 person-years, 21 times higher than in the general pediatric population (0.2 per 1000 person-years). Patients with FD with a G-tube and a Nissen fundoplication had a higher risk of a subsequent gastrointestinal bleeding.

The cost burden of hospital-treated tap water scald burns in the United States.

OBJECTIVE: We aimed to determine the cost burden and epidemiology of hospital-treated, tap water scald burns in the United States to inform consideration of policy proposals to require thermostatic mixing valves with all new water heaters. METHODS: A retrospective, cross-sectional study was performed using the 2016-2018 National Inpatient Sample (NIS) and Nationwide Emergency Department Sample (NEDS) from the Healthcare Cost and Utilisation Project (HCUP). We queried the samples to examine the prevalence, cost, and epidemiology of hospital-treated, tap water scald burns. RESULTS: The NIS and NEDS identified 52 088 (weighted) emergency department (ED) visits, 7270 (weighted) hospitalisations and 110 hospital-based deaths attributable to tap water scald burns in 2016-2018. The average cost for each encounter was $572 per ED visit and $28 431 per hospitalisation. In aggregate, the direct healthcare cost of these initial encounters was $206.69 million for inpatient (IP) visits and $29.79 million for ED visits. Medicare paid $109.54 million of these costs and Medicaid paid $18.3 million. Multiple body surfaces were involved in 35.4% of IP visits and 16.1% of ED visits. CONCLUSIONS: NIS and NEDS are valuable tools to examine the cost burden and epidemiology of hospital-treated, tap water scald burns. The high injuries, deaths, and overall cost of these scald burns suggest policy proposals are needed to require the use of thermostatic mixing valves.The additional detail provided by using the International Classification of Diseases (ICD)-10 External Cause of Morbidity Code allows for a better understanding of the size and scope of tap water scald injuries than was possible with ICD-9.

The Role of Latina Peer Mentors in the Implementation of the Alma Program for Women With Perinatal Depression.

This study examines the role that compañeras (peer mentors) play in the implementation of a program, Alma, which was designed to support Latina mothers who are experiencing depression during pregnancy or early parenting and implemented in the rural mountain West of the United States. Drawing from the fields of dissemination and implementation and Latina mujerista (feminist) scholarship, this ethnographic analysis demonstrates how the Alma compañeras facilitate the delivery of Alma by creating and inhabiting intimate mujerista spaces with other mothers and create relationships of mutual and collective healing in the context of relationships de confianza (of trust and confidence). We argue that these Latina women, in their capacity as compañeras, draw upon their cultural funds of knowledge to bring Alma to life in ways that prioritizes flexibility and responsiveness to the community. Shedding light on contextualized processes by which Latina women facilitate the implementation of Alma illustrates how the task-sharing model is well suited to the delivery of mental health services for Latina immigrant mothers and how lay mental health providers can be agents of healing.

Statin Medications and Amyotrophic Lateral Sclerosis Incidence and Mortality.

Studies of statins and amyotrophic lateral sclerosis (ALS) incidence and survival have had conflicting findings possibly related to difficulties with confounding by indication. We considered potency of statins used and duration of use to explore confounding by indication. Within the Clalit Health Services in Israel, we identified 948 ALS case patients from 2004 through 2017 and matched them with 1,000 control subjects each. Any statin use up to 3 years before ALS onset was not associated with ALS incidence but was associated with a reduced hazard ratio (HR) for death. Odds of ALS did not vary by statin potency, but use of only lower-potency statins was associated with longer survival (HR = 0.82, 95% CI: 0.68, 0.98), whereas the association with higher-potency statins was null compared with those case patients who did not use statins. However, duration of statin use appeared to account for these findings. Those who used statins only up to 3 years had longer survival (HR = 0.77, 95% CI: 0.61, 0.96) than did case patients who did not use statins, but those who used statins for >3 years did not. Although other explanations are possible, these findings could suggest a protective effect of statins on ALS survival that is partially masked by a worse prognosis from underlying reasons for taking statins that deserves further exploration.

