Growth Faltering and Failure to Thrive in Children.

Growth faltering, previously known as failure to thrive, is a broad term describing children who do not reach their expected weight, length, or body mass index for age. Growth is assessed with standardized World Health Organization charts for children younger than two years and Centers for Disease Control and Prevention charts for children two years and older. Traditional criteria for growth faltering can be imprecise and difficult to track over time; therefore, use of anthropometric z scores are now recommended. These scores can be calculated with a single set of measurements to assess malnutrition severity. Inadequate caloric intake, the most common cause of growth faltering, is identified with a detailed feeding history and physical examination. Diagnostic testing is reserved for those who have severe malnutrition or symptoms concerning for high-risk conditions, or if initial treatment fails. In older children or those with comorbidities, it is important to screen for underlying eating disorders (e.g., avoidant/restrictive food intake disorder, anorexia nervosa, bulimia). Growth faltering can usually be managed by the primary care physician. If comorbid disease is identified, a multidisciplinary team (e.g., nutritionist, psychologist, pediatric subspecialists) may be beneficial. Failure to recognize and treat growth faltering in the first two years of life may result in decreased adult height and cognitive potential.

Is it too complex? A survey of pediatric residency program's educational approach for the care of children with medical complexity.

BACKGROUND: Although Entrustable Professional Activities (EPAs) regarding pediatric training in care for children with medical complexity (CMC) exist, it is unknown what US pediatric training programs provide for education related to care of CMC and whether educators perceive that pediatric residents are prepared to care for CMC upon graduation. METHODS: From June, 2021 through March 2022, we surveyed US pediatric residency program delegates about practice settings, current educational offerings, perception of resident preparedness regarding care of CMC, and likelihood to implement CMC education in the future. RESULTS: Response rate was 29% (56 /195). A third of responding programs (34%, n = 19) provide a specific educational CMC offering including combinations of traditional didactics (84%, n = 16), asynchronous modules/reading (63%, n = 12), experiential learning (58%, n = 11), and simulation-based didactics (26%, n = 5). The majority (93%, n = 52) of respondents agreed residents should be competent in providing primary care for CMC upon graduation and CMC should receive primary care from a resident (84%, n = 47). A total of 49% (n = 27) of respondents reported their residents are very or extremely well prepared to care for CMC after graduation. A total of 33% (n = 18) of programs reported CMC receive primary care from residents. Respondent average perception of resident preparedness was significantly higher in programs with educational offerings in five of eleven EPAs (nutrition and weight, transitions, feeding tubes, advocacy, and care coordination). The majority (78%, n = 29) of programs without educational offerings are at least somewhat likely to implement CMC curricula in the next three years. CONCLUSION: Pediatric residency programs report residents should be competent in care for CMC upon graduation. Pediatric residents are exposed to a wide variety of clinical care models for CMC. The minority of responding programs have intentional CMC educational offerings. Of those programs that provide CMC education, the offerings are variable and are associated with a perception of improved preparedness to care for CMC upon graduation.

Provision and uptake of sexual and reproductive health services during the COVID-19 pandemic: The case of Mali.

A qualitative study assessed the effects of the COVID-19 epidemic on Malian sexual and reproductive health services. Sexual and reproductive health (SRHR) providers in 25 purposively selected public health facilities in urban Bamako, rural Kita (western Mali) and Koutiala (southeast Mali) were interviewed. Disruptions within SRH supply, staffing, the prioritization of SRHR services, and patients' ability to seek, obtain and pay for services were reported across urban and rural settings at all levels of public health care, and by all cadres of SRHR providers. Most facilities in the study areas sustained some SRHR services at the height of the COVID-19 epidemic through innovative outreach and phone-based consultations. This study offers critical lessons for SRHR service provision during future waves of the pandemic or during periods of comparable emergency.

Determinants of malaria testing at health facilities: the case of Uganda.

