Creation and assessment of a clinical predictive calculator and mortality associated with Candida krusei bloodstream infections

Abstract Background Candida krusei bloodstream infection (CK BSI) is associated with high mortality, but whether this is due to underlying comorbidities in affected patients or the organism itself is unknown. Identifying patient characteristics that are associated with CK BSI is crucial for clinical decision-making and prognosis. Methods We conducted a retrospective analysis of hospitalized patients with Candida BSI at our institution between 2002 and 2015. Data were collected on demographics, comorbidities, medications, procedures, central lines, vital signs, and laboratory values. Multivariable logistic and Cox regression were used to identify risk factors associated with CK and mortality, respectively. Results We identified 1873 individual patients who developed Candida BSI within the study period, 59 of whom had CK BSI. CK BSI was predicted by hematologic malignancy, gastric malignancy, neutropenia, and the use of prophylactic azole antifungals, monoclonal antibodies, and β-lactam/β-lactamase inhibitor combinations. The C-statistic was 0.86 (95% confidence interval, 0.81–0.91). The crude mortality rates were 64.4% for CK BSI and 41.4% for non-CK BSI. Although CK was associated with higher mortality in univariable Cox regression, this relationship was no longer significant with the addition of the following confounders: lymphoma, neutropenia, glucocorticoid use, chronic liver disease, and elevated creatinine. Conclusions Six patient comorbidities predicted the development of CK BSI with high accuracy. Although patients with CK BSI have higher crude mortality rates than patients with non-CK BSI, this difference is not significant when accounting for other patient characteristics. </jats:sec

Outpatient antibiotic prescription trends in the United States: A national cohort study

OBJECTIVETo characterize trends in outpatient antibiotic prescriptions in the United StatesDESIGNRetrospective ecological and temporal trend study evaluating outpatient antibiotic prescriptions from 2013 to 2015SETTINGNational administrative claims data from a pharmacy benefits manager PARTICIPANTS. Prescription pharmacy beneficiaries from Express Scripts Holding CompanyMEASUREMENTSAnnual and seasonal percent change in antibiotic prescriptionsRESULTSApproximately 98 million outpatient antibiotic prescriptions were filled by 39 million insurance beneficiaries during the 3-year study period. The most commonly prescribed antibiotics were azithromycin, amoxicillin, amoxicillin/clavulanate, ciprofloxacin, and cephalexin. No significant changes in individual or overall annual antibiotic prescribing rates were found during the study period. Significant seasonal variation was observed, with antibiotics being 42% more likely to be prescribed during February than September (peak-to-trough ratio [PTTR], 1.42; 95% confidence interval [CI], 1.39–1.61). Similar seasonal trends were found for azithromycin (PTTR, 2.46; 95% CI, 2.44–3.47), amoxicillin (PTTR, 1.52; 95% CI, 1.42–1.89), and amoxicillin/clavulanate (PTTR, 1.78; 95% CI, 1.68–2.29).CONCLUSIONSThis study demonstrates that annual national outpatient antibiotic prescribing practices remained unchanged during our study period. Furthermore, seasonal peaks in antibiotics generally used to treat viral upper respiratory tract infections remained unchanged during cold and influenza season. These results suggest that inappropriate prescribing of antibiotics remains widespread, despite the concurrent release of several guideline-based best practices intended to reduce inappropriate antibiotic consumption; however, further research linking national outpatient antibiotic prescriptions to associated medical conditions is needed to confirm these findings.Infect Control Hosp Epidemiol 2018;39:584–589</jats:sec

Evaluation of a hybrid antimicrobial restriction process at a large academic medical center

We conducted a retrospective review of a hybrid antimicrobial restriction process demonstrating adherence to appropriate use criteria in 72% of provisional-only orders, in 100% of provisional orders followed by ID orders, and in 97% of ID-initiated orders. Therapy interruptions occurred in 24% of provisional orders followed by ID orders

Evaluation of a community pharmacy-based intervention for improving patient adherence to antihypertensives: a randomised controlled trial

BackgroundThe majority of patients using antihypertensive medications fail to achieve their recommended target blood pressure. Poor daily adherence with medication regimens and a lack of persistence with medication use are two of the major reasons for failure to reach target blood pressure. There is no single intervention to improve adherence with antihypertensives that is consistently effective. Community pharmacists are in an ideal position to promote adherence to chronic medications. This study aims to test a specific intervention package that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications - Hypertension Adherence Program in Pharmacy (HAPPY).Methods/DesignThe HAPPY trial is a multi-centre prospective randomised controlled trial. Fifty-six pharmacies have been recruited from three Australian states. To identify potential patients, a software application (MedeMine CVD) extracted data from a community pharmacy dispensing software system (FRED Dispense&reg;). The pharmacies have been randomised to either \u27Pharmacist Care Group\u27 (PCG) or \u27Usual Care Group\u27 (UCG). To check for \u27Hawthorne effect\u27 in the UCG, a third group of patients \u27Hidden Control Group\u27 (HCG) will be identified in the UCG pharmacies, which will be made known to the pharmacists at the end of six months. Each study group requires 182 patients. Data will be collected at baseline, three and six months in the PCG and at baseline and six months in the UCG. Changes in patient adherence and persistence at the end of six months will be measured using the self-reported Morisky score, the Tool for Adherence Behaviour Screening and medication refill data.DiscussionTo our knowledge, this is the first research testing a comprehensive package of evidence-based interventions that could be integrated into the community pharmacy workflow to enable pharmacists to improve patient adherence and/or persistence with antihypertensive medications. The unique features of the HAPPY trial include the use of MedeMine CVD to identify patients who could potentially benefit from the service, control for the \u27Hawthorne effect\u27 in the UCG and the offer of the intervention package at the end of six months to patients in the UCG, a strategy that is expected to improve retention.Trial RegistrationAustralian New Zealand Clinical Trial Registry ACTRN12609000705280<br /

