AI-based differential diagnosis of dementia etiologies on multimodal data.

Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an artificial intelligence (AI) model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a microaveraged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the microaveraged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in clinical settings and drug trials. Further prospective studies are needed to confirm its ability to improve patient care.

AI-based differential diagnosis of dementia etiologies on multimodal data.

Differential diagnosis of dementia remains a challenge in neurology due to symptom overlap across etiologies, yet it is crucial for formulating early, personalized management strategies. Here, we present an AI model that harnesses a broad array of data, including demographics, individual and family medical history, medication use, neuropsychological assessments, functional evaluations, and multimodal neuroimaging, to identify the etiologies contributing to dementia in individuals. The study, drawing on 51,269 participants across 9 independent, geographically diverse datasets, facilitated the identification of 10 distinct dementia etiologies. It aligns diagnoses with similar management strategies, ensuring robust predictions even with incomplete data. Our model achieved a micro-averaged area under the receiver operating characteristic curve (AUROC) of 0.94 in classifying individuals with normal cognition, mild cognitive impairment and dementia. Also, the micro-averaged AUROC was 0.96 in differentiating the dementia etiologies. Our model demonstrated proficiency in addressing mixed dementia cases, with a mean AUROC of 0.78 for two co-occurring pathologies. In a randomly selected subset of 100 cases, the AUROC of neurologist assessments augmented by our AI model exceeded neurologist-only evaluations by 26.25%. Furthermore, our model predictions aligned with biomarker evidence and its associations with different proteinopathies were substantiated through postmortem findings. Our framework has the potential to be integrated as a screening tool for dementia in various clinical settings and drug trials, with promising implications for person-level management.

Creation and Expansion of a Mixed Patient Intermediate Care Unit to Improve ICU Capacity.

OBJECTIVES: ICU capacity strain is associated with worsened outcomes. Intermediate care units (IMCs) comprise one potential option to offload ICUs while providing appropriate care for intermediate acuity patients, but their impact on ICU capacity has not been thoroughly characterized. The aims of this study are to describe the creation of a medical-surgical IMC and assess how the IMC affected ICU capacity. DESIGN: Descriptive report with retrospective cohort review. SETTING: Six hundred seventy-three-bed tertiary care academic medical center with 77 ICU beds. PATIENTS: Adult inpatients who were admitted to the IMC. INTERVENTIONS: An interdisciplinary working group created an IMC which was located on a general ward. The IMC was staffed by hospitalists and surgeons and supported by critical care consultants. The initial maximum census was three, but this number increased to six in response to heightened critical care demand. IMC admission criteria also expanded to include advanced noninvasive respiratory support defined as patients requiring high-flow nasal cannula, noninvasive positive pressure ventilation, or mechanical ventilation in patients with tracheostomies. MEASUREMENTS AND MAIN RESULTS: The primary outcome entailed the number of ICU bed-days saved. Adverse outcomes, including ICU transfer, intubation, and death, were also recorded. From August 2021 to July 2022, 230 patients were admitted to the IMC. The most frequent IMC indications were respiratory support for medical patients and post-operative care for surgical patients. A total of 1023 ICU bed-days were made available. Most patients were discharged from the IMC to a general ward, while 8% of all patients required transfer to an ICU within 48 hours of admission. Intubation (2%) and death (1%) occurred infrequently within 48 hours of admission. Respiratory support was the indication associated with the most ICU transfers. CONCLUSIONS: Despite a modest daily census, an IMC generated substantial ICU bed capacity during a time of peak critical care demand.

Organoid-based in vitro systems to model Cryptosporidium parvum infection in 2D and 3D.

Typical cancer cell-based culture systems cannot support the full life cycle of Cryptosporidium parvum, despite its monoxenous life cycle which is completed in the small intestine of a single host. There is a block to fertilization and zygote formation in vitro. In this paper, we adapted a 2D organoid derived monolayer system and a 3D inverted enteroid system for use in C. parvum culture. 3D inverted enteroids were successfully infected by C. parvum without the need for microinjection and supported subculture of C. parvum. Using the 2D organoid derived monolayer (ODM) system, the infection can be maintained for at least 3 weeks with new oocyst production throughout. Fertilization was confirmed based on successful mating of two strains of C. parvum. We demonstrated that the apparent block to fertilization in typical cell culture is overcome using ODMs.

