Browsing by Subject "Cohort Studies"
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Item Open Access A comparison of minimally invasive transforaminal lumbar interbody fusion and decompression alone for degenerative lumbar spondylolisthesis.(Neurosurgical focus, 2019-05) Chan, Andrew K; Bisson, Erica F; Bydon, Mohamad; Glassman, Steven D; Foley, Kevin T; Potts, Eric A; Shaffrey, Christopher I; Shaffrey, Mark E; Coric, Domagoj; Knightly, John J; Park, Paul; Wang, Michael Y; Fu, Kai-Ming; Slotkin, Jonathan R; Asher, Anthony L; Virk, Michael S; Kerezoudis, Panagiotis; Alvi, Mohammed Ali; Guan, Jian; Haid, Regis W; Mummaneni, Praveen VOBJECTIVEThe optimal minimally invasive surgery (MIS) approach for grade 1 lumbar spondylolisthesis is not clearly elucidated. In this study, the authors compared the 24-month patient-reported outcomes (PROs) after MIS transforaminal lumbar interbody fusion (TLIF) and MIS decompression for degenerative lumbar spondylolisthesis.METHODSA total of 608 patients from 12 high-enrolling sites participating in the Quality Outcomes Database (QOD) lumbar spondylolisthesis module underwent single-level surgery for degenerative grade 1 lumbar spondylolisthesis, of whom 143 underwent MIS (72 MIS TLIF [50.3%] and 71 MIS decompression [49.7%]). Surgeries were classified as MIS if there was utilization of percutaneous screw fixation and placement of a Wiltse plane MIS intervertebral body graft (MIS TLIF) or if there was a tubular decompression (MIS decompression). Parameters obtained at baseline through at least 24 months of follow-up were collected. PROs included the Oswestry Disability Index (ODI), numeric rating scale (NRS) for back pain, NRS for leg pain, EuroQol-5D (EQ-5D) questionnaire, and North American Spine Society (NASS) satisfaction questionnaire. Multivariate models were constructed to adjust for patient characteristics, surgical variables, and baseline PRO values.RESULTSThe mean age of the MIS cohort was 67.1 ± 11.3 years (MIS TLIF 62.1 years vs MIS decompression 72.3 years) and consisted of 79 (55.2%) women (MIS TLIF 55.6% vs MIS decompression 54.9%). The proportion in each cohort reaching the 24-month follow-up did not differ significantly between the cohorts (MIS TLIF 83.3% and MIS decompression 84.5%, p = 0.85). MIS TLIF was associated with greater blood loss (mean 108.8 vs 33.0 ml, p < 0.001), longer operative time (mean 228.2 vs 101.8 minutes, p < 0.001), and longer length of hospitalization (mean 2.9 vs 0.7 days, p < 0.001). MIS TLIF was associated with a significantly lower reoperation rate (14.1% vs 1.4%, p = 0.004). Both cohorts demonstrated significant improvements in ODI, NRS back pain, NRS leg pain, and EQ-5D at 24 months (p < 0.001, all comparisons relative to baseline). In multivariate analyses, MIS TLIF-as opposed to MIS decompression alone-was associated with superior ODI change (β = -7.59, 95% CI -14.96 to -0.23; p = 0.04), NRS back pain change (β = -1.54, 95% CI -2.78 to -0.30; p = 0.02), and NASS satisfaction (OR 0.32, 95% CI 0.12-0.82; p = 0.02).CONCLUSIONSFor symptomatic, single-level degenerative spondylolisthesis, MIS TLIF was associated with a lower reoperation rate and superior outcomes for disability, back pain, and patient satisfaction compared with posterior MIS decompression alone. This finding may aid surgical decision-making when considering MIS for degenerative lumbar spondylolisthesis.Item Open Access A meta-analysis of four genome-wide association studies of survival to age 90 years or older: the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.(J Gerontol A Biol Sci Med Sci, 2010-05) Newman, Anne B; Walter, Stefan; Lunetta, Kathryn L; Garcia, Melissa E; Slagboom, P Eline; Christensen, Kaare; Arnold, Alice M; Aspelund, Thor; Aulchenko, Yurii S; Benjamin, Emelia J; Christiansen, Lene; D'Agostino, Ralph B; Fitzpatrick, Annette L; Franceschini, Nora; Glazer, Nicole L; Gudnason, Vilmundur; Hofman, Albert; Kaplan, Robert; Karasik, David; Kelly-Hayes, Margaret; Kiel, Douglas P; Launer, Lenore J; Marciante, Kristin D; Massaro, Joseph M; Miljkovic, Iva; Nalls, Michael A; Hernandez, Dena; Psaty, Bruce M; Rivadeneira, Fernando; Rotter, Jerome; Seshadri, Sudha; Smith, Albert V; Taylor, Kent D; Tiemeier, Henning; Uh, Hae-Won; Uitterlinden, André G; Vaupel, James W; Walston, Jeremy; Westendorp, Rudi GJ; Harris, Tamara B; Lumley, Thomas; van Duijn, Cornelia M; Murabito, Joanne MBACKGROUND: Genome-wide association studies (GWAS) may yield insights into longevity. METHODS: We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort. RESULTS: There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x 10(-8). Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x 10(-7) for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage. CONCLUSION: Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings.Item Open Access A mutation in TNNC1-encoded cardiac troponin C, TNNC1-A31S, predisposes to hypertrophic cardiomyopathy and ventricular fibrillation.