The Experience of Implementing a Low-Threshold Buprenorphine Treatment Program in a Non-Urban Medical Practice.

BACKGROUND: To respond to the U.S. opioid crisis, new models of healthcare delivery for opioid use disorder treatment are essential. We used a qualitative approach to describe the implementation of a low-threshold buprenorphine treatment program in an independent, community-based medical practice in Ithaca, NY. METHODS: We conducted 17 semi-structured interviews with program staff, leadership, and external stakeholders. Then we analyzed these data using content analysis. We used purposeful sampling aiming for variation in job title for program staff, and in organizational affiliation for external stakeholders. RESULTS: We found that opening an independent medical practice allowed for low-threshold buprenorphine treatment with less regulatory oversight, but state-certification was ultimately required to ensure financial sustainability. Relying on health insurance reimbursement alone led to funding shortfalls and additional funding sources were also required. The practice's ability to build relationships with licensed substance use treatment programs, community organizations, the legal system, and government agencies in the region differed depending on how much these entities supported a harm reduction philosophy compared to abstinence-based treatment. Finally, expanding the practice to a second location in a different region, co-located with a syringe service program, required adapting to a new cultural and political environment. CONCLUSION: The results from this study provide insight about the challenges that independent medical practices might face in delivering low-threshold buprenorphine treatment. They support policy efforts to address the financial burdens associated with providing low-threshold buprenorphine therapy and inform the external relationships that other providers would need to consider when delivering novel treatment models.

A Harm Reduction Approach to Treating Opioid Use Disorder in an Independent Primary Care Practice: a Qualitative Study.

BACKGROUND: Stigma is a barrier to the uptake of buprenorphine to treat opioid use disorder. Harm reduction treatment models intend to minimize this stigma by organizing care around non-judgmental interactions with people who use drugs. There are few examples of implementing buprenorphine treatment using a harm reduction approach in a primary care setting in the USA. METHODS: We conducted a qualitative study by interviewing leadership, staff, and external stakeholders at Respectful, Equitable Access to Compassionate Healthcare (REACH) Medical in Ithaca, NY. REACH is a freestanding medical practice that provides buprenorphine treatment for opioid use disorder since 2018. We conducted semi-structured interviews with 17 participants with the objective of describing REACH's model of care. We selected participants based on their position at REACH or in the community. Interviews were recorded, transcribed, and analyzed for themes using content analysis, guided by the CDC Evaluation Framework. RESULTS: REACH provided buprenorphine, primary care, and mental health services in a low-threshold model. We identified three themes related to delivery of buprenorphine treatment. First, an organizational mission to provide equitable and low-stigma healthcare, which was a key to organizational identity. Second, a low-threshold buprenorphine treatment approach that was critical, but caused concern about over-prescribing and presented logistical challenges. Third, creation and retention of a harm reduction-oriented workforce by offering value-based work and by removing administrative barriers providers may face elsewhere to providing buprenorphine treatment. CONCLUSIONS: A harm reduction primary care model can help reduce stigma for people who use drugs and engage in buprenorphine treatment. Further research is needed to evaluate whether this model leads to improved patient outcomes, can overcome community stakeholder concerns, and is sustainable.

Case Management may Reduce Emergency Department Frequent use in a Universal Health Coverage System: a Randomized Controlled Trial.