Evaluating the SPIKES Model for Improving Peer-to-Peer Feedback Among Internal Medicine Residents: a Randomized Controlled Trial.

BACKGROUND: Feedback improves trainee clinical performance, but the optimal way to provide it remains unclear. Peer feedback offers unique advantages but comes with significant challenges including a lack of rigorously studied methods. The SPIKES framework is a communication tool adapted from the oncology and palliative care literature for teaching trainees how to lead difficult conversations. OBJECTIVE: To determine if a brief educational intervention focused on the SPIKES framework improves peer feedback between internal medicine trainees on inpatient medicine services as compared to usual practice. DESIGN: Randomized, controlled trial at an academic medical center during academic year 2017-2018. PARTICIPANTS: Seventy-five PGY1 and 49 PGY2 internal medicine trainees were enrolled. PGY2s were randomized 1:1 to the intervention or control group. INTERVENTION: The intervention entailed a 30-min, case-based didactic on the SPIKES framework followed by a refresher email on SPIKES sent to PGY2s before each inpatient medicine rotation. PGY1s were blinded as to which PGY2s underwent the training. MAIN MEASURES: The primary outcome was PGY1 evaluation of the extent of feedback provided by PGY2s. Secondary outcomes included PGY1 report of feedback quality and PGY2 self-report of feedback quantity and quality. Outcomes were obtained via anonymous online survey and reported using a Likert scale with a range of one to four. KEY RESULTS: PGY1s completed 207 surveys (51% response rate) and PGY2s completed 61 surveys (42% response rate). PGY1s reported a higher extent of feedback (2.5 vs 2.2; p = 0.02; Cohen's d = 0.31), more specific feedback (2.3 vs 2.0; p < 0.01; d = 0.33), and higher satisfaction with feedback (2.6 vs 2.2; p < 0.01; d = 0.47) from intervention PGY2s. There were no significant differences in PGY2 self-reported outcomes. CONCLUSIONS: With modest implementation requirements and notable limitations, a brief educational intervention focused on SPIKES increased PGY1 perception of the extent, specificity, and satisfaction with feedback from PGY2s.

Glioblastoma and malignant melanoma: Serendipitous or anticipated association?

We describe a patient who had primary glioblastoma (GB) and malignant melanoma (MM). A 78-year-old man presented with several weeks to months of history of gait disturbance, confusion, memory disturbance, and worsening speech. Imaging studies performed on admission revealed a large frontotemporal lobe mass associated with the surrounding zone of vasogenic edema. Given the patient's medical history of incomplete biopsy of a midback tumor performed three weeks before, the presumptive clinical diagnosis was metastatic MM. Pathological examination of frozen sections of fragmented specimens obtained at stereotactic biopsy performed on admission revealed a high-grade malignant neoplasm characterized by discohesive cells in a blue myxoid background and abundant foci of tumor necrosis. Given these features, in conjunction with the abovementioned pathological report, the frozen section diagnosis by the neuropathologist was "neoplasm identified, favor melanoma." Due to the paucity of lesional tissue, a limited immunohistochemistry performed on the permanent sections revealed positive staining of lesional cells for Sox10 alone using a multiplex MART1/Sox10 immunostain and S-100 protein, an immunohistochemical profile supporting the presumptive frozen section diagnosis. A tumor debulk procedure, performed two weeks later, revealed histopathologic features most compatible with GB, IDH wild-type. Thus, additional immunohistochemistry on the permanent sections revealed positive staining of glial fibrillary acidic protein (GFAP), Sox10, and S-100 protein as well as negative staining of gp100, a complex carbohydrate matrix protein in embryonic melanosomes, using a specific antibody HMB45. The concomitant occurrence of MM and GB in our patient underscores the association between these two entities. Our literature review suggests that the sporadic co-occurrence of these two conditions is likely not serendipitous.

Triggered Palliative Care Consults: A Systematic Review of Interventions for Hospitalized and Emergency Department Patients.

