Prior Drug Research Articles

A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens

The transition from occasional to escalated psychostimulant use is accelerated by prior drug exposure. These behavioral observations may be related to long-lasting transcriptional and/or epigenetic changes induced by the drug pre-exposure. Herein, we investigated if a single methamphetamine (METH) injection would enhance METH self-administration (SA) and impact any METH SA-induced epigenetic or transcriptional alterations. We thus injected a single METH dose (10 mg/kg) or saline to rats before training them to self-administer METH or saline. There were three experimental groups in SA experiments: (1) a single saline injection followed by saline SA (SS); (2) a single saline injection followed by METH SA (SM); and (3) a single METH injection followed by METH SA (MM). METH-pretreated rats escalated METH SA earlier and took more METH than saline-pretreated animals. Both groups showed similar incubation of cue-induced METH craving. Because compulsive METH takers and METH-abstinent rats show differences in potassium (K+) channel mRNA levels in their nucleus accumbens (NAc), we wondered if K+ channel expression might also help to distinguish between SM and MM groups. We found increases in mRNA and protein expression of shaker-related voltage-gated K+ channels (Kv1: Kcna1, Kcna3, and Kcna6) and calcium-activated K+ channels (Kcnn1) in the SM compared to MM rats. SM rats also showed decreased DNA methylation at the CpG-rich sites near the promoter region of Kcna1, Kcna3 and Kcnn1 genes in comparison to MM rats. Together, these results provide additional evidence for potentially using K+ channels as therapeutic targets against METH use disorder.

Updated Analysis of Bellini, a Phase 3 Study of Venetoclax or Placebo in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma

Updated Analysis of Bellini, a Phase 3 Study of Venetoclax or Placebo in Combination with Bortezomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma

Cocaine experience abolishes the motivation suppressing effect of CRF in the ventral midbrain

Stress affects dopamine-dependent behaviors in part through the actions of corticotropin releasing factor (CRF) in the ventral tegmental area (VTA). For example, acute stress engages CRF signaling in the VTA to suppress the motivation to work for food rewards. In contrast, acute stress promotes drug-seeking behavior through the actions of CRF in the VTA. These diverging behavioral effects in food- and drug-based tasks could indicate that CRF modulates goal-directed actions in a reinforcer-specific manner. Alternatively, prior drug experience could functionally alter how CRF in the VTA regulates dopamine-dependent behavior. To address these possibilities, we examined how intra-VTA injections of CRF influenced cocaine intake and whether prior drug experience alters how CRF modulates the motivation for food rewards. Our results demonstrate that intra-VTA injections of CRF had no effect on drug intake when self-administering cocaine under a progressive ratio reinforcement schedule. We also found that a prior history of either contingent or noncontingent cocaine infusions abolished the capacity for CRF to reduce the motivation for food rewards. Furthermore, voltammetry recordings in the nucleus accumbens illustrate that CRF in the VTA had no effect on cocaine-evoked dopamine release. These results collectively illustrate that exposure to abused substances functionally alters how neuropeptides act within the VTA to influence motivated behavior.

753. Outpatient Parenteral Antibiotic Therapy (OPAT) in a Large Urban Safety Net Hospital Setting: Therapy for Vulnerable Populations at Home

