A machine learning framework for optimizing obesity care by simulating clinical trajectories and targeted interventions.

OBJECTIVE: This study aimed to determine the important clinical management bottlenecks that contribute to underuse of weight loss surgery (WLS) and assess risk factors for attrition at each of them. METHODS: A multistate conceptual model of progression from primary care to WLS was developed and used to study all adults who were seen by a primary care provider (PCP) and eligible for WLS from 2016 to 2017 at a large institution. Outcomes were progression from each state to each subsequent state in the model: PCP visit, endocrine weight management referral, endocrine weight management visit, WLS referral, WLS visit, and WLS. RESULTS: Beginning with an initial PCP visit, the respective 2-year Kaplan-Meier estimate for each outcome was 35% (n = 2063), 15.6% (n = 930), 6.3% (n = 400), 4.7% (n = 298), and 1.0% (n = 69) among 5876 eligible patients. Individual providers and clinics differed significantly in their referral practices. Female patients, younger patients, those with higher BMI, and those seen by trainees were more likely to progress. A simulated intervention to increase referrals among PCPs would generate about 49 additional WLS procedures over 3 years. CONCLUSIONS: This study discovered novel insights into the specific dynamics underlying low WLS use rates. This methodology permits in silico testing of interventions designed to optimize obesity care prior to implementation.

Uncovering the brain-wide pattern of synaptic input to vasopressin-expressing neurons in the paraventricular nucleus of the hypothalamus.

Arginine vasopressin (AVP) is a neuropeptide critical for the mammalian stress response and social behavior. AVP produced in the hypothalamus regulates water osmolality and vasoconstriction in the body, and in the brain, it regulates social behavior, aggression, and anxiety. However, the circuit mechanisms that link AVP to social behavior, homeostatic function, and disease are not well understood. This study investigates the circuit configurations of AVP-expressing neurons in the rodent hypothalamus and characterizes synaptic input from the entire brain. We targeted the paraventricular nucleus (PVN) using retrograde viral tracing techniques to identify direct afferent synaptic connections made onto AVP-expressing neurons. AVP neurons in the PVN display region-specific anatomical configurations that reflect their unique contributions to homeostatic function, motor behaviors, feeding, and affiliative behavior. The afferent connections identified were similar in both sexes and subsequent molecular investigation of these inputs shows that those local hypothalamic inputs are overwhelmingly nonpeptidergic cells indicating a potential interneuron nexus between hormone cell activation and broader cortical connection. This proposed work reveals new insights into the organization of social behavior circuits in the brain, and how neuropeptides act centrally to modulate social behaviors.

Using i-PARIHS to assess implementation of the Surgical Safety Checklist: an international qualitative study.

BACKGROUND: Strategies selected to implement the WHO's Surgical Safety Checklist (SSC) are key factors in its ability to improve patient safety. Underutilization of implementation frameworks for informing implementation processes hinders our understanding of the checklists' varying effectiveness in different contexts. This study explored the extent to which SSC implementation practices could be assessed through the i-PARIHS framework and examined how it could support development of targeted recommendations to improve SSC implementation in high-income settings. METHODS: This qualitative study utilized interviews with surgical team members and health administrators from five high-income countries to understand the key elements necessary for successful implementation of the SSC. Using thematic analysis, we identified within and across-case themes that were mapped to the i-PARIHS framework constructs. Gaps in current implementation strategies were identified, and the utility of i-PARIHS to guide future efforts was assessed. RESULTS: Fifty-one multi-disciplinary clinicians and health administrators completed interviews. We identified themes that impacted SSC implementation in each of the four i-PARIHS constructs and several that spanned multiple constructs. Within innovation, a disconnect between the clinical outcomes-focused evidence in the literature and interviewees' patient-safety focus on observable results reduced the SSC's perceived relevance. Within recipients, existing surgical team hierarchies impacted checklist engagement, but this could be addressed through a shared leadership model. Within context, organizational priorities resulting in time pressures on surgical teams were at odds with SSC patient safety goals and reduced fidelity. At a health system level, employing surgical team members through the state or health region resulted in significant challenges in enforcing checklist use in private vs public hospitals. Within its facilitation construct, i-PARIHS includes limited definitions of facilitation processes. We identified using multiple interdisciplinary champions; establishing checklist performance feedback mechanisms; and modifying checklist processes, such as implementing a full-team huddle, as facilitators of successful SSC implementation. CONCLUSION: The i-PARIHS framework enabled a comprehensive assessment of current implementation strategies, identifying key gaps and allowed for recommending targeted improvements. i-PARIHS could serve as a guide for planning future SSC implementation efforts, however, further clarification of facilitation processes would improve the framework's utility. TRIAL REGISTRATION: No health care intervention was performed.

