AI-Generated Draft Replies Integrated Into Health Records and Physicians' Electronic Communication.

Importance: Timely tests are warranted to assess the association between generative artificial intelligence (GenAI) use and physicians' work efforts. Objective: To investigate the association between GenAI-drafted replies for patient messages and physician time spent on answering messages and the length of replies. Design, Setting, and Participants: Randomized waiting list quality improvement (QI) study from June to August 2023 in an academic health system. Primary care physicians were randomized to an immediate activation group and a delayed activation group. Data were analyzed from August to November 2023. Exposure: Access to GenAI-drafted replies for patient messages. Main Outcomes and Measures: Time spent (1) reading messages, (2) replying to messages, (3) length of replies, and (4) physician likelihood to recommend GenAI drafts. The a priori hypothesis was that GenAI drafts would be associated with less physician time spent reading and replying to messages. A mixed-effects model was used. Results: Fifty-two physicians participated in this QI study, with 25 randomized to the immediate activation group and 27 randomized to the delayed activation group. A contemporary control group included 70 physicians. There were 18 female participants (72.0%) in the immediate group and 17 female participants (63.0%) in the delayed group; the median age range was 35-44 years in the immediate group and 45-54 years in the delayed group. The median (IQR) time spent reading messages in the immediate group was 26 (11-69) seconds at baseline, 31 (15-70) seconds 3 weeks after entry to the intervention, and 31 (14-70) seconds 6 weeks after entry. The delayed group's median (IQR) read time was 25 (10-67) seconds at baseline, 29 (11-77) seconds during the 3-week waiting period, and 32 (15-72) seconds 3 weeks after entry to the intervention. The contemporary control group's median (IQR) read times were 21 (9-54), 22 (9-63), and 23 (9-60) seconds in corresponding periods. The estimated association of GenAI was a 21.8% increase in read time (95% CI, 5.2% to 41.0%; P = .008), a -5.9% change in reply time (95% CI, -16.6% to 6.2%; P = .33), and a 17.9% increase in reply length (95% CI, 10.1% to 26.2%; P < .001). Participants recognized GenAI's value and suggested areas for improvement. Conclusions and Relevance: In this QI study, GenAI-drafted replies were associated with significantly increased read time, no change in reply time, significantly increased reply length, and some perceived benefits. Rigorous empirical tests are necessary to further examine GenAI's performance. Future studies should examine patient experience and compare multiple GenAIs, including those with medical training.

Type 2 diabetes-related health measures during the initial COVID-19 surge at an academic internal medicine practice.

The COVID-19 pandemic disrupted chronic disease management in the United States and across the world. This study reports minimal effects of the initial COVID-19 surge on body mass index, blood pressure, cholesterol, and blood glucose control in ambulatory general internal medicine patients with Type 2 diabetes at a single academic center.

The Office of Belonging, Equity, Diversity, and Inclusion in The Warren Alpert Medical School: Aligning Goals, Programming, and Outcomes for Health Equity.

Although United States (US) medical institutions discuss the importance of diversity, equity, and inclusion, there is little guidance about the process by which these concepts can be attained programmatically within institutions. The Office of Belonging, Equity, Diversity, and Inclusion (OBEDI) at The Warren Alpert Medical School of Brown University intends to rise to the challenge and share knowledge and experience with other institutions. Program design models, and the alignment of inputs, outputs, and outcomes for the short-term and long-term are illustrated. OBEDI's unique model of how each of these concepts contribute towards health equity, from the individual to the community, is also explained. Finally, OBEDI shares promising practices and future directions.

The Use of Flexible Rhinolaryngoscopy for Allergy-Immunology Practice.

Flexible rhinolaryngoscopy is an underused procedure that can provide allergists-immunologists and other physicians with several benefits over existing imaging techniques. In this article, we highlight the many benefits of flexible rhinolaryngoscopy and expand on its safety, cost-effectiveness, and convenience. This article also covers current procedure techniques and assesses the most common indications and relevant clinical findings for which flexible rhinolaryngoscopy can be used to evaluate the nasopharyngeal tract. Videos for the clinician showing some of the most common findings are included.

Patient Voices: Doctors and Diabetes Management.

