Roslyn A. Stone

Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial

BACKGROUND Although practice guidelines recommend outpatient care for selected, haemodynamically stable patients with pulmonary embolism, most treatment is presently inpatient based. We aimed to assess non-inferiority of outpatient care compared with inpatient care. METHODS We undertook an open-label, randomised non-inferiority trial at 19 emergency departments in Switzerland, France, Belgium, and the USA. We randomly assigned patients with acute, symptomatic pulmonary embolism and a low risk of death (pulmonary embolism severity index risk classes I or II) with a computer-generated randomisation sequence (blocks of 2-4) in a 1:1 ratio to initial outpatient (ie, discharged from hospital ≤24 h after randomisation) or inpatient treatment with subcutaneous enoxaparin (≥5 days) followed by oral anticoagulation (≥90 days). The primary outcome was symptomatic, recurrent venous thromboembolism within 90 days; safety outcomes included major bleeding within 14 or 90 days and mortality within 90 days. We used a non-inferiority margin of 4% for a difference between inpatient and outpatient groups. We included all enrolled patients in the primary analysis, excluding those lost to follow-up. This trial is registered with ClinicalTrials.gov, number NCT00425542. FINDINGS Between February, 2007, and June, 2010, we enrolled 344 eligible patients. In the primary analysis, one (0·6%) of 171 outpatients developed recurrent venous thromboembolism within 90 days compared with none of 168 inpatients (95% upper confidence limit [UCL] 2·7%; p=0·011). Only one (0·6%) patient in each treatment group died within 90 days (95% UCL 2·1%; p=0·005), and two (1·2%) of 171 outpatients and no inpatients had major bleeding within 14 days (95% UCL 3·6%; p=0·031). By 90 days, three (1·8%) outpatients but no inpatients had developed major bleeding (95% UCL 4·5%; p=0·086). Mean length of stay was 0·5 days (SD 1·0) for outpatients and 3·9 days (SD 3·1) for inpatients. INTERPRETATION In selected low-risk patients with pulmonary embolism, outpatient care can safely and effectively be used in place of inpatient care. FUNDING Swiss National Science Foundation, Programme Hospitalier de Recherche Clinique, and the US National Heart, Lung, and Blood Institute. Sanofi-Aventis provided free drug supply in the participating European centres.

OCMAP-PLUS: a program for the comprehensive analysis of occupational cohort data.

The Occupational Cohort Mortality Analysis Program (OCMAP) has been redesigned for optimal microcomputer use and extended to include new computing algorithms. The new program, OCMAP-PLUS, offers a comprehensive, flexible, and efficient analysis of incidence or mortality rates and standardized measures in relation to multiple and diverse work history and exposure measures. New features include executable code, minimization of memory requirements, disk file storage of person-day arrays, stratified analyses by geographic area, employment status and up to eight exposure variables, a data imputation algorithm for study members with unknown race, and enhanced algorithms for constructing several time-dependent exposure measures. New modules create grouped data files for Poisson and logistic regression and risk set files for use in relative risk regression analysis. The Mortality and Population Data System (MPDS) provides external comparison rates and proportional mortalities. Analysis from two recent cohort mortality studies illustrate several new features.

Active Care Management Supported by Home Telemonitoring in Veterans with Type 2 Diabetes: (The DiaTel Randomized Controlled Trial)

OBJECTIVE We compared the short-term efficacy of home telemonitoring coupled with active medication management by a nurse practitioner with a monthly care coordination telephone call on glycemic control in veterans with type 2 diabetes and entry A1C ≥7.5%. RESEARCH DESIGN AND METHODS Veterans who received primary care at the VA Pittsburgh Healthcare System from June 2004 to December 2005, who were taking oral hypoglycemic agents and/or insulin for ≥1 year, and who had A1C ≥7.5% at enrollment were randomly assigned to either active care management with home telemonitoring (ACM+HT group, n = 73) or a monthly care coordination telephone call (CC group, n = 77). Both groups received monthly calls for diabetes education and self-management review. ACM+HT group participants transmitted blood glucose, blood pressure, and weight to a nurse practitioner using the Viterion 100 TeleHealth Monitor; the nurse practitioner adjusted medications for glucose, blood pressure, and lipid control based on established American Diabetes Association targets. Measures were obtained at baseline, 3-month, and 6-month visits. RESULTS Baseline characteristics were similar in both groups, with mean A1C of 9.4% (CC group) and 9.6% (ACM+HT group). Compared with the CC group, the ACM+HT group demonstrated significantly larger decreases in A1C at 3 months (1.7 vs. 0.7%) and 6 months (1.7 vs. 0.8%; P < 0.001 for each), with most improvement occurring by 3 months. CONCLUSIONS Compared with the CC group, the ACM+HT group demonstrated significantly greater reductions in A1C by 3 and 6 months. However, both interventions improved glycemic control in primary care patients with previously inadequate control.

