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Richard I Horowitz,1,2 Phyllis R Freeman2 1Health and Human Services, Tick-Borne Disease Working Group, Washington, DC 20201 USA; 2Hudson Valley Healing Arts Center, Hyde Park, NY 12538, USA Purpose: We collected data from an online survey of 200 of our patients, which evaluated the efficacy of dapsone (diaminodiphenyl sulfone, ie, DDS) combined with other antibiotics and agents that disrupt biofilms for the treatment of chronic Lyme disease/post-treatment Lyme disease syndrome (PTLDS). We also collected aggregate data from direct retrospective chart review, including laboratory testing for Lyme, other infections, and associated tick-borne coinfections. This helped us to determine the frequency of exposure to other infections/coinfections among a cohort of chronically ill Lyme patients, evaluate the efficacy of newer “persister” drug regimens like DDS, and determine how other infections and tick-borne coinfections may be contributing to the burden of chronic illness leading to resistant symptomatology. Patients and methods: A total of 200 adult patients recruited from a specialized Lyme disease medical practice had been ill for at least 1 year. We regularly monitored laboratory values and participants’ symptom severity, and the patients completed the online symptom questionnaire both before beginning treatment and after 6 months on DDS combination therapy (DDS CT). Paired-samples t-tests and Wilcoxon signed-rank nonparametric test were performed on each of eight major Lyme symptoms, both before DDS CT and after 6 months of therapy. Results: DDS CT statistically improved the eight major Lyme symptoms. We found multiple species of intracellular bacteria including rickettsia, Bartonella, Mycoplasma, Chlamydia, Tularemia, and Brucella contributing to the burden of illness and a high prevalence of Babesia complicating management with probable geographic spread of Babesia WA1/duncani to the Northeast. Borrelia, Bartonella, and Mycoplasma species, as well as Babesia microti had variable manifestations and diverse seroreactivity, with evidence of persistence despite commonly prescribed courses of anti-infective therapies. Occasional reactivation of viral infections including human herpes virus 6 was also seen in immunocompromised individuals. Conclusion: DDS CT decreased eight major Lyme symptoms severity and improved treatment outcomes among patients with chronic Lyme disease/PTLDS and associated coinfections. Keywords: Lyme disease, babesiosis, bartonella, tick-borne co-infections, Multiple Systemic Infectious Disease Syndrome, MSIDS, persister bacteria, immune deficiency

Maryalice Citera,1 Phyllis R Freeman,2 Richard I Horowitz2 1Department of Psychology, State University of New York at New Paltz, New Paltz, NY, 2Hudson Valley Healing Arts Center, Hyde Park, NY, USA Purpose: Lyme disease is spreading worldwide, with multiple Borrelia species causing a broad range of clinical symptoms that mimic other illnesses. A validated Lyme disease screening questionnaire would be clinically useful for both providers and patients. Three studies evaluated such a screening tool, namely the Horowitz Multiple Systemic Infectious Disease Syndrome (MSIDS) Questionnaire. The purpose was to see if the questionnaire could accurately distinguish between Lyme patients and healthy individuals.Methods: Study 1 examined the construct validity of the scale examining its factor structure and reliability of the questionnaire among 537 individuals being treated for Lyme disease. Study 2 involved an online sample of 999 participants, who self-identified as either healthy (N=217) or suffering from Lyme now (N=782) who completed the Horowitz MSIDS Questionnaire (HMQ) along with an outdoor activity survey. We examined convergent validity among components of the scale and evaluated discriminant validity with the Big Five personality characteristics. The third study compared a sample of 236 patients with confirmed Lyme disease with an online sample of 568 healthy individuals.Results: Factor analysis results identified six underlying latent dimensions; four of these overlapped with critical symptoms identified by Horowitz – neuropathy, cognitive dysfunction, musculoskeletal pain, and fatigue. The HMQ showed acceptable levels of internal reliability using Cronbach’s coefficient alpha and exhibited evidence of convergent and divergent validity. Components of the HMQ correlated more highly with each other than with unrelated traits.Discussion: The results consistently demonstrated that the HMQ accurately differentiated those with Lyme disease from healthy individuals. Three migratory pain survey items (persistent muscular pain, arthritic pain, and nerve pain/paresthesias) robustly identified individuals with verified Lyme disease. The results support the use of the HMQ as a valid, efficient, and low-cost screening tool for medical practitioners to decide if additional testing is warranted to distinguish between Lyme disease and other illnesses. Keywords: Lyme disease, Borrelia burgdorferi, Babesia, MSIDS, Multiple Systemic Infectious Disease Syndrome, factor analysis, PTLDS, Post-Treatment Lyme Disease Syndrome

Objective: Identify characteristics of Kentucky community pharmacists and community pharmacists’ practice environment associated with utilization of the Kentucky All Schedule Prescription Electronic Reporting Program (KASPER). Methods: Surveys were mailed to all 1,018 Kentucky pharmacists with a KASPER account and an additional 1,000 licensed pharmacists without an account. Bivariate analyses examined the association between KASPER utilization and practice type (independent or chain) and practice location (rural or urban). A multivariate Poisson regression model with robust error variance estimated risk ratios (RR) of KASPER utilization by characteristics of pharmacists’ practice environment. Results: Responses were received from 563 pharmacists (response rate 27.9%). Of these, 402 responses from community pharmacists were included in the analyses. A majority of responding pharmacists (84%) indicated they or someone in their pharmacy had requested a patient’s controlled substance history since KASPER’s inception. Bivariate results showed that pharmacists who practiced in independent pharmacies reported greater KASPER utilization (94%) than pharmacists in chain pharmacies (75%; p

Background: People incarcerated in jails are highly impacted by the opioid epidemic, and overdose education and naloxone distribution (OEND) is an effective strategy to reduce opioid overdose deaths. This study examines barriers and facilitators of fast-track OEND implementation within the jails in the Wave 1 Kentucky counties of the HEALing Communities Study during the COVID-19 pandemic., Methods: Meeting minutes with jail stakeholders were qualitatively coded using the Practical, Robust Implementation and Sustainability Model (PRISM) as the coding framework. The analysis highlighted the top barriers and facilitators to fast-track OEND implementation within the PRISM framework., Results: Space and staffing shortages related to the COVID-19 pandemic, disruptions in interorganizational programming from pandemic-related service suspensions, and a lack of technological solutions (e.g., reliable Internet access) for socially distanced delivery were the top barriers to fast-track OEND implementation. In addition, there were limitations on non-jail staff access to jails during COVID-19. Top facilitators included jail leadership support, the option to prioritize high-risk groups, and the incorporation of OEND processes into existing communications and management software. While the COVID-19 pandemic strained jail infrastructure, jail and partner agency collaboration led to creative implementation strategies for the successful integration of OEND into jail operations. Urban jails were more likely than rural jails to be early adopters of OEND during the public health emergency., Conclusions: Understanding the barriers to and facilitators of OEND within jails will improve implementation efforts seeking to curb opioid overdose deaths. Jail leadership support and interorganizational efforts were key facilitators to implementation; therefore, it is recommended to increase buy-in with multiple agencies to promote success. Challenges brought on by COVID-19 have resulted in a need for innovative solutions for implementation., Clinical Trial Information: ClinicalTrials.gov, NCT04111939, Submitted 30 September 2019, https://clinicaltrials.gov/study/NCT04111939?titles=HEALing%20Communities%20Study&rank=1 ., (© 2024. The Author(s).)