A modified Delphi approach to develop a trial protocol for antibiotic de-escalation in patients with suspected sepsis

Background: Early administration of antibiotics in sepsis is associated with improved patient outcomes, but safe and generalizable approaches to de-escalate or discontinue antibiotics after suspected sepsis events are unknown. Methods: We used a modified Delphi approach to identify safety criteria for an opt-out protocol to guide de-escalation or discontinuation of antibiotic therapy after 72 hours in non-ICU patients with suspected sepsis. An expert panel with expertise in antimicrobial stewardship and hospital epidemiology rated 48 unique criteria across 3 electronic survey rating tools. Criteria were rated primarily based on their impact on patient safety and feasibility for extraction from electronic health record review. The 48 unique criteria were rated by anonymous electronic survey tools, and the results were fed back to the expert panel participants. Consensus was achieved to either retain or remove each criterion. Results: After 3 rounds, 22 unique criteria remained as part of the opt-out safety checklist. These criteria included high-risk comorbidities, signs of severe illness, lack of cultures during sepsis work-up or antibiotic use prior to blood cultures, or ongoing signs and symptoms of infection. Conclusions: The modified Delphi approach is a useful method to achieve expert-level consensus in the absence of evidence suifficient to provide validated guidance. The Delphi approach allowed for flexibility in development of an opt-out trial protocol for sepsis antibiotic de-escalation. The utility of this protocol should be evaluated in a randomized controlled trial

Risk Factors of Not Reaching MCID after Elective Lumbar Spine Surgery: A Case Control Study

Background The therapeutic effect of spine surgery has been traditionally evaluated by physical examination, radiographic findings, and general perception of patient’s health status. However, these assessments are often insufficient to represent surgical outcomes.Patient-reported outcomes (PROs) are tools developed to measures quality outcomes following spinal surgery. Examples include the Patient-Reported Outcomes Measurement Information System Function 4-item Short Form (PROMIS-PF), Visual Analogue Scale (VAS), ODI (Oswestry Disability Index), SF-36 (Short Form Health Survey), and EQ-5D (EuroQuol-5D). The minimum clinically important difference (MCID) is an assessment tool to note the smallest clinical difference in PROs and provides the threshold where patients experience clinical benefit that justifies treatment plans or procedures despite the cost and side effects. MCID results reflect patient-perceived functional improvement, which can be a core metric in lumbar surgery for degenerative disease. Clinical and sociodemographic risk factors may serve to identify high-risk patients via MCID assessment. This study aims to identify risk factors associated with failure of reaching MCID based on PROMIS PF after elective lumbar spine surgery and the data registry from Michigan Spine Surgery Spine Surgery Improvement Collaborative (MSSIC). The results of this study can provide opportunities to optimize medical conditions of patients in prior to any elective lumbar surgery. METHODS MSSIC is a state-wide quality-improvement initiative database including 29 hospitals and 200 orthopedic- and neurosurgeons from various settings. Member hospitals are required to perform an annual minimum of 200 spine surgeries. MSSIC reviews elective spine surgeries for degenerative disease but excludes non-degenerative and/or complex pathology (i.e., spinal cord injury, traumatic fractures, pre-existing infection, grade 3 or 4 spondylolisthesis, scoliosis greater than 25◦, congenital anomalies, or ≥ 4-level fusion). Utilizing MSSIC, 10,922 patients who had undergone elective lumbar spine surgery were selected with 90 day follow up, and 7,200 patients with 1-year follow up. Patients with missing data were excluded from the study. Patient demographics, clinical presentation, medical history, surgical procedure, details of hospital stay, postsurgical adverse events within 90 days of surgery, and patient-reported outcome after surgery were reviewed. A patient was considered to have achieved MCID if there was an increase in ≥4.5 points. RESULTS Of 10,922 patients with 90-day follow-up, 4,453 patients (40.8%) did not reach MCID. Of 7,200 patients with 1-year follow up, 2,361 patients (23.8%) did not achieve MCID. There were significant baseline differences in demographic profiles and operative characteristics for those who had follow-up at 90 days and 1 year after their surgery. At 90 days after surgery, significant factors of not reaching MCID and their relative risk included symptom duration more than 1 year (1.34), previous spine surgery (1.25), African American descent (1.25), chronic opiate use (1.23), less than high school education (1.20), morbid obesity (1.15), ASA class \u3e2 (1.15), current smoking (1.14), chronic obstructive pulmonary disease (COPD) (1.13), depression (1.09), history of DVT (1.08), scoliosis (1.06), anxiety (1.06), baseline PROMIS (1.06), and surgery invasiveness (1.02). At 1 year after surgery, significant factors of not reaching MCID and their relative risk included symptom duration more than 1 year (1.41), less than high school education (1.34), previous spine surgery (1.30), morbid obesity (1.30), chronic opiate use (1.25), age (1.21), current smoking (1.21), African American descent (1.20), ASA class \u3e2 (1.18), history of DVT (1.12), depression (1.10), chronic obstructive pulmonary disease (COPD) (1.09), and baseline PROMIS (1.06). Independent ambulatory status (0.83 and 0.88 for 90-day and 1-year follow-up, respectively) and private insurance (0.83 and 0.85 for 90-day and 1-year follow-up, respectively) were associated with higher likelihood of reaching MCID. CONCLUSION This case control study identifies relevant risk factors of not reaching MCID after elective lumbar spine surgery. The results may assist clinicians in identifying high risk patients and optimizing patients’ medical conditions prior to spinal surgery

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p