Validation of a clinical prognostic model to identify low-risk patients with pulmonary embolism

Objective.  To validate the Pulmonary Embolism Severity Index (PESI), a clinical prognostic model which identifies low‐risk patients with pulmonary embolism (PE).

Comparison of a disease-specific and a generic severity of illness measure for patients with community-acquired pneumonia

AbstractOBJECTIVE: To compare the performances of a disease-specific severity of illness index and a prototypical generic severity of illness measure, MedisGroups Admission Severity Groups (ASGs), for patients with community-acquired pneumonia. DESIGN: A retrospective database study. PATIENTS: Adult patients (aged ≥ 18 years) with an ICD-9-CM principal diagnosis of pneumonia in 78 MedisGroups Comparative Database hospitals. METHODS: The pneumonia severity of illness index (PSI) was developed to predict hospital mortality using logistic regression analyses in a 70% random sample of study patients. The performances of the PSI and the generic severity measure were assessed among the remaining 30% of patients by comparing observed mortalities within the five PSI and ASG severity classes, and areas under their receiver operating characteristic (ROC) curves. Both the PSI and the generic severity measure were used to estimate the 95% confidence interval of the expected number of deaths in each of the 78 study hospitals. Hospitals with an observed number of deaths outside these limits were identified as outliers. RESULTS: There were 14,199 study patients who had community-acquired pneumonia, and 1,542 (10.9%) died during hospitalization. In comparison with the generic severity measure, the PSI more accurately identified patients at extremely low risk of death, and had a larger area under its ROC curve (0.84 vs 0.79; p<0.0001). Of the 78 study hospitals, 17 (21.8%) were classified as outliers for mortality by at least one severity adjustment system. Among the 11 low-outlier hospitals, six were classified by the generic severity measure alone, two by the PSI alone, and three by both systems; among the six high-outlier hospitals, one was classified by the generic measure alone, three by the PSI alone, and two by both systems. CONCLUSIONS: The PSI provided more accurate estimates of hospital mortality and classified different hospital outliers for mortality than did the generic severity of illness measure for patients with community-acquired pneumonia.

Discordant Responses to Potent Antiretroviral Treatment in Previously Naive HIV-1-Infected Adults Initiating Treatment in Resource-Constrained Countries The Antiretroviral Therapy in Low-Income Countries (ART-LINC) Collaboration

Objectives:To assess the frequency of and risk factors for discordant responses at 6 months on highly active antiretroviral therapy (HAART) in previously treatment-naive HIV patients from resource-limited countries. Methods:The Antiretroviral Therapy in Low-Income Countries Collaboration is a network of clinics providing care and treatment to HIV-infected patients in Africa, Latin America, and Asia. Patients who initiated therapy between 1996 and 2004, were aged 16 years or older, and had a baseline CD4 cell count were included in this analysis. Responses were defined based on plasma viral load (PVL) and CD4 cell count at 6 months as complete virologic and immunologic (VR+IR+), virologic only (VR+IR−), immunologic only (VR−IR+), and nonresponse (VR−IR−). Multinomial logistic regression was used to assess the association between therapy responses and clinical and demographic variables. Results:Of the 3111 patients eligible for analysis, 1914 had available information at 6 months of therapy: 1074 (56.1%) were VR+IR+, 364 (19.0%) were VR+IR−, 283 (14.8%) were (VR−IR+), and 193 (10.1%) were VR−IR−. Compared with complete responders, virologic-only responders were older, had a higher baseline CD4 cell count, had a lower baseline PVL, and were more likely to have received a nonstandard HAART regimen; immunologic-only responders were younger, had a lower baseline CD4 cell count, had a higher baseline PVL, and were more likely to have received a protease inhibitor-based regimen. Conclusions:The frequency of and risk factors for discordant responses were comparable to those observed in developed countries. Longer follow-up is needed to assess the long-term impact of discordant responses on mortality in these resource-limited settings.

