Implementing Foundry: A cohort study describing the regional and virtual expansion of a youth integrated service in British Columbia, Canada.

AIM: Integrated youth services (IYS) have been identified as a national priority in response to the youth mental health and substance use (MHSU) crisis in Canada. In British Columbia (BC), an IYS initiative called Foundry expanded to 11 physical centres and launched a virtual service. The aim of the study was to describe the demographics of Foundry clients and patterns of service utilization during this expansion, along with the impact of the COVID-19 pandemic. METHODS: Data were analysed for all youth (ages 12-24) accessing both in-person (April 27th, 2018-March 31st, 2021) and virtual (May 1st, 2020-March 31st, 2021) services. Cohorts containing all clients from before (April 27th, 2018-March 16th, 2020) and during (March 17th, 2020-March 31st, 2021) the COVID-19 pandemic were also examined. RESULTS: A total of 23 749 unique youth accessed Foundry during the study period, with 110 145 services provided. Mean client age was 19.54 years (SD = 3.45) and 62% identified as female. Over 60% of youth scored 'high' or 'very high' for distress and 29% had a self-rated mental health of 'poor', with similar percentages seen for all services and virtual services. These ratings stayed consistent before and during the COVID-19 pandemic. CONCLUSIONS: Foundry has continued to reach the target age group, with a 65% increase in number of clients during the study period compared with the pilot stage. This study highlights lessons learned and next steps to promote youth-centred data capture practices over time within an integrated youth services context.

Priority measures for publicly reporting primary care performance: Results of public engagement through deliberative dialogues in 3 Canadian provinces.

OBJECTIVE: While public reporting of hospital-based performance measurement is commonplace, it has lagged in the primary care sector, especially in Canada. Despite the increasing recognition of patients as active partners in the health-care system, little is known about what information about primary care performance is relevant to the Canadian public. We explored patient perspectives and priorities for the public reporting of primary care performance measures. METHODS: We conducted six deliberative dialogue sessions across three Canadian provinces (British Columbia, Ontario, Nova Scotia). Participants were asked to rank and discuss the importance of collecting and reporting on specific dimensions and indicators of primary care performance. We conducted a thematic analysis of the data. RESULTS: Fifty-six patients participated in the dialogue sessions. Measures of access to primary care providers, communication with providers and continuity of information across all providers involved in a patient's care were identified as the highest priority indicators of primary care performance from a patient perspective. Several common measures of quality of care, such as rates of cancer screening, were viewed as too patient dependent to be used to evaluate the health system or primary care provider's performance. CONCLUSIONS: Our findings suggest that public reporting aimed at patient audiences should focus on a nuanced measure of access, incorporation of context reported alongside measurement that is for public audiences, clear reporting on provider communication and a measure of information continuity. Participants highlighted the importance the public places on their providers staying up to date with advances in care.

Population segments as a tool for health care performance reporting: an exploratory study in the Canadian province of British Columbia.

BACKGROUND: Primary care serves all age groups and individuals with health states ranging from those with no chronic conditions to those who are medically complex, or frail and approaching the end of life. For information to be actionable and guide planning, there must be some population disaggregation based on differences in expected needs for care. Promising approaches to segmentation in primary care reflect both the breadth and severity of health states, the types and amounts of health care utilization that are expected, and the roles of the primary care provider. The purpose of this study was to assess population segmentation as a tool to create distinct patient groups for use in primary care performance reporting. METHODS: This cross-sectional study used administrative data (patient characteristics, physician and hospital billings, prescription medicines data, emergency department visits) to classify the population of British Columbia (BC), Canada into one of four population segments: low need, multiple morbidities, medically complex, and frail. Each segment was further classified using socioeconomic status (SES) as a proxy for patient vulnerability. Regression analyses were used to examine predictors of health care use, costs and selected measures of primary care attributes (access, continuity, coordination) by segment. RESULTS: Average annual health care costs increased from the low need ($ 1460) to frail segment ($10,798). Differences in primary care cost by segment only emerged when attributes of primary care were included in regression models: accessing primary care outside business hours and discontinuous primary care (≥5 different GP's in a given year) were associated with higher health care costs across all segments and higher continuity of care was associated with lower costs in the frail segment (cost ratio = 0.61). Additionally, low SES was associated with higher costs across all segments, but the difference was largest in the medically complex group (cost ratio = 1.11). CONCLUSIONS: Population segments based on expected need for care can support primary care measurement and reporting by identifying nuances which may be lost when all patients are grouped together. Our findings demonstrate that variables such as SES and use of regression analyses can further enhance the usefulness of segments for performance measurement and reporting.

