"The Facts in the Case of M. Valdemar": Undead Bodies and Medical Technology.

This paper examines the relationship between medical technology and liminal states of "undeath" as presented in "The Facts in the Case of M. Valdemar" and the real-life case of Jahi McMath, who was maintained on life support for over four years following a diagnosis of brain death. Through this juxtaposition, "Valdemar" comes to function as a modern fable, an uneasy herald of medical technology's potential to create liminal states between life and death. The ability to transgress these boundaries bears a cost, however: both Valdemar and Jahi McMath lose the autonomy to direct their respective narratives. Yet, their utterances "from beyond the grave" highlight the precarious nature of their position and the ethical concerns therein. Poe's literary performance of "undeath" therefore serves to caution real-life cases in which life support is used to sustain an individual reported to be brain-dead. Such application of life-sustaining technology complicates the fundamental binary of life/death, allowing its subjects to resist textual closure. Even as Poe's work represents an imaginative interrogation of the scientific enterprise, this nineteenth-century story holds a mirror to contemporary medical practice, inviting a reconsideration of the ethics, language, and power relations surrounding the fraught relationship between death and medical technology.

Biparental Inheritance of Mitochondrial DNA in Humans.

Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is generally believed that mitochondria and mtDNA are exclusively maternally inherited in humans. Here, we identified three unrelated multigeneration families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a total of 17 individuals. Heteroplasmy of mtDNA was independently examined by high-depth whole mtDNA sequencing analysis in our research laboratory and in two Clinical Laboratory Improvement Amendments and College of American Pathologists-accredited laboratories using multiple approaches. A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring. Elucidating the molecular mechanism for this unusual mode of inheritance will provide new insights into how mtDNA is passed on from parent to offspring and may even lead to the development of new avenues for the therapeutic treatment for pathogenic mtDNA transmission.

Genotype-Directed Dosing Leads to Optimized Voriconazole Levels in Pediatric Patients Receiving Hematopoietic Stem Cell Transplantation.

Invasive fungal infections are a significant cause of morbidity and mortality in recipients of hematopoietic stem cell transplantation (HSCT), warranting antifungal prophylaxis as a standard of care in these patients. Voriconazole is commonly used in this setting because of its broad-spectrum activity and available dosage forms. There is wide well-known inter- and intrapatient variability in voriconazole concentrations, in part because concentrations are affected by common CYP2C19 polymorphisms. In 2 successive studies we have optimized voriconazole dosing to achieve target voriconazole serum concentrations using a genotype-specific dosing algorithm for antifungal prophylaxis in the post-HSCT period. In our pilot study all patients undergoing HSCT who received voriconazole antifungal prophylaxis were prospectively followed. Voriconazole concentrations were monitored weekly and doses adjusted until concentrations reached between 1 and 5.5 µg/L. The most common CYP2C19 polymorphisms were determined and correlated with voriconazole dose and time required to reach the target concentration range. In the subsequent study patients receiving voriconazole prophylaxis were dosed based on their CYP2C19 genotype and followed prospectively. In the pilot study 25 patients received voriconazole as antifungal prophylaxis for a median of 49 days (range, 15 to 196 days). The median time to reach the target concentration was 34 days for extensive metabolizers and 11 days for poor metabolizers. Three patients were genotyped as intermediate metabolizers; they reached the target concentration in a median of 56 days. Similarly, 2 patients who were genotyped as ultrarapid metabolizers reached the target range in 18 and 25 days. The time and dose required to reach the adequate concentration showed a trend toward correlation with individual CYP2C19 genotype, although voriconazole concentrations showed large interpatient variability in wild-type patients (extensive metabolizers). In our follow-up study, 20 patients received voriconazole prophylaxis prospectively dosed based on their CYP2C19 genotype. The median times to reach the target concentration using genotype-guided dosing were 9, 6.5, and 4 days for ultrarapid, extensive, and intermediate metabolizers, respectively. Overall, the median time to reach the target concentration with genotype-guided dosing was 6.5 days compared with a median time of 29 days when all patients were started on the same dose regardless of CYP2C19 genotype (P < .001). Our data show that traditional voriconazole dosing does not lead to timely achievement of target levels for fungal prophylaxis. However, a genotype-directed dosing algorithm allows patients to reach the voriconazole target range significantly sooner, providing better prophylaxis against fungal infections in the immediate post-transplant period.

Initiatives to Enhance Primary Care Delivery: Two Examples from the Field.

