Browsing by Subject "Severity of Illness Index"

Now showing 1 - 20 of 112
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    ItemOpen Access
    A community approach to mortality prediction in sepsis via gene expression analysis.
    (Nature communications, 2018-02) Sweeney, Timothy E; Perumal, Thanneer M; Henao, Ricardo; Nichols, Marshall; Howrylak, Judith A; Choi, Augustine M; Bermejo-Martin, Jesús F; Almansa, Raquel; Tamayo, Eduardo; Davenport, Emma E; Burnham, Katie L; Hinds, Charles J; Knight, Julian C; Woods, Christopher W; Kingsmore, Stephen F; Ginsburg, Geoffrey S; Wong, Hector R; Parnell, Grant P; Tang, Benjamin; Moldawer, Lyle L; Moore, Frederick E; Omberg, Larsson; Khatri, Purvesh; Tsalik, Ephraim L; Mangravite, Lara M; Langley, Raymond J
    Improved risk stratification and prognosis prediction in sepsis is a critical unmet need. Clinical severity scores and available assays such as blood lactate reflect global illness severity with suboptimal performance, and do not specifically reveal the underlying dysregulation of sepsis. Here, we present prognostic models for 30-day mortality generated independently by three scientific groups by using 12 discovery cohorts containing transcriptomic data collected from primarily community-onset sepsis patients. Predictive performance is validated in five cohorts of community-onset sepsis patients in which the models show summary AUROCs ranging from 0.765-0.89. Similar performance is observed in four cohorts of hospital-acquired sepsis. Combining the new gene-expression-based prognostic models with prior clinical severity scores leads to significant improvement in prediction of 30-day mortality as measured via AUROC and net reclassification improvement index These models provide an opportunity to develop molecular bedside tests that may improve risk stratification and mortality prediction in patients with sepsis.
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    A cross-site, comparative effectiveness study of an integrated HIV and substance use treatment program.
    (AIDS Patient Care STDS, 2010-10) Proeschold-Bell, Rae Jean; Heine, Amy; Pence, Brian Wells; McAdam, Keith; Quinlivan, Evelyn Byrd
    Co-occurrence of HIV and substance abuse is associated with poor outcomes for HIV-related health and substance use. Integration of substance use and medical care holds promise for HIV patients, yet few integrated treatment models have been reported. Most of the reported models lack data on treatment outcomes in diverse settings. This study examined the substance use outcomes of an integrated treatment model for patients with both HIV and substance use at three different clinics. Sites differed by type and degree of integration, with one integrated academic medical center, one co-located academic medical center, and one co-located community health center. Participants (n=286) received integrated substance use and HIV treatment for 12 months and were interviewed at 6-month intervals. We used linear generalized estimating equation regression analysis to examine changes in Addiction Severity Index (ASI) alcohol and drug severity scores. To test whether our treatment was differentially effective across sites, we compared a full model including site by time point interaction terms to a reduced model including only site fixed effects. Alcohol severity scores decreased significantly at 6 and 12 months. Drug severity scores decreased significantly at 12 months. Once baseline severity variation was incorporated into the model, there was no evidence of variation in alcohol or drug score changes by site. Substance use outcomes did not differ by age, gender, income, or race. This integrated treatment model offers an option for treating diverse patients with HIV and substance use in a variety of clinic settings. Studies with control groups are needed to confirm these findings.
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    A dimensional approach to understanding severity estimates and risk correlates of marijuana abuse and dependence in adults.
    (International journal of methods in psychiatric research, 2012-06) Wu, Li-Tzy; Woody, George E; Yang, Chongming; Pan, Jeng-Jong; Reeve, Bryce B; Blazer, Dan G
    While item response theory (IRT) research shows a latent severity trait underlying response patterns of substance abuse and dependence symptoms, little is known about IRT-based severity estimates in relation to clinically relevant measures. In response to increased prevalences of marijuana-related treatment admissions, an elevated level of marijuana potency, and the debate on medical marijuana use, we applied dimensional approaches to understand IRT-based severity estimates for marijuana use disorders (MUDs) and their correlates while simultaneously considering gender- and race/ethnicity-related differential item functioning (DIF). Using adult data from the 2008 National Survey on Drug Use and Health (N = 37,897), Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for MUDs among past-year marijuana users were examined by IRT, logistic regression, and multiple indicators-multiple causes (MIMIC) approaches. Among 6917 marijuana users, 15% met criteria for a MUD; another 24% exhibited subthreshold dependence. Abuse criteria were highly correlated with dependence criteria (correlation = 0.90), indicating unidimensionality; item information curves revealed redundancy in multiple criteria. MIMIC analyses showed that MUD criteria were positively associated with weekly marijuana use, early marijuana use, other substance use disorders, substance abuse treatment, and serious psychological distress. African Americans and Hispanics showed higher levels of MUDs than Whites, even after adjusting for race/ethnicity-related DIF. The redundancy in multiple criteria suggests an opportunity to improve efficiency in measuring symptom-level manifestations by removing low-informative criteria. Elevated rates of MUDs among African Americans and Hispanics require research to elucidate risk factors and improve assessments of MUDs for different racial/ethnic groups.
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    ItemOpen Access
    A randomized clinical trial of a coping improvement group intervention for HIV-infected older adults.
    (J Behav Med, 2011-04) Heckman, Timothy G; Sikkema, Kathleen J; Hansen, Nathan; Kochman, Arlene; Heh, Victor; Neufeld, Sharon; AIDS and Aging Research Group