BACKGROUND: The World Health Organization (WHO) recommends prompt malaria diagnosis with either microscopy or malaria rapid diagnostic tests (RDTs) and treatment with an effective anti-malarial, as key interventions to control malaria. However, in sub-Saharan Africa, malaria diagnosis is still often influenced by clinical symptoms, with patients and care providers often interpreting all fevers as malaria. The Ministry of Health in Uganda defines suspected malaria cases as those with a fever. A target of conducting testing for at least 75% of those suspected to have malaria was established by the National Malaria Reduction Strategic Plan 2014-2020. METHODS: This study investigated factors that affect malaria testing at health facilities in Uganda using data collected in March/April 2017 in a cross-sectional survey of health facilities from the 52 districts that are supported by the US President's Malaria Initiative (PMI). The study assessed health facility capacity to provide quality malaria care and treatment. Data were collected from all 1085 public and private health facilities in the 52 districts. Factors assessed included supportive supervision, availability of malaria management guidelines, laboratory infrastructure, and training health workers in the use of malaria rapid diagnostic test (RDT). Survey data were matched with routinely collected health facility malaria data obtained from the district health information system Version-2 (DHIS2). Associations between testing at least 75% of suspect malaria cases with several factors were examined using multivariate logistic regression. RESULTS: Key malaria commodities were widely available; 92% and 85% of the health facilities reported availability of RDTs and artemether-lumefantrine, respectively. Overall, 933 (86%) of the facilities tested over 75% of patients suspected to have malaria. Predictors of meeting the testing target were: supervision in the last 6 months (OR: 1.72, 95% CI 1.04-2.85) and a health facility having at least one health worker trained in the use of RDTs (OR: 1.62, 95% CI 1.04-2.55). CONCLUSION: The study findings underscore the need for malaria control programmes to provide regular supportive supervision to health facilities and train health workers in the use of RDTs.

Caring for Transgender and Gender-Diverse Persons: What Clinicians Should Know.

Persons whose experienced or expressed gender differs from their sex assigned at birth may identify as transgender. Transgender and gender-diverse persons may have gender dysphoria (i.e., distress related to this incongruence) and often face substantial health care disparities and barriers to care. Gender identity is distinct from sexual orientation, sex development, and external gender expression. Each construct is culturally variable and exists along continuums rather than as dichotomous entities. Training staff in culturally sensitive terminology and transgender topics (e.g., use of chosen name and pronouns), creating welcoming and affirming clinical environments, and assessing personal biases may facilitate improved patient interactions. Depending on their comfort level and the availability of local subspecialty support, primary care clinicians may evaluate gender dysphoria and manage applicable hormone therapy, or monitor well-being and provide primary care and referrals. The history and physical examination should be sensitive and tailored to the reason for each visit. Clinicians should identify and treat mental health conditions but avoid the assumption that such conditions are related to gender identity. Preventive services should be based on the patient's current anatomy, medication use, and behaviors. Gender-affirming hormone therapy, which involves the use of an estrogen and antiandrogen, or of testosterone, is generally safe but partially irreversible. Specialized referral-based surgical services may improve outcomes in select patients. Adolescents experiencing puberty should be evaluated for reversible puberty suppression, which may make future affirmation easier and safer. Aspects of affirming care should not be delayed until gender stability is ensured. Multidisciplinary care may be optimal but is not universally available.

The Effect of Intraoperative Systemic Lidocaine on Postoperative Persistent Pain Using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials Criteria Assessment Following Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To compare the incidence in postsurgical persistent pain following breast cancer surgery in women receiving intravenous lidocaine compared to saline using validated pain instruments in accordance with the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations. METHODS: The study was a randomized, double-blinded, placebo-controlled, clinical trial. Subjects were randomized into Group 1 (1.5 mg/kg bolus of intravenous lidocaine followed by a 2 mg/kg/hour infusion) or Group 2 (normal saline at the same bolus and infusion rate). Patients were evaluated at 3 and 6 months for the presence of chronic persistent postsurgical pain. RESULTS: One hundred forty-eight patients were included in the study analysis. There were no differences in quality of recovery, pain burden, or opioid consumption between groups at 24 hours. Pain (yes/no) at 6 months attributed to surgery was reported in 29% of Group 2 vs. 13% of Group 1 patients (P = 0.04); however, only 3 subjects (5%) in Group 1 and 2 subjects (3%) in Group 2 met IMMPACT criteria for persistent postoperative pain (P = 0.99). DISCUSSION: Perioperative infusion of lidocaine has been reported to decrease the incidence of postsurgical pain at 3 and 6 months following mastectomy using dichotomous (yes/no) scoring. Although intravenous lidocaine reduced the reported incidence of pain at rest at 6 months, pain with activity, pain qualities, and the physical or emotional impact of the pain were unaffected. Future studies evaluating postsurgical persistent pain should adhere to the IMMPACT recommendations in order to more accurately describe the effect of an intervention on persistent pain.

Elective cholecystectomy reduces morbidity of cholelithiasis in pediatric sickle cell disease.

