Microclimate evaluation of strap-based wheelchair seating systems for persons with spinal cord injury: A pilot study.

STUDY PURPOSE: The purpose of this pilot study was to assess microclimate characteristics of two versions of a strap-based wheelchair seating system (perforated and solid straps) and to conduct preliminary microclimate comparisons of subjects' current wheelchair seating systems. MATERIALS AND METHODS: In this pilot study, the microclimate properties of two variations (solid and perforated) of a strap-based seating system were compared with two commonly used seating systems. Six subjects sat on three different seating systems each for 100-min test periods, while temperature and relative humidity were measured with a single sensor adjacent to the skin-seat interface. Additionally, thermal images of the seat interface were collected before and after each test period. RESULTS: The thermal images revealed that the maximum surface temperature of the solid-strap-based seating system was significantly lower than the other seating systems, -1.21 °C. (95% CI -2.11 to -0.30, p = 0.02), immediately following transfer out of the seat. Five minutes after transferring out of the seat, the perforated-strap seat was significantly cooler than the other seats -0.94 °C. (95% CI -1.59 to -0.30), p = 0.01, as was the solid-strap-based seat, -1.66 °C. (95% CI -2.69 to -0.63), p = 0.01. There were no significant differences in interface temperature or relative humidity measured with the single sensor near the skin-seat interface. CONCLUSION: This pilot study offers preliminary evidence regarding the microclimate of the strap-based seating systems compared with other common seating systems. Clinically, the strap-based seating system may offer another option for those who struggle with microclimate management.

Association of Implantable Cardioverter Defibrillators With Survival in Patients With and Without Improved Ejection Fraction: Secondary Analysis of the Sudden Cardiac Death in Heart Failure Trial.

Importance: Improvement in left ventricular ejection fraction (EF) to >35% occurs in many patients with reduced EF at baseline. To our knowledge, whether implantable cardioverter defibrillator (ICD) therapy improves survival for these patients is unknown. Objective: To examine the efficacy of ICD therapy in reducing risk of all-cause mortality and sudden cardiac death among patients with an EF ≤35% at baseline, with or without an improvement in EF to >35% during follow-up. Design, Setting, and Participants: This retrospective analysis examined data collected in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), which randomly assigned 2521 patients to placebo, amiodarone, or ICD between 1997 and 2001. A subset of 1902 participants (75.4%) of the SCD-HeFT had a repeated assessment of EF a mean (SD) of 13.5 (6) months after randomization. We stratified these patients by EF ≤35% and >35% based on the first repeated EF measurement after randomization and compared all-cause mortality in 649 patients randomized to placebo vs 624 patients randomized to ICD. Follow-up started with the repeated EF assessment. Analysis was performed between January 2016 and July 2016. Exposures: Implantable cardioverter-defibrillator therapy. Main Outcomes and Measures: All-cause mortality and sudden cardiac death. Results: Of the included 1273 patients, the mean (SD) age was 59 (12) years, and 977 (76.7%) were male and 1009 (79.3%) were white. Repeated EF was >35% in 186 participants (29.8%) randomized to ICD and 185 participants (28.5%) randomized to placebo. During a median follow-up of 30 months, the all-cause mortality rate was lower in the ICD vs placebo group, both in patients whose EF remained ≤35% (7.7 vs 10.7 per 100 person-year follow-up) and in those whose EF improved to >35% (2.6 vs 4.5 per 100 person-year follow-up). Compared with placebo, the adjusted hazard ratio for the effect of ICD on mortality was 0.64 (95% CI, 0.48-0.85) in patients with a repeated EF of ≤35% and 0.62 (95% CI, 0.29-1.30) in those with a repeated EF >35%. There was no interaction between treatment assignment and repeated EF for predicting mortality. Conclusions and Relevance: Among participants in the SCD-HeFT who had a repeated EF assessment during the course of follow-up, those who had an improvement in EF to >35% accrued a similar relative reduction in mortality with ICD therapy as those whose EF remained ≤35%. Prospective randomized clinical trials are needed to test ICD efficacy in patients with an EF >35%. Trial Registration: clinicaltrials.gov Identifier: NCT01114269.

Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction: From the TOPCAT Trial.

