Are Illinois Contraceptive Providers Comfortable Providing Care to Adolescents? Results From a Statewide Provider Needs Assessment.

OBJECTIVES: Legislation allows adolescents to access comprehensive contraceptive care; however, provider practices remain unclear. We examined predictors of provider knowledge and comfort surrounding the provision of contraceptive care to adolescents. METHODS: We mailed a survey to Illinois contraceptive providers (n = 251). Study outcomes include 1) knowledge of adolescent consent laws, 2) comfort asking for time alone with adolescents, 3) comfort providing contraception to adolescents without parental consent, and 4) comfort providing long-acting reversible contraception (LARC) to adolescents without parental consent. Using multivariable logistic regression, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Most providers are knowledgeable of consent laws (90%) and report being comfortable asking for time alone with adolescents (94%) and comfortable providing contraception to adolescents without parental consent (88%). Having a large proportion of patients who are eligible for family planning services was associated with increased comfort asking for time alone with adolescents (aOR, 7.03; 95% CI, 1.58-31.3) and providing contraception to adolescents (aOR, 4.0; 95% CI, 1.4-11.1). Only one-half (54%) were comfortable providing LARC methods to adolescents, with higher comfort among providers who: received more than 2 days of formal family planning training (aOR, 2.77; 95% CI, 1.2-6.2), specialized in obstetrics-gynecology (aOR, 5.64; 95% CI, 2.1-15.1), and had a patient population with more than 50% patients from minoritized racial/ethnic groups (aOR, 2.9; 95% CI, 1.2-6.6). CONCLUSIONS: Although knowledge of consent laws was high, gaps remain. Only one-half of our sample indicated comfort with the provision of LARC methods without parental consent. Additional efforts to increase provider comfort with all contraceptive methods and training on adolescent-centered practices may be required to meet the needs of adolescent patients.

Development of a Scientific Writing Course to Increase Fellow Scholarship.

Physicians in training are often taught how to conduct original research but may lack the skills necessary to write their results in a paper for the peer-reviewed medical literature. To help our critical care fellows increase their publication rates, we implemented an 8-hour scientific writing course that provides a structured approach to writing an academic research paper. We have demonstrated an increase in publication rate during fellowship from an average of 0.7 manuscripts per fellow just before course inception to 3.7 manuscripts per fellow in the current graduating class. We highlight strategies for developing a writing course aligned with adult learning theory within three key areas: planning, pedagogy, and implementation. Planning strategies center around creating a case for change, including multiple stakeholders with diverse backgrounds, including the research mentor, and ensuring accountability among stakeholders. Pedagogical strategies focus on harnessing the power of experiential learning, considering a flipped classroom approach, and peer teaching to leverage social and cognitive congruence. Implementation strategies include breaking down the writing process into manageable tasks, organizing the writing process according to learner needs, using peer review processes to drive learning, and celebrating the accomplishments of learners within the course. These strategies represent broad initiatives that can be tailored to local training needs and instituted across a wide variety of teaching platforms.

Police Enforcement of Sex Work Criminalization Laws in an "End Demand" City: The Persistence of Quality-of-Life Policing and Seller Arrests.

The purported goals of commercial sex work criminalization policies in the United States have shifted over the past two decades as local jurisdictions have adopted End Demand reforms. These reforms aim to refocus arrest from individuals who sell sexual services to buyers and facilitators, representing a departure from the quality-of-life, nuisance-focused approach of the late twentieth century. This article presents a case study examining enforcement of commercial sex laws in Chicago, a city that has been heralded as a leader in End Demand reforms. Our case study utilized annualized arrest statistics from 1998 to 2017 and individual arrest reports (n = 575) from 2015 to 2017. Commercial sex arrests by the Chicago Police Department have declined substantially over the past two decades, falling 98.4% from its peak. However, our analysis suggests that sellers of sexual services continue to face the heaviest burden of arrest (80.5%) and officers generally continue to approach commercial sex as a quality-of-life issue. We argue that this divergence between the goals and implementation of End Demand are the result of three institutional factors: street-level bureaucracy, logics of spatial governmentality, and participatory security. Our results suggest that the ideals of End Demand may be incompatible with the institutional realties of urban policing.

A potent Lassa virus antiviral targets an arenavirus virulence determinant.