BACKGROUND: Cholelithiasis is a frequent complication in pediatric sickle cell disease (SCD). Though it is standard practice to perform a cholecystectomy in pediatric SCD patients with symptoms of cholelithiasis, the use of elective cholecystectomy for asymptomatic patients remains controversial. PROCEDURE: Records of 191 pediatric sickle cell patients with cholelithiasis who underwent cholecystectomy were retrospectively reviewed. Patients classified as follows: (i) elective-no preoperative symptoms, cholelithiasis on screening ultrasound, comprehensive preoperative plan; (ii) symptomatic-preoperative symptoms of cholelithiasis on diagnostic ultrasound, comprehensive preoperative plan; or (iii) emergent-hospitalization for acute cholecystitis symptoms, cholelithiasis on diagnostic ultrasound, limited preoperative preparation. We compared the morbidity of cholecystectomy by examining pre- and post-cholecystectomy hospital admission days, length of stay for cholecystectomy, and surgical complications. RESULTS: Patients with SCD underwent a total of 191 cholecystectomies over a 10-year period: 51 elective, 110 symptomatic, and 30 emergent. Patients who required emergent cholecystectomy had a longer postoperative hospitalization time than elective or symptomatic cholecystectomy (7.3 vs 4.3, P < 0.001). Baseline values for total bilirubin and aspartate aminotransferase (AST) were significantly elevated (P < 0.02 and P < 0.07, respectively) in patients requiring emergent cholecystectomy. CONCLUSIONS: This represents the largest reported retrospective review of pediatric cholelithiasis and cholecystectomy in SCD to date. These data strongly suggest that elective cholecystectomy decreases morbidity associated with emergent cholecystectomy. The overall outcomes for symptomatic and elective patients are favorable. However, our study indicates the need for prospective studies to identify clinical indicators for those emergent patients.

A hemoglobin variant associated with neonatal cyanosis and anemia.

Globin-gene mutations are a rare but important cause of cyanosis. We identified a missense mutation in the fetal Gγ-globin gene (HBG2) in a father and daughter with transient neonatal cyanosis and anemia. This new mutation modifies the ligand-binding pocket of fetal hemoglobin by means of two mechanisms. First, the relatively large side chain of methionine decreases both the affinity of oxygen for binding to the mutant hemoglobin subunit and the rate at which it does so. Second, the mutant methionine is converted to aspartic acid post-translationally, probably through oxidative mechanisms. The presence of this polar amino acid in the heme pocket is predicted to enhance hemoglobin denaturation, causing anemia.

Income and Household Material Hardship in Children With Medical Complexity.

BACKGROUND AND OBJECTIVES: Household economic hardship negatively impacts child health but may not be adequately captured by income. We sought to determine the prevalence of household material hardship (HMH), a measure of household economic hardship, and to examine the relationship between household poverty and material hardship in a population of children with medical complexity. METHODS: We conducted a cross-sectional survey study of parents of children with medical complexity receiving primary care at a tertiary children's hospital. Our main predictor was household income as a percentage of the federal poverty limit (FPL): <50% FPL, 51% to 100% FPL, and >100% FPL. Our outcome was HMH measured as food, housing, and energy insecurity. We performed logistic regression models to calculate adjusted odds ratios of having ≥1 HMH, adjusted for patient and clinical characteristics from surveys and the Pediatric Health Information System. RESULTS: At least 1 material hardship was present in 40.9% of participants and 28.2% of the highest FPL group. Families with incomes <50% FPL and 51% to 100% FPL had ∼75% higher odds of having ≥1 material hardship compared with those with >100% FPL (<50% FPL: odds ratio 1.74 [95% confidence interval: 1.11-2.73], P = .02; 51% to 100% FPL: 1.73 [95% confidence interval: 1.09-2.73], P = .02). CONCLUSIONS: Poverty underestimated household economic hardship. Although households with incomes <100% FPL had higher odds of having ≥1 material hardship, one-quarter of families in the highest FPL group also had ≥1 material hardship.

Changes in hospitalization populations by level of complexity at children's hospitals.

It is important for hospitals to understand how hospitalizations for children are changing to adapt and best accommodate the future needs of all patient populations. This study aims to understand how hospitalizations for children with medical complexity (CMC) and non-CMC have changed over time at children's hospitals, and how hospitalizations for these children will look in the future. Children with 3+ complex chronic conditions (CCC) accounted for 7% of discharges and over one-quarter of days and one-third of costs during the study period (2012-2022). The number of CCCs was associated with increased growth in discharges, hospital days, and costs. Understanding these trends can help hospitals better allocate resources and training to prepare for pediatric patients across the spectrum of complexity.