Citizen perspectives on the use of publicly reported primary care performance information: Results from citizen-patient dialogues in three Canadian provinces.

OBJECTIVE: Performance measurement and reporting is proliferating in all sectors of the healthcare system, including primary care, despite a dearth of evidence on how the public uses reports on primary care performance. We explored how the public might use this information, to guide the development of effective reporting systems for primary care. METHODS: We conducted six full-day deliberative dialogue sessions with a purposive sample of 56 citizen-patients across three Canadian provinces (British Columbia, Ontario and Nova Scotia). Participants identified how they would use publicly reported performance data. We conducted a thematic analysis of the data by region. RESULTS: Common uses for primary care performance information emerged across all sessions. Participants most often discussed the utility of this information for community advocacy and participation in health system decision making. Similar barriers for using performance information to choose a primary care provider were identified in each region including the perceived lack of choice of providers and the high value placed on relationships with current providers. Finally, the value of public performance reporting in enhancing trust that people would receive good care was also a common theme. CONCLUSIONS: Citizen-patient perspectives highlight that public reporting on primary care performance could promote the health system's responsiveness by enabling public engagement in decision making at the community level. The role of public reporting in promoting trust rather than empowering patient choice may reflect unique elements of the Canadian health system's context.

Promoting cross-jurisdictional primary health care research: developing a set of common indicators across 12 community-based primary health care teams in Canada.

AimTo describe the process by which the 12 community-based primary health care (CBPHC) research teams worked together and fostered cross-jurisdictional collaboration, including collection of common indicators with the goal of using the same measures and data sources. BACKGROUND: A pan-Canadian mechanism for common measurement of the impact of primary care innovations across Canada is lacking. The Canadian Institutes for Health Research and its partners funded 12 teams to conduct research and collaborate on development of a set of commonly collected indicators. METHODS: A working group representing the 12 teams was established. They undertook an iterative process to consider existing primary care indicators identified from the literature and by stakeholders. Indicators were agreed upon with the intention of addressing three objectives across the 12 teams: (1) describing the impact of improving access to CBPHC; (2) examining the impact of alternative models of chronic disease prevention and management in CBPHC; and (3) describing the structures and context that influence the implementation, delivery, cost, and potential for scale-up of CBPHC innovations.FindingsNineteen common indicators within the core dimensions of primary care were identified: access, comprehensiveness, coordination, effectiveness, and equity. We also agreed to collect data on health care costs and utilization within each team. Data sources include surveys, health administrative data, interviews, focus groups, and case studies. Collaboration across these teams sets the foundation for a unique opportunity for new knowledge generation, over and above any knowledge developed by any one team. Keys to success are each team's willingness to engage and commitment to working across teams, funding to support this collaboration, and distributed leadership across the working group. Reaching consensus on collection of common indicators is challenging but achievable.

Insights from linking routinely collected data across Australian health jurisdictions: a case study of end-of-life health service use.