BackgroundAdoption of outpatient parenteral antibiotic therapy (OPAT) is accelerating due to proven safety and value, but experience in safety-net settings remains limited, especially in those with history of illicit drug use. Emerging reports from safety-net settings have featured OPAT delivered in nursing facilities, respite care centers, and infusion centers (including some persons who inject drugs [PWID]), but literature is sparse on home-based OPAT for vulnerable patients. In a new home antibiotics program at San Francisco General Hospital, we sought to describe early safety and efficacy outcomes among adults without active injection drug use but with high rates of substance use and comorbid illnesses.MethodsWe conducted a cohort study of patients discharged from a large urban county medical center and enrolled in an outpatient IV antibiotics program from September 2017 to January 2019. We collected demographic and clinical data and computed outcomes of safety (30- and 90-day readmission for infection, vascular access complications, and death) and efficacy (completion of antibiotic therapy).ResultsOverall, 47 courses of antibiotics were given to 45 patients. Of these, 39/47 (83%) of antibiotic courses were administered in a residential setting, and 8/47 (17%) via the hospital outpatient infusion center. Comorbid conditions were common, including 9/45 (20%) with hepatitis B/C and 8/45 (18%) with HIV (Table 1). Present or prior illicit drug use was seen in 17/45 patients (38%), including recent or active illicit drug use in 11/45 (24%) (Table 1). Most common indications for antibiotics were osteomyelitis and bacteremia (Table 2). Efficacy in the OPAT program was high: overall, 44/47 (94%) courses of outpatient IV antibiotics were completed, and the 30-day and 90-day readmission rates were 13% and 20% respectively, with zero 30-day readmissions related to OPAT (Table 3).ConclusionAn OPAT program embedded within a safety net hospital system delivering care in patients’ homes had high completion rate and low readmission rate, despite patients’ high prevalence of underlying comorbid conditions and noninjection illicit drug use. Home-based OPAT should be considered for broader adoption in safety-net hospital systems. Disclosures All authors: No reported disclosures.

764. Patients with Substance Use Disorder Discharged from Safety Net Hospital to Skilled Nursing Facility for OPAT: Baseline Characteristics and Clinical Outcomes

BackgroundSelf-administered Outpatient Parenteral Antimicrobial Therapy (S-OPAT) is offered at Parkland Memorial Hospital for uninsured patients requiring an extended course of intravenous (IV) antibiotics to complete treatment at home.1 At Parkland, S-OPAT has been demonstrated to be safe and effective with >70,000 inpatient bed days avoided to date, lower 30-day readmission rates, and significant cost savings.1 Patients with a history of substance use are not eligible for S-OPAT and are discharged to skilled nursing facilities (SNF) to complete IV antibiotic therapy. This study aims to describe clinical outcomes of a patient population with history of substance use discharged to SNF for OPAT.MethodsThe electronic medical record was used to identify patients with substance use discharged to an SNF for OPAT between January 1, 2017 and April 30, 2018. Data were retrospectively reviewed for demographics, substance use history, treatment plan and clinical outcomes.Results76 patients with history of substance use were discharged to SNFs for OPAT in the study period. 62% of patients reported non-IV drug use and 38% reported IV drug use (IVDU). The mean age for patients with non-IV drug use was 47 (83% male) vs. 43 years for patients with IVDU (86% male). Of patients with non-IV drug use, 30% reported cocaine use, 11% methamphetamine use and 59% polysubstance use or other. Of patients with IVDU, 38% reported heroin use, 10% methamphetamine use and 52% polysubstance use or other. When comparing outcomes of IVDU vs. non-IV drug use patients, 34% vs. 21% did not complete the prescribed treatment course, 28% vs. 11% left against medical advice (AMA), and 20% vs. 15% were readmitted to the hospital within 30 days.ConclusionThe majority of patients with substance use, 74%, completed their prescribed IV antibiotic course when sent to an SNF. However, a subset of these patients is at risk for poor clinical outcomes. A greater proportion of patients with prior IVDU compared with patients with prior non-IV drug use left treatment AMA and were readmitted to our hospital within 30 days of discharge. Future efforts to identify patients with substance use disorder who may be appropriate for S-OPAT with integration of addiction medicine services may improve clinical outcomes. DisclosuresAnk E. Nijhawan, MD, MPH, Gilead Sciences, Inc.: Research Grant.

