Maternal adverse childhood experiences (ACEs) and DNA methylation of newborns in cord blood.

BACKGROUND: Adverse childhood experiences (ACEs) increase the risk of poor health outcomes later in life. Psychosocial stressors may also have intergenerational health effects by which parental ACEs are associated with mental and physical health of children. Epigenetic programming may be one mechanism linking parental ACEs to child health. This study aimed to investigate epigenome-wide associations of maternal preconception ACEs with DNA methylation patterns of children. In the Center for the Health Assessment of Mothers and Children of Salinas study, cord blood DNA methylation was measured using the Illumina HumanMethylation450 BeadChip. Preconception ACEs, which occurred during the mothers' childhoods, were collected using a standard ACE questionnaire including 10 ACE indicators. Maternal ACE exposures were defined in this study as (1) the total number of ACEs; (2) the total number of ACEs categorized as 0, 1-3, and > 4; and (3) individual ACEs. Associations of ACE exposures with differential methylated positions, regions, and CpG modules determined using weighted gene co-expression network analysis were evaluated adjusting for covariates. RESULTS: Data on maternal ACEs and cord blood DNA methylation were available for 196 mother/newborn pairs. One differential methylated position was associated with maternal experience of emotional abuse (cg05486260/FAM135B gene; q value < 0.05). Five differential methylated regions were significantly associated with the total number of ACEs, and 36 unique differential methylated regions were associated with individual ACEs (Sidák p value < 0.05). Fifteen CpG modules were significantly correlated with the total number of ACEs or individual ACEs, of which 8 remained significant in fully adjusted models (p value < 0.05). Significant modules were enriched for pathways related to neurological and immune development and function. CONCLUSIONS: Maternal ACEs prior to conception were associated with cord blood DNA methylation of offspring at birth. Although there was limited overlap between differential methylated regions and CpGs in modules associated with ACE exposures, statistically significant regions and networks were related to genes involved in neurological and immune function. Findings may provide insights to pathways linking psychosocial stressors to health. Further research is needed to understand the relationship between changes in DNA methylation and child health.

Mental health outcomes of adults hospitalized for COVID-19: A systematic review.

BACKGROUND: Patients hospitalized for COVID-19 may be at high risk of mental health (MH) disorders. This systematic review assesses MH outcomes among adults during and after hospitalization for COVID-19 and ascertains MH care utilization and resource needs. METHODS: We searched multiple medical literature databases for studies published December 2019 to March 2021. Studies of ≥ 200 participants were synthesized. One reviewer completed article selection, data abstraction and assessed study quality and strength of evidence, with verification by a second. RESULTS: Fifty articles met preliminary inclusion criteria; 19 articles that included ≥ 200 participants were synthesized. Evidence from these primarily fair-quality studies suggests many patients experience symptoms of depression (9-66%), anxiety (30-39%), and insomnia (24-40%) during and 3 months after hospitalization for COVID-19. However, patients infrequently receive a new MH disorder diagnosis 6 months after hospitalization (5% are diagnosed with a new mood disorder, 7% anxiety disorder, and 3% insomnia). Some hospitalized patients - including women and those with more severe COVID-19 - may be at higher risk of poor MH outcomes. Data on MH care utilization and resource needs are currently limited. LIMITATIONS: Most included studies were small, did not report the proportion of participants with preexisting MH disorders, and did not use comparison groups. CONCLUSIONS: While many patients experience MH symptoms after hospitalization for COVID-19, most do not go on to develop a new MH disorder. Future studies should report whether participants have preexisting MH disorders and compare patients hospitalized for COVID-19 to patients hospitalized for other causes.

Implementing High-Reliability Organization Principles Into Practice: A Rapid Evidence Review.