OBJECTIVE: To assess the challenges of managing diabetes experienced by clients of a community-based social services organization via qualitative interviews; to develop recommendations for more effective diabetes education programming at the organization based on themes identified in the interviews. METHODS: Staff at Progreso Latino in Central Falls recruited clients with diabetes and prediabetes to participate in interviews during the summer of 2019. Each interview used a structured question set and was conducted in the participant's preferred language of Spanish or English. Investigators analyzed the interview transcripts and identified predominant themes. RESULTS: Analysis of fourteen interviews yielded four predominant themes: uncertainty about diagnosis and treatment, fear as part of the discussion with providers, language barriers, and cultural barriers. CONCLUSIONS: To strengthen diabetes education programming at a community-based organization, we recommend utilization of community health workers, development of culturally appropriate dietary recommendations, and creation of educational videos in clients' preferred languages.

Financial Vulnerability of American College of Surgeons-Verified Trauma Centers: A Statewide Analysis.

BACKGROUND: Although trauma centers represent an integral part of healthcare in the US, characterization of their financial vulnerability has not been reported. We sought to characterize the financial health and vulnerability among California trauma centers and identify factors associated with high and low vulnerability. STUDY DESIGN: The RAND Hospital Data financial dataset was used to evaluate all American College of Surgeons (ACS)-verified trauma centers in California. Financial vulnerability of each center was calculated using 6 metrics to calculate a composite Financial Vulnerability Score (FVS). Tertiles of the FVS were generated to classify trauma centers as high, medium, or low financial vulnerability. Hospital characteristics were also analyzed and compared. RESULTS: Forty-seven ACS trauma centers were identified. Nine were Level I, 27 were Level II, and 8 were Level III. Level I centers encompassed the greatest proportion of the high FVS tier (44%), whereas Level II and III centers were the most likely to be in the middle and lower tiers, respectively (44%; 63%). Lower FVS centers had greater asset:liability ratios, operating margins, and days cash on hand compared with the 2 higher tiers, whereas high FVS centers showed a greater proportion of uncompensated care, outpatient share rates, outpatient surgeries, and longer days in net accounts. Lower FVS centers were more likely to be teaching hospitals and members of a larger corporate entity. CONCLUSION: Many ACS trauma centers are at moderate/high risk for financial vulnerability and disparate impacts of stressor events, and the FVS may represent a novel metric that could be used at the local or statewide level.

Surgical management and outcomes of adhesive small bowel obstruction: teaching versus non-teaching hospitals.

BACKGROUND: The relationship between surgical management of adhesive small bowel obstruction (ASBO) and hospital teaching status is not well known. We sought to elucidate the association between hospital teaching status and clinical metrics for ASBO. METHODS: Using the 2007-2017 California Office of Statewide Health Planning and Development database, we identified adult ASBO patients hospitalized for surgical intervention. Hospital teaching status was categorized as major teaching (MajT), minor teaching (MinT), and non-teaching (NT). Cox proportional hazards modeling was used to evaluate risk of death and other adverse outcomes. RESULTS: Of 25,047 admissions, 15.4% were at MajT, 32.0% at MinT, and 52.6% at NT; 2.9% died. Patients at MajT had longer overall hospital stays (HLOS) than those at MinT or NT (median days 9 vs. 8 vs. 8; p = 0.005), longer post-ASBO procedure HLOS (median days 7 vs. 6 vs. 6; p = 0.0001) and higher rates of small bowel resection (27.1% vs. 21.7% vs. 21.7%; p < 0.0001). Mean time to first surgery at MajT was 3.3 days compared with 2.6 days (p = 0.004) at MinT and NT. Compared with patients at NT, those at MajT were significantly less likely to die (HR 0.62, p < 0.0001), develop pneumonia (HR 0.57, p = 0.001), or experience adverse discharge disposition (HR 0.79, p < 0.0001). CONCLUSION: Mortality and morbidity of ASBO surgery were reduced at MajT; however, time to surgery, HLOS, and rate of small bowel resection were greater. These findings may guide improvements in the management of ASBO patients.

Fragmentation of care in the blunt abdominal trauma patient: Capturing our true outcomes and impact on care.