Importance: Controlled substances have regulatory requirements under the US Federal Controlled Substance Act that must be met before pharmacies can stock and dispense them. However, emerging evidence suggests there are pharmacy-level barriers in access to buprenorphine for treatment for opioid use disorder even among pharmacies that dispense other opioids., Objective: To estimate the proportion of Medicaid-participating community retail pharmacies that dispense buprenorphine, out of Medicaid-participating community retail pharmacies that dispense other opioids and assess if the proportion dispensing buprenorphine varies by Medicaid patient volume or rural-urban location., Design, Setting, and Participants: This serial cross-sectional study included Medicaid pharmacy claims (2016-2019) data from 6 states (Kentucky, Maine, North Carolina, Pennsylvania, Virginia, West Virginia) participating in the Medicaid Outcomes Distributed Research Network (MODRN). Community retail pharmacies serving Medicaid-enrolled patients were included, mail-order pharmacies were excluded. Analyses were conducted from September 2022 to August 2023., Main Outcomes and Measures: The proportion of pharmacies dispensing buprenorphine approved for opioid use disorder among pharmacies dispensing an opioid analgesic or buprenorphine prescription to at least 1 Medicaid enrollee in each state. Pharmacies were categorized by median Medicaid patient volume (by state and year) and rurality (urban vs rural location according to zip code)., Results: In 2016, 72.0% (95% CI, 70.9%-73.0%) of the 7038 pharmacies that dispensed opioids also dispensed buprenorphine to Medicaid enrollees, increasing to 80.4% (95% CI, 79.5%-81.3%) of 7437 pharmacies in 2019. States varied in the percent of pharmacies dispensing buprenorphine in Medicaid (range, 73.8%-96.4%), with significant differences between several states found in 2019 (χ2 P < .05), when states were most similar in the percent of pharmacies dispensing buprenorphine. A lower percent of pharmacies with Medicaid patient volume below the median dispensed buprenorphine (69.1% vs 91.7% in 2019), compared with pharmacies with above-median patient volume (χ2 P < .001)., Conclusions and Relevance: In this serial cross-sectional study of Medicaid-participating pharmacies, buprenorphine was not accessible in up to 20% of community retail pharmacies, presenting pharmacy-level barriers to patients with Medicaid seeking buprenorphine treatment. That some pharmacies dispensed opioid analgesics but not buprenorphine suggests that factors other than compliance with the Controlled Substance Act influence pharmacy dispensing decisions.

Background: Dentists and oral surgeons are leading prescribers of opioids to adolescents and young adults (AYA), who are at high risk for developing problematic opioid use after an initial exposure. Most opioids are prescribed after tooth extraction, but non-opioid analgesics provide similar analgesia and are recommended by multiple professional organizations., Methods: This multi-site stepped wedge cluster-randomized trial will assess whether a multicomponent behavioral intervention can influence opioid prescribing behavior among dentists and oral surgeons compared to usual practice. Across up to 12 clinical practices (clusters), up to 33 dentists/oral surgeons (provider participants) who perform tooth extractions for individuals 12-25 years old will be enrolled. After enrollment, all provider participants will receive the intervention at a time based on the sequence to which their cluster is randomized. The intervention consists of prescriber education via academic detailing plus provision of standardized patient post-extraction instructions and blister packs of acetaminophen and ibuprofen. Provider participants will dispense the blister packs and distribute the patient instructions at their discretion to AYA undergoing tooth extraction, with or without additional analgesics. The primary outcome is a binary, patient-level indicator of electronic post-extraction opioid prescription. Data for the primary outcome will be collected from the provider participant's electronic health records quarterly throughout the study. Provider participants will complete a survey before and approximately 3 months after transitioning into the intervention condition to assess implementation outcomes. AYA patients undergoing tooth extraction will be offered a survey to assess pain control and satisfaction with pain management in the week after their extraction. Primary analyses will use generalized estimating equations to compare the binary patient-level indicator of being prescribed a post-extraction opioid in the intervention condition compared to usual practice. Secondary analyses will assess provider participants' perceptions of feasibility and appropriateness of the intervention, and patient-reported pain control and satisfaction with pain management. Analyses will adjust for patient-level factors (e.g., sex, number of teeth extracted, etc.)., Discussion: This real-world study will address an important need, providing information on the effectiveness of a multicomponent intervention at modifying dental prescribing behavior and reducing opioid prescriptions to AYA., Clinicaltrials: GOV: NCT06275191., (© 2024. The Author(s).)

Introduction: Many rural communities bear a disproportionate share of drug-related harms. Innovative harm reduction service models, such as vending machines or kiosks, can expand access to services that reduce drug-related harms. However, few kiosks operate in the USA, and their implementation, impact and cost-effectiveness have not been adequately evaluated in rural settings. This paper describes the Kentucky Outreach Service Kiosk (KyOSK) Study protocol to test the effectiveness, implementation outcomes and cost-effectiveness of a community-tailored, harm reduction kiosk in reducing HIV, hepatitis C and overdose risk in rural Appalachia., Methods and Analysis: KyOSK is a community-level, controlled quasi-experimental, non-randomised trial. KyOSK involves two cohorts of people who use drugs, one in an intervention county (n=425) and one in a control county (n=325). People who are 18 years or older, are community-dwelling residents in the target counties and have used drugs to get high in the past 6 months are eligible. The trial compares the effectiveness of a fixed-site, staffed syringe service programme (standard of care) with the standard of care supplemented with a kiosk. The kiosk will contain various harm reduction supplies accessible to participants upon valid code entry, allowing dispensing data to be linked to participant survey data. The kiosk will include a call-back feature that allows participants to select needed services and receive linkage-to-care services from a peer recovery coach. The cohorts complete follow-up surveys every 6 months for 36 months (three preceding kiosk implementation and four post-implementation). The study will test the effectiveness of the kiosk on reducing risk behaviours associated with overdose, HIV and hepatitis C, as well as implementation outcomes and cost-effectiveness., Ethics and Dissemination: The University of Kentucky Institutional Review Board approved the protocol. Results will be disseminated in academic conferences and peer-reviewed journals, online and print media, and community meetings., Trial Registration Number: NCT05657106., Competing Interests: Competing interests: AF-B is a co-founder of Voices of Hope, the contracted recovery community organisation providing the recovery coaching services. The device to facilitate syringe disposal and dispensing that will be installed in conjunction with the kiosk is intellectual property of the University of Kentucky, with AMY designated as the inventor. CC is a paid consultant on the implementation of harm reduction vending machines, including on the described project., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Opioid overdoses differentially affect demographic groups. Strategies to reduce overdose deaths, specifically overdose education and naloxone distribution (OEND), are not consistently delivered equitably., Methods: The HEALing Communities Study SM (HCS) is a cluster-randomized trial designed to implement evidence-based practices, including OEND, to reduce overdose deaths across communities. Individuals receiving OEND in eight Kentucky counties between January 2020 and June 2022 provided demographics and overdose history. Recipient characteristics were compared to opioid overdose decedent characteristics to evaluate whether OEND was equitably delivered to the target population. Recipient characteristics were also analyzed based on whether OEND was delivered in criminal justice, behavioral health, or health care facilities., Results: A total of 26,273 demographic records were analyzed from 137 partner agencies. Most agencies were in behavioral health (85.6 %) or criminal justice sectors (10.4 %). About half of OEND recipients were male (50.6 %), which was significantly lower than the 70.3 % of overdose decedents who were male, (p<0.001). OEND recipients tended to be younger than overdose decedents, but there were not significant differences in race/ethnicity between OEND recipients and overdose decedents. Over 40 % of OEND recipients had overdosed, and 68.9 % had witnessed a prior overdose. There were notable differences across facility types, as males and Black individuals accounted for fewer OEND recipients in addiction treatment facilities compared to jails., Conclusion: Although OEND recipients' demographics resembled those of decedents, specific attention should be paid to ensuring equitable OEND access. Variation in OEND uptake by facility type may reflect biases and barriers to care., Competing Interests: The authors have no conflicts of interest., (© 2024 The Authors. Published by Elsevier B.V.)

