Factors associated with functional arteriovenous fistula at hemodialysis start and arteriovenous fistula non-use in a single-center cohort.

BACKGROUND: The gold standard of commencing hemodialysis with a functional arteriovenous fistula (AVF) is challenging. We aim to review factors associated with functional AVF at hemodialysis start at a tertiary hospital. METHODS: We retrospectively reviewed incident hemodialysis patients or who had AVF creation at a single tertiary hospital from 2011 to 2016. Data was extracted for patient comorbidities, duration from referral to AVF creation and hemodialysis start, estimated glomerular filtration rate (eGFR) at surgical referral, referring nephrologist, events accelerating eGFR decline, and revisions for "failing to mature" AVF to assess factors associated with non-functioning AVF or late AVF creation, using multinomial logistic regression. RESULTS: Two hundred two patients received hemodialysis and 51 had AVF creation but did not dialyze (AVF futility rate 20%). Of these, 133 (66%) commenced hemodialysis with a central venous catheter (CVC) and 69 (34%) with an AVF. Patients with functional AVFs at hemodialysis start were referred earlier than those with non-functional AVFs (median 256 vs 66 days before hemodialysis start, p = 0.001). Age, sex, eGFR at surgical referral, and comorbidities were not predictive of patients with functional AVFs. Events accelerating eGFR decline were associated with an increased incidence of CVC at hemodialysis start (risk ratio (RR) 4.21, 95% confidence interval (CI) 1.96-9.03, p < 0.0001). Referring nephrologists external to our renal unit may be associated with non-functional AVF at hemodialysis start (RR 6.60, 95% CI 1.74-25.13, p = 0.006). CONCLUSIONS: We found that functional AVFs required referral a median of 256 days prior to hemodialysis start and events accelerating eGFR decline increase the incidence of CVC at hemodialysis start. Age, sex, eGFR at surgical referral, and comorbidities did not inform the likelihood of timely AVF creation and evaluation of further predictive pre-dialysis factors is necessary to identify patients requiring early AVF creation whilst minimizing the cost of unnecessary procedures.

Depression-related stigma among primary care providers.

INTRODUCTION: Depression is one of the most common mental illnesses in the United States and is often treated in primary care settings. Despite its prevalence, depression remains underdiagnosed and undertreated for a variety of reasons, including stigma. This may result in suboptimal management of depression. Studies evaluating stigma in US primary care providers (PCP) are scarce. The main objective of this study was to describe stigma in a cohort of PCPs. METHODS: We utilized a validated questionnaire to measure stigma (score range 15 to 75 with lower scores indicating lower stigma levels). PCPs in 2 academic internal medicine clinics were sent an electronic questionnaire and received a small monetary incentive for responding. In addition to the stigma survey, we collected demographic data, including age, provider type, gender, and other data related to social proximity to mental illness. To describe stigma, differences in stigma between provider characteristics were evaluated using t tests and ANOVA tests as appropriate. RESULTS: Of 107 PCPs, 71 responded (66.4% response rate). Male responders displayed higher stigma scores than females (31.8 vs 27.4, P = .0021). Medical residents displayed higher stigma scores than nonresidents (31.3 vs 27.2, P = .0045). Providers with personal exposure to mental illness and those who reported they frequently treated depression had less stigma. DISCUSSION: Overall, a range of stigma was present among PCPs surveyed. Higher levels of stigma were found in men, medical residents, those without personal exposure to mental illness, younger PCPs, and those who reported treating depression less frequently. Future studies should utilize larger sample sizes and focus on the impact of stigma on quality of care.

Validation of algorithms to identify elective percutaneous coronary interventions in administrative databases.