BACKGROUND: Trauma care is associated with unplanned readmissions, which may occur at facilities other than the index treatment facility. This "fragmentation of care" may be associated with adverse outcomes. We evaluated a statewide database that includes readmissions to analyze the incidence and impact of FC. METHODS: The California Office of Statewide Health Planning and Development patient discharge data set was evaluated for calendar years 2016 to 2018. Patients 15 years or older diagnosed with blunt abdominal solid organ injury during the index admission were identified. Readmissions were evaluated postdischarge at 1, 3, and 6 months. Patients readmitted within 6 months to a facility other than the index admission facility (fragmented care [FC]) were compared with those readmitted to their index admission facility (non-FC). Logistic regression modeling was used to evaluate risk of FC. RESULTS: Of the total 1,580 patients, there were 752 FC (47.6%) and 828 (52.4%) non-FC. Readmissions representing FC at months 1, 3, and 6 were 40.3%, 49.3%, and 53.4%, respectively. At index admission, the groups were demographically and clinically similar, with similar rates of abdominal operations and complications. Non-FC patients had a higher rate of abdominal reoperation at readmission (5.8% non-FC vs. 2.9% FC, p = 0.006). In an adjusted model, multiple readmissions (odds ratio [OR] 1.11, p = 0.014), readmission >30 days after index facility discharge (OR, 1.98; p < 0.001), and discharge to a nonmedical facility (OR, 2.46; p < 0.0001) were associated with increased odds of FC. Operative intervention at index admission was associated with lower odds of FC (OR, 0.77; p = 0.039). However, FC was not independently associated with demographic or insurance characteristics. CONCLUSION: The rate of FC among patients with blunt abdominal injury is high. The risk of FC is mitigated when patients are managed operatively during the index admission. Trauma systems should implement measures to ensure that these patients are followed postdischarge. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III; Care management, level IV.

Isolated Intracranial Hemorrhage in Elderly Patients With Pre-Injury Anticoagulation: Is Full Trauma Team Activation Necessary?

BACKGROUND: Traumatic intracranial hemorrhage (ICH) is a highly morbid injury, particularly among elderly patients on preinjury anticoagulants (AC). Many trauma centers initiate full trauma team activation (FTTA) for these high-risk patients. We sought to determine if FTTA was superior compared with those who were evaluated as a trauma consultation (CON). METHODS: Patients aged ≥55 on preinjury AC who presented from January 2015 to December 2019 with blunt isolated head injury (non-head AIS ≤2) and confirmed ICH were identified. CON patients and FTTA patients were matched by age and head AIS. Cox proportional hazard model was used to assess patient and injury characteristics with mortality and survivor discharge disposition. REASULTS: There were 45 CON patients and 45 FTTA patients. Mean age was 80 years in both groups. Fall was the most common mechanism (98% CON vs. 92% FTTA). Glasgow Coma Score (GCS) was lower in FTTA (14 vs. 15, p<0.01). CON had a significantly longer time from arrival to CT scan (1.3 vs. 0.4 hrs, p<0.01). Hospital days were similar (CON: 3.9 vs. FTTA: 3.7 days). However, CON had increased ventilator use (p=0.03). Lower admission GCS was the only factor associated with increased risk of death. Among survivors, only head AIS increased the risk of discharge to a level of care higher than that of preinjury (p=0.01). CONCLUSION: There was no difference in mortality or adverse discharge disposition between FTTA and CON, although FTTA was associated with a more rapid evaluation and diagnosis. Any alteration in GCS was strongly associated with mortality and should prompt evaluation by FTTA.

Revealing the scope of surgical device malfunctions: Analysis of the "hidden" Food and Drug Administration device database.

BACKGROUND: We compared surgical device malfunction reports in the Food and Drug Administration (FDA) public Manufacturer and User Facility Device Experience (MAUDE) with those in the FDA nonpublic Alternative Summary Reporting (ASR). METHODS: General surgery device product code categories in MAUDE and ASR from 1999 to 2018 were identified. Changes in the rates of categories and adverse events were evaluated by Poisson regression. RESULTS: There were 283,308 (72%) general surgical device malfunctions in MAUDE and 109,954 (28%) in ASR. Reports increased annually in ASR versus MAUDE, particularly for surgical staplers and clip devices (p < 0.05). ASR contained approximately 80% of these reports; MAUDE 20%. In MAUDE, 42.9% of surgical device malfunctions and 20.2% of stapler/clip malfunctions resulted in patient injury or death. ASR listed no injury or death information. CONCLUSIONS: ASR contained a significant portion of surgical device malfunctions hidden from public scrutiny. Access to such data is essential to safe surgical care.