BACKGROUND: Frequent emergency department (ED) users account for a disproportionately high number of ED visits. Studies on case management (CM) interventions to reduce frequent ED use have shown mixed results, and few studies have been conducted within a universal health coverage system. OBJECTIVE: To determine whether a CM intervention-compared to standard emergency care-reduces ED attendance. DESIGN: Randomized controlled trial. PARTICIPANTS: Two hundred fifty frequent ED users (5 or more visits in the prior 12 months) who visited a public urban ED at the Lausanne University Hospital between May 2012 and July 2013 were allocated to either an intervention (n = 125) or control (n = 125) group, and monitored for 12 months. INTERVENTIONS: An individualized CM intervention consisting of concrete assistance in obtaining income entitlements, referral to primary or specialty medical care, access to mental health care or substance abuse treatment, and counseling on at-risk behaviors and health care utilization (in addition to standard care) at baseline and 1, 3, and 5 months. MAIN MEASURES: We used a generalized linear model for count data (negative binomial distribution) to compare the number of ED visits during the 12-month follow-up between CM and usual care, from an intention-to-treat perspective. KEY RESULTS: At 12 months, there were 2.71 (±0.23) ED visits in the intervention group versus 3.35 (±0.32) visits among controls (ratio = 0.81, 95 % CI = 0.63; 1.02). In the multivariate model, the effect of the CM intervention on the number of ED visits approached statistical significance (b = -0.219, p = 0.075). The presence of poor social determinants of health was a significant predictor of ED use in the multivariate model (b = 0.280, p = 0.048). CONCLUSIONS: CM may reduce ED use by frequent users through an improved orientation to the health care system. Poor social determinants of health significantly increase use of the ED by frequent users.

Characterizing the vulnerability of frequent emergency department users by applying a conceptual framework: a controlled, cross-sectional study.

BACKGROUND: Frequent emergency department (ED) users meet several of the criteria of vulnerability, but this needs to be further examined taking into consideration all vulnerability's different dimensions. This study aimed to characterize frequent ED users and to define risk factors of frequent ED use within a universal health care coverage system, applying a conceptual framework of vulnerability. METHODS: A controlled, cross-sectional study comparing frequent ED users to a control group of non-frequent users was conducted at the Lausanne University Hospital, Switzerland. Frequent users were defined as patients with five or more visits to the ED in the previous 12 months. The two groups were compared using validated scales for each one of the five dimensions of an innovative conceptual framework: socio-demographic characteristics; somatic, mental, and risk-behavior indicators; and use of health care services. Independent t-tests, Wilcoxon rank-sum tests, Pearson's Chi-squared test and Fisher's exact test were used for the comparison. To examine the -related to vulnerability- risk factors for being a frequent ED user, univariate and multivariate logistic regression models were used. RESULTS: We compared 226 frequent users and 173 controls. Frequent users had more vulnerabilities in all five dimensions of the conceptual framework. They were younger, and more often immigrants from low/middle-income countries or unemployed, had more somatic and psychiatric comorbidities, were more often tobacco users, and had more primary care physician (PCP) visits. The most significant frequent ED use risk factors were a history of more than three hospital admissions in the previous 12 months (adj OR:23.2, 95%CI = 9.1-59.2), the absence of a PCP (adj OR:8.4, 95%CI = 2.1-32.7), living less than 5 km from an ED (adj OR:4.4, 95%CI = 2.1-9.0), and household income lower than USD 2,800/month (adj OR:4.3, 95%CI = 2.0-9.2). CONCLUSIONS: Frequent ED users within a universal health coverage system form a highly vulnerable population, when taking into account all five dimensions of a conceptual framework of vulnerability. The predictive factors identified could be useful in the early detection of future frequent users, in order to address their specific needs and decrease vulnerability, a key priority for health care policy makers. Application of the conceptual framework in future research is warranted.

Barriers to Telephone Quitline Use Among Methadone-Maintained Smokers.

INTRODUCTION: Drug users have high rates of tobacco use and tobacco-related disease. Telephone quitlines promote smoking cessation, but their reach among drug users is unknown. We thus aimed to assess utilization of and barriers to telephone quitlines among methadone-maintained smokers. METHODS: Subjects were opioid-dependent smokers in Bronx, New York, methadone treatment programs who were enrolled in a clinical trial of varenicline. All subjects were offered referral to a free, proactive quitline. We examined quitline records, surveyed barriers to quitline use, and queried reasons for declining referral. RESULTS: Of the 112 subjects enrolled, 47% were male, 54% were Hispanic, and 28% were Black. All subjects were offered referral, and 25 (22% of study participants) utilized the quitline. Quitline utilizers (vs. nonutilizers) were significantly more likely to have landline phone service (72 vs. 42%, p = .01), interest in quitline participation (92 vs. 62%, p < .01), and willingness to receive calls (96 vs. 76%, p = .02). Nonutilizers were significantly more likely to report cell phone service lapse (38 vs. 14%, p = .04), and difficulty charging cell phones (19 vs. 0%, p = .02). Reasons for quitline refusal included: (a) skepticism of quitline efficacy; (b) aversion to telephone communication; (c) competing life demands (e.g., drug treatment, shelter); and (d) problems with cell phone service or minutes. CONCLUSIONS: Despite several limitations to quitline access among methadone-maintained smokers, routine quitline referral was associated with 22% utilization. To expand provision of smoking cessation treatment to opioid-dependent smokers, interventions to promote routine quitline referral in substance abuse treatment programs warrant investigation.

