Publications by authors named "Feng-Chang Lin"

134 Publications

Musculoskeletal Health Literacy is Associated With Outcome and Satisfaction of Total Knee Arthroplasty.

J Arthroplasty 2021 Mar 6. Epub 2021 Mar 6.

Department of Orthopaedics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Background: The purpose of this study was to investigate if there is an association between musculoskeletal health literacy with outcome and satisfaction after total knee arthroplasty (TKA).

Methods: A cross-sectional study was performed at our tertiary center to include patients between one and six years postoperatively after primary TKA. Patients were provided a survey including basic demographics, validated musculoskeletal health literacy scale (Literacy in Musculoskeletal Problems), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and TKA satisfaction (whether they would choose to undergo the same operation again). Patients were categorized as either low or normal health literacy based on number of questions (cutoff 6 out of 9) answered correctly on the Literacy in Musculoskeletal Problems. Statistical analysis included multivariate regression with significance at P < .05.

Results: Four hundred fifty-three individuals fully completed the survey of eligible participants. Two hundred ninety-six individuals (65.3%) had normal health literacy, and one hundred fifty-seven individuals (34.7%) had low health literacy. Average WOMAC (/96) was 18.0 ± 19.7 in the low and 12.1 ± 15.4 in the normal health literacy groups. Patients with low health literacy had significantly higher WOMAC (worse function) than those with normal health literacy (P = .001). Patients with normal musculoskeletal health literacy were significantly more likely to undergo the same operation again (P = .01, odds ratio 2.163).

Conclusion: This study shows that patients with low musculoskeletal health literacy have worse outcome scores and are less likely to be satisfied with their TKA. By identifying these patients preoperatively, emphasis can be placed on enhancing procedure expectations and understanding to improve outcome measures and overall satisfaction.
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http://dx.doi.org/10.1016/j.arth.2021.02.075DOI Listing
March 2021

Roles of autophagy in orthodontic tooth movement.

Am J Orthod Dentofacial Orthop 2021 Mar 23. Epub 2021 Mar 23.

Department of Orthodontics, School of Dentistry, University of North Carolina, Chapel Hill, Nc. Electronic address:

Introduction: Orthodontic tooth movement (OTM) relies on efficient remodeling of alveolar bone. While a well-controlled inflammatory response is essential during OTM, the mechanism regulating inflammation is unknown. Autophagy, a conserved catabolic pathway, has been shown to protect cells from excess inflammation in disease states. We hypothesize that autophagy plays a role in regulating inflammation during OTM.

Methods: A split-mouth design was used to force load molars in adult male mice, carrying a GFP-LC3 transgene for in vivo detection of autophagy. Confocal microscopy, Western blot, and quantitative polymerase chain reaction analyses were used to evaluate autophagy activation in tissues of loaded and control molars at time points after force application. Rapamycin, a Food and Drug Administration-approved immunosuppressant, was injected to evaluate induction of autophagy.

Results: Autophagy activity increases shortly after loading, primarily on the compression side of the tooth, and is closely associated with inflammatory cytokine expression and osteoclast recruitment. Daily administration of rapamycin, an autophagy activator, led to reduced tooth movement and osteoclast recruitment, suggesting that autophagy downregulates the inflammatory response and bone turnover during OTM.

Conclusions: This is the first demonstration that shows that autophagy is induced by orthodontic loading and plays a role during OTM, likely via negative regulation of inflammatory response and bone turnover. Exploring roles of autophagy in OTM holds great promise, as aberrant autophagy is associated with periodontal disease and its related systemic inflammatory disorders.
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http://dx.doi.org/10.1016/j.ajodo.2020.01.027DOI Listing
March 2021

High household transmission of SARS-CoV-2 in the United States: living density, viral load, and disproportionate impact on communities of color.

medRxiv 2021 Mar 12. Epub 2021 Mar 12.

Background: Few prospective studies of SARS-CoV-2 transmission within households have been reported from the United States, where COVID-19 cases are the highest in the world and the pandemic has had disproportionate impact on communities of color.

Methods And Findings: This is a prospective observational study. Between April-October 2020, the UNC CO-HOST study enrolled 102 COVID-positive persons and 213 of their household members across the Piedmont region of North Carolina, including 45% who identified as Hispanic/Latinx or non-white. Households were enrolled a median of 6 days from onset of symptoms in the index case. Secondary cases within the household were detected either by PCR of a nasopharyngeal (NP) swab on study day 1 and weekly nasal swabs (days 7, 14, 21) thereafter, or based on seroconversion by day 28. After excluding household contacts exposed at the same time as the index case, the secondary attack rate (SAR) among susceptible household contacts was 60% (106/176, 95% CI 53%-67%). The majority of secondary cases were already infected at study enrollment (73/106), while 33 were observed during study follow-up. Despite the potential for continuous exposure and sequential transmission over time, 93% (84/90, 95% CI 86%-97%) of PCR-positive secondary cases were detected within 14 days of symptom onset in the index case, while 83% were detected within 10 days. Index cases with high NP viral load (>10^6 viral copies/ul) at enrollment were more likely to transmit virus to household contacts during the study (OR 4.9, 95% CI 1.3-18 p=0.02). Furthermore, NP viral load was correlated within families (ICC=0.44, 95% CI 0.26-0.60), meaning persons in the same household were more likely to have similar viral loads, suggesting an inoculum effect. High household living density was associated with a higher risk of secondary household transmission (OR 5.8, 95% CI 1.3-55) for households with >3 persons occupying <6 rooms (SAR=91%, 95% CI 71-98%). Index cases who self-identified as Hispanic/Latinx or non-white were more likely to experience a high living density and transmit virus to a household member, translating into an SAR in minority households of 70%, versus 52% in white households (p=0.05).

Conclusions: SARS-CoV-2 transmits early and often among household members. Risk for spread and subsequent disease is elevated in high-inoculum households with limited living space. Very high infection rates due to household crowding likely contribute to the increased incidence of SARS-CoV-2 infection and morbidity observed among racial and ethnic minorities in the US. Quarantine for 14 days from symptom onset of the first case in the household is appropriate to prevent onward transmission from the household. Ultimately, primary prevention through equitable distribution of effective vaccines is of paramount importance.