Background: Scaling up overdose education and naloxone distribution (OEND), an evidence-based practice for reducing opioid overdose mortality, in communities remains a challenge. Novel models and intentional implementation strategies are needed. Drawing upon the EPIS model's phases of Exploration, Preparation, Implementation, and Sustainment (Aarons et al. in Adm Policy Ment Health 38:4-23, 2011), this paper describes the development of the University of Kentucky's unique centralized "Naloxone Hub with Many Spokes" approach to implementing OEND as part of the HEALing Communities Study (HCS-KY)., Methods: To scale up OEND in eight Kentucky counties, implementation strategies were utilized at two levels: a centralized university-based naloxone dispensing unit ("Naloxone Hub") and adopting organizations ("Many Spokes"). Implementation strategies varied across the EPIS phases, but heavily emphasized implementation facilitation. The Naloxone Hub provided technical assistance, overdose education resources, and no-cost naloxone to partner organizations. Implementation outcomes across the EPIS phases were measured using data from internal study management trackers and naloxone distribution data submitted by partner organizations., Results: Of 209 organizations identified as potential partners, 84.7% (n = 177) engaged in the Exploration/Preparation phase by participating in an initial meeting with an Implementation Facilitator about the HCS-KY OEND program. Adoption of the HCS-KY OEND program, defined as receipt of at least one shipment of naloxone, was achieved with 69.4% (n = 145) of all organizations contacted. During the Implementation phase, partner organizations distributed 40,822 units of naloxone, with partner organizations distributing a mean of 281.5 units of naloxone (SD = 806.2). The mean number of units distributed per county was 5102.8 (SD = 3653.3; range = 1057 - 11,053) and the mean county level distribution rate was 8396.5 units per 100,000 residents (SD = 8103.1; range = 1709.5-25,296.3). Of the partner organizations that adopted the HCS-KY OEND program, 87.6% (n = 127) attended a sustainability meeting with an Implementation Facilitator and agreed to transition to the state-funded naloxone program., Conclusions: These data demonstrate the feasibility of this "Hub with Many Spokes" model for scaling up OEND in communities highly affected by the opioid epidemic. Trial registration ClinicalTrials.gov, NCT04111939. Registered 30 September 2019, https://clinicaltrials.gov/ct2/show/NCT04111939 ., (© 2023. The Author(s).)

Background: Bystander administration of naloxone is a critical strategy to mitigate opioid overdose mortality. To ensure bystanders' willingness to carry and administer naloxone in response to a suspected overdose, it is critical to select products for community distribution with the highest likelihood of being utilized. This study examines bystanders' preference for and willingness to administer three naloxone products approved by the FDA for bystander use and identify product features driving preference., Methods: The population was a convenience sample of individuals who attended the Kentucky State Fair, August 18-28, 2022, in Louisville, Kentucky. Participants (n = 503) watched a standardized overdose education and naloxone training video, rated their willingness to administer each of three products (i.e., higher-dose nasal spray, lower-dose nasal spray, intramuscular injection), selected a product to take home, and rated factors affecting choice., Results: After training, 44.4% chose the higher-dose nasal spray, 30.1% chose the intramuscular injection, and 25.5% chose the lower-dose nasal spray. Factors most influencing choice on a 10-point Likert scale were ease of use (9 [7-10]), naloxone dose (8 [5-10]), and product familiarity (5 [5-9])., Conclusions: Bystanders expressed high willingness to administer all studied formulations of naloxone products. Product choice preference varied as a function of product features. As the number and variety of available products continue to increase, continuous evaluation of formulation acceptability, in addition to including individuals with lived experience who are receiving and administering overdose reversal agents, is critical to support adoption and save lives., (© 2023. The Author(s).)

Twenty-five patients with relapsing and remitting Borreliosis, Babesiosis, and bartonellosis despite extended anti-infective therapy were prescribed double-dose dapsone combination therapy (DDDCT), followed by one or several courses of High Dose Dapsone Combination Therapy (HDDCT). A retrospective chart review of these 25 patients undergoing DDDCT therapy and HDDCT demonstrated that 100% improved their tick-borne symptoms, and patients completing 6-7 day pulses of HDDCT had superior levels of improvement versus 4-day pulses if Bartonella was present. At the completion of treatment, 7/23 (30.5%) who completed 8 weeks of DDDCT followed by a 5-7 day pulse of HDDCT remained in remission for 3-9 months, and 3/23 patients (13%) who recently finished treatment were 1 ½ months in full remission. In conclusion, DDDCT followed by 6-7 day pulses of HDDCT could represent a novel, effective anti-infective strategy in chronic Lyme disease/Post Treatment Lyme Disease Syndrome (PTLDS) and associated co-infections, including Bartonella , especially in individuals who have failed standard antibiotic protocols.

