Precision Medicine Using Simultaneous Monitoring and Assessment with Imaging and Biomarkers to Manage Mechanical Ventilation in ARDS.

Acute respiratory distress syndrome (ARDS) has a ~ 40% mortality rate with an increasing prevalence exacerbated by the COVID-19 pandemic. Mechanical ventilation is the primary means for life-saving support to buy time for lung healing in ARDS patients, however, it can also lead to ventilator-induced lung injury (VILI). Effective strategies to reduce or prevent VILI are necessary but are not currently delivered. Therefore, we aim at evaluating the current imaging technologies to visualize where pressure and volume being delivered to the lung during mechanical ventilation; and combining plasma biomarkers to guide management of mechanical ventilation. We searched PubMed and Medline using keywords and analyzed the literature, including both animal models and human studies, to examine the independent use of computed tomography (CT) to evaluate lung mechanics, electrical impedance tomography (EIT) to guide ventilation, ultrasound to monitor lung injury, and plasma biomarkers to indicate status of lung pathophysiology. This investigation has led to our proposal of the combination of imaging and biomarkers to precisely deliver mechanical ventilation to improve patient outcomes in ARDS.

Epilepsy panels in clinical practice: Yield, variants of uncertain significance, and treatment implications.

OBJECTIVE: There has been increasing utilization of genetic testing for pediatric epilepsy in recent years. Little systematic data is available examining how practice changes have impacted testing yields, diagnostic pace, incidence of variants of uncertain significance (VUSs), or therapeutic management. METHODS: A retrospective chart review was performed at Children's Hospital Colorado from February 2016 through February 2020. All patients under 18 years for whom an epilepsy gene panel was sent were included. RESULTS: A total of 761 epilepsy gene panels were sent over the study period. During the study period, there was a 292% increase in the average number of panels sent per month. The time from seizure onset to panel result decreased over the study period from a median of 2.9 years to 0.7 years. Despite the increase in testing, the percentage of panels yielding a disease-causing result remained stable at 11-13%. A total of 90 disease-causing results were identified, > 75% of which provided guidance in management. Children were more likely to have a disease-causing result if they were < 3 years old at seizure onset (OR 4.4, p < 0.001), had neurodevelopmental concerns (OR 2.2, p = 0.002), or had a developmentally abnormal MRI (OR 3.8, p < 0.001). A total of 1417 VUSs were identified, equating to 15.7 VUSs per disease-causing result. Non-Hispanic white patients had a lower average number of VUSs than patients of all other races/ethnicities (1.7 vs 2.1, p < 0.001). SIGNIFICANCE: Expansion in the volume of genetic testing corresponded to a decrease in the time from seizure onset to testing result. Diagnostic yield remained stable, resulting in an increase in the absolute number of disease-causing results annually-most of which have implications for management. However, there has also been an increase in total VUSs, which likely resulted in additional clinical time spent on VUS resolution.

Interactions between impulsivity and MDPV self-administration in rats.

Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), are recreational drugs of abuse often identified in 'bath salts' preparations. Humans report compulsive patterns of bath salts use, and previous work suggests that a subset of rats develop unusually high levels of MDPV self-administration. This study aims to test the hypothesis that high levels of impulsivity (e.g., inability to withhold responding for a sucrose reward) will predispose rats to high levels of MDPV self-administration relative to rats with lower levels of impulsivity. The 1-choice serial reaction time task (1-CSRTT) was used to assess impulsivity (i.e., premature responding) in 10 female and 10 male Sprague Dawley rats. Rats were then allowed to self-administer 0.032 mg/kg/inf MDPV or 0.32 mg/kg/inf cocaine, after which full dose-response curves for MDPV (0.001-0.1 mg/kg/inf) or cocaine (0.01-1 mg/kg/inf) were generated under a FR5 schedule of reinforcement. After a history of self-administering MDPV or cocaine, impulsivity was reassessed under the 1-CSRTT, prior to evaluating the acute effects of MDPV (0.032-0.32 mg/kg) or cocaine (0.1-1 mg/kg) on impulsivity. Level of impulsivity was not correlated with subsequent levels of either MDPV or cocaine self-administration, and level of drug self-administration was also not correlated with subsequent levels of impulsivity, although acute administration of MDPV and cocaine did increase premature responding. In failing to find direct relationships between either impulsivity and subsequent drug-taking behaviour, or drug-taking behaviour and subsequent assessments of impulsivity, these findings highlight the complexity inherent in the associations between impulsive behaviour and drug-taking behaviour in both animal models and humans.