Authors Summary: Understanding the secondary attack rate and the timing of transmission of SARS-CoV-2 within households is important to determine the role of household transmission in the larger pandemic and to guide public health policies about quarantine.Prospective studies looking at the determinants of household transmission are sparse, particularly studies including substantial racial and ethnic minorities in the United States and studies with adequate follow-up to detect sequential transmission events.Identifying individuals at high risk of transmitting and acquiring SARS-CoV-2 will inform strategies for reducing transmission in the household, or reducing disease in those exposed. Between April-November 2020, the UNC CO-HOST study enrolled 102 households across the Piedmont region of North Carolina, including 45% with an index case who identified as racial or ethnic minorities.Overall secondary attack rate was 60% with two-thirds of cases already infected at study enrollment.Despite the potential for sequential transmission in the household, the majority of secondary cases were detected within 10 days of symptom onset of the index case.Viral loads were correlated within families, suggesting an inoculum effect.High viral load in the index case was associated with a greater likelihood of household transmission.Spouses/partners of the COVID-positive index case and household members with obesity were at higher risk of becoming infected.High household living density contributed to an increased risk of household transmission.Racial/ethnic minorities had an increased risk of acquiring SARS-CoV-2 in their households in comparison to members of the majority (white) racial group. Household transmission often occurs quickly after a household member is infected.High viral load increases the risk of transmission.High viral load cases cluster within households - suggesting high viral inoculum in the index case may put the whole household at risk for more severe disease.Increased household density may promote transmission within racial and ethnic minority households.Early at-home point-of-care testing, and ultimately vaccination, is necessary to effectively decrease household transmission.
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http://dx.doi.org/10.1101/2021.03.10.21253173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987030PMC
March 2021

3D morphometric quantification of maxillae and defects for patients with unilateral cleft palate via deep learning-based CBCT image auto-segmentation.

Orthod Craniofac Res 2021 Mar 12. Epub 2021 Mar 12.

Division of Orthodontics, College of Dentistry, The Ohio State University, Columbus, OH, USA.

Objective: This study aimed to quantify the 3D asymmetry of the maxilla in patients with unilateral cleft lip and palate (UCP) and investigate the defect factors responsible for the variability of the maxilla on the cleft side using a deep-learning-based CBCT image segmentation protocol.

Setting And Sample Population: Cone beam computed tomography (CBCT) images of 60 patients with UCP were acquired. The samples in this study consisted of 39 males and 21 females, with a mean age of 11.52 years (SD = 3.27 years; range of 8-18 years).

Materials And Methods: The deep-learning-based protocol was used to segment the maxilla and defect initially, followed by manual refinement. Paired t-tests were performed to characterize the maxillary asymmetry. A multiple linear regression was carried out to investigate the relationship between the defect parameters and those of the cleft side of the maxilla.

Results: The cleft side of the maxilla demonstrated a significant decrease in maxillary volume and length as well as alveolar length, anterior width, posterior width, anterior height and posterior height. A significant increase in maxillary anterior width was demonstrated on the cleft side of the maxilla. There was a close relationship between the defect parameters and those of the cleft side of the maxilla.

Conclusions: Based on the 3D volumetric segmentations, significant hypoplasia of the maxilla on the cleft side existed in the pyriform aperture and alveolar crest area near the defect. The defect structures appeared to contribute to the variability of the maxilla on the cleft side.
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http://dx.doi.org/10.1111/ocr.12482DOI Listing
March 2021

Inverse probability weighted estimation for recurrent events data with missing category.

Stat Med 2021 Mar 4. Epub 2021 Mar 4.

Pediatric Pulmonology, University of North Carolina, Chapel Hill, North Carolina, USA.

Modeling recurrent event data with multiple event types has drawn interest in recent biomedical studies due to its flexibility for understanding different risk factors for multiple recurrent event processes. However, in such data type, missing event type appears frequently because of various reasons such as recording ignorance or resource limitation. In this study, we aim to propose an inverse probability weighted estimation that is commonly used in the missing data literature to correct possibly biased estimation by a complete-case analysis. This approach is not limited to a specific form of the recurrent event model. We derive the large sample theory in a general form. We demonstrate that our approach can be applied to either multiplicative or additive rates model with practical sample size via comprehensive simulations. Nonmucoid and mucoid Pseudomonas aeruginosa infections of 14 888 patients in 2016 Cystic Fibrosis Foundation Patient Registry data are analyzed to show that, without including 12% events with missing event type in the analysis, several factors may be misidentified as risk factors for the nonmucoid type of infections.
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http://dx.doi.org/10.1002/sim.8927DOI Listing
March 2021

Practical strategies for SARS-CoV-2 RT-PCR testing in resource-constrained settings.

medRxiv 2021 Feb 25. Epub 2021 Feb 25.

Alternatives to nasopharyngeal sampling are needed to increase capacity for SARS-CoV-2 testing. Among 275 participants, we piloted the collection of nasal mid-turbinate swabs amenable to self-testing, including polyester flocked swabs as well as 3D printed plastic lattice swabs, placed into viral transport media or an RNA stabilization agent. Flocked nasal swabs identified 104/121 individuals who were PCR-positive for SARS-CoV-2 by nasopharyngeal sampling (sensitivity 87%, 95% CI 79-92%), mostly missing those with low viral load (<10 viral copies/uL). 3D-printed nasal swabs showed similar sensitivity. When nasal swabs were placed directly into RNA preservative, the mean 1.4 log decrease in viral copies/uL compared to nasopharyngeal samples was reduced to <1 log, even when samples were left at room temperature for up to 7 days. We also evaluated pooling strategies that involved pooling specimens in the lab versus pooling swabs at the point of collection, finding both successfully detected samples >10 viral copies/uL.
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http://dx.doi.org/10.1101/2021.02.18.21251999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924294PMC
February 2021

Pre-Post Evaluation of Collaborative Oncology Palliative Care for Patients With Stage IV Cancer.

J Pain Symptom Manage 2021 Feb 27. Epub 2021 Feb 27.

Division of General Internal Medicine, University of Pittsburgh School of Medicine (N.C.E.), Pittsburgh, Pennsylvania, USA.

Context: The Collaborative Care Model improves care processes and outcomes but has never been tested for palliative care.

Objectives: To develop and evaluate a model of collaborative oncology palliative care for Stage IV cancer.

Methods: We conducted a pre-post evaluation of Collaborative Oncology Palliative Care (CO-Pal), enrolling patients with Stage IV lung, breast or genitourinary cancers and acute illness hospitalization. CO-Pal has 4 components: 1) oncologist communication skills training; 2) patient tracking; 3) palliative care needs assessment; and 4) care coordination stratified by high vs. low palliative care need. Health record reviews from hospital admission through 60 days provided data on outcomes - goals-of-care discussions (primary outcome), advance care planning, symptom treatment, specialty palliative care and hospice use, and hospital transfers.

Results: We enrolled 256 patients (n = 114 pre and n = 142 post-intervention); 60-day mortality was 32%. Comparing patients pre vs post-intervention, CO-Pal did not increase overall goals-of-care discussions, but did increase advance care planning (48% vs 63%, P = 0.021) and hospice use (19% vs 31%, P = 0.034). CO-Pal did not impact symptom treatment, overall treatment plans, or 60-day hospital transfers. During the intervention phase, high-need vs low-need patients had more goals-of-care discussions (60% vs. 15%, P < 0.001) and more use of specialty palliative care (64% vs 22%, P < 0.001) and hospice (44% vs 16%, P < 0.001).