Background: The shift from prescription to illicit drugs involved in drug poisoning deaths raises questions about the current utility of prescription drug monitoring program (PDMP) data to inform drug poisoning (overdose) prevention efforts. In this study, we describe relations between specific drugs involved in Kentucky drug poisoning deaths and antecedent controlled substance (CS) dispensing., Methods: The study used linked death certificates and PDMP data for 2,248 Kentucky resident drug poisoning deaths in 2021. Death certificate literal text analysis identified drugs mentioned with involvement (DMI) in drug poisoning deaths. We characterized the concordance between each DMI and the CS dispensing history for this drug at varying timepoints since 2008., Results: Overall, 25.5% of all decedents had dispensed CS in the month before fatal drug poisoning. Over 80% of decedents were dispensed opioid(s) since 2008; the percentage was similar regardless of opioid involvement in the poisoning death. One-third of decedents had dispensed buprenorphine for treatment of opioid use disorder since 2008, but only 6.1% had dispensed buprenorphine in the month preceding death. Fentanyl/fentanyl analogs were DMI in 1,568 (69.8%) deaths, yet only 3% had received a fentanyl prescription since 2008. The highest concordance in the month preceding death was observed for clonazepam (43.6%)., Conclusion: Overall, concordance between CS dispensing history and the drugs involved in poisoning deaths was low, suggesting a need to reevaluate the complex relationships between prescription medication exposure and overdose death and to expand harm reduction interventions both within and outside the healthcare system to reduce drug poisoning mortality., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Expanding access to naloxone is one of the most impactful interventions in decreasing opioid-related mortality. However, state distribution rates of naloxone are insufficient to meet community need. The current study sought to better understand this gap by focusing on state policies that may facilitate or impede naloxone distribution in four states highly impacted by fatal opioid overdoses - Kentucky, Massachusetts, New York, and Ohio., Methods: We provide a descriptive analysis of the policy landscape impacting naloxone distribution through pharmacy and community channels in the four states participating in the HEALing Communities Study (HCS). Publicly available data and the expertise of the research team were used to describe each state's naloxone access laws (NALs), Medicaid coverage of naloxone, and community overdose education and naloxone distribution infrastructure. Data presented in this study represent the most current policy landscape through September 2022., Results: Variation exists between specific components of the NALs of each state, the structure of Medicaid coverage of naloxone, and the community distribution infrastructure networks. Massachusetts and New York have a statewide standing order, but other states use different strategies short of a statewide standing order to expand access to naloxone. Quantity limits specific to naloxone may limit access to Medicaid beneficiaries in some states., Conclusion: States participating in the HCS have developed innovative but different mechanisms to ensure naloxone access. Policies were dynamic and moved towards greater access. Research should consider the policy landscape in the implementation and sustainability of interventions as well as the analysis of outcomes., Competing Interests: Declaration of Competing Interest No conflicts declared.

Objectives: Increased drug overdose mortality among non-Hispanic Black people in the United States in the past 5 years highlights the need for better tailored programs and services. We evaluated (1) changes in drug overdose mortality for various racial and ethnic groups and (2) drug involvement to inform drug overdose prevention efforts in Kentucky., Methods: We used Kentucky death certificates and postmortem toxicology reports from 2016-2020 (provisional data) to estimate changes in age-adjusted drug overdose death rates per 100 000 standard population., Results: The age-adjusted drug overdose death rate per 100 000 standard population among non-Hispanic Black residents doubled from 2016 (21.2) to 2020 (46.0), reaching the rate among non-Hispanic White residents in 2020 (48.7; P = .48). From 2016 to 2020, about 80% of these drug overdose deaths involved opioids; heroin involvement declined about 20 percentage points; fentanyl involvement increased about 30 percentage points. The number of psychostimulant-involved drug overdose deaths increased 513% among non-Hispanic Black residents and 191% among non-Hispanic White residents. Cocaine-involved drug overdose deaths increased among non-Hispanic Black residents but declined among non-Hispanic White residents. Drug overdose death rates were significantly lower among Hispanic residents than among non-Hispanic White residents., Conclusions: Increased opioid-involved overdose deaths among non-Hispanic Black residents in Kentucky in combination with rapidly expanding concomitant psychostimulant involvement require increased understanding of the social, cultural, and illicit market circumstances driving these rapid trend changes. Our findings underscore the urgent need to expand treatment and harm reduction services to non-Hispanic Black residents with substance use disorder.

Purpose: Developing effective deprescribing interventions relies on understanding attitudes, beliefs, and communication challenges of those involved in the deprescribing decision-making process, including the patient, the primary care clinician, and the pharmacist. The objective of this study was to assess patients' beliefs and attitudes and identify facilitators of and barriers to deprescribing., Methods: As part of a larger study, we recruited patients ⩾18 years of age taking ⩾3 chronic medications. Participants were recruited from retail pharmacies associated with the University of Kentucky HealthCare system. They completed an electronic survey that included demographic information, questions about communication with their primary care clinician and pharmacists, and the revised Patients' Attitudes Toward Deprescribing (rPATD) questionnaire., Results: Our analyses included 103 participants ( n  = 65 identified as female and n  = 74 as White/Caucasian) with a mean age of 50.4 years [standard deviation (SD) = 15.5]. Participants reported taking an average of 8.4 daily medications (SD = 6.1). Most participants reported effective communication with clinicians and pharmacists (66.9%) and expressed willingness to stop one of their medications if their clinician said it was possible (83.5%). Predictors of willingness to accept deprescribing were older age [odds ratio (OR) = 2.99, 95% confidence interval (CI) = 1.45-6.2], college/graduate degree (OR = 55.25, 95% CI = 5.74-531.4), perceiving medications as less appropriate (OR = 8.99, 95% CI = 1.1-73.62), and perceived effectiveness of communication with the clinician or pharmacist (OR = 4.56, 95% CI = 0.85-24.35)., Conclusion: Adults taking ⩾3 chronic medications expressed high willingness to accept deprescribing of medications when their doctor said it was possible. Targeted strategies to facilitate communication within the patient-primary care clinician-pharmacist triad that consider patient characteristics such as age and education level may be necessary ingredients for developing successful deprescribing interventions., Plain Language Summary: Are patients willing to accept stopping medications? Sometimes, medicines that a patient takes regularly become inappropriate. In other words, the risks of adverse effects might be greater than a medicine's potential benefits. The decision to stop such medicines should involve the patient and consider their preferences. We surveyed a group of patients taking multiple medicines to see how they felt about having those medicines stopped. We also asked patients whether and how much they talk to their primary care clinician and pharmacists about their medicines. To qualify for this study, patients had to be at least 18 years old and to take three or more medicines daily; they also needed to speak English. Participants provided demographic information and answered questions about their medicines, their communication with primary care clinicians and pharmacists, and their feelings about having one or more of their medicines stopped. We recruited 107 people and were able to use responses from 103 of them. Their average age was 50 years; 65 of them identified as female, and 75 identified as White/Caucasian. Most of our participants mentioned having conversations with primary care clinicians and pharmacists and said they would be willing to stop a medication if their clinician said it was possible. Older participants, those with more years of education, those who thought their medications might lead to side effects, and those who communicated with their clinician or pharmacists were more willing to have one of their medicines stopped.Our results indicate that patient characteristics and communication with clinicians and pharmacists are factors to consider when designing interventions to reduce the use of inappropriate medicines., Competing Interests: Competing interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A seven- to eight-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission in approximately 50% of patients for one year or longer, with published culture studies indicating higher doses of dapsone demonstrate efficacy against resistant biofilm forms of Borrelia burgdorferi . The purpose of this study was, therefore, to evaluate higher doses of dapsone in the treatment of resistant CLD/PTLDS and associated co-infections. A total of 25 patients with a history of Lyme and associated co-infections, most of whom had ongoing symptoms despite several courses of DDDCT, took one or more courses of high dose pulsed dapsone combination therapy (200 mg dapsone × 3-4 days and/or 200 mg BID × 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in eight major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just the treatment length, positively affected outcomes. High dose pulsed dapsone combination therapy may represent a novel therapeutic approach for the treatment of resistant CLD/PTLDS, and should be confirmed in randomized, controlled clinical trials.

