Pharmacy staff-reported adaptations to naloxone provision and over-the-counter (OTC) syringe sales during the COVID-19 pandemic: Experiences across multiple states and 2 pharmacy chains.

BACKGROUND: Access to harm reduction materials was greatly disrupted during coronavirus disease 2019 (COVID-19). Community pharmacies often continued provision of harm reduction materials as part of their usual operations during the pandemic, but little is known about what, if any, adaptations were made and the perceived impact of these actions from the perspective of pharmacy staff. OBJECTIVES: We explored how pharmacy staff across 4 states in 2 major pharmacy chains adapted to the COVID-19 pandemic for ongoing naloxone and over-the-counter (OTC) syringe access and how staff perceived the pandemic affected drug use in the community they served and their pharmacy's volume of syringe sales and naloxone provision. METHODS: We analyzed 134 pharmacy staff responses to a 12-month follow-up assessment for an educational intervention conducted in 2 pharmacy chains in Oregon, Washington, Massachusetts, and New Hampshire. Respondents answered closed- and open-ended questions collected online from July 2020 to February 2022. Questions measured prevalence of adaptations and perceived uptake of naloxone and OTC syringe services. Descriptive statistics summarized adaptations and perceived impact and chi-square tests explored differences by state and pharmacy chain. Open-ended responses were reviewed and analyzed to identify summary points and themes. RESULTS: With few differences by state or pharmacy chain detected, pharmacy staff reported more naloxone mailing, requests by phone, streamlined counseling, and drive-thru provision adaptations to OTC syringe sales and naloxone provision during the pandemic. Most staff perceived adaptations as increasing or maintaining naloxone provision and OTC syringe sales. Respondents described specific aspects of the pharmacy that contributed to successful adaptations, including tailoring to specific product demand, inventory levels, drive-thru access, and a perception of extraordinary public health need at a time of and in places affected by the opioid crisis. CONCLUSIONS: Pharmacy OTC syringe and naloxone access continued during the COVID-19 pandemic through streamlining workflows and innovating no-contact harm reduction services, reinforcing pharmacy's public health role.

Economic Evaluation of a Point-of-Care Test for Bacterial Vaginosis Among Women With Vaginal Symptoms.

BACKGROUND: There is an unmet need for a clinical diagnostic technology to detect bacterial vaginosis (BV) rapidly and accurately. Novel point-of-care (POC) tests have the potential to fulfill this gap. Our objective was to determine the cost-effectiveness of a hypothetical clinician-administered POC test for diagnosing BV in the United States. METHODS: We developed a state-transition microsimulation model to evaluate the cost-effectiveness of using the POC test versus usual care among women of reproductive age with vaginal symptoms. We adopted a healthcare sector perspective that included relevant healthcare costs and a societal perspective that further incorporated productivity costs. Model parameters were empirically estimated based on commercial insurance claims data or derived from published literature. The primary model outcome was incremental cost-effectiveness ratio. We started with analyzing a hypothetical POC test with a sensitivity and specificity of 0.9 and a cost of $40, followed by extensive sensitivity analyses. RESULTS: Using the hypothetical POC test to diagnose BV increased costs by $16 and quality-adjusted life-years by 0.0005 per person compared with the usual care, leading to an incremental cost-effectiveness ratio of $31,108 per quality-adjusted life-year gained. When also capturing the productivity costs, the POC test resulted in an average cost savings of $57. The sensitivity analyses showed that the POC test's sensitivity was more influential on its cost-effectiveness than specificity. CONCLUSIONS: Using the POC test to diagnose BV is likely to be cost-effective relative to usual care, especially with a high sensitivity or a substantial positive effect on productivity.

Real-world treatment patterns and economic burden of post-cataract macular edema.