OBJECTIVES: The jurisdictional nature of routinely collected health data in Australia has created challenges for linking data across state/territory and federal government boundaries. This has impeded understanding of the interplay between service use across hospital and community care. Our objective was to demonstrate the value-add of cross-jurisdictional data using a case study of health service use and the factors associated with healthcare use towards the end of life. STUDY TYPE: Retrospective cohort study using routinely collected health data. METHODS: We used two decedent cohorts of people aged ≥65 years who died in New South Wales (NSW), Australia, in 2006 or 2007. The population cohort comprised the general NSW population linked to NSW data collections; the other cohort comprised Australian Government Department of Veterans' Affairs (DVA) clients (with full healthcare entitlements) linked to NSW and Commonwealth data. We compared information available on health services received during the last 6 months of life and ran multivariable analyses for both cohorts to demonstrate the added value of the Commonwealth data. RESULTS: We included 37 567 decedents in the population cohort and 11 259 in the DVA cohort. Cancer was the cause of death for 27% of the NSW cohort and 22% of the DVA cohort; approximately 40% of decedents in each cohort had a cancer history. We summarise information on hospital services for both cohorts and examine community care (general practitioner consultations, specialist presentations, prescriptions dispensed) for the DVA cohort only. Multivariable analyses in the DVA cohort demonstrated that high rates of emergency department (ED) presentations and hospitalisation were associated with higher rates of use of all health services, including community care. Use of primary care did not reduce ED or hospital use. We were not able to examine the interplay between community and hospital care in the NSW population cohort. CONCLUSIONS: In our case study, we demonstrated the value-add of Commonwealth data for understanding the drivers of hospital services use, which has implications for service delivery and resource allocation. There is an abundance of routinely collected health data in Australia that can be used to describe whole-of-healthcare use for a broad range of issues.

Health care use and costs at the end of life: a comparison of elderly Australian decedents with and without a cancer history.

BACKGROUND: There is limited population-level research on end-of-life care in Australia that considers health care use and costs across hospital and community sectors. The aim of this study was to quantify health care use and costs in the last 6 months of life in a cohort of elderly Australian decedents and to examine the factors associated with end-of-life resource use and costs. METHODS: A retrospective cohort study using routinely collected health data from Australian Government Department of Veterans' Affairs clients. The study included two cohorts of elderly Australians who died between 2005 and 2009; one cohort with a recorded cancer diagnosis and a comparison cohort with no evidence of a cancer history. We examined hospitalisations, emergency department (ED) visits, prescription drugs, clinician visits, pathology, and procedures and associated costs in the last 6 months of life. We used negative binominal regression to explore factors associated with health service use and costs. RESULTS: The cancer cohort had significantly higher rates of health service use and 27% higher total health care costs than the comparison cohort; in both cohorts, costs were driven primarily by hospitalisations. Older age was associated with lower costs and those who died in residential aged care incurred half the costs of those who died in hospital. CONCLUSIONS: The results suggest differences in end-of-life care pathways dependent on patient factors, with younger, community-dwelling patients and those with a history of cancer incurring significantly greater costs. There is a need to examine whether the investment in end-of-life care meets patient and societal needs.

Primary Care Performance Measurement and Reporting at a Regional Level: Could a Matrix Approach Provide Actionable Information for Policy Makers and Clinicians?

OBJECTIVE: Primary care services form the foundation of modern healthcare systems, yet the breadth and complexity of services and diversity of patient populations may present challenges for creating comprehensive primary care information systems. Our objective is to develop regional-level information on the performance of primary care in Canada. METHODS: A scoping review was conducted to identify existing initiatives in primary care performance measurement and reporting across 11 countries. The results of this review were used by our international team of primary care researchers and clinicians to propose an approach for regional-level primary care reporting. RESULTS: We found a gap between conceptual primary care performance measurement frameworks in the peer-reviewed literature and real-world primary care performance measurement and reporting activities. We did not find a conceptual framework or analytic approach that could readily form the foundation of a regional-level primary care information system. Therefore, we propose an approach to reporting comprehensive and actionable performance information according to widely accepted core domains of primary care as well as different patient population groups. CONCLUSIONS: An approach that bridges the gap between conceptual frameworks and real-world performance measurement and reporting initiatives could address some of the potential pitfalls of existing ways of presenting performance information (i.e., by single diseases or by age). This approach could produce meaningful and actionable information on the quality of primary care services.

Health service use and costs in the last 6 months of life in elderly decedents with a history of cancer: a comprehensive analysis from a health payer perspective.