Neonatal fractures as a presenting feature of LMOD3-associated congenital myopathy.

Nemaline myopathy is a rare inherited disorder characterized by weakness, hypotonia, and depressed deep tendon reflexes. It is clinically and genetically heterogeneous, with the most severe phenotype presenting as perinatal akinesia, severe muscle weakness, feeding difficulties and respiratory failure, leading to early mortality. Pathogenic variants in 12 genes, encoding components of the sarcomere or factors related to myogenesis, have been reported in patients affected with the disorder. Here, we describe an early, lethal presentation of decreased fetal movements, hypotonia, muscle weakness, and neonatal respiratory failure requiring ventilator support in three siblings from a consanguineous family. All exhibited perinatal fractures, and thus, a skeletal dysplasia was considered as possibly contributing to the phenotype. However, whole exome sequencing revealed a homozygous, loss-of-function pathogenic variant in LMOD3, which has recently been associated with nemaline myopathy and, in a subset of patients, perinatal fractures. This case demonstrates the importance of considering congenital neuromuscular disorders in the differential diagnosis of perinatal fractures.

Discriminative Stimulus Effects of Binary Drug Mixtures: Studies with Cocaine, MDPV, and Caffeine.

Illicit drug preparations often include more than one pharmacologically active compound. For example, cocaine and synthetic cathinones [e.g., 3,4-methylenedioxypyrovalerone (MDPV)] are often mixed with caffeine before sale. Caffeine is likely added to these preparations because it is inexpensive and legal; however, caffeine might also mimic or enhance some of the effects of cocaine or MDPV. In these studies, male Sprague-Dawley rats were trained to discriminate 10 mg/kg cocaine from saline, and the discriminative stimulus effects of cocaine, caffeine, and MDPV were evaluated alone and as binary mixtures (cocaine and caffeine, MDPV and caffeine, and cocaine and MDPV) at fixed-dose ratios of 3:1, 1:1, and 1:3 relative to the dose of each drug that produced 50% cocaine-appropriate responding. Dose-addition analyses were used to determine the nature of the drug-drug interactions for each mixture (e.g., additive, supra-additive, or subadditive). Although additive interactions were observed for most mixtures, supra-additive interactions were observed at the 50% effect level for the 1:1 mixture of cocaine and caffeine and at the 80% effect level for all three mixtures of cocaine and caffeine, as well as for the 3:1 and 1:3 mixtures of cocaine and MDPV. These results demonstrate that with respect to cocaine-like discriminative stimulus effects, caffeine can function as a substitute in drug preparations containing either cocaine or MDPV, with enhancements of cocaine-like effects possible under certain conditions. Further research is needed to determine whether similar interactions exist for other abuse-related or toxic effects of drug preparations, including cocaine, synthetic cathinones, and caffeine.

Measuring value at the provider level in the management of cleft lip and palate patients.

"Value" has become a buzzword in current health-care discussions. This study demonstrates a provider-led strategy to measuring costs, an understudied component of the value equation, for a complex diagnosis for the purposes of improvement. A retrospective, microcosting methodology was used to measure costs for all hospital and physician services and costs to the patient over 18 months of multidisciplinary care for patients with cleft lip and palate. Short-term outcomes were also recorded. Overall costs to all parts of the system ranged from $35,826 to $56,611 for different subtypes, and insight was gained into major cost drivers and variations in care that will drive internal improvement efforts. It is critical that providers learn to work together and become familiar with their own costs in conjunction with outcomes as insurers increase pressure to reduce payments or accept alternative payments so that well-informed decisions can be made.