    This research tested if a 12-session coping improvement group intervention (n = 104) reduced depressive symptoms in HIV-infected older adults compared to an interpersonal support group intervention (n = 105) and an individual therapy upon request (ITUR) control condition (n = 86). Participants were 295 HIV-infected men and women 50-plus years of age living in New York City, Cincinnati, OH, and Columbus, OH. Using A-CASI assessment methodology, participants provided data on their depressive symptoms using the Geriatric Depression Screening Scale (GDS) at pre-intervention, post-intervention, and 4- and 8-month follow-up. Whether conducted with all participants (N = 295) or only a subset of participants diagnosed with mild, moderate, or severe depressive symptoms (N = 171), mixed models analyses of repeated measures found that both coping improvement and interpersonal support group intervention participants reported fewer depressive symptoms than ITUR controls at post-intervention, 4-month follow-up, and 8-month follow-up. The effect sizes of the differences between the two active interventions and the control group were greater when outcome analyses were limited to those participants with mild, moderate, or severe depressive symptoms. At no assessment period did coping improvement and interpersonal support group intervention participants differ in depressive symptoms.
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    A risk score for in-hospital death in patients admitted with ischemic or hemorrhagic stroke.
    (J Am Heart Assoc, 2013-01-28) Smith, Eric E; Shobha, Nandavar; Dai, David; Olson, DaiWai M; Reeves, Mathew J; Saver, Jeffrey L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C; Schwamm, Lee H
    BACKGROUND: We aimed to derive and validate a single risk score for predicting death from ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS AND RESULTS: Data from 333 865 stroke patients (IS, 82.4%; ICH, 11.2%; SAH, 2.6%; uncertain type, 3.8%) in the Get With The Guidelines-Stroke database were used. In-hospital mortality varied greatly according to stroke type (IS, 5.5%; ICH, 27.2%; SAH, 25.1%; unknown type, 6.0%; P<0.001). The patients were randomly divided into derivation (60%) and validation (40%) samples. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model in the overall population and in the subset with the National Institutes of Health Stroke Scale (NIHSS) recorded (37.1%). The c statistic, a measure of how well the models discriminate the risk of death, was 0.78 in the overall validation sample and 0.86 in the model including NIHSS. The model with NIHSS performed nearly as well in each stroke type as in the overall model including all types (c statistics for IS alone, 0.85; for ICH alone, 0.83; for SAH alone, 0.83; uncertain type alone, 0.86). The calibration of the model was excellent, as demonstrated by plots of observed versus predicted mortality. CONCLUSIONS: A single prediction score for all stroke types can be used to predict risk of in-hospital death following stroke admission. Incorporation of NIHSS information substantially improves this predictive accuracy.
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    Abuse and dependence on prescription opioids in adults: a mixture categorical and dimensional approach to diagnostic classification.
    (Psychological medicine, 2011-03) Wu, L-T; Woody, GE; Yang, C; Pan, J-J; Blazer, DG
    For the emerging DSM-V, it has been recommended that dimensional and categorical methods be used simultaneously in diagnostic classification; however, little is known about this combined approach for abuse and dependence.Using data (n=37 708) from the 2007 National Survey on Drug Use and Health (NSDUH), DSM-IV criteria for prescription opioid abuse and dependence among non-prescribed opioid users (n=3037) were examined using factor analysis (FA), latent class analysis (LCA, categorical), item response theory (IRT, dimensional), and factor mixture (hybrid) approaches.A two-class factor mixture model (FMM) combining features of categorical latent classes and dimensional IRT estimates empirically fitted more parsimoniously to abuse and dependence criteria data than models from FA, LCA and IRT procedures respectively. This mixture model included a severely affected group (7%) with a comparatively moderate to high probability (0.32-0.88) of endorsing all abuse and dependence criteria items, and a less severely affected group (93%) with a low probability (0.003-0.16) of endorsing all criteria. The two empirically defined groups differed significantly in the pattern of non-prescribed opioid use, co-morbid major depression, and substance abuse treatment use.A factor mixture model integrating categorical and dimensional features of classification fits better to DSM-IV criteria for prescription opioid abuse and dependence in adults than a categorical or dimensional approach. Research is needed to examine the utility of this mixture classification for substance use disorders and treatment response.
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    An item response theory modeling of alcohol and marijuana dependences: a National Drug Abuse Treatment Clinical Trials Network study.
    (Journal of studies on alcohol and drugs, 2009-05) Wu, Li-Tzy; Pan, Jeng-Jong; Blazer, Dan G; Tai, Betty; Stitzer, Maxine L; Brooner, Robert K; Woody, George E; Patkar, Ashwin A; Blaine, Jack D
    OBJECTIVE:The aim of this study was to examine psychometric properties of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), diagnostics criteria for alcohol and marijuana dependences among 462 alcohol users and 311 marijuana users enrolled in two multisite trials of the National Drug Abuse Treatment Clinical Trials Network. METHOD:Diagnostic questions were assessed by the DSM-IV checklist. Data were analyzed by the item response theory and the multiple indicators-multiple causes method procedures. RESULTS:Criterion symptoms of alcohol and marijuana dependences exhibited a high level of internal consistency. All individual symptoms showed good discrimination in distinguishing alcohol or marijuana users between high and low severity levels of the continuum. In both groups, "withdrawal" appeared to measure the most severe symptom of the dependence continuum. There was little evidence of measurement nonequivalence in assessing symptoms of dependence by gender, age, race/ethnicity, and educational level. CONCLUSIONS:These findings highlight the clinical utility of the DSM-IV checklist in assessing alcohol- and marijuana dependence syndromes among treatment-seeking substance users.
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    Assessment of Surgical Treatment Strategies for Moderate to Severe Cervical Spinal Deformity Reveals Marked Variation in Approaches, Osteotomies, and Fusion Levels.
    (World neurosurgery, 2016-07) Smith, Justin S; Klineberg, Eric; Shaffrey, Christopher I; Lafage, Virginie; Schwab, Frank J; Protopsaltis, Themistocles; Scheer, Justin K; Ailon, Tamir; Ramachandran, Subaraman; Daniels, Alan; Mundis, Gregory; Gupta, Munish; Hostin, Richard; Deviren, Vedat; Eastlack, Robert; Passias, Peter; Hamilton, D Kojo; Hart, Robert; Burton, Douglas C; Bess, Shay; Ames, Christopher P; International Spine Study Group