(The Journal of biological chemistry, 2012-09) Parvatiyar, MS; Landstrom, AP; Figueiredo-Freitas, C; Potter, JD; Ackerman, MJ; Pinto, JRDefined as clinically unexplained hypertrophy of the left ventricle, hypertrophic cardiomyopathy (HCM) is traditionally understood as a disease of the cardiac sarcomere. Mutations in TNNC1-encoded cardiac troponin C (cTnC) are a relatively rare cause of HCM. Here, we report clinical and functional characterization of a novel TNNC1 mutation, A31S, identified in a pediatric HCM proband with multiple episodes of ventricular fibrillation and aborted sudden cardiac death. Diagnosed at age 5, the proband is family history-negative for HCM or sudden cardiac death, suggesting a de novo mutation. TnC-extracted cardiac skinned fibers were reconstituted with the cTnC-A31S mutant, which increased Ca(2+) sensitivity with no effect on the maximal contractile force generation. Reconstituted actomyosin ATPase assays with 50% cTnC-A31S:50% cTnC-WT demonstrated Ca(2+) sensitivity that was intermediate between 100% cTnC-A31S and 100% cTnC-WT, whereas the mutant increased the activation of the actomyosin ATPase without affecting the inhibitory qualities of the ATPase. The secondary structure of the cTnC mutant was evaluated by circular dichroism, which did not indicate global changes in structure. Fluorescence studies demonstrated increased Ca(2+) affinity in isolated cTnC, the troponin complex, thin filament, and to a lesser degree, thin filament with myosin subfragment 1. These results suggest that this mutation has a direct effect on the Ca(2+) sensitivity of the myofilament, which may alter Ca(2+) handling and contribute to the arrhythmogenesis observed in the proband. In summary, we report a novel mutation in the TNNC1 gene that is associated with HCM pathogenesis and may predispose to the pathogenesis of a fatal arrhythmogenic subtype of HCM.Item Open Access A new algorithm for predicting time to disease endpoints in Alzheimer's disease patients.(J Alzheimers Dis, 2014) Razlighi, Qolamreza R; Stallard, Eric; Brandt, Jason; Blacker, Deborah; Albert, Marilyn; Scarmeas, Nikolaos; Kinosian, Bruce; Yashin, Anatoliy I; Stern, YaakovBACKGROUND: The ability to predict the length of time to death and institutionalization has strong implications for Alzheimer's disease patients and caregivers, health policy, economics, and the design of intervention studies. OBJECTIVE: To develop and validate a prediction algorithm that uses data from a single visit to estimate time to important disease endpoints for individual Alzheimer's disease patients. METHOD: Two separate study cohorts (Predictors 1, N = 252; Predictors 2, N = 254), all initially with mild Alzheimer's disease, were followed for 10 years at three research centers with semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. The prediction algorithm was based on a longitudinal Grade of Membership model developed using the complete series of semiannually-collected Predictors 1 data. The algorithm was validated on the Predictors 2 data using data only from the initial assessment to predict separate survival curves for three outcomes. RESULTS: For each of the three outcome measures, the predicted survival curves fell well within the 95% confidence intervals of the observed survival curves. Patients were also divided into quintiles for each endpoint to assess the calibration of the algorithm for extreme patient profiles. In all cases, the actual and predicted survival curves were statistically equivalent. Predictive accuracy was maintained even when key baseline variables were excluded, demonstrating the high resilience of the algorithm to missing data. CONCLUSION: The new prediction algorithm accurately predicts time to death, institutionalization, and need for full-time care in individual Alzheimer's disease patients; it can be readily adapted to predict other important disease endpoints. The algorithm will serve an unmet clinical, research, and public health need.Item Open Access A School-Based SARS-CoV-2 Testing Program: Testing Uptake and Quarantine Length After In-School Exposures.(Pediatrics, 2022-02) Boutzoukas, Angelique E; Zimmerman, Kanecia O; Mann, Tara K; Moorthy, Ganga S; Blakemore, Ashley; McGann, Kathleen A; Smith, Michael J; Nutting, Boen; Kerley, Karen; Brookhart, M Alan; Edwards, Laura; Rak, Zsolt; Benjamin, Daniel K; Kalu, Ibukunoluwa CObjectives
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related quarantines, which are required after close contact with infected individuals, have substantially disrupted in-person education for kindergarten through 12th grade (K-12) students. In recent recommendations, shortened durations of quarantine are allowed if a negative SARS-CoV-2 test result is obtained at 5 to 7 days postexposure, but access to testing remains limited. We hypothesized that providing access to in-school SARS-CoV-2 testing postexposure would increase testing and reduce missed school days.Methods
This prospective cohort study was conducted in one large public K-12 school district in North Carolina and included 2 periods: preimplementation (March 15, 2021, to April 21, 2021) and postimplementation (April 22, 2021, to June 4, 2021), defined around initiation of an in-school SARS-CoV-2 testing program in which on-site access to testing is provided. Number of quarantined students and staff, testing uptake, test results, and number of missed school days were analyzed and compared between the preimplementation and postimplementation periods.Results
Twenty-four schools, including 12 251 in-person learners, participated in the study. During preimplementation, 446 close contacts were quarantined for school-related exposures; 708 close contacts were quarantined postimplementation. Testing uptake after school-related exposures increased from 6% to 40% (95% confidence interval: 23% to 45%) after implementation, and 89% of tests were conducted in-school. After in-school testing implementation, close contacts missed ∼1.5 fewer days of school (95% confidence interval: -2 to -1).Conclusions