Using time-driven activity-based costing to identify value improvement opportunities in healthcare.

As healthcare providers cope with pricing pressures and increased accountability for performance, they should be rededicating themselves to improving the value they deliver to their patients: better outcomes and lower costs. Time-driven activity-based costing offers the potential for clinicians to redesign their care processes toward that end. This costing approach, however, is new to healthcare and has not yet been systematically implemented and evaluated. This article describes early time-driven activity-based costing work at several leading healthcare organizations in the United States and Europe. It identifies the opportunities they found to improve value for patients and demonstrates how this costing method can serve as the foundation for new bundled payment reimbursement approaches.

Nasoalveolar molding in cleft care: is it efficacious?

In the era of evidence-based medicine, new treatment protocols and interventions should be routinely evaluated for their efficacy by reviewing the available evidence. In the cleft literature, nasoalveolar molding has garnered attention over the last decade as a new option for improving nasal form and symmetry before primary surgical repair. Systematic review of the evidence is, however, currently lacking. This review evaluates whether nasoalveolar molding can improve nasal symmetry and form toward the norm, as well as whether nasoalveolar molding demonstrates advantages over other protocols in achieving this goal. A literature search of five databases plus relevant reference lists retrieved 98 articles regarding nasoalveolar molding, 21 of which reported objective outcome measures of nasal symmetry and form, and six of which were able to be given evidence level ratings, all in the unilateral cleft population. Statistical analysis was not possible given the range of techniques and outcomes. Studies of bilateral cleft were not given evidence level ratings, given the inability to separate the effects of nasoalveolar molding from other primary nasal interventions in studies that would have otherwise been rated. In unilateral cleft lip-cleft palate, there was some evidence that nasoalveolar molding may improve nasal outcomes, though comparison with other techniques was limited. Despite a relative paucity of high-level evidence, nasoalveolar molding appears to be a promising technique that deserves further study.

Cost of treating sagittal synostosis in the first year of life.

BACKGROUND: Endoscopically assisted suturectomy (EAS) has been reported to reduce the morbidity and cost of treating sagittal synostosis when compared with traditional open cranial vault remodeling (CVR) procedures. Whereas the former claim is well substantiated and intuitive, the latter has not been validated by rigorous cost analysis. METHODS: Patient medical records and financial database reports were culled retrospectively to determine the total cost associated with both EAS and CVR during 1 year of care. Recorded cost data included physician and hospital services, orthotic equipment and fittings, and indirect patient cost. RESULTS: Ten patients treated with CVR were compared with 10 patients who underwent EAS. The CVR patients incurred greater costs in nearly all categories studied, including overall 1-year costs, physician services, hospital services, supplies/equipment, medications/intravenous fluids, and laboratory and blood bank services. Postoperative costs were greater in the EAS group, primarily because of the cost associated with orthotic services and indirect patient costs for travel and lost work. However, overall indirect patient costs for the whole year did not differ between the groups. One-year median costs were $55,121 for CVR and $23,377 for EAS. Early clinical results were similar for the 2 groups. CONCLUSIONS: Cranial vault remodeling was more costly in the first year of treatment than EAS, although indirect patient costs were similar. The favorable cost of EAS compared with CVR provides further justification to consider this procedure as first-line treatment of sagittal synostosis in young infants.

Patient Protection and Affordable Care Act: implications for pediatric plastic surgery.