The rising tide of methamphetamine use in elderly trauma patients.

BACKGROUND: Methamphetamine (METH) is associated with an elevated risk of injury and the outcomes in the elderly remain unclear. We analyzed METH's impact in elderly trauma patients. METHODS: Retrospective analysis (2009-2018) of trauma patients at a Level I trauma center. Elderly patients were defined as age ≥55. Substance use was identified by blood alcohol test and urine drug screen. Cox proportional hazard model was used to assess patient and injury characteristics with mortality. RESULTS: Of 15,770 patient encounters with substance use testing, 5278 (34%) were elderly. Elderly METH use quadrupled over time (2%-8%; p < 0.01). Elderly METH + patients were more likely to require surgical intervention (35% vs. 17%), mechanical ventilation (15% vs. 7%), and a longer hospitalization (6.5 vs. 3.6 days) compared with elderly substance negative. Multivariate analysis showed increasing age, ventilator use, and injury severity were associated with mortality (ps < 0.01); METH was not related to mortality. CONCLUSION: Substance use in elderly trauma patients increased significantly. METH use in elderly trauma patients is a risk factor for significantly greater resource utilization.

Novel Hydroquinone-Alumina Composites Stabilizing a Guest-Free Clathrate Structure: Applications in Gas Processing.

Organic clathrates formed by hydroquinone (HQ) and gases such as CO2 and CH4 are solid supramolecular host-guest compounds in which the gaseous guest molecules are encaged in a host framework of HQ molecules. Not only are these inclusion compounds fascinating scientific curiosities but they can also be used in practical applications such as gas separation. However, the development and future use of clathrate-based processes will largely depend on the effectiveness of the reactive materials used. These materials should enable fast and selective enclathration and have a large gas storage capacity. This article discusses the properties and performance of a new composite material able to form gas clathrates with hydroquinone (HQ) deposited on alumina particles. Apart from the general characterization of the HQ-alumina composite, one of the most remarkable observations is the unexpected formation of a guest-free clathrate structure with long-term stability (>2 years) inside the composite. Interestingly enough, in addition to a slight improvement in the enclathration kinetics of pure CO2 compared to powdered HQ, preferential capture of CO2 molecules is observed when the HQ-alumina composite is exposed to an equimolar CO2/CH4 gas mixture. In terms of gas capture selectivity toward CO2, the performance of this new composite exceeds that of pure HQ and HQ-silica composites developed in a previous study, opening up new opportunities for the design and use of these novel materials for gas separation.

Long-term evaluation of response to omalizumab therapy in real life by a novel multimodular approach: The Real-life Effectiveness of Omalizumab Therapy (REALITY) study.

BACKGROUND: The evidence on long-term real-life response measures to omalizumab therapy in moderate to severe asthma is limited. A universal assessment tool is needed to adequately evaluate response to omalizumab in these patients. OBJECTIVE: To design a multimodular response assessment tool and use it to measure and define response to omalizumab therapy in real-world settings. METHODS: The Real-life Effectiveness of Omalizumab Therapy (REALITY) study is a retrospective, long-term, real-life clinical study that evaluates response in individuals with allergic asthma who received omalizumab between 2004 and 2011. The Standardized Measure to Assess Response to Therapy (SMART) tool was designed to define response (1 year before to after treatment) by 3 modules: (1) physician's subjective assessment of asthma symptoms and control; (2) objective assessment of 6 parameters: improvement by 50% or more for asthma exacerbation, steroid bursts, emergency department visits, and hospitalizations; increase in forced expiratory volume in 1 second of 200 mL or greater; and improved Asthma Control Test score of 3 or higher; -and (3) true responders (patient meeting both module 1 and 2 criteria). Response was assessed and compared for 3 modules at desired time points. RESULTS: A total of 198 patients (mean age, 31.7 years [range, 3-77 years]; 98 [49%] female; mean omalizumab therapy duration, 2.49 years [range, 3 months to 8 years]; mean omalizumab dosage, 473 mg every 4 weeks; median baseline IgE level, 433 IU/mL) were included in this analysis. Overall visit adherence was 78%, although the adherence rate decreased annually by 20%. Response rates assessed by SMART modules were 61.3%, 60.8%, and 41.8% at 16 weeks, 84.8%, 72.2%, and 64.6% at 1 year, 82.4%, 71.2%, and 63.2% at 2 years, and 95.1%, 87.8%, and 85.4% at 5 years for modules 1, 2, and 3, respectively. There were no significant adverse reactions. CONCLUSION: The REALITY study has demonstrated long-term effectiveness of omalizumab therapy in individuals with allergic asthma in real-life settings. The SMART tool is promising as a potential standard assessment tool to measure and define response to asthma therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01776177.