Providing access to in-school testing may be a worthwhile mechanism to increase testing uptake after in-school exposures and minimize missed days of in-person learning, thereby mitigating the pandemic's ongoing impact on children.Item Open Access Access to Reconstructive Hand Surgery in the United States-Investigating the Obstacles: A Scoping Review.(Hand (New York, N.Y.), 2023-07) Kohan, Joshua; Mangan, Jack; Patel, AshitBackground
Mechanisms that affect access to surgical hand care appear to be complex and multifaceted. This scoping review aims to investigate the available literature describing such mechanisms and provide direction for future investigation.Methods
The methodological framework outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews was used to guide this review. In November 2021, MEDLINE and EMBASE databases were searched. A narrative summary of the characteristics and key findings of each paper is used to present the data to facilitate the integration of diverse evidence.Results
Of 471 initial studies, 49 were included in our final analysis. Of these, 33% were cohort studies; 27% reported that underinsured patients are less likely to get an appointment with a hand specialist or to receive treatment. Overburdened emergency departments accounted for the second-most reported reason (16%) for diminished access to surgical hand care. Elective procedure financial incentives, poor emergency surgical hand coverage, distance to treatment, race, and policy were also notably reported across the literature.Conclusions
This study describes the vast mechanisms that hinder access to surgical hand care and highlights their complexity. Possible solutions and policy changes that may help improve access have been described.Item Open Access Adjuvant radiotherapy in the treatment of invasive intraductal papillary mucinous neoplasm of the pancreas: an analysis of the surveillance, epidemiology, and end results registry.(Ann Surg Oncol, 2012-04) Worni, M; Akushevich, I; Gloor, B; Scarborough, J; Chino, JP; Jacobs, DO; Hahn, SM; Clary, BM; Pietrobon, R; Shah, ABACKGROUND: Management and outcomes of patients with invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas are not well established. We investigated whether adjuvant radiotherapy (RT) improved cancer-specific survival (CSS) and overall survival (OS) among patients undergoing surgical resection for invasive IPMN. METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry was used in this retrospective cohort study. All adult patients with resection of invasive IPMN from 1988 to 2007 were included. CSS and OS were analyzed using Kaplan-Meier curves. Unadjusted and propensity-score-adjusted Cox proportional-hazards modeling were used for subgroup analyses. RESULTS: 972 patients were included. Adjuvant RT was administered to 31.8% (n=309) of patients. There was no difference in overall median CSS or OS in patients who received adjuvant RT (5-year CSS: 26.5 months; 5-year OS: 23.5 months) versus those who did not (CSS: 28.5 months, P=0.17; OS: 23.5 months, P=0.23). Univariate predictors of survival were lymph node (LN) involvement, T4-classified tumors, and poorly differentiated tumor grade (all P<0.05). In the propensity-score-adjusted analysis, adjuvant RT was associated with improved 5-year CSS [hazard ratio (HR): 0.67, P=0.004] and 5-year OS (HR: 0.73, P=0.014) among all patients with LN involvement, though further analysis by T-classification demonstrated no survival differences among patients with T1/T2 disease; patients with T3/T4-classified tumors had improved CSS (HR: 0.71, P=0.022) but no difference in OS (HR: 0.76, P=0.06). CONCLUSION: On propensity-score-adjusted analysis, adjuvant RT was associated with improved survival in selected subsets of patients with invasive IPMN, particularly those with T3/T4 tumors and LN involvement.Item Open Access Age trajectories of physiological indices in relation to healthy life course.(Mech Ageing Dev, 2011-03) Arbeev, Konstantin G; Ukraintseva, Svetlana V; Akushevich, Igor; Kulminski, Alexander M; Arbeeva, Liubov S; Akushevich, Lucy; Culminskaya, Irina V; Yashin, Anatoliy IWe analysed relationship between the risk of onset of "unhealthy life" (defined as the onset of cancer, cardiovascular diseases, or diabetes) and longitudinal changes in body mass index, diastolic blood pressure, hematocrit, pulse pressure, pulse rate, and serum cholesterol in the Framingham Heart Study (Original Cohort) using the stochastic process model of human mortality and aging. The analyses demonstrate how decline in resistance to stresses and adaptive capacity accompanying human aging can be evaluated from longitudinal data. We showed how these components of the aging process, as well as deviation of the trajectories of physiological indices from those minimising the risk at respective ages, can lead to an increase in the risk of onset of unhealthy life with age. The results indicate the presence of substantial gender difference in aging related decline in stress resistance and adaptive capacity, which can contribute to differences in the shape of the sex-specific patterns of incidence rates of aging related diseases.Item Open Access Age-specific differences in oncogenic pathway deregulation seen in human breast tumors.