Family cascade screening for equitable identification of familial hypercholesterolemia: study protocol for a hybrid effectiveness-implementation type III randomized controlled trial.

BACKGROUND: Familial hypercholesterolemia (FH) is a heritable disorder affecting 1.3 million individuals in the USA. Eighty percent of people with FH are undiagnosed, particularly minoritized populations including Black or African American people, Asian or Asian American people, and women across racial groups. Family cascade screening is an evidence-based practice that can increase diagnosis and improve health outcomes but is rarely implemented in routine practice, representing an important care gap. In pilot work, we leveraged best practices from behavioral economics and implementation science-including mixed-methods contextual inquiry with clinicians, patients, and health system constituents-to co-design two patient-facing implementation strategies to address this care gap: (a) an automated health system-mediated strategy and (b) a nonprofit foundation-mediated strategy with contact from a foundation-employed care navigator. This trial will test the comparative effectiveness of these strategies on completion of cascade screening for relatives of individuals with FH, centering equitable reach. METHODS: We will conduct a hybrid effectiveness-implementation type III randomized controlled trial testing the comparative effectiveness of two strategies for implementing cascade screening with 220 individuals with FH (i.e., probands) per arm identified from a large northeastern health system. The primary implementation outcome is reach, or the proportion of probands with at least one first-degree biological relative (parent, sibling, child) in the USA who is screened for FH through the study. Our secondary implementation outcomes include the number of relatives screened and the number of relatives meeting the American Heart Association criteria for FH. Our secondary clinical effectiveness outcome is post-trial proband cholesterol level. We will also use mixed methods to identify implementation strategy mechanisms for implementation strategy effectiveness while centering equity. DISCUSSION: We will test two patient-facing implementation strategies harnessing insights from behavioral economics that were developed collaboratively with constituents. This trial will improve our understanding of how to implement evidence-based cascade screening for FH, which implementation strategies work, for whom, and why. Learnings from this trial can be used to equitably scale cascade screening programs for FH nationally and inform cascade screening implementation efforts for other genetic disorders. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05750667. Registered 15 February 2023-retrospectively registered, https://clinicaltrials.gov/study/NCT05750667 .

Adaptation and Uncertainty: A Qualitative Examination of Provider Experiences With Prone Positioning for Intubated Patients With COVID-19 ARDS.

BACKGROUND: Prone positioning was widely adopted for use in patients with ARDS from COVID-19. However, proning was also delivered in ways that differed from historical evidence and practice. In implementation research, these changes are referred to as adaptations, and they occur constantly as evidence-based interventions are used in real-world practice. Adaptations can alter the delivered intervention, impacting patient and implementation outcomes. RESEARCH QUESTION: How have clinicians adapted prone positioning to COVID-19 ARDS, and what uncertainties remain regarding optimal proning use? STUDY DESIGN AND METHODS: We conducted a qualitative study using semi-structured interviews with ICU clinicians from two hospitals in Baltimore, MD, from February to July 2021. We interviewed physicians (MDs), registered nurses (RNs), respiratory therapists (RTs), advanced practice providers (APPs), and physical therapists (PTs) involved with proning mechanically ventilated patients with COVID-19 ARDS. We used thematic analysis of interviews to classify proning adaptations and clinician uncertainties about best practice for prone positioning. RESULTS: Forty ICU clinicians (12 MDs, 4 APPs, 12 RNs, 7 RTs, and 5 PTs) were interviewed. Clinicians described several adaptations to the practice of prone positioning, including earlier proning initiation, extended duration of proning sessions, and less use of concomitant neuromuscular blockade. Clinicians expressed uncertainty regarding the optimal timing of initiation and duration of prone positioning. This uncertainty was viewed as a driver of practice variation. Although prescribers intended to use less deep sedation and paralysis in proned patients compared with historical evidence and practice, this raised concerns regarding patient comfort and safety amongst RNs and RTs. INTERPRETATION: Prone positioning in patients with COVID-19 ARDS has been adapted from historically described practice. Understanding the impact of these adaptations on patient and implementation outcomes and addressing clinician uncertainties are priority areas for future research to optimize the use of prone positioning.

Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry.

Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by early-onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a "real-world" setting. Untreated low-density lipoprotein cholesterol levels were lower in adults than children (533 versus 776 mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.