BACKGROUND: Post-cataract macular edema (PCME) is a condition that can occur in patients following cataract surgery without risk factors and complications. Although 80% of patients experience spontaneous resolution after 3 to 12 months, in persistent cases, it can lead to permanent vision loss if left untreated. There are currently no standardized treatment guidelines for PCME, and there have been limited studies showing the impact of PCME on annual Medicare spending and ophthalmology-related outpatient visits per case compared to those without the complication. This study aims to evaluate real-world treatment patterns and the economic burden of patients with PCME. METHODS: This retrospective claims analysis identified patients from the IBM® MarketScan® Commercial and Medicare Supplemental databases. Patients with (n = 2430) and without (n = 7290) PCME 1 year post cataract surgery were propensity score matched 1:3 based on age, geographic region, diabetes presence, cataract surgery type, and Charlson Comorbidity Index. Treatment pattern analysis for each PCME patient summarized the distribution of medications across lines of therapy. Economic burden analysis compared the mean number and costs of eye-related outpatient visits, optical coherence tomography imaging scans, and ophthalmic medications between the 2 groups using linear regression models. RESULTS: Treatment pattern analysis found 27 different treatment combinations across 6 treatment lines. The most common first-line treatments were topical steroid drops (372 [30%]), topical nonsteroidal anti-inflammatory drug drops (321 [27%]), and intraocular or periocular injectable steroids (189 [15%]). Compared to match controls, PCME patients averaged 6 additional eye-related outpatient office visits (95% CI: 5.7-6.2) resulting in an additional $3,897 (95% CI: $3,475 - $4,319) in total costs. Patients filled 3 more ophthalmology-related outpatient prescription medications (95% CI: 2.8-3.2), adding $371 in total cost (95% CI: $332 - $410). CONCLUSIONS: PCME treatment patterns showed wide clinical variability in treatments and time, specifically regarding injectable treatments and combination therapy. Additionally, significantly higher healthcare resource use and economic burden were found for both patients and payers when comparing PCME patients to non-PMCE controls. These results highlight the need for treatment standardization and demonstrate that interventions targeted at preventing PCME may be valuable.

Reasons for use and experiences of using phenibut, a mixed methods analysis of online reports.

Background: Phenibut is a drug similar in structure to gabapentin and pregabalin. It is available online without prescription, often marketed as a dietary supplement or amino acid derivative. Little is known about phenibut use despite its increased popularity in the United States over the last decade.Objective: To clarify reasons for taking phenibut, circumstances, and effects of use.Methods: Reports of phenibut, gabapentin, and pregabalin use were downloaded from a publicly-available database, Erowid.org. A mixed methods approach utilizing qualitative content analysis was used.Results: Of 229 reports, 211 were from male authors. People usually purchased phenibut online and reportedly used it for recreation, to manage a medical or psychiatric problem (primarily insomnia, anxiety), as a substitute for other drugs (especially benzodiazepines), to manage withdrawal from another substance (including benzodiazepines, opioids), and/or for performance enhancement. While it shared many reported effects with pregabalin and gabapentin such as anxiolysis, increased talkativeness, and impaired motor coordination, reports of gastrointestinal distress and sedation were more commonly attributed to phenibut. Several people reported difficulty in restricting their use and managing withdrawal.Conclusions: Phenibut reports suggest that phenibut may have some benefits for some people. Use also, however, carries risks of adverse effects, a potentially dangerous withdrawal syndrome, and addiction. Not dissimilar to unprescribed gabapentin or pregabalin, self-medication is a common motive for phenibut use. Physicians should continue to ask their patients about use of any non-prescribed medications, dietary supplements, or "amino acid derivatives."Abbreviation: PWUPh: people who use phenibut; PWUG: people who use gabapentin; PWUPr: people who use pregabalin.

Community pharmacist intervention to close statin gaps in diabetes care: The GuIDE-S study.

BACKGROUND: Statin therapy is recommended for people with type 2 diabetes (T2D) to lower cardiovascular risk; however, evidence suggests that significant gaps in statin therapy exist. OBJECTIVE: To evaluate (1) the impact of a community pharmacist-led model for initiating statin therapy in people with type 2 diabetes (T2D) on statin initiation and (2) pharmacists' self-reported perceptions of the intervention feasibility and fidelity to the intervention. METHODS: This was a type 1 hybrid effectiveness-implementation study of 9 intervention and 18 control pharmacies within a community pharmacy chain. Pharmacy staff proactively identified patients with T2D not taking a statin and prescribed a statin via a collaborative practice agreement or facilitated acquisition of a prescription from the patient's preferred prescriber. The eligible population included patients aged 18-84 years with T2D, who had filled ≥60 days' supply of one, noninsulin, diabetes medication in a rolling 6-month period, and who had not filled a statin during the same period. A Cox proportional hazards model was used to compare time to statin initiation. Pharmacists at intervention pharmacies completed a survey at 6 and 12 months after implementation (March and August 2019, respectively) to assess intervention feasibility and fidelity. RESULTS: For the statin initiation analysis, 1670 intervention patients were matched to 3358 control patients. Overall, 26.3% (n=442) of intervention patients and 25.4% (n=854) of control patients initiated a statin within 12 months of their index date. There was no difference in statin initiation likelihood between intervention and control patients (hazard ratio: 1.00; 95% CI: 0.83, 1.21). Fifteen pharmacists completed the 6-month survey (33% response rate), and 12 completed the 12-month survey (26%). The intervention's feasibility score was 4.0 at 6 months and 4.2 at 12 months, indicating an increase in perceived feasibility. Fidelity decreased from 6 to 12 months. CONCLUSION: The community pharmacist-led intervention resulted in more patients initiating statin therapy as compared to usual care; however, the differences were not statistically significant. Pharmacists perceived the intervention to be feasible; however, fidelity decreased over time.