OBJECTIVES: The aims of this study were to explore the relationship of baseline levels of natriuretic peptides (NPs) with outcomes and to test for an interaction between baseline levels of NPs and the effects spironolactone. BACKGROUND: Plasma NPs are considered to be helpful in the diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF), and elevated levels are associated with adverse outcomes. Levels of NPs higher than certain cutoffs are often used as inclusion criteria in clinical trials of HFpEF to increase the likelihood that patients have HF and to select patients at higher risk for events. Whether treatments have a differential effect on outcomes across the spectrum of NP levels is unclear. METHODS: The TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) trial randomized patients with HFpEF and either prior hospitalization for HF or elevated natriuretic peptide levels (B-type NP [BNP] ≥100 pg/ml or N-terminal proBNP ≥360 pg/ml) to spironolactone or placebo. Baseline BNP (n = 430) or N-terminal proBNP (n = 257) levels were available in 687 patients enrolled from the Americas in the elevated-NP stratum of TOPCAT. RESULTS: Higher levels of NPs were independently associated with an increased risk for TOPCAT's primary endpoint of cardiovascular mortality, aborted cardiac arrest, or hospitalization for HF when analyzed either continuously or grouped by terciles, adjusting for region of enrollment, age, sex, atrial fibrillation, diabetes, renal function, body mass index, and heart rate. There was a significant interaction between the effect of spironolactone and baseline NP terciles for the primary outcome (p = 0.017), with greater benefit of the drug in the lower compared with higher NP terciles. CONCLUSIONS: Similar to the effects of irbesartan in the I-PRESERVE (Irbesartan in Heart Failure With Preserved Ejection Fraction) trial, a greater benefit of spironolactone was observed in the group with lower levels of NPs and overall risk in TOPCAT. Elevated NPs in HFpEF identify patients at higher risk for events but who may be less responsive to treatment. The mechanism of this apparent interaction between disease severity and response to therapy requires further exploration. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302).

Effect of an Automated Tracking Registry on the Rate of Tracking Failure in Incidental Pulmonary Nodules.

OBJECTIVE: Following incidental lung nodules with interval CT scanning is an accepted method to detect early lung cancer, but delayed tracking or failure to track is reported in up to 40% of patients. METHODS: Our institution developed and implemented an automated lung nodule registry tracking system. This system uses a code at the time that a suspicious nodule is discovered to populate the registry. Suspicious nodules were defined as any nodule, solid or ground glass, <3 cm that the radiologist recorded as a potential malignancy or recommended for follow-up imaging. We exported the system to eight other Veterans Administration Medical Centers (VAMCs) with over 10,000 patients enrolled. We retrospectively reviewed 200 sequential CT scan reports containing incidental nodule(s) from two tertiary care university-affiliated VAMCs, both before and after the implementation of the registry tracking system. The primary outcome was the rate of tracking failure, defined as suspicious nodules that had no follow-up imaging or whose follow-up was delayed when compared with published guidelines. Secondary outcomes were predictors of tracking failure and reasons for tracking failure. RESULTS: After implementation of the registry tracking system in the two VAMCs, we found a significant decrease in tracking failure, from a preimplementation rate of 74% to a postimplementation rate of 10% (P < .001). We found that age, nodule size, number, and nodule characteristics were significant predictors. CONCLUSIONS: The automated lung nodule registry tracking system can be exported to other health care facilities and significantly reduces the rate of tracking failure.

Prognostic Value of Insulin-Like Growth Factor-Binding Protein 7 in Patients with Heart Failure and Preserved Ejection Fraction.