Patient Characteristics Associated With Phone Versus Video Telemedicine Visits for Substance Use Treatment during COVID-19.

OBJECTIVES: Although video visits may offer some benefits over the telephone, not all patients may be equipped to access video telemedicine, raising questions surrounding access disparities. The aim of this study is to examine patient characteristics associated with the use of phone versus video-enabled tele-medication for opioid use disorders (MOUD) during COVID-19. METHODS: This study uses data from a nonurban integrated substance use disorder treatment site in New York to examine patient characteristics associated with the modality of tele-MOUD care. The provider did not offer in-person care. Multivariable regression models were used to assess the association between patient's primary mode of tele-MOUD and patient demographic characteristics. Additional analysis of new patient inductions examined associations between mode of tele-MOUD induction and 30-day follow-up receipt. RESULTS: Of the 4557 tele-MOUD encounters, 76.92% were video and 23.08% were telephone visits. Older patients had significantly higher odds of primarily using telephone (odds ratio [OR]: 0.580; 95% confidence interval [CI]: 0.045, 1.115). Patients with higher education (OR: -0.791; 95% CI: -1.418, -0.168), recent overdose (OR: -0.40; 95% CI: -0.793, -0.010), and new patients (OR: 0.484; 95% CI: -0.945, 0.023) were significantly less likely to rely on telephone. Of 336 new patient initiations, 31 were conducted by telephone while 305 were conducted through video. The mode of new patient initiation was not associated with a follow-up visit within 30 days of initiation. CONCLUSIONS: Telemedicine may increase access to MOUD, though certain patients may rely on different forms of telemedicine. Attention must be paid to policies that promote equitable access to both video and telephone tele-MOUD visits.

Students explore livable communities.

In 2006 and 2007, undergraduate and certificate students in gerontology at the University of Massachusetts Boston investigated the elder livability of seven area communities. Elder "livability" refers to features of a local community that support residents who wish to age in place--characteristics such as the availability of appropriate services, transportation options, and affordable housing. A survey developed by AARP guided the research and facilitated its completion within a single academic semester. With its potential to benefit both students and researched cities and towns, the Livable Communities project is recommended to gerontology educators and action researchers as a meaningful, real-world inquiry into factors affecting the ability of older adults to age in place.

Characteristics and predictors of mortality among frequent users of an Emergency Department in Switzerland.

OBJECTIVES: Frequent Emergency Department (ED) users have an elevated mortality, yet little is known about risk factors. Our aim was to characterize deceased frequent ED users and determine predictors of mortality. METHODS: This is a post-hoc analysis of all-cause mortality among frequent ED users participating in a randomized clinical trial on case management at the Lausanne University Hospital (Switzerland). We enrolled 250 frequent ED users (5+ visits/past year) in a 12-month randomized clinical trial; those with an estimated survival of fewer than 18 months were excluded. The primary outcome was 12-month all-cause mortality. We performed descriptive statistics to compare the baseline characteristics of living and deceased participants, and examined predictors of all-cause mortality using logistic regressions, including age adjustment. RESULTS: Twenty of the 250 (8%) frequent users died during the 12-month follow-up. Seven (35%) deaths were because of cardiac causes and six (30%) were because of cancer. The median age at death was 71 years. Deceased participants were older and more likely to report any somatic determinant, chronic illness, and medical comorbidity. Age (odds ratio 1.07, 95% confidence interval 1.04-1.11) and medical comorbidity (odds ratio 4.76, 95% confidence interval 1.86-12.15) were statistically significant predictors of mortality. CONCLUSION: Despite excluding those with an estimated survival of fewer than 18 months, 8% of frequent ED users died during the study. Age and medical comorbidity were significant predictors of mortality. Interventions, such as case management, should target older frequent ED users and those with multiple medical conditions, and future research should explore their potential impact on mortality.