CONTEXT: Palliative care improves the quality of care and may reduce utilization, but delays or the absences of such services are common and costly in inpatient and emergency department settings. Triggered palliative care consults (PCCs) offer one way to identify patients who would benefit from palliative care and to connect them with services early in their course. Consensus reports recommend use of triggers to identify patients for PCC, but no standards exist to guide trigger design or implementation. OBJECTIVES: To conduct a systematic review of published trigger tools for PCC. METHODS: Studies included quality improvement and prospective analyses of triggers for PCC for adults in the emergency department and inpatient settings since 2008. Paired reviewers evaluated the studies for inclusion criteria and extracted data related to study demographics, trigger processes, trigger criteria, and study bias. RESULTS: The search yielded 5773 citations. Twenty studies were included for final analysis with more than 17,000 patients represented. Trigger processes and composition were heterogeneous, although frequently used categories, such as cancer, dementia, and chronic comorbidities, were identified. Three-quarters of the studies were deemed to have moderate or high risk of bias. CONCLUSION: We present a range of trigger tools spanning different hospital settings and patient populations. Common themes in implementation and content arose, but the limitations of these studies are notable, and further rigorous randomized comparisons are needed to generate standards of care. In addition, future studies should focus on developing triggers that identify patients requiring primary-level vs. specialty-level palliative care.

Adjuvant treatments for ependymomas.

Ependymomas are rare primary central nervous system tumors occurring in children and young adults. They can be indolent or locally aggressive depending on location, histology, and extent of resection. Treatment involves maximal surgical resection and usually focal radiation therapy, depending on the presence of residual disease and tumor grade. Chemotherapy has been studied for both adults and children but do not have an established role in adjuvant therapy. In both age groups, treatment with mainly cisplatin based regimens can be considered in the setting of residual disease after surgery or for salvage therapy when surgery or further radiation is not indicated. In children, chemotherapy can be considered in very young children to delay radiation or to increase the likelihood of complete resection in second look surgery. Targeted agents such as bevacizumab and lapatinib do not have a role in adjuvant therapy for ependymomas but are being explored for recurrent disease. This review discusses adjuvant therapy in both adult and child populations.

Emergency Department-Initiated Palliative Care in Advanced Cancer: A Randomized Clinical Trial.

IMPORTANCE: The delivery of palliative care is not standard of care within most emergency departments (EDs). OBJECTIVE: To compare quality of life, depression, health care utilization, and survival in ED patients with advanced cancer randomized to ED-initiated palliative care consultation vs care as usual. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, randomized clinical trial of ED-initiated palliative care consultation for patients with advanced cancer vs usual care took place from June 2011 to April 2014 at an urban, academic ED at a quaternary care referral center. Adult patients with advanced cancer who were able to pass a cognitive screen, had never been seen by palliative care, spoke English or Spanish, and presented to the ED met eligibility criteria; 136 of 298 eligible patients were approached and enrolled in the ED and randomized via balanced block randomization. INTERVENTIONS: Intervention participants received a comprehensive palliative care consultation by the inpatient team, including an assessment of symptoms, spiritual and/or social needs, and goals of care. MAIN OUTCOMES AND MEASURES: The primary outcome was quality of life as measured by the change in Functional Assessment of Cancer Therapy-General Measure (FACT-G) score at 12 weeks. Secondary outcomes included major depressive disorder as measured by the Patient Health Questionnaire-9, health care utilization at 180 days, and survival at 1 year. RESULTS: A total of 136 participants were enrolled, and 69 allocated to palliative care (mean [SD], 55.1 [13.1] years) and 67 were randomized to usual care (mean [SD], 57.8 [14.7] years). Quality of life, as measured by a change in FACT-G score from enrollment to 12 weeks, was significantly higher in patients randomized to the intervention group, who demonstrated a mean (SD) increase of 5.91 (16.65) points compared with 1.08 (16.00) in controls (P = .03 using the nonparametric Wilcoxon test). Median estimates of survival were longer in the intervention group than the control group: 289 (95% CI, 128-453) days vs 132 (95% CI, 80-302) days, although this did not reach statistical significance (P = .20). There were no statistically significant differences in depression, admission to the intensive care unit, and discharge to hospice. CONCLUSIONS AND RELEVANCE: Emergency department-initiated palliative care consultation in advanced cancer improves quality of life in patients with advanced cancer and does not seem to shorten survival; the impact on health care utilization and depression is less clear and warrants further study. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01358110.

Emergency department-triggered palliative care in advanced cancer: proof of concept.