BACKGROUND: The prognostic merit of insulin-like growth factor-binding protein 7 (IGFBP7) is unknown in heart failure and preserved ejection fraction (HFpEF). METHODS AND RESULTS: Baseline IGFBP7 (BL-IGFBP7; n = 302) and 6-month change (Δ; n = 293) were evaluated in the Irbesartan in Heart Failure and Preserved Ejection Fraction (I-PRESERVE) trial. Primary outcome was all-cause mortality or cardiovascular hospitalization with median follow-up of 3.6 years; secondary outcomes included HF events. Median BL-IGFBP7 concentration was 218 ng/mL. BL-IGFBP7 was significantly correlated with age (R2 = 0.13; P < .0001), amino-terminal pro-B-type NP (R2 = 0.22; P < .0001), and estimated glomerular filtration rate (eGFR; R2 = 0.14; P < .0001), but not with signs/symptoms of HFpEF. BL-IGFBP7 was significantly associated with the primary outcome (hazard ratio [HR] = 1.007 per ng/mL; P < .001), all-cause mortality (HR = 1.008 per ng/mL; P < .001), and HF events (HR = 1.007 per ng/mL; P < .001). IGFBP7 remained significant for each outcome after adjustment for ln amino-terminal pro-B-type NP and eGFR but not all variables in the I-PRESERVE prediction model. After 6 months, IGFBP7 did not change significantly in either treatment group. ΔIGFBP7 was significantly associated with decrease in eGFR in patients randomized to irbesartan (R2 = 0.09; P = .002). ΔIGFBP7 was not independently associated with outcome. CONCLUSIONS: Higher concentrations of IGFBP7 were associated with increased risk of cardiovascular events, but after multivariable adjustment this association was no longer present. Further studies of IGFBP7 are needed to elucidate its mechanism. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT00095238.

Quality of Chronic Obstructive Pulmonary Disease-Related Health Care in Rural and Urban Veterans Affairs Clinics.

Only minor disparities were found between patients at rural and urban clinics in this examination of the differences in the quality of health care for patients with COPD.

Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery (CRIPES): A Prospective, Randomized, Sham-Controlled Phase II Clinical Trial.

BACKGROUND: Remote ischemic preconditioning (RIPC) has been shown to reduce infarct size in animal models. We hypothesized that RIPC before an elective vascular operation would reduce the incidence and amount of a postoperative rise of the cardiac troponin level. METHODS AND RESULTS: Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery (CRIPES) was a prospective, randomized, sham-controlled phase 2 trial using RIPC before elective vascular procedures. The RIPC protocol consisted of 3 cycles of 5-minute forearm ischemia followed by 5 minutes of reperfusion. The primary endpoint was the proportion of subjects with a detectable increase in cardiac troponin I (cTnI) and the distribution of such increases. From June 2011 to September 2015, 201 male patients (69±7, years) were randomized to either RIPC (n=100) or a sham procedure (n=101). Indications for vascular surgery included an expanding abdominal aortic aneurysm (n=115), occlusive peripheral arterial disease of the lower extremities (n=37), or internal carotid artery stenosis (n=49). Of the 201 patients, 47 (23.5%) had an increase in cTnI above the upper reference limit within 72 hours of the vascular operation, with no statistically significant difference between those patients assigned to RIPC (n=22; 22.2%) versus sham procedure (n=25; 24.7%; P=0.67). Among the cohort with increased cTnI, the median peak values (interquartile range) in the RIPC and control group were 0.048 (0.004-0.174) and 0.017 (0.003-0.105), respectively (P=0.54). CONCLUSIONS: In this randomized, controlled trial of men with increased perioperative cardiac risks, elevation in cardiac troponins was common following vascular surgery, but was not reduced by a strategy of RIPC. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01558596.

Frequency of Increase in Cardiac Troponin Levels After Peripheral Arterial Operations (Carotid Endarterectomy, Abdominal Aorta Procedure, Distal Bypass) and Their Effect on Medical Management.

The utility of measuring cardiac troponins (cTn) in asymptomatic patients during the perioperative period has been controversial. In the present substudy of the Cardiac Remote Ischemic Preconditioning Prior to Elective Vascular Surgery Trial (NCT01558596), we hypothesized that surveillance of myocardial injury with cTnI in the perioperative period would lead to initiation or intensification of medical therapies for coronary artery disease. Increases in cTnI ≥0.01 µg/l in the perioperative period were considered clinically significant. Intensification of medical therapy was defined as initiation of aspirin or initiation or increases in the dose of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers, statins, or ß blockers and was left to the discretion of treating physicians. From June 2011 to April 2015, a total of 185 patients (mean age 68 ± 7 years, 100% men) were enrolled in the trial. A total of 28 patients (15%) had significant increases in cTnI after vascular surgery, and 38 (20.5%) had their medical therapies intensified in the perioperative period. Among patients with increases in cTnI, 11 (39%) had intensification of medical therapy versus 27 patients (17%) with no or smaller increases in cTnI (p = 0.02). Among those patients with ΔcTnI ≥0.01 µg/l, hospital readmissions at 3 to 6 months were 7.6% for the intensification group versus 25% for the no intensification group (p = 0.18). Mortality rate at 6 months was low in both groups (2.6% vs 0%, respectively, p = 0.13). In conclusion, among patients undergoing vascular surgery, perioperative increases in cTn were associated with initiation or intensification of medical therapies for coronary artery disease at the time of discharge.