OBJECTIVE: To promote a safety culture and reduce harm, health care systems are adopting high-reliability organization (HRO) principles. This rapid review synthesizes HRO frameworks, metrics, and implementation effects to help inform health systems' efforts toward becoming HROs. METHODS: Bibliographic databases were searched from 2010 to 2019. One reviewer used prespecified criteria to assess articles for inclusion, evaluate study quality, extract data, and grade strength of evidence with second reviewer checking. RESULTS: Twenty-three articles were identified: 8 described frameworks, 9 examined metrics, and 9 evaluated implementation outcomes. Five common strategies for HRO implementation emerged (developing leadership, supporting a culture of safety, providing training and learning, building data systems, and implementing quality improvement interventions). The Joint Commission's and Institute for Healthcare Improvement's frameworks emerged as the most comprehensive and widely applicable. The Joint Commission's Oro 2.0 metric for evaluating HRO progress similarly stood out as it was developed through broad stakeholder input and was validated by external researchers. Multicomponent HRO interventions delivered for at least 2 years were associated with improved process and patient safety outcomes. Because each HRO intervention was only supported by a single poor or fair-quality study-none of which contained a concurrent control group-a causal relationship between any HRO initiative and outcomes could not be established. CONCLUSIONS: Health care system adoption of HRO principles is associated with improved safety outcomes, yet the level of evidence is low. Priorities for future HRO studies include use of concurrent control groups and examination of specific outcomes measurements.

Fludrocortisone for orthostatic hypotension.

BACKGROUND: Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition. OBJECTIVES: To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension. SEARCH METHODS: We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries. SELECTION CRITERIA: We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss. DATA COLLECTION AND ANALYSIS: We used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE. MAIN RESULTS: We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs. We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants). For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal. Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.

Treatment of Lower Extremity Fractures in Chronic Spinal Cord Injury: A Systematic Review of the Literature.

OBJECTIVE: To review the literature regarding outcomes of surgical and nonsurgical management of lower extremity (LE) fractures in chronic spinal cord injury (SCI). TYPE: Systematic review. LITERATURE SURVEY: Medline (PubMed), Embase, Cochrane Database of Systemic Reviews, Cochrane Central, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, International Clinical Trials Registry Platform, and International Standard Randomized Controlled Trials were searched from January 1, 1966, to March 1, 2019. METHODOLOGY: Search was restricted to English language and adults (age ≥ 18 yr). Titles and abstracts were reviewed for relevance to study topics for inclusion. Case reports, reviews, non-SCI population studies, and studies examining fractures at the time of acute SCI were excluded. References of included articles from the original search and task force and external submissions yielded two additional articles that were included in the review after voting by task force members. Data extraction was performed by four task force members using a data extraction form, glossary, and instructions created in Microsoft Excel. Quality assessment was performed by three methodologists using prespecified criteria. SYNTHESIS: Twenty-three articles were included. Use of surgery to treat LE fractures in chronic SCI has increased, though nonoperative management was still more frequently reported. Regardless of type of management, amputations, nonunion/malunion, and pressure injuries were among the most commonly reported complications. Functional and quality of life outcomes were less frequently reported. CONCLUSIONS: There is insufficient evidence to support operative versus nonoperative management as best practice for management of LE fracture of SCI. Existing literature was limited by small sample sizes, lack of randomization or matched study designs, significant heterogeneity in populations and treatment strategies studied, and variability in defining and reporting outcomes of interest. The field would benefit from future research to address study design issues and standardization of outcome reporting to facilitate comparison of outcomes of operative versus nonoperative management.

Racial and Ethnic Disparities in COVID-19-Related Infections, Hospitalizations, and Deaths : A Systematic Review.

BACKGROUND: Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups. PURPOSE: To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them. DATA SOURCES: English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020. STUDY SELECTION: Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings. DATA EXTRACTION: Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence. DATA SYNTHESIS: 37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM Research Lab were included. African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (mostly reported as in-hospital mortality) (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to comorbid conditions (low-strength evidence). LIMITATIONS: Selection bias, missing race/ethnicity data, and incomplete outcome assessments in cohort and cross-sectional studies must be considered. In addition, adjustment for key demographic covariates was lacking in ecological studies. CONCLUSION: African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality but similar rates of case fatality. Differences in health care access and exposure risk may be driving higher infection and mortality rates. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. (PROSPERO: CRD42020187078).

Barriers and Facilitators to the Use of Medications for Opioid Use Disorder: a Rapid Review.

