Ten most notable family medicine research studies in Canada

Objective

To identify 10 noteworthy Canadian family medicine research studies that have affected practice in order to demonstrate the unique value that Canadian family medicine research offers.

Composition of the committee

Representatives from the Section of Researchers (SOR) and the Health Policy and Government Relations department of the College of Family Physicians of Canada developed a framework for inclusion and identified an initial list of articles. Members of the SOR Council and research directors from the 17 Canadian departments of family medicine reviewed the preliminary list and suggested additional studies.

Methods

The authors developed an initial list of studies carried out by Canadian family medicine researchers from those researchers who had received awards from the College of Family Physicians of Canada since 2002. Additional studies were proposed by members of the SOR Council and the university research directors. A total of 36 published articles were reviewed by the SOR authors, and an annotated short list of 16 articles was prepared. From that list, the other authors identified 7 noteworthy studies that were used to form the basis of advocacy materials. The SOR authors, along with 3 additional members of the SOR Executive, used an informal consensus process to select the final 3 articles to arrive at the top 10.

Report

The top 10 most noteworthy family medicine research studies are presented in this article and represent the unique contribution that Canadian family medicine research brings to health care in Canada. They have helped advance health care quality and improve care delivery, beneficially influencing health care practices, health care policy, and patient experiences.

Conclusion

This project has identified 10 classic Canadian family medicine research studies that continue to influence practice today. In addition to their usefulness as tools for teaching, advocating, and championing the contribution of research to modern family practice, these studies are important examples of the value of research to patient health in Canada and around the world.     

Survivorship care in breast cancer: Perceptions of patients and primary care physicians

Objective

To compare the perceptions of breast cancer survivors and primary care physicians (PCPs) about PCPs’ ability to deliver survivorship care in breast cancer.

Design

Mailed survey.

Setting

British Columbia.

Participants

A total of 1065 breast cancer survivors who had completed treatment of nonmetastatic breast cancer within the previous year, and 587 PCPs who had patients with nonmetastatic breast cancer discharged to their care within the preceding 18 months.

Main outcome measures

Breast cancer survivors’ and PCPs’ confidence ratings of PCPs’ ability to deliver the following aspects of care: screening for recurrence; managing osteoporosis, lymphedema, endocrine therapy, menopausal symptoms, and anxiety about or fear of recurrence; and providing nutrition and exercise counseling, sex and body image counseling, and family counseling. Response options for each question included low, adequate, or good. Responses were summarized as frequencies and compared using χ² tests.

Results

Response rates for breast cancer survivors and PCPs were 47% and 59%, respectively. Responses were statistically different in all categories (P < .05). Both groups were most confident in the ability of PCPs to screen for recurrence, but breast cancer survivors were 10 times as likely to indicate low confidence (10% of breast cancer survivors vs 1% of PCPs) in this aspect of care. More breast cancer survivors (23%) expressed low confidence in PCPs’ ability to provide counseling about fear of recurrence compared with PCPs (3%). Aspects of care in which both breast cancer survivors and PCPs were most likely to express low confidence included sex and body image counseling (35% of breast cancer survivors vs 26% of PCPs) and family counseling (33% of breast cancer survivors vs 24% of PCPs). Primary care physicians (24%) described low confidence in their ability to manage lymphedema.

Conclusion

Breast cancer survivors and PCPs are reasonably confident in a PCP-based model of survivorship care. Primary care physicians are confident in their ability to manage physical effects related to breast cancer, with the exception of lymphedema. Low confidence ratings among both groups in psychosocial aspects of care suggest an area for improvement.     

Promoting the use of enduring powers of attorney in older adults: A literature review

This review aims to identify factors that facilitate the establishment of enduring powers of attorney (EPOAs), and those that create a barrier to their establishment. The primary aim was to provide guidance about how to encourage future planning while people are cognitively able to make such important decisions. A detailed search of the literature was conducted to identify research looking at the motivating factors behind putting future‐planning strategies in place. The literature highlighted a number of broad areas motivating the establishment of EPOAs, including: demographic factors; intrapersonal