Spectra in low-rank localized layers (SpeLLL) for interpretable time-frequency analysis.

The time-varying frequency characteristics of many biomedical time series contain important scientific information. However, the high-dimensional nature of the time-varying power spectrum as a surface in time and frequency limits its direct use by applied researchers and clinicians for elucidating complex mechanisms. In this article, we introduce a new approach to time-frequency analysis that decomposes the time-varying power spectrum in to orthogonal rank-one layers in time and frequency to provide a parsimonious representation that illustrates relationships between power at different times and frequencies. The approach can be used in fully nonparametric analyses or in semiparametric analyses that account for exogenous information and time-varying covariates. An estimation procedure is formulated within a penalized reduced-rank regression framework that provides estimates of layers that are interpretable as power localized within time blocks and frequency bands. Empirical properties of the procedure are illustrated in simulation studies and its practical use is demonstrated through an analysis of heart rate variability during sleep.

Dynamic changes in the pancreatitis activity scoring system during hospital course in a multicenter, prospective cohort.

BACKGROUND AND AIM: The primary aim was to validate the Pancreatitis Activity Scoring System (PASS) in a multicenter prospectively ascertained acute pancreatitis (AP) cohort. Second, we investigated the association of early PASS trajectories with disease severity and length of hospital stay (LOS). METHODS: Data were prospectively collected through the APPRENTICE consortium (2015-2018). AP severity was categorized based on revised Atlanta classification. Delta PASS (ΔPASS) was calculated by subtracting activity score from baseline value. PASS trajectories were compared between severity subsets. Subsequently, the cohort was subdivided into three LOS subgroups as short (S-LOS): 2-3 days; intermediate (I-LOS): 3-7 days; and long (L-LOS): ≥7 days. The generalized estimating equations model was implemented to compare PASS trajectories. RESULTS: There were 434 subjects analyzed including 322 (74%) mild, 86 (20%) moderately severe, and 26 (6%) severe AP. Severe AP subjects had the highest activity levels and the slowest rate of decline in activity (P = 0.039). Focusing on mild AP, L-LOS subjects (34%) had 28 points per day slower decline; whereas, S-LOS group (13%) showed 34 points per day sharper decrease compared with I-LOS (53%; P < 0.001). We noticed an outlier subset with a median admission-PASS of 466 compared with 140 in the rest. Morphine equivalent dose constituted 80% of the total PASS in the outliers (median morphine equivalent dose score = 392), compared with only 25% in normal-range subjects (score = 33, P value < 0.001). CONCLUSIONS: This study highlighted that PASS can quantify AP activity. Significant differences in PASS trajectories were found both in revised Atlanta classification severity and LOS groups, which can be harnessed in AP monitoring/management (ClincialTrials.gov number, NCT03075618).

Association of Serum Triglyceride Levels with Severity in Acute Pancreatitis: Results from an International, Multicenter Cohort Study.

BACKGROUND: Hypertriglyceridemia (HTG) is considered within the top 5 etiologies in acute pancreatitis (AP), but the association of serum triglyceride (TG) levels with the clinical course of AP remains controversial. OBJECTIVES: This study aims to examine the effect of TG levels on severity of AP. METHODS: Patients were enrolled prospectively through APPRENTICE. High TG levels were defined based on the Endocrine Society Clinical Practice Guidelines. HTG was categorized as mild (serum TG levels 150-199 mg/dL), moderate (200-999 mg/dL), severe (1,000-1,999 mg/dL), and very severe (≥2,000 mg/dL). Severity of AP was based on the revised Atlanta classification criteria. RESULTS: Early TG levels were measured in 764 subjects and found elevated in 342 (120 with mild; 176, moderate; and 46, severe/very severe HTG). Patients with increased TG levels were younger (age ≥60, 16.7 vs. 30.3%), more likely to be male (66.1 vs. 51.2%), with more frequent alcohol use (62.8 vs. 50.7%), and diabetes mellitus (30.2 vs. 12.3%; all p ≤ 0.005). Severe AP (24.9 vs. 10.0%), ICU admission (32.5 vs. 19.7%), and mortality (5.3 vs. 1.7%; all p ≤ 0.005) were more frequently seen in patients with elevated TG levels. Based on multivariable analysis, elevated TG levels were independently associated with severe AP (p < 0.05). CONCLUSION: This large multicenter study confirms that elevated TG levels are associated with severe disease regardless of AP etiology.