(PLoS One, 2008-01-02) Anders, Carey K; Acharya, Chaitanya R; Hsu, David S; Broadwater, Gloria; Garman, Katherine; Foekens, John A; Zhang, Yi; Wang, Yixin; Marcom, Kelly; Marks, Jeffrey R; Mukherjee, Sayan; Nevins, Joseph R; Blackwell, Kimberly L; Potti, AnilPURPOSE: To define the biology driving the aggressive nature of breast cancer arising in young women. EXPERIMENTAL DESIGN: Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young or=65 years), 411 eligible patients (n = 200or=65 years) with clinically-annotated Affymetrix microarray data were identified. GSEA, signatures of oncogenic pathway deregulation and predictors of chemotherapy sensitivity were evaluated within the two age-defined cohorts. RESULTS: In comparing deregulation of oncogenic pathways between age groups, a higher probability of PI3K (p = 0.006) and Myc (p = 0.03) pathway deregulation was observed in breast tumors arising in younger women. When evaluating unique patterns of pathway deregulation, a low probability of Src and E2F deregulation in tumors of younger women, concurrent with a higher probability of PI3K, Myc, and beta-catenin, conferred a worse prognosis (HR = 4.15). In contrast, a higher probability of Src and E2F pathway activation in tumors of older women, with concurrent low probability of PI3K, Myc and beta-catenin deregulation, was associated with poorer outcome (HR = 2.7). In multivariate analyses, genomic clusters of pathway deregulation illustrate prognostic value. CONCLUSION: Results demonstrate that breast cancer arising in young women represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathways that are prognostic, independent of currently available clinico-pathologic variables. These results should enable refinement of targeted treatment strategies in this clinically challenging situation.Item Open Access Altered gene expression and DNA damage in peripheral blood cells from Friedreich's ataxia patients: cellular model of pathology.(PLoS Genet, 2010-01-15) Haugen, Astrid C; Di Prospero, Nicholas A; Parker, Joel S; Fannin, Rick D; Chou, Jeff; Meyer, Joel N; Halweg, Christopher; Collins, Jennifer B; Durr, Alexandra; Fischbeck, Kenneth; Van Houten, BennettThe neurodegenerative disease Friedreich's ataxia (FRDA) is the most common autosomal-recessively inherited ataxia and is caused by a GAA triplet repeat expansion in the first intron of the frataxin gene. In this disease, transcription of frataxin, a mitochondrial protein involved in iron homeostasis, is impaired, resulting in a significant reduction in mRNA and protein levels. Global gene expression analysis was performed in peripheral blood samples from FRDA patients as compared to controls, which suggested altered expression patterns pertaining to genotoxic stress. We then confirmed the presence of genotoxic DNA damage by using a gene-specific quantitative PCR assay and discovered an increase in both mitochondrial and nuclear DNA damage in the blood of these patients (p<0.0001, respectively). Additionally, frataxin mRNA levels correlated with age of onset of disease and displayed unique sets of gene alterations involved in immune response, oxidative phosphorylation, and protein synthesis. Many of the key pathways observed by transcription profiling were downregulated, and we believe these data suggest that patients with prolonged frataxin deficiency undergo a systemic survival response to chronic genotoxic stress and consequent DNA damage detectable in blood. In conclusion, our results yield insight into the nature and progression of FRDA, as well as possible therapeutic approaches. Furthermore, the identification of potential biomarkers, including the DNA damage found in peripheral blood, may have predictive value in future clinical trials.Item Open Access An Analysis of the Incidence and Outcomes of Major Versus Minor Neurological Decline After Complex Adult Spinal Deformity Surgery: A Subanalysis of Scoli-RISK-1 Study.(Spine, 2018-07) Kato, So; Fehlings, Michael G; Lewis, Stephen J; Lenke, Lawrence G; Shaffrey, Christopher I; Cheung, Kenneth MC; Carreon, Leah Y; Dekutoski, Mark B; Schwab, Frank J; Boachie-Adjei, Oheneba; Kebaish, Khaled M; Ames, Christopher P; Qiu, Yong; Matsuyama, Yukihiro; Dahl, Benny T; Mehdian, Hossein; Pellisé, Ferran; Berven, Sigurd HStudy design
A subanalysis from a prospective, multicenter, international cohort study in 15 sites (Scoli-RISK-1).Objective
To report detailed information regarding the severity of neurological decline related to complex adult spine deformity (ASD) surgery and to examine outcomes based on severity.Summary of background data
Postoperative neurological decline after ASD surgeries can occur due to nerve root(s) or spinal cord dysfunction. The impact of decline and the pattern of recovery may be related to the anatomic location and the severity of the injury.Methods
An investigation of 272 prospectively enrolled complex ASD surgical patients with neurological status measured by American Spinal Injury Association Lower Extremity Motor Scores (LEMS) was undertaken. Postoperative neurological decline was categorized into "major" (≥5 points loss) versus "minor" (<5 points loss) deficits. Timing and extent of recovery in LEMS were investigated for each group.Results
Among the 265 patients with LEMS available at discharge, 61 patients (23%) had neurological decline, with 20 (33%) experiencing major decline. Of note, 90% of the patients with major decline had deficits in three or more myotomes. Full recovery was seen in 24% at 6 weeks and increased to 65% at 6 months. However, 34% continued to experience some neurological decline at 24 months, with 6% demonstrating no improvement. Of 41 patients (67%) with minor decline, 73% had deficits in one or two myotomes. Full recovery was seen in 49% at 6 weeks and increased to 70% at 6 months. Of note, 26% had persistence of some neurological deficit at 24 months, with 18% demonstrating no recovery.Conclusion
