An "Engage to Sustain" Intervention to Improve Process Performance Measures in Ambulatory Care.

In ambulatory care, monitoring process performance measures (PPMs) is essential to meet regulatory requirements, establish targets for care, seek reimbursement, and evaluate patient care responsibilities. We implemented a comprehensive program, "Engage to Sustain," for licensed practical nurses (LPNs) and certified medical assistants (CMAs) to practice at the top of their licensure/certification. Screening rates for 4 key PPMs (depression screening, fall risk screening, and tobacco use screening and counseling) markedly increased following this intervention across 18 ambulatory departments with more than 2 million patient visits. These results suggest that shifting responsibilities for patient screening from physicians and advanced practitioners to LPNs and CMAs may improve screening rates.

Cognitive deficits in methamphetamine addiction: Independent contributions of dependence and intelligence.

BACKGROUND: Methamphetamine's effects on brain function have been associated with cognitive deficits, which have a negative impact on clinical outcomes. However, it remains unclear if cognitive deficits relate to methamphetamine dependence (potentially amenable to abstinence and retraining) or background characteristics, mental health and other drug use. We tested the association between methamphetamine dependence and cognitive performance, while factoring in the impact of background characteristics, depressive symptoms and tobacco, alcohol and cannabis use. METHOD: The sample comprised 108 treatment-seeking participants who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV TR) criteria for methamphetamine dependence and 50 socio-demographically matched controls. We administered a comprehensive neuropsychological test battery (delay discounting, decision making, disinhibition, episodic and working memory) and examined cognitive deficits in methamphetamine users after taking into account socio-demographic characteristics, tobacco, alcohol and cannabis use, and depressive symptoms. RESULTS: Hierarchical multiple regression analyses showed that methamphetamine dependence was associated with poorer performance in decision-making and disinhibition over and above other predictors, while IQ better explained performance in episodic and working memory. Although duration of methamphetamine use was linked to disinhibition, other patterns of methamphetamine use (including dose and frequency) were not consistently related to performance. CONCLUSIONS: Methamphetamine dependence impacts inhibitory control and decision-making, whereas lower IQ associates with memory/working memory deficits among methamphetamine users. Findings suggest the need to target disinhibition and impulsive decision-making as part of methamphetamine dependence treatment, while buffering the impact of IQ on memory systems.

Retrospective analysis of drug therapy problems identified with a telephonic appointment-based model of medication synchronization.

OBJECTIVES: To describe the drug therapy problems (DTPs) identified for patients enrolled in an Appointment Based Model (ABM) for medication synchronization, describe the pharmacist-delivered clinical interventions, and assess what patient characteristics are associated with the number of DTPs identified. METHODS: A cross-sectional chart review of 1 month of pharmacist notes for telephone ABM encounters at one independent community pharmacy in the Midwest U.S. was performed for a systematic random sample of patients active in the program during September 2017. Included patients were 18 years and older and took one or more synchronized medications. Data included months in the program, gender, age, insurance type, refill interval, medications (synchronized and total), DTP category, and intervention category. Descriptive statistics were calculated, and a multiple linear regression tested the association between patient characteristics and the number of DTPs identified. RESULTS: The study involved 209 subjects, 54% women, with a mean age of 69.5 years and. The average number of medications synchronized was 4.7, the mean total number of medications was 6.3, and mean length of time in the program was 20 months. The DTPs (n=334) identified included needs additional drug therapy (43.1%), inappropriate adherence (31.4%), unnecessary drug therapy (15.0%), and adverse drug reaction (9.6%). The regression showed age and number of medications was positively associated with number of DTPs identified, but months enrolled was not. CONCLUSIONS: This ABM approach identified several hundred DTPs with corresponding interventions within a one-month period, suggesting that ABMs have a significant potential to improve patient care. The data also suggest that pharmacist interventions within an ABM program are valuable beyond the first few fills as patients move into maintenance use of their medications, especially for patients of advancing age and polypharmacy.

Fluoroquinolone Prophylaxis Is Highly Effective for the Prevention of Central Line-Associated Bloodstream Infections in Autologous Stem Cell Transplant Patients.