Clinical features of hypertriglyceridemia-induced acute pancreatitis in an international, multicenter, prospective cohort (APPRENTICE consortium).

BACKGROUND: The clinical features and outcomes of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) are not well-established. OBJECTIVE: To evaluate the clinical characteristics of HTG-AP in an international, multicenter prospective cohort. METHODS: Data collection was conducted prospectively through APPRENTICE between 2015 and 2018. HTG-AP was defined as serum TG levels >500 mg/dl in the absence of other common etiologies of AP. Three multivariate logistic regression models were performed to assess whether HTG-AP is associated with SIRS positive status, ICU admission and/or moderately-severe/severe AP. RESULTS: 1,478 patients were included in the study; 69 subjects (4.7%) were diagnosed with HTG-AP. HTG-AP patients were more likely to be younger (mean 40 vs 50 years; p < 0.001), male (67% vs 52%; p = 0.018), and with a higher BMI (mean 30.4 vs 27.5 kg/m2; p = 0.0002). HTG-AP subjects reported more frequent active alcohol use (71% vs 49%; p < 0.001), and diabetes mellitus (59% vs 15%; p < 0.001). None of the above risk factors/variables was found to be independently associated with SIRS positive status, ICU admission, or severity in the multivariate logistic regression models. These results were similar when including only the 785 subjects with TG levels measured within 48 h from admission. CONCLUSION: HTG-AP was found to be the 4th most common etiology of AP. HTG-AP patients had distinct baseline characteristics, but their clinical outcomes were similar compared to other etiologies of AP.

Patent foramen ovale repair at the time of double lung transplantation: Necessary or not?

INTRODUCTION: Patient foramen ovale (PFO) is a common and often incidental intraoperative finding during lung transplantation (LTx). We sought to characterize the potential outcomes related to the decision making of whether the PFO was repaired or left unrepaired. METHODS: We retrospectively evaluated bilateral LTx recipients between 2005 and 2015 from our prospective database. Incidence of postoperative stoke, 90-day mortality, and overall survival was compared between the PFO-positive and PFO-negative groups, and secondly compared between repaired PFO (rPFO) and non-repaired PFO (nrPFO) groups. RESULTS: A total of 831 LTx recipients were analyzed: 185 PFO-positive (140 nrPFO, 45 rPFO) and 646 PFO-negative. Study groups were similar with regard to age and comorbidity. The presence of PFO was not associated with a difference in postoperative stroke (P = .89) or 90-day mortality (P = .64). In patients with PFO, intraoperative repair resulted in a lower, but non-significant rate of stroke (0% vs 5%; P = .20) and no difference in mortality (P = .26). As expected, PFO and PFO repair were both associated with a higher incidence of cardiopulmonary bypass utilization, but no difference in pump-related complications. CONCLUSIONS: The protective effect of PFO repair remains unclear. However, it is not associated with an increased incidence of stroke or postoperative mortality following LTx.

Maternal Vascular Lesions in the Placenta Predict Vascular Impairments a Decade After Delivery.