Community pharmacist intervention to optimize statin adherence in diabetes care: The GuIDE-S study.

BACKGROUND: Statin use in people with type 2 diabetes (T2D) reduces cardiovascular events, yet adherence remains suboptimal. OBJECTIVE: This study evaluated the impact of a community pharmacist intervention on statin adherence in new users with T2D. METHODS: As part of a quasi-experimental study, community pharmacy staff proactively identified adult patients with T2D who were not prescribed a statin. When appropriate, the pharmacist prescribed a statin via a collaborative practice agreement or facilitated acquisition of a prescription from another prescriber. Patients received individualized education and follow-up and monitoring for 1 year. Adherence was defined as the proportion of days covered (PDC) by a statin over 12 months. Linear and logistic regression were used to compare the effect of the intervention on continuous and a binary adherence threshold, defined as PDC ≥ 80%, respectively. RESULTS: Overall, 185 patients started statin therapy and were matched to 370 control patients for analysis. Adjusted average PDC was 3.1% higher in the intervention group (95% CI -0.037 to 0.098). Patients in the intervention group were 21.2% more likely to have PDC ≥ 80% (95% CI 0.828-1.774). CONCLUSION: The intervention resulted in higher statin adherence than usual care; however, the differences were not statistically significant.

Readiness of community pharmacies to implement an opioid safety intervention.

BACKGROUND: We report on efforts to measure readiness to adopt opioid safety initiatives in community pharmacies within 2 large chains. Previous studies identified lack of knowledge, confidence, or enthusiasm in addressing harm reduction efforts. We implemented an intervention that provided training to improve opioid safety. The goal was to increase naloxone prescribing and nonprescription syringe sales, reduce stigma, and decrease opioid overdoses among patients and customers. OBJECTIVES: To assess pharmacy readiness for intervention delivery, by characterizing pharmacy culture around opioid safety; describing current practices and challenges interacting with patients and customers on naloxone, nonprescription syringe sales, and buprenorphine; and determining pharmacy defined goals for implementing the intervention. METHODS: The sample included pharmacy managers and staff pharmacists from 2 large chains who completed a brief phone interview. Interviews consisted of Likert-scale and open-ended, theoretically driven questions. Questions focused on workplace culture, patient engagement, naloxone and buprenorphine prescribing, nonprescription syringe sales, and intervention goals. Coding categories for the open-ended questions were derived using a thematic review of responses. RESULTS: A total of 163 respondents described both workplace culture and how they encourage patient opioid safety as including public health awareness, patient engagement, and naloxone prescribing. Sale of nonprescription syringes exhibited high variability: no sales barriers (53.9%), sales with barriers (21.5%), and no sales (20.9%). Half of pharmacists (50.3%) interacted with buprenorphine prescribers outside of medication fills. Most respondents (68.7%) endorsed being ready to promote the intervention. Pharmacists named goals in adopting the intervention of wanting more knowledge and educational materials, talking points with patients, and best practices for offering naloxone. CONCLUSION: Community pharmacists, before implementation, described awareness of and receptiveness to opioid safety initiatives, with substantial barriers around nonprescription syringe sales. Assessed knowledge level, culture, and identified barriers that emerged in the readiness assessments can be used to tailor future pharmacy-specific programming.

Implementation of an academic detailing intervention to increase naloxone distribution and foster engagement in harm reduction from the community clinician.