Factors Influencing the Implementation of Prone Positioning during the COVID-19 Pandemic: A Qualitative Study.

Rationale: The adoption of prone positioning for patients with acute respiratory distress syndrome (ARDS) has historically been poor. However, in mechanically ventilated patients with coronavirus disease (COVID-19) ARDS, proning has increased. Understanding the factors influencing this change is important for further expanding and sustaining the use of prone positioning in appropriate clinical settings. Objectives: To characterize factors influencing the implementation of prone positioning in mechanically ventilated patients with COVID-19 ARDS. Methods: We conducted a qualitative study using semistructured interviews with 40 intensive care unit (ICU) team members (physicians, nurses, advanced practice providers, respiratory therapists, and physical therapists) working at two academic hospitals. We used the Consolidated Framework for Implementation Research, a widely used implementation science framework outlining important features of implementation, to structure the interview guide and thematic analysis of interviews. Results: ICU clinicians reported that during the COVID-19 pandemic, proning was viewed as standard early therapy for COVID-19 ARDS rather than salvage therapy for refractory hypoxemia. By caring for large volumes of proned patients, clinicians gained increased comfort with proning and now view proning as a low-risk, high-benefit intervention. Within ICUs, adequate numbers of trained staff members, increased team agreement around proning, and the availability of specific equipment (e.g., to limit pressure injuries) facilitated greater proning use. Hospital-level supports included proning teams, centralized educational resources specific to the management of COVID-19 (including a recommendation for prone positioning), and an electronic medical record proning order. Important implementation processes included informal dissemination of best practices through on-the-job learning and team interactions during routine bedside care. Conclusions: The implementation of prone positioning for COVID-19 ARDS took place in the context of evolving clinician viewpoints and ICU team cultures. Proning was facilitated by hospital support and buy-in and leadership from bedside clinicians. The successful implementation of prone positioning during the COVID-19 pandemic may serve as a model for the implementation of other evidence-based therapies in critical care.

Obstructive Sleep Apnea and Pain Intensity in Young Adults.

Rationale: Prior research studies on the association of obstructive sleep apnea (OSA) and pain intensity have examined older patients; there is a need to understand the relationship between OSA and pain intensity among younger adults.Objectives: To examine whether young adults with diagnosed OSA are more likely to report higher pain intensity compared with those without OSA.Methods: We conducted a cross-sectional analysis of a cohort study of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn veterans who had at least one visit to a Veterans Health Administration primary care clinic between 2001 and 2014. OSA was identified using one inpatient or two outpatient International Classification of Diseases, Ninth Revision codes from electronic medical records. Average pain intensity (based on the self-reported 0-10 numeric rating scale over a 12-month period) was categorized as no pain/mild (0-3; no pain) and moderate/severe (4-10; significant pain). Covariates included age, sex, education, race, mental health diagnoses, headache diagnoses, pain diagnoses, hypertension, diabetes, body mass index, and smoking status. Multivariate logistic regression models were used, and multiple imputation was performed to generate values for missing variables.Results: We identified 858,226 young adults (mean age 30 yr [SD = 7]), of whom 91,244 (10.6%) had a diagnosis of OSA and 238,587 (27.8%) reported moderate/severe pain for the 12-month average. with young adults without OSA, those with OSA were more likely to report moderate/severe pain intensity (adjusted odds ratio, 1.09; 95% confidence interval, 1.08-1.11) even after controlling for covariates.Conclusions: We found that young adults with OSA have greater odds of comorbid moderate/severe pain. Because of the high prevalence of chronic pain in younger adults, this study highlights the need to understand the impact of OSA diagnosis and treatment on pain intensity. Future work is needed to determine the role of effective OSA treatment on pain intensity over time in these young adults.

ATS Core Curriculum 2020. Adult Critical Care Medicine.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3- to 4-year recurring cycle of topics. These topics will be presented at the 2020 International Conference. Below is the adult critical care medicine core including complications of chemotherapy, acute-on-chronic liver failure, alcohol withdrawal syndrome, mechanical circulatory support, direct oral anticoagulants, upper gastrointestinal hemorrhage, and vasopressor selection.

Iatrogenic Nontraumatic CPAP-Induced Pneumocephalus in a Patient With Meningitis.

