Patterns of metformin use and glycated haemoglobin trends among patients with newly diagnosed type 2 diabetes in Alberta, Canada.

AIM: Canadian guidelines recommend metformin as first-line therapy for incident uncomplicated type 2 diabetes and the vast majority of patients are treated accordingly. However, only 54% 65% remain on treatment after 1 year, with the highest discontinuation rates within the first 3 months. The purpose of this study was: (a) to identify individual and clinical factors associated with metformin discontinuation among patients with newly diagnosed uncomplicated type 2 diabetes in Alberta, Canada, and (b) describe glycated haemoglobin (HbA1c) trajectories in the first 12 months after initiation of pharmacotherapy, stratified by metformin usage pattern. MATERIALS AND METHODS: We conducted a retrospective cohort study using linked administrative datasets from 2012 to 2017 to define a cohort of individuals with uncomplicated incident type 2 diabetes. Using logistic regression, we determined individual and clinical characteristics associated with metformin discontinuation. We categorized individuals based on patterns of metformin use and then used mean HbA1c measurements over a 12-month follow-up period to determine glycaemic trajectories for each pattern. RESULTS: Characteristics associated with metformin discontinuation were younger age, lower baseline HbA1c and having fewer comorbidities. Sex, income and location (urban/rural) were not significantly associated with metformin discontinuation. Individuals who continued metformin with higher adherence and individuals who discontinued metformin entirely had lowest HbA1c values at 12 months from treatment initiation. Those who changed therapy or had additional therapies added had higher HbA1c values at 12 months. CONCLUSION: Identifying characteristics associated with discontinuation of metformin and individuals' medication usage patterns provide an opportunity for targeted interventions to support patients' glycaemic management.

The Los Angeles County hub-and-provider network for promoting the sustained use of extended-release naltrexone (XR-NTX) in Los Angeles County (2010-2015).

Extended-release naltrexone (XR-NTX) is a medication-assisted treatment (MAT) that is used in conjunction with psychosocial treatment for substance use disorder. It is associated with a reduction in the number of days that patients use alcohol or opioids, in cravings and drug-seeking behaviors, and in healthcare utilization costs, as well as improved medication adherence rates for patients in substance use disorder (SUD) treatment programs and improved quality of life. Despite the clinical effectiveness of XR-NTX, its clinical use has been slow to develop. There is little research describing the utilization of XR-NTX over time at the treatment-system level and few documented attempts to promote MAT by creating a system to explicitly promote and sustain MAT use. This study examines changes between April 1, 2010, and March 30, 2015, in the utilization patterns of XR-NTX for SUDs as promoted and delivered in a system of "medication hubs," comprised of community providers and a medication coordinating center, and training efforts. This system was implemented as part of a large demonstration project that was designed to provide access to XR-NTX in Los Angeles County. Our findings indicated an increase in the initiation of XR-NTX (59% increase) and subsequent doses (89% increase) from Year 1 to Year 5 of the project (p<0.001). These findings suggest that it is possible to improve MAT utilization (in this case XR-NTX) through the use of a system of care that minimizes MAT payment issues for providers and patients, provides an infrastructure (medication hubs and SUD treatment providers), promotes system coordination, and educates providers.

Effectiveness of extended release naltrexone to reduce alcohol cravings and use behaviors during treatment and at follow-up.

Changes in cravings to drink alcohol and alcohol use behaviors were examined among 337 patients who were administered extended-release naltrexone (XR-NTX) in conjunction with psychosocial treatment in community-based substance use disorder treatment programs. Cravings and use behaviors were assessed at multiple time points (baseline; weeks 1, 2, and 3 after the first dose; monthly after the first four assessments; and at 30- and 60-days after the last dose). A total of 863 doses (M=2.6, SD=1.8) were administered and the majority of patients (65%) took more than one dose. Alcohol craving scores decreased from 19 to 5.7 after the first dose of XR-NTX. Days of primary alcohol use at admission (M=10.5, SD=10.1) were reduced at discharge (M=to 1.2, SD=4.6). At the first follow-up, 79.8% reported no alcohol use and 77.8% reported no alcohol use at the second follow-up. The expected side effects were reported but the medication was well tolerated and there was no relationship between side effects and subsequent dose. Unexamined or unaccounted for variables (e.g., motivation, external pressures to remain in treatment) are "real world" consequences that may have impacted the outcome of this study. Results indicated that use of the antagonist medication XR-NTX may be related to significant decreases in alcohol craving and use while a patient is in treatment, as well as at 30- and 60-days after the final dose.