A NATIONWIDE SURVEY OF ANTIFUNGAL PROPHYLAXIS IN LUNG TRANSPLANT

SESSION TITLE: Contemporary Lung Transplant Outcomes SESSION TYPE: Original Investigations PRESENTED ON: 10/20/2019 2:15 PM - 3:15 PM PURPOSE: Fungal infections in lung transplant recipients are associated with a 3-fold increase in mortality. While most experts agree on the need for antifungal prophylaxis in lung transplant, no standard of care exists. We surveyed lung transplant centers to determine the current goals, types, duration, and barriers of antifungal prophylaxis. METHODS: We developed and refined our survey through an iterative process. The ACCP Transplant Network endorsed our survey, and it was emailed to a physician representative at each adult lung transplant center in the United States. Transplant centers were eligible for participation if the center had completed 1 or more lung transplants in 2017. Non-responders were contacted on 2 more occasions. Surveys were collected from 11/29/2018-2/15/2019. Descriptive statistics were used to report findings. RESULTS: 44 of 62 (70.9%) eligible lung transplant centers completed the survey, representing all 11 OPTN regions. The median number of transplants performed per center was 26.5 (IQR 37.5). Four (9.1%) centers reported using pre-transplant prophylaxis to prevent post-transplant tracheobronchitis (3 of 4) and invasive fungal infections (4 of 4), with nebulized amphotericin (2), posaconazole (1), or voriconazole (1). Universal and selective/pre-emptive post-transplant prophylaxis was used by 35 (79.5%) and 4 (9.1%) centers, respectively, with the goal of preventing tracheobronchitis (23; 52.3%), invasive fungal infections (35; 79.5%), and chronic lung allograft dysfunction (11; 25.0%). Fungal colonization or donor marijuana use was the indication for selective prophylaxis. Nebulized amphotericin (27; 61.4%) and itraconazole (11; 25.0%) were the most commonly preferred antifungal medications, with most centers using ≥2 medications (33; 75.0%). Newer antifungals, posaconazole and isavuconazole, were preferred agents for 10 (22.7%) centers. Duration of post-transplant prophylaxis ranged from post-transplant hospitalization to lifelong. The most commonly reported barriers to antifungal prophylaxis were insurance prior authorizations (28; 63.6%), drug cost (24; 54.5%), and insurance coverage denial (23; 52.3%). CONCLUSIONS: The majority of transplant centers use post-transplant antifungal prophylaxis. While the goal of prophylaxis is similar among centers, the medication and duration of prophylaxis varies. In comparison to a prior survey in 2008, we observed an increase in preference for newer antifungal agents and a predilection for universal prophylaxis. Cultural acceptance of marijuana likely led to donor marijuana use becoming a selective criterion for some transplant centers. CLINICAL IMPLICATIONS: Almost universally, drug cost and insurance coverage are barriers to antifungal prophylaxis. Disparate practice patterns will continue to allow insurance companies to deny coverage for these medications until a standard of care is developed. DISCLOSURES: No relevant relationships by Patricio Escalante, source=Web Response No relevant relationships by Cassie Kennedy, source=Web Response No relevant relationships by Kelly Pennington, source=Web Response No relevant relationships by Raymund Razonable, source=Web Response No relevant relationships by Kathleen Yost, source=Web Response