Passage of the Patient Protection and Affordable Care Act (PPACA) has stimulated wide debate in the medical and surgical community. Endorsed by the American Medical Association and a number of primary care-focused organizations, the American College of Surgeons (ACS) and nearly all other surgical associations opposed the bill. This divergence stems not from direct disagreement over provisions in the bill but from opposition to or support of certain provisions with direct implications for the physicians represented by a given organization, as well as the relative importance of provisions for which these organizations share a common opinion. Regarding the field of pediatric plastic surgery, the surgical perspective of the ACS and the American Society of Plastic Surgeons and the medical perspective of the American Academy of Pediatrics align on many issues. Given the lack of specificity of any of the provisions for a field as specialized as pediatric plastic surgery, this review will focus on broader implications of the PPACA both for medical and surgical needs of pediatric patients and for the surgeons providing their care. The provisions of the PPACA are distributed along an implementation timeline, with some major changes having already occurred. The popularity of some of the early provisions, many pertaining to the pediatric population, has implications for any attempt at repeal of the law as a whole in coming years. Despite its daunting length, the PPACA can be approached by considering its provisions in 4 major categories: increased consumer protections, increased accountability for insurers, increased access to affordable care, and quality and cost improvement.

Cost differences between the anterior and posterior approaches to the iliac crest for alveolar bone grafting in patients with cleft lip/palate.

PURPOSE: There has been debate in the literature regarding the advantages of an anterior versus posterior approach to the iliac crest harvest for alveolar bone grafting (ABG) in patients with cleft lip and palate. The purpose of this study was to add a cost perspective to the discussion. MATERIALS AND METHODS: This was a retrospective microcost analysis for the perioperative period for 2 approaches to graft harvest for ABG in patients with cleft lip and palate. Patient charts and hospital and physician financial databases were searched for detailed cost data in the 30 days before and after ABG for 18 patients who underwent anterior or posterior iliac crest harvest at Children's Hospital Boston. In addition, short-term outcomes for these 18 patients were documented (duration of operation, need for physical therapy services, complications, and hospital length of stay) and compared with the larger study group at the same institution. RESULTS: There was a trend toward lower overall median costs for posterior compared with anterior iliac crest harvest ($18,269 vs $21,801, respectively; P = .15). The differences in cost were seen in inpatient hospital services after the operation, including ward and physical therapy costs, which were significantly lower for the posterior versus the anterior approach. This corresponded with a shorter median length of stay (1 day vs 2 days, respectively; P = .03). There was no significant difference in operating room, recovery room, or outpatient costs. More patients undergoing posterior harvest had bilateral ABG, offsetting the decreased inpatient costs with increased physician costs. CONCLUSIONS: The overall cost for ABG in patients with cleft lip and palate was not significantly different between the anterior and posterior approached to iliac crest harvest. Inpatient cost was lower in the posterior group because of a shorter length of stay.

Timeliness of surgical care in children with special health care needs: delayed palate repair for publicly insured and minority children with cleft palate.

BACKGROUND/PURPOSE: Disparities in access to health care are known to exist for the most vulnerable pediatric population, children with special health care needs. Timely access to surgical care in this population is critical, yet poorly studied. METHODS: A national database of pediatric hospitals in the United States was searched for nonsyndromic, healthy patients younger than 24 months who underwent cleft palate repair from 2003 to 2008. A multivariate, linear regression model was constructed to determine the relationship of public payer status and race with age at palatal repair. RESULTS: Age at palate repair was significantly delayed for patients who were publicly insured (1.2 weeks, P = .01), were of nonwhite race/ethnicity (1.5-3.5 weeks, P = .009), and had a diagnosis of cleft lip in addition to cleft palate (3.4 weeks, P = .006) compared to their counterparts in a sample of 2995 patients with cleft palate. CONCLUSION: There is a small but significant delay in age at repair for patients who are publicly insured or of nonwhite race/ethnicity. These results may herald broader access disparities that could adversely affect clinical outcomes and should be investigated further.

The value proposition: using a cost improvement map to improve value for patients with nonsyndromic, isolated cleft palate.