All-cause hospitalizations for inflammatory bowel diseases: Can the reason for admission provide information on inpatient resource use? A study from a large veteran affairs hospital.

BACKGROUND: Inflammatory bowel diseases (IBDs) are group of chronic inflammatory illnesses with a remitting and relapsing course that may result in appreciable morbidity and high medical costs secondary to repeated hospitalizations. The study's objectives were to identify the reasons for hospitalization among patients with inflammatory bowel diseases, and compare inpatient courses and readmission rates for IBD-related admissions versus non-IBD-related admissions. METHODS: A retrospective chart review was performed on all patients with IBD admitted to the Minneapolis VA Medical Center between September 2010 and September 2012. RESULTS: A total of 111 patients with IBD were admitted during the 2-year study period. IBD flares/complications accounted for 36.9 % of the index admissions. Atherothrombotic events comprised the second most common cause of admissions (14.4 %) in IBD patients. Patients with an index admission directly related to IBD were significantly younger and had developed IBD more recently. Unsurprisingly, the IBD admission group had significantly more gastrointestinal endoscopies and abdominal surgeries, and was more likely to be started on medication for IBD during the index stay. The median length of stay (LOS) for the index hospitalization for an IBD flare or complication was 4 (2-8) days compared with 2 (1-4) days for the other patients (P = 0.001). A smaller percentage of the group admitted for an IBD flare/complication had a shorter ICU stay compared with the other patients (9.8 % vs. 15.7 %, respectively); however, their ICU LOSs tended to be longer (4.5 vs. 2.0 days, respectively, P = 0.17). Compared to the other admission types, an insignificantly greater percentage of the group whose index admission was related to an IBD flare or complication had at least one readmission within 6 months of discharge (29 % versus 21 %; P = 0.35). The rate of admission was approximately 80 % greater in the group whose index admission was related to an IBD flare or complication compared to the other types of admission (rate ratio 1.8, 95 % confidence interval 0.96 to 3.4), although this difference did not reach statistical significance (P = 0.07). CONCLUSION: Identifying the reasons for the patients' index admission, IBD flares versus all other causes, may provide valuable information concerning admission care and the subsequent admission history.

Heart Failure With Improved Ejection Fraction: Clinical Characteristics, Correlates of Recovery, and Survival: Results From the Valsartan Heart Failure Trial.

BACKGROUND: Heart failure with recovered or improved ejection fraction (HFiEF) has been proposed as a new category of HF. Whether HFiEF is clinically distinct from HF with persistently reduced ejection fraction remains to be validated. METHODS AND RESULTS: Of the 5010 subjects enrolled in the Valsartan Heart Failure Trial (Val-HeFT), 3519 had a baseline left ventricular EF of <35% and a follow-up echocardiographic assessment of EF at 12 months. Of these, 321 (9.1%) patients who had a 12-month EF of >40% constituted the subgroup with HFiEF. EF improved from 28.7±5.6% to 46.5±5.6% in the subgroup with HFiEF and remained reduced (25.2±6.2% and 27.5±7.1%) in the subgroup with HF with reduced ejection fraction. The group with HFiEF had a less severe hemodynamic, biomarker, and neurohormonal profile, and it was treated with a more intense HF medication regimen. Subjects who had higher blood pressure and those treated with a ß-blocker or randomized to valsartan had greater odds of being in the HFiEF group, whereas those with an ischemic pathogenesis, a more dilated left ventricle, and a detectable hs-troponin had lower odds of an improvement in EF. Recovery of the EF to >40% was associated with a better survival compared with persistently reduced EF. CONCLUSIONS: Our data support HFiEF as a stratum of HF with reduced ejection fraction with a more favorable outcome, which occurs in a minority of patients with HF with reduced ejection fraction who have a lower prevalence of ischemic heart disease, a less severe hemodynamic, biomarker, and neurohormonal profile, and who are treated with a more intense HF medication regimen. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.