BACKGROUND: There is growing interest in end-of-life care in cancer patients. We aim to characterise health service use and costs in decedents with cancer history and examine factors associated with resource use and costs at life's end. METHODS: We used routinely collected claims data to quantify health service use and associated costs in two cohorts of elderly Australians diagnosed with cancer: one cohort died from cancer (n=4271) and the other from non-cancer causes (n=3072). We used negative binomial regression to examine the factors associated with these outcomes. RESULTS: Those who died from cancer had significantly higher rates of hospitalisations and medicine use but lower rates of emergency department use than those who died from non-cancer causes. Overall health care costs were significantly higher in those who died from cancer than those dying from other causes; and 40% of costs were expended in the last month of life. CONCLUSIONS: We analysed health services use and costs from a payer perspective, and highlight important differences in patterns of care by cause of death in patients with a cancer history. In particular, there are growing numbers of highly complex patients approaching the end of life and the heterogeneity of these populations may present challenges for effective health service delivery.

Resource use, costs and quality of end-of-life care: observations in a cohort of elderly Australian cancer decedents.

BACKGROUND: The last year of life is one of the most resource-intensive periods for people with cancer. Very little population-based research has been conducted on end-of-life cancer care in the Australian health care setting. The objective of this program is to undertake a series of observational studies examining resource use, costs and quality of end-of-life care in a cohort of elderly cancer decedents using linked, routinely collected data. METHODS/DESIGN: This study forms part of an ongoing cancer health services research program. The cohorts for the end-of-life research program comprise Australian Government Department of Veterans' Affairs decedents with full health care entitlements, residing in NSW for the last 18 months of life and dying between 2005 and 2009. We used cancer and death registry data to identify our decedent cohorts and their causes of death. The study population includes 9,862 decedents with a cancer history and 15,483 decedents without a cancer history. The median age at death is 86 and 87 years in the cancer and non-cancer cohorts, respectively. We will examine resource use and associated costs in the last 6 months of life using linked claims data to report on health service use, hospitalizations, emergency department visits and medicines use. We will use best practice methods to examine the nature and extent of resource use, costs and quality of care based on previously published indicators. We will also examine factors associated with these outcomes. DISCUSSION: This will be the first Australian research program and among the first internationally to combine routinely collected data from primary care and hospital-based care to examine comprehensively end-of-life care in the elderly. The research program has high translational value, as there is limited evidence about the nature and quality of care in the Australian end-of-life setting.

Studies using Australia's Pharmaceutical Benefits Scheme data for pharmacoepidemiological research: a systematic review of the published literature (1987-2013).

PURPOSE: Research using dispensing claims is used increasingly to study post-market medicines use and outcomes. The purpose of this review is to catalogue more than 25 years of published literature using Australia's Pharmaceutical Benefits Scheme (PBS) dispensing records. METHODS: We searched MEDLINE, PreMEDLINE and Embase and conducted author searches for studies published from 1987 to 2013. Independent reviewers screened abstracts of 3209 articles and reviewed 264 full-text manuscripts. Included studies used PBS dispensing data to measure patterns and/or outcomes of prescribed medicines use or dispensing claims to derive a proxy for a specific disease cohort or health outcome. RESULTS: Of the 228 studies identified, 106 used PBS claims only (56 using claims-level data and 50 using individual-level data) and 63 studies linked individual-level PBS claims to other health data. Most commonly, studies examined trends in drug utilisation (33%), clinician and patient practices (26%), drug use and outcomes (18%) and evaluations of intervention impacts (17%). Sixty-two percent of studies using individual-level data were based on a subset of elderly Australians. Most studies focused on drug classes acting on the nervous system (36%), cardiovascular system (15%) and alimentary tract (11%). Few studies examined prescribed medicines use in children and pregnant women. CONCLUSIONS: Pharmaceutical Benefits Scheme claims represent a significant resource to examine Australia's billion-dollar annual investment in prescribed medicines. The body of research is growing and has increased in complexity over time. Australia has great potential to undertake world-class, whole-of-population pharmacoepidemiological studies. Recent investment in data linkage infrastructure will significantly enhance these opportunities.

Retrospective studies of end-of-life resource utilization and costs in cancer care using health administrative data: a systematic review.