BACKGROUND: As health care costs rise exponentially in the United States, increasing emphasis is being placed on measuring value, which incorporates both quality and costs. Although the concept of continuous quality improvement has taken a firm foothold in health care, techniques for measuring and continuously improving costs at the patient or system level are lacking. METHODS: A retrospective, microcosting analysis mapped detailed medical costs over 18 months for 25 patients with nonsyndromic, isolated cleft palate to illustrate the concept of a continuous cost improvement map in a complex, multidisciplinary condition. RESULTS: Care for patients with nonsyndromic, isolated cleft palate was mapped to three timelines based on diagnostic subtype. Patients with Robin sequence requiring early surgical intervention for airway or feeding management (n = 4) had median costs that were triple those of Robin patients managed conservatively (n = 5) ($87,841 versus $27,864, respectively) as compared with patients without Robin sequence (n = 16) ($15,698). Inpatient services accounted for 85 to 95 percent of all costs, which were driven by the operating room, intensive care unit, and inpatient ward. More detailed analysis of each cost driver is reported. CONCLUSIONS: The cost improvement map provides a counterpart to the quality improvement map to illustrate how costs may be incorporated into value improvement efforts for complex, multidisciplinary conditions. The transparency and level of detail provided by this methodology are critical for internal improvement efforts and offer valuable insight for health care managers and policy makers, whose decisions should be based on accurate, patient-centered data.

A microcosting approach for isolated, unilateral cleft lip care in the first year of life.

BACKGROUND: The concept of value-based health care underlies many new improvement initiatives in U.S. health care. To determine value, accurate measures of both outcomes and costs are essential, which may then be compared for the same provider or system over time or between providers, to foster improvement. Although outcomes measurement has received a great deal of attention since the quality movement began in the United States, costing methodologies are lacking. METHODS: A basic microcosting methodology was used to obtain direct medical costs, including physician compensation, for individuals with isolated, unilateral cleft lip deformity receiving their full course of care from one surgeon. The authors analyzed costs associated with the timeline of care during the first year of life. RESULTS: The median cost for the first year of life was $13,013 (range, $10,426 to $16,115; n = 12). Ninety-one percent of costs were associated with the cleft lip repair, which occurred at a median age of 3.7 months. The majority of these costs stemmed from time in the operating room and the inpatient stay, which accounted for 68 and 19 percent of first-year costs, respectively. CONCLUSIONS: Using a microcosting approach, the authors identified specific cost drivers and outlined a distinct timeline of care for patients with isolated cleft lip in the first year of life. This approach may serve as a template for the cost side of the value equation, for which accurate methodologies are needed. When combined with key outcomes measures, it will be possible to measure and improve value at the patient and provider levels.

Marginal zone B-cell lymphoma of the infratemporal fossa: a rare case and review.

Although it represents the second most common neoplasm of the head and neck, lymphoma is generally not surgically managed and thus may be less familiar to otolaryngologists than other malignancies. However, otolaryngologists are often involved in the initial diagnosis, and should be aware of unusual presentations and the main lymphoma subtypes. We present a case of an extranodal marginal zone B-cell lymphoma, an indolent non-Hodgkin's lymphoma subtype. This type of lymphoma most commonly occurs in the stomach, but was found in the infratemporal fossa. This is the first report of an extranodal marginal zone B-cell lymphoma occurring in this location.

Value-based cleft lip-cleft palate care: a progress report.

BACKGROUND: The health care debate in the United States centers on a concept that is fundamental to any service-based profession yet minimally integrated into the health care community: value creation. Value in health care has been defined as outcome achieved per dollar spent, and focuses on the patient. Many of the new strategies proposed to restructure health care delivery in the United States aim to study and improve both components of this equation. Indeed, it is a near guarantee that providers will soon be responsible for reporting their outcomes and resource use and will be benchmarked by these metrics. In addition, patients have a right to understand the value they receive from their care providers. METHODS: In this report, the authors evaluate the current state of preparedness for the assessment of value in care delivery in the field of cleft lip-cleft palate based on literature review. RESULTS: There has been important progress in the definition and assessment of basic outcomes in cleft lip-cleft palate care, largely through formation of intercenter collaborations. However, many fundamental challenges face the cleft community, especially in North America. Standardization of data collection and outcomes measurement and reporting are particularly lacking. In addition, few data exist regarding the cost of cleft care. CONCLUSIONS: The weight of the evidence reveals that the cleft community is not prepared to assess, and thus improve, the value offered to patients. The authors address key challenges and outline future directions.