    Objective

    Although previous reports suggest that surgery can improve the pain and disability of cervical spinal deformity (CSD), techniques are not standardized. Our objective was to assess for consensus on recommended surgical plans for CSD treatment.

    Methods

    Eighteen CSD cases were assembled, including a clinical vignette, cervical imaging (radiography, computed tomography/magnetic resonance imaging), and full-length standing radiography. Fourteen deformity surgeons (10 orthopedic, 4 neurosurgery) were queried regarding recommended surgical plans.

    Results

    There was marked variation in treatment plans across all deformity types. Even for the least complex deformities (moderate midcervical apex kyphosis), there was lack of agreement on approach (50% combined anterior-posterior, 25% anterior only, 25% posterior only), number of anterior (range, 2-6) and posterior (range, 4-16) fusion levels, and types of osteotomies. As the kyphosis apex moved caudally (cervical-thoracic junction/upper thoracic spine) and for cases with chin-on-chest kyphosis, >80% of surgeons agreed on a posterior-only approach and >70% recommended a pedicle subtraction osteotomy or vertebral column resection, but the range in number of anterior (4-8) and posterior (4-27) fusion levels was exceptionally broad. Cases of cervical/cervical-thoracic scoliosis had the least agreement for approach (48% posterior only, 33% combined anterior-posterior, 17% anterior-posterior-anterior or posterior-anterior-posterior, 2% anterior only) and had broad variation in the number of anterior (2-5) and posterior (6-19) fusion levels, and recommended osteotomies (41% pedicle subtraction osteotomy/vertebral column resection).

    Conclusions

    Among a panel of deformity surgeons, there was marked lack of consensus on recommended surgical approach, osteotomies, and fusion levels for CSD. Further study is warranted to assess whether specific surgical treatment approaches are associated with better outcomes.
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    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, Jessilyn