Arenaviruses are a significant cause of hemorrhagic fever, an often-fatal disease for which there is no approved antiviral therapy. Lassa fever in particular generates high morbidity and mortality in West Africa, where the disease is endemic, and a recent outbreak in Nigeria was larger and more geographically diverse than usual. We are developing LHF-535, a small-molecule viral entry inhibitor that targets the arenavirus envelope glycoprotein, as a therapeutic candidate for Lassa fever and other hemorrhagic fevers of arenavirus origin. Using a lentiviral pseudotype infectivity assay, we determined that LHF-535 had sub-nanomolar potency against the viral envelope glycoproteins from all Lassa virus lineages, with the exception of the glycoprotein from the LP strain from lineage I, which was 100-fold less sensitive than that of other strains. This reduced sensitivity was mediated by a unique amino acid substitution, V434I, in the transmembrane domain of the envelope glycoprotein GP2 subunit. This position corresponds to the attenuation determinant of Candid#1, a live-attenuated Junín virus vaccine strain used to prevent Argentine hemorrhagic fever. Using a virus-yield reduction assay, we determined that LHF-535 potently inhibited Junín virus, but not Candid#1, and the Candid#1 attenuation determinant, F427I, regulated this difference in sensitivity. We also demonstrated that a daily oral dose of LHF-535 at 10 mg/kg protected mice from a lethal dose of Tacaribe virus. Serial passage of Tacaribe virus in LHF-535-treated Vero cells yielded viruses that were resistant to LHF-535, and the majority of drug-resistant viruses exhibited attenuated pathogenesis. These findings provide a framework for the clinical development of LHF-535 as a broad-spectrum inhibitor of arenavirus entry and provide an important context for monitoring the emergence of drug-resistant viruses.

Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) restores carbapenem susceptibility to NDM-1-positive pathogens in vitro and in vivo.

Objectives: The objective of this study was to test the efficacy of an inhibitor of the New Delhi metallo-ß- lactamase (NDM-1). Inhibiting expression of this type of antibiotic-resistance gene has the potential to restore antibiotic susceptibility in all bacteria carrying the gene. Methods: We have constructed a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) that selectively inhibits the expression of NDM-1 and examined its ability to restore susceptibility to meropenem in vitro and in vivo . Results: In vitro , the PPMO reduced the MIC of meropenem for three different genera of pathogens that express NDM-1. In a murine model of lethal E. coli sepsis, the PPMO improved survival (92%) and reduced systemic bacterial burden when given concomitantly with meropenem. Conclusions: These data show that a PPMO can restore antibiotic susceptibility in vitro and in vivo and that the combination of PPMO and meropenem may have therapeutic potential against certain class B carbapenem-resistant infections in multiple genera of Gram-negative pathogens.

The electronic medication complete communication (EMC2) study: Rationale and methods for a randomized controlled trial of a strategy to promote medication safety in ambulatory care.

BACKGROUND: Adverse drug events (ADEs) affect millions of patients annually and place a significant burden on the healthcare system. The Food and Drug Administration (FDA) has developed patient safety information for high-risk medications that pose serious public health concerns. However, there are currently few assurances that patients receive this information or are able to identify or respond correctly to ADEs. OBJECTIVE: To evaluate the effectiveness of the Electronic Medication Complete Communication (EMC2) Strategy to promote safe medication use and reporting of ADEs in comparison to usual care. METHODS: The automated EMC2 Strategy consists of: 1) provider alerts to counsel patients on medication risks, 2) the delivery of patient-friendly medication information via the electronic health record, and 3) an automated telephone assessment to identify potential medication concerns or ADEs. The study will take place in two community health centers in Chicago, IL. Adult, English or Spanish-speaking patients (N=1200) who have been prescribed a high-risk medication will be enrolled and randomized to the intervention arm or usual care based upon practice location. The primary outcomes of the study are medication knowledge, proper medication use, and reporting of ADEs; these will be measured at baseline, 4weeks, and three months. Intervention fidelity as well as barriers and costs of implementation will be evaluated. CONCLUSIONS: The EMC2 Strategy automates a patient-friendly risk communication and surveillance process to promote safe medication use while minimizing clinic burden. This trial seeks to evaluate the effectiveness and feasibility of this strategy in comparison to usual care.