BACKGROUND: There has been an increase in observational studies using health administrative data to examine the nature, quality, and costs of care at life's end, particularly in cancer care. AIM: To synthesize retrospective observational studies on resource utilization and/or costs at the end of life in cancer patients. We also examine the methods and outcomes of studies assessing the quality of end-of-life care. DESIGN: A systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (A Measurement Tool to Assess Systematic Reviews) methodology. DATA SOURCES: We searched MEDLINE, Embase, CINAHL, and York Centre for Research and Dissemination (1990-2011). Independent reviewers screened abstracts of 14,424 articles, and 835 full-text manuscripts were further reviewed. Inclusion criteria were English-language; at least one resource utilization or cost outcome in adult cancer decedents with solid tumors; outcomes derived from health administrative data; and an exclusive end-of-life focus. RESULTS: We reviewed 78 studies examining end-of-life care in over 3.7 million cancer decedents; 33 were published since 2008. We observed exponential increases in service use and costs as death approached; hospital services being the main cost driver. Palliative services were relatively underutilized and associated with lower expenditures than hospital-based care. The 15 studies using quality indicators demonstrated that up to 38% of patients receive chemotherapy or life-sustaining treatments in the last month of life and up to 66% do not receive hospice/palliative services. CONCLUSION: Observational studies using health administrative data have the potential to drive evidence-based palliative care practice and policy. Further development of quality care markers will enhance benchmarking activities across health care jurisdictions, providers, and patient populations.

How do medical doctors use a web-based oncology protocol system? A comparison of Australian doctors at different levels of medical training using logfile analysis and an online survey.

BACKGROUND: Electronic decision support is commonplace in medical practice. However, its adoption at the point-of-care is dependent on a range of organisational, patient and clinician-related factors. In particular, level of clinical experience is an important driver of electronic decision support uptake. Our objective was to examine the way in which Australian doctors at different stages of medical training use a web-based oncology system (http://www.eviq.org.au). METHODS: We used logfiles to examine the characteristics of eviQ registrants (2009-2012) and patterns of eviQ use in 2012, according to level of medical training. We also used a web-based survey to evaluate the way doctors at different levels of medical training use the online system and to elicit perceptions of the system's utility in oncology care. RESULTS: Our study cohort comprised 2,549 eviQ registrants who were hospital-based medical doctors across all levels of training. 65% of the cohort used eviQ in 2012, with 25% of interns/residents, 61% of advanced oncology trainees and 47% of speciality-qualified oncologists accessing eviQ in the last 3 months of 2012. The cohort accounted for 445,492 webhits in 2012. On average, advanced trainees used eviQ up to five-times more than other doctors (42.6 webhits/month compared to 22.8 for specialty-qualified doctors and 7.4 webhits/month for interns/residents). Of the 52 survey respondents, 89% accessed eviQ's chemotherapy protocols on a daily or weekly basis in the month prior to the survey. 79% of respondents used eviQ at least weekly to initiate therapy and to support monitoring (29%), altering (35%) or ceasing therapy (19%). Consistent with the logfile analysis, advanced oncology trainees report more frequent eviQ use than doctors at other stages of medical training. CONCLUSIONS: The majority of the Australian oncology workforce are registered on eviQ. The frequency of use directly mirrors the clinical role of doctors and attitudes about the utility of eviQ in decision-making. Evaluations of this kind generate important data for system developers and medical educators to drive improvements in electronic decision support to better meet the needs of clinicians. This end-user focus will optimise the uptake of systems which will translate into improvements in processes of care and patient outcomes.

Uptake of a web-based oncology protocol system: how do cancer clinicians use eviQ cancer treatments online?