    Importance

    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.
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    Association of Preceding Antithrombotic Treatment With Acute Ischemic Stroke Severity and In-Hospital Outcomes Among Patients With Atrial Fibrillation.
    (JAMA, 2017-03) Xian, Ying; O'Brien, Emily C; Liang, Li; Xu, Haolin; Schwamm, Lee H; Fonarow, Gregg C; Bhatt, Deepak L; Smith, Eric E; Olson, DaiWai M; Maisch, Lesley; Hannah, Deidre; Lindholm, Brianna; Lytle, Barbara L; Pencina, Michael J; Hernandez, Adrian F; Peterson, Eric D
    Importance:Antithrombotic therapies are known to prevent stroke for patients with atrial fibrillation (AF) but are often underused in community practice. Objectives:To examine the prevalence of patients with acute ischemic stroke with known history of AF who were not receiving guideline-recommended antithrombotic treatment before stroke and to determine the association of preceding antithrombotic therapy with stroke severity and in-hospital outcomes. Design, Setting, and Participants:Retrospective observational study of 94 474 patients with acute ischemic stroke and known history of AF admitted from October 2012 through March 2015 to 1622 hospitals participating in the Get With the Guidelines-Stroke program. Exposures:Antithrombotic therapy before stroke. Main Outcomes and Measures:Stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS; range of 0-42, with a higher score indicating greater stroke severity and a score ≥16 indicating moderate or severe stroke), and in-hospital mortality. Results:Of 94 474 patients (mean [SD] age, 79.9 [11.0] years; 57.0% women), 7176 (7.6%) were receiving therapeutic warfarin (international normalized ratio [INR] ≥2) and 8290 (8.8%) were receiving non-vitamin K antagonist oral anticoagulants (NOACs) preceding the stroke. A total of 79 008 patients (83.6%) were not receiving therapeutic anticoagulation; 12 751 (13.5%) had subtherapeutic warfarin anticoagulation (INR <2) at the time of stroke, 37 674 (39.9%) were receiving antiplatelet therapy only, and 28 583 (30.3%) were not receiving any antithrombotic treatment. Among 91 155 high-risk patients (prestroke CHA2DS2-VASc score ≥2), 76 071 (83.5%) were not receiving therapeutic warfarin or NOACs before stroke. The unadjusted rates of moderate or severe stroke were lower among patients receiving therapeutic warfarin (15.8% [95% CI, 14.8%-16.7%]) and NOACs (17.5% [95% CI, 16.6%-18.4%]) than among those receiving no antithrombotic therapy (27.1% [95% CI, 26.6%-27.7%]), antiplatelet therapy only (24.8% [95% CI, 24.3%-25.3%]), or subtherapeutic warfarin (25.8% [95% CI, 25.0%-26.6%]); unadjusted rates of in-hospital mortality also were lower for those receiving therapeutic warfarin (6.4% [95% CI, 5.8%-7.0%]) and NOACs (6.3% [95% CI, 5.7%-6.8%]) compared with those receiving no antithrombotic therapy (9.3% [95% CI, 8.9%-9.6%]), antiplatelet therapy only (8.1% [95% CI, 7.8%-8.3%]), or subtherapeutic warfarin (8.8% [95% CI, 8.3%-9.3%]). After adjusting for potential confounders, compared with no antithrombotic treatment, preceding use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio [95% CI], 0.56 [0.51-0.60], 0.65 [0.61-0.71], and 0.88 [0.84-0.92], respectively) and in-hospital mortality (adjusted odds ratio [95% CI], 0.75 [0.67-0.85], 0.79 [0.72-0.88], and 0.83 [0.78-0.88], respectively). Conclusions and Relevance:Among patients with atrial fibrillation who had experienced an acute ischemic stroke, inadequate therapeutic anticoagulation preceding the stroke was prevalent. Therapeutic anticoagulation was associated with lower odds of moderate or severe stroke and lower odds of in-hospital mortality.
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    Avascular necrosis in pediatric systemic lupus erythematosus: a brief report and review of the literature.
    (Pediatr Rheumatol Online J, 2015-04-23) Gurion, Reut; Tangpricha, Vin; Yow, Eric; Schanberg, Laura E; McComsey, Grace A; Robinson, Angela Byun; Atherosclerosis Prevention in Pediatric Lupus Erythematosus Investigators
    UNLABELLED: Avascular necrosis (AVN) occurs in several chronic illnesses, including systemic lupus erythematosus (SLE), but can also occur in healthy children. There are multiple theories to explain why and how AVN occurs, but an exact mechanism has yet to be unraveled. AVN in the pediatric lupus population is understudied. The Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, provides an excellent venue to conduct an exploratory analysis to assess associations between AVN and demographics, SLE disease activity and vitamin D deficiency. Herein we present a brief report describing our findings, as well as reviewing the literature on AVN in SLE and other entities. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00065806.
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    Baseline Frailty Status Influences Recovery Patterns and Outcomes Following Alignment Correction of Cervical Deformity.
    (Neurosurgery, 2021-05) Pierce, Katherine E; Passias, Peter G; Daniels, Alan H; Lafage, Renaud; Ahmad, Waleed; Naessig, Sara; Lafage, Virginie; Protopsaltis, Themistocles; Eastlack, Robert; Hart, Robert; Burton, Douglas; Bess, Shay; Schwab, Frank; Shaffrey, Christopher; Smith, Justin S; Ames, Christopher

    Background

    Frailty severity may be an important determinant for impaired recovery after cervical spine deformity (CD) corrective surgery.

    Objective

    To evaluate postop clinical recovery among CD patients between frailty states undergoing primary procedures.

    Methods

    Patients >18 yr old undergoing surgery for CD with health-related quality of life (HRQL) data at baseline, 3-mo, and 1-yr postoperative were identified. Patients were stratified by the modified CD frailty index scale from 0 to 1 (no frailty [NF] <0.3, mild/severe fraily [F] >0.3). Patients in NF and F groups were propensity score matched for TS-CL (T1 slope [TS] minus angle between the C2 inferior end plate and the C7 inferior end plate [CL]) to control for baseline deformity. Area under the curve was calculated for follow-up time intervals determining overall normalized, time-adjusted HRQL outcomes; Integrated Health State (IHS) was compared between NF and F groups.