A longitudinal study of theory of mind and listening comprehension: Is preschool theory of mind important?

Theory of mind has been shown to be important for listening comprehension for children at a range of ages. However, there is a lack of longitudinal evidence for a relationship between early theory of mind and later listening comprehension. The aim of this study was to examine whether preschool theory of mind has a longitudinal direct effect on later listening comprehension over and above the effects of concurrent theory of mind. A total of 147 children were tested on measures of theory of mind, working memory, vocabulary, and grammatical knowledge at Time 1 (mean age = 4;1 [years;months]) and Time 2 (mean age = 5;11). In addition, at Time 2 listening comprehension, comprehension monitoring, and inference making measures were taken. Data were fitted to concurrent and longitudinal models of listening comprehension. Concurrent findings at Time 2 showed theory of mind to have a direct effect on listening comprehension. However, longitudinal findings showed that earlier theory of mind in preschool (Time 1) did not have a direct effect on listening comprehension 22 months later; instead, there was only an indirect effect of earlier theory of mind on later listening comprehension via concurrent theory of mind (Time 2). Taken together, the results give further support for the importance of theory of mind for listening comprehension but show that there are limited additional benefits of early theory of mind acquisition. Implications for the development of children's listening comprehension are discussed.

The Impact of the COVID-19 Pandemic on Elective Inpatient Surgical Admissions: Evidence From Maryland.

BACKGROUND: The COVID-19 pandemic led to large-scale cancellation and deferral of elective surgeries. We quantified volume declines, and subsequent recoveries, across all hospitals in Maryland. MATERIALS AND METHODS: Data on elective inpatient surgical volumes were assembled from the Maryland Health Service Cost Review Commission for years 2019-2020. The data covered all hospitals in the state. We compared the volume of elective inpatient surgeries in the second (Q2) and fourth quarters (Q4) of 2020 to those same quarters in 2019. Analysis was stratified by patient, hospital, and service characteristics. RESULTS: Surgical volumes were 55.8% lower in 2020 Q2 than in 2019 Q2. Differences were largest for orthopedic surgeries (74.3% decline), those on Medicare (61.4%), and in urban hospitals (57.3%). By 2020 Q4, volumes for most service lines were within 15% of volumes in 2019 Q4. Orthopedic surgery remained most affected (44.5% below levels in 2019 Q4) and Plastic Surgery (21.9% lower). CONCLUSIONS: COVID-19 led to large volume declines across hospitals in Maryland followed by a partial recovery. We observed large variability, particularly across service lines. These results can help contextualize case-specific experiences and inform research studying potential health effects of these delays and cancellations.

Branded Price Variation in the United States Drug Market, 2010 to 2019.

The transaction price for branded drugs in the United States often varies widely by the eventual payer, a fact that can complicate research and policy discussions surrounding drug pricing. We combine publicly-available data on branded drug prices from a host of sources-prices paid by Medicare (Parts B and D), the Veterans Affairs Administration (VA), those included in the Federal Supply Schedule (FSS), invoice prices paid by pharmacies described in National Average Drug Acquisition Costs (NADAC), list prices, and payments ultimately received by drug makers-to illustrate how prices vary across the U.S. market and how these relationships changed from 2010 to 2019. We document large variation across payers and find VA prices are generally the lowest, averaging nearly 50% below list prices during our study period, which is meaningfully lower than the average prices manufacturers ultimately receive. Some net prices, like those in Part D and average payments received by manufacturers, have diverged substantially from list prices in the last decade and are now much closer to the published VA and FSS prices. In part, this reflects unexpected net price increases among published VA and FSS prices that is worthy of future study.

Development and validation of a machine learning-based postpartum depression prediction model: A nationwide cohort study.