BACKGROUND: The American College of Emergency Physicians and the American Society of Clinical Oncology recommend early palliative care consultation for patients with advanced, life-limiting illnesses, such as metastatic cancer. OBJECTIVES: The objectives were to assess the process of early referral from the emergency department (ED) to palliative care for patients with advanced, incurable cancer as part of a randomized controlled trial and to compare the proportion and timing of consultation to a care as usual group. METHODS: A single-blind randomized controlled trial (ClinicalTrials.gov ID NCT01358110) compared early, ED-based referrals to palliative care for patients admitted with advanced, incurable cancer to physician-driven consultation (i.e., care as usual). Participants had to speak English or Spanish and have no history of palliative care consultation. They were randomized via balanced block randomization to the intervention or control group. Each intervention subject was referred by a research staff member to the palliative care team for consultation. The usual care group received palliative care only if requested by the admitting physician. Analysis was based on intention to treat. A chart review was performed to assess proportion and timing of palliative care consults during the index admission, defined as: (1) completed palliative care consult documented in the chart and (2) days from admission to palliative care consult. RESULTS: A total of 134 participants were enrolled and randomized. For patients in the intervention group, 88% (60 of 68) had documented palliative care consultations during their index admissions (95% confidence interval [CI] = 80.5 to 95.5), compared to 18% (12 of 66) in the control group (95% CI = 8.8 to 27.5; p < 0.01). The 60 intervention patients received palliative care consultations on average 1.48 days from admission (95% CI = 1.19 to 1.76), compared to 2.9 days from admission in the 12 control patients (95% CI = 1.03 to 4.79; p = 0.15). CONCLUSIONS: This study documented a low baseline rate of palliative care involvement as part of usual care in patients with advanced cancer being admitted from the ED. Early referral to palliative care in the context of a research study significantly increased the likelihood that patients received a consult, thus meriting further investigation of how to generalize this approach.

The bronchodilator response to salmeterol is maintained with regular, long-term use in patients with COPD.

Long-acting beta(2)-agonists (LABAs) are recommended in the management of patients with chronic obstructive pulmonary disease (COPD). Previous studies have demonstrated that the LABA, salmeterol, improves lung function, symptoms and quality of life in patients with COPD. In this study, we have performed additional analyses of the combined data from two previous double-blind, placebo-controlled, parallel studies of salmeterol (50 microg, b.i.d) in patients with COPD. The new analyses reveal that the significant improvements seen in pre-dose and 2-h post-dose forced expiratory volume in 1 s (FEV(1)) compared to placebo, occur early in the treatment period, and are sustained for at least 24 weeks. Moreover, improvements in peak expiratory flow rate occur as early as Day 1, and are sustained throughout the 24-week period. Additional analyses of 12-h FEV(1) data also show that salmeterol is associated with an increase in the area under the curve at Week 12 compared with Day 1, adding further support to evidence that it results in a sustained bronchodilator response, with no evidence of tolerance.

Relationship between quality of life and clinical status in asthma: a factor analysis.

Many studies have shown that correlation between clinical asthma status and asthma-specific quality of life is only weak to moderate. However, this relationship has never been explored to determine whether the weakness is due to noise of measurement or whether quality of life is a distinct component of asthma health status. With a database from three clinical trials (n = 763), factor analysis was used to explore the relationships between quality of life, measured by the Asthma Quality of Life Questionnaire (AQLQ), and conventional measures of asthma clinical status (symptoms, airway calibre and rescue beta2-agonist use). The analysis revealed that although patients with severe, poorly controlled asthma tend to have worse quality of life than milder, well-controlled patients, overall asthma health status has four components (factors): asthma-specific quality of life; airway calibre; daytime symptoms and daytime beta2-agonist use, and night-time symptoms and night-time beta2-agonist use. The clean loading of all 21 outcomes onto four distinct and clinically identifiable factors suggests that, although some weakness of correlation between clinical indices and quality of life may be due to noise of measurement, it is mainly attributable to asthma health status being composed of distinct components.

Comparison of fluticasone propionate-salmeterol combination therapy and montelukast in patients who are symptomatic on short-acting beta(2)-agonists alone.