Response to culturally competent drug treatment among homeless persons with different living arrangements.

This study investigated the association between program cultural competence and homeless individuals' drug use after treatment in Los Angeles County, California. Los Angeles County has the largest and most diverse population of homeless individuals in the nation. We randomly selected for analysis 52 drug-treatment programs and 2158 participants who identified as homeless in the Los Angeles County Participant Reporting System in 2011. We included their living arrangements (indoors and stable, indoors and unstable, and outdoors) and individual and program characteristics (particularly whether their programs used six culturally competent practices) in multilevel regression analyses. The outcome was days of primary drug use at discharge.Results showed that higher levels of staff personal involvement in minority communities (IRR=0.437; 95% CI=0.222, 0.861) and outreach to minority communities (IRR = 0.406; 95% CI=0.213, 0.771) were associated with fewer days of drug use at discharge. Homeless individuals living outdoors used their primary drug more often than any other group. Yet, compared to individuals with other living arrangements, when outdoor homeless individuals were treated by programs with the highest community resources and linkages (IRR=0.364; 95% CI=0.157, 0.844), they reported the fewest days of drug use. We discuss implications for program evaluation and community engagement policies and practices.

Abstinence at Successful Discharge in Publicly Funded Addiction Health Services.

Abstinence at successful discharge in substance use disorder treatment is important to reducing relapse rates and increasing long-term recovery from substance use disorders. However, few studies have examined abstinence as an essential component of successful discharge. This study examined rates and correlates of reported abstinence (nonuse of drugs 30 days prior to successful discharge) among clients attending publicly funded treatment in Los Angeles County, California. Finding show that only 36% of clients who were successfully discharged reported abstinence. Black clients were less likely than non-Hispanic Whites to report abstinence at successful discharge. Clients in methadone treatment programs were less likely than outpatient clients to report abstinence, whereas clients referred to treatment through the legal system (Proposition 36) were more likely to report abstinence compared to self-referred clients. Findings underscore the importance of systematic assessment of abstinence in determining successful discharge and provide a basis for further examination of strategies to improve abstinence and reduce relapse.

A demonstration project implementing extended-release naltrexone in Los Angeles County.

BACKGROUND: Extended-released naltrexone (XR-NTX) is a Food and Drug Administration (FDA)-approved medication associated with higher rates of abstinence, reduced cravings, and delayed relapse to use. However, there is a dearth of literature on real-world implementation of XR-NTX. The Los Angeles County Department of Public Health, in collaboration with UCLA Integrated Substance Abuse Programs, developed a demonstration project to increase access to XR-NTX. This article describes that project, along with data on the expansion of XR-NTX service delivery and patient uptake. METHODS: A secondary descriptive data analysis of demographics, substance use history, current substance use behaviors, health-related variables, and dosing records was conducted on 609 patients who received XR-NTX from Los Angeles County substance use disorder (SUD) treatment facilities from April 2010 through July 2013. A geographic information system approach mapped the distribution of XR-NTX-referring agencies across Los Angeles County. RESULTS: Of the 609 records analyzed, a majority of patients (64%) obtained more than 1 dose of XR-NTX. Most XR-NTX patients reported alcohol use disorder (71.9%; n = 438). Compared with the general Los Angeles County substance use disorder patients, XR-NTX recipients reported more severe substance use histories. Finally, XR-NTX was accessed by providers in 6 of the 8 Service Planning Areas of Los Angeles County. CONCLUSIONS: These findings reflect a higher XR-NTX cessation rate and a lower average number of doses, in contrast to similar demonstration projects in community settings with patients on parole or probation. However, this study shows that it is feasible to engage treatment providers in the use XR-NTX among their patients with alcohol or opioid use disorders. Several implications for future research and implementation are discussed.