BACKGROUND: Currently, postpartum depression (PPD) screening is mainly based on self-report symptom-based assessment, with lack of an objective, integrative tool which identifies women at increased risk, before the emergent of PPD. We developed and validated a machine learning-based PPD prediction model utilizing electronic health record (EHR) data, and identified novel PPD predictors. METHODS: A nationwide longitudinal cohort that included 214,359 births between January 2008 and December 2015, divided into model training and validation sets, was constructed utilizing Israel largest health maintenance organization's EHR-database. PPD was defined as new diagnosis of a depressive episode or antidepressant prescription within the first year postpartum. A gradient-boosted decision tree algorithm was applied to EHR-derived sociodemographic, clinical, and obstetric features. RESULTS: Among the birth cohort, 1.9% (n = 4104) met the case definition of new-onset PPD. In the validation set, the prediction model achieved an area under the curve (AUC) of 0.712 (95% confidence interval, 0.690-0.733), with a sensitivity of 0.349 and a specificity of 0.905 at the 90th percentile risk threshold, identifying PPDs at a rate more than three times higher than the overall set (positive and negative predictive values were 0.074 and 0.985, respectively). The model's strongest predictors included both well-recognized (e.g., past depression) and less-recognized (differing patterns of blood tests) PPD risk factors. CONCLUSIONS: Machine learning-based models incorporating EHR-derived predictors, could augment symptom-based screening practice by identifying the high-risk population at greatest need for preventive intervention, before development of PPD.

Frequency and burden of gastrointestinal symptoms in familial dysautonomia.

PURPOSE: Familial dysautonomia (FD) is a rare hereditary sensory and autonomic neuropathy (HSAN-3) that is clinically characterized by impaired pain and temperature perception and abnormal autonomic function. Patients with FD have gastrointestinal dysmotility and report a range of gastrointestinal symptoms that have yet to be systematically evaluated. The aim of this study was to establish the frequency and severity of gastrointestinal symptoms in patients with FD. METHODS: The validated National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) survey questionnaire, together with additional FD-specific questions, were distributed to 202 living patients with genetically confirmed FD who had been identified from the New York University FD Patient Registry or, when relevant, to their respective caretaker. As a comparison group, we used a general US adult population for whom PROMIS scores were available (N = 71,812). RESULTS: Of the 202 questionnaires distributed, 77 (38%) were returned, of which 53% were completed by the patient. Median age of the respondents was 25 years, and 44% were male. Gastrostomy tube was the sole nutrition route for 25% of the patients, while 53% were reliant on the gastrostomy tube only for liquid intake. The prevalence of gastrointestinal symptoms was significantly higher in each of the eight domains of PROMIS in patients with FD than in the controls. Gastrointestinal symptoms as measured by raw scores on the PROMIS scale were significantly less severe in the FD patient group than in the control population in all domains with the exception of the abdominal pain domain. The surveys completed by caregivers reported the same burden of symptoms as those completed only by patients. CONCLUSION: Gastrointestinal symptoms affect nearly all patients with FD. Gastrointestinal symptoms are more prevalent in adult patients with FD than in the average US adult population but are less severe in the former.

United States trends in healthcare charges for pediatric firearm injuries.