Conclusion: Collaborative oncology palliative care is efficient and feasible. While it did not increase overall goals-of-care discussions, it was effective to increase overall advance care planning and hospice use for patients with Stage IV cancer.
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http://dx.doi.org/10.1016/j.jpainsymman.2021.02.032DOI Listing
February 2021

Missed Opportunities for Prevention of Sudden Death.

N C Med J 2021 Mar-Apr;82(2):95-99

Professor of medicine, University of North Carolina Division of Cardiology, Chapel Hill, North Carolina.

Background: We assessed patterns of health care utilization to further characterize chronic comorbidities prior to sudden death.

Method: From March 1, 2013, through February 28, 2015, all out-of-hospital deaths aged 18-64 reported by emergency medical services in Wake County, North Carolina, were screened to adjudicate 399 sudden death victims. Retrospective analysis of clinical records on victims determined health care utilization. Health care utilization frequency was assessed by latent growth curve analysis.

Results: Medical records were available for 264 victims (aged 53.5 ± 9.2) who were predominantly male (65%) and white (64%). Of these, 210 (80%) victims had at least one visit within two years of death and 73 (28%) had a visit within one month of death. Over the two years prior to death, there was an increasing frequency of doctor visits ( < .001). Victims averaged 3.7 ± 4.6 yearly visits and were categorized into low (0.4 visits/year), medium (3.3 visits/year), and high (11.4 visits/year) tiers of visit frequency. The high visit tier had a greater prevalence of coronary artery disease (38%), hypertension (80%), diabetes (58%), depression (74%), anxiety (64%), and substance misuse (46%) ( < .001).

Limitations: Those who were non-free-living, minors, without formal medical records, and adults aged 65 and older were excluded from the analysis.

Conclusions: A majority of sudden death victims utilized health care within two years prior to death and had comorbidities that may have contributed to their unexpected death. The increasing frequency of visits prior to death provided an opportunity for health care providers to address potential victims' chronic medical conditions to potentially prevent death.
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http://dx.doi.org/10.18043/ncm.82.2.95DOI Listing
March 2021

High Prevalence of Diabetes Mellitus and Mental Illness Among Victims of Sudden Death.

South Med J 2021 02;114(2):86-91

From the Department of Internal Medicine, Yale-New Haven Medical Center, Waterbury, Connecticut, the Department of Medicine, Division of Endocrinology, Maine Medical Partners Endocrinology & Diabetes Center, Scarborough, Maine, the Department of Medicine, Division of Endocrinology, University of North Carolina, Chapel Hill, the Department of Medicine, Division of Cardiology, University of North Carolina, Chapel Hill, the Division of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, and the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill.

Objectives: Diabetes mellitus (DM) increases the risk of cardiovascular disease and is associated with sudden death. Mental illness among individuals with DM may confound medical care. This study assessed the association of mental illness with DM and poorly controlled DM in sudden death victims.

Methods: We screened out-of-hospital deaths ages 18 to 64 years in Wake County, North Carolina from 2013 to 2015 to adjudicate sudden deaths. We abstracted demographics and clinical characteristics from health records. Mental illness included anxiety, schizophrenia, bipolar disorder, or depression. Poorly controlled DM was defined as a hemoglobin A1c >8 or taking ≥3 medications for glycemic control. Logistic regression assessed the association between DM and mental illness.

Results: Among victims with available records, 109 (29.4%) had DM. Of those, 62 (56.9%) had mental illness. Mental illness was present in 53.42% and 63.89% of victims with mild and poorly controlled DM, respectively. Mental illness was associated with DM (adjusted odds ratio 2.46, 95% confidence interval 1.57-3.91). Victims with poorly controlled DM were more likely to have mental illness (adjusted odds ratio 2.66, 95% confidence interval 1.14-6.18).

Conclusions: DM is a common comorbid condition in sudden death victims. Among victims, mental illness is associated with the control of DM. Early management of comorbid mental illnesses may improve the care of patients with DM and reduce the incidence of sudden death.
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http://dx.doi.org/10.14423/SMJ.0000000000001213DOI Listing
February 2021

Systematic Isolation of Key Parameters for Estimating Skeletal Maturity on Knee Radiographs.

J Bone Joint Surg Am 2021 Jan 28. Epub 2021 Jan 28.

Department of Orthopaedics, Case Western Reserve University School of Medicine, Cleveland, Ohio.

Background: The ability to estimate skeletal maturity using a knee radiograph would be useful in anterior cruciate ligament (ACL) injuries and limb-length discrepancy in immature patients. Currently, a quick, accurate, and reproducible method is lacking.

Methods: Serial knee radiographs made 3 years before to 2 years following the chronologic age associated with 90% of final height (an enhanced skeletal maturity gold standard compared with peak height velocity) were analyzed in 78 children. The Pyle and Hoerr (PH) knee method was simplified by developing discrete stages for the distal part of the femur, the proximal part of the tibia, the proximal part of the fibula, and the patella. The Roche-Wainer-Thissen (RWT) knee method was simplified from the 36 original parameters to 14 parameters by removing parameters that were poorly defined, were not relevant to the peripubertal age range, were poorly correlated with 90% final height, or were poorly reliable on a 20-radiograph pilot analysis. We also compared the recently described central peak value (CPV) of the distal part of the femur. The Greulich and Pyle (GP) left-hand bone age was included for comparison.

Results: In this study, 326 left knee radiographs from 41 girls (age range, 7 to 15 years) and 37 boys (age range, 9 to 17 years) were included. Stepwise linear regression showed higher correlation in predicting years from 90% final height using the modified RWT and demographic characteristics (R2 = 0.921) compared with demographic characteristics alone (R2 = 0.840), CPV and demographic characteristics (R2 = 0.866), GP and demographic characteristics (R2 = 0.899), and PH and demographic characteristics (R2 = 0.902). Seven parameters were excluded from the RWT and demographic characteristics model using stepwise linear regression and generalized estimating equations analysis, leaving 7 parameters (2 femoral, 4 tibial, and 1 fibular) in the final model. Compared with RWT and demographic characteristics (R2 = 0.921), there were minimal incremental increases by adding CPV (R2 = 0.921), GP (R2 = 0.925), or PH (R2 = 0.931).

Conclusions: This large analysis of knee skeletal maturity systems isolated 7 discrete radiographic knee parameters that theoretically outperform the GP bone age in estimating skeletal maturity.

Clinical Relevance: We present a modified knee skeletal maturity system that can potentially preclude the need for additional imaging of the hand and wrist in reliably estimating skeletal maturity.
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http://dx.doi.org/10.2106/JBJS.20.00404DOI Listing
January 2021

Variations in blood pressure control by medical comorbidities prior to sudden death.