BACKGROUND: Elective percutaneous coronary interventions (PCI) are difficult to discriminate from non-elective PCI in administrative data due to non-specific encounter codes, limiting the ability to track outcomes, ensure appropriate medical management, and/or perform research on patients who undergo elective PCI. The objective of this study was to assess the abilities of several algorithms to identify elective PCI procedures using administrative data containing diagnostic, utilization, and/or procedural codes. METHODS AND RESULTS: For this retrospective study, administrative databases in an integrated healthcare delivery system were queried between 1/1/2015 and 6/31/2016 to identify patients who had an encounter for a PCI. Using clinical criteria, each encounter was classified via chart review as a valid PCI, then as elective or non-elective. Cases were tested against nine pre-determined algorithms. Performance statistics (sensitivity, specificity, positive predictive value, and negative predictive value) and associated 95% confidence intervals (CI) were calculated. Of 521 PCI encounters reviewed, 497 were valid PCI, 93 of which were elective. An algorithm that excluded emergency room visit events had the highest sensitivity (97.9%, 95%CI 92.5%-99.7%) while an algorithm that included events occurring within 90 days of a cardiologist visit and coronary angiogram or stress test had the highest positive predictive value (62.2%, 95%CI 50.8%-72.7%). CONCLUSIONS: Without an encounter code specific for elective PCI, an algorithm excluding procedures associated with an emergency room visit had the highest sensitivity to identify elective PCI. This offers a reasonable approach to identify elective PCI from administrative data.

Universal hepatitis B screening and management in patients with cancer who received immunosuppressive chemotherapy.

BACKGROUND: Clinical data to guide management of patients with cancer and hepatitis B virus (HBV) infection who are treated with immunosuppressive chemotherapy are lacking. The purpose of this study was to describe HBV+ rates in a population of patients with cancer and evaluate a risk-stratified management protocol for the prevention of HBV reactivation (HBVr). METHODS: This was a descriptive study conducted in an integrated healthcare delivery system. Patients with cancer and hepatitis B virus infection who received immunosuppressive chemotherapy between 1 January 2014 and 31 January 2016 were included. A risk-stratified management protocol that continued for six months after chemotherapy completion or 12 months after completion of B-cell targeted chemotherapy was assessed. Outcomes included the proportion of patients who were HBV+ and amongst patients who initiated immunosuppressive therapy, proportions who received hepatitis B virus monitoring or anti-hepatitis B virus prophylaxis, or experienced HBVr or hepatitis B virus-related complications. RESULTS: There were 2463 patients with cancer screened for hepatitis B virus with 114 (4.6%) HBV+ of whom 59 (51.8%) initiated chemotherapy. Included patients were primarily older, male, and white with gastrointestinal or hematologic cancers and initiated intermediate/low-risk cytotoxic chemotherapy. During follow-up, 41 (69.5%) received hepatitis B virus DNA monitoring and 17 (28.8%) initiated anti-hepatitis B virus prophylaxis. No HBVr was observed. ALT and AST abnormalities were common but mostly Grade 1 and primarily related to the patient's malignancy or medications. CONCLUSIONS: Universal hepatitis B virus screening coupled with a risk-stratified management strategy utilizing HBVr monitoring and anti-hepatitis B virus prophylaxis in HBV+ patients receiving immunosuppressive chemotherapy for cancer may prevent HBVr.

Investigation of elevation as a risk factor for hypertensive disorders of pregnancy among Colorado women between 2007 and 2015.

OBJECTIVE: The purpose of this study is to determine the association between high elevation and hypertensive disorders of pregnancy (HDP). METHODS: Retrospective cohort study using Colorado birth certificate data to compare HDP at high (≥8,000 ft), moderate (4,501-7,999 ft), or low (≤4,500 ft) elevation using logistic regression. RESULTS: Among the cohort (n = 314,431), 3.4% of women developed a HDP. High or moderate elevation was not significantly associated with HDP relative to low elevation (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 0.93-1.43; aOR 1.14, 95% CI 0.98-1.31, respectively). CONCLUSION: Women living at high or moderate elevation do not have higher odds of HDP.

A Predictive Model to Identify Skilled Nursing Facility Residents for Pharmacist Intervention.