Developmental and environmental factors supporting the health and well-being of Aboriginal adolescents.

Little progress has been made in the past 30 years in closing the gap between Aboriginal and non-Aboriginal Australians in terms of their educational outcomes, rates of incarceration, risks for chronic illnesses and reduced life-expectancy. The Western Australian Aboriginal Child Health Survey is the first population based survey of its kind developed specifically to inform policy and planning to improve the developmental health of Aboriginal children and youth. A random representative sample of 5,289 Aboriginal children aged 0-17 years, including 1,480 adolescents aged 12-17 years was surveyed through household based interviews with carers and adolescents, questionnaire data from schools and consensual record linkage to health service and education system data. The findings describe the prevalence and relative impact of developmental and environmental factors associated with the health and mental outcomes of Aboriginal adolescents. The major portion of the overall burden of disorder is now evident in the more urbanised living settings of Aboriginal families. Some health risk behaviours such as poor dietary intake, smoking, unprotected sex and insufficient physical exercise are more common in Aboriginal adolescents. However, others such as alcohol and marijuana use and suicidal behaviour occur at similar levels to those seen in non-Aboriginal youth.

Treatment of implanted mammary tumors with recombinant vesicular stomatitis virus targeted to Her2/neu.

Vesicular stomatitis virus (VSV) is being developed for cancer therapy. We have created a recombinant replicating VSV (rrVSV) that targeted to Her2/neu expressing breast cancer cells and expresses mouse GM-CSF. We now tested the efficacy of this rrVSV in the treatment of peritoneal tumor implants of D2F2/E2 cells, a BALB/c mouse mammary tumor cell line, which was stably transfected to express Her2/neu. Mice were treated 1 day following tumor implantation with either 2 x 10(8) infectious doses rrVSV or conditioned media (CM). All control animals developed massive peritoneal tumor with a median survival of 16 days. Nine of 10 rrVSV treated mice survived long term with no evidence of tumor. rrVSV had much less efficacy in treating implants of the parent D2F2 cells that did not express Her2/neu. The median survival was 13.5 days in mice treated with CM and 21 days in those treated with rrVSV. There was one long term survivor in the rrVSV treated group. None of the rrVSV treated animals showed evidence of viral toxicity. Three of 7 long term survivors did not develop tumor when rechallenged first with D2F2/E2 and then with D2F2 cells. Both successful therapy and resistance to rechallenge were T-cell dependent. These studies demonstrate that targeted rrVSV eliminated peritoneal implants of Her2/neu expressing tumor and elicited an anti-tumor T-cell immunologic response.

Rapid adaptation of a recombinant vesicular stomatitis virus to a targeted cell line.

Vesicular stomatitis virus (VSV) is being developed for cancer therapy. We created a recombinant replicating VSV (rrVSV) that preferentially infected Her2/neu-expressing breast cancer cells. This rrVSV did not express the native VSV-G glycoprotein (gp). Instead, it expressed a chimeric Sindbis gp which included a single-chain antibody (SCA) directed to the human Her2/neu receptor. The virus infected mouse mammary carcinoma cells (D2F2/E2) expressing Her2/neu 23-fold better than the parent cells (D2F2). However, viral growth in cultured D2F2/E2 cells was curtailed after several cycles, and viral yield was very poor at 2 x 10(4) infectious doses (ID)/ml. We performed in vitro serial passage in D2F2/E2 cells to evolve a virus with improved growth that could be used for preclinical therapy trials in mice. Fifteen passes generated an adapted virus that progressed through multiple cycles in cultured D2F2/E2 cells until all cells were infected and had a viral yield of 1 x 10(8) ID/ml. Sequencing of the entire viral genomes found only 2 mutations in the adapted virus. Both mutations occurred in the gp gene segment coding for the SCA. An additional N-glycosylation site was created by one of the mutations. The adapted virus showed higher density of gp on the viral envelope, improved infectivity, much greater stability, higher burst size, and decreased induction of cellular interferon. The specificity for cells expressing the Her2/neu receptor was unchanged. These studies demonstrate that serial passage can be used to rapidly evolve a VSV genome encoding an improved chimeric glycoprotein.