The objective of this study was to determine whether initial maintenance therapy for the treatment of inflammation and bronchoconstriction associated with persistent asthma is more effective with a combination product (100 microg of fluticasone propionate and 50 microg of salmeterol [FSC]) administered twice daily through the Diskus device (GlaxoWellcome, Research Triangle Park, NC) or with montelukast at 10 mg once daily. A 12-wk, randomized, double-blind, double-dummy, multicenter study was conducted with 423 patients 15 yr of age and older with asthma and who were symptomatic while receiving short-acting beta(2)-agonists alone. At end point, FSC resulted in significantly greater increases in morning predose FEV(1) (0.54 +/- 0.03 vs. 0.27 +/- 0.03 L), morning peak expiratory flow (PEF) (89.9 +/- 6.7 vs. 34.2 +/- 4.7 L/min), evening PEF (69.9 +/- 5.8 vs. 31.1 +/- 4.5 L/min), the percentage of symptom-free days (48.9 +/- 2.9 vs. 21.7 +/- 2.5%), the percentage of rescue-free days (53.0 +/- 2.8 vs. 26.2 +/- 2.5%), and the percentage of nights with no awakenings (23.0 +/- 2.5 vs. 15.5+/-2.4%) compared with montelukast (p < or = 0.001, all comparisons). FSC significantly reduced asthma symptom scores (-1.0 +/- 0.1 vs. -0.6 +/- 0.1), rescue albuterol use (-3.3 +/- 0.2 vs. -1.9 +/- 0.2 puffs/d), and the number of exacerbations (0 vs. 11) compared with montelukast (p < 0.001). Both treatments were well tolerated. In summary, treatment of the two main components of asthma (inflammation and bronchoconstriction) with fluticasone propionate and salmeterol in a combination product was a more effective initial maintenance treatment strategy than treatment with montelukast, a single-mediator antagonist.

Salmeterol powder provides significantly better benefit than montelukast in asthmatic patients receiving concomitant inhaled corticosteroid therapy.

STUDY OBJECTIVES: Comparison of inhaled salmeterol powder vs oral montelukast treatment in patients with persistent asthma who remained symptomatic while receiving inhaled corticosteroids. DESIGN: Randomized, double-blind, double-dummy, parallel-group, multicenter trials of 12-week duration. SETTING: Outpatients in private and university-affiliated clinics. PATIENTS: Male and female patients > or = 15 years of age with a diagnosis of asthma (baseline FEV(1) of 50 to 80% of predicted) and symptomatic despite receiving inhaled corticosteroids. INTERVENTIONS: Inhaled salmeterol xinafoate powder, 50 microg bid, or oral montelukast, 10 mg qd. MEASUREMENTS AND RESULTS: Treatment with salmeterol powder resulted in significantly greater improvements from baseline compared with montelukast for most efficacy measurements, including morning peak expiratory flow (35.0 L/min vs 21.7 L/min; p < 0.001), percentage of symptom-free days (24% vs 16%; p < 0.001), and the percentage of rescue-free days (27% vs 20%; p = 0.002). Total supplemental albuterol use was decreased significantly more in the salmeterol group compared with the montelukast group (- 1.90 puffs per day vs - 1.66 puffs per day; p = 0.004) and nighttime awakenings per week decreased significantly more with salmeterol than with montelukast (- 1.42 vs - 1.32; p = 0.015). Patients treated with inhaled salmeterol were significantly more satisfied with their treatment regimen and how well, how fast, and how long it worked than were patients who were treated with oral montelukast. The safety profiles for the two treatments were similar. CONCLUSION: In patients with persistent asthma who remain symptomatic while receiving inhaled corticosteroids, adding inhaled salmeterol powder provided significantly greater improvement in lung function and asthma symptoms and was preferred by patients over oral montelukast.

Salmeterol plus theophylline combination therapy in the treatment of COPD.

BACKGROUND: Patients with COPD often require multiple therapies to improve lung function and decrease symptoms and exacerbations. Salmeterol and theophylline are indicated for the treatment of COPD, but the use of these agents in combination has not been extensively studied. OBJECTIVES: To compare the efficacy and safety of salmeterol plus theophylline vs either agent alone in COPD. METHODS: Randomized, double-blind, double-dummy, parallel-group trial in 943 patients with COPD. After an open-label theophylline titration period (serum levels, 10 to 20 microg/mL), patients were randomly assigned to receive salmeterol (42 microg bid) plus theophylline, salmeterol (42 microg bid), or theophylline for 12 weeks. Serial pulmonary function tests were completed on day 1 and treatment week 12. Patients kept diary cards and noted their peak flow rates, symptom scores, and albuterol use, and periodically completed quality-of-life and dyspnea questionnaires. RESULTS: All three groups significantly improved compared with baseline. Combination treatment with salmeterol plus theophylline provided significantly (p < or = 0.045) greater improvements in pulmonary function; significantly (p < or = 0.048) greater decreases in symptoms, dyspnea, and albuterol use; and significantly fewer COPD exacerbations (p = 0.023 vs theophylline). In general, treatment with salmeterol provided greater improvement in lung function and satisfaction with treatment compared with theophylline. Salmeterol treatment was also associated with significantly fewer drug-related adverse events (p < or = 0.042) than either treatment that included theophylline. The safety profile (adverse events, vital signs, and ECG findings) of the two treatments that included theophylline were similar. CONCLUSION: Patients with COPD may benefit from combination treatment with salmeterol plus theophylline, without a resulting increase in adverse events or other adverse sequelae.