1666 A Rare Case of Colonic Malakoplakia in an Immunocompetent Man With Prior Chronic Hepatitis C Virus Infection

INTRODUCTION: Malakoplakia is a rare chronic granulomatous condition related to a defect in macrophage phagolysosomal response in which engulfed bacteria are not destroyed. The urinary bladder is the most common site for malakoplakia to present and the gastrointestinal tract is a distant secondly reported site. Malakoplakia is often associated with conditions that cause immunodeficiency. We report a rare case of colonic malakoplakia (CM) in an asymptomatic, immunocompetent man with history of successfully treated hepatitis C virus (HCV) infection. CASE DESCRIPTION/METHODS: A 70-year-old African American man with a past medical history of treated HCV due to prior intravenous drug use, was referred by his primary care provider for screening colonoscopy. He was asymptomatic and clinical history was negative for inflammatory or other infectious diseases. He denied use of immunosuppressant medications. HCV RNA was undetectable. HIV serology was negative. No remarkable findings on physical examination. During colonoscopy, a single 5 mm sessile polyp was noted in the transverse colon and was removed (Figure 1). Histopathological analysis of polyp identified targetoid calcospherites on Von Kossa calcium stain consistent with Michaels-Gutman bodies, diagnostic of malakoplakia (Figures 2 and 3). On repeat colonoscopy four months later, a single 14 mm sessile polyp was found in the proximal descending colon with histopathology consistent with tubular adenoma. No findings suggestive of malakoplakia was noted, however, exam may have been limited due to poor bowel prep. DISCUSSION: In summary, malakoplakia has been reported to involve the urinary tract in approximately 75% of cases while the gastrointestinal tract is involved less than 10% of reported cases. CM is often associated with neoplasms such as adenocarcinoma, adenoma, and lymphoma and other non-neoplastic conditions such as infections, sarcoidosis, diabetes mellitus, alcoholic liver disease, immunosuppressive therapy, or other conditions of immunodeficiency. Though not previously reported, HCV could have played a role in development of CM. HCV as been reported to be associated with the development of cutaneous malakoplakia; therefore, we cannot exclude association of other extrahepatic manifestations. In conclusion, CM is a rare chronic granulomatous condition that can be incidentally found in immunocompetent individuals, more studies warranted to evaluate any association with HCV.

2751 Endoscopic Folie à Deux: Atypical Manifestations of Gastric Amyloid in Concurrent Cases

INTRODUCTION: Gastrointestinal amyloidosis is rare with variable, nonspecific presentations, signs, and endoscopic findings. We describe two cases featuring unusual endoscopic findings produced by histologically confirmed gastric amyloid. CASE DESCRIPTION/METHODS: Case 1: A 60 year old man with Child B cirrhosis due to chronic hepatitis C virus (HCV) infection, hidradenitis suppurativa, and end-stage renal disease from biopsy-proven amyloidosis on hemodialysis presented with melena and severe anemia. EGD showed diffuse gastric hemorrhagic, fibrinous exudates (Figure 1). On biopsy, Congo red stain showed apple green birefringence with plane polarized light microscopy consistent with amyloid. Four months later, after recurrent melena and bloody diarrhea, along with severe hypotension due to newly diagnosed adrenal insufficiency, the patient died while on comfort care. Case 2: A 63 year old man with Child C cirrhosis from chronic HCV, end-stage renal disease on hemodialysis, and prior intravenous drug use presented with hyperkalemia after missing his scheduled dialysis session. During his hospitalization, he developed melena and underwent an EGD, which showed scattered patchy moderate submucosal hemorrhages in a partially ringed pattern throughout the gastric body (Figure 2). On biopsy, Congo red stain showed apple green birefringence with plane polarized light microscopy; protein identification showed AA-type amyloid (Figure 3). Three months later, and to-date, the patient is hospitalized in the ICU for altered mental status, septic shock, and respiratory failure, with his hospital course complicated by repeated episodes of GI bleeding. DISCUSSION: These two cases of melena had distinctive, initially puzzling endoscopic findings, with biopsy results indicating gastric amyloid, a rare and atypical presentation of systemic amyloidosis. It is interesting that both patients in these cases had HCV infection. While AA-type, secondary amyloid can be caused by a chronic infectious state, there are no studies thus far that establish a causal link between HCV and amyloidosis. The patients in these two cases also carry other risk factors for amyloidosis, including hidradenitis suppurativa, end-stage renal disease, and intravenous drug use. Thus, while gastric amyloid is rare, endoscopists should keep it in the differential and note its potential for causing GI bleeding, especially in patients with risk factors, as it is a difficult condition to treat and its endoscopic findings can be dramatic.