In patients undergoing complex ASD correction, a rate of postoperative neurological decline of 23% was noted with 33% of these being "major." Although most patients showed substantial recovery by 6 months, approximately one-third continued to experience neurological dysfunction.Level of evidence
2.Item Open Access Analysis of Successful Versus Failed Radiographic Outcomes After Cervical Deformity Surgery.(Spine, 2018-07) Protopsaltis, Themistocles S; Ramchandran, Subaraman; Hamilton, D Kojo; Sciubba, Daniel; Passias, Peter G; Lafage, Virginie; Lafage, Renaud; Smith, Justin S; Hart, Robert A; Gupta, Munish; Burton, Douglas; Bess, Shay; Shaffrey, Christopher; Ames, Christopher P; International Spine Study Group (ISSG)Study design
Prospective multicenter cohort study with consecutive enrollment.Objective
To evaluate preoperative alignment and surgical factors associated with suboptimal early postoperative radiographic outcomes after surgery for cervical deformity.Summary of background data
Recent studies have demonstrated correlation between cervical sagittal alignment and patient-reported outcomes. Few studies have explored cervical deformity correction prospectively, and the factors that result in successful versus failed cervical alignment corrections remain unclear.Methods
Patients with adult cervical deformity (ACD) included with either cervical kyphosis more than 10°, C2-C7 sagittal vertical axis (cSVA) of more than 4 cm, or chin-brow vertical angle of more than 25°. Patients were categorized into failed outcomes group if cSVA of more than 4 cm or T1 slope and cervical lordosis (TS-CL) of more than 20° at 6 months postoperatively.Results
A total of 71 patients with ACD (mean age 62 yr, 56% women, 41% revisions) were included. Fourty-five had primary cervical deformities and 26 at the cervico-thoracic junction. Thirty-three (46.4%) had failed radiographic outcomes by cSVA and 46 (64.7%) by TS-CL. Failure to restore cSVA was associated with worse preoperative C2 pelvic tilt angle (CPT: 64.4° vs. 47.8°, P = 0.01), worse postoperative C2 slope (35.0° vs. 23.8°, P = 0.004), TS-CL (35.2° vs. 24.9°, P = 0.01), CPT (47.9° vs. 28.2°, P < 0.001), "+" Schwab modifiers (P = 0.007), revision surgery (P = 0.05), and failure to address the secondary, thoracolumbar driver of the deformity (P = 0.02). Failure to correct TS-CL was associated with worse preoperative cervical kyphosis (10.4° vs. -2.1°, P = 0.03), CPT (52.6° vs. 39.1°, P = 0.04), worse postoperative C2 slope (30.2° vs. 13.3°, P < 0.001), cervical lordosis (-3.6° vs. -15.1°, P = 0.01), and CPT (37.7° vs. 24.0°, P < 0.001). Multivariate analysis revealed postoperative distal junctional kyphosis associated with suboptimal outcomes by cSVA (odds ratio 0.06, confidence interval 0.01-0.4, P = 0.004) and TS-CL (odds ratio 0.15, confidence interval 0.02-0.97, P = 0.05).Conclusion
Factors associated with failure to correct the cSVA included revision surgery, worse preoperative CPT, and concurrent thoracolumbar deformity. Failure to correct the TS-CL mismatch was associated with worse preoperative cervical kyphosis and CPT. Occurrence of early postoperative distal junctional kyphosis significantly affects postoperative radiographic outcomes.Level of evidence
3.Item Open Access Antenatal haemoglobin A1c and risk of large-for-gestational-age infants in a multi-ethnic cohort of women with gestational diabetes.(Paediatric and perinatal epidemiology, 2012-05) Katon, Jodie; Reiber, Gayle; Williams, Michelle A; Yanez, David; Miller, EdithGestational diabetes mellitus (GDM) is a risk factor for delivering a large-for-gestational-age (LGA) infant. Haemoglobin A1c (A1C) is an indicator of glycaemic control. The objective of this study was to test whether higher A1C quartile at the time of diagnosis of GDM is associated with increased risk of delivering a LGA or macrosomic infant. Women with singleton pregnancies treated for GDM at a large diabetes and pregnancy programme located in Charlotte, North Carolina, were eligible for inclusion in this retrospective cohort study. Clinical information, including A1C at diagnosis, treatment, prior medical and obstetric history, and birth data were abstracted from medical records. LGA was defined as birthweight >90th percentile for gestational age and sex and macrosomia as birthweight >4000 g. Logistic regression was used to analyse the association of A1C at GDM diagnosis with risk of delivering LGA or macrosomic infants. This study included 502 women. Prevalences of LGA and macrosomia were 4% and 6% respectively. After adjustment there was no detectable trend of increased risk for LGA (P for trend = 0.12) or macrosomia (P for trend = 0.20) across increasing quartiles of A1C at GDM diagnosis. A1C at GDM diagnosis may not be linearly associated with LGA or macrosomia, possibly because of the mediating effect of strict glycaemic control in this clinical setting.Item Open Access Antistaphylococcal β-Lactams versus Vancomycin for Treatment of Infective Endocarditis Due to Methicillin-Susceptible Coagulase-Negative Staphylococci: a Prospective Cohort Study from the International Collaboration on Endocarditis.