BACKGROUND: Respond to Prevent (R2P) is a randomized clinical trial which sought to accelerate distribution of naloxone and other harm reduction materials from community pharmacies. R2P combined an online continuing education course with in-store materials, specifically designed for use in community pharmacies, and then supported implementation through the one-on-one educational technique of academic detailing. OBJECTIVE: The objective of this paper is to describe and synthesize our experiences providing academic detailing as part of the R2P randomized trial. METHODS: Closed-ended items from standardized post detailing questionnaires were analyzed with descriptive statistics. Open-ended items were content analyzed for key themes using immersion-crystallization qualitative methods. RESULTS: A total of 176 pharmacies participated in R2P with 175 receiving their initial academic detailing visit between August 2019 and May 2021. Initial visits were in-person and lasted a median of 35 minutes (interquartile range, 20-45 minutes). The R2P naloxone guide was the most common topic covered (n = 162, 92.6%). Following a fidelity check to assess adequacy of the R2P program implementation, 80 pharmacies (45.7%) required secondary academic detailing. Secondary detailing was more targeted and most frequently focused on the sale of nonprescription syringes (n = 28; 35.2%) or disposal container distribution (n = 30; 37.5%). Analysis of the open-ended items identified factors that the detailers perceived to affect the quality of academic detailing sessions, including the pharmacy environment, participant knowledge of and attitudes toward the subject matter, and ability of the detailer to remain flexible yet consistent. CONCLUSION: R2P provided a standardized process to foster naloxone distribution and engagement in harm reduction with demonstrated implementation in 175 community pharmacies across 4 states. Academic detailing was perceived to be well-received and effective at providing education and promoting distribution of naloxone and nonprescription syringes in community pharmacies. Additional research is needed to confirm these perceptions through evaluation post-intervention behavioral and attitude changes.

More Than Results: The Clinical and Research Relationship in the Evolving Detection and Surveillance of SARS-CoV-2.

INTRODUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, real-time reverse transcription polymerase chain reaction (RT-PCR) became an essential tool for laboratories to provide high-sensitivity qualitative diagnostic testing for patients and real-time data to public health officials. Here we explore the predictive value of quantitative data from RT-PCR cycle threshold (Ct) values in epidemiological measures, symptom presentation, and variant transition. METHODS: To examine the association with hospitalizations and deaths, data from 74,479 patients referred to the Avera Institute for Human Genetics (AIHG) for COVID-19 testing in 2020 were matched by calendar week to epidemiological data reported by the South Dakota Department of Health. We explored the association between symptom data, patient age, and Ct values for 101 patients. We also explored changes in Ct values during variant transition detected by genomic surveillance sequencing of the AIHG testing population during 2021. RESULTS: Measures from AIHG diagnostic testing strongly explain variance in the South Dakota state positivity percentage (R2 = 0.758), a two-week delay in hospitalizations (R2 = 0.856), and a four-week delay in deaths (R2 = 0.854). Based on factor analysis of patient symptoms, three groups could be distinguished which had different presentations of age, Ct value, and time from collection. Additionally, conflicting Ct value results among SARSCoV- 2 variants during variant transition may reflect the community transmission dynamics. CONCLUSIONS: Measures of Ct value in RT-PCR diagnostic assays combined with routine screening have valuable applications in monitoring the dynamics of SARS-CoV-2 within communities.

Preclinical Characterization of LY3209590, a Novel Weekly Basal Insulin Fc-Fusion Protein.

The benefit of once-weekly basal insulin is less frequent dosing, which has the potential to reduce the barrier to injection therapy and impact patient activation, adherence and compliance, quality of life, and outcomes. Basal Insulin Fc (BIF, LY3209590, or insulin efsitora alfa) is a once-weekly basal insulin in clinical testing for type 1 and type 2 diabetes mellitus. BIF is comprised of a novel single-chain variant of insulin fused to a human IgG2 fragment crystallizable region of an antibody domain using a peptide linker. The in vitro binding affinity of BIF for the human insulin receptor (IR) was two orders of magnitude weaker relative to human insulin. BIF stimulated IR phosphorylation in cells with reduced potency, yet full agonism, and exhibited a significantly faster dephosphorylation kinetic profile than human insulin or AspB10 insulin. BIF stimulated de novo lipogenesis in 3T3-L1 adipocytes and cell proliferation in SAOS-2 and H4IIE cells with ≥70-fold reduction in in vitro potency compared with human insulin. BIF possessed markedly reduced binding to hIGF-1R, making definitive measurements unattainable. In vivo pharmacology studies using streptozotocin-treated diabetic rats demonstrated a significant decrease in blood glucose compared with vehicle-treated animals 24 hours post-injection, persisting through 336 hours following subcutaneous administration. In streptozotocin-treated rats, BIF reached time at maximum concentration at 48 hours and possessed a clearance rate of ∼0.85 ml/h per kg, with a terminal half-life of ∼120 hours following subcutaneous administration. These results demonstrate BIF has an in vitro pharmacological profile similar to native insulin, with significantly reduced potency and an extended time-action profile in vivo that supports once-weekly dosing in humans. SIGNIFICANCE STATEMENT: BIF is a novel basal insulin Fc-fusion protein designed for once-weekly dosing. In this study, we demonstrate that BIF has an in vitro pharmacological profile similar to human insulin, but with weaker potency across assays for IR binding and activity. BIF has a PD and PK profile in STZ-treated rats supportive of weekly dosing in humans.