Women with adverse pregnancy outcomes later experience excess hypertension and cardiovascular disease, but how the events are linked is unknown. Examination of the placenta may provide clues to vascular impairments after delivery. Maternal vascular malperfusion lesions (MVMs) were abstracted from clinical reports, validated and characterized using clinical guidelines and severity score. A total of 492 women (170 with MVMs and 322 without MVMs) participated in a study visit 8 to 10 years after delivery to assess blood pressure, cardiometabolic factors, and sublingual microvascular features using sidestream dark field imaging. Covariates included age, race, adverse pregnancy outcomes (preeclampsia, small for gestational age, and preterm birth), and health behaviors. Women with versus without MVM had a distinct sublingual microvascular profile comprised of (1) lower microvascular density (-410 µm/mm2, P=0.015), (2) higher red blood cell filling as a marker of perfusion (2%, P=0.004), and (3) smaller perfused boundary region (-0.07 µm, P=0.025) as a measure of glycocalyx integrity, adjusted for covariates including adverse pregnancy outcomes. Women with MVM also had higher adjusted diastolic blood pressure (+2.6 mm Hg, P=0.021), total and LDL (low-density lipoprotein)-cholesterol (+11.2 mg/dL, P=0.016; +8.7 mg/dL, P=0.031). MVM associations with subsequent cardiovascular measures did not vary by type of adverse pregnancy outcome, except among women with preterm births where blood pressure was higher only among those with MVM. Results were similar when evaluated as MVM severity. A decade after delivery, women with placental vascular lesions had an adverse cardiovascular profile comprised of microvascular rarefaction, higher blood pressure and more atherogenic lipids. Placental histopathology may reveal a woman's early trajectory toward subsequent vascular disease.

The use of pancreatic enzyme replacement therapy in patients with a diagnosis of chronic pancreatitis and pancreatic cancer in the US is infrequent and inconsistent.

BACKGROUND: Patients with chronic pancreatitis or pancreatic cancer commonly develop exocrine pancreatic insufficiency, and may not be adequately treated with pancreatic enzyme replacement therapy (PERT). AIMS: To estimate the frequency of diagnostic testing for exocrine insufficiency, and appropriate use of PERT, in a commercially insured population in the US. METHODS: We utilised a nationally representative administrative database representing 48.67 million individuals in over 80 US healthcare plans to assess testing for and treatment of exocrine insufficiency in patients who received a diagnosis of chronic pancreatitis (n = 37 061) or pancreatic cancer (n = 32 461) from 2001 to 2013. We identified the details of any testing for exocrine insufficiency and PERT use. We defined appropriate PERT use as a dosage of ≥120 000 USP units of lipase daily. Multiple logistic regression was used to identify predictors of appropriate use of PERT. RESULTS: In patients with chronic pancreatitis, 6.5% had any testing for exocrine insufficiency, 30.4% filled a prescription for PERT, and 8.5% were prescribed an adequate dose. In those with pancreatic cancer, 1.9% had testing for exocrine insufficiency, 21.9% filled a prescription for PERT, and 5.5% were prescribed an adequate dose. Number of comorbidities, testing for exocrine insufficiency, pancreatic surgery and duration of enrolment were independent predictors for use and appropriate dosing. CONCLUSIONS: Testing for exocrine insufficiency, and appropriate dosing of PERT in patients with chronic pancreatitis or pancreatic cancer, is infrequent and inconsistent in an insured US population. Efforts are needed to educate medical providers on the best practices for managing exocrine pancreatic insufficiency in these patients.

Access to Lung Transplantation in the United States: The Potential Impact of Access to a High-volume Center.

BACKGROUND: Health disparities plague our healthcare system. Utilizing a novel approach, we sought to assess the effects of geographic disparities on access to lung transplantation (LT) in the United States. METHODS: A total of 13 743 LT adult recipients in the United Network for Organ Sharing Database were identified between May 2005 and December 2014 with a zip code status. Geographic access was defined by global spherical distance from patient zip code centroid to transplant center. Measures analyzed included the association among socioeconomic status (SES), distance to a transplant center, and center switching behavior. RESULTS: Median distance traveled was 62.9 miles. There was an inverse relationship between Diez Roux SES and median distance traveled (90 versus 80.1 versus 60.5 versus 30, P < 0.001). There was no association found between 5-y survival and distance traveled (P = 0.099). However, traveling >158.7 miles was associated with worse survival (hazard ration 1.1; 95% confidence interval, 1.0-1.2; P = 0.005). Over 80% of patients exhibiting center switching were transplanted at a high-volume center than their home institution. Those more likely to switch to a high-volume center were those with an associates/bachelor (P < 0.005) or graduate-level degree (P < 0.05). Recipients with high-volume home institutions had the lowest probability of switching to an alternative center (odds ratio, 0.009; P < 0.001). There was no difference in survival when comparing those transplanted at their home institution versus those who sought transplantation at an alternative institution (55.3% versus 55.0%, P = 0.41). CONCLUSIONS: Although there was no association among SES, distance traveled, and survival, access to LT services varies among populations in the United States.