Addition of salmeterol to low-dose fluticasone versus higher-dose fluticasone: an analysis of asthma exacerbations.

BACKGROUND: Adding salmeterol to low-dose fluticasone propionate (FP) produces greater improvements in pulmonary function and symptom control than increasing the dose of FP in patients who remain symptomatic with low-dose FP. OBJECTIVE: We sought to compare the rates and characteristics of asthma exacerbations in patients after adding salmeterol to low-dose FP with the rates and characteristics of exacerbations in patients receiving higher dose FP. METHODS: In 2 multicenter, double-blind studies, 925 patients 12 years of age and older receiving 88 microg twice daily FP randomly received either 42 microg of salmeterol and 88 microg of FP or an increased dose of FP (220 microg) twice daily for 24 weeks. Exacerbation rates and clinical measures of asthma worsening were assessed for all patients who experienced an asthma exacerbation. RESULTS: The addition of salmeterol resulted in a significantly lower rate and number of exacerbations compared with higher dose FP. A total of 41 (8.8%) patients experienced 47 exacerbations with the addition of salmeterol compared with 63 (13.8%) patients with 75 exacerbations in the group receiving increased-dose FP (P =.017). Salmeterol plus low-dose FP was significantly more protective than increased-dose FP in preventing asthma exacerbations, as assessed by the time to first exacerbation (P <.05). In both groups clinical indicators of worsening asthma showed parallel changes before asthma exacerbation, and greater improvements were observed after exacerbation with salmeterol compared with higher dose FP. CONCLUSION: Salmeterol plus low-dose FP was more effective than higher dose FP alone in reducing asthma exacerbations in patients with persistent asthma. The ability to detect deteriorating asthma and the severity of exacerbation was similar between groups.

Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast.

BACKGROUND: Asthma is a disease of chronic inflammation and bronchoconstriction. Inhaled corticosteroids (ICSs) provide important anti-inflammatory treatment but may not provide optimal control of asthma when taken alone. Two therapeutic alternatives for enhanced asthma control are to substitute the combination of fluticasone propionate (FP) and salmeterol (FP/Salm Combo) through the Diskus inhaler or to add montelukast to existing ICS therapy. OBJECTIVE: We compared the efficacy and safety of FP/Salm Combo through the Diskus inhaler versus montelukast added to FP (FP + montelukast) in patients whose symptoms were suboptimally controlled with ICS therapy. METHODS: We performed a multicenter, double-blind, double-dummy, parallel-group, 12-week study in 447 patients with asthma who were symptomatic at baseline while receiving low-dose FP. Patients were treated for 12 weeks with one of the following: (1) combination of FP 100 microg plus salmeterol 50 microg twice daily through the Diskus inhaler, or (2) FP 100 microg twice daily through the Diskus inhaler plus oral montelukast 10 mg once daily. RESULTS: FP/Salm Combo treatment provided better overall asthma control than FP + montelukast with significantly greater improvements in morning peak expiratory flow (+24.9 L/min vs +13.0 L/min, P <.001), evening peak expiratory flow (+18.9 L/min vs +9.6 L/min, P <.001), and forced expiratory volume in 1 second (+0.34 L vs +0.20 L, P <.001), as well as a change in the percentage of days with no albuterol use (+26.3% vs +19.1%, P =.032) and the shortness of breath symptom score (-0.56 vs -0.40, P =.017). The groups had comparable improvements in chest tightness, wheeze, and overall symptom scores. Asthma exacerbation rates were significantly lower (P =.031) in the FP/Salm Combo group (4 patients, 2%) than in the FP + montelukast group (13 patients, 6%). Adverse event profiles were comparable. CONCLUSION: Symptomatic patients on low-dose ICS therapy had significantly greater improvement in asthma control when switched to the FP/Salm Combo than when montelukast was added to ICS therapy.