J Clin Hypertens (Greenwich) 2021 Feb 2;23(2):389-391. Epub 2021 Jan 2.

Division of Cardiology, University of North Carolina, Chapel Hill, NC, USA.

Patients with hypertension have increased risk of sudden death, but the impact of blood pressure control in sudden death is not clear. To better understand potential opportunities to prevent sudden, we assessed blood pressure control, comorbidities, and the number of recent medical encounters among all-cause sudden death victims. Less than 40% of sudden death victims with hypertension had controlled blood pressure prior to death. Furthermore, increased frequency of medical visits and number of comorbidities were associated with better blood pressure control Strategies to address clinical inertia in hypertension treatment particularly for patients with fewer comorbidities may attenuate the risk of sudden death.
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http://dx.doi.org/10.1111/jch.14164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956134PMC
February 2021

Mortality Risk for Patients With Stage IV Cancer and Acute Illness Hospitalization.

J Pain Symptom Manage 2021 Apr 20;61(4):797-804. Epub 2020 Oct 20.

Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Context: Cancer prognosis data often come from clinical trials which exclude patients with acute illness.

Objectives: For patients with Stage IV cancer and acute illness hospitalization to 1) describe predictors of 60-day mortality and 2) compare documented decision-making for survivors and decedents.

Methods: Investigators studied a consecutive prospective cohort of patients with Stage IV cancer and acute illness hospitalization. Structured health record and obituary reviews provided data on 60-day mortality (outcome), demographics, health status, and treatment; logistic regression models identified mortality predictors.

Results: Four hundred ninety-two patients with Stage IV cancer and acute illness hospitalization had median age of 60.2 (51% female, 38% minority race/ethnicity); 156 (32%) died within 60 days, and median survival for decedents was 28 days. Nutritional insufficiency (odds rato [OR] 1.83), serum albumin (OR 2.15 per 1.0 g/dL), and hospital days (OR 1.04) were associated with mortality; age, gender, race, cancer, and acute illness type were not predictive. On admission, 79% of patients had orders indicating Full Code. During 60-day follow-up, 42% of patients discussed goals of care. Documented goals of care discussions were more common for decedents than survivors (70% vs. 28%, P < 0.001), as were orders for do not resuscitate/do not intubate (68% vs. 24%, P < 0.001), stopping cancer-directed therapy (29% vs. 10%, P < 0.001), specialty Palliative Care (79% vs. 44%, P < 0.001), and Hospice (68% vs. 14%, P < 0.001).

Conclusion: Acute illness hospitalization is a sentinel event in Stage IV cancer. Short-term mortality is high; nutritional decline increases risk. For patients with Stage IV cancer, acute illness hospitalization should trigger goals of care discussions.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.10.015DOI Listing
April 2021

Outcomes of pediatric liver transplant are unaffected by the time or day of surgery.

Pediatr Transplant 2020 12 18;24(8):e13826. Epub 2020 Oct 18.

Department of Biostatistics, Gilling's School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Background: In adults, the time of day for LT does not affect post-transplant outcomes. Whether this is true or not in children is unknown. In this study, we aimed to evaluate if weekend and weeknight liver transplants are associated with worse patient and graft survival in children.

Methods: We interrogated the UNOS database for outcomes of pediatric liver transplants that occurred between 1988 and 2018. We excluded liver transplants in patients >17 years as well as all multiple organ transplants. We compared weeknight and weekday, as well as weekend transplant operations. We used Cox proportional hazard ratios to determine patient and graft survival by 7, 30, 90, and 365 days post-transplant after controlling for confounding factors.

Results: In total, 12,610 pediatric liver transplants were included in the analysis. A total of 4590 transplants occurred during weekdays, 3671 transplants occurred during weeknights, and 4349 occurred during weekends. After controlling for confounding variables, 1-year patient survival was not associated with worse outcomes if the transplant occurred on the weeknight (HR 0.94, 95%CI 0.74-1.21) or weekend (HR 0.95, 95%CI 0.75-1.20) compared to the weekday. One-year graft survival was also not associated with worse outcomes if the transplant occurred on the weeknight (HR 0.91, 95%CI 0.76-1.09) or weekend (HR 0.91, 95%CI 0.77-1.09) compared to the weekday.

Conclusion: Weekday, weeknight, and weekend procedures resulted in similar 1-year survival rates. Pediatric patient and graft survival outcomes are not affected by the time or day of surgery.
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http://dx.doi.org/10.1111/petr.13826DOI Listing
December 2020

Association between lone star tick bites and increased alpha-gal sensitization: evidence from a prospective cohort of outdoor workers.

Parasit Vectors 2020 Sep 14;13(1):470. Epub 2020 Sep 14.

Department of Medicine, Thurston Research Center, Division of Allergy, Immunology and Rheumatology, Chapel Hill, North Carolina, USA.

Background: Alpha-gal is an oligosaccharide implicated in delayed anaphylaxis following red meat consumption. Exposure to tick bites has been correlated with development of an allergic response to alpha-gal. However, evidence prospectively linking exposure to a single tick species and an immune response to alpha-gal is lacking.

Methods: We used serum samples from a prior study cohort of outdoor workers in North Carolina, USA, with high exposure to the lone star tick, Amblyomma americanum, to prospectively evaluate the relationship between tick bites and anti-alpha-gal IgE antibodies.

Results: Individuals who reported exposure to one or more tick bites were significantly more likely to have a positive change in anti-alpha-gal IgE compared to individuals with no reported tick bites. This relationship was not dependent on time. A trend toward increasing number of tick bites and increased anti-alpha-gal IgE levels was observed but not statistically significant.

Conclusion: To our knowledge, this is the first study to prospectively link documented exposure to A. americanum bites and increased sensitization to alpha-gal in a cohort of outdoor workers. Our results support the role of A. americanum as likely agents for eliciting an allergic response to red meat, and highlight the importance of preventing tick bites.
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http://dx.doi.org/10.1186/s13071-020-04343-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490856PMC
September 2020

The Relationship of Travel Distance to Postoperative Follow-up Care on Glaucoma Surgery Outcomes.

J Glaucoma 2020 11;29(11):1056-1064

Departments of Ophthalmology.

PRéCIS:: This study addresses the paucity of literature examining glaucoma patients' distance from clinic on postoperative follow-up outcomes. Greater distance from clinic was associated with higher likelihood of loss to follow-up and missed appointments.

Purpose: To investigate the relationship of patient travel distance and interstate access to glaucoma surgery postoperative follow-up visit attendance.

Methods And Participants: Retrospective longitudinal chart review of all noninstitutionalized adult glaucoma patients with initial trabeculectomies or drainage device implantations between April 4, 2014 and December 31, 2018. Patients were stratified into groups on the basis of straight-line distance from residence to University of North Carolina at Chapel Hill's Kittner Eye Center and distance from residence to interstate access. Corrective procedures, visual acuity, appointment cancellations, no-shows, and insurance data were recorded. Means were compared using 2-tailed Student t-test, Pearson χ, analysis of variance, and multivariate logistical regression determined odds ratios for loss to follow-up.