Routine deep vein thrombosis screening after lung transplantation: Incidence and risk factors.

BACKGROUND: Deep vein thrombosis (DVT) remains a common complication following lung transplantation despite universal routine DVT screening. Moreover, many of the previously reported risk factors are incompletely defined. We sought to explore the influence of DVT screening and to more definitively assess predisposing risk factors. METHODS: A single-institution, retrospective, cohort study of 1141 patients undergoing lung transplantation from January 1, 2005, to December 31, 2014, was performed evaluating for the rate of DVT. Patients were given prophylactic subcutaneous heparin postoperatively. DVT events were noted if they occurred before 90 days after transplant. We compared DVT rates before and after 2008 when universal screening was implemented. We also evaluated the timing of DVT event and location (above the knee vs below the knee). DVTs were treated with standard anticoagulation therapy or an inferior cava filter when patients were unable to tolerate anticoagulation treatment. Univariable and multivariable models were used to identify risk factors for occurrence. A propensity match was performed to match groups across the eras, and a Cox regression was performed to identify differences in 1-year survival trajectory between cohorts. RESULTS: The rates of DVT before and after routine screening were 8.8% (36 DVT out of 412 transplants) and 17.3% (126 out of 729 transplants), respectively. These 2 rates were significantly different (P < .01); moreover, the observed DVT incidence per year was not significantly different across the 6 years after universal DVT screening was implemented (P > .90 for all comparisons). Observed DVT incidence at day 0 and day 14 were 3.8% and 3.8%, respectively, for the cohort before DVT protocols were established. Observed DVT incidence for the cohort after protocols were established at the same time points was 8.7% and 3.7%, respectively. Univariable analysis revealed that significant factors associated with a DVT include hypercholesterolemia (odds ratio [OR], 6.90; 95% confidence interval [CI], 1.82-26.13; P < .01), the number of days in the intensive care unit (OR, 1.03; 95% CI, 1.00-1.01; P < .01), and the length of stay in the hospital (OR, 1.01; 95% CI, 1.01-1.02; P < .01), whereas having quit smoking (vs never smoked) was associated with a decrease in DVT development (OR, 0.50; 95% CI, 0.33-0.75; P < .01). Multivariable analysis revealed 2 significant variables: hypercholesterolemia (OR, 8.13; 95% CI, 1.22-54.37; P = .03) and length of stay (OR, 1.03; 95% CI, 1.01-1.05; P < .01). There was a trend for better 1-year survival in the post-2008 era (Exp[ß], 1.49; P = .09). CONCLUSIONS: The rate of DVT diagnosis significantly increased after universal DVT screening was implemented. Furthermore, those patients undergoing lung transplantation with extended length of stay and hypercholesterolemia were prone to increased rates of DVT. There was a trend toward better 1-year survival in DVT-screened patients, suggesting DVT screening may result in beneficial outcomes.

Etiology and treatment outcomes of persistent postoperative inflammation in primary resident-performed cataract surgeries at a large tertiary care public hospital.