Pediatrician perspectives on barriers and facilitators to discharge instruction comprehension and adherence for parents of children with medical complexity.

BACKGROUND: High rates of posthospitalization errors are observed in children with medical complexity (CMC). Poor parent comprehension of and adherence to complex discharge instructions can contribute to errors. Pediatrician views on common barriers and facilitators to parent comprehension and adherence are understudied. OBJECTIVE: To examine pediatrician perspectives on barriers and facilitators experienced by parents in comprehension of and adherence to inpatient discharge instructions for CMC. DESIGN, SETTINGS, AND PARTICIPANTS: We conducted a qualitative, descriptive study of attending pediatricians (n = 20) caring for CMC in inpatient settings (United States and Canada) and belonging to listservs for pediatric hospitalists/complex care providers. We used purposive/maximum variation sampling to ensure heterogeneity (e.g., hospital, region). MAIN OUTCOME AND MEASURES: A multidisciplinary team designed and piloted a semistructured interview guide with pediatricians who care for CMC. Team members conducted semistructured interviews via phone or video call. Interviews were audiorecorded and transcribed. We analyzed transcripts using content analysis; codes were derived a priori from a conceptual framework (based on the Pediatric Self-Management Model) and a preliminary transcript analysis. We applied codes and identified emerging themes. RESULTS: Pediatricians identified three themes as barriers and facilitators to discharge instruction comprehension and adherence: (1) regimen complexity, (2) access to the healthcare team (e.g., inpatient team, outpatient pediatrician, home nursing) and resources (e.g., medications, medical equipment), and (3) need for a family centered and health literacy-informed approach to discharge planning and education. Next steps include the assessment of parent perspectives on barriers and facilitators to discharge instruction comprehension and adherence for prents of CMC and the development of intervention strategies.

The effectiveness of police custody assessments in identifying suspects with intellectual disabilities and attention deficit hyperactivity disorder.

BACKGROUND: Intellectual Disabilities (ID) and Attention Deficit Hyperactivity Disorder (ADHD) are recognized psychological vulnerabilities in police interviews and court proceedings in England and Wales. The aims of this study were to investigate: (a) the prevalence of ID and/or ADHD among suspects detained at a large London metropolitan police station and their relationship with conduct disorder (CD), (b) the impact of their condition on police staff resources, (c) the effectiveness of current custody assessment tools in identifying psychological vulnerabilities, and (d) the use of 'Appropriate Adults' in interviews. METHOD: A total of 200 individuals in a police custody suite were interviewed and screened for ID, ADHD (current symptoms) and CD. RESULTS: The screening rates for these three disorders were 6.7%, 23.5% and 76.3%, respectively. ADHD contributed significantly to increased requests being made of staff after controlling for CD and duration of time in custody. This is a novel finding. Reading and writing difficulties and mental health problems were often identified from the custody risk assessment tools, but they were not used effectively to inform on the need for the use of an Appropriate Adult. The frequency with which Appropriate Adults were provided to support detainees in police interviews (4.2%) remains almost identical to that found in a similar study conducted 20 years previously. CONCLUSIONS: The current findings suggest that in spite of reforms recently made in custodial settings, procedures may not have had the anticipated impact of improving safeguards for vulnerable suspects. Detainees with ID and ADHD require an Appropriate Adult during police interviews and other formal custody procedures, which they commonly do not currently receive. The findings of the current study suggest this may be due, in large part, to the ineffective use of risk-assessment tools and healthcare professionals, which represent missed opportunities to identify such vulnerabilities.

Accuracy of the Exeter Hospitalizations-Office Visits-Medical Conditions-Extra Care-Social Concerns Index for Identifying Children With Complex Chronic Medical Conditions in the Clinical Setting.