Lead optimization of an acylhydrazone scaffold possessing antiviral activity against Lassa virus.

Previously we reported the optimization of antiviral scaffolds containing benzimidazole and related heterocycles possessing activity against a variety of arenaviruses. These series of compounds were discovered through an HTS campaign of a 400,000 small molecule library using lentivirus-based pseudotypes incorporated with the Lassa virus envelope glycoprotein (LASV GP). This screening also uncovered an alternate series of very potent arenavirus inhibitors based upon an acylhydrazone scaffold. Subsequent SAR analysis of this chemical series involved various substitutions throughout the chemical framework along with assessment of the preferred stereochemistry. These studies led to an optimized analog (ST-161) possessing subnanomolar activity against LASV and submicromolar activity against a number of other viruses in the Arenaviridae family.

Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole.

A chemically diverse library of about 400,000 small molecules was screened for antiviral activity against lentiviral pseudotypes with the Lassa virus envelope glycoprotein (LASV GP) gene incorporated. High-throughput screening resulted in discovery of a hit compound (ST-37) possessing a benzimidazole core which led to a potent compound series. Herein, we report SAR studies which involved structural modifications to the phenyl rings and methylamino linker portion attached to the benzimidazole core. Many analogs in this study possessed single digit nanomolar potency against LASV pseudotypes. Compounds in this benzimidazole series also exhibited nanomolar antiviral activity against pseudotypes generated from other arenavirus envelopes indicating the potential for development of a broad-spectrum inhibitor. Ultimately, lead compound ST-193 was identified and later found to be efficacious in a lethal LASV guinea pig model showing superior protection compared to ribavirin treatment.

Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole and related heterocycles.

A series of potent arenavirus inhibitors sharing a benzimidazole core were previously reported by our group. SAR studies were expanded beyond the previous analysis, which involved the attached phenyl rings and methylamino linker portion, to include modifications focused on the benzimidazole core. These changes included the introduction of various substituents to the bicyclic benzimidazole ring system along with alternate core heterocycles. Many of the analogs containing alternate nitrogen-based bicyclic ring systems were found to retain antiviral potency compared to the benzimidazole series from which we derived our lead compound, ST-193. In fact, 21 h, built on an imidazopyridine core, possessed a near tenfold increase in potency against Lassa virus pseudotypes compared to ST-193. As found with the benzimidazole series, broad-spectrum arenavirus activity was also observed for a number of the analogs discovered during this study.

SAR analysis of a series of acylthiourea derivatives possessing broad-spectrum antiviral activity.

A series of acylthiourea derivatives were designed, synthesized, and evaluated for broad-spectrum antiviral activity with selected viruses from Poxviridae (vaccinia virus) and two different genera of the family Bunyaviridae (Rift Valley fever and La Crosse viruses). A compound selected from a library screen, compound 1, displayed submicromolar antiviral activity against both vaccinia virus (EC(50)=0.25 µM) and La Crosse virus (EC(50)=0.27 µM) in cytopathic effect (CPE) assays. SAR analysis was performed to further improve antiviral potency and to optimize drug-like properties of the initial hits. During our analysis, we identified 26, which was found to be nearly fourfold more potent than 1 against both vaccinia and La Crosse viruses. Selected compounds were further tested to more fully characterize the spectrum of antiviral activity. Many of these possessed single digit micromolar and sub-micromolar antiviral activity against a diverse array of targets, including influenza virus (Orthomyxoviridae), Tacaribe virus (Arenaviridae), and dengue virus (Flaviviridae).

Group interventions for co-morbid insomnia and osteoarthritis pain in primary care: the lifestyles cluster randomized trial design.