2836 Association of Body Mass Index (Bmi) and Sedative Use During Screening Colonoscopy

INTRODUCTION: Colonoscopy is a key tool for colorectal cancer screening, but like any procedure, it is not without risk. The procedure can be done with conscious sedation. Risks from sedation include hypotension or hypoxia, sometimes requiring hospitalization and even endotracheal intubation. Therefore, endoscopists aim to minimize the amount of sedation needed to keep a patient comfortable and still be able to complete the procedure. We sought to examine the relationship between a patient’s body mass index (BMI) and the amount of sedation used during colonoscopy. METHODS: Data was collected on 640 patients undergoing conscious sedation screening colonoscopies at Louisville Veterans Affairs Medical Center, and 501 were excluded based on specific exclusion criteria, including known colonic disorders (e.g., IBD history, pre-existing malignancies) and lack of documented sedative use. Of 139 patients included, median age was 62, 86% patients were male, and 72% were white. Data were gathered by retrospective chart review of patient’s BMI as well as dosage of Midazolam, Fentanyl, and Diphenhydramine used during colonoscopy. Multiple Regression Model was used for analysis with corresponding P-values calculated. Statistical significance was set at P < 0.05. The total number of polyps detected was controlled for, as this was thought to affect the duration of colonoscopy. RESULTS: Our study indicates that, although a higher BMI was hypothesized to be associated with increased sedative use, the association was not statistically significant for any of the three sedatives in this study. This is most likely due to the fact that there was little variability between the doses of each sedative and the small sample size. CONCLUSION: Data in literature is scarce regarding the association between BMI and sedation use for colonoscopy. Most society guidelines on sedation in obesity are based on expert opinion. Factors affecting sedation use include longer cecal intubation times due to difficult technique in patients with obesity, reluctance to use higher amounts of sedation in patients with obesity due to increased risk of airway compromise, and prior alcohol or drug use. Larger studies are needed to further explore these findings, which may have future clinical implications regarding the introduction of specific guidelines for sedative use in patients with obesity.

Pharmacy involvement in an oral anticancer management program: Drug acquisition and safety in an ambulatory comprehensive care center.

85 Background: Oral anticancer agents (OACA) offer benefits of convenience, flexibility and quality of life; however, similar to intravenous therapy, OACA can be prone to medication ordering errors, drug-interactions, and administration errors. Additionally, they carry unique challenges such as treatment delay due to acquisition barriers and errors related to self-administration and monitoring. An oral anticancer management program was implemented to address vulnerable aspects of the outpatient OACA medication use process. Pharmacy benefit specialists (PBS) assist with prior authorizations (PA) and drug acquisitions; while, clinical pharmacists perform medication assessments and patient education. Methods: A retrospective review of patients prescribed OACAs between January 1 - March 31, 2019 was performed. A review of all PAs facilitated by our PBS was conducted and included date of prescription, date of submission to insurance, and date of PA approval. An assessment of pharmacist interventions on the prevention of medication-related errors and toxicity was conducted and was defined by any clarification or recommendation regarding medication dose, administration instructions, drug interactions, symptom management, medication reconciliation, and/or medication monitoring. Results: A total of 567 PAs were processed. Twenty-eight PA requests were denied and 539 were approved. The average time to approval was 1.5 days (range 0-13 days). 299 of the 567 patients were prescribed a new OACA and were enrolled into our education program. Pharmacists educated 191 patients. Pharmacists intervened 175 times for the 191 patients counseled. Interventions included recommendations/clarifications for symptom management (21.5%), medication reconciliation (19.5%), drug administration (16.2%), drug interactions (13.6%), and medication monitoring (7.3%). Conclusions: Pharmacy staff can make a valuable contribution to drug acquisition and overall clinical care of patients receiving OACAs. Our PBS reduced delays in acquisition and clinical pharmacists minimized medication-related errors and toxicity.