Objective: Evaluate beliefs and behaviors pertaining to abuse-deterrent opioids (ADFs)., Design: Survey in 2019 by invitation to all licensed physicians., Setting: Commonwealth of Kentucky., Participants: 374 physicians., Methods: Descriptive statistics, and hypothesis test that early adopter prescribers would have greater endorsement of opioid risk management., Results: Of all prescribers, 55% believed all opioid analgesics should have ADF requirements (15% were unsure); 74% supported mandating insurance coverage. Only one-third considered whether an opioid was ADF when prescribing, motivated by patient family diversion (94%) and societal supply reduction (88%). About half believed ADFs were equally effective in preventing abuse by intact swallowing, injection, chewing, snorting, smoking routes. Only 4% of OxyContin prescribers chose it primarily because of ADF properties. Instead, the most common reason (33%) was being started by another prescriber. A quarter of physicians chose not to prescribe ADFs because of heroin switching potential. Early adopters strongly believed ADFs were effective in reducing abuse (PR 3.2; 95% CI 1.5, 6.6) compared to mainstream physicians. Early-adopter risk-management practices more often included tools increasing agency and measurement: urine drug screens (PR 2.0; 1.3, 3.1), risk screening (PR 1.3; 0.94, 1.9). While nearly all respondents (96%) felt that opioid abuse was a problem in the community, only 57% believed it was a problem among patients in their practice. Attribution theory revealed an externalization of opioid abuse problems that deflected blame from patients on to family members., Conclusions: The primary motivator for prescribing ADFs was preventing diversion by family members, not patient-level abuse concerns., (© 2021. The Author(s).)

Background: Expanding access to sterile syringes in rural areas is vital, as injection-related epidemics expand beyond metropolitan areas globally. While pharmacies have potential to be an easily accessible source of sterile syringes, research in cities has identified moral, legal and ethical barriers that preclude over-the-counter (OTC) sales to people who inject drugs (PWID). The current study builds on prior urban-based research by elucidating (1) pharmacy OTC policies and (2) pharmacists' rationale for, and barriers and facilitators to, OTC syringe sales in a US rural area hard hit by drug-related epidemics., Methods: We conducted 14 semi-structured interviews with pharmacists recruited from two Eastern Kentucky health districts. Interview domains included experiences with, and attitudes toward, selling OTC syringes to PWID. Constructivist grounded theory methods were used to analyze verbatim transcripts., Results: Most pharmacists operated "restrictive OTC" pharmacies (n = 8), where patients were required to have a prescription or proof of medical need to purchase a syringe. The remainder (n = 6) operated "open OTC" pharmacies, which allowed OTC syringe sales to most patients. Both groups believed their pharmacy policies protected their community and pharmacy from further drug-related harm, but diverging policies emerged because of stigma toward PWID, perceptions of Kentucky law, and belief OTC syringe sales were harmful rather than protective to the community., Conclusion: Our results suggest that restrictive OTC pharmacy policies are rooted in stigmatizing views of PWID. Anti-stigma education about substance use disorder (SUD), human immunodeficiency virus (HIV), and Hepatitis C (HCV) is likely needed to truly shift restrictive pharmacy policy., (© 2022. The Author(s).)

The factors associated with chronic opioid therapy (COT) in patients with HIV is understudied. Using Medicaid data (2002-2009), this retrospective cohort study examines COT in beneficiaries with HIV who initiated standard combination anti-retroviral therapy (cART). We used generalized estimating equations on logistic regression models with backward selection to identify significant predictors of COT initiation. COT was initiated among 1014 out of 9615 beneficiaries with HIV (male: 10.4%; female: 10.7%). Those with older age, any malignancy, Hepatitis C infection, back pain, arthritis, neuropathy pain, substance use disorder, polypharmacy, (use of) benzodiazepines, gabapentinoids, antidepressants, and prior opioid therapies were positively associated with COT. In sex-stratified analyses, multiple predictors were shared between male and female beneficiaries; however, chronic obstructive pulmonary disease, liver disease, any malignancy, and antipsychotic therapy were unique to female beneficiaries. Comorbidities and polypharmacy were important predictors of COT in Medicaid beneficiaries with HIV who initiated cART., (© 2021. The Author(s).)

Background: Practice guidelines recommend urine drug monitoring (UDM) at least annually in the setting of chronic opioid therapy as an objective assessment of substance use. However, empirical evidence on who gets tested and how often testing occurs is lacking., Objectives: This study investigates 10-year UDM trends in the United States based on 2 factors: (1) the duration of prescription opioid treatment, and (2) having an opioid use disorder (OUD) diagnosis and medications for opioid use disorder (MOUD) prescriptions., Study Design: Observational cross-sectional study., Setting: Research was conducted using administrative claims data from Optum's deidentified Clinformatics Data Mart Database for the period 2007 to 2016. The dataset contained information on the plan enrollment and health care claims from 50 states and the District of Columbia., Methods: To examine trends in UDM based on the duration of prescription opioid treatment, persons receiving prescription opioid analgesics were categorized into 4 groups based on the number of days covered: (a) less than 90 days, (b) 90 to 179 days, (c) 180 to 269 days, and (d) at least 270 days. To examine trends based on an OUD diagnosis and MOUD prescriptions, persons diagnosed with OUD were identified and categorized based on the presence of MOUD prescriptions as follows: (a) OUD with buprenorphine (BPN) and naltrexone (NTX) in the same year; (b) OUD with BPN only; (c) OUD with NTX only; (d) OUD with chronic prescription opioid analgesics (>= 90 days); (e) OUD without prescription opioid analgesics, BPN, or NTX; and (f) chronic prescription opioid analgesics (>= 90 days) without an OUD diagnosis. For analysis, the percent receiving UDM was estimated per group per year. Then the data were restricted to those receiving at least one UDM to estimate the average number of UDM per person., Results: Data included an average of 364,485 persons per year receiving prescription opioid analgesics for chronic use, and 10,277 per year receiving an OUD diagnosis. Among those receiving prescription opioid analgesics, less than 50% received UDM. For those receiving at least one UDM, one additional UDM was performed per person as the duration of opioids increased by 90 days. Among persons with OUD, the percent receiving UDM was the highest for those receiving both BPN and NTX (87%), followed by those receiving BPN only (80%), chronic opioids (79%), NTX only (72%), and those not receiving any MOUD/opioids (54%)., Limitations: Methadone dispensing for OUD treatments was not captured in administrative claims data., Conclusions: Although recommended for patients with chronic pain, UDM is provided less than half of the time for these patients. However, once patients received at least one UDM, they would continue to receive it on a fairly regular basis. Compared with those with chronic pain, persons diagnosed with OUD are more likely to receive UDM at a more frequent interval.