Intermittent claudication treatment patterns in the commercially insured non-Medicare population.

OBJECTIVE: Despite published guidelines and data for Medicare patients, it is uncertain how younger patients with intermittent claudication (IC) are treated. Additionally, the degree to which treatment patterns have changed over time with the expansion of endovascular interventions and outpatient centers is unclear. Our goal was to characterize IC treatment patterns in the commercially insured non-Medicare population. METHODS: The IBM MarketScan Commercial Database, which includes more than 8 billion US commercial insurance claims, was queried for patients newly diagnosed with IC from 2007 to 2016. Patient demographics, medication profiles, and open/endovascular interventions were evaluated. Time trends were modeled using simple linear regression and goodness-of-fit was assessed with coefficients of determination (R2). A patient-centered cohort sample and a procedure-focused dataset were analyzed. RESULTS: Among 152,935,013 unique patients in the database, there were 300,590 patients newly diagnosed with IC. The mean insurance coverage was 4.4 years. The median patients age was 58 years and 56% of patients were male. The prevalence of statin use was 48% among patients at the time of IC diagnosis and increased to 52% among patients after one year from diagnosis. Interventions were performed in 14.3%, of whom 20% and 6% underwent two or more and three or more interventions, respectively. The median time from diagnosis to intervention decreased from 230 days in 2008 days to 49 days in 2016 (R2 = 0.98). There were 16,406 inpatient and 102,925 ambulatory interventions for IC over the study period. Among ambulatory interventions, 7.9% were performed in office-based/surgical centers. The proportion of atherectomies performed in the ambulatory setting increased from 9.7% in 2007 to 29% in 2016 (R2 = 0.94). In office-based/surgical centers, 57.6% of interventions for IC used atherectomy in 2016. Atherectomy was used in ambulatory interventions by cardiologists in 22.6%, surgeons in 15.2%, and radiologists in 13.6% of interventions. Inpatient atherectomy rates remained stable over the study period. Open and endovascular tibial interventions were performed in 7.9% and 7.8% of ambulatory and inpatient IC interventions, respectively. Tibial bypasses were performed in 8.2% of all open IC interventions. CONCLUSIONS: There has been shorter time to intervention in the treatment of younger, commercially insured patients with IC, with many receiving multiple interventions. Statin use was low. Ambulatory procedures, especially in office-based/surgical centers, increasingly used atherectomy, which was not observed in inpatient settings.

Development and validation of machine learning models to predict gastrointestinal leak and venous thromboembolism after weight loss surgery: an analysis of the MBSAQIP database.

BACKGROUND: Postoperative gastrointestinal leak and venous thromboembolism (VTE) are devastating complications of bariatric surgery. The performance of currently available predictive models for these complications remains wanting, while machine learning has shown promise to improve on traditional modeling approaches. The purpose of this study was to compare the ability of two machine learning strategies, artificial neural networks (ANNs), and gradient boosting machines (XGBs) to conventional models using logistic regression (LR) in predicting leak and VTE after bariatric surgery. METHODS: ANN, XGB, and LR prediction models for leak and VTE among adults undergoing initial elective weight loss surgery were trained and validated using preoperative data from 2015 to 2017 from Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. Data were randomly split into training, validation, and testing populations. Model performance was measured by the area under the receiver operating characteristic curve (AUC) on the testing data for each model. RESULTS: The study cohort contained 436,807 patients. The incidences of leak and VTE were 0.70% and 0.46%. ANN (AUC 0.75, 95% CI 0.73-0.78) was the best-performing model for predicting leak, followed by XGB (AUC 0.70, 95% CI 0.68-0.72) and then LR (AUC 0.63, 95% CI 0.61-0.65, p < 0.001 for all comparisons). In detecting VTE, ANN, and XGB, LR achieved similar AUCs of 0.65 (95% CI 0.63-0.68), 0.67 (95% CI 0.64-0.70), and 0.64 (95% CI 0.61-0.66), respectively; the performance difference between XGB and LR was statistically significant (p = 0.001). CONCLUSIONS: ANN and XGB outperformed traditional LR in predicting leak. These results suggest that ML has the potential to improve risk stratification for bariatric surgery, especially as techniques to extract more granular data from medical records improve. Further studies investigating the merits of machine learning to improve patient selection and risk management in bariatric surgery are warranted.