Clinical Utility of Cell-Free DNA for the Detection of ALK Fusions and Genomic Mechanisms of ALK Inhibitor Resistance in Non-Small Cell Lung Cancer.

Purpose: Patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor anaplastic lymphoma kinase (ALK) gene fusions benefit from treatment with ALK inhibitors (ALKi). Analysis of cell-free circulating tumor DNA (cfDNA) may provide a noninvasive way to identify ALK fusions and actionable resistance mechanisms without an invasive biopsy.Patients and Methods: The Guardant360 (G360; Guardant Health) deidentified database of NSCLC cases was queried to identify 88 consecutive patients with 96 plasma-detected ALK fusions. G360 is a clinical cfDNA next-generation sequencing (NGS) test that detects point mutations, select copy number gains, fusions, insertions, and deletions in plasma.Results: Identified fusion partners included EML4 (85.4%), STRN (6%), and KCNQ, KLC1, KIF5B, PPM1B, and TGF (totaling 8.3%). Forty-two ALK-positive patients had no history of targeted therapy (cohort 1), with tissue ALK molecular testing attempted in 21 (5 negative, 5 positive, and 11 tissue insufficient). Follow-up of 3 of the 5 tissue-negative patients showed responses to ALKi. Thirty-one patients were tested at known or presumed ALKi progression (cohort 2); 16 samples (53%) contained 1 to 3 ALK resistance mutations. In 13 patients, clinical status was unknown (cohort 3), and no resistance mutations or bypass pathways were identified. In 6 patients with known EGFR-activating mutations, an ALK fusion was identified on progression (cohort 4; 4 STRN, 1 EML4; one both STRN and EML4); five harbored EGFR T790M.Conclusions: In this cohort of cfDNA-detected ALK fusions, we demonstrate that comprehensive cfDNA NGS provides a noninvasive means of detecting targetable alterations and characterizing resistance mechanisms on progression. Clin Cancer Res; 24(12); 2758-70. ©2018 AACR.

Thermodiffusion in multicomponent n-alkane mixtures.

Compositional grading within a mixture has a strong impact on the evaluation of the pre-exploitation distribution of hydrocarbons in underground layers and sediments. Thermodiffusion, which leads to a partial diffusive separation of species in a mixture due to the geothermal gradient, is thought to play an important role in determining the distribution of species in a reservoir. However, despite recent progress, thermodiffusion is still difficult to measure and model in multicomponent mixtures. In this work, we report on experimental investigations of the thermodiffusion of multicomponent n-alkane mixtures at pressure above 30 MPa. The experiments have been conducted in space onboard the Shi Jian 10 spacecraft so as to isolate the studied phenomena from convection. For the two exploitable cells, containing a ternary liquid mixture and a condensate gas, measurements have shown that the lightest and heaviest species had a tendency to migrate, relatively to the rest of the species, to the hot and cold region, respectively. These trends have been confirmed by molecular dynamics simulations. The measured condensate gas data have been used to quantify the influence of thermodiffusion on the initial fluid distribution of an idealised one dimension reservoir. The results obtained indicate that thermodiffusion tends to noticeably counteract the influence of gravitational segregation on the vertical distribution of species, which could result in an unstable fluid column. This confirms that, in oil and gas reservoirs, the availability of thermodiffusion data for multicomponent mixtures is crucial for a correct evaluation of the initial state fluid distribution.

A randomized trial of the efficacy and safety of quilizumab in adults with inadequately controlled allergic asthma.