(Antimicrobial agents and chemotherapy, 2016-10) Carugati, M; Petti, CA; Arnold, C; Miro, JM; Pericàs, JM; Garcia de la Maria, C; Kanafani, Z; Durante-Mangoni, E; Baddley, J; Wray, D; Klein, JL; Delahaye, F; Fernandez-Hidalgo, N; Hannan, MM; Murdoch, D; Bayer, A; Chu, VHThe phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of the presence of the mecA gene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with antistaphylococcal β-lactams (ASB) versus vancomycin (VAN) in a multicenter cohort study based on data from the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases. The ICE-PCS database contains prospective data on 5,568 patients with IE collected between 2000 and 2006, while the ICE-Plus database contains prospective data on 2,019 patients with IE collected between 2008 and 2012. The primary endpoint was in-hospital mortality. Secondary endpoints were 6-month mortality and survival time. Of the 7,587 patients in the two databases, there were 280 patients with methicillin-susceptible CoNS IE. Detailed treatment and outcome data were available for 180 patients. Eighty-eight patients received ASB, while 36 were treated with VAN. In-hospital mortality (19.3% versus 11.1%; P = 0.27), 6-month mortality (31.6% versus 25.9%; P = 0.58), and survival time after discharge (P = 0.26) did not significantly differ between the two cohorts. Cox regression analysis did not show any significant association between ASB use and the survival time (hazard ratio, 1.7; P = 0.22); this result was not affected by adjustment for confounders. This study provides no evidence for a difference in outcome with the use of VAN versus ASB for methicillin-susceptible CoNS IE.Item Open Access Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy.(Int J Cancer, 2015-11-15) Zhang, Fenghua; Sturgis, Erich M; Sun, Yan; Zhang, Yang; Wei, Qingyi; Zhang, Caiyun; Zheng, Hongliang; Li, GuojunSingle nucleotide polymorphisms (SNPs) in the promoter region of FAS and FASLG may alter their transcriptional activity. Thus, we determined the associations between four FAS and FASLG promoter variants (FAS1377G>A, rs2234767; 670A>G, rs1800682; FASLG844T>C, rs763110 and 124A>G, rs5030772) and the risk of recurrence of squamous cell carcinoma of the oropharynx (SCCOP). We evaluated the associations between FAS and FASLG genetic variants and the risk of recurrence in a cohort of 1,008 patients. The log-rank test and multivariate Cox models were used to evaluate the associations. Compared with patients with common homozygous genotypes of FAS670 and FASLG844 polymorphisms, patients with variant genotypes had lower disease-free survival rates (log-rank p < 0.0001 and p < 0.0001, respectively) and an approximately threefold higher risk of SCCOP recurrence (HR, 3.2;95% CI, 2.2-4.6; and HR, 3.1; 95% CI, 2.2-4.4, respectively) after multivariate adjustment. Furthermore, among patients with HPV16-positive tumors, those with variant genotypes of these two polymorphisms had lower disease-free survival rates (log-rank, p < 0.0001 and p < 0.0001, respectively) and a higher recurrence risk than did patients with common homozygous genotypes (HR, 12.9; 95% CI, 3.8-43.6; and HR, 8.1; 95% CI, 3.6-18.6, respectively), whereas no significant associations were found for FAS1377 and FASLG124 polymorphisms. Our findings suggest that FAS670 and FASLG844 polymorphisms modulate the risk of recurrence of SCCOP, particularly in patients with HPV16-positive tumors. Larger studies are needed to validate these results.Item Open Access Aspiration Risk Factors, Microbiology, and Empiric Antibiotics for Patients Hospitalized With Community-Acquired Pneumonia.(Chest, 2021-01) Marin-Corral, Judith; Pascual-Guardia, Sergi; Amati, Francesco; Aliberti, Stefano; Masclans, Joan R; Soni, Nilam; Rodriguez, Alejandro; Sibila, Oriol; Sanz, Francisco; Sotgiu, Giovanni; Anzueto, Antonio; Dimakou, Katerina; Petrino, Roberta; van de Garde, Ewoudt; Restrepo, Marcos I; GLIMP investigatorsBackground
Aspiration community-acquired pneumonia (ACAP) and community-acquired pneumonia (CAP) in patients with aspiration risk factors (AspRFs) are infections associated with anaerobes, but limited evidence suggests their pathogenic role.Research question
What are the aspiration risk factors, microbiology patterns, and empiric anti-anaerobic use in patients hospitalized with CAP?Study design and methods
This is a secondary analysis of GLIMP, an international, multicenter, point-prevalence study of adults hospitalized with CAP. Patients were stratified into three groups: (1) ACAP, (2) CAP/AspRF+ (CAP with AspRF), and (3) CAP/AspRF- (CAP without AspRF). Data on demographics, comorbidities, microbiological results, and anti-anaerobic antibiotics were analyzed in all groups. Patients were further stratified in severe and nonsevere CAP groups.Results
We enrolled 2,606 patients with CAP, of which 193 (7.4%) had ACAP. Risk factors independently associated with ACAP were male, bedridden, underweight, a nursing home resident, and having a history of stroke, dementia, mental illness, and enteral tube feeding. Among non-ACAP patients, 1,709 (70.8%) had CAP/AspRF+ and 704 (29.2%) had CAP/AspRF-. Microbiology patterns including anaerobes were similar between CAP/AspRF-, CAP/AspRF+ and ACAP (0.0% vs 1.03% vs 1.64%). Patients with severe ACAP had higher rates of total gram-negative bacteria (64.3% vs 44.3% vs 33.3%, P = .021) and lower rates of total gram-positive bacteria (7.1% vs 38.1% vs 50.0%, P < .001) when compared with patients with severe CAP/AspRF+ and severe CAP/AspRF-, respectively. Most patients (>50% in all groups) independent of AspRFs or ACAP received specific or broad-spectrum anti-anaerobic coverage antibiotics.Interpretation