PURPOSE: To determine the risk factors, intraoperative and postoperative complications, therapeutic interventions, and visual outcomes for persistent postoperative inflammation in primary resident-performed cataract surgeries. SETTING: Ben Taub General Hospital, Houston, Texas, USA. DESIGN: Retrospective case series. METHODS: Primary resident-performed cataract surgeries from January 2012 to June 2015 were analyzed for persistent postoperative inflammation, defined as persistent anterior chamber inflammatory reaction after a standard 1-month topical corticosteroid and nonsteroidal antiinflammatory drug (NSAID) drops taper. Preoperative characteristics, operative complications, therapeutic modalities, and duration of therapy were analyzed. The primary outcome measures were duration of corticosteroid and NSAID therapy, treatment modalities, and postoperative visual outcomes at the 1-month postoperative visit. RESULTS: The study assessed 1290 primary resident-performed cataract surgeries. Persistent postoperative inflammation occurred in 82 eyes (6.6%). The presumed etiology was classified as idiopathic persistent postoperative inflammation, nonadherence to topical therapy, and complicated cataract surgery. Patients with persistent postoperative inflammation were more likely of African American descent, had hypertension, or used aspirin, anticoagulants, or prostaglandins (P = .019, P = .027, P = .028, P = .020, respectively). The complicated cataract subgroup required a longer duration of therapy (P = .021) and was the only subgroup to require injections or systemic corticosteroids. There was no significant difference in postoperative corrected distance visual acuity (CDVA) when comparing patients with persistent postoperative inflammation with those without inflammation or between the subgroups. CONCLUSIONS: The idiopathic and nonadherent subgroups were successfully treated with topical antiinflammatory therapy; the complicated subgroup required longer duration and multiple modalities of treatment. Visual outcomes were comparable to the general cataract population with no differences in postoperative CDVA.

Outcomes and complication rates of primary resident-performed cataract surgeries at a large tertiary-care county hospital.

PURPOSE: To identify the preoperative risk factors, intraoperative events, and postoperative complications increasing the risk for poor visual outcomes in resident-performed cataract surgeries at a tertiary-care county hospital. SETTING: Ben Taub General Hospital, Houston, Texas, USA. DESIGN: Retrospective case series. METHODS: Resident-performed cataract surgeries were analyzed for risk factors, comorbidities, and intraoperative and postoperative complications. The main outcome measures were preoperative and postoperative uncorrected distance visual acuity and corrected distance visual acuity (CDVA), which were correlated with preoperative demographics, intraoperative and postoperative events, and resident training level. The data were subdivided into cases without events and cases with events to determine which complications led to poor visual outcomes. RESULTS: The study analyzed 1290 resident-performed cataract surgeries. The mean visual acuity improved significantly after surgery in all patients (P < .001), with 80.5% of patients without complications and 70.7% with complications attaining a CDVA of 20/40 or better (P < .002). Poor visual outcomes were associated with α-antagonist use (P = .043) and pseudoexfoliation syndrome (P = .001). The most common intraoperative complications were vitreous loss (6.7%) and posterior capsule tear (7.0%). The mean postoperative visual acuity did not vary by trainee year, and the rate of dropped nucleus during surgery declined as residents progressed in training (P < .05). All other complication rates were similar between levels of training. CONCLUSION: Despite more complicated cataracts and advanced comorbidities, primary resident-performed cataract surgery in a tertiary-care county hospital system achieved visual outcomes and complication rates similar to those found in other training hospitals.

Coarse-graining intermittent intracellular transport: Two- and three-dimensional models.

Viruses and other cellular cargo that lack locomotion must rely on diffusion and cellular transport systems to navigate through a biological cell. Indeed, advances in single particle tracking have revealed that viral motion alternates between (a) diffusion in the cytoplasm and (b) active transport along microtubules. This intermittency makes quantitative analysis of trajectories difficult. Therefore, the purpose of this paper is to construct mathematical methods to approximate intermittent dynamics by effective stochastic differential equations. The coarse-graining method that we develop is more accurate than existing techniques and applicable to a wide range of intermittent transport models. In particular, we apply our method to two- and three-dimensional cell geometries (disk, sphere, and cylinder) and demonstrate its accuracy. In addition to these specific applications, we also explain our method in full generality for use on future intermittent models.