Objective Develop a predictive model to identify patients in a skilled nursing facility (SNF) who require a clinical pharmacist intervention. Design Retrospective, cross-sectional. Setting Nine freestanding SNFs within an integrated health care delivery system. Patients Patients who received a clinical pharmacist medication review between January 1, 2016, and April 30, 2017. Identified patients (n = 2,594) were randomly assigned to derivation and validation cohorts. Interventions Multivariable logistic regression modeling was performed to identify factors predictive of patients who required an intervention (i.e., medication dose adjustment, initiation, or discontinuation). Patient-specific factors (e.g., demographics, medication dispensings, diagnoses) were collected from administrative databases. A parsimonious model based on clinical judgment and statistical assessment was developed in the derivation cohort and assessed for fit in the validation cohort. Main Outcome Measures Model to predict patients requiring clinical pharmacist intervention. Secondary outcome was a comparison of factors between patients who did and did not receive a clinical pharmacist intervention. Results Ninety-five factors were assessed. The derivation (n = 1,299) model comprised 22 factors (area under the curve [AUC] = 0.79, 95% confidence interval [CI] 0.74-0.84). A clopidogrel dispensing (odds ratio [OR] = 2.42, 95% CI 1.19-4.91), fall (OR = 2.47, 95% CI 1.59-3.83), or diagnosis for vertebral fracture (OR = 2.33, 95% CI 1.34-4.05) in the 180 days prior to clinical pharmacist medication review were predictive of requiring an intervention. The model fit the validation cohort (n = 1,295) well, AUC = 0.79 (95% CI 0.74-0.84). Conclusion Administrative data predicted patients in a SNF who required clinical pharmacist intervention. Application of this model in real-time could result in clinical pharmacist time-savings and improved pharmacy services through more directed patient care.

Risk Factors for Utilization of Acute Care Services for Lithium Toxicity.

OBJECTIVE: This study evaluated risk factors for utilization of acute care services (ACS) (hospitalization or emergency department or urgent care visit) for lithium toxicity and the prevalence of lithium toxicity in a large, ambulatory population. METHODS: A nested case-control study compared lithium users with ACS utilization for lithium toxicity (case group) to lithium users without toxicity (control group) by using data from Kaiser Permanente Colorado for patients with at least one lithium prescription purchase. Patients in the case group were matched 1:5 with patients in the control group who had purchased lithium within 39 days of the ACS encounter. Possible lithium toxicity, identified by lithium level or diagnosis, was confirmed by chart review. Multivariable, conditional logistic regression analysis was used to identify patient and prescription characteristics associated with ACS utilization for lithium toxicity. The prevalence of lithium toxicity was determined. RESULTS: Of 3,115 individuals who took lithium, 70 experienced lithium toxicity, with or without ACS utilization, for a prevalence of 2.2%. Identified risk factors for ACS utilization for lithium toxicity included a newly initiated potentially interacting medication (odds ratio [OR]=30.30, 95% confidence interval [CI]=2.32-394.95), a higher number of treated chronic diseases (OR=1.28, CI=1.12-1.45), older age (OR=1.05, CI=1.02-1.09), and higher total daily lithium dose (OR=1.00, CI=1.00-1.00). CONCLUSIONS: Newly initiated, potentially interacting medications are a major preventable driver of ACS use for lithium toxicity, whereas age, chronic disease, and total daily lithium dose are small but significant factors. Clinicians should use extra caution when initiating a potentially interacting medication.

Evaluation of a Clinical Pharmacist-Led Multidisciplinary Antidepressant Telemonitoring Service in the Primary Care Setting.

Guidelines recommend patient follow-up within 2 weeks of antidepressant initiation or uptitration to minimize treatment discontinuation and suicidal ideation risks; however, time constraints and lack of systematic processes remain barriers in primary care. A pharmacist-led multidisciplinary telemonitoring service aimed to address these barriers. This was a retrospective, observational study of adults with depression initiated or uptitrated on an antidepressant between May and October 2016. Outcomes included the proportion of eligible patients successfully contacted, adherence, adverse effects, suicidal ideations, and pharmacist interventions. Clinical pharmacists successfully reached 258 of 380 (68%) patients and provided follow-up in 298 calls. Patients endorsed antidepressant nonadherence during 56 (19%) calls, adverse effects in 81 (27%) calls, and suicidal ideations in 13 (4%) calls. Pharmacists provided 109 total interventions for 102 patients. The clinical pharmacist-led multidisciplinary antidepressant telemonitoring service is an alternative resource to monitor patients after antidepressant initiation or titration in primary care settings.

A Role for Low Density Lipoprotein Receptor-Related Protein 1 in the Cellular Uptake of Tissue Plasminogen Activator in the Lungs.