Preferential targeting of vesicular stomatitis virus to breast cancer cells.

Vesicular stomatitis virus (VSV) is a candidate for development for cancer therapy. We created a recombinant replicating VSV (rrVSV) with an altered surface protein that targeted preferentially to breast cancer cells. The rrVSV genome contained a single glycoprotein (gp) gene derived from Sindbis virus. This gene expressed a chimeric Sindbis E2 binding gp and the native Sindbis E1 fusion gp. The chimeric E2 binding gp, called Sindbis-SCA-erbb2, was modified to reduce its native binding function and to contain a single chain antibody (SCA) with specificity for the human epidermal growth factor receptor Her2/neu protein, erbb2. These viruses selectively infected, replicated in and killed cells expressing erbb2. The titer of rrVSV on SKBR3 cells, a human breast cancer cell line which highly expresses erbb2 was 3.1 x 10(7)/ml compared with a titer of 7.3 x 10(5)/ml on 143 cells, a human osteosarcoma cell line which does not express erbb2. The titer of rrVSV on D2F2/E2 cells, a mouse mammary cancer cell line stably transfected to express human erbb2 was 2.46 x 10(6)/ml compared with a titer of 5 x 10(4)/ml on the parent D2F2 cells which do not express erbb2. When titered on erbb2-negative cells, non-replicating pseudotype VSV coated with Sindbis-SCA-erbb2 had <3% the titer of pseudotype VSV coated with wild type Sindbis gp indicating that the chimeric Sindbis gp had severely impaired binding to the natural receptor. Analysis of the protein composition of the rrVSV found low expression of the modified Sindbis gp on the virus.

Vesicular stomatitis virus expressing a chimeric Sindbis glycoprotein containing an Fc antibody binding domain targets to Her2/neu overexpressing breast cancer cells.

Vesicular stomatitis virus (VSV) is a candidate for development for cancer therapy. It is an oncolytic virus that is safe in humans. Recombinant virus can be made directly from plasmid components. We attempted to create a virus that targeted specifically to breast cancer cells. Nonreplicating and replicating pseudotype VSV were created whose only surface glycoprotein (gp) was a Sindbis gp, called Sindbis-ZZ, modified to severely reduce its native binding function and to contain the Fc-binding domain of Staphylococcus aureus protein A. When titered on Her2/neu overexpressing SKBR3 human breast cancer cells, pseudotype VSV coated with Sindbis-ZZ had <1% the titer of pseudotype VSV coated with wild-type Sindbis gp. Titer was increased 50-fold when the Sindbis-ZZ pseudotype was conjugated with 4D5, a mouse monoclonal antibody directed against the Her2/neu receptor. Titers of antibody-conjugated virus were increased 36-fold on a second human breast cancer cell line, MCF7/H2, which expressed lower concentrations of Her2/neu receptor on the cell surface. At multiple concentrations of antibody, titers on SKBR3 cells were significantly greater when the virus was incubated with Herceptin, an antibody with a human Fc, than with 4D5, a mouse antibody, reflecting the known higher affinity of the protein A Fc-binding domain for human Fc. Analysis of the protein composition of the pseudotype VSV found low expression of the modified Sindbis gp on the virus accounting, in part, for a viral titer that did not exceed 1.2 x 10(5)/ml. This work demonstrates the ability to easily create, directly from plasmid components, an oncolytic replicating VSV with a restricted host cell range.