Results: In total, 199 patients met all inclusion criteria. Six-month postoperatively, patients >50 miles from clinic had greater odds of loss to follow-up compared with patients <25 miles (odds ratios, 3.47; 95% confidence interval, 1.24-4.12; P<0.05). Patients >50 miles from clinic had significantly more missed appointments than patients 25 to 50 miles away, and patients <25 miles away (P=0.008). Patients >20 miles from interstate access had greater loss to follow-up than those <10 miles (t(150)=2.05; P<0.05). Mean distance from clinic was 12.59 miles farther for patients lost to follow-up (t(197)=3.29; P<0.01). Patients with Medicaid coverage had more missed appointments than those with Medicare plans (t(144)=-2.193; P<0.05).

Conclusions: Increased distance from clinic and interstate access are associated with increased missed appointments and loss to follow-up. Glaucoma specialists should consider these factors when choosing surgical interventions requiring frequent postoperative evaluations.
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http://dx.doi.org/10.1097/IJG.0000000000001609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658019PMC
November 2020

Association of Dry Eye Disease With Dyslipidemia and Statin Use.

Am J Ophthalmol 2020 10 12;218:54-58. Epub 2020 May 12.

Department of Ophthalmology, University of Auckland, Auckland, New Zealand.

Purpose: To determine whether an association exists between dry eye disease (DED) and statin use and/or dyslipidemia.

Design: Retrospective, case-control study.

Methods: Setting: University of North Carolina (UNC)-affiliated healthcare facilities.

Study Population: 72,931 patients seen at UNC ophthalmology clinics over a 10-year period.

Main Outcome Measures: Odds ratios (ORs) calculated between DED and a history of low, moderate, or high-intensity statin use; and ORs calculated between DED and abnormal lipid panel values.

Results: Total of 39,336 individuals (53.9% female) were analyzed after exclusion of individuals with confounding risk factors for DED. Of these, 3,399 patients (8.6%) carried a diagnosis of DED. Low-, moderate-, and high-intensity statin regimens were used by 751 subjects (1.9%), 2,655 subjects (6.8%), and 1,036 subjects (2.6%). Lipid abnormalities were identified as total cholesterol >200 mg/dL, 4,558 subjects (11.6%); high-density lipoprotein (HDL) <40 mg/dL, 2,078 subjects (5.3%); low-density lipoprotein (LDL) >130 mg/dL, 2,756 subjects (7.0%); and triglycerides (TGs) >150 mg/dL, 2,881 subjects (7.3%). The odds ratios (OR) of carrying a diagnosis of DED given the presence of low-, moderate-, and high-intensity statin use were 1.39 (95% confidence interval [CI]: 1.13-1.72); OR 1.47 (95% CI: 1.30-1.65), and OR 1.46 (95% CI: 1.21-1.75), respectively. The OR of carrying a diagnosis of DED given the presence of total cholesterol >200 mg/dL, HDL <40 mg/dL, LDL >130 mg/dL, and TGs >150 mg/dL were 1.66 (95% CI: 1.52-1.82), 1.45 (95% CI: 1.26-1.67), 1.55 (95% CI: 1.39-1.74), and 1.43 (95% CI: 1.27-1.61), respectively.

Conclusions: A history of statin use or dyslipidemia is associated with an increased odds of having a DED diagnosis. Further studies are needed to determine whether statin use and/or dyslipidemia increases the risk of DED.
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http://dx.doi.org/10.1016/j.ajo.2020.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034500PMC
October 2020

Trends in open shoulder surgery among early career orthopedic surgeons: who is doing what?

J Shoulder Elbow Surg 2020 Jul 24;29(7):e269-e278. Epub 2020 Apr 24.

Department of Orthopaedics, University of North Carolina, Chapel Hill, NC, USA.

Background: The incidence of various open shoulder procedures has changed over time. In addition, various fellowships provide overlapping training in open shoulder surgery. There is a lack of information regarding the relationship between surgeon training and open shoulder procedure type and incidence in early career orthopedic surgeons.

Methods: The American Board of Orthopaedic Surgery Part-II database was queried from 2002 to 2016 for reported open shoulder procedures. The procedures were categorized as follows: arthroplasty, revision arthroplasty, open instability, trauma, and open rotator cuff. We evaluated procedure trends as well as their relationship to surgeon fellowship categorized by Sports, Shoulder/Elbow, Hand, Trauma, and "Other" fellowship as well as no fellowship training. We additionally evaluated complication data as it related to procedure, fellowship category, and volume.

Results: Over the 2002-2016 study period, there were increasing cases of arthroplasty, revision arthroplasty, and trauma (P < .001). There were decreasing cases in open instability and open rotator cuff (P < .001). Those with Sports training reported the largest overall share of open shoulder cases. Those with Shoulder/Elbow training reported an increasing overall share of arthroplasty cases and higher per candidate case numbers. The percentage of early career orthopedic surgeons reporting 5 or more arthroplasty cases was highest among Shoulder/Elbow candidates (P < .001). Across all procedures, those without fellowship training were least likely to report a complication (odds ratio [OR], 0.76; 95% confidence interval, 0.67-0.86; P < .001). Shoulder/Elbow candidates were least likely to report an arthroplasty complication (OR, 0.84, P = .03) as was any surgeon reporting 5 or more arthroplasty cases (OR, 0.81; 95% confidence interval, 0.70-0.94; P = .006).

Conclusion: The type and incidence of open shoulder surgery procedures continues to change. Among early career surgeons, those with more specific shoulder training are now performing the majority of arthroplasty-related procedures, and early career volume inversely correlates with complications.
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http://dx.doi.org/10.1016/j.jse.2020.01.075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305957PMC
July 2020

Protective Effectiveness of Long-Lasting Permethrin Impregnated Clothing Against Tick Bites in an Endemic Lyme Disease Setting: A Randomized Control Trial Among Outdoor Workers.

J Med Entomol 2020 09;57(5):1532-1538

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC.