OBJECTIVE: Our objective was to determine the accuracy of a point-of-care instrument, the Hospitalizations-Office Visits-Medical Conditions-Extra Care-Social Concerns (HOMES) instrument, in identifying patients with complex chronic conditions (CCCs) compared to an algorithm used to identify patients with CCCs within large administrative data sets. METHODS: We compared the HOMES to Feudtner's CCCs classification system. Using administrative algorithms, we categorized primary care patients at a children's hospital into 3 categories: no chronic conditions, non-complex chronic conditions, and CCCs. We randomly selected 100 patients from each category. HOMES scoring was completed for each patient. We performed an optimal cut-point analysis on 80% of the sample to determine which total HOMES score best identified children with ≥1 CCC and ≥2 CCCs. Using the optimal cut points and the remaining 20% of the study population, we determined the odds and area under the curve (AUC) of having ≥1 CCC and ≥2 CCCs. RESULTS: The median (interquartile range [IQR]) age was 4 (IQR: 0, 8). Using optimal cut points of ≥7 for ≥1 CCC and ≥11 for ≥2 CCCs, the odds of having ≥1 CCC was 19 times higher than lower scores (odds ratio [OR] 19.1 [95% confidence interval [CI]: 9.75, 37.5]) and of having ≥2 CCCs was 32 times higher (OR 32.3 [95% CI: 12.9, 50.6]). The AUCs were 0.76 for ≥1 CCC (sensitivity 0.82, specificity 0.80) and 0.74 for ≥2 CCCs (sensitivity 0.92, specificity 0.74). CONCLUSIONS: The HOMES accurately identified patients with CCCs.

A retrospective cohort study of the effect of rapid versus delayed-result procalcitonin testing on antibiotic use at a community hospital.

BACKGROUND: Procalcitonin is a serum biomarker used to distinguish bacterial infection from viral or noninfectious syndromes. Primary literature shows mixed data on use of procalcitonin for de-escalation of antimicrobials. Delays in test results of send-out procalcitonin assays may result in prolonged antimicrobial durations. It is unknown whether availability of rapid-result assays may shorten time to antibiotic de-escalation. AIM: This retrospective, cohort study compared antibiotic durations of treatment between groups with rapid-result versus delayed send-out, procalcitonin test modality. This study was exempt from Ethics Committee Approval, as determined by the Institutional Review Board at the study site. METHOD: Adult hospitalized patients were included if they had at least one procalcitonin test performed during the study period. The primary outcome compared mean duration of antimicrobial therapy between groups receiving a rapid-result procalcitonin test and a send-out test. Secondary outcomes included incidence of Clostridiodes difficile infection, mention of procalcitonin testing in the electronic medical record in reference to antimicrobial therapy decision making, and presence of comorbidities which affect procalcitonin levels independent of infection. RESULTS: A total of 350 lab results were analyzed. The duration of antimicrobial treatment between groups was not statistically different with the median duration of treatment in the send-out group being 2.95 days compared to 3.35 in the rapid result group, p = 0.856. Patient comorbidities with potential to lead to a noninfectious elevation or falsely high level of procalcitonin were common. CONCLUSION: Use of a rapid-result procalcitonin assay does not reduce hospital antimicrobial therapy duration as compared with send-out testing.

Psychosocial Considerations for the Child with Rare Disease: A Review with Recommendations and Calls to Action.

Rare diseases (RD) affect children, adolescents, and their families infrequently, but with a significant impact. The diagnostic odyssey undertaken as part of having a child with RD is immense and carries with it practical, emotional, relational, and contextual issues that are not well understood. Children with RD often have chronic and complex medical conditions requiring a complicated milieu of care by numerous clinical caregivers. They may feel isolated and may feel stigmas in settings of education, employment, and the workplace, or a lack a social support or understanding. Some parents report facing similar loneliness amidst a veritable medicalization of their homes and family lives. We searched the literature on psychosocial considerations for children with rare diseases in PubMed and Google Scholar in English until 15 April 2022, excluding publications unavailable in full text. The results examine RD and their psychosocial ramifications for children, families, and the healthcare system. The domains of the home, school, community, and medical care are addressed, as are the implications of RD management as children transition to adulthood. Matters of relevant healthcare, public policies, and more sophisticated translational research that addresses the intersectionality of identities among RD are proposed. Recommendations for interventions and supportive care in the aforementioned domains are provided while emphasizing calls to action for families, clinicians, investigators, and advocacy agents as we work toward establishing evidence-based care for children with RD.

Hypertensive Conditions: Essential (Primary) Hypertension in Adults.

Blood pressure (BP) screening using an office-based measurement is recommended for adults 18 years and older without a history of hypertension. If abnormal, the BP measurement should be repeated twice with the average of those final two readings used to determine the BP category. Home BP monitoring and ambulatory BP monitoring are beneficial in patients for whom there is a concern for masked or white-coat hypertension. Guidelines differ regarding the BP cutoff used for the diagnosis of hypertension. Lifestyle modifications are the foundation of hypertension management with the Dietary Approaches to Stop Hypertension (DASH) diet being the most effective dietary modification. First-line pharmacotherapy should include one or more of the following: an angiotensin-converting enzyme inhibitor, an angiotensin receptor blocker, a dihydropyridine calcium channel blocker, and a thiazide or thiazidelike diuretic. Compared with standard BP control, intensive BP control (ie, systolic BP less than 120 mm Hg) leads to a decrease in atherosclerotic cardiovascular disease and all-cause mortality in patients with elevated risk but increases adverse effects, including hypotension, electrolyte abnormalities, acute kidney injury, and syncope.

