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BACKGROUND: Female surgeons face increased rates of fertility challenges compared to the general population. We aim to understand surgical trainees' understanding and perspectives on family planning. METHODS: A 35-question survey was emailed to program directors at all US surgical residency programs for distribution to residents. Descriptive analyses were performed to evaluate resident understanding and perspectives on family planning and fertility treatments. RESULTS: A total of 121 residents responded to the survey. Most were female (n â= â78; 65 â%). Responders indicated the need to postpone pregnancy during training (female: n â= â48, 64 â% vs male n â= â18, 45 â%; p â= â0.09). Potential negative career consequences (n â= â50; 42 â%), limited leave benefits (n â= â47; 39 â%), and lack of childcare (n â= â45; 38 â%) were primary reasons for postponing pregnancy. Only nine responders (8 â%) received fertility-preservation education. CONCLUSION: Surgical trainees delay pregnancy for career and social support concerns and are interested in reproductive preservation. Fertility education could provide needed support for trainees.
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Ex-situ machine perfusion of the liver has surmounted traditional limitations associated with static cold storage in the context of organ preservation. This innovative technology has changed the landscape of liver transplantation by mitigating ischemia perfusion injury, offering a platform for continuous assessment of organ quality, and providing an avenue for optimizing use of traditionally marginal allografts. This review summarizes the contemporary clinical applications of machine perfusion devices, and discusses potential future strategies for real-time viability assessment, therapeutic interventions, and modulation of organ function after recovery.
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To determine if decreasing lifetime use of methamphetamines, cocaine, ecstasy, and inhalants among high school students occurring from 2009 to 2019 in the U.S. also occurred in five southeastern states, Youth Risk Behavior Survey data representative of high school students in grades 9-12 in 2009 and 2019 were analyzed. In a classroom setting, lifetime use of methamphetamines, cocaine, ecstasy, and inhalants were self-reported. Students nationwide (n = 30,087) were compared to students in Alabama, Georgia, Louisiana, Mississippi, and South Carolina (n = 18,237). Lifetime methamphetamine use significantly increased from 4.8% in 2009 to 6.2% in 2019 in the southeast but decreased from 4.1 to 2.2% nationwide. Use of cocaine, ecstasy, and inhalants remained stable in the southeast while decreasing significantly nationwide from 2009 to 2019. During a period when use of methamphetamines, cocaine, ecstasy, and inhalants among high school students in the U.S. decreased, use in southeastern states did not change. Culturally specific programs and interventions may be needed to prevent illicit drug use in communities of southeastern states where youth remain at risk.
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Smoldering multiple myeloma (SMM) is a precursor stage that precedes multiple myeloma (MM). SMM is heterogenous with nearly 40% of patients progressing to MM in the first 5 years. The high rate of progression of SMM patients highlights the need for early intervention, which underscores the importance of identifying SMM patients with the highest risk of progression. Several risk stratification models showed utility in identifying high-risk SMM patients; however, these systems showed limited sensitivity. To date, identifying high-risk SMM patients remains an important clinical need. In this study, we present the 3-dimensional telomere profiling as a structural biomarker capable of stratifying SMM patients as a function of genomic instability. Quantifying telomere dysfunction using the TeloView technology showed utility in risk stratification of cancer patients, particularly hematological malignancies. In this study, we analyzed 168 SMM patients. We report an AUC in ROC analysis of 0.8 using a subset of the patients as a training dataset. We then conducted a blind validation on a different cohort and demonstrated a positive predictive value of 85% and negative predictive value of 73%, with sensitivity and specificity of 83% and 76%, respectively. We examined the correlation between the TeloView prediction and the 20-2-20 scoring system, and cytogenetic abnormalities. We report a correlation of 53% with the 20-2-20 scores and over 60% correlation with cytogenetic abnormalities. The result of this study presents the telomere profiling as an effective biomarker able to stratify SMM patients to their respective risk groups with high sensitivity and specificity.