Tick-borne diseases are a growing threat to public health in the United States, especially among outdoor workers who experience high occupational exposure to ticks. Long-lasting permethrin-impregnated clothing has demonstrated high initial protection against bites from blacklegged ticks, Ixodes scapularis Say (Acari: Ixodidae), in laboratory settings, and sustained protection against bites from the lone star tick, Amblyomma americanum (L.) (Acari: Ixodidae), in field tests. However, long-lasting permethrin impregnation of clothing has not been field tested among outdoor workers who are frequently exposed to blacklegged ticks. We conducted a 2-yr randomized, placebo-controlled, double-blinded trial among 82 outdoor workers in Rhode Island and southern Massachusetts. Participants in the treatment arm wore factory-impregnated permethrin clothing, and the control group wore sham-treated clothing. Outdoor working hours, tick encounters, and bites were recorded weekly to assess protective effectiveness of long-lasting permethrin-impregnated garments. Factory-impregnated clothing significantly reduced tick bites by 65% in the first study year and by 50% in the second year for a 2-yr protective effect of 58%. No significant difference in other tick bite prevention method utilization occurred between treatment and control groups, and no treatment-related adverse outcomes were reported. Factory permethrin impregnation of clothing is safe and effective for the prevention of tick bites among outdoor workers whose primary exposure is to blacklegged ticks in the northeastern United States.
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http://dx.doi.org/10.1093/jme/tjaa061DOI Listing
September 2020

Systematic Review and Meta-Analysis of Cycling and Erectile Dysfunction.

Sex Med Rev 2021 Apr 6;9(2):304-311. Epub 2020 Mar 6.

Department of Urology, University of North Carolina School of Medicine, Chapel Hill, NC, USA; UNC Fertility LLC, Raleigh, NC, USA.

Introduction: Conflicting evidence exists on the relationship between bicycle riding and erectile dysfunction (ED). A major limitation to several prior studies is the lack of a validated measure of ED.

Objective: To assess the relationship between cycling and clinically validated ED based on existing literature.

Methods: We searched several major databases from database inception through 2018 using a variety of search terms relating to "cycling" and "erectile dysfunction." Studies were included if they were written in English, reported original data, compared ED between cyclists and non-cycling controls, and used a validated measure of ED, such as the International Index of Erectile Function or the subset Sexual Health Inventory for Men (SHIM). Age, SHIM score, and comorbidities were extracted for all groups. Primary outcomes for each group were mean SHIM score and presence of ED (SHIM ≤ 21). A generalized linear mixed-effects model was used to fit the collected data for meta-analysis. Main outcome measures were unadjusted odds ratios of ED for cyclists and non-cyclists, mean SHIM score difference between cyclists and noncyclists, and both of these measures adjusted for age and comorbidities.

Results: After a systematic evaluation of 843 studies, 6 studies met our inclusion criteria, encompassing 3,330 cyclists and 1,524 non-cycling controls. When comparing cyclists to non-cyclists in an unadjusted analysis, there were no significant differences in the odds of having ED or mean SHIM score. However, when controlling for age and comorbidities, cyclists had significantly higher odds of having ED (odds ratio: 2.00; 95% confidence interval: 1.57, 2.55).

Conclusions: Limited evidence supports a positive correlation between cycling and ED when adjusting for age and several comorbidities. Heterogeneity among studies suggests that further investigation into certain populations of cyclists that may be more vulnerable to ED may be beneficial. Gan ZS, Ehlers ME, Lin FC, et al. Systematic Review and Meta-Analysis of Cycling and Erectile Dysfunction. Sex Med 2021;9:304-311.
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http://dx.doi.org/10.1016/j.sxmr.2020.01.002DOI Listing
April 2021

Relapse or reinfection: Classification of malaria infection using transition likelihoods.

Biometrics 2020 12 3;76(4):1351-1363. Epub 2020 Mar 3.

Institute of Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina.

In patients with Plasmodium vivax malaria treated with effective blood-stage therapy, the recurrent illness may occur due to relapse from latent liver-stage infection or reinfection from a new mosquito bite. Classification of the recurrent infection as either relapse or reinfection is critical when evaluating the efficacy of an anti-relapse treatment. Although one can use whether a shared genetic variant exists between baseline and recurrence genotypes to classify the outcome, little has been suggested to use both sharing and nonsharing variants to improve the classification accuracy. In this paper, we develop a novel classification criterion that utilizes transition likelihoods to distinguish relapse from reinfection. When tested in extensive simulation experiments with known outcomes, our classifier has superior operating characteristics. A real data set from 78 Cambodian P. vivax malaria patients was analyzed to demonstrate the practical use of our proposed method.
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http://dx.doi.org/10.1111/biom.13226DOI Listing
December 2020

Factor XIII deficiency does not prevent FeCl-induced carotid artery thrombus formation in mice.

Res Pract Thromb Haemost 2020 Jan 6;4(1):111-116. Epub 2019 Nov 6.

Department of Pathology and Laboratory Medicine University of North Carolina at Chapel Hill Chapel Hill NC USA.

Background: The compositions of venous (red blood cell-rich) and arterial (platelet-rich) thrombi are mediated by distinct pathophysiologic processes; however, fibrin is a major structural component of both. The transglutaminase factor XIII (FXIII) stabilizes fibrin against mechanical and biochemical disruption and promotes red blood cell retention in contracted venous thrombi. Previous studies have shown factor XIII (FXIII) inhibition decreases whole blood clot mass and therefore, may be a therapeutic target for reducing venous thrombosis. The role of FXIII in arterial thrombogenesis is less studied, and the particular contribution of platelet FXIII remains unresolved.

Objective: To determine whether FXIII reduction prevents experimental arterial thrombogenesis.

Methods: Using wild-type mice and mice with genetically imposed deficiency in FXIII, we measured thrombus formation and stability following ferric chloride-induced arterial thrombosis. We also determined the impact of FXIII on the mass of contracted platelet-rich plasma clots.

Results: Following vessel injury, , , and mice developed occlusive arterial thrombi. FXIII deficiency did not significantly reduce the incidence or prolong the time to occlusion. FXIII deficiency also did not alter the timing of reflow events or decrease platelet-rich clot mass.

Conclusions: FXIII does not significantly alter the underlying pathophysiology of experimental arterial thrombus formation.
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http://dx.doi.org/10.1002/rth2.12278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971319PMC
January 2020

Physical activity calorie expenditure (PACE) labels in worksite cafeterias: effects on physical activity.

BMC Public Health 2019 Nov 29;19(1):1596. Epub 2019 Nov 29.

Department of Family Medicine and Community Health, Duke University School of Medicine, 2200 West Main Street, Suite 400, Durham, NC, 27705, USA.

Background: Regular physical activity is an important component of healthy living and wellbeing. Current guidelines recommend that adults participate in at least 150 min of moderate or vigorous-intensity physical activity weekly. In spite of the benefits, just over half of U.S. adults meet these recommendations. Calorie-only food labels at points of food purchase have had limited success in motivating people to change eating behaviors and increase physical activity. One new point of purchase approach to promote healthy behaviors is the addition of food labels that display the physical activity requirement needed to burn the calories in a food item (e.g. walk 15 min).

Methods: The Physical Activity Calorie Expenditure (PACE) Study compared activity-based calorie-expenditure food labels with calorie-only labels at three Blue Cross and Blue Shield of North Carolina worksite cafeterias. After 1 year of baseline data collection, one cafeteria had food items labeled with PACE labels, two others had calorie-only food labels. Cohort participants were asked to wear an accelerometer and complete a self-report activity questionnaire on two occasions during the baseline year and twice during the intervention year.