Patients undergoing stem cell transplant (SCT) for the treatment of hematologic malignancy are at increased risk for central line-associated bloodstream infections (CLABSIs). The use of prophylactic antibiotics to prevent CLABSIs in the setting of autologous SCT is of unclear benefit. We aimed to evaluate the impact of levofloxacin prophylaxis on reducing CLABSIs in this high-risk population. Patients undergoing autologous SCT at a tertiary care hospital received levofloxacin prophylaxis from January 13, 2016 to January 12, 2017. Levofloxacin was administered from autologous SCT (day 0) until day 13, absolute neutrophil count > 500/mm3, or neutropenic fever, whichever occurred first. Clinical outcomes were compared with a baseline group who underwent autologous SCT but did not receive antibacterial prophylaxis during the previous year. The primary endpoint was incidence of CLABSIs assessed using Cox proportional hazards regression. A total of 324 patients underwent autologous SCT during the entire study period, with 150 receiving levofloxacin prophylaxis during the intervention period. The rate of CLABSIs was reduced from 18.4% during the baseline period to 6.0% during the intervention period. On multivariable analysis levofloxacin prophylaxis significantly reduced CLABSI incidence (hazard ratio, .33; 95% confidence interval [CI], .16 to .69; P = .003). There was also a reduction in the risk of neutropenic fever (odds ratio [OR], .23; 95% CI, .14 to .39; P < .001) and a trend toward a reduction in intensive care unit transfer for sepsis (OR, .33; 95% CI, .09 to 1.24; P = .10) in patients receiving levofloxacin prophylaxis. Notably, there was no increase in Clostridium difficile infection in the levofloxacin group (OR, .66; 95% CI, .29 to 1.49; P = .32). Levofloxacin prophylaxis was effective in reducing CLABSIs and neutropenic fever in patients undergoing autologous SCT. Further studies are needed to identify specific patient groups who will benefit most from antibiotic prophylaxis.

Size and conformation limits to secretion of disulfide-bonded loops in autotransporter proteins.

Autotransporters are a superfamily of virulence factors typified by a channel-forming C terminus that facilitates translocation of the functional N-terminal passenger domain across the outer membrane of Gram-negative bacteria. This final step in the secretion of autotransporters requires a translocation-competent conformation for the passenger domain that differs markedly from the structure of the fully folded secreted protein. The nature of the translocation-competent conformation remains controversial, in particular whether the passenger domain can adopt secondary structural motifs, such as disulfide-bonded segments, while maintaining a secretion-competent state. Here, we used the endogenous and closely spaced cysteine residues of the plasmid-encoded toxin (Pet) from enteroaggregative Escherichia coli to investigate the effect of disulfide bond-induced folding on translocation of an autotransporter passenger domain. We reveal that rigid structural elements within disulfide-bonded segments are resistant to autotransporter-mediated secretion. We define the size limit of disulfide-bonded segments tolerated by the autotransporter system demonstrating that, when present, cysteine pairs are intrinsically closely spaced to prevent congestion of the translocator pore by large disulfide-bonded regions. These latter data strongly support the hairpin mode of autotransporter biogenesis.

The gingipains: scissors and glue of the periodontal pathogen, Porphyromonas gingivalis.

The anaerobic bacterium, Porphyromonas gingivalis, is associated with chronic periodontal disease (periodontitis or gum disease). The disease is not only the leading cause of tooth loss in the developed world, but is associated with a number of systemic diseases, such as cardiovascular disease and diabetes. The most potent virulence factors of this bacterium are the gingipains, three cysteine proteases that bind and cleave a wide range of host proteins. This article summarizes current knowledge of the structure and function of the enzymes, with a particular focus on what remains to be elucidated regarding the structure and function of the nonenzymatic adhesin domains of the high-molecular-weight forms of the proteases.

High molecular weight gingipains from Porphyromonas gingivalis induce cytokine responses from human macrophage-like cells via a nonproteolytic mechanism.

Periodontal disease is an oral inflammatory disease affecting the supporting structures of teeth. Porphyromonas gingivalis, a major pathogenic agent for the disease, expresses a number of virulence factors, including cysteine proteases called the gingipains. The arginine- and lysine-specific gingipains, HRgpA and Kgp, respectively, are expressed as high molecular weight forms containing both catalytic and adhesin subunits. We examined the expression pattern of cytokines and their receptors in differentiated macrophages following exposure to active and inactive forms of the gingipains, using a cDNA array, quantitative PCR and ELISA analysis. Amongst other pro-inflammatory cytokines, results from the cDNA array suggested that interleukin-1beta, granulocyte-macrophage colony stimulatory factor and interferon-gamma were upregulated after exposure of the macrophages to the gingipains. Quantitative PCR analysis substantiated these observations and indicated that active or inactive forms of the high molecular weight gingipains were able to upregulate expression of transcripts for these cytokines. The strongly enhanced production of interleukin-1beta and granulocyte-macrophage colony stimulatory factor by differentiated macrophages in response to active or inactive forms of the high molecular weight gingipains was confirmed at the protein level by ELISA analysis. The results indicate that the adhesin subunits of the gingipains mediate strong upregulation of the expression of pro-inflammatory cytokines in macrophages.