BACKGROUND: The use of computerized systems to support evidence-based practice is commonplace in contemporary medicine. Despite the prolific use of electronic support systems there has been relatively little research on the uptake of web-based systems in the oncology setting. Our objective was to examine the uptake of a web-based oncology protocol system (http://www.eviq.org.au) by Australian cancer clinicians. METHODS: We used web-logfiles and Google Analytics to examine the characteristics of eviQ registrants from October 2009-December 2011 and patterns of use by cancer clinicians during a typical month. RESULTS: As of December 2011, there were 16,037 registrants; 85% of whom were Australian health care professionals. During a typical month 87% of webhits occurred in standard clinical hours (08:00 to 18:00 weekdays). Raw webhits were proportional to the size of clinician groups: nurses (47% of Australian registrants), followed by doctors (20%), and pharmacists (14%). However, pharmacists had up to three times the webhit rate of other clinical groups. Clinicians spent five times longer viewing chemotherapy protocol pages than other content and the protocols viewed reflect the most common cancers: lung, breast and colorectal. CONCLUSIONS: Our results demonstrate eviQ is used by a range of health professionals involved in cancer treatment at the point-of-care. Continued monitoring of electronic decision support systems is vital to understanding how they are used in clinical practice and their impact on processes of care and patient outcomes.

An evaluation of web-based clinical practice guidelines for managing problems associated with cannabis use.

BACKGROUND: Cannabis is the most widely used illicit substance, and multiple treatment options and avenues exist for managing its use. There has been an increase in the development of clinical practice guidelines (CPGs) to improve standards of care in this area, many of which are disseminated online. However, little is known about the quality and accessibility of these online CPGs. OBJECTIVE: The purpose of study 1 was to determine the extent to which cannabis-related CPGs disseminated online adhere to established methodological standards. The purpose of study 2 was to determine if treatment providers are familiar with these guidelines and to assess their perceived quality of these guidelines. METHODS: Study 1 involved a systematic search using the Google Scholar search engine and the National Drugs Sector Information Service (NDSIS) website of the Alcohol and Other Drugs Council of Australia (ADCA) to identify CPGs disseminated online. To be included in the current study, CPGs needed to be free of charge and provide guidance on psychological interventions for reducing cannabis use. Four trained reviewers independently assessed the quality of the 7 identified guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. Study 2 assessed 166 Australian cannabis-use treatment providers' (mean age = 45.47 years, SD 12.14) familiarity with and opinions of these 7 guidelines using an online survey. Treatment providers were recruited using online advertisements that directed volunteers to a link to complete the survey, which was posted online for 6 months (January to June 2012). Primary study outcomes included quality scores and rates of guideline familiarity, guideline use, and discovery methods. RESULTS: Based on the AGREE II, the quality of CPGs varied considerably. Across different reporting domains, adherence to methodological standards ranged from 0% to 92%. Quality was lowest in the domains of rigor of development (50%), applicability (46%), and editorial independence (30%). Although examination of AGREE II domain scores demonstrated that the quality of the 7 guidelines could be divided into 3 categories (high quality, acceptable to low quality, and very low quality), review of treatment providers' quality perceptions indicated all guidelines fell into 1 category (acceptable quality). Based on treatment providers' familiarity with and usage rates of the CPGs, a combination of peer/colleagues, senior professionals, workshops, and Internet dissemination was deemed to be most effective for promoting cannabis use CPGs. Lack of time, guideline length, conflicts with theoretical orientation, and prior content knowledge were identified as barriers to guideline uptake. CONCLUSIONS: Developers of CPGs should improve their reporting of development processes, conflicts of interest, and CPGs' applicability to practice, while remaining cognizant that long guidelines may deter implementation. Treatment providers need to be aware that the quality of cannabis-related CPGs varies substantially.

eviQ cancer treatments online: how does the web-based protocol system fare in a comprehensive quality assessment?

AIMS: There have been few evaluations of the quality of computerized decision support tools in medical oncology despite their widespread use in clinical practice. In this article, we provide an in-depth quality assessment of eviQ, an Australian web-based protocol system. METHODS: We used the Appraisal of Guidelines for Research and Evaluation (AGREE-II) instrument to examine the quality of eviQ chemotherapy protocols across six domains: scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, editorial independence and overall quality rating. Domain scores were categorized as high quality (scores of >70%), moderate quality (30-70%), and low quality (<30%). RESULTS: eviQ was rated highly with respect to articulating its scope and purpose, clarity of presentation, applicability and on the overall rating item (scores of 72-80%). Domains addressing the involvement of stakeholders in the development process and the rigor with which protocols were developed were of moderate quality (scores of 34-37%) and the management of editorial independence and conflict of interest issues were rated in the low quality range (22%). CONCLUSION: Our evaluation demonstrated the eviQ protocol system is generally of high quality. However, we identified a number of areas in which eviQ could improve either its development processes or the means by which these processes are communicated to end-users. This research represents the first comprehensive evaluation of oncology protocols and paves the way for continued quality assurance research to ensure that these tools meet their objective of facilitating evidence-based medicine, standardizing treatment and, ultimately, improving patient outcomes.