Hospitalized patients with ACAP or CAP/AspRF+ had similar anaerobic flora compared with patients without aspiration risk factors. Gram-negative bacteria were more prevalent in patients with severe ACAP. Despite having similar microbiological flora between groups, a large proportion of CAP patients received anti-anaerobic antibiotic coverage.Item Open Access Assessment of Long-Term Bowel Symptoms After Segmental Resection of Deeply Infiltrating Endometriosis: A Matched Cohort Study.(J Minim Invasive Gynecol, 2016-07) Soto, Enrique; Catenacci, Michelle; Bedient, Carrie; Jelovsek, J Eric; Falcone, TommasoSTUDY OBJECTIVE: To assess long-term bowel symptoms in women who underwent segmental bowel resection for deep-infiltrating endometriosis (DIE) compared with women who underwent resection of severe endometriosis without bowel resection. DESIGN: Cohort study with matched controls (Canadian Task Force classification II-2). SETTING: Cleveland Clinic. PATIENTS: 71 patients (36 cases and 35 controls). INTERVENTIONS: Patients who were at least 4 years out from undergoing segmental bowel resection due to DIE were matched with patients who had undergone resection of stage III/IV endometriosis without bowel resection. The patients completed validated questionnaires, and data were analyzed using the Wilcoxon rank-sum, χ(2), and Fisher exact tests. MEASUREMENTS AND MAIN RESULTS: The Bristol Stool Form Scale, Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM), and St Mark's Vaizey Fecal Incontinence Grading System were used to elicit information. The median duration of follow-up was 10.1 years (range, 4-18 years). The mean patient age and body mass index were comparable in the cases and the controls. A larger proportion of cases than controls reported new bowel symptoms (58% [21 of 36] vs 14% [5 of 35]; p = .001), as well as abdominal pain, incomplete bowel movements, and false alarms on the PAC-SYM questionnaire; however, total PAC-SYM and Vaizey Fecal Incontinence Grading System scores were similar in the 2 groups (median, 8 [interquartile range, 8-10] vs 8 [8-10]; p = .86). Similarly, the proportion of patients with normal stool consistency (Bristol Stool Form Scale score 2-6) was similar in the 2 groups (80.6% [29 of 36] vs 94.3% [33 of 35]; p = .59). CONCLUSION: Segmental bowel resection for DIE may be associated with a higher incidence of new bowel symptoms (possibly due to abdominal pain, incomplete bowel movements, and/or false alarms), but not with worse constipation or fecal incontinence, compared with surgery without bowel resection.Item Open Access Assessment of the Feasibility of Using Noninvasive Wearable Biometric Monitoring Sensors to Detect Influenza and the Common Cold Before Symptom Onset.(JAMA network open, 2021-09) Grzesiak, Emilia; Bent, Brinnae; McClain, Micah T; Woods, Christopher W; Tsalik, Ephraim L; Nicholson, Bradly P; Veldman, Timothy; Burke, Thomas W; Gardener, Zoe; Bergstrom, Emma; Turner, Ronald B; Chiu, Christopher; Doraiswamy, P Murali; Hero, Alfred; Henao, Ricardo; Ginsburg, Geoffrey S; Dunn, JessilynImportance
Currently, there are no presymptomatic screening methods to identify individuals infected with a respiratory virus to prevent disease spread and to predict their trajectory for resource allocation.Objective
To evaluate the feasibility of using noninvasive, wrist-worn wearable biometric monitoring sensors to detect presymptomatic viral infection after exposure and predict infection severity in patients exposed to H1N1 influenza or human rhinovirus.Design, setting, and participants
The cohort H1N1 viral challenge study was conducted during 2018; data were collected from September 11, 2017, to May 4, 2018. The cohort rhinovirus challenge study was conducted during 2015; data were collected from September 14 to 21, 2015. A total of 39 adult participants were recruited for the H1N1 challenge study, and 24 adult participants were recruited for the rhinovirus challenge study. Exclusion criteria for both challenges included chronic respiratory illness and high levels of serum antibodies. Participants in the H1N1 challenge study were isolated in a clinic for a minimum of 8 days after inoculation. The rhinovirus challenge took place on a college campus, and participants were not isolated.Exposures
Participants in the H1N1 challenge study were inoculated via intranasal drops of diluted influenza A/California/03/09 (H1N1) virus with a mean count of 106 using the median tissue culture infectious dose (TCID50) assay. Participants in the rhinovirus challenge study were inoculated via intranasal drops of diluted human rhinovirus strain type 16 with a count of 100 using the TCID50 assay.Main outcomes and measures
The primary outcome measures included cross-validated performance metrics of random forest models to screen for presymptomatic infection and predict infection severity, including accuracy, precision, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUC).Results
A total of 31 participants with H1N1 (24 men [77.4%]; mean [SD] age, 34.7 [12.3] years) and 18 participants with rhinovirus (11 men [61.1%]; mean [SD] age, 21.7 [3.1] years) were included in the analysis after data preprocessing. Separate H1N1 and rhinovirus detection models, using only data on wearble devices as input, were able to distinguish between infection and noninfection with accuracies of up to 92% for H1N1 (90% precision, 90% sensitivity, 93% specificity, and 90% F1 score, 0.85 [95% CI, 0.70-1.00] AUC) and 88% for rhinovirus (100% precision, 78% sensitivity, 100% specificity, 88% F1 score, and 0.96 [95% CI, 0.85-1.00] AUC). The infection severity prediction model was able to distinguish between mild and moderate infection 24 hours prior to symptom onset with an accuracy of 90% for H1N1 (88% precision, 88% sensitivity, 92% specificity, 88% F1 score, and 0.88 [95% CI, 0.72-1.00] AUC) and 89% for rhinovirus (100% precision, 75% sensitivity, 100% specificity, 86% F1 score, and 0.95 [95% CI, 0.79-1.00] AUC).Conclusions and relevance
