The Impact of Primary Care Clinic and Family Physician Continuity on Patient Health Outcomes: A Retrospective Analysis From Alberta, Canada.

Purpose: Continuity of care is broadly associated with better patient health outcomes. The relative contributions of continuity with an individual physician and with a practice, however, have not generally been distinguished. This retrospective observational study examined the impact of continuity of care for patients seen at their main clinic but by different family physicians.

"Navigating chaos": Urban, Rural, and Remote Patient Experiences in Accessing Healthcare with Indigenous and Non-Indigenous Perspectives of Living with Chronic Low Back Pain.

Background: Healthcare access for chronic low back pain is complex and should consider not only the health system, but patient care seeking experiences as well. People who live in rural and remote communities and/or identify as being Indigenous may often encounter additional barriers to accessing care for chronic low back pain; thus, these contexts must be considered to fully understand barriers and facilitators.

Aims: The aim of this study was to understand care-seeking experiences of people living with chronic back pain in Saskatchewan and determine unique experiences facing urban, rural, remote, and/or Indigenous peoples.

Family physician count and service provision in Ontario and Alberta between 2005/06 and 2017/18: a cross-sectional study.

Background: Five million Canadians lack a family doctor or primary care team. Our goal was to examine trends over time in family physician workforce and service provision in Ontario and Alberta, with a view to informing policy discussions on primary care supply and delivery of services.

Methods: We used cross-sectional analyses in Ontario and Alberta for 2005/06, 2012/13 and 2017/18 to examine family physician provision of service days by provider demographic characteristics and geographic location.

Healthcare Access Challenges and Facilitators for Back Pain Across the Rural-Urban Continuum in Saskatchewan, Canada: Cross-Sectional Results From a Provincial-Wide Telephone Survey.

Background: Chronic back pain is a common musculoskeletal disorder, disproportionately affecting rural and Indigenous people. Saskatchewan has a relatively high proportion of rural and Indigenous residents; therefore, understanding barriers and facilitators to accessing healthcare are needed to improve healthcare service delivery.

Methods: A provincial-wide telephone survey explored experiences and perceived healthcare access barriers and facilitators among 384 Saskatchewan residents who experienced chronic low back pain.

Magnetic resonance imaging detects white adipose tissue beiging in mice following PDE10A inhibitor treatment.

Weight gain is a common harmful side effect of atypical antipsychotics used for schizophrenia treatment. Conversely, treatment with the novel phosphodiesterase-10A (PDE10A) inhibitor MK-8189 in clinical trials led to significant weight reduction, especially in patients with obesity. This study aimed to understand and describe the mechanism underlying this observation, which is essential to guide clinical decisions.

Experiences of Health Care Access Challenges for Back Pain Care Across the Rural-Urban Continuum in Canada: Protocol for Cross-sectional Research.

Background: Back pain is common and costly, with negative impacts on both individuals and the health care system. Rural, remote, and Indigenous populations are at greater risk of experiencing back pain compared to urban and non-Indigenous populations. Potential barriers to health care access among Canadians with chronic back pain (CBP) have been identified; however, no study has used lived experiences of people with CBP to drive the selection, analysis, and interpretation of variables most meaningful to patients.

Leaving the Walkman and ICD-9 Behind: Modernizing the Disease Classification System Used by Canadian Physicians.

The International Classification of Diseases, Ninth Revision (ICD-9) was released in the 1970s and adopted in Canada for physician billing claims in 1979 (CIHI n.d.b.

Rural-Urban Disparities in Realized Spatial Access to General Practitioners, Orthopedic Surgeons, and Physiotherapists among People with Osteoarthritis in Alberta, Canada.

Rural Canadians have high health care needs due to high prevalence of osteoarthritis (OA) but lack access to care. Examining realized access to three types of providers (general practitioners (GPs), orthopedic surgeons (Ortho), and physiotherapists (PTs)) simultaneously helps identify gaps in access to needed OA care, inform accessibility assessment, and support health care resource allocation. Travel time from a patient's postal code to the physician's postal code was calculated using origin-destination network analysis.

Rural-Urban Differences in Non-Local Primary Care Utilization among People with Osteoarthritis: The Role of Area-Level Factors.

The utilization of non-local primary care physicians (PCP) is a key primary care indicator identified by Alberta Health to support evidence-based healthcare planning. This study aims to identify area-level factors that are significantly associated with non-local PCP utilization and to examine if these associations vary between rural and urban areas. We examined rural-urban differences in the associations between non-local PCP utilization and area-level factors using multivariate linear regression and geographically weighted regression (GWR) models.