OBJECTIVES: Increasing demands on primary care providers have created a need for systems-level initiatives to improve primary care delivery. The purpose of this paper is to describe and present outcomes for two such initiatives: the Pennsylvania Academy of Family Physicians' Residency Program Collaborative (RPC) and the St. Johnsbury Vermont Community Health Team (CHT). METHODS: Researchers conducted case studies of the initiatives using mixed methods, including: secondary analysis of program and electronic health record data, systematic document review and interviews. RESULTS: RPC is a learning collaborative that teaches quality improvement and patient-centeredness to primary care providers, residents, clinical support staff, and administrative staff in residency programs. Results show that participation in a higher number of live learning sessions resulted in a significant increase in patient centered medical home recognition attainment and significant improvements in performance in diabetic process measures including eye exams (14.3%, p=0.004), eye referrals (13.82%, p=0.013), foot exams (15.73%, p=0.003), smoking cessation (15.83%, p=0.012), and self-management goals (25.45%, p=0.001). As a community-clinical linkages model, CHT involves primary care practices, community health workers (CHWs), and community partners. Results suggest that CHT members successfully work together to coordinate comprehensive care for the individuals they serve. Further, individuals exposed to CHWs experienced increased stability in access to health insurance (p=0.001) and prescription drugs (p=0.000), and the need for health education counseling (p=0.000). CONCLUSION: Findings from this study indicate that these two system-level strategies have the promise to improve primary care delivery. Additional research can determine the extent to which these strategies can improve other health outcomes.

Training and technical assistance for compliance with beverage and physical activity components of New York City's regulations for early child care centers.

INTRODUCTION: In 2006, the New York City Department of Health and Mental Hygiene (DOHMH) passed regulations for child care centers that established standards for beverages provided to children and set a minimum amount of time for daily physical activity. DOHMH offered several types of training and technical assistance to support compliance with the regulations. This article analyzes the association between training and technical assistance provided and compliance with the regulations in a sample of 174 group child care centers. METHODS: Compliance was measured by using a site inventory of beverages stored on premises and a survey of centers' teachers regarding the amount of physical activity provided. Training and technical assistance measures were based on the DOHMH records of training and technical assistance provided to the centers in the sample and on a survey of center directors. Ordinal logistic regression was used to assess the association between training and technical assistance measures and compliance with the regulations. RESULTS: Measures of training related to physical activity the center received: the number of staff members who participated in Sport, Play and Active Recreation for Kids (SPARK) and other training programs in which a center participated were associated with better compliance with the physical activity regulations. Neither training nor technical assistance were associated with compliance with the regulations related to beverages. CONCLUSION: Increased compliance with regulations pertaining to physical activity was not related to compliance with beverage regulations. Future trainings should be targeted to the specific regulation requirements to increase compliance.

Compliance with New York City's beverage regulations and beverage consumption among children in early child care centers.

INTRODUCTION: This article examines the association between the New York City regulations on beverages served in child care centers and beverage consumption among enrolled children. The regulations include requirements related to beverages served to children throughout the day. METHODS: Beverage consumption data were collected on 636 children enrolled in 106 group child care centers in New York City. Data on compliance with the regulations were collected through direct observation, interviews with center staff, and a site inventory. Logistic regression for rare events was used to test associations between compliance with the regulations and beverage consumption. RESULTS: Compliance with the regulations was associated with lower odds of children consuming milk with more than 1% fat content and sugar-sweetened beverages during meals and snacks. There was not a significant relationship between compliance with the regulations and children's consumption of water. CONCLUSION: The findings suggest a strong, direct relationship between what a center serves and what a child consumes, particularly regarding consumption of higher-fat milk and sugar-sweetened beverages. Therefore, policies governing the types of beverages served in child care centers may increase children's consumption of more healthful beverages and reduce the consumption of less healthful ones.

Evaluation design of New York City's regulations on nutrition, physical activity, and screen time in early child care centers.

This article describes the multi-method cross-sectional design used to evaluate New York City Department of Health and Mental Hygiene's regulations of nutrition, physical activity, and screen time for children aged 3 years or older in licensed group child care centers. The Center Evaluation Component collected data from a stratified random sample of 176 licensed group child care centers in New York City. Compliance with the regulations was measured through a review of center records, a facility inventory, and interviews of center directors, lead teachers, and food service staff. The Classroom Evaluation Component included an observational and biometric study of a sample of approximately 1,400 children aged 3 or 4 years attending 110 child care centers and was designed to complement the center component at the classroom and child level. The study methodology detailed in this paper may aid researchers in designing policy evaluation studies that can inform other jurisdictions considering similar policies.

Measurement of compliance with New York City's regulations on beverages, physical activity, and screen time in early child care centers.

INTRODUCTION: Policy interventions designed to change the nutrition environment and increase physical activity in child care centers are becoming more common, but an understanding of the implementation of these interventions is yet to be developed. The objective of this study was to explore the extent and consistency of compliance with a policy intervention designed to promote nutrition and physical activity among licensed child care centers in New York City. METHODS: We used a multimethod cross-sectional approach and 2 independent components of data collection (Center Evaluation Component and Classroom Evaluation Component). The methods were designed to evaluate the impact of regulations on beverages served, physical activity, and screen time at child care centers. We calculated compliance scores for each evaluation component and each regulation and percentage agreement between compliance in the center and classroom components. RESULTS: Compliance with certain requirements of the beverage regulations was high and fairly consistent between components, whereas compliance with the physical activity regulation varied according to the data collection component. Compliance with the regulation on amount and content of screen time was high and consistent. CONCLUSION: Compliance with the physical activity regulation may be a more fluid, day-to-day issue, whereas compliance with the regulations on beverages and television viewing may be easier to control at the center level. Multiple indicators over multiple time points may provide a more complete picture of compliance - especially in the assessment of compliance with physical activity policies.