Readiness Of Medical Providers In The Military Health System: Overview Of Operational And Policy Considerations.

US military forces have diverse missions, including combat, response to natural disasters, humanitarian assistance, training, and diplomacy. The military's medical forces, composed of clinical providers from the Army, Navy, and Air Force, support these operations-often on a moment's notice. The Military Health System (MHS) must ensure that medical providers are always trained and equipped to deliver care when deployed on missions in often austere environments. As part of its approach to this challenge, the MHS has initiated a data-driven effort to determine required clinical competencies by identifying and measuring the knowledge, skills, and abilities required for care in these environments. These efforts are being implemented while the MHS is undergoing significant organizational change. In this article we describe past and current efforts to maintain a "ready medical force" as well as current challenges and opportunities related to maintaining the readiness of medical providers while the MHS intends to evolve into an integrated health system.

Author Correction: Task-dependent representations of stimulus and choice in mouse parietal cortex.

In the original version of this Article, the Acknowledgements section was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

Task-dependent representations of stimulus and choice in mouse parietal cortex.

The posterior parietal cortex (PPC) has been implicated in perceptual decisions, but whether its role is specific to sensory processing or sensorimotor transformation is not well understood. Here, we trained mice to perform a go/no-go visual discrimination task and imaged the activity of neurons in primary visual cortex (V1) and PPC during engaged behavior and passive viewing. Unlike V1 neurons, which respond robustly to stimuli in both conditions, most PPC neurons respond exclusively during task engagement. To test whether signals in PPC primarily encoded the stimulus or the animal's impending choice, we image the same neurons before and after re-training mice with a reversed sensorimotor contingency. Unlike V1 neurons, most PPC neurons reflect the animal's choice of the new target stimulus after re-training. Mouse PPC is therefore strongly task-dependent, reflects choice more than stimulus, and may play a role in the transformation of visual inputs into motor commands.

Untangling the Neural Circuits for Sexual Behavior.

In this issue, Ishii and colleagues identify an anatomically and genetically defined circuit by which a single compound, exocrine gland-secreted peptide-1 (ESP1), enhances reproductive behavior in female mice.

Distinct roles of visual, parietal, and frontal motor cortices in memory-guided sensorimotor decisions.

Mapping specific sensory features to future motor actions is a crucial capability of mammalian nervous systems. We investigated the role of visual (V1), posterior parietal (PPC), and frontal motor (fMC) cortices for sensorimotor mapping in mice during performance of a memory-guided visual discrimination task. Large-scale calcium imaging revealed that V1, PPC, and fMC neurons exhibited heterogeneous responses spanning all task epochs (stimulus, delay, response). Population analyses demonstrated unique encoding of stimulus identity and behavioral choice information across regions, with V1 encoding stimulus, fMC encoding choice even early in the trial, and PPC multiplexing the two variables. Optogenetic inhibition during behavior revealed that all regions were necessary during the stimulus epoch, but only fMC was required during the delay and response epochs. Stimulus identity can thus be rapidly transformed into behavioral choice, requiring V1, PPC, and fMC during the transformation period, but only fMC for maintaining the choice in memory prior to execution.

Factors associated with psychiatric evacuation among service members deployed to Operation Enduring Freedom and Operation Iraqi Freedom, January 2004 to September 2010.