Hypertensive Conditions: Secondary Causes of Hypertension in Adults.

Secondary hypertension (HTN) refers to high blood pressure (BP) caused by an identifiable and potentially correctable condition or disease. Common causes of secondary HTN include renovascular disease, renal parenchymal disease, primary hyperaldosteronism, drug and substance use, and obstructive sleep apnea; less common etiologies include pheochromocytoma/paraganglioma, Cushing syndrome, thyroid and parathyroid conditions, congenital adrenal hyperplasia, and aortic coarctation. An identifiable secondary cause of HTN is present in approximately 10% of adult patients with HTN. Early recognition of suggestive clinical findings and laboratory results enables the timely diagnosis of specific secondary causes of HTN. Correct diagnosis of a causative underlying condition can lead to more effective, even curative management and subsequent cardiovascular risk reduction. Management involves treating the underlying condition. Some patients may benefit from referral to a specialist with specific expertise in treating the causative condition.

Hypertensive Conditions: Hypertension in Children and Adolescents.

Hypertension (HTN) in children and adolescents is a spectrum of disease, ranging from elevated blood pressure (BP) to stage 1 and 2 HTN. The prevalence of elevated BP and HTN in this age group has increased significantly over the past 20 years, particularly in girls. Screening for HTN in asymptomatic children and adolescents is controversial. Primary HTN is now the predominant cause of HTN among the pediatric population in the United States, especially among adolescents. Secondary pediatric HTN is high BP due to an underlying medical condition and is more common among children 6 years and younger. Ambulatory BP monitoring should be considered in pediatric patients with repeatedly elevated office BP measurements. All children with BP greater than the 90th percentile should be encouraged to adopt lifestyle changes, but those with persistent or severe elevations in BP may benefit from pharmacotherapy.

Hypertensive Conditions: Hypertensive Disorders in Pregnancy.

Hypertensive disorders in pregnancy (HDP) represent a spectrum of disease that affect women through pregnancy and the immediate postpartum period. These conditions are associated with significant morbidity and mortality during and after pregnancy and have been linked to cardiovascular disease later in life. The HDP spectrum includes gestational hypertension (HTN), preeclampsia, eclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, chronic HTN, and chronic HTN with superimposed preeclampsia. Low-dose aspirin is recommended as a preventive drug after 12 weeks' gestation in women who are at high risk of preeclampsia. In HDP, close blood pressure (BP) monitoring, laboratory evaluation, and fetal assessment are warranted. Labetalol and nifedipine extended release are first-line oral antihypertensives for outpatient BP management of chronic HTN; labetalol, hydralazine, and nifedipine immediate release are used for hospitalized patients. HDP may develop or progress in the postpartum period; continued vigilance is important in the puerperium.

DNA Methylation-Based Epigenetic Repression of SLC22A4 Promotes Resistance to Cytarabine in Acute Myeloid Leukemia.

Reduced expression of the uptake transporter, OCTN1 (SLC22A4), has been reported as a strong predictor of poor event-free and overall survival in multiple cohorts of patients with acute myeloid leukemia (AML) receiving the cytidine nucleoside analog, cytarabine (Ara-C). To further understand the mechanistic basis of interindividual variability in the functional expression of OCTN1 in AML, we hypothesized a mechanistic connection to DNA methylation-based epigenetic repression of SLC22A4. We found increased basal SLC22A4 methylation was associated with decreased Ara-C uptake in AML cell lines. Pre-treatment with hypomethylating agents, 5-azacytidine, or decitabine, restored SLC22A4 mRNA expression, increased cellular uptake of Ara-C, and was associated with increased cellular sensitivity to Ara-C compared with vehicle-treated cells. Additionally, lower SLC22A4 methylation status was associated with distinct clinical advantages in both adult and pediatric patients with AML. These findings suggest a regulatory mechanism is involved in the interindividual variability in response to Ara-C, and provides a basis for the integration of hypomethylating agents into Ara-C-based treatment regimens.