This cohort study suggests that the use of a noninvasive, wrist-worn wearable device to predict an individual's response to viral exposure prior to symptoms is feasible. Harnessing this technology would support early interventions to limit presymptomatic spread of viral respiratory infections, which is timely in the era of COVID-19.Item Open Access Assisted Fluid Management Software Guidance for Intraoperative Fluid Administration.(Anesthesiology, 2021-08) Maheshwari, Kamal; Malhotra, Gaurav; Bao, Xiaodong; Lahsaei, Peiman; Hand, William R; Fleming, Neal W; Ramsingh, Davinder; Treggiari, Miriam M; Sessler, Daniel I; Miller, Timothy E; Assisted Fluid Management Study TeamBackground
Excessive or inadequate fluid administration causes complications, but despite this, fluid administration during noncardiac surgery is highly variable. Goal-directed management helps optimize the amount and timing of fluid administration; however, implementation is difficult because algorithms are complex. The authors therefore tested the performance of the Acumen Assisted Fluid Management software (Edwards Lifesciences, USA), which is designed to guide optimal intravenous fluid administration during surgery.Methods
In this multicenter, prospective, single-arm cohort evaluation, the authors enrolled 330 adults scheduled for moderate- to high-risk noncardiac surgery that required arterial catheter insertion and mechanical ventilation. Clinicians chose a fluid strategy based on a desired 10%, 15%, or 20% increase in stroke volume (SV) in response to a fluid bolus. Dedicated fluid management software prompted "test" or "recommended" boluses, and clinicians were free to initiate a "user" bolus of 100 to 500 ml of crystalloid or colloid. Clinicians were free to accept or decline the software prompts. The authors primarily compared the fraction of software-recommended boluses that produced suitable increases in SV to a 30% reference rate. On an exploratory basis, we compared responses to software-recommended and clinician-initiated boluses.Results
Four hundred twenty-four of 479 (89%) software-recommended fluid boluses and 508 of 592 (86%) clinician-initiated fluid boluses were analyzed per protocol. Of those, 66% (95% CI, 62 to 70%) of delivered fluid boluses recommended by the software resulted in desired increases in SV, compared with the 30% reference rate, whereas only 41% (95% CI, 38 to 44%) of clinician-initiated boluses did (P < 0.0001). The mean ± SD increase in SV after boluses recommended by the software was 14.2 ± 13.9% versus 8.3 ± 12.1% (P < 0.0001) for those initiated by clinicians.Conclusions
Fluid boluses recommended by the software resulted in desired SV increases more often, and with greater absolute SV increase, than clinician-initiated boluses. Automated assessment of fluid responsiveness may help clinicians optimize intraoperative fluid management during noncardiac surgery.Editor’s perspective
Item Open Access Association between hospital volume and network membership and an analgesia, sedation and delirium order set quality score: a cohort study.(Critical care (London, England), 2012-06) Dale, Christopher R; Hayden, Shailaja J; Treggiari, Miriam M; Curtis, J Randall; Seymour, Christopher W; Yanez, N David; Fan, Vincent SIntroduction
Protocols for the delivery of analgesia, sedation and delirium care of the critically ill, mechanically ventilated patient have been shown to improve outcomes but are not uniformly used. The extent to which elements of analgesia, sedation and delirium guidelines are incorporated into order sets at hospitals across a geographic area is not known. We hypothesized that both greater hospital volume and membership in a hospital network are associated with greater adherence of order sets to sedation guidelines.Methods
Sedation order sets from all nonfederal hospitals without pediatric designation in Washington State that provided ongoing care to mechanically ventilated patients were collected and their content systematically abstracted. Hospital data were collected from Washington State sources and interviews with ICU leadership in each hospital. An expert-validated score of order set quality was created based on the 2002 four-society guidelines. Clustered multivariable linear regression was used to assess the relationship between hospital characteristics and the order set quality score.Results
Fifty-one Washington State hospitals met the inclusion criteria and all provided order sets. Based on expert consensus, 21 elements were included in the analgesia, sedation and delirium order set quality score. Each element was equally weighted and contributed one point to the score. Hospital order set quality scores ranged from 0 to 19 (median = 8, interquartile range 6 to 14). In multivariable analysis, a greater number of acute care days (P = 0.01) and membership in a larger hospital network (P = 0.01) were independently associated with a greater quality score.Conclusions
Hospital volume and membership in a larger hospital network were independently associated with a higher quality score for ICU analgesia, sedation and delirium order sets. Further research is needed to determine whether greater order-set quality is associated with improved outcomes in the critically ill. The development of critical care networks might be one strategy to improve order set quality scores.