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Progresión de la Enfermedad , Mieloma Múltiple Quiescente , Telómero , Humanos , Mieloma Múltiple Quiescente/genética , Mieloma Múltiple Quiescente/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Mieloma Múltiple/genética , Mieloma Múltiple/diagnóstico , Valor Predictivo de las PruebasRESUMEN
Alzheimer's disease (AD) is an age-related neurodegenerative disease that is characterized by memory loss and multiple cognitive impairments. AD is pathologically characterized by age-dependent accumulation of amyloid-ß protein and the phosphorylation of tau protein in the brains of patients with AD. Clinically, manifestations of AD include cognitive decline, dementia, alterations of high-order brain functions, and movement disorders. Double-stranded DNA breaks are a lethal form of DNA damage and are typically repaired via non-homologous end joining and homologous recombination. However, in AD brain, repair mechanism is disrupted, leading to a cascade of events, cognitive dysfunction, organ failure and reduced lifespan. Increased circulating cell-free DNA in the blood, cerebrospinal fluid, and urine in patients with AD, can be used as early detectable biomarkers for AD. The purpose of our article is to explore the potential uses of cell-free DNA and double-stranded DNA breaks as prognostic markers for AD and examine the recent research on the application of these markers in studies.
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Importance: The primary care workforce shortage is significant and persistent, with organizational and policy leaders urgently seeking interventions to enhance retention and recruitment. Time constraints are a valuable focus for action; however, designing effective interventions requires deeper understanding of how time constraints shape employees' experiences and outcomes of work. Objective: To examine how time constraints affect primary care physicians' work experiences and careers. Design, Setting, and Participants: Between May 1, 2021, and September 31, 2022, US-based primary care physicians who trained in family or internal medicine were interviewed. Using qualitative analysis of in-depth interviews, this study examined how participants experience and adapt to time constraints during a typical clinic day, taking account of their professional and personal responsibilities. It also incorporates physicians' reflections on implications for their careers. Main Outcomes and Measures: Thematic analysis of in-depth interviews and a measure of well-being (American Medical Association Mini-Z survey). Results: Interviews with 25 primary care physicians (14 [56%] female and 11 [44%] male; median [range] age, 43 [34-63] years) practicing in 11 US states were analyzed. Two physicians owned their own practice, whereas the rest worked as employees. The participants represented a wide range of years in practice (range, 1 to ≥21), with 11 participants (44%) in their first 5 years. Physicians described that the structure of their work hours did not match the work that was expected of them. This structural mismatch between time allocation and work expectations created a constant experience of time scarcity. Physicians described having to make tradeoffs between maintaining high-quality patient care and having their work overflow into their personal lives. These experiences led to feelings of guilt, disillusionment, and dissatisfaction. To attempt to sustain long-term careers in primary care, many sought ways to see fewer patients. Conclusions and Relevance: These findings suggest that organizational leaders must align schedules with work expectations for primary care physicians to mitigate physicians' withdrawal from work as a coping mechanism. Specific strategies are needed to achieve this realignment, including incorporating more slack into schedules and establishing realistic work expectations for physicians.
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Satisfacción en el Trabajo , Médicos de Atención Primaria , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adaptación Psicológica , Actitud del Personal de Salud , Médicos de Atención Primaria/psicología , Investigación Cualitativa , Presión del Tiempo , Estados UnidosRESUMEN
INTRODUCTION: The advent of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) have transformed the management of immune-mediated rheumatic diseases, including spondylarthritis (SpA). However, the data about combining b/ts DMARDs in the treatment of SpA are scarce. The study objectives were to assess the efficacy and safety of combination b/tsDMARD in SpA. METHODS: We conducted systematic literature review (PubMed and Medline) with two independent reviewers, one adjudicator, exploring the efficacy and safety of combination b/tsDMARDs in the treatment of SpA. Inclusion criteria were studies published in last 20 years, English language, interventions included use of two b/tsDMARDs, and minimal three-month follow-up. RESULTS: Out of 1936 initial hits, 28 manuscripts fulfilled the inclusion criteria. Two were randomized controlled trials, and the remaining were retrospective cohort studies or case series. Combination of apremilast with bDMARD, or TNF inhibitor plus IL12/23 inhibitor were the commonest and reported good efficacy with no increased safety signal. CONCLUSIONS: There is not enough data to fully evaluate efficacy and safety of combination b/tsDMARDs in SpA treatment. Limited information shows apremilast plus bDMARD, or TNF inhibitor plus IL12/23 inhibitor combination to be efficacious and safe. Randomized controlled trials and larger cohort with a longer follow-up are required.