ABSTRACT: Pneumocephalus, or air within the cranium, can be caused by trauma, intracranial infections, or tumors, and can also occur as a complication of neurosurgery and lumbar puncture. Continuous positive airway pressure (CPAP) therapy can precipitate or worsen pneumocephalus in cases of known head trauma. However, nontraumatic pneumocephalus being caused by CPAP is a highly unexpected clinical event. We describe a case of a patient who presented with meningitis due to an atypical organism that usually resides in the oral cavity, and who developed nontraumatic pneumocephalus in the hospital due to CPAP therapy. The underlying cause, a cerebrospinal fluid leak, was likely the mediator for both pathologies. In the setting of the increasing prevalence of obstructive sleep apnea, physicians can benefit from being aware of this atypical presentation of meningitis and atypical complication of CPAP therapy.

The Association of Obstructive Sleep Apnea and Pain Outcomes in Adults: A Systematic Review.

Objective: The specific link between obstructive sleep apnea (OSA) and pain is unknown, but it has been hypothesized that OSA patients are hyperalgesic because of fragmented sleep and hypoxemia that enhance sensitivity to pain, promote inflammation, and increase spontaneous pain. We conducted a systematic review of the literature assessing whether OSA is a risk factor for subjective pain intensity and experimental pain tolerance and threshold. Design/Participants: A search of published studies in English in MEDLINE, PubMed, Embase, and the Cochrane Database of Systematic Reviews from database inception through May 2017 was performed. Search terms included "sleep apnea," "continuous positive airway pressure," "CPAP," "pain," and "chronic pain." Methods: We included any study that reported an association between OSA or polysomnogram assessments with pain outcomes or reported the effect of CPAP on pain outcomes. Controlled studies, cohort studies, and case-control studies were included. Results: We identified 448 studies from PubMed and 959 studies from Embase, giving a combined 1,333 studies after removing duplicates. After detailed selection, 28 articles were reviewed in full and 12 met study inclusion criteria. Whereas several studies found an association between OSA and pain intensity or experimental pain, there was considerable variability among study outcomes. Delivery of CPAP may improve pain and decrease opioid use, although the exact nature of the relationship between pain and the various pathophysiologic components of OSA is unclear. Conclusions: This systematic review summarizes the current evidence for the association of OSA and pain outcomes. Further research is needed to identify the differential effects of nocturnal hypoxemia and fragmented sleep on pain intensity. Clinicians might consider screening patients with chronic pain for OSA.

Incidence and acute complications of asymptomatic central venous catheter-related deep venous thrombosis in critically ill children.

OBJECTIVE: To determined the current incidence and acute complications of asymptomatic central venous catheter (CVC)-related deep venous thrombosis (DVT) in critically ill children. STUDY DESIGN: We performed a prospective cohort study in 3 pediatric intensive care units. A total of 101 children with newly inserted untunneled CVC were included. CVC-related DVT was diagnosed using compression ultrasonography with color Doppler. RESULTS: Asymptomatic CVC-related DVT was diagnosed in 16 (15.8%) children, which equated to 24.7 cases per 1000 CVC-days. Age was independently associated with DVT. Compared with children aged <1 year, children aged >13 years had significantly higher odds of DVT (aOR, 14.1, 95% CI, 1.9-105.8; P = .01). Other patient demographics, interventions (including anticoagulant use), and CVC characteristics did not differ between children with and without DVT. Mortality-adjusted duration of mechanical ventilation, a surrogate for pulmonary embolism, was statistically similar in the 2 groups (22 ± 9 days in children with DVT vs 23 ± 7 days in children without DVT; P = .34). Mortality-adjusted intensive care unit and hospital lengths of stay also were similar in the 2 groups. CONCLUSION: Asymptomatic CVC-related DVT is common in critically ill children. However, the acute complications do not seem to differ between children with and without DVT. Larger studies are needed to confirm these results. Future studies should also investigate the chronic complications of asymptomatic CVC-related DVT.

Guidelines for animal-assisted interventions in health care facilities.

Many hospitals and long-term care facilities in North America currently permit animals to visit with their patients; however, the development of relevant infection control and prevention policies has lagged, due in large part to the lack of scientific evidence regarding risks of patient infection associated with animal interaction. This report provides standard guidelines for animal-assisted interventions in health care facilities, taking into account the available evidence.