Six weekly sessions of group cognitive-behavioral therapy for insomnia and osteoarthritis pain (CBT-PI), and for osteoarthritis pain alone (CBT-P) were compared to an education only control (EOC). Basic education about pain and sleep was comparable, so EOC controlled for information and group participation. Active interventions differed from EOC in training pain coping skills (CBT-P and CBT-PI) and sleep enhancement techniques (CBT-PI). Persons with osteoarthritis age 60 or older were screened for osteoarthritis pain and insomnia severity via mailed survey. Primary outcomes were pain severity (pain intensity and interference ratings from the Graded Chronic Pain Scale) and insomnia severity (Insomnia Severity Index). Secondary outcomes were arthritis pain (AIMS-2 symptom scale) and sleep efficiency assessed by wrist actigraphy. Ancillary outcomes included: cognitive function, depression, and health care use. A clustered randomized design provided adequate power to identify moderate effects on primary outcomes (effect size>0.35). Modified intent to treat analyses, including all participants who attended the first session, assessed effects across CBT-PI, CBT-P, and EOC groups. Treatment effects were assessed post-intervention (2 months) and at 9 months, with durability of intervention effects evaluated at 18 months. The trial was executed in 6 primary clinics, randomizing 367 participants, with 93.2% of randomized patients attending at least 4 group sessions. Response rates for post-intervention and 9 month assessments were 96.7% and 92.9% respectively. This hybrid efficacy-effectiveness trial design evaluates whether interventions yield specific benefits for clinical and behavioral outcomes relative to an education only control when implemented in a primary care setting.

Frequency of comorbid insomnia, pain, and depression in older adults with osteoarthritis: predictors of enrollment in a randomized treatment trial.

OBJECTIVE: This paper examines the prevalence and severity of comorbid pain, insomnia, and depression in a population sample of older adults with osteoarthritis (OA), and assesses characteristics distinguishing participants from non-participants in a randomized clinical trial to improve pain and sleep. METHODS: Potential subjects were Group Health Cooperative members, aged 60+, who had an electronic medical record OA diagnosis in the prior 3 years. Participants were recruited using a low-cost mailed survey. Fifty-five percent of surveys were completed and returned (n=3321). Persons with Grade II-IV arthritis pain on the Graded Chronic Pain Scale and reporting sleep difficulties 3+ nights/week during the past month with daytime dysfunction (n=834) were invited to participate in one of three group-format behavioral self-management interventions. A total of 367 participants attended the first group class. RESULTS: One-third (36.4%) of survey respondents had clinically elevated levels of OA pain and insomnia. Group participants and non-participants did not differ in ratings of pain severity, sleep disturbance, depression, or receipt of prescription medications for pain or sleep. Participants were significantly older (p<.001) and more likely to be retired (p<.001) than subjects who were eligible to participate but did not. CONCLUSION: Participation in a group-format behavioral intervention for pain and insomnia was not related to participant clinical characteristics, but only to factors associated with ability to attend a daytime class (age and retirement status). We conclude that population-based recruitment yielded randomized trial participants who are clinically generalizable to the population of OA patients with significant pain and insomnia.

Evaluation of admission blood glucose levels in the intensive care unit.

OBJECTIVE: To assess the availability and clinical value of blood glucose (BG) testing at the time of admission to the intensive care unit (ICU) after such testing was implemented as routine care in the ICU. METHODS: We studied ICU admission BG testing rates and the prevalence of hyperglycemia. In this effort, we assessed the frequency of baseline BG testing in 330 consecutive patients during a period of 3 months and then implemented routine BG monitoring in 1,147 consecutive ICU patients during a 7-month period. RESULTS: Of the total study population, 25% had previously diagnosed diabetes (PDD). At baseline, 70% had BG measured within 4 hours before or after ICU admission (99% of patients with and 60% of patients without PDD). After implementation of routine BG monitoring, there was a significant increase in testing (70% before versus 87% after, P<0.001; 70% during the baseline 3-month period versus 93% in the final 3 months of the study, P<0.001). In patients without PDD, 41% had BG levels < or =140 mg/dL, and 8% had BG concentrations < or =200 mg/dL. Overall in the ICU setting, 57% of BG values < or =140 mg/dL and 33% of BG levels < or =200 mg/dL were in patients without PDD. Frequencies of BG testing by admission diagnosis included the following (at baseline and during the final 3 months after implementation of routine BG tests): postsurgical status (46%, 85%), peripheral vascular disease (51%, 90%), neurologic disease (52%, 83%), gastrointestinal disease (58%, 91%), infection (69%, 100%), and diabetes (100%, 100%). CONCLUSION: Rates of routine BG testing are low in ICU patients without PDD. Elevations in BG levels were detected in 41% of our study patients without PDD, suggesting that routine implementation of BG monitoring in an ICU will identify patients at increased risk for hyperglycemia-associated higher morbidity and mortality.