Objective: Lyme disease is a tick-borne, multisystemic disease caused by Borrelia burgdorferi. Standard treatments for early Lyme disease include short courses of oral antibiotics but relapses often occur after discontinuation of treatment. Several studies have suggested that ongoing symptoms may be due to a highly antibiotic resistant form of B. burgdorferi called biofilms. Our recent clinical study reported the successful use of an intracellular mycobacterium persister drug used in treating leprosy, diaminodiphenyl sulfone (dapsone), in combination therapy for the treatment of Lyme disease. In this in vitro study, we evaluated the effectiveness of dapsone individually and in combination with cefuroxime and/or other antibiotics with intracellular activity including doxycycline, rifampin, and azithromycin against Borrelia biofilm forms utilizing crystal violet biofilm mass, and dimethyl methylene blue glycosaminoglycan assays combined with Live/Dead fluorescent microscopy analyses., Results: Dapsone, alone or in various combinations with doxycycline, rifampin and azithromycin produced a significant reduction in the mass and protective glycosaminoglycan layer and overall viability of B. burgdorferi biofilm forms. This in vitro study strongly suggests that dapsone combination therapy could represent a novel and effective treatment option against the biofilm form of B. burgdorferi.

The availability of large healthcare datasets offers the opportunity for researchers to navigate the traditional clinical and translational science research stages in a nonlinear manner. In particular, data scientists can harness the power of large healthcare datasets to bridge from preclinical discoveries (T0) directly to assessing population-level health impact (T4). A successful bridge from T0 to T4 does not bypass the other stages entirely; rather, effective team science makes a direct progression from T0 to T4 impactful by incorporating the perspectives of researchers from every stage of the clinical and translational science research spectrum. In this exemplar, we demonstrate how effective team science overcame challenges and, ultimately, ensured success when a diverse team of researchers worked together, using healthcare big data to test population-level substance use disorder (SUD) hypotheses generated from preclinical rodent studies. This project, called Advancing Substance use disorder Knowledge using Big Data (ASK Big Data), highlights the critical roles that data science expertise and effective team science play in quickly translating preclinical research into public health impact., Competing Interests: The authors have no conflicts of interest to declare., (© The Association for Clinical and Translational Science 2020.)

About 20% of individuals with attention deficit hyperactivity disorder are first diagnosed during adolescence. While preclinical experiments suggest that adolescent-onset exposure to attention deficit hyperactivity disorder medication is an important factor in the development of substance use disorder phenotypes in adulthood, the long-term impact of attention deficit hyperactivity disorder medication initiated during adolescence has been largely unexplored in humans. Our analysis of 11,624 adolescent enrollees with attention deficit hyperactivity disorder in the Truven database indicates that temporal medication features, rather than stationary features, are the most important factors on the health consequences related to substance use disorder and attention deficit hyperactivity disorder medication initiation during adolescence.

Objective: To test whether Medicaid expansion is associated with (a) a greater number of naloxone prescriptions dispensed and (b) a higher proportion of naloxone prescriptions paid by Medicaid., Data Sources/study Setting: We used the IQVIA National Prescription Audit to obtain data on per state per quarter naloxone prescription dispensing for the period 2011-16., Study Design: In this quasi-experimental design study, the impact of Medicaid expansion on naloxone prescription dispensing was examined using difference-in-difference estimation models. State-level covariates including pharmacy-based naloxone laws (standing/protocol orders and direct authority to dispense naloxone), third-party prescribing laws, opioid analgesic prescribing rates, opioid-involved overdose death rates, and population size were controlled for in the analysis., Principal Findings: Medicaid expansion was associated with 38 additional naloxone prescriptions dispensed per state per quarter compared to nonexpansion controls, on average (P = .030). Also, Medicaid expansion resulted in an average increase of 9.86 percent in the share of naloxone prescriptions paid by Medicaid per state per quarter (P < .001)., Conclusions: Our study found that Medicaid expansion increased naloxone availability. This finding suggests that it will be important to consider naloxone access when making federal- and state-level decisions affecting Medicaid coverage., (© Health Research and Educational Trust.)

Background: Gabapentin is prescribed for a variety of conditions and is often used off label. It is important to understand the prevalence of gabapentin prescribing and the characteristics of individuals who are prescribed gabapentin, given increasing concern regarding its potential for misuse., Objectives: To (a) examine state- and region-level prevalence and trends in gabapentin prescribing from 2009 to 2016 and (b) characterize demographic and clinical characteristics of individuals prescribed gabapentin in a nationwide population of commercially insured adults., Methods: This retrospective, longitudinal study examined trends in gabapentin prescribing from 2009 to 2016. The study population included individuals aged 18-64 years who were enrolled in a commercial insurance plan at any point from 2009 to 2016. Individuals who were prescribed gabapentin were defined as beneficiaries with at least 1 gabapentin prescription claim in a calendar year (CY). A cross-sectional descriptive analysis was performed to examine differences in demographic and clinical characteristics of individuals prescribed or not prescribed gabapentin in CY 2016., Results: The prevalence of gabapentin prescribing nearly doubled from 2009 to 2016. During this time, gabapentin prescribing increased in every state (range: 44%-179%). State-specific prevalence rates in 2016 varied from 12.7 to 43.9 per 1,000 beneficiaries. Overall, 2.7% of beneficiaries filled ≥ 1 gabapentin prescription in 2016. Individuals prescribed gabapentin were more likely to fill opioid prescriptions (60.8% vs. 16.5%, P < 0.01); reside in the South (53.7% vs. 47%, P < 0.01); be female (62.5% vs. 52.3%, P < 0.01); and be aged 55-64 years (41.7% vs. 21.2%, P < 0.01) compared with the comparator. Individuals who were prescribed gabapentin also had significantly higher rates of seizure disorders, neuropathic pain, mental health disorders, substance use disorders, and diabetes., Conclusions: The prevalence of gabapentin prescribing among a U.S. privately insured population has increased steadily in recent years. Additional research should examine coprescribing of gabapentin in the context of the opioid epidemic., Disclosures: The project described in this study was supported by the NIH National Center for Advancing Translational Sciences through grant number UL1TR001998. This study was also partially supported by grant number 2017-PM-BX-K026 (Data-Driven Responses to Prescription Drug Misuse in Kentucky) awarded by the Bureau of Justice Assistance. Viewpoints or opinions in this document are those of the authors and do not necessarily represent the official position or policies of the U.S. Department of Justice or the official views of the NIH. The authors do not have any conflicts of interest to report. Portions of this study have been previously presented in poster presentations at the 2019 Academy Health Annual Research Meeting; June 2-4, 2019; Washington, DC, and the 2019 University of Kentucky Substance Use Research Day; March 3, 2019; Lexington, KY.