Assessing bleeding rates, related clinical impact and factor utilization in German hemophilia B patients treated with extended half-life rIX-FP compared to prior drug therapy

Objective: An extended half-life factor IX (FIX) fusion protein linking recombinant FIX with recombinant human albumin (rIX-FP), indicated for the treatment of hemophilia B, was approved by the European Medicines Agency in May 2016. We aimed to compare clinical outcomes and drug utilization in patients who switched from prior FIX therapies to rIX-FP.Methods: Anonymized patient chart data were collected from German institutions treating patients with hemophilia B. Patients were included if they had been treated with rIX-FP for ≥8 weeks at the time of data collection. Bleeding rates and FIX consumption were compared between rIX-FP and patients’ prior FIX products.Results: Data were obtained for 81 male patients treated with rIX-FP, including 59 who received prophylaxis with both their prior drug and rIX-FP (prophylaxis-to-prophylaxis group). Mean factor consumption in this group was 44.2 IU/kg/wk for rIX-FP compared with 82.3 IU/kg/wk for all prior FIX products. In addition, intra-patient analysis of factor consumption showed lower consumption of rIX-FP compared with prior FIX in 56 of 59 patients. Among the patients for whom bleed data were available (n = 42), annualized bleeding rate decreased from a mean (standard deviation) of 2.6 ± 2.9 on prior product to 0.3 ± 0.6 on rIX-FP. The proportion of patients with zero bleeds increased from 24% with prior therapy to 81% with rIX-FP.Conclusion: rIX-FP was associated with substantial reductions in bleeding rates and consumption of FIX compared with standard half-life products that require more frequent administration.

Contribution of genetic polymorphism of methylene tetrahydrofolate reductase on the effect of methotrexate in ectopic pregnancy patients.

BackgroundMethotrexate (MTX) is the prior drug in ectopic pregnancy (EP). However, approximately 10% of patients suffer from failure by MTX therapy. Reduced folate carrier 1 (RFC1), methylene tetrahydrofolate reductase (MTHFR), and dihydrofolate reductase (DHFR) are involved in the transport and effects of MTX in vivo. In the present study, we aim to investigate the relationship between the genetic polymorphisms of RFC1, MTHFR, and DHFR and the clinical efficacy of MTX in tubal pregnancies.Methods100 patients of EP were enrolled in this study. Polymorphisms of RFC1 G80A, MTHFR C677T, and DHFR A‐317G were genotyped. β‐hCG level was detected in day 0, 4, and 7 after MTX injection. Association of MTX efficacy and genetic polymorphisms was analyzed.ResultsMethylene tetrahydrofolate reductase C677T was associated with MTX treatment (P = .017). The success rate of first MTX injection was superior in patients with harboring mutation allele of MTHFR gene than that in patients with wild‐type gene (P = .001). However, there was no significant association between the polymorphisms of RFC1 G80A, DHFR A‐317G, and surgical treatment (P = .709 and .476, respectively). In addition, β‐hCG level decrement was not significantly changed by MTX injection with different polymorphisms of RFC1, MTHFR, and DHFR on either day 4 (P = .214, 0.197 and 0.270, respectively) or day 7 (P = .172, .554, and .726, respectively).ConclusionOur results suggested that the reliable indicator was polymorphism of MTHFR C677T in failure by MTX injection.

Real-World Adherence to Oral Methotrexate Measured Electronically in Patients With Established Rheumatoid Arthritis.

ObjectiveTo assess methotrexate (MTX) adherence using the Medication Event Monitoring System (MEMS) and characterize associations with adherence in patients with rheumatoid arthritis (RA).MethodsEligible patients participated in Forward, the National Databank for Rheumatic Diseases, and recently (12 months or sooner) initiated oral MTX. MEMS was used to compile MTX weekly dosing over 24 weeks. The Beliefs about Medicines Questionnaire (BMQ) was completed, and baseline demographics and disease characteristics obtained. MTX adherence (percentage of weeks dose taken correctly), implementation (percentage of weeks dose taken correctly from initiation until last dose), and persistence (duration from initiation to last dose) were calculated. Analyses measured associations between patient characteristics and adherence, modeled using logistic generalized estimating equations and censored Poisson regression, and persistence modeled using Cox regression.ResultsOverall, 60 of 119 eligible patients were included in the analysis. MTX adherence, implementation, and persistence were 75%, 80%, and 83%, respectively, at 24 weeks. Demographics and disease characteristics were generally similar between patients with 1 week or less and 2 weeks or more of missed MTX. Unemployment, less disability, higher Patient Global scores, and no prior disease‐modifying antirheumatic drug (DMARD) use were associated with correct dosing. No significant differences in adherence were observed between patients receiving concomitant MTX versus MTX monotherapy, and biologic DMARD‐experienced versus biologic DMARD‐naïve patients. Higher scores in BMQ Specific Necessity (indicating a greater belief in the necessity of the medication) was associated with a decreased likelihood of dosing at an interval shorter than prescribed (odds ratio 0.89).ConclusionEven in a participatory group over a short period, MTX adherence was suboptimal and associated with certain demographics, medication experience, and beliefs about medicines. This suggests a need for screening and alternative treatment opportunities in nonadherent MTX patients with RA.