Examination of CK2α and NF-κB p65 expression in human benign prostatic hyperplasia and prostate cancer tissues.

Protein kinase CK2 plays a critical role in cell growth, proliferation, and suppression of cell death. CK2 is overexpressed, especially in the nuclear compartment, in the majority of cancers, including prostate cancer (PCa). CK2-mediated activation of transcription factor nuclear factor kappa B (NF-κB) p65 is a key step in cellular proliferation, resulting in translocation of NF-κB p65 from the cytoplasm to the nucleus. As CK2 expression and activity are also elevated in benign prostatic hyperplasia (BPH), we sought to increase the knowledge of CK2 function in benign and malignant prostate by examination of the relationships between nuclear CK2 and nuclear NF-κB p65 protein expression. The expression level and localization of CK2α and NF-κB p65 proteins in PCa and BPH tissue specimens was determined. Nuclear CK2α and NF-κB p65 protein levels are significantly higher in PCa compared with BPH, and these proteins are positively correlated with each other in both diseases. Nuclear NF-κB p65 levels correlated with Ki-67 or with cytoplasmic NF-κB p65 expression in BPH, but not in PCa. The findings provide information that combined analysis of CK2α and NF-κB p65 expression in prostate specimens relates to the disease status. Increased nuclear NF-κB p65 expression levels in PCa specifically related to nuclear CK2α levels, indicating a possible CK2-dependent relationship in malignancy. In contrast, nuclear NF-κB p65 protein levels related to both Ki-67 and cytoplasmic NF-κB p65 levels exclusively in BPH, suggesting a potential separate impact for NF-κB p65 function in proliferation for benign disease as opposed to malignant disease.

Evaluation of a Potential Interaction Between New Regimens to Treat Hepatitis C and Warfarin.

OBJECTIVE: New regimens to treat hepatitis C virus infection have expanded the eligible patient population to include more patients receiving concurrent warfarin. The primary objective of this study was to assess whether a drug interaction occurs when these regimens are added to warfarin therapy. METHODS: This was a retrospective cohort design using a nationwide database of the Veterans Affairs Health System. Patients on warfarin therapy treated with sofosbuvir or ombitasvir, paritaprevir-ritonavir, and dasabuvir (OBV-PTV/r-DSV) from March 2014 through October 2015 were identified. The warfarin dose response was calculated using a warfarin sensitivity index (WSI) defined as the steady-state INR divided by the mean daily warfarin dose. The primary outcome was the change in WSI from hepatitis C treatment initiation to completion. RESULTS: The final sample consisted of 271 patients. The WSI decreased 23% from a mean baseline value of 0.53 to 0.39 (decrease of 0.14; 95% CI = 0.11 to 0.16; P < 0.001). OBV-PTV/r-DSV produced a significantly greater decrease than any sofosbuvir regimen. Concurrent ribavirin accounted for an additional decrease in warfarin sensitivity of -0.09 (95% CI = -0.06 to -0.12; P < 0.001). The percentage of subtherapeutic INR results increased from 26% prior to hepatitis C treatment to 58% during treatment. CONCLUSIONS: Results indicate a clinically significant reduction in warfarin dose-response when hepatitis C treatment regimens were added to warfarin. They were most profound with OBV-PTV/r-DSV. Ribavirin was associated with an additive effect. Clinicians should be aware of this potential drug interaction to closely monitor and minimize subtherapeutic levels of anticoagulation.

Blood Biomarkers of Chronic Inflammation in Gulf War Illness.