BACKGROUND: From 2009 to 2016, >21,000 children died and an estimated 118,000 suffered non-fatal injuries from firearms in the United States. Limited data is available on resource utilization by injury intent. We use hospital charges as a proxy for resource use and sought to: 1) estimate mean charges for initial ED and inpatient care for acute firearm injuries among children in the U.S.; 2) compare differences in charges by firearm injury intent among children; and 3) evaluate trends in charges for pediatric firearm injuries over time, including within intent subgroups. METHODS: In this repeated cross-sectional analysis of the 2009-2016 Nationwide Emergency Department Sample, we identified firearm injury cases among children aged ≤19 years using ICD-9-CM and ICD-10-CM external cause of injury codes (e-codes). Injury intent was categorized using e-codes as unintentional, assault-related, self-inflicted, or undetermined. Linear regressions utilizing survey weighting were used to examine associations between injury intent and healthcare charges, and to evaluate trends in mean charges over time. RESULTS: Among 21,951 unweighted cases representing 102,072 pediatric firearm-related injuries, mean age was 16.6 years, and a majority were male (88.2%) and publicly insured (51.5%). Injuries were 53.9% assault-related, 37.7% unintentional, 1.8% self-inflicted, and 6.7% undetermined. Self-inflicted injuries had higher mean charges ($98,988) than assault-related ($52,496) and unintentional ($28,618) injuries (p < 0.001). Self-inflicted injuries remained associated with higher mean charges relative to unintentional injuries, after adjusting for patient demographics, hospital characteristics, and injury severity (p = 0.015). Mean charges for assault-related injuries also remained significantly higher than charges for unintentional injuries in multivariable models (p < 0.001). After adjusting for inflation, mean charges for pediatric firearm-related injuries increased over time (p-trend = 0.018) and were 23.1% higher in 2016 versus 2009. Mean charges increased over time among unintentional injuries (p-trend = 0.002), but not among cases with assault-related or self-inflicted injuries. CONCLUSIONS: Self-inflicted and assault-related firearm injuries are associated with higher mean healthcare charges than unintentional firearm injuries among children. Mean charges for pediatric firearm injuries have also increased over time. These findings can help guide prevention interventions aimed at reducing the substantial burden of firearm injuries among children.

Combined Effects of Carotenoids and Polyphenols in Balancing the Response of Skin Cells to UV Irradiation.

Oral carotenoids and polyphenols have been suggested to induce photo-protective effects. The aim of the study was to test whether the combination of carotenoids and polyphenols produce greater protective effects from UV-induced damage to skin cells. Such damage is characterized by inflammation and oxidative stress; thus, the photo-protective effect can be partially explained by modulating the nuclear factor kappa B (NFκB) and antioxidant response element/Nrf2 (ARE/Nrf2) transcription systems, known as important regulators of these two processes. Indeed, it was found in keratinocytes that carotenoids and polyphenols inhibit UVB-induced NFκB activity and release of cytokine IL-6. A combination of tomato extract with rosemary extract inhibited UVB-induced release of IL-6 more than each of the compounds alone. Moreover, this combination synergistically activated ARE/Nrf2 transcription systems. Inflammatory cytokines such as IL-6 and TNFα induce the expression of matrix metalloproteinases (MMPs), which leads to collagen breakdown; thus, it is important to note that carnosic acid reduced TNFα-induced MMP-1 secretion from human dermal fibroblasts. The in vitro results suggest beneficial effects of phytonutrient combinations on skin health. To assure that clinical experiments to prove such effects in humans are feasible, the human bioavailability of carotenoids from tomato extract was tested, and nearly a twofold increase in their plasma concentrations was detected. This study demonstrates that carotenoids and polyphenols cooperate in balancing UV-induced skin cell damage, and suggests that NFκB and ARE/Nrf2 are involved in these effects.

Decision-making about motherhood among women living with HIV in Canada: a negotiation of multidimensional risks.

Little research in Canada has examined the perspectives of women living with HIV on decision-making across the stages of motherhood. In 2004-2005, semi-structured interviews were conducted with 42 African, Caucasian and Haitian HIV-positive women recruited in Montreal. All were or wished to be biological mothers. Transcripts underwent thematic analysis organised by three culturally informed models of motherhood described by the participants, which influenced decision-making and perceived risks. For women who saw motherhood as 'self-fulfilment and completeness', vertical HIV transmission was a primary concern. It threatened their identity as a 'good mother', which also meant adhering to antiretrovirals. For women who viewed motherhood as a 'social realisation' (all African or Haitian), fears of compromised fertility dominated. Not becoming pregnant threatened their social status and presumed health within their community. Antiretrovirals were abandoned after delivery, fearing they would reveal their HIV status. For women endorsing a 'personal growth' model of motherhood (all Caucasian), threats to personal health were paramount. Pregnancy meant purifying body and soul. Antiretrovirals, seen as pollutants, were stopped after delivery. These findings can inform current research and sensitise health providers to the complex biological, psychological, social and spiritual risks that HIV-positive women negotiate in motherhood-related decision-making, towards more patient-centred care.