Patterns of medical marijuana use among individuals sampled from medical marijuana dispensaries in los angeles.

The proliferation of medical marijuana (MM) dispensaries has led to concerns that they will lead to more widespread use of marijuana. The aim of the current study was to collect descriptive data on individuals using MM dispensaries in Los Angeles County. A mixed-method approach was employed that consisted of focus groups with 30 individuals and a survey of dispensary users (N = 182) in Los Angeles County. Differences between younger (less than 30 years old) and older individuals were examined in the survey sample. Most individuals in both samples had initiated marijuana use in adolescence. Nearly one-half of survey respondents had indications of risky alcohol use and one-fifth reported recent use of illicit drugs or misuse of prescription medications. Younger individuals had higher rates of tobacco use, visited dispensaries more frequently, and had more socially embedded patterns of use, but they were similar to older individuals in terms of their reasons for use. Nearly all participants believed that MM was beneficial in treating their health problems, although 65% reported symptoms of psychological distress in the past year. Interventions aimed at MM users should stress the related effects of tobacco and risky alcohol use as well as mental health needs.

Utilization of emergency and hospital services among individuals in substance abuse treatment.

BACKGROUND: To examine risk factors for use of hospital services among racial and ethnic minority clients in publicly funded substance abuse treatment in Los Angeles County, California. We explored cross-sectional annual data (2006 to 2009) from the Los Angeles County Participant Reporting System for adult participants (n=73,251) who received services from treatment programs (n=231). METHODS: This retrospective analysis of county admission data relied on hierarchical linear negative binomial regression models to explore number of hospital visits, accounting for clients nested in programs. Client data were collected during personal interviews at admission. FINDINGS: Our findings support previous work that noted increased use of emergency rooms among individuals suffering from mental health- and substance use-related issues and extend the knowledge base by highlighting other important features such as treatment need, i.e., residential compared to outpatient treatment. CONCLUSIONS: These findings have implications for health care policy in terms of the need to increase prevention services and reduce costly hospitalization for a population at significant risk of co-occurring mental and physical disorders.

Spanish language proficiency among providers and Latino clients' engagement in substance abuse treatment.

Quality of care, such as provision of services in Spanish, is a common factor believed to improve treatment engagement among Spanish-speaking Latinos in health care. However, there is little evidence that Spanish language proficiency among providers increases treatment access and retention in publicly funded substance abuse treatment. We analyzed client and program data collected in 2010-2011 from publicly funded treatment programs in Los Angeles County, California. An analytic sample of 1903 Latino clients nested within 40 treatment programs located in minority communities was analyzed using multilevel negative binomial regressions on days to initiate and spent in treatment. As hypothesized, Spanish language proficiency was negatively associated with client wait time and positively associated with retention in treatment, after controlling for individual and program characteristics. The path analysis models showed that Spanish language proficiency played a mediating role between professional accreditation and client wait time and retention. These preliminary findings provide an evidentiary base for the role of providers' Spanish language proficiency and Latino engagement in treatment for a population at high risk of treatment dropout. Implications related to health care reform legislation, which seeks to enhance linguistically competent care, are discussed.

Life history and biology of the invasive Turkestan cockroach (Dictyoptera: Blattidae).

The Turkestan cockroach, Blatta lateralis (Walker), has become an important invasive species throughout the southwestern United States and has been reported in the southern United States. It is rapidly replacing the oriental cockroach, Blatta orientalis (L.), in urban areas of the southwestern United States as the most important peri-domestic species. They typically inhabit in-ground containers such as water meter, irrigation, and electrical boxes, raises of concrete, cracks and crevices, and hollow block walls. On occasion, they will invade dwellings. At 26.7 degrees C, male and female nymphs developed into adults in an average of 222 and 224 d, respectively. Both males and females had five nymphal instars. Adult females deposited up to 25 oothecae. The oothecae averaged 16.8 eggs and 13.9 nymphs emerged per egg capsule, resulting in an 82.7% hatch rate. Adults lived for at least 612 d. Two parameters that might contribute to the success of Turkestan cockroaches compared with oriental cockroaches are that the developmental period of the nymphs of Turkestan cockroaches are shorter and adult female Turkestan cockroaches produce considerably more oothecae than do oriental cockroaches. These may explain the observations by Pest Management Professionals that Turkestan cockroaches are displacing oriental cockroaches in outdoor habitats throughout the southwestern United States.