Background: Kentucky Medicaid enrollees, particularly those in the rural Appalachian region, face disproportionate smoking rates and tobacco-related disease burden relative to the rest of the United States (US). The Affordable Care Act (ACA) mandated tobacco cessation treatment coverage by the US public health insurance program Medicaid. Medicaid coverage was also expanded in Kentucky, in 2013, with laxer income eligibility requirements. This short report describes tobacco use incidence and tobacco cessation treatment utilization, comparing by Appalachian status before and after ACA-mandated cessation treatment coverage., Methods: The study design was a retrospective cross-sectional analysis from 2013 to 2015. Subjects were Medicaid enrollees with 1) diagnosis of any tobacco use (2013 n = 541,349; 2014 n = 864,183; 2015 n = 1,090,274); and/or (2) procedure claim for tobacco cessation counseling, and/or (3) pharmaceutical claim for varenicline or any nicotine replacement product. Primary measures included tobacco use incidence and proportion of users receiving cessation treatment. Analysis was via chi square testing of change by year., Results: Overall, the proportion of tobacco users utilizing cessation treatment decreased (4.75% tobacco users in 2013; 3.15% in 2015). Tobacco users receiving counseling decreased from 2.06% pre-ACA (2013) to 1.06% post-ACA (2015, p < 0.001), as did the proportion receiving nicotine replacement products post-ACA (2.69% in 2013 to 1.55% by 2015; p < 0.001). More Appalachians received cessation treatment than non-Appalachians in 2013 (2.72% vs. 2.03%), but by 2015 non-Appalachians received more treatment overall (1.50% vs. 1.65%; p < 0.001). Appalachians received more counseling and NRT, but less varenicline, than non-Appalachians., Conclusions: Utilization of all forms of tobacco cessation treatment throughout Kentucky, and particularly in rural Appalachia, remained limited despite Medicaid enrollment as well as coverage expansions. These findings suggest that barriers persist in access to tobacco cessation treatment for individuals in Medicaid.

This paper examines network prominence in a co-prescription network as an indicator of opioid doctor shopping (i.e., fraudulent solicitation of opioids from multiple prescribers). Using longitudinal data from a large commercially insured population, we construct a network where a tie between patients is weighted by the number of shared opioid prescribers. Given prior research suggesting that doctor shopping may be a social process, we hypothesize that active doctor shoppers will occupy central structural positions in this network. We show that network prominence, operationalized using PageRank, is associated with more opioid prescriptions, higher predicted risk for dangerous morphine dosage, opioid overdose, and opioid use disorder, controlling for number of prescribers and other variables. Moreover, as a patient's prominence increases over time, so does their risk for these outcomes, compared to their own average level of risk. Results highlight the importance of co-prescription networks in characterizing high-risk social dynamics., Competing Interests: The authors have declared that no competing interests exist.

Importance: To mitigate the opioid overdose crisis, states have implemented a variety of legal interventions aimed at increasing access to the opioid antagonist naloxone. Recently, Virginia and Vermont mandated the coprescription of naloxone for potentially at-risk patients., Objective: To assess the association between naloxone coprescription legal mandates and naloxone dispensing in retail pharmacies., Design, Setting, and Participants: This was a population-based, state-level cohort study. The sample included all prescriptions dispensed for naloxone in the retail pharmacy setting contained in IQVIA's national prescription audit, which represents 90% of all retail pharmacies in the United States. The unit of observation was state-month and the study period was January 1, 2011, to December 31, 2017., Exposures: State legal intervention mandating naloxone coprescription., Main Outcomes and Measures: Number of naloxone prescriptions dispensed. State rates of naloxone prescriptions dispensed per month per 100 000 standard population were calculated., Results: The rate of naloxone dispensing increased after implementation of legal mandates for naloxone coprescription. An estimated 88 naloxone prescriptions per 100 000 were dispensed in Virginia and 111 prescriptions per 100 000 were dispensed in Vermont during the first full month the legal requirement was effective. In comparison, 16 naloxone prescriptions per 100 000 were dispensed in the 10 states (including the District of Columbia) with the highest opioid overdose death rates and 6 prescriptions per 100 000 were dispensed in the 39 remaining states. The number of naloxone prescriptions dispensed was associated with the legal mandate for naloxone coprescription (incidence rate ratio [IRR], 7.75; 95% CI, 1.22-49.35). Implementation of the naloxone coprescription mandate was associated with an estimated 214 additional naloxone prescriptions dispensed per month in the period following the mandates, holding all other variables constant. Among covariates, naloxone access laws (IRR, 1.37; 1.05-1.78), opioid overdose death rates (IRR, 1.06; 95% CI, 1.04-1.08), the percentage of naloxone prescriptions paid by third-party payers (IRR 1.009; 1.008-1.010), and time (IRR, 1.06; 95% CI, 1.05-1.07) were significantly associated with naloxone prescription dispensing., Conclusions and Relevance: These study findings suggest that legally mandated naloxone prescription for those at risk for opioid overdose may be associated with substantial increases in naloxone dispensing and further reduction in opioid-related harm.

Background: Given the controversy around the effectiveness of opioid treatment for chronic pain and the lack of detailed guidance for prescribing opioids in older adults, the objectives of this study were to estimate the trajectories and predictors of opioid use in older adults., Methods: Data were extracted from the National Alzheimer's Coordinating Center (2005-2017). Group-based trajectory modeling was used to identify the patterns of opioid use (any or strong) among participants age 65+. We used multivariable logistic regression with backward selection to evaluate demographics and comorbidities as potential predictors of trajectory membership., Results: Among 13,059 participants, four trajectories were identified for the use of both any opioids and strong opioids (minimal-users, incident chronic-users, discontinuing-users, and prevalent chronic-users). For any opioids, female sex (adjusted odds ratio = 1.23; 95% confidence interval = 1.03-1.46), black vs. white (1.47; 1.18-1.82), year of education (0.96; 0.94-0.99), type of residence (independent group vs. private: 1.77; 1.38-2.26, care facility vs. private: 1.89; 1.20-2.97), hypertension (1.44; 1.20-1.72), cardiovascular disease (1.30; 1.09-1.55), urinary incontinence (1.45; 1.19-1.78), dementia (0.73; 0.57-0.92), number of medications (1 to 4 vs. none: 0.48; 0.36-0.64, 5 or more vs. none: 0.67; 0.50-0.88), and antidepressant agent (1.38; 1.14-1.67) were associated with incident chronic-use vs. non-use. For strong opioids, female sex (1.27; 1.04-1.56), type of residence (independent group vs. private: 1.90; 1.43-2.53, care facility vs. private: 2.37; 1.44-3.90), current smoking (1.68; 1.09-2.60), hypertension (1.49; 1.21-1.83), urinary incontinence (1.45; 1.14-1.84), dementia (0.73; 0.55-0.97), number of medications (1 to 4 vs. none: 0.46; 0.32-0.65, 5 or more vs. none: 0.59; 0.42-0.83), and antidepressant agent (1.55; 1.24-1.93) were associated with incident chronic-use vs. non-use., Conclusion: Given that chronic opioid use was more prevalent in participants who were more vulnerable (i.e., older age, with multiple comorbidities, and polypharmacy), further studies should evaluate the safety and efficacy of using opioids in this population., Competing Interests: The authors have declared that no competing interests exist.