Qualitative inquiry into perceptions of HIV pre-exposure prophylaxis among people who inject drugs living with hepatitis C in Seattle, WA, USA.

BACKGROUND: The incidence of HIV among persons who inject drugs (PWID) in the USA has been increasing since 2014, signaling the need to identify effective ways to engage PWID in HIV prevention services, namely pre-exposure prophylaxis (PrEP). Yet, the uptake of PrEP in this population is minimal compared to other populations at risk of HIV acquisition. In this work, we sought to explore knowledge, attitudes, and perspectives of PrEP acceptability among PWID. METHODS: In the context of a pilot study to explore the acceptability of pharmacy-based hepatitis C virus (HCV) treatment, we conducted semi-structured interviews (n = 24) and focus groups (n = 4, 16 participants) with people who were living with HCV and reported active injection drug use (≤ 90 days since last use). Participants were asked open-ended questions about their familiarity with and motivation to use PrEP. As part of a sub-analysis focused on PrEP, qualitative data were analyzed using a Rapid Assessment Process, where three coders used structured templates to summarize qualitative data and iteratively reviewed coded templates to identify themes. Participants also completed short quantitative questionnaires regarding drug use history and attitudes toward health concerns. RESULTS: Forty-seven percent of participants expressed having little or no concern regarding HIV acquisition. Targeted analyses focused on HIV prevention identified three themes, which help characterize behavioral determinants of nonadoption. First, knowledge of PrEP was limited among PWID and influenced by infrequent open community discussions around HIV risk. Second, PWID perceived sexual behaviors-but not injection drug use-as a motivator for HIV risk prevention. Finally, PWID identified many individual and environmental barriers that hinder PrEP uptake. CONCLUSION: Among PWID, PrEP is rarely discussed and concerns about the feasibility of using daily PrEP are common. Taken with the prevalent perception that drug use is not a high risk for HIV acquisition, our findings point to opportunities for public health work to target PrEP education to PWID and to leverage other successful interventions for PWID as an opportunity to provide PrEP to this vulnerable population.

Study protocol for the Respond to Prevent Study: a multi-state randomized controlled trial to improve provision of naloxone, buprenorphine and nonprescription syringes in community pharmacies.

Access to the opioid antidote naloxone is a critical component of addressing the opioid crisis. Naloxone is a population-level prevention intervention associated with substantial reductions in overdose mortality and reduction of nonfatal overdose. Pharmacies' pivotal role in dispensing medications like buprenorphine for the treatment of opioid use disorder and selling nonprescription syringes places them at the crossroads of opioid access and risk mitigation methods like naloxone provision. Testing ways to optimize pharmacy-based naloxone provision will be key as the country expands the implementation of naloxone through the medical system. In the Respond to Prevent Study, we conducted a large, practical study of a pharmacy-focused intervention in a sample of Washington, Oregon, Massachusetts and New Hampshire community chain pharmacies to increase naloxone dispensing and improve opioid safety. The intervention integrated two evidence-based educational toolkits and streamlined materials to enhance the focus on naloxone policy, stigma reduction, and patient communications around naloxone, nonprescription syringes and buprenorphine access. The real-world study implemented a stepped wedge, clustered randomized trial design across 175 community chain pharmacies to evaluate the effectiveness of the Respond to Prevent intervention in increasing: (a) pharmacy based naloxone distribution rates, naloxone-related patient engagement, and pharmacist and technicians' attitudes, knowledge, perceived behavioral control and self-efficacy toward naloxone; and (b) pharmacy nonprescription syringe sales, and pharmacist and technicians' attitudes, knowledge, perceived behavioral control and self-efficacy toward dispensing buprenorphine for opioid use disorder (secondary outcomes). This commentary provides a brief narrative about the study and presents insights on the design and adaptations to our study protocol, including those adopted during the unprecedented COVID-19 pandemic further compounded by Western wildfires in 2020.

Opportunities and Barriers to Rural Telerobotic Surgical Health Care in 2021: Report and Research Agenda from a Stakeholder Workshop.