BACKGROUND: Despite evidence that medications to treat opioid use disorder (OUD) are effective, most people who could benefit from this treatment do not receive it. This rapid review synthesizes evidence on current barriers and facilitators to buprenorphine/naloxone and naltrexone at the patient, provider, and system levels to inform future interventions aimed at expanding treatment. METHODS: We systematically searched numerous bibliographic databases through May 2020 and selected studies published since 2014. Study selection, data abstraction, coding of barriers and facilitators, and quality assessment were first completed by one reviewer and checked by a second. RESULTS: We included 40 studies of buprenorphine (5 also discussed naltrexone). Four types of patient and provider-level barriers to OUD medication use emerged-stigma related to OUD medications, treatment experiences and beliefs (positive or negative), logistical issues (time and costs as well as insurance and regulatory requirements), and knowledge (high or low) of OUD and the role of medications. Stigma was the most common barrier among patients, while logistical issues were the most common barriers among providers. Facilitators for both patients and providers included peer supports. Most administrator-identified or system-level barriers and facilitators fit into the category of logistical issues. We have moderate confidence in buprenorphine findings but low confidence in naltrexone findings due to the small number of studies. DISCUSSION: Stigma, treatment experiences, logistical issues, and knowledge gaps are the main barriers associated with low utilization of OUD medications. These barriers can overlap and mutually reinforce each other, but given that, it is plausible that reducing one barrier may lead to reductions in others. The highest priority for future research is to evaluate interventions to reduce stigma. Other priorities for future research include better identification of barriers and facilitators for specific populations, such as those with OUD related to prescription opioids, and for naltrexone use. PROTOCOL REGISTRATION: PROSPERO; CRD42019133394.

Managing Acute Pain in Patients Taking Medication for Opioid Use Disorder: a Rapid Review.

BACKGROUND: Managing acute pain in patients with opioid use disorder (OUD) on medication (methadone, buprenorphine, or naltrexone) can be complicated by patients' higher baseline pain sensitivity and need for higher opioid doses to achieve pain relief. This review aims to evaluate the benefits and harms of acute pain management strategies for patients taking OUD medications and whether strategies vary by OUD medication type or cause of acute pain. METHODS: We systematically searched multiple bibliographic sources until April 2020. One reviewer used prespecified criteria to assess articles for inclusion, extract data, rate study quality, and grade our confidence in the body of evidence, all with second reviewer checking. RESULTS: We identified 12 observational studies-3 with control groups and 9 without. Two of the studies with control groups suggest that continuing buprenorphine and methadone in OUD patients after surgery may reduce the need for additional opioids and that ineffective pain management in patients taking methadone can result in disengagement in care. A third controlled study found that patients taking OUD medications may need higher doses of additional opioids for pain control, but provided insufficient detail to apply results to clinic practice. The only case study examining naltrexone reported that postoperative pain was managed using tramadol. We have low confidence in these findings as no studies directly addressed our question by comparing pain management strategies and few provided adequate descriptions of the dosage, timing, or rationale for clinical decisions. DISCUSSION: We lack rigorous evidence on acute pain management in patients taking medication for OUD; however, evidence supports the practice of continuing methadone or buprenorphine for most patients during acute pain episodes. Well-described, prospective studies of adjuvant pain management strategies when OUD medications are continued would add to the existing literature base. Studies on nonopioid treatments are also needed for patients taking naltrexone. PROTOCOL REGISTRATION: PROSPERO; CRD42019132924.

Association Between Traumatic Brain Injury and Dementia in Veterans: A Rapid Systematic Review.