BACKGROUND: Quilizumab, a humanized IgG1 monoclonal antibody, targets the M1-prime segment of membrane-expressed IgE, leading to depletion of IgE-switched and memory B cells. In patients with mild asthma, quilizumab reduced serum IgE and attenuated the early and late asthmatic reaction following whole lung allergen challenge. This study evaluated the efficacy and safety of quilizumab in adults with allergic asthma, inadequately controlled despite high-dose inhaled corticosteroids (ICS) and a second controller. METHODS: Five hundred seventy-eight patients were randomized to monthly or quarterly dosing regimens of subcutaneous quilizumab or placebo for 36 weeks, with a 48-week safety follow-up. Quilizumab was evaluated for effects on the rate of asthma exacerbations, lung function, patient symptoms, serum IgE, and pharmacokinetics. Exploratory analyses were conducted on biomarker subgroups (periostin, blood eosinophils, serum IgE, and exhaled nitric oxide). RESULTS: Quilizumab was well tolerated and reduced serum total and allergen-specific IgE by 30-40 %, but had no impact on asthma exacerbations, lung function, or patient-reported symptom measures. At Week 36, the 300 mg monthly quilizumab group showed a 19.6 % reduction (p = 0.38) in the asthma exacerbation rate relative to placebo, but this was neither statistically nor clinically significant. Biomarker subgroups did not reveal meaningful efficacy benefits following quilizumab treatment. CONCLUSIONS: Quilizumab had an acceptable safety profile and reduced serum IgE. However, targeting the IgE pathway via depletion of IgE-switched and memory B cells was not sufficient for a clinically meaningful benefit for adults with allergic asthma uncontrolled by standard therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01582503.

Patient Perspectives on the Need for and Barriers to Professional Medical Interpretation.

BACKGROUND: Individuals with limited English proficiency (LEP) constitute an increasing share of the patient population in American healthcare settings. Few studies have described the patient's perspective on barriers to medical interpretation and experiences in the clinical setting. METHODS: We conducted focus groups with 22 LEP Spanish-speaking adults. Focus groups were transcribed and analyzed in their original Spanish. RESULTS: LEP patients face significant challenges when accessing health care services due to inadequate or insufficient access to professional interpreters. Predominant themes include: lack of interpreter availability, fear of disclosing limited English skills, and language discordant providers overestimating LEP patients' understanding of English. Many participants felt they had received poorer quality care. CONCLUSIONS: LEP patients face multiple barriers to accessing adequate interpretation leading to a perceived worsening in the quality of care. In order to improve health outcomes for LEP patients, routine provision of adequate interpretation is essential.

Efficacy of omalizumab in asthmatic patients with IgE levels above 700 IU/mL: a retrospective study.

BACKGROUND: Omalizumab is approved for patients with poorly controlled asthma with serum IgE levels between 30 and 700 IU/mL and positive test results for perennial allergens. Its efficacy in patients with IgE levels greater than 700 IU/mL is unclear. OBJECTIVE: To evaluate the response of asthmatic patients treated with omalizumab with IgE levels greater than 700 IU/mL. METHODS: Asthmatic patients treated with omalizumab for 6 months or longer with elevated IgE levels were evaluated retrospectively. Emergency department (ED) visits, hospitalizations, change in forced expiratory volume in 1 second, corticosteroid bursts, and Asthma Control Test (ACT) scores were recorded for a period of 6 months before and after treatment. RESULTS: Twenty-six patients with an IgE level greater than 700 IU/mL (group 1) were matched by age, sex, and severity of asthma to patients with an IgE of 30 to 700 IU/mL (group 2). The mean numbers of ED visits before and after treatment were 0.96 vs 0.23 (P = .008) in group 1 and 0.65 vs 015 (P = .02) in group 2. Both group 1 and group 2 had an improvement in asthma control based on the mean ACT score before and after treatment (15.6 vs 18.9 [P = .02] and 15.4 vs 19 [P = .006], respectively). There was also a significant reduction in the frequency of systemic corticosteroid use during the 6 months before and after treatment (2.58 vs 0.96 [P < .001] and 2.62 vs 1.23 [P < .001] systemic steroid treatments, respectively). CONCLUSION: Omalizumab was as effective in reducing ED visits, controlling asthma symptoms, and reducing the need for systemic corticosteroids in patients with IgE levels greater than 700 IU/mL compared with patients with levels of 30 to 700 IU/mL.