A parent-of-origin analysis of paternal genetic variants and increased risk of conotruncal heart defects.

The association between conotruncal heart defects (CTHDs) and maternal genetic and environmental exposures is well studied. However, little is known about paternal genetic or environmental exposures and risk of CTHDs. We assessed the effect of paternal genetic variants in the folate, homocysteine, and transsulfuration pathways on risk of CTHDs in offspring. We utilized National Birth Defects Prevention Study data to conduct a family-based case only study using 616 live-born infants with CTHDs, born October 1997-August 2008. Maternal, paternal and infant DNA was genotyped using an Illumina® Golden Gate custom single nucleotide polymorphism (SNP) panel. Relative risks (RR) and 95% confidence intervals (CI) from log-linear models determined parent of origin effects for 921 SNPs in 60 candidate genes involved in the folate, homocysteine, and transsulfuration pathways on risk of CTHDs. The risk of CTHD among children who inherited a paternally derived copy of the A allele on GLRX (rs17085159) or the T allele of GLRX (rs12109442) was 0.23 (95%CI: 0.12, 0.42; p = 1.09 × 10-6 ) and 0.27 (95%CI: 0.14, 0.50; p = 2.06 × 10-5 ) times the risk among children who inherited a maternal copy of the same allele. The paternally inherited copy of the GSR (rs7818511) A allele had a 0.31 (95%CI: 0.18, 0.53; p = 9.94 × 10-6 ] risk of CTHD compared to children with the maternal copy of the same allele. The risk of CTHD is less influenced by variants in paternal genes involved in the folate, homocysteine, or transsulfuration pathways than variants in maternal genes in those pathways.

A Transparent and Consistent Approach to Assess US Outpatient Drug Costs for Use in Cost-Effectiveness Analyses.

BACKGROUND: Assessment of drug costs for cost-effectiveness analyses (CEAs) in the United States is not straightforward because the prices paid for drugs are not publicly available and differ between payers. CEAs have relied on list prices that do not reflect the rebates and discounts known to be associated with these purchases. OBJECTIVES: To review available cost measures and propose a novel strategy that is transparent, consistent, and applicable to all CEAs taking a US health care sector perspective or a societal payer's perspective. METHODS: We propose using the National Average Drug Acquisition Cost (NADAC), the Veterans Affairs Federal Supply Schedule (VAFSS), and their midpoint as the upper bound, lower bound, and base case, respectively, to estimate net drug prices for various payers. We compare this approach with wholesale acquisition cost (WAC), the most common measure observed in our literature review. The minimum WAC is used to provide the most conservative comparison. RESULTS: Our sample consists of 1436 brand drugs and 1599 generic drugs. On average, the upper bound (NADAC) is 1% and 9.8% lower than the WAC for brand and generic drugs respectively, whereas the lower bound (VAFSS) is 48.3% and 54.2% lower than the WAC. The NADAC is less than the WAC in 89.6% of drug groups. The distributions of these relationships do not show a clear mode and have wide variation. CONCLUSIONS: Our study suggests that the WAC may be an overestimate for the base case because the minimum WAC is higher than the NADAC for most drugs. Our approach balances uncertainty and lack of data for the cost of pharmaceuticals with the need for a transparent and consistent approach for valid CEAs.

The University-Public Health Partnership for Public Health Research Training in Quebec, Canada.

Enhancing effective preventive interventions to address contemporary public health problems requires improved capacity for applied public health research. A particular need has been recognized for capacity development in population health intervention research to address the complex multidisciplinary challenges of developing, implementing, and evaluating public health practices, intervention programs, and policies. Research training programs need to adapt to these new realities. We have presented an example of a 2003 to 2015 training program in transdisciplinary research on public health interventions that embedded doctoral and postdoctoral trainees in public health organizations in Quebec, Canada. This university-public health partnership for research training is an example of how to link science and practice to meet emerging needs in public health.