OBJECTIVE: To systematically review the prevalence of dementia in Veterans versus civilians and the association between previous traumatic brain injuries (TBIs) and the risk and timing of dementia onset in Veterans. DESIGN: We systematically searched MEDLINE, PsycINFO, and Cochrane Central Register of Controlled Trials from database inception to October 2018. One reviewer assessed articles for inclusion, evaluated study quality, graded strength of evidence, and extracted data, with second reviewer checking. RESULTS: Forty articles were included, among which 10 presented the best evidence. Evidence suggests that dementia rates are likely similar between Veterans and civilians (10.7% vs 8.8%-11.6%, respectively). Dementia prevalence is likely higher in those with TBI (6%-16%) than in those without (3%-10%), with a possible dose-response relationship between the two. There may also be an association between TBI and early-onset dementia, although this evidence has important limitations. No studies evaluated whether dementia prevalence varied on the basis of combat deployment history or era of conflict. CONCLUSION: Dementia prevalence is likely similar in Veteran and civilian populations, and the risk of dementia is likely increased by TBI. To inform development of screening, prevention, and rehabilitation efforts, research is still needed addressing the mechanism of association and timing of dementia onset. PROTOCOL: PROSPERO; CRD42018107926.

Rapid Evidence Review of Mobile Applications for Self-management of Diabetes.

BACKGROUND: Patients with diabetes lack information on which commercially available applications (apps) improve diabetes-related outcomes. We conducted a rapid evidence review to examine features, clinical efficacy, and usability of apps for self-management of type 1 and type 2 diabetes in adults. METHODS: Ovid/Medline and the Cochrane Database of Systematic Reviews were searched for systematic reviews and technology assessments. Reference lists of relevant systematic reviews were examined for primary studies. Additional searches for primary studies were conducted online, through Ovid/Medline, Embase, CINAHL, and ClinicalTrials.gov . Studies were evaluated for eligibility based on predetermined criteria, data were extracted, study quality was assessed using a risk of bias tool, information on app features was collected, and app usability was assessed. Results are summarized qualitatively. RESULTS: Fifteen articles evaluating 11 apps were identified: six apps for type 1 and five apps for type 2 diabetes. Common features of apps included setting reminders and tracking blood glucose and hemoglobin A1c (HbA1c), medication use, physical activity, and weight. Compared with controls, use of eight apps, when paired with support from a healthcare provider or study staff, improved at least one outcome, most often HbA1c. Patients did not experience improvements in quality of life, blood pressure, or weight, regardless of app used or type of diabetes. Study quality was variable. Of the eight apps available for usability testing, two were scored "acceptable," three were "marginal," and three were "not acceptable." DISCUSSION: Limited evidence suggests that use of some commercially available apps, when combined with additional support from a healthcare provider or study staff, may improve some short-term diabetes-related outcomes. The impact of these apps on longer-term outcomes is unclear. More rigorous and longer-term studies of apps are needed. REGISTRATION: This review was funded by the Agency for Healthcare Research and Quality (AHRQ). The protocol is available at: http://www.effectivehealthcare.ahrq.gov/topics/diabetes-mobile-devices/research-protocol .

Health Disparities in Veterans: A Map of the Evidence.

BACKGROUND: Goals for improving the quality of care for all Veterans and eliminating health disparities are outlined in the Veterans Health Administration Blueprint for Excellence, but the degree to which disparities in utilization, health outcomes, and quality of care affect Veterans is not well understood. OBJECTIVES: To characterize the research on health care disparities in the Veterans Health Administration by means of a map of the evidence. RESEARCH DESIGN: We conducted a systematic search for research studies published from 2006 to February 2016 in MEDLINE and other data sources. We included studies of Veteran populations that examined disparities in 3 outcome categories: utilization, quality of health care, and patient health. MEASURES: We abstracted data on study design, setting, population, clinical area, outcomes, mediators, and presence of disparity for each outcome category. We grouped the data by population characteristics including race, disability status, mental illness, demographics (age, era of service, rural location, and distance from care), sex identity, socioeconomic status, and homelessness, and created maps illustrating the evidence. RESULTS: We reviewed 4249 citations and abstracted data from 351 studies which met inclusion criteria. Studies examining disparities by race/ethnicity comprised by far the vast majority of the literature, followed by studies examining disparities by sex, and mental health condition. Very few studies examined disparities related to lesbian, gay, bisexual, or transgender identity or homelessness. Disparities findings vary widely by population and outcome. CONCLUSIONS: Our evidence maps provide a "lay of the land" and identify important gaps in knowledge about health disparities experienced by different Veteran populations.