BACKGROUND: More than twenty years following the end of the 1990-1991 Gulf War it is estimated that approximately 300,000 veterans of this conflict suffer from an unexplained chronic, multi-system disorder known as Gulf War Illness (GWI). The etiology of GWI may be exposure to chemical toxins, but it remains only partially defined, and its case definition is based only on symptoms. Objective criteria for the diagnosis of GWI are urgently needed for diagnosis and therapeutic research. OBJECTIVE: This study was designed to determine if blood biomarkers could provide objective criteria to assist diagnosis of GWI. DESIGN: A surveillance study of 85 Gulf War Veteran volunteers identified from the Department of Veterans Affairs Minnesota Gulf War registry was performed. All subjects were deployed to the Gulf War. Fifty seven subjects had GWI defined by CDC criteria, and 28 did not have symptomatic criteria for a diagnosis of GWI. Statistical analyses were performed on peripheral blood counts and assays of 61 plasma proteins using the Mann-Whitney rank sum test to compare biomarker distributions and stepwise logistic regression to formulate a diagnostic model. RESULTS: Lymphocyte, monocyte, neutrophil, and platelet counts were higher in GWI subjects. Six serum proteins associated with inflammation were significantly different in GWI subjects. A diagnostic model of three biomarkers-lymphocytes, monocytes, and C reactive protein-had a predicted probability of 90% (CI 76-90%) for diagnosing GWI when the probability of having GWI was above 70%. SIGNIFICANCE: The results of the current study indicate that inflammation is a component of the pathobiology of GWI. Analysis of the data resulted in a model utilizing three readily measurable biomarkers that appears to significantly augment the symptom-based case definition of GWI. These new observations are highly relevant to the diagnosis of GWI, and to therapeutic trials.

Outcomes of Citalopram Dosage Risk Mitigation in a Veteran Population.

OBJECTIVE: A public safety communication issued by the Food and Drug Administration declared that citalopram dosages exceeding 40 mg/day were no longer considered safe because of a newly recognized risk of dosage-dependent QT interval prolongation. The authors compared the incidence of hospitalizations and mortality when higher dosages of citalopram were or were not reduced to ≤40 mg/day. METHOD: National electronic medical records compiled by the Veterans Health Administration were used to conduct a retrospective study of a population filling citalopram prescriptions for more than 40 mg/day when the safety communication was first issued in August 2011. Hospitalizations and mortality after dosages of citalopram were or were not reduced to ≤40 mg/day were compared using multivariable Cox regression. RESULTS: The at-risk cohort of 35,848 veterans (mean age, 58 years [SD=11]; 92% male) had citalopram prescriptions for 64 mg/day (SD=8.3), on average. Within 180 days after the safety communication was issued, 60% had filled prescriptions for ≤40 mg/day. All-cause hospitalizations or deaths were found to significantly increase after dosage reductions (adjusted hazard ratio=4.5, 95% CI=4.1-5.0), as were hospitalizations for depression or all-cause death (adjusted hazard ratio=2.2, 95% CI=1.8-2.6). Mortality did not decline (adjusted hazard ratio=1.0, 95% CI=0.8-1.3), and neither did hospitalizations for arrhythmias or all-cause deaths (adjusted hazard ratio=1.3, 95% CI=1.0-1.7). CONCLUSIONS: Reduction of prescribed citalopram dosages to a new safety limit was associated with a higher rate of hospitalization in a large patient population who had been treated with substantially higher dosages. Stipulating a safety limit for citalopram dosages before the benefits and risks of doing so were firmly established appears to have had unintended clinical consequences.

Pharmacist-Led Chronic Disease Management: A Systematic Review of Effectiveness and Harms Compared With Usual Care.

BACKGROUND: Increased involvement of pharmacists in patient care may increase access to health care and improve patient outcomes. PURPOSE: To determine the effectiveness and harms of pharmacist-led chronic disease management for community-dwelling adults. DATA SOURCES: MEDLINE, Cochrane Library, CINAHL, and International Pharmaceutical Abstracts from 1995 through February 2016, and reference lists of systematic reviews and included studies. STUDY SELECTION: 65 patient populations in 63 studies conducted in the United States of any design reported outcomes of pharmacist-led chronic disease management versus a comparator for community-dwelling adults in the United States. Studies set in retail pharmacies were excluded. DATA EXTRACTION: Data extraction done by a single investigator was confirmed by a second investigator; risk of bias was assessed by 2 investigators; and strength of evidence was determined by consensus. DATA SYNTHESIS: Pharmacist-led care was associated with similar numbers of office visits, urgent care or emergency department visits, and hospitalizations (moderate-strength evidence) and medication adherence (low-strength evidence) compared with usual care (typically continuing a prestudy visit schedule). Pharmacist-led care increased the number or dose of medications received and improved study-selected glycemic, blood pressure, and lipid goal attainment (moderate-strength evidence). Mortality and clinical events were similar (low-strength evidence). Evidence on patient satisfaction was mixed and insufficient. The reporting of harms was limited. LIMITATIONS: Interventions were heterogeneous. Studies were typically short-term and designed to assess physiologic intermediate outcomes rather than clinical events. Reporting of many clinical outcomes of interest was limited, and often they were not the study-defined primary end points. CONCLUSION: Pharmacist-led chronic disease management was associated with effects similar to those of usual care for resource utilization and may improve physiologic goal attainment. Further research is needed to determine whether increased medication utilization and goal attainment improve clinical outcomes. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.