Results: A total of 366 study participants were included in the analysis. In the PACE-label group, self-reported physical activity increased by 13-26% compared to the calorie-only label group. Moderate-to-vigorous physical activity (MVPA) increased by 24 min per week in the PACE-label group compared to the calorie-label group (p = 0.06). Changes in accelerometer measured steps, sedentary time, and MVPA had modest increases. Change ranged from 1 to 12% with effect size values from 0.08 to 0.15. Baseline physical activity level significantly moderated the intervention effects for all physical activity outcomes. Participants in both label groups starting in the lowest tertile of activity saw the largest increase in their physical activity.

Conclusion: Results suggest small positive effects for the PACE labels on self-reported and objective physical activity measures. Minutes of weekly MVPA, strength training, and exercise activities showed modest increases. These results suggest that calorie-expenditure food labels may result in some limited increases in physical activity.
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http://dx.doi.org/10.1186/s12889-019-7960-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884791PMC
November 2019

Efficient Transmission of Mixed Plasmodium falciparum/vivax Infections From Humans to Mosquitoes.

J Infect Dis 2020 01;221(3):428-437

Institute of Global Health and Infectious Diseases, University of North Carolina, Chapel Hill.

Background: In Southeast Asia, people are often coinfected with different species of malaria (Plasmodium falciparum [Pf] and Plasmodium vivax [Pv]) as well as with multiple clones of the same species. Whether particular species or clones within mixed infections are more readily transmitted to mosquitoes remains unknown.

Methods: Laboratory-reared Anopheles dirus were fed on blood from 119 Pf-infected Cambodian adults, with 5950 dissected to evaluate for transmitted infection. Among 12 persons who infected mosquitoes, polymerase chain reaction and amplicon deep sequencing were used to track species and clone-specific transmission to mosquitoes.

Results: Seven of 12 persons that infected mosquitoes harbored mixed Pf/Pv infection. Among these 7 persons, all transmitted Pv with 2 transmitting both Pf and Pv, leading to Pf/Pv coinfection in 21% of infected mosquitoes. Up to 4 clones of each species were detected within persons. Shifts in clone frequency were detected during transmission. However, in general, all parasite clones in humans were transmitted to mosquitoes, with individual mosquitoes frequently carrying multiple transmitted clones.

Conclusions: Malaria diversity in human hosts was maintained in the parasite populations recovered from mosquitoes fed on their blood. However, in persons with mixed Pf/Pv malaria, Pv appears to be transmitted more readily, in association with more prevalent patent gametocytemia.
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http://dx.doi.org/10.1093/infdis/jiz388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184918PMC
January 2020

Machine learning in orthodontics: .

Angle Orthod 2020 01 12;90(1):77-84. Epub 2019 Aug 12.

Objectives: To (1) introduce a novel machine learning method and (2) assess maxillary structure variation in unilateral canine impaction for advancing clinically viable information.

Materials And Methods: A machine learning algorithm utilizing Learning-based multi-source IntegratioN frameworK for Segmentation (LINKS) was used with cone-beam computed tomography (CBCT) images to quantify volumetric skeletal maxilla discrepancies of 30 study group (SG) patients with unilaterally impacted maxillary canines and 30 healthy control group (CG) subjects. Fully automatic segmentation was implemented for maxilla isolation, and maxillary volumetric and linear measurements were performed. Analysis of variance was used for statistical evaluation.

Results: Maxillary structure was successfully auto-segmented, with an average dice ratio of 0.80 for three-dimensional image segmentations and a minimal mean difference of two voxels on the midsagittal plane for digitized landmarks between the manually identified and the machine learning-based (LINKS) methods. No significant difference in bone volume was found between impaction ([2.37 ± 0.34] [Formula: see text] 10 mm) and nonimpaction ([2.36 ± 0.35] [Formula: see text] 10 mm) sides of SG. The SG maxillae had significantly smaller volumes, widths, heights, and depths ( .05) than CG.

Conclusions: The data suggest that palatal expansion could be beneficial for those with unilateral canine impaction, as underdevelopment of the maxilla often accompanies that condition in the early teen years. Fast and efficient CBCT image segmentation will allow large clinical data sets to be analyzed effectively.
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http://dx.doi.org/10.2319/012919-59.1DOI Listing
January 2020

On the self-triggering Cox model for recurrent event data.

Stat Med 2019 09 8;38(22):4240-4252. Epub 2019 Aug 8.

Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina.

Recurrent event data frequently occur in longitudinal studies when subjects experience more than one event during the observation period. Often, the occurrence of subsequent events is associated with the experience of previous events. Such dependence is commonly ignored in the application of standard recurrent event methodology. In this paper, we utilize a Cox-type regression model with time-varying triggering effect depending on the number and timing of previous events to enhance both model fit and prediction. Parameter estimation and statistical inference is achieved via the partial likelihood. A statistical test procedure is provided to assess the existence of the triggering effects. We demonstrate our approach via comprehensive simulation studies and a real data analysis on chronic pseudomonas infections in young cystic fibrosis patients. Our model provides significantly better predictions than standard recurrent event models.
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http://dx.doi.org/10.1002/sim.8285DOI Listing
September 2019

Analysis of clustered failure time data with cure fraction using copula.

Stat Med 2019 09 4;38(21):3961-3973. Epub 2019 Jun 4.

Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina.

Clustered survival data in the presence of cure has received increasing attention. In this paper, we consider a semiparametric mixture cure model which incorporates a logistic regression model for the cure fraction and a semiparametric regression model for the failure time. We utilize Archimedean copula (AC) models to assess the strength of association for both susceptibility and failure times between susceptible individuals in the same cluster. Instead of using the full likelihood approach, we consider a composite likelihood function and a two-stage estimation procedure for both marginal and association parameters. A Jackknife procedure that takes out one cluster at a time is proposed for the variance estimation of the estimators. Akaike information criterion is applied to select the best model among ACs. Simulation studies are performed to validate our estimating procedures, and two real data sets are analyzed to demonstrate the practical use of our proposed method.
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http://dx.doi.org/10.1002/sim.8213DOI Listing
September 2019

Three-Dimensional Outcome Assessments of Cleft Lip and Palate Patients Undergoing Maxillary Advancement.

Plast Reconstr Surg 2019 06;143(6):1255e-1265e

From the Departments of Orthodontics and Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital; College of Medicine, Chang Gung University; the Department of Biostatistics, University of North Carolina at Chapel Hill; and the Department of Orthodontics, School of Dentistry, Pusan National University.

Background: The aim of this retrospective case series study was to compare three-dimensional postsurgical outcomes of patients with cleft lip and palate following maxillary advancement.