Background: There are well-recognized challenges to delivering specialty health care in rural settings. These challenges are particularly evident for specialized surgical health care due to the lack of trained operators in rural communities. Telerobotic surgery could have a significant impact on the rural-urban health care gap, but thus far, the promise of this method of health care delivery has gone unrealized. With the increasing adoption of telehealth over the past year, along with the maturation of telecommunication and robotic technologies over the past 2 decades, a reappraisal of the opportunities and barriers to widespread implementation of telerobotic surgery is warranted. Here we report the outcome of a rural telerobotic stakeholder workshop to explore modern-day issues critical to the advancement of telerobotic surgical health care. Materials and Methods: We assembled a multidisciplinary stakeholder panel to participate in a 2-day Rural Telerobotic Surgery Stakeholder Workshop. Participants had diverse expertise, including specialty surgeons, technology experts, and representatives of the broader telerobotic health care ecosystem, including economists, lawyers, regulatory consultants, public health advocates, rural hospital administrators, nurses, and payers. The research team reviewed transcripts from the workshop with themes identified and research questions generated based on stakeholder comments and feedback. Results: Stakeholder discussions fell into four general themes, including (1) operating room team interactions, (2) education and training, (3) network and security, and (4) economic issues. The research team then identified several research questions within each of these themes and provided specific research strategies to address these questions. Conclusions: There are still important unanswered questions regarding the implementation and adoption of rural telerobotic surgery. Based on stakeholder feedback, we have developed a research agenda along with suggested strategies to address outstanding research questions. The successful execution of these research opportunities will fill critical gaps in our understanding of how to advance the widespread adoption of rural telerobotic health care.

Long-term survival trends in patients with unresectable stage III non-small cell lung cancer receiving chemotherapy and radiation therapy: a SEER cancer registry analysis.

BACKGROUND: To evaluate the value of new therapies for non-small cell lung cancer (NSCLC), it is necessary to understand overall survival (OS) rates associated with previous standard therapies and how these rates have evolved over time. METHODS: We retrospectively analyzed data from patients enrolled in the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Adults with unresectable, stage III NSCLC treated with chemoradiotherapy were grouped by diagnosis year (2000-2002; 2003-2005; 2006-2008; 2009-2011; 2012-2013). The primary endpoint was OS (data cut-off, December 31, 2014), estimated using the Kaplan-Meier estimator. Temporal survival-trend significance was tested using a two-sided log-rank trend test. RESULTS: Of 12,865 eligible patients, 59.1% were male, 59.9% had stage IIIB disease, and 62.7% had non-squamous histology. Median age at diagnosis was 67 years. Overall, 10,899 (84.7%) patients died and 1966 (15.3%) were censored/lost to follow-up. Median follow-up (95% confidence interval [CI]) was 80 (77-82) months; median OS (95% CI) was 15 (15-16) months; 1- and 3-year survival probabilities (95% CI) were 57.7% (56.9-58.6) and 24.1% (23.3-24.8), respectively. Stratification by diagnosis year showed consistent improvements in survival over time (p < 0.0001 for trend). Median OS was 12, 14, 15, 18, and 19 months in successive cohorts. CONCLUSIONS: OS in patients diagnosed with unresectable, stage III NSCLC between 2003 and 2013 was consistent with that from clinical studies of sequential/concurrent chemoradiotherapy. Despite improvement over time, median OS was < 2 years and mortality remained high during the first year post-diagnosis.

Photodegradable Hydrogels for Rapid Screening, Isolation, and Genetic Characterization of Bacteria with Rare Phenotypes.

Screening mutant libraries (MLs) of bacteria for strains with specific phenotypes is often a slow and laborious process that requires assessment of tens of thousands of individual cell colonies after plating and culturing on solid media. In this report, we develop a three-dimensional, photodegradable hydrogel interface designed to dramatically improve the throughput of ML screening by combining high-density cell culture with precision extraction and the recovery of individual, microscale colonies for follow-up genetic and phenotypic characterization. ML populations are first added to a hydrogel precursor solution consisting of polyethylene glycol (PEG) o-nitrobenzyl diacrylate and PEG-tetrathiol macromers, where they become encapsulated into 13 µm thick hydrogel layers at a density of 90 cells/mm2, enabling parallel monitoring of 2.8 × 104 mutants per hydrogel. Encapsulated cells remain confined within the elastic matrix during culture, allowing one to track individual cells that grow into small, stable microcolonies (45 ± 4 µm in diameter) over the course of 72 h. Colonies with rare growth profiles can then be identified, extracted, and recovered from the hydrogel in a sequential manner and with minimal damage using a high-resolution, 365 nm patterned light source. The light pattern can be varied to release motile cells, cellular aggregates, or microcolonies encapsulated in protective PEG coatings. To access the benefits of this approach for ML screening, an Agrobacterium tumefaciens C58 transposon ML was screened for rare, resistant mutants able to grow in the presence of cell free culture media from Rhizobium rhizogenes K84, a well-known inhibitor of C58 cell growth. Subsequent genomic analysis of rare cells (9/28,000) that developed into microcolonies identified that seven of the resistant strains had mutations in the acc locus of the Ti plasmid. These observations are consistent with past research demonstrating that the disruption of this locus confers resistance to agrocin 84, an inhibitory molecule produced by K84. The high-throughput nature of the screen allows the A. tumefaciens genome (approximately 5.6 Mbps) to be screened to saturation in a single experimental trial, compared to hundreds of platings required by conventional plating approaches. As a miniaturized version of the gold-standard plating assay, this materials-based approach offers a simple, inexpensive, and highly translational screening technique that does not require microfluidic devices or complex liquid handling steps. The approach is readily adaptable to other applications that require isolation and study of rare or phenotypically pure cell populations.