Pharmacological enhancement of fear reduction: preclinical models.

Anxiety disorders have a high prevalence, and despite the substantial advances in the psychological treatment of anxiety, relapse is still a common problem. One approach to improving existing psychological treatments for anxiety has been to develop pharmacological agents that can be used to enhance the processes underlying exposure therapy, which is the most commonly used and empirically validated psychological treatment for anxiety during which individuals are taught to appropriately inhibit fear. Animal models of exposure therapy, particularly fear extinction, have proved to be a very useful way of examining the neural and molecular correlates of fear inhibition, which has in turn led to the identification of numerous drugs that enhance these processes in rats. Several of these drugs have subsequently been tested as novel pharmacological adjuncts to exposure therapy in humans with a range of anxiety disorders. The purpose of this review is to outline the key animal models of exposure therapy and to describe how these have been used to develop potential pharmacological adjuncts for anxiety disorders. Drugs that are currently in clinical use, as well as those currently in the preclinical stages of investigation, are described.

The effect of D-cycloserine on immediate vs. delayed extinction of learned fear.

We compared the effect of D-cycloserine (DCS) on immediate (10 min after conditioning) and delayed (24 h after conditioning) extinction of learned fear in rats. DCS facilitated both immediate and delayed extinction when the drug was administered after extinction training. However, DCS did not facilitate immediate extinction when administered prior to extinction training (i.e., when the interval between drug administration and shock was reduced). In addition, administering five, but not two, shocks prior to extinction training disrupted the facilitating effects of DCS on delayed extinction. These results suggest that aversive experiences prior to DCS administration can prevent it from facilitating extinction.

The temporal specificity of the switch from NMDAr-dependent extinction to NMDAr-independent re-extinction.

Recent findings show that the switch from NMDAr-dependent extinction to NMDAr-independent re-extinction is both context and stimulus specific. In this study we examined whether this switch was temporally specific as well. Re-extinction was found to be NMDAr-independent when it occurred 2 days after initial extinction but NMDAr-dependent when it occurred 21 days following initial extinction, thereby illustrating the importance of time as a type of context that modulates the mechanisms involved in extinction.

The role of context in the re-extinction of learned fear.

Extinction of learned fear is both amygdala- and NMDA receptor (NMDAr)-dependent. Recent studies, however, have shown that extinction the second time (re-extinction) does not involve the amygdala and is NMDAr-independent. The present study compared the effects of context change on extinction and re-extinction in adult Sprague-Dawley rats. Experiment 1 showed that both extinction and re-extinction are context-specific with a renewal effect occurring in both cases. Experiment 2 then examined whether the transition from an NMDAr-dependent to an NMDAr-independent process was context-specific. As expected, the results showed that MK-801 (0.1 mg/kg) impaired initial extinction but did not impair re-extinction (i.e., re-extinction was found to be NMDAr-independent). A novel finding was that if re-extinction occurred in a context different from initial extinction, then MK-801 impaired re-extinction. In other words, re-extinction is NMDAr-dependent (i.e., like initial extinction) when it occurs in a different context to initial extinction. Therefore, the switch from NMDAr-dependent to NMDAr-independent extinction is both stimulus [Langton, J.M., Richardson, R. (2008). D-cycloserine facilitates extinction the first time but not the second time: An examination of the role of NMDA across the course of repeated extinction sessions. Neuropsychopharmacology, 33, 3096-3102.] and context-specific (the present study). The precise conditions that govern whether extinction requires NMDAr activation are of considerable theoretical interest and remain to be fully characterized.