MicroRNA-137 promoter methylation in oral rinses from patients with squamous cell carcinoma of the head and neck is associated with gender and body mass index

Head and neck cancer represents 3.3% of all new malignancies and 2.0% of cancer deaths in the USA, the majority of which are squamous in origin. The overall 5 year survival is 60% and worsens with increasing stage at diagnosis. Thus, novel biomarkers for early detection of squamous cell carcinoma of the head and neck (SCCHN) are needed. MicroRNA-137 (miR-137) plays a role in cell cycle control and seems to undergo promoter methylation in oral squamous cell carcinoma tissue. The main objectives of this study were to ascertain whether miR-137 promoter methylation is detectable in oral rinse samples, assess its association with SCCHN and identify potential risk factors for its occurrence. Oral rinse samples were collected from 99 SCCHN patients with no prior history of cancer and 99 cancer-free controls, frequency matched on gender; tumor tissue for 64 patients was also tested. Methylation of the miR-137 promoter, assessed using methylation-specific polymerase chain reaction, was detected in 21.2% oral rinses from SCCHN patients and 3.0% from controls [odds ratio (OR) = 4.80, 95% confidence interval (CI): 1.23-18.82]. Among cases, promoter methylation of miR-137 was associated with female gender (OR = 5.30, 95% CI: 1.20-23.44) and inversely associated with body mass index (BMI) (OR = 0.88, 95% CI: 0.77-0.99). Promoter methylation of miR-137 appears to be a relatively frequently detected event in oral rinse of SCCHN patients and may have future utility as a biomarker in DNA methylation panels. The observed associations with gender and BMI help to shed light on potential risk factors for an altered methylation state in SCCHN.

Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: a randomized controlled trial

PURPOSE Patients with pneumonia often remain hospitalized after they are stable clinically, and the duration of intravenous antibiotic therapy is a rate-limiting step for discharge. The purpose of this study was to determine whether implementation of an evidence-based guideline would reduce the duration of intravenous antibiotic therapy and length of stay for patients hospitalized with pneumonia. METHODS In a seven-site, cluster randomized clinical trial, we enrolled 325 control and 283 intervention patients who were admitted by one of 116 physician groups. Within site, physician groups were assigned randomly to receive a practice guideline alone (control arm) or a practice guideline that was implemented using a multifaceted strategy (intervention arm). The effectiveness of guideline implementation was measured by the duration of intravenous antibiotic therapy and length of stay; differences in the rates of discontinuation and hospital discharge were assessed with proportional hazards models. Medical outcomes were assessed at 30 days. RESULTS Intravenous antibiotic therapy was discontinued somewhat more quickly in the intervention group (hazard ratio [HR] =1.23; 95% confidence interval [CI]: 1.00 to 1.52; P = 0.06) than in the control group. Intervention patients were discharged more quickly, but the difference was not statistically significant (HR = 1.16; 95% CI: 0.97 to 1.38; P = 0.11). Fewer intervention (55% [157/283]) than control (63% [206/325]) patients had medical complications during the index hospitalization (P = 0.04), with no differences in other medical outcomes, including mortality, rehospitalization, and return to usual activities, between treatment arms. CONCLUSIONS The multifaceted guideline implementation strategy resulted in a slight reduction in the duration of intravenous antibiotic therapy and a nonsignificant reduction in length of stay, without affecting patient outcomes.

MicroRNA-137 promoter methylation is associated with poorer overall survival in patients with squamous cell carcinoma of the head and neck.

The overall 5‐year survival rate of approximately 60% for head and neck cancer patients has remained essentially unchanged over the past 30 years. MicroRNA‐137 (miR‐137) plays an essential role in cell‐cycle control at the G1/S‐phase checkpoint. However, the aberrant miR‐137 promoter methylation observed in squamous cell carcinoma of the head and neck (SCCHN) suggests a tumor‐specific molecular defect that may contribute to disease progression.

Consensus Guidelines for Oral Dosing of Primarily Renally Cleared Medications in Older Adults

OBJECTIVES: To establish consensus oral dosing guidelines for primarily renally cleared medications prescribed for older adults.