    Results

    A total of 106 CD patients were included (61.7 yr, 66% F, 27.7 kg/m2)-by frailty group: 52.8% NF, 47.2% F. After propensity score matching for TS-CL (mean: 38.1°), 38 patients remained in each of the NF and F groups. IHS-adjusted HRQL outcomes from baseline to 1 yr showed a significant difference in Euro-Qol 5 Dimension scores (NF: 1.02, F: 1.07, P = .016). No significant differences were found in the IHS Neck Disability Index (NDI) and modified Japanese Orthopedic Association between frailty groups (P > .05). F patients had more postop major complications (31.3%) compared to the NF (8.9%), P = .004, though DJK occurrence and reoperation between the groups was not significant.

    Conclusion

    While all groups exhibited improved postop disability and pain scores, frail patients experienced greater amount of improvement in overall health state compared to baseline disability. This signifies that with frailty severity, patients have more room for improvement postop compared to baseline quality of life.
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    Baseline Visual Field Findings in the RUSH2A Study: Associated Factors and Correlation With Other Measures of Disease Severity.
    (American journal of ophthalmology, 2020-11) Duncan, Jacque L; Liang, Wendi; Maguire, Maureen G; Audo, Isabelle; Ayala, Allison R; Birch, David G; Carroll, Joseph; Cheetham, Janet K; Esposti, Simona Degli; Durham, Todd A; Erker, Laura; Farsiu, Sina; Ferris, Frederick L; Heon, Elise; Hufnagel, Robert B; Iannaccone, Alessandro; Jaffe, Glenn J; Kay, Christine N; Michaelides, Michel; Pennesi, Mark E; Sahel, José-Alain; Foundation Fighting Blindness Consortium Investigator Group

    Purpose

    To report baseline visual fields in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study.

    Design

    Cross-sectional study within a natural history study.

    Methods

    Setting: multicenter, international.

    Study population

    Usher syndrome type 2 (USH2) (n = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) (n = 47) associated with biallelic disease-causing sequence variants in USH2A.

    Observation procedures

    Repeatability of full-field static perimetry (SP) and between-eye symmetry of kinetic perimetry (KP) were evaluated with intraclass correlation coefficients (ICCs). The association of demographic and clinical characteristics with total hill of vision (VTOT) was assessed with general linear models. Associations between VTOT and other functional and morphologic measures were assessed using Spearman correlation coefficients and t tests.

    Main outcome measures

    VTOT (SP) and III4e isopter area (KP).

    Results

    USH2 participants had more severe visual field loss than ARRP participants (P < .001, adjusting for disease duration, age of enrollment). Mean VTOT measures among 3 repeat tests were 32.7 ± 24.1, 31.2 ± 23.4, and 31.7 ± 23.9 decibel-steradians (intraclass correlation coefficient [ICC] = 0.96). Better VA, greater photopic ERG 30-Hz flicker amplitudes, higher mean microperimetry sensitivity, higher central subfield thickness, absence of macular cysts, and higher III4e seeing area were associated with higher VTOT (all r > .48; P < .05). Mean III4e isopter areas for left (4561 ± 4426 squared degrees) and right eyes (4215 ± 4300 squared degrees) were concordant (ICC = 0.94).

    Conclusions

    USH2 participants had more visual field loss than participants with USH2A-related ARRP, adjusting for duration of disease and age of enrollment. VTOT was repeatable and correlated with other functional and structural metrics, suggesting it may be a good summary measure of disease severity in patients with USH2A-related retinal degeneration.
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    Clinical and radiographic parameters that distinguish between the best and worst outcomes of scoliosis surgery for adults.
    (European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2013-02) Smith, Justin S; Shaffrey, Christopher I; Glassman, Steven D; Carreon, Leah Y; Schwab, Frank J; Lafage, Virginie; Arlet, Vincent; Fu, Kai-Ming G; Bridwell, Keith H; Spinal Deformity Study Group

    Purpose

    Predictors of marked improvement versus failure to improve following surgery for adult scoliosis have not been identified. Our objective was to identify factors that distinguish between patients with the best and worst outcomes following surgery for adult scoliosis.

    Methods

    This is a secondary analysis of a prospective, multicenter spinal deformity database. Inclusion criteria included: age 18-85, scoliosis (Cobb ≥ 30°), and 2-year follow-up. Based on the Oswestry Disability Index (ODI) and the SRS-22 at 2-year follow-up, patients with the best and worst outcomes were identified for younger (18-45) and older (46-85) adults with scoliosis. Clinical and radiographic factors were compared between patients with the best and worst outcomes.

    Results

    276 patients met inclusion criteria (89 younger and 187 older patients). Among younger patients, predictors of poor outcome included: depression/anxiety, smoking, narcotic medication use, older age, greater body mass index (BMI) and greater severity of pain prior to surgery. Among older patients, predictors of poor outcome included: depression/anxiety, narcotic medication use, greater BMI and greater severity of pain prior to surgery. None of the other baseline or peri-operative factors assessed distinguished the best and worst outcomes for younger or older patients, including severity of deformity, operative parameters, or the occurrence of complications.