Integrating Formal Technology Assessment into an Integrated Healthcare Delivery System: Smart Innovation.

OBJECTIVES: We designed, developed, and implemented a new hospital-based health technology assessment (HB-HTA) program called Smart Innovation. Smart Innovation is a decision framework that reviews and makes technology adoption decisions. Smart Innovation was meant to replace the fragmented and complex process of procurement and adoption decisions at our institution. Because use of new medical technologies accounts for approximately 50 percent of the growth in healthcare spending, hospitals and integrated delivery systems are working to develop better processes and methods to sharpen their approach to adoption and management of high cost medical innovations. METHODS: The program has streamlined the decision-making process and added a robust evidence review for new medical technologies, aiming to balance efficiency with rigorous evidence standards. To promote system-wide adoption, the program engaged a broad representation of leaders, physicians, and administrators to gain support. RESULTS: To date, Smart Innovation has conducted eleven HB-HTAs and made clinician-led adoption decisions that have resulted in over $5 million dollars in cost avoidance. These are comprised of five laboratory tests, three software-assisted systems, two surgical devices, and one capital purchase. CONCLUSIONS: Smart Innovation has achieved cost savings, avoided uncertain or low-value technologies, and assisted in the implementation of new technologies that have strong evidence. The keys to its success have been the program's collaborative and efficient decision-making systems, partnerships with clinicians, executive support, and proactive role with vendors.

Identification of Critical Surface Parameters Driving Lectin-Mediated Capture of Bacteria from Solution.

Lectin-functional interfaces are useful for isolation of bacteria from solution because they are low-cost and allow nondestructive, reversible capture. This study provides a systematic investigation of physical and chemical surface parameters that influence bacteria capture over lectin-functionalized polymer interfaces and then applies these findings to construct surfaces with significantly enhanced bacteria capture. The designer block copolymer poly(glycidyl methacrylate)- block-poly(vinyldimethyl azlactone) was used as a lectin attachment layer, and lectin coupling into the polymer film through azlactone-lectin coupling reactions was first characterized. Here, experimental parameters including polymer areal chain density, lectin molecular weight, and lectin coupling buffer were systematically varied to identify parameters driving highest azlactone conversions and corresponding lectin surface densities. To introduce physical nanostructures into the attachment layer, nanopillar arrays (NPAs) of varied heights (300 and 2100 nm) were then used to provide an underlying surface template for the functional polymer layer. Capture of Escherichia coli on lectin-polymer surfaces coated over both flat and NPA surfaces was then investigated. For flat polymer interfaces, bacteria were detected on the surface after incubation at a solution concentration of 103 cfu/mL, and a corresponding detection limit of 1.7 × 103 cfu/mL was quantified. This detection limit was 1 order of magnitude lower than control lectin surfaces functionalized with standard, carbodiimide coupling chemistry. NPA surfaces containing 300 nm tall pillars further improved the detection limit to 2.1 × 102 cfu/mL, but also reduced the viability of captured cells. Finally, to investigate the impact of cell surface parameters on capture, we used Agrobacterium tumefaciens cells genetically modified to allow manipulation of exopolysaccharide adhesin production levels. Statistical analysis of surface capture levels revealed that lectin surface density was the primary factor driving capture, as opposed to exopolysaccharide adhesin expression. These findings emphasize the critical importance of the synthetic interface and the development of surfaces that combine high lectin densities with tailored physical features to drive high levels of capture. These insights will aid in design of biofunctional interfaces with physicochemical surface properties favorable for capture and isolation of bacteria cells from solutions.