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Antirreumáticos , Productos Biológicos , Quimioterapia Combinada , Espondiloartritis , Humanos , Antirreumáticos/uso terapéutico , Productos Biológicos/uso terapéutico , Espondiloartritis/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Talidomida/análogos & derivados , Talidomida/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: There is growing, widespread recognition that expectations of US primary care vastly exceed the time and resources allocated to it. Little research has directly examined how time scarcity contributes to harm or patient safety incidents not readily capturable by population-based quality metrics. OBJECTIVE: To examine near-miss events identified by primary care physicians in which taking additional time improved patient care or prevented harm. DESIGN: Qualitative study based on semi-structured interviews. PARTICIPANTS: Twenty-five primary care physicians practicing in the USA. APPROACH: Participants completed a survey that included demographic questions, the Ballard Organizational Temporality Scale and the Mini-Z scale, followed by a one hour qualitative interview over video-conference (Zoom). Iterative thematic qualitative data analysis was conducted. KEY RESULTS: Primary care physicians identified several types of near-miss events in which taking extra time during visits changed their clinical management. These were evident in five types of patient care episodes: high-risk social situations, high-risk medication regimens requiring patient education, high acuity conditions requiring immediate workup or treatment, interactions of physical and mental health, and investigating more subtle clinical suspicions. These near-miss events highlight the ways in which unreasonably large patient panels and packed schedules impede adequate responses to patient care episodes that are time sensitive and intensive or require flexibility. CONCLUSIONS: Primary care physicians identify and address patient safety issues and high-risk situations by spending more time than allotted for a given patient encounter. Current quality metrics do not account for this critical aspect of primary care work. Current healthcare policy and organization create time scarcity. Interventions to address time scarcity and to measure its prevalence and implications for care quality and safety are urgently needed.
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Seguridad del Paciente , Atención Primaria de Salud , Humanos , Seguridad del Paciente/normas , Atención Primaria de Salud/normas , Femenino , Masculino , Persona de Mediana Edad , Adulto , Médicos de Atención Primaria , Calidad de la Atención de Salud/normas , Investigación Cualitativa , Factores de TiempoRESUMEN
Genome editing technologies have the potential to transform our understanding of how genetic variation gives rise to complex traits through the systematic engineering and phenotypic characterization of genetic variants. However, there has yet to be a system with sufficient efficiency, fidelity, and throughput to comprehensively identify causal variants at the genome scale. Here we explored the ability of templated CRISPR editing systems to install natural variants genome-wide in budding yeast. We optimized several approaches to enhance homology-directed repair (HDR) with donor DNA templates, including donor recruitment to target sites, single-stranded donor production by bacterial retrons, and in vivo plasmid assembly. We uncovered unique advantages of each system that we integrated into a single superior system named MAGESTIC 3.0. We used MAGESTIC 3.0 to dissect causal variants residing in 112 quantitative trait loci across 32 environmental conditions, revealing an enrichment for missense variants and loci with multiple causal variants. MAGESTIC 3.0 will facilitate the functional analysis of the genome at single-nucleotide resolution and provides a roadmap for improving template-based genome editing systems in other organisms.