PURPOSE: To gain knowledge of lung clearance mechanisms of inhaled tissue plasminogen activator (tPA). METHODS: Using an in vivo mouse model and ex vivo murine whole organ cell suspensions, we examined the capability of the lungs to utilize LRP1 receptor-mediated endocytosis (RME) for the uptake of exogenous tPA with and without an LRP1 inhibitor, receptor associated protein (RAP), and quantitatively compared it to the liver. We also used a novel imaging technique to assess the amount LRP1 in sections of mouse liver and lung. RESULTS: Following intratracheal administration, tPA concentrations in the bronchoalveolar lavage fluid (BALF) declined over time following two-compartment pharmacokinetics suggestive of a RME clearance mechanism. Ex vivo studies showed that lung and liver cells are similarly capable of tPA uptake via LRP1 RME which was reduced by ~50% by RAP. The comparable lung and liver uptake of tPA is likely due to equivalent amounts of LRP1 of which there was an abundance in the alveolar epithelium. CONCLUSIONS: Our findings indicate that LRP1 RME is a candidate clearance mechanism for inhaled tPA which has implications for the development of safe and effective dosing regimens of inhaled tPA for the treatment of plastic bronchitis and other fibrin-inflammatory airway diseases in which inhaled tPA may have utility.

Cardiotonic steroids stabilize regulator of G protein signaling 2 protein levels.

Regulator of G protein signaling 2 (RGS2), a G(q)-specific GTPase-activating protein, is strongly implicated in cardiovascular function. RGS2(-/-) mice are hypertensive and prone to heart failure, and several rare human mutations that accelerate RGS2 degradation have been identified among patients with hypertension. Therefore, pharmacological up-regulation of RGS2 protein levels might be beneficial. We used a ß-galactosidase complementation method to screen several thousand compounds with known pharmacological functions for those that increased RGS2 protein levels. Several cardiotonic steroids (CTSs), including ouabain and digoxin, increased RGS2 but not RGS4 protein levels. CTSs increased RGS2 protein levels through a post-transcriptional mechanism, by slowing protein degradation. RGS2 mRNA levels in primary vascular smooth muscle cells were unaffected by CTS treatment, whereas protein levels were increased 2- to 3-fold. Na(+)/K(+)-ATPase was required for the increase in RGS2 protein levels, because the effect was lost in Na(+)/K(+)-ATPase-knockdown cells. Furthermore, we demonstrated that CTS-induced increases in RGS2 levels were functional and reduced receptor-stimulated, G(q)-dependent, extracellular signal-regulated kinase phosphorylation. Finally, we showed that in vivo treatment with digoxin led to increased RGS2 protein levels in heart and kidney. CTS-induced increases in RGS2 protein levels and function might modify several deleterious mechanisms in hypertension and heart failure. This novel CTS mechanism might contribute to the beneficial actions of low-dose digoxin treatment in heart failure. Our results support the concept of small-molecule modulation of RGS2 protein levels as a new strategy for cardiovascular therapy.

Prospective, longitudinal study of plastic bronchitis cast pathology and responsiveness to tissue plasminogen activator.

Plastic bronchitis (PB) is a rare disease that often occurs in patients with congenital heart disease (CHD) who have undergone staged single-ventricle palliation. It is characterized by the formation of rubbery "casts" in the airways. PB treatment frequently includes inhaled tissue plasminogen activator (tPA). However, the efficacy of tPA to reduce cast burden is unknown. This is further complicated by our lack of knowledge of cast composition. We obtained spontaneously expectorated PB casts from children (n = 4) with CHD and one adult patient with idiopathic PB. Pathological assessment was made from paraffin-preserved samples. Casts were treated with phosphate-buffered saline (PBS) or tPA. Cast response to tPA was assessed by changes in cast weight and the production of fibrin D-dimer. Independent of dose, tPA reduced cast weight compared with PBS-treatment (P = 0.001) and increased D-dimer levels. Histological staining showed that PB casts from all patients were composed of fibrin and contained notable numbers of lymphocytes. Cast composition did not change over time. Collectively, these data support that in our PB patients, casts are composed of fibrin and are responsive to tPA treatment. This makes inhaled tPA a potentially viable option for symptomatic relief of PB while we work to unravel the complexity of PB pathogenesis.