Structures of active-state orexin receptor 2 rationalize peptide and small-molecule agonist recognition and receptor activation.

Narcolepsy type 1 (NT1) is a chronic neurological disorder that impairs the brain's ability to control sleep-wake cycles. Current therapies are limited to the management of symptoms with modest effectiveness and substantial adverse effects. Agonists of the orexin receptor 2 (OXR) have shown promise as novel therapeutics that directly target the pathophysiology of the disease.

Calculating physician supply using a service day method and the income percentiles method: a descriptive analysis.

Background: It is important to have an accurate count of physicians and a measurable understanding of their service provision for physician resource planning. Our objective was to compare 2 methods (income percentiles [IP] and service day activities [SVD]) for calculating the supply of full-time (FT) and part-time (PT) primary care physicians (PCPs) as measures of both physician supply counts and level of provider continuity.

Methods: Using an observational study design, we compared 2 methods of calculating the supply of PT and FT PCPs for 2011-2015.

Geospatial patterns of comorbidity prevalence among people with osteoarthritis in Alberta Canada.

Background: Knowledge of geospatial pattern in comorbidities prevalence is critical to an understanding of the local health needs among people with osteoarthritis (OA). It provides valuable information for targeting optimal OA treatment and management at the local level. However, there is, at present, limited evidence about the geospatial pattern of comorbidity prevalence in Alberta, Canada.

High-volume general practitioners in Alberta: a descriptive analysis.

Background: Alberta is considering capping daily fee-for-service physician billings, but little is known about high-volume practice in the province and its impact on patient health outcomes. In this initial study, we conducted a descriptive analysis of general practitioners' patient volumes and billing practices in relation to associated practitioner demographic characteristics.

Methods: We conducted a retrospective descriptive analysis of the associations of practitioner characteristics, including full-time versus non-full-time practice, provider sex, years in practice, geographic location and international medical graduate status, with high-volume (> 50 visits/d) practice using general practice billing data from 2011 to 2016.

Discovery of highly potent and selective orexin 1 receptor antagonists (1-SORAs) suitable for in vivo interrogation of orexin 1 receptor pharmacology.

While a correlation between blockade of the orexin 2 receptor (OXR) with either a dual orexin receptor antagonist (DORA) or a selective orexin 2 receptor antagonist (2-SORA) and a decrease of wakefulness is well established, less is known about selective blockade of the orexin 1 receptor (OXR). Therefore, a highly selective orexin 1 antagonist (1-SORA) with suitable properties to allow in vivo interrogation of OXR specific pharmacology in preclinical species remains an attractive target. Herein, we describe the discovery of an optimized 1-SORA series in the piperidine ether class.

Pharmacological evaluation of orexin receptor antagonists in preclinical animal models of pain.

Orexin signaling, known to modulate arousal and vigilance, is also involved in nociception as orexin neurons project to regions of the brain and spinal cord involved in pain processing, and the administration of orexin peptides can alter pain response in a wide range of preclinical models. Pharmacological treatment with the potent, selective and structurally distinct dual orexin receptor antagonists (ORAs) DORA-12 and DORA-2 significantly reduced pain responses during both phases I and II of the mouse formalin pain model and significantly reversed hyperalgesia in the rat complete Freund's adjuvant pain model, respectively. Significant antinociceptive effects of DORA-12 in the formalin model were also observed in orexin 1 receptor (OX1R) knockout mice, but not orexin 2 receptor (OX2R) or OX1R/OX2R double knockout mice.

Differential sleep-promoting effects of dual orexin receptor antagonists and GABAA receptor modulators.

Background: The current standard of care for insomnia includes gamma-aminobutyric acid receptor A (GABAA) activators, which promote sleep as well as general central nervous system depression. Dual orexin receptor antagonists (DORAs) represent an alternative mechanism for insomnia treatment that induces somnolence by blocking the wake-promoting effects of orexin neuropeptides. The current study compares the role and interdependence of these two mechanisms on their ability to influence sleep architecture and quantitative electroencephalography (qEEG) spectral profiles across preclinical species.

Dual orexin receptor antagonists show distinct effects on locomotor performance, ethanol interaction and sleep architecture relative to gamma-aminobutyric acid-A receptor modulators.