Epidemiologic Shift in Candidemia Driven by Candida auris, South Africa, 2016–20171

Abstract Candida auris is an invasive healthcare-associated fungal pathogen. Cases of candidemia, defined as illness in patients with Candida cultured from blood, were detected through national laboratory-based surveillance in South Africa during 2016–2017. We identified viable isolates by using mass spectrometry and sequencing. Among 6,669 cases (5,876 with species identification) from 269 hospitals, 794 (14%) were caused by C. auris. The incidence risk for all candidemia at 133 hospitals was 83.8 (95% CI 81.2–86.4) cases/100,000 admissions. Prior systemic antifungal drug therapy was associated with a 40% increased adjusted odds of C. auris fungemia compared with bloodstream infection caused by other Candida species (adjusted odds ratio 1.4 [95% CI 0.8–2.3]). The crude in-hospital case-fatality ratio did not differ between Candida species and was 45% for C. auris candidemia, compared with 43% for non–C. auris candidemia. C. auris has caused a major epidemiologic shift in candidemia in South Africa.

Epidemiologic Shift in Candidemia Driven by Candida auris, South Africa, 2016-20171.

Candida auris is an invasive healthcare-associated fungal pathogen. Cases of candidemia, defined as illness in patients with Candida cultured from blood, were detected through national laboratory-based surveillance in South Africa during 2016–2017. We identified viable isolates by using mass spectrometry and sequencing. Among 6,669 cases (5,876 with species identification) from 269 hospitals, 794 (14%) were caused by C. auris. The incidence risk for all candidemia at 133 hospitals was 83.8 (95% CI 81.2–86.4) cases/100,000 admissions. Prior systemic antifungal drug therapy was associated with a 40% increased adjusted odds of C. auris fungemia compared with bloodstream infection caused by other Candida species (adjusted odds ratio 1.4 [95% CI 0.8–2.3]). The crude in-hospital case-fatality ratio did not differ between Candida species and was 45% for C. auris candidemia, compared with 43% for non–C. auris candidemia. C. auris has caused a major epidemiologic shift in candidemia in South Africa.

The effect of current and prior smoking, alcohol consumption, and drug abuse on IVF outcomes

The effect of current and prior smoking, alcohol consumption, and drug abuse on IVF outcomes

Author Reply

Thank you for your insight and the authors agree with your comments. We agree that it is difficult to ascertain the direct role media sources played on patient decision-making in this retrospective study. Overall, the American Urogynecologic Society /Society for Urodynamics Female Pelvic Medicine and Urogenital Reconstruction statements have made preoperative counseling visits more productive and helps the surgeon dispel some of the negative connotations associated with synthetic mesh products. As you mentioned, the synthetic midurethral sling has endured collateral damage from prior Foods and Drug Administration notifications on transvaginal mesh. It will be interesting to see if the Foods and Drug Administration's recent order to manufacturers of all remaining surgical mesh products indicated for transvaginal repair of pelvic organ prolapse to stop selling and distributing their products in the United States immediately, will have an equally deleterious effect on midurethral sling utilization despite our best efforts to educate our patients. 1 Food and Drug Administration. https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/UroGynSurgicalMesh/default.htm. Accessed June 5, 2019 Google Scholar

Effect of disease duration and prior disease-modifying antirheumatic drug use on treatment outcomes in patients with rheumatoid arthritis

ObjectivesTo determine if disease duration and number of prior disease-modifying antirheumatic drugs (DMARDs) affect response to therapy in patients with established rheumatoid arthritis (RA).MethodsAssociations between disease duration or number of...