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Tuberculosis (TB), a respiratory disease caused by Mycobacterium tuberculosis (Mtb), is a significant cause of mortality worldwide. The lung, a breeding ground for Mtb, was once thought to be a sterile environment, but has now been found to host its own profile of microbes. These microbes are critical in the development of the host immune system and can produce metabolites that aid in host defense against various pathogens. Mtb infection as well as antibiotics can shift the microbial profile, causing dysbiosis and dampening the host immune response. Additionally, increasing cases of drug resistant TB have impacted the success rates of the traditional therapies of isoniazid, rifampin, pyrazinamide, and ethambutol. Recent years have produced tremendous research into the human microbiome and its role in contributing to or attenuating disease processes. Potential treatments aimed at altering the gut-lung bacterial axis may offer promising results against drug resistant TB and help mitigate the effects of TB.
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Importance: Concerns have been raised that frequent consumption of 100% fruit juice may promote weight gain. Current evidence on fruit juice and weight gain has yielded mixed findings from both observational studies and clinical trials. Objective: To synthesize the available evidence on 100% fruit juice consumption and body weight in children and adults. Data Sources: MEDLINE, Embase, and Cochrane databases were searched through May 18, 2023. Study Selection: Prospective cohort studies of at least 6 months and randomized clinical trials (RCTs) of at least 2 weeks assessing the association of 100% fruit juice with body weight change in children and adults were included. In the trials, fruit juices were compared with noncaloric controls. Data Extraction and Synthesis: Data were pooled using random-effects models and presented as ß coefficients with 95% CIs for cohort studies and mean differences (MDs) with 95% CIs for RCTs. Main Outcomes and Measures: Change in body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was assessed in children and change in body weight in adults. Results: A total of 42 eligible studies were included in this analysis, including 17 among children (17 cohorts; 0 RCTs; 45â¯851 children; median [IQR] age, 8 [1-15] years) and 25 among adults (6 cohorts; 19 RCTs; 268â¯095 adults; median [IQR] age among cohort studies, 48 [41-61] years; median [IQR] age among RCTs, 42 [25-59]). Among cohort studies in children, each additional serving per day of 100% fruit juice was associated with a 0.03 (95% CI, 0.01-0.05) higher BMI change. Among cohort studies in adults, studies that did not adjust for energy showed greater body weight gain (0.21 kg; 95% CI, 0.15-0.27 kg) than studies that did adjust for energy intake (-0.08 kg; 95% CI, -0.11 to -0.05 kg; P for meta-regression <.001). RCTs in adults found no significant association of assignment to 100% fruit juice with body weight but the CI was wide (MD, -0.53 kg; 95% CI, -1.55 to 0.48 kg). Conclusion and Relevance: Based on the available evidence from prospective cohort studies, in this systematic review and meta-analysis, 1 serving per day of 100% fruit juice was associated with BMI gain among children. Findings in adults found a significant association among studies unadjusted for total energy, suggesting potential mediation by calories. Further trials of 100% fruit juice and body weight are desirable. Our findings support guidance to limit consumption of fruit juice to prevent intake of excess calories and weight gain.
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Jugos de Frutas y Vegetales , Aumento de Peso , Adolescente , Adulto , Niño , Preescolar , Humanos , Lactante , Persona de Mediana Edad , Índice de Masa Corporal , Peso Corporal , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Isatuximab is a CD38-directed antibody indicated for the treatment of relapsed or refractory multiple myeloma. The Division of Pharmacovigilance at the U.S. Food and Drug Administration (FDA) reviewed case reports from postmarketing sources, including the FDA Adverse Event Reporting System (FAERS), PubMed, and Embase, to investigate a potential association between isatuximab and the risk of varicella zoster virus (VZV) reactivation. We identified 20 reports of which 15 met our case definition and causality criteria. All 15 patients (80% male, median age = 60 years) received isatuximab for a hematologic neoplasm; eight (53%) for previously untreated multiple myeloma. All cases described additional risk factors for VZV reactivation, including concomitant proteasome inhibitor and/or immunomodulatory drug (n = 10, 67%) use. Based on this postmarket analysis, the U.S. Prescribing Information for isatuximab was updated to include this new safety information, including recommendations for antiviral prophylaxis.