Dual orexin receptor antagonists (DORAs) are a potential treatment for insomnia that function by blocking both the orexin 1 and orexin 2 receptors. The objective of the current study was to further confirm the impact of therapeutic mechanisms targeting insomnia on locomotor coordination and ethanol interaction using DORAs and gamma-aminobutyric acid (GABA)-A receptor modulators of distinct chemical structure and pharmacological properties in the context of sleep-promoting potential. The current study compared rat motor co-ordination after administration of DORAs, DORA-12 and almorexant, and GABA-A receptor modulators, zolpidem, eszopiclone, and diazepam, alone or each in combination with ethanol.

The duration of sleep promoting efficacy by dual orexin receptor antagonists is dependent upon receptor occupancy threshold.

Background: Drugs targeting insomnia ideally promote sleep throughout the night, maintain normal sleep architecture, and are devoid of residual effects associated with morning sedation. These features of an ideal compound are not only dependent upon pharmacokinetics, receptor binding kinetics, potency and pharmacodynamic activity, but also upon a compound's mechanism of action.

Results: Dual orexin receptor antagonists (DORAs) block the arousal-promoting activity of orexin peptides and, as demonstrated in the current work, exhibit an efficacy signal window dependent upon oscillating levels of endogenous orexin neuropeptide.

Quantitative electroencephalography within sleep/wake states differentiates GABAA modulators eszopiclone and zolpidem from dual orexin receptor antagonists in rats.

Dual orexin receptor antagonists (DORAs) induce sleep by blocking orexin 1 and orexin 2 receptor-mediated activities responsible for regulating wakefulness. DORAs represent a potential alternative mechanism to the current standard of care that includes the γ-aminobutyric acid (GABA)A receptor-positive allosteric modulators, eszopiclone and zolpidem. This work uses an innovative method to analyze electroencephalogram (EEG) spectral frequencies within sleep/wake states to differentiate the effects of GABAA modulators from DORA-22, an analog of the DORA MK-6096, in Sprague-Dawley rats.

Orexin receptor antagonists differ from standard sleep drugs by promoting sleep at doses that do not disrupt cognition.

Current treatments for insomnia, such as zolpidem (Ambien) and eszopiclone (Lunesta), are γ-aminobutyric acid type A (GABAA)-positive allosteric modulators that carry a number of side effects including the potential to disrupt cognition. In an effort to develop better tolerated medicines, we have identified dual orexin 1 and 2 receptor antagonists (DORAs), which promote sleep in preclinical animal models and humans. We compare the effects of orally administered eszopiclone, zolpidem, and diazepam to the dual orexin receptor antagonist DORA-22 on sleep and the novel object recognition test in rat, and on sleep and two cognition tests (delayed match to sample and serial choice reaction time) in the rhesus monkey.

Discovery of 3-substituted aminocyclopentanes as potent and orally bioavailable NR2B subtype-selective NMDA antagonists.

A series of 3-substituted aminocyclopentanes has been identified as highly potent and selective NR2B receptor antagonists. Incorporation of a 1,2,4-oxadiazole linker and substitution of the pendant phenyl ring led to the discovery of orally bioavailable analogues that showed efficient NR2B receptor occupancy in rats. Unlike nonselective NMDA antagonists, the NR2B-selective antagonist 22 showed no adverse affects on motor coordination in the rotarod assay at high dose.

Design, synthesis, and evaluation of novel 3,6-diaryl-4-aminoalkoxyquinolines as selective agonists of somatostatin receptor subtype 2.

Agonists of somatostatin receptor subtype 2 (sst(2)) have been proposed as therapeutics for the treatment of proliferative diabetic retinopathy and exudative age-related macular degeneration. An HTS screen identified 2-quinolones as weak agonists of sst(2), and these were optimized to provide small molecules with sst(2) binding and functional potency comparable to peptide agonists. Agonist 21 was shown to inhibit rat growth hormone secretion following systemic administration and to inhibit ocular neovascular lesion formation after local administration.

Allosteric modulation of group III metabotropic glutamate receptor 4: a potential approach to Parkinson's disease treatment.

Parkinson's disease (PD) is a debilitating movement disorder that afflicts >1 million people in North America. Current treatments focused on dopamine-replacement strategies ultimately fail in most patients because of loss of efficacy and severe adverse effects that worsen as the disease progresses. The recent success of surgical approaches suggests that a pharmacological intervention that bypasses the dopamine system and restores balance in the basal ganglia motor circuit may provide an effective treatment strategy.