Impact of initiatives to reduce prescription opioid risks on medically attended injuries in people using chronic opioid therapy.

PURPOSE: The purpose of the study is to determine whether initiatives to improve the safety of opioid prescribing decreased injuries in people using chronic opioid therapy (COT). METHODS: We conducted an interrupted time series analysis using data from Group Health (GH), an integrated health care delivery system in the United States. In 2007, GH implemented initiatives which substantially reduced daily opioid dose and increased patient monitoring. Among GH members age 18 or older receiving COT between 2006 and 2014, we compared injury rates for patients in GH's integrated group practice (IGP; exposed to the initiatives) vs patients cared for by contracted providers (not exposed). Injuries were identified using a validated algorithm. We calculated injury incidence during the baseline (preintervention) period from 2006 to 2007; the dose reduction period, 2008 to 2010; and the risk stratification and monitoring period, 2010 to 2014. Using modified Poisson regression, we estimated adjusted relative risks (RRs) representing the relative change per year in injury rates. RESULTS: Among 21 853 people receiving COT in the IGP and 8260 in contracted care, there were 2679 injuries during follow-up. The baseline injury rate was 1.0% per calendar quarter in the IGP and 0.9% in contracted care. Risk reduction initiatives did not decrease injury rates: Within the IGP, the RR in the dose reduction period was 1.01 (95% CI, 0.95-1.07) and in the risk stratification and monitoring period, 0.99 (95% CI, 0.95-1.04). Injury trends did not differ between the two care settings. CONCLUSIONS: Risk reduction initiatives did not decrease injuries in people using COT.

Price elasticities of pharmaceuticals in a value based-formulary setting.

Empirical estimates of price elasticities of demand (PED) for pharmaceuticals suggest that they are relatively price inelastic. However, in many settings, a medication and its substitutes and complements face simultaneous differential changes in prices that affect the observed "composite" PED. We exploit an implementation of a value-based formulary (VBF) that utilized drug-specific incremental cost-effectiveness ratios (ICERs) to inform drug copayments, resulting in increases in copayments for some medications and decreases in copayments for others. We first show theoretically that by changing the price of a medication and its substitute in opposite directions, VBF designs can leverage cross-price effects to increase the range of composite PEDs. We then empirically estimate PED and welfare effects using a consumer surplus approach. Overall PED was -0.16, similar to the RAND Health Insurance Experiment estimate. However, there was substantial dispersion of PED across the VBF copayment tiers ranging from -0.09 to -0.87 with a statistically significant trend aligned with the levels of value as reflected by the ICER estimates (p < 0.001). The net welfare increase was $147,000 for the cohort or $28 per member over the postpolicy year. Further experimentations of VBF designs with alternative cost-effectiveness thresholds, copayment levels and value definitions could be quite promising for improving welfare.

Impact of Opioid Dose Reduction and Risk Mitigation Initiatives on Chronic Opioid Therapy Patients at Higher Risk for Opioid-Related Adverse Outcomes.

Objective: We aimed to determine if opioid risk reduction initiatives including dose reduction and risk mitigation strategies for chronic noncancer pain patients receiving chronic opioid therapy (COT) had a differential impact on average daily opioid doses of COT patients at higher risk for opioid-related adverse outcomes compared with lower-risk patients. Design: Interrupted time series. Setting: Group Health Cooperative (GH), a health care delivery system and insurance within Washington State, between 2006 and 2014. Population: GH enrollees on COT defined as receiving a supply of 70 or more days of opioids within 90 days using electronic pharmacy data for filled prescriptions. Methods: We compared the average daily morphine equivalent doses (MED) of COT patients with and without each of the following higher-risk characteristics: mental disorders, substance use disorders, sedative use, and male gender. Results: In all four pairwise comparisons, the higher-risk subgroup had a higher average daily MED than the lower-risk subgroup across the study period. Adjusted for covariates, modest differences in the annual rate of reduction in average daily MED were noted between higher- and lower-risk subgroups in three pairwise comparisons: those with mental disorders vs without (-8.2 mg/y vs -5.2 mg/y, P = 0.005), with sedative use vs without (-9.2 mg/y vs -5.8 mg/y, P = 0.004); mg), in men vs women (-8.8 mg/y vs -5.9 mg/y, P = 0.01). Conclusion: Using clinical policy initiatives in a health care system, dose reductions were achieved among COT patients at higher risk for opioid-related adverse outcomes that were at least as large as those among lower-risk patients.