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Herpes Zóster , Mieloma Múltiple , Humanos , Masculino , Persona de Mediana Edad , Femenino , Herpesvirus Humano 3 , Mieloma Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Herpes Zóster/inducido químicamente , Herpes Zóster/tratamiento farmacológicoAsunto(s)
Carcinoma de Células de Merkel , Neoplasias de los Párpados , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/diagnóstico , Carcinoma de Células de Merkel/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias de los Párpados/tratamiento farmacológico , Neoplasias de los Párpados/patología , Párpados/patologíaRESUMEN
BACKGROUND: In the United States, more than 19 million people of reproductive age need access to publicly funded hormonal contraception or live in areas where it is not readily available. These include rural areas of the country, commonly known as contraception deserts. Pharmacist prescribing has been proposed to increase access, but little is known about its implementation in such areas. OBJECTIVE: This study quantified the extent of pharmacists' furnishing (prescribing) of hormonal contraception in California's Central Valley community pharmacies and identified barriers and facilitators to implementation. METHODS: The researchers conducted a cross-sectional, mixed methods, observational study by (1) contacting all community pharmacies in the 11 counties of the Central Valley to determine furnishing rates and (2) surveying and interviewing pharmacies that indicated they furnished hormonal contraception. RESULTS: Overall, 13% of pharmacies within the Central Valley reported that they furnished hormonal contraception. Pharmacists reported that barriers to furnishing included costs to patients and the pharmacy, lack of time and staff, lack of training and certifications, limited patient awareness of pharmacists' ability to furnish, pharmacists' limited confidence in furnishing, and patient use of emergency contraception as an alternative to hormonal contraception. Pharmacists reported that patients often sought hormonal contraception from pharmacists owing to ease of accessibility to a pharmacist; some other facilitators included advertising, confidentiality, low cost to patients, and referrals from other providers. CONCLUSIONS: Common barriers were identified across pharmacies that furnished hormonal contraception, indicating the need for strategies that reduce these barriers to help expand patient's access to these services and to increase pharmacists' ability and confidence to prescribe.
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Anticoncepción Hormonal , Farmacéuticos , Humanos , Estados Unidos , Estudios Transversales , Prescripciones de Medicamentos , Accesibilidad a los Servicios de Salud , Anticoncepción , CaliforniaRESUMEN
Classically, pre-eclampsia and eclampsia are considered hypertensive disorders of pregnancy, and current diagnostic criteria include hypertension with proteinuria or other laboratory abnormalities or symptoms suggestive of end-organ damage. However, atypical presentations can occur in the absence of elevated blood pressures. We present the case of a pregnant patient who developed status epilepticus at 24 weeks and 4 days of gestation, followed by altered mental status and severely elevated transaminases. She had no elevated blood pressures during her prenatal care or hospital course. Following delivery, she experienced normalization of transaminase levels and a return to her baseline mental status. Pre-eclampsia and eclampsia can occur in the absence of elevated blood pressures, which highlights the limitations of using standard diagnostic criteria in normotensive patients with end-organ damage. In such cases, it is important to include pre-eclampsia and eclampsia in the differential diagnosis, as the diagnosis usually warrants preterm delivery to minimize maternal morbidity and mortality.