OBJECTIVES: To calculate the annual rate of psychiatric evacuation of U.S. Service members out of Iraq and Afghanistan and identify risk factors for evacuation. METHODS: Descriptive and regression analyses were performed using deployment records for Service members evacuated from January 2004 through September 2010 with a psychiatric diagnosis, and a 20% random sample of all other deployers (N = 364,047). RESULTS: A total of 5,887 deployers psychiatrically evacuated, 3,951 (67%) of which evacuated on first deployment. The rate increased from 72.9 per 100,000 in 2004 to 196.9 per 100,000 in 2010. Evacuees were overrepresented in both combat and supporting duty assignments. In multivariate analysis, Army active duty had the highest odds of evacuation relative to Army National Guard (adjusted odds ratio [AOR] 0.852, 95% confidence interval [CI] 0.790-0.919), Army Reserve (AOR 0.825, 95% CI 0.740-0.919), and all other components. Accessions in 2005 had the highest risk (AOR 1.923, 95% CI 1.621-2.006) relative to pre-2001 accessions. CONCLUSIONS: Risk for psychiatric evacuation is highest among the Army Active Component. A strong link between multiple deployments or combat-related exposure and psychiatric evacuation is not apparent. Increased risk among post-2001 accessions suggests further review of changes in recruitment, training, and deployment policies and practices.

ß2-Adrenergic receptor agonist ameliorates phenotypes and corrects microRNA-mediated IGF1 deficits in a mouse model of Rett syndrome.

Rett syndrome is a severe childhood onset neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein 2 (MECP2), with known disturbances in catecholamine synthesis. Here, we show that treatment with the ß2-adrenergic receptor agonist clenbuterol increases survival, rescues abnormalities in respiratory function and social recognition, and improves motor coordination in young male Mecp2-null (Mecp2(-/y)) mice. Importantly, we demonstrate that short-term treatment with clenbuterol in older symptomatic female heterozygous (Mecp2(-/+)) mice rescues respiratory, cognitive, and motor coordination deficits, and induces an anxiolytic effect. In addition, we reveal abnormalities in a microRNA-mediated pathway, downstream of brain-derived neurotrophic factor that affects insulin-like growth factor 1 (IGF1) expression in Mecp2(-/y) mice, and show that treatment with clenbuterol restores the observed molecular alterations. Finally, cotreatment with clenbuterol and recombinant human IGF1 results in additional increases in survival in male null mice. Collectively, our data support a role for IGF1 and other growth factor deficits as an underlying mechanism of Rett syndrome and introduce ß2-adrenergic receptor agonists as potential therapeutic agents for the treatment of the disorder.

Functional recovery with recombinant human IGF1 treatment in a mouse model of Rett Syndrome.

Rett Syndrome is a neurodevelopmental disorder that arises from mutations in the X-linked gene methyl-CpG binding protein 2 (MeCP2). MeCP2 has a large number of targets and a wide range of functions, suggesting the hypothesis that functional signaling mechanisms upstream of synaptic and circuit maturation may contribute to our understanding of the disorder and provide insight into potential treatment. Here, we show that insulin-like growth factor-1 (IGF1) levels are reduced in young male Mecp2-null (Mecp2(-/y)) mice, and systemic treatment with recombinant human IGF1 (rhIGF1) improves lifespan, locomotor activity, heart rate, respiration patterns, and social and anxiety behavior. Furthermore, Mecp2-null mice treated with rhIGF1 show increased synaptic and activated signaling pathway proteins, enhanced cortical excitatory synaptic transmission, and restored dendritic spine densities. IGF1 levels are also reduced in older, fully symptomatic heterozygous (Mecp2(-/+)) female mice, and short-term treatment with rhIGF1 in these animals improves respiratory patterns, reduces anxiety levels, and increases exploratory behavior. In addition, rhIGF1 treatment normalizes abnormally prolonged plasticity in visual cortex circuits of adult Mecp2(-/+) female mice. Our results provide characterization of the phenotypic development of Rett Syndrome in a mouse model at the molecular, circuit, and organismal levels and demonstrate a mechanism-based therapeutic role for rhIGF1 in treating Rett Syndrome.