Evaluation of Sacubitril/Valsartan Prescribing and Monitoring at a Veterans Affairs Hospital

Introduction Heart Failure (HF) readmissions is a burden to the patient, family and healthcare system. The PARADIGM-HF trial demonstrated that patients on maintenance doses of sacubitril/valsartan 97/103 mg twice daily experienced a reduction in cardiovascular mortality and heart failure hospitalizations compared with enalapril. The Veterans Affairs (VA) Pharmacy Benefit Management (PBM) criteria for use recommends that patients follow-up with a provider within two to four weeks of therapy initiation for serum potassium, renal function, and blood pressure monitoring, and to ensure dose titration to the target maintenance dose. The objective of this medication use evaluation was to evaluate the prescribing and monitoring of patients on sacubitril/valsartan at a Veterans Affairs facility. Methods A retrospective chart review was conducted of heart failure patients who were initiated on sacubitril/valsartan at a Veterans Affairs facility. Patients with a prior authorization drug request (PADR) and who had an active prescription order for sacubitril/valsartan between September 2016 through January 2018 were included. Data collected were patient adherence to provider follow up, timing of patient follow up appointments, and laboratory monitoring, and the patient's adherence to medication (using the medication possession ratio). All data were analyzed using descriptive statistics. Results Initially, thirty-five PADR requests were identified. Sixteen were approved and included in the medication use evaluation. After drug initiation, approximately 75% (n=12) of patients on sacubitril/valsartan are being sub optimally monitored while on therapy. Of the 25% of patients reevaluated within two to four weeks, hypotension limited further dose titration in all these patients. Two patients achieved target maintenance dose 97/103 mg twice daily. Approximately 69% (n=11) of patients were determined to be adherent to sacubitril/valsartan. Conclusions Patients on sacubitril/valsartan are being sub optimally monitored while on therapy. It is essential that patients are titrated to the goal sacubitril/valsartan dose of 97/103 mg twice daily to optimize clinical outcomes. As shown in the PARADIGM trial, it is essential that patients are titrated to the goal sacubitril/valsartan dose of 97/103 mg twice daily, when possible, to optimize clinical outcomes. The results of this quality improvement project were presented to the P&T Committee (Pharmacy and Therapeutics). Informational “Dear Provider” letters were sent out to remind providers to optimize dosing. Subsequent follow up of the original sixteen patients is currently pending and results of the intervention will be followed up with P&T, and presented at HFSA.

Identification with drug use among young adults who are at risk of transitioning to more serious use

Understanding the drug use trajectories for at risk young adults can help reduce harms associated with serious drug use. This longitudinal study tracked young people to assess whether implicit and explicit identification with substance use predicts changes in use over time and whether patterns of use impacts identification with drugs. Two hundred and twenty-eight participants were initially recruited from homeless shelters, youth centers, drug health services, and parks where young people who use drugs are known to frequent. Over a 20-month period, 78 of these original participants were successfully recontacted and surveyed again. The survey assessed implicit and explicit identification with drug use, along with known risk factors, to determine if identification predicts changes in drug use over time as assessed by frequency, recency, and multiple drug use. Results revealed that implicit and explicit identification with drug use were stronger among participants who used more frequently, more recently, and used multiple drugs, although this finding only emerged cross-sectionally and not longitudinally. Overall, these results suggest that patterns of drug use are associated with the identity of the individual and that identification with drug use is a marker of drug-using behavior, but identification with drug use does not appear to be predictive of future behavior nor an outcome of prior drug use.