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Eclampsia , Hipertensión , Preeclampsia , Embarazo , Femenino , Recién Nacido , Humanos , Eclampsia/diagnóstico , Preeclampsia/diagnóstico , Presión Sanguínea , TransaminasasRESUMEN
Background Polypharmacy is common among older people and may be associated with adverse drug events (ADEs) and poor health outcomes. Pharmacists are well-positioned to reduce polypharmacy and potentially inappropriate medications. Objective The objective of this narrative review was to summarize the results from randomized-controlled trials that evaluated pharmacist-led interventions with the goal or effect to deprescribe medications in older individuals. Data Sources We searched Medline, Embase, CINAHL Complete, APA PsycInfo, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials. Data Synthesis Of the 25 studies included, the interventions were conducted in nursing facilities (n = 8), outpatient/community dwellings (n = 8), or community pharmacies (n = 9). Interventions were categorized as comprehensive medication reviews (n = 10), comprehensive medication reviews with pharmacist follow-up (n = 11), and educational interventions provided to patients and/or providers (n = 4). Pharmacist-led interventions had a beneficial effect on 22 out of 32 total medication-related outcomes (eg, number of medications, potentially inappropriate medications, or discontinuation). Most (n = 18) studies reported no evidence of an effect for other outcomes such as health care use, mortality, patient-centered outcomes (falls, cognition, function, quality of life), and ADEs. Discussion Interventions led to improvement in 69% of the medication-related outcomes examined across study settings. Five studies measured ADEs with none accounting for adverse drug-withdrawal events. Large well-designed studies that are powered to find an effect on patient-centered outcomes are needed. Conclusion Pharmacist-led interventions had a significant beneficial effect on medication-related outcomes. There was little evidence of benefit on other outcomes.
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Deprescripciones , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Anciano , Farmacéuticos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & controlRESUMEN
We compared circulating miRNA profiles of hospitalized COVID-positive patients (n = 104), 27 with acute respiratory distress syndrome (ARDS) and age- and sex-matched healthy controls (n = 18) to identify miRNA signatures associated with COVID and COVID-induced ARDS. Meta-analysis incorporating data from published studies and our data was performed to identify a set of differentially expressed miRNAs in (1) COVID-positive patients versus healthy controls as well as (2) severe (ARDS+) COVID vs moderate COVID. Gene ontology enrichment analysis of the genes these miRNAs interact with identified terms associated with immune response, such as interferon and interleukin signaling, as well as viral genome activities associated with COVID disease and severity. Additionally, we observed downregulation of a cluster of miRNAs located on chromosome 14 (14q32) among all COVID patients. To predict COVID disease and severity, we developed machine learning models that achieved AUC scores between 0.81-0.93 for predicting disease, and between 0.71-0.81 for predicting severity, even across diverse studies with different sample types (plasma versus serum), collection methods, and library preparations. Our findings provide network and top miRNA feature insights into COVID disease progression and contribute to the development of tools for disease prognosis and management.
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COVID-19 , MicroARN Circulante , Síndrome de Dificultad Respiratoria , Humanos , COVID-19/genética , Progresión de la Enfermedad , Pronóstico , Síndrome de Dificultad Respiratoria/genética , Masculino , FemeninoRESUMEN
People with serious mental illness (SMI) diagnoses who become pregnant are particularly vulnerable to symptom recurrence and resulting potential lack of decision-making capacity (Taylor et al. J Psychiatr Res 104:100-107, 2018; Bagadia et al. Int J Soc Psychiatry 66:792-798, 2020). In these situations, prenatal and behavioral health providers have little legally viable guidance on what medical and/or psychiatric care the patient desires (Aneja and Arora Indian J Med Ethics V:133-139, 2020). We created a "Reproductive Psychiatric Advance Directive (PAD)," grounded in Reproductive Justice principles, that promotes patient autonomy by proactively articulating perinatal medical and psychiatric care preferences. We conducted a medical and legal literature review using two sets of terms related to (1) PADs and (2) reproductive health. We convened an expert working group of legal, medical, psychiatric, peer, and advocacy leaders and community-based organizations to develop a Reproductive PAD. Our literature review yielded no results about Reproductive PADs. We created de novo a Reproductive PAD template with sections on medical and psychiatric history, informed consent for critical medical and psychiatric care, family planning and custody preferences, and optional sections on abortion and on electroconvulsive therapy. The Reproductive PAD provides a possible legal mechanism for people of childbearing age with SMI diagnoses to articulate their medical and psychiatric care choices around reproduction and pregnancy. Future research should evaluate the Reproductive PAD as an effective tool for protecting patient autonomy during pregnancy and postpartum and guiding medical and psychiatric providers.