Disparities in completion of substance abuse treatment among Latino subgroups in Los Angeles County, CA.

RATIONALE: A growing body of research has revealed disparities with respect to drug use patterns within Latino subgroups. However, the extent to which these potential disparities enable different Latino subgroups to respond favorably to treatment is unclear. METHODS: This study analyzed a subset of multicross-sectional data (2006-2009) on Latinos collected from publicly funded facilities in Los Angeles County, CA (N=12,871). We used multilevel logistic regressions to examine individual and service-level factors associated with treatment completion among subgroups of first-time Latino treatment clients. RESULTS: Univariate analysis showed that Cubans and Puerto Ricans were less likely to complete treatment than Mexicans and other Latinos. Cubans and Puerto Ricans entered treatment at an older age and with higher formal education than Mexicans, yet they were more likely to report mental health issues and use of cocaine and heroin as primary drugs of choice respectively. Multivariate analysis showed that age, having mental health issues, reporting high use of drugs at intake, and use of methamphetamines and marijuana were associated with decreased odds of completing treatment among all Latino subgroups. In contrast, age at first drug use, treatment duration, and referral monitoring by the criminal system increased the odds of completing treatment for all members. CONCLUSION: These findings have implications for targeting interventions for members of different Latinos groups during their first treatment episode. Promising individual and service factors associated with treatment completion can inform the design of culturally specific recovery models that can be evaluated in small-scale randomized pilot studies.

Identification of SD-0006, a potent diaryl pyrazole inhibitor of p38 MAP kinase.

Starting from an initial HTS screening lead, a novel series of C(5)-substituted diaryl pyrazoles were developed that showed potent inhibition of p38alpha kinase. Key to this outcome was the switch from a pyridyl to pyrimidine at the C(4)-position leading to analogs that were potent in human whole blood based cell assay as well as in a number of animal efficacy models for rheumatoid arthritis. Ultimately, we identified a clinical candidate from this substrate; SD-0006.

Defining process design space for biotech products: case study of Pichia pastoris fermentation.

The concept of "design space" has been proposed in the ICH Q8 guideline and is gaining momentum in its application in the biotech industry. It has been defined as "the multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality." This paper presents a stepwise approach for defining process design space for a biologic product. A case study, involving P. pastoris fermentation, is presented to facilitate this. First, risk analysis via Failure Modes and Effects Analysis (FMEA) is performed to identify parameters for process characterization. Second, small-scale models are created and qualified prior to their use in these experimental studies. Third, studies are designed using Design of Experiments (DOE) in order for the data to be amenable for use in defining the process design space. Fourth, the studies are executed and the results analyzed for decisions on the criticality of the parameters as well as on establishing process design space. For the application under consideration, it is shown that the fermentation unit operation is very robust with a wide design space and no critical operating parameters. The approach presented here is not specific to the illustrated case study. It can be extended to other biotech unit operations and processes that can be scaled down and characterized at small scale.

Enhancing the production of Fc fusion protein in fed-batch fermentation of Pichia pastoris by design of experiments.

This study focuses on the feasibility of producing a therapeutic Fc fusion protein in Pichia pastoris (P. pastoris) and presents an optimization design of experiment (DOE) strategy in a well-defined experimental space. The parameters examined in this study include pH, temperature, salt supplementation, and batch glycerol concentration. The effects of these process conditions were captured by statistical analysis focusing on growth rate and titer responses. Batch medium and fermentation conditions were also investigated prior to the DOE study in order to provide a favorable condition to enable the production of this Fc fusion protein. The results showed that approximately 373 mg/L of the Fc fusion protein could be produced. The pH was found to be particularly critical for the production of this Fc fusion protein. It was significantly higher than the conventional, recommended pH for P. pastoris fermentation. The development of this process shows that protein production in P. pastoris is protein specific, and there is not a set of pre-defined conditions that can work well for all types of proteins. Thorough process development would need to be performed for every type of protein in order for large-scale production in P. pastoris to be feasible.