    Conclusions

    Not all patients achieve favorable outcomes following surgery for adult scoliosis. Baseline and peri-operative factors distinguishing between patients with the best and worst outcomes were predominantly patient factors, including BMI, depression/anxiety, smoking, and pain severity; not comorbidities, severity of deformity, operative parameters, or complications.
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    Clinician judgment vs formal scales for predicting intracerebral hemorrhage outcomes.
    (Neurology, 2016-01-12) Hwang, David Y; Dell, Cameron A; Sparks, Mary J; Watson, Tiffany D; Langefeld, Carl D; Comeau, Mary E; Rosand, Jonathan; Battey, Thomas WK; Koch, Sebastian; Perez, Mario L; James, Michael L; McFarlin, Jessica; Osborne, Jennifer L; Woo, Daniel; Kittner, Steven J; Sheth, Kevin N
    OBJECTIVE: To compare the performance of formal prognostic instruments vs subjective clinical judgment with regards to predicting functional outcome in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: This prospective observational study enrolled 121 ICH patients hospitalized at 5 US tertiary care centers. Within 24 hours of each patient's admission to the hospital, one physician and one nurse on each patient's clinical team were each asked to predict the patient's modified Rankin Scale (mRS) score at 3 months and to indicate whether he or she would recommend comfort measures. The admission ICH score and FUNC score, 2 prognostic scales selected for their common use in neurologic practice, were calculated for each patient. Spearman rank correlation coefficients (r) with respect to patients' actual 3-month mRS for the physician and nursing predictions were compared against the same correlation coefficients for the ICH score and FUNC score. RESULTS: The absolute value of the correlation coefficient for physician predictions with respect to actual outcome (0.75) was higher than that of either the ICH score (0.62, p = 0.057) or the FUNC score (0.56, p = 0.01). The nursing predictions of outcome (r = 0.72) also trended towards an accuracy advantage over the ICH score (p = 0.09) and FUNC score (p = 0.03). In an analysis that excluded patients for whom comfort care was recommended, the 65 available attending physician predictions retained greater accuracy (r = 0.73) than either the ICH score (r = 0.50, p = 0.02) or the FUNC score (r = 0.42, p = 0.004). CONCLUSIONS: Early subjective clinical judgment of physicians correlates more closely with 3-month outcome after ICH than prognostic scales.
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    Comparison of Clinical Care and In-Hospital Outcomes of Asian American and White Patients With Acute Ischemic Stroke.
    (JAMA neurology, 2019-04) Song, Sarah; Liang, Li; Fonarow, Gregg C; Smith, Eric E; Bhatt, Deepak L; Matsouaka, Roland A; Xian, Ying; Schwamm, Lee H; Saver, Jeffrey L
    Importance:Although overall stroke incidence and mortality in the United States is improving, little is known about the characteristics and clinical outcomes of acute ischemic stroke in Asian American individuals. Objective:To compare the characteristics, care, and outcomes of Asian American and white patients with acute ischemic stroke. Design, Setting, Participants:Retrospective analysis of Asian American and white patients admitted with a primary diagnosis of acute ischemic stroke to hospitals participating in the Get With The Guidelines-Stroke (GWTG-Stroke) program between April 1, 2004, and July 31, 2016. The GWTG-Stroke database is a prospectively collected stroke quality improvement registry sponsored by the American Heart Association/American Stroke Association. Main Outcomes and Measures:Multivariable logistic regression models assessed the association of Asian American race/ethnicity, clinical outcomes, and quality measures. Results:The study population of 1 772 299 patients (mean [SD] age, 72.4 [14.2] years; 51.3% female) consisted of 64 337 Asian American patients (3.6%) and 1 707 962 white patients (96.4%) admitted to 2171 GWTG-Stroke hospitals with acute ischemic stroke. After adjustment for patient and hospital variables, Asian American patients were seen with greater stroke severity compared with white patients (National Institutes of Health Stroke Scale [NIHSS] score ≥16) (odds ratio [OR], 1.35; 95% CI, 1.30-1.40; P < .001), manifested higher in-hospital mortality (OR, 1.14; 95% CI, 1.09-1.19; P < .001), had longer length of stay (OR, 1.17; 95% CI, 1.14-1.20; P < .001), and were less likely to ambulate independently at discharge (OR, 0.84; 95% CI, 0.79-0.90; P < .001). Although Asian American patients had fewer intravenous tissue plasminogen activator (IV tPA) administrations than white patients (OR, 0.95; 95% CI, 0.91-0.98; P = .003), they had more symptomatic hemorrhage after tPA (OR, 1.36; 95% CI, 1.20-1.55; P < .001) and overall post-tPA complications (OR, 1.31; 95% CI, 1.18-1.46; P < .001). Asian American patients had better quality measure adherence overall than white patients, including rehabilitation (OR, 1.27; 95% CI, 1.18-1.36; P < .001), door to tPA within 60 minutes (OR, 1.14; 95% CI, 1.06-1.22; P < .001), and intensive statin therapy (OR, 1.14; 95% CI, 1.10-1.18; P < .001). After adjustment for stroke severity, Asian American patients had lower in-hospital mortality than white patients (OR, 0.95; 95% CI, 0.91-0.99; P = .008). Conclusions and Relevance:Asian American patients manifested more severe ischemic strokes, were less likely to receive IV tPA, and had worse functional outcomes than white patients. These findings warrant additional research toward improving clinical outcomes for Asian American patients with acute ischemic stroke.
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    Comparison of Structural Disease Burden to Health-related Quality of Life Scores in 264 Adult Spinal Deformity Patients With 2-Year Follow-up: Novel Insights into Drivers of Disability.
    (Clinical spine surgery, 2017-03) Bakhsheshian, Joshua; Scheer, Justin K; Gum, Jeffrey L; Horner, Lance; Hostin, Richard; Lafage, Virginie; Bess, Shay; Protopsaltis, Themistocles S; Burton, Douglas C; Keefe, Malla; Hart, Robert A; Mundis, Gregory M; Shaffrey, Christopher I; Schwab, Frank; Smith, Justin S; Ames, Christopher P; International Spine Study Group (ISSG)