Comparative dose response using the intravenous versus enteral route of administration for potassium replenishment.

OBJECTIVE: To compare the change in potassium concentration (dose-response) using the intravenous versus enteral route for potassium replenishment. RESEARCH METHODOLOGY/DESIGN: Cross-sectional analysis of individual potassium chloride doses with resulting changes in plasma potassium concentrations in intensive care patients. Potassium chloride was administered according to potassium replenishment protocols. For inclusion, doses were required to have pre- and post-dose plasma potassium concentrations obtained within 8hours of administration. SETTING: Medical and surgical intensive care units of a United States Veterans Affairs Medical Center. MAIN OUTCOME MEASURES: The primary outcome was the dose-response slope for intravenous versus enteral potassium administration as estimated by linear regression analysis. Multivariable linear regression was employed to adjust for potential confounders. RESULTS: The sample had 278 potassium chloride doses administered to 142 patients. The potassium concentration change per 20mmol of potassium chloride was similar for intravenous and enteral routes, 0.25mmol/L (95% confidence interval 0.16-0.33) versus 0.27mmol/L (0.15-0.39) respectively (p=0.73). Multivariable linear regression did not alter results. The success of achieving a minimum potassium concentration defined by the specific protocol was similar for intravenous (61%) and enteral (59%) administration. Overall, 77% of potassium chloride doses were administered at a time when patients were eligible to receive an enteral dosage form. CONCLUSION: The enteral route was as effective as the intravenous route in increasing the plasma potassium concentration. The enteral route was widely available for potassium replenishment. Despite enteral route availability and the well-known reliability of potassium chloride absorption, the majority of doses were administered intravenously.

Extended Follow-Up of Patients With Heart Failure Receiving Autonomic Regulation Therapy in the ANTHEM-HF Study.

OBJECTIVE: Evaluate the effects of a novel autonomic regulation therapy (ART) via vagus nerve stimulation (VNS) in patients with chronic heart failure (HF) and reduced left ventricular ejection fraction during a 12-month follow-up period. METHODS: The Autonomic Regulation Therapy for the Improvement of Left Ventricular Function and Heart Failure Symptoms (ANTHEM-HF) study enrolled 60 subjects with New York Heart Association class II-III HF and low left ventricular ejection fraction (≤40%), who received open-loop ART using VNS randomized to left or right cervical vagus nerve placement and followed for 6 months after titration to a therapeutic output current (2.0 ± 0.6 mA). Patients received chronic stimulation at a frequency of 10 Hz and pulse duration of 250 µsec. Forty-nine subjects consented to participate in an extended follow-up study for an additional 6 months (12 months total posttitration) to determine whether the effects of therapy were maintained. RESULTS: During the 6-month extended follow-up period, there were no device malfunctions or device-related serious adverse effects. There were 7 serious adverse effects unrelated to the device, including 3 deaths (2 sudden cardiac deaths, 1 worsening HF death). There were 5 nonserious adverse events that were adjudicated to be device-related. Safety and tolerability were similar, and there were no significant differences in efficacy between left- and right-sided ART. Overall, mean efficacy measure values at 12 months were not significantly different from mean values at 6 months. CONCLUSIONS: Chronic open-loop ART via left- or right-sided VNS continued to be feasible and well-tolerated in patients with HF with reduced EF. Improvements in cardiac function and HF symptoms seen after 6 months of ART were maintained at 12 months.