Methods: Fifty consecutive cleft lip and palate patients who underwent whole-pieced Le Fort I advancements were assigned to the major (advancement ≥ 5 mm) or minor (advancement < 5 mm) groups. Three-dimensional surgical simulation was used for presurgical evaluation and planning. Virtual triangles of the presurgical, simulated, and 6-month postoperative stages were used for comparison. Translational and angular changes of each endpoint (A-point, MxR, and MxL) on the virtual triangles and reference planes were recorded and analyzed. Relationships between possible related variables and outcome discrepancies from simulations among all subgroups were also investigated.

Results: Analysis of covariance and the least significant difference test revealed that the outcome discrepancy measurements were affected by different combinations of independent variables. The reliability test showed high consistency of the authors' method for three-dimensional measurements.

Conclusions: The actual surgical outcomes of cleft lip and palate patients differed from the virtual simulations. The outcome discrepancies are impacted by multiple factors. The outcome discrepancies of all rotational surgical corrections (roll, yaw, and pitch) were positively correlated to the degree of planned surgical movement. Meanwhile, bilateral cleft lip and palate patients are more likely to incur outcome discrepancies in yaw correction with major maxillary advancement. However, a maxillary advancement cutoff value of 5 mm would not necessarily lead to significant translational outcome discrepancies among cleft lip and palate patients.

Clinical Question/level Of Evidence: Therapeutic, IV.
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http://dx.doi.org/10.1097/PRS.0000000000005646DOI Listing
June 2019

Racial and Ethnic Differences in the Association Between Diabetes Mellitus and Dry Eye Disease.

Ophthalmic Epidemiol 2019 10 26;26(5):295-300. Epub 2019 Apr 26.

Department of Ophthalmology, University of North Carolina , Chapel Hill.

:To examine the association between dry eye and diabetes mellitus among a large North Carolina patient population. :A retrospective cross-sectional study of patients seen within the University of North Carolina medical system between July 1, 2008, and September 1, 2017, was performed. De-identified medical records contained within the Carolina Data Warehouse of adult patients who have had an ocular evaluation were studied. Four categories of disease states were identified by ICD-9 and ICD-10 codes. Patients were grouped based on being diagnosed with Dry Eye Disease (ICD-9: 375.15, 370.33, and ICD-10: H04.12, H16.221), Diabetes Mellitus (ICD-9: 250.00-250.93 and ICD-10: E08-E11, E13), neither, or both diseases. Odds ratios of the association between diabetes and dry eye were calculated for the following racial/ethnic groups: Non-Hispanic White, Non-Hispanic Black/African American, Asian, and Hispanic. :A total of 81,480 patients were included in the analysis; of those, 8978 patients had dry eye disease and 18,361 patients had diabetes. The remaining 54,141 patients had neither disease. Dry eye prevalence among patients with diabetes was 14.39% (95% CI: 13.89-14.91%) and 10.11% (95%CI: 9.88-10.35%) among patients without diabetes. The odds of a patient with diabetes having dry eye are 1.15 (95% CI: 1.09-1.21) times that of a patient without diabetes. Asian patients with diabetes demonstrated the highest odds of having dry eye at 1.49 (95% CI: 1.12-1.98). :Dry eye is common among patients with diabetes, and the association between these diseases is strongest among Asian patients. Race and ethnicity are important demographic factors that may guide providers in the diagnosis and treatment of dry eye in the setting of diabetes.
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http://dx.doi.org/10.1080/09286586.2019.1607882DOI Listing
October 2019

Dysfunctional endogenous FIX impairs prophylaxis in a mouse hemophilia B model.

Blood 2019 05 16;133(22):2445-2451. Epub 2019 Apr 16.

Department of Biology and Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC.

Factor IX (FIX) binds to collagen IV (Col4) in the subendothelial basement membrane. In hemophilia B, this FIX-Col4 interaction reduces the plasma recovery of infused FIX and plays a role in hemostasis. Studies examining the recovery of infused BeneFix (FIX) in null (cross-reactive material negative, CRM) hemophilia B mice suggest the concentration of Col4 readily available for binding FIX is ∼405 nM with a 95% confidence interval of 374 to 436 nM. Thus, the vascular cache of FIX bound to Col4 is several-fold the FIX level measured in plasma. In a mouse model of prophylactic therapy (testing hemostasis by saphenous vein bleeding 7 days after infusion of 150 IU/kg FIX), FIX and the increased half-life FIXs Alprolix (FIX) and Idelvion (FIX) produce comparable hemostatic results in CRM mice. In bleeding CRM hemophilia B mice, the times to first clot at a saphenous vein injury site after the infusions of the FIX agents are significantly different, at FIX < FIX < FIX Dysfunctional forms of FIX, however, circulate in the majority of patients with hemophilia B (CRM). In the mouse prophylactic therapy model, none of the FIX products improves hemostasis in CRM mice expressing a dysfunctional FIX, FIX, that nevertheless competes with infused FIX for Col4 binding and potentially other processes involving FIX. The results in this mouse model of CRM hemophilia B demonstrate that the endogenous expression of a dysfunctional FIX can deleteriously affect the hemostatic response to prophylactic therapy.
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http://dx.doi.org/10.1182/blood.2018884015DOI Listing
May 2019

Multi-state models of transitions in depression and anxiety symptom severity and cardiovascular events in patients with coronary heart disease.

PLoS One 2019 7;14(3):e0213334. Epub 2019 Mar 7.

Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.

Objective: Patients with coronary heart disease (CHD) commonly suffer from depression and anxiety, yet transitions of symptom severity and cardiovascular events (CVE) over time are not well characterized.

Methods: We included 997 patients with stable CHD from a prospective cohort study. We estimated 5- and 10-year transition probabilities of depression and anxiety symptom severity levels and fatal- and non-fatal adverse CVE. Depression and anxiety symptoms were measured with the Hospital Anxiety and Depression Scale 5 times over 13 years and categorized as no, mild, or moderate/severe symptoms. Using multi-state modeling, we calculated 5- and 10-year transition probabilities for depression and anxiety symptom severity and CVE and calculated transition intensity ratios for factors associated with symptom severity progression and regression.

Results: At 5 years, only approximately half of participants with moderate or severe symptom severity at baseline transitioned to no symptom severity. Patients with low physical activity (<1x/week or never) had a higher probability of worse symptom severity after 5 and 10 years and a higher probability of a CVE after 5 and 10 years regardless of their depression status at baseline compared to higher physical activity groups. Higher body mass index, <10 years of education, and lower physical activity were associated with depression symptom progression; female and lower physical activity were associated with anxiety symptom progression.

Conclusions: Patients with CHD had a consistent burden of depression and anxiety symptoms. Secondary prevention strategies should target depression and anxiety and include a physical activity component.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213334PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405099PMC
December 2019