We present a precision medical perspective to assist in the definition, diagnosis, and management of Post Treatment Lyme Disease Syndrome (PTLDS)/chronic Lyme disease. PTLDS represents a small subset of patients treated for an erythema migrans (EM) rash with persistent or recurrent symptoms and functional decline. The larger population with chronic Lyme disease is less understood and well defined. Multiple Systemic Infectious Disease Syndrome (MSIDS) is a multifactorial model for treating chronic disease(s), which identifies up to 16 overlapping sources of inflammation and their downstream effects. A patient symptom survey and a retrospective chart review of 200 patients was therefore performed on those patients with chronic Lyme disease/PTLDS to identify those variables on the MSIDS model with the greatest potential effect on regaining health. Results indicate that dapsone combination therapy decreased the severity of eight major Lyme symptoms, and multiple sources of inflammation (other infections, immune dysfunction, autoimmunity, food allergies/sensitivities, leaky gut, mineral deficiencies, environmental toxins with detoxification problems, and sleep disorders) along with downstream effects of inflammation may all affect chronic symptomatology. In part two of our observational study and review paper, we postulate that the use of this model can represent an important and needed paradigm shift in the diagnosis and treatment of chronic disease., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Background: Pharmacists' role in harm reduction is expanding in many states, yet there are limited data on pharmacists' willingness to participate in harm reduction activities. This study assessed community pharmacists' willingness to participate in one harm reduction initiative: syringe/needle exchange., Methods: In 2015, all Kentucky pharmacists with active licenses were emailed a survey that examined attitudes towards participation in syringe/needle exchange. Response frequencies were calculated for community pharmacist respondents. Ordinal logistic regression estimated the impact of community pharmacist characteristics and attitudes on willingness to provide clean needles/syringes to people who inject drugs and to dispose of used syringes/needles, where both dependent variables were defined as Likert-type questions on a scale of 1 (not at all willing) to 6 (very willing)., Results: Of 4699 practicing Kentucky pharmacists, 1282 pharmacists responded (response rate = 27.3%); the majority (n = 827) were community pharmacists. Community pharmacists were divided on willingness to provide clean needles/syringes, with 39.1% not willing (score 1 or 2 of 6) and 30% very willing (score 5 or 6 of 6). Few were willing to dispose of used needles/syringes, with only 18.7% willing. Community pharmacists who agreed that pharmacists could have significant public health impact by providing access to clean needles expressed 3.56 times more willingness to provide clean needles (95% CI 3.06-4.15), and 2.04 times more willingness to dispose of used needles (95% CI 1.77-2.35). Chain/supermarket pharmacists (n = 485, 58.6% of community pharmacies) were 39% less likely to express willingness to dispose of used needles (95% CI 0.43-0.87) when compared with independent community pharmacists (n = 342, 41.4% of community pharmacies). Independent pharmacists reported different barriers (workflow) than their chain/supermarket pharmacist colleagues (concerns of clientele)., Conclusions: Kentucky community pharmacists were more willing to provide clean needles than to dispose of used needles. Strategies to mitigate barriers to participation in syringe/needle exchange are warranted.

Objective: To examine whether the sociodemographic and morbidity characteristics of populations influence their use of the following community heath services: district nursing, health visiting, chiropody, community maternity, community mental illness, and the professions allied to medicine., Design: Observational study., Setting: Nationally representative sample of provider trusts in England., Main Outcome Measures: Activity levels for each service calculated for enumeration districts within the catchment areas of the sample of trusts and standardised to allow for differences in age structure. Regression analysis to determine whether the standardised activity rates for each service could be predicted by a range of socio-demographic and morbidity proxies., Results: Morbidity or deprivation, or both, seemed to influence the use of services in each of the care programmes examined., Conclusions: The allocation of funds for community health services should allow for differences in the health and socio-demographic characteristics of health authorities.

Event-related potentials (ERPs) have been shown to be different between alcoholics and non-alcoholics. Of particular interest to investigators has been the P300 wave. Because it has been shown that alcohol-induced neural damage can alter P300 waves, particularly amplitude, we attempted to examine alcoholics who most likely suffered little damage because they drank heavily for relatively few years (mean = 6.9 years). The effects of long-term sobriety (mean = 5.0) were also investigated to determine if cognitive functioning, as measured by auditory-evoked P300 waves, varies with increased abstinence. Because family history for alcoholism has also been shown to influence P300 amplitude and latency, alcoholics and controls with and without family history were examined. The alcoholic group had significantly longer latencies in P300 measures in both the family history positive and negative groups; P300 amplitudes between alcoholics and non-alcoholics did not vary, regardless of family history. P300 waves were unaffected by sobriety length or drinking history. The results support the hypothesis that P300 differences can be seen between alcoholics and those at risk for alcoholism.

Enprostil, a prostaglandin E2 analogue, is effective in healing acute duodenal ulcer but its value in preventing recurrence, when given daily for maintenance therapy, is uncertain. In this three-centre study we compared enprostil and ranitidine maintenance therapy; the latter is known to reduce duodenal ulcer relapse rates. Patients whose duodenal ulcers had been healed by treatment with an H2-receptor antagonist were randomized to receive single-blind treatment with either 35 micrograms enprostil (n = 64) or 150 mg ranitidine (n = 64) at bedtime for periods of up to 1 year. Endoscopy was routinely performed at 3 months at one centre, and at 6 and 12 months at all three centres, or whenever ulcer symptoms recurred. Clinical assessment and laboratory investigations were performed every 3 months. Relapse, defined as recurrent ulcer with or without pain, or erosions with pain, was significantly greater in patients on enprostil, the comparative rates at 3, 6 and 12 months were: enprostil 23, 31 and 36% ranitidine 6, 12 and 17% (P = 0.013; P = 0.03 and P = 0.03, respectively). Thirty-one patients reported adverse events, the most common being headache (enprostil = 6, ranitidine = 2) and mild diarrhoea (enprostil = 6, ranitidine = 0). Four patients on enprostil were withdrawn for adverse events, although none terminated because of diarrhoea. There were no clinically significant changes in haematology or biochemistry. Enprostil may reduce duodenal ulcer relapse but at a dose of 35 micrograms nightly, it is less effective than 150 mg ranitidine nightly.