    Study design

    This is a review of a prospective multicenter database.

    Objective

    To investigate the relationship between preoperative disability and sagittal deformity in patients with high Oswestry Disability Index (ODI) and no sagittal malalignment, or low ODI and high sagittal malalignment.

    Summary of background data

    The relationship between ODI and sagittal malalignment varies between each adult spinal deformity (ASD) patient.

    Methods

    A prospective multicenter database of 365 patients with ASD undergoing surgical reconstruction was analyzed. Inclusion criteria entailed: age 18 years or above and the presence of spinal deformity as defined by a coronal Cobb angle≥20 degrees, sagittal vertical axis (SVA)≥5 cm, pelvic tilt (PT) angle≥25 degrees, or thoracic kyphosis≥60 degrees. Radiographic and health-related quality of life (HRQOL) variables were examined and compared, preoperatively and at 2-year postoperative follow-up. Group 1 (low disability high sagittal-LDHS) consisted of ODI<40 and SVA≥5 cm or PT≥25 degrees or pelvic incidence-lumbar lordosis≥11 degrees and group 2 (high disability low sagittal-HDLS) consisted of ODI>40 and SVA<5 cm and PT<25 degrees and pelvic incidence-lumbar lordosis<11 degrees.

    Results

    Of 264 patients with follow-up, 58 (22.0%) patients were included in LDHS and 30 (11.4%) were included in HDLS. Both groups had similar demographics and preoperative coronal angles. HDLS had worse baseline HRQOL for all measures (P<0.05) except leg and back pain. HDLS had a higher rate of self-reported leg weakness, arthritis, depression and neurological disorder. Both groups had similar 2-year improvements in HRQOL (P>0.05), except only HDLS had a significant Scoliosis Research Society Mental improvement and a significantly higher rate of reaching minimal clinically important differences in Scoliosis Research Society Mental scores (P<0.05).

    Conclusions

    There is an association of worse baseline HRQOL measures, weakness, arthritis, and mental disease in HDLS. Furthermore, HDLS patients demonstrated similar improvements to LDHS. However, HDLS had greater improvements in the mental domains, perhaps indicating the responsiveness of the mental disability to surgical treatment.

    Level of evidence

    Level III.
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    Consistent improvement with eculizumab across muscle groups in myasthenia gravis.
    (Annals of clinical and translational neurology, 2020-08) Mantegazza, Renato; O'Brien, Fanny L; Yountz, Marcus; Howard, James F; REGAIN study group

    Objective

    To assess whether eculizumab, a terminal complement inhibitor, improves patient- and physician-reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups.

    Methods

    Patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open-label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open-label extension were analyzed.

    Results

    Of the 125 patients who participated in REGAIN, 117 enrolled in the open-label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open-label extension.

    Interpretation

    Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti-acetylcholine receptor antibody-positive generalized myasthenia gravis.
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    Continuous intravenous cimetidine decreases stress-related upper gastrointestinal hemorrhage without promoting pneumonia.
    (Crit Care Med, 1993-01) Martin, LF; Booth, FV; Karlstadt, RG; Silverstein, JH; Jacobs, DM; Hampsey, J; Bowman, SC; D'Ambrosio, CA; Rockhold, FW
    OBJECTIVES: To determine whether a continuous i.v. infusion of cimetidine, a histamine-2 (H2) receptor antagonist, is needed to prevent upper gastrointestinal (GI) hemorrhage when compared with placebo and if that usage is associated with an increased risk of nosocomial pneumonia. Due to the importance of this latter issue, data were collected to examine the occurrence rate of nosocomial pneumonia under the conditions of this study. DESIGN: A multicenter, double-blind, placebo-controlled study. INTERVENTIONS: Patients were randomized to receive cimetidine (n = 65) as an iv infusion of 50 to 100 mg/hr or placebo (n = 66). SETTING: Intensive care units in 20 institutions. PATIENTS: Critically ill patients (n = 131), all of whom had at least one acute stress condition that previously had been associated with the development of upper GI hemorrhage. MEASUREMENTS AND MAIN RESULTS: Samples of gastric fluid from nasogastric aspirates were collected every 2 hrs for measurement of pH and were examined for the presence of blood. Upper GI hemorrhage was defined as bright red blood or persistent (continuing for > 8 hrs) "coffee ground material" in the nasogastric aspirate. Baseline chest radiographs were performed and sputum specimens were collected from all patients, and those patients without clear signs of pneumonia (positive chest radiograph, positive cough, fever) at baseline were followed prospectively for the development of pneumonia while receiving the study medication. Cimetidine-infused patients experienced significantly (p = .009) less upper GI hemorrhage than placebo-infused patients: nine (14%) of 65 cimetidine vs. 22 (33%) of 66 placebo patients. Cimetidine patients demonstrated significantly (p = .0001) higher mean intragastric pH (5.7 vs. 3.9), and had intragastric pH values at > 4.0 for a significantly (p = .0001) higher mean percentage of time (82% vs. 41%) than placebo patients. Differences in pH variables were not found between patients who had upper GI hemorrhage and those patients who did not, although there was no patient in the cimetidine group who bled with a pH < 3.5 compared with 11 such patients in the placebo group. Also, the upper GI hemorrhage rate in patients with one risk factor (23%) was similar to that rate in patients with two or more risk factors (25%). Of the 56 cimetidine-infused patients and 61 placebo-infused patients who did not have pneumonia at baseline, no cimetidine-infused patient developed pneumonia while four (7%) placebo-infused patients developed pneumonia. CONCLUSIONS: The continuous i.v. infusion of cimetidine was highly effective in controlling intragastric pH and in preventing stress-related upper GI hemorrhage in critically ill patients without increasing their risk of developing nosocomial pneumonia. While the number of risk factors and intragastric pH may have pathogenic importance in the development of upper GI hemorrhage, neither the risk factors nor the intragastric pH was predictive. Therefore, short-term administration of continuously infused cimetidine offers benefits in patients who have sustained major surgery, trauma, burns, hypotension, sepsis, or single organ failure.
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    Coronal plane spinal malalignment and Parkinson's disease: prevalence and associations with disease severity.
    (The spine journal : official journal of the North American Spine Society, 2015-01) Choi, Hong June; Smith, Justin S; Shaffrey, Christopher I; Lafage, Virginie C; Schwab, Frank J; Ames, Christopher P; Matsumoto, Morio; Baik, Jong Sam; Ha, Yoon

    Background context

    Parkinson's disease (PD) is a progressive degenerative disorder of the central nervous system. Patients with PD often present with abnormal posturing.

    Purpose

    To investigate coronal plane deformities in patients with PD, and to evaluate the correlation between clinical features, coronal parameters related to spine alignment, and disease severity.

    Study design

    A cross-sectional study.

    Patient sample

    Eighty-nine patients with PD and 89 controls were included.

    Outcome measures

    A medical history was collected from the medical records.

    Methods

    This study was a prospective assessment of consecutive patients with PD. Clinical and demographic parameters were collected from medical records and outpatient interviews. Full-length standing anteroposterior and lateral spine radiographs were used to assess the spinal parameters. The threshold for scoliosis was set at a 10° Cobb angle, and the curve type was classified using Schwab classification.

    Results

    A total of 178 patients (89 in PD and 89 in control groups) were included. Scoliosis was identified in 27 patients (30%) and 22 controls (p=.502). However, coronal imbalance was more common in patients with PD than in controls (11 vs. 0 patients, p=.001). Scoliosis was more common in women than in men (male:female=8:19, p=.04). Back pain was more common in patients with scoliosis than in those without scoliosis (14 of 27 vs. 17 of 62, p=.036). Schwab Type IV (thoracolumbar major) was the most common type of scoliosis in patients with PD and Type V (lumbar major) was the most common type in controls. With adjustment for patient age and gender, multiple linear regression analysis revealed that severity of PD (Unified Parkinson's Disease Rating Scale, p=.037) and magnitude of global coronal malalignment (p=.003) were associated with the scoliosis Cobb angle (p=.037, B=0.139). Direction of scoliosis and side of global coronal malalignment were not significantly correlated with the laterality of predominant PD symptoms (p>.05).

    Conclusions

    Global coronal malalignment is more prevalent in patients with PD than in controls. Greater severity of PD was significantly associated with greater magnitude of scoliosis Cobb angle, even after adjusting for the effects of patient age and gender. However, direction of scoliosis and side of global coronal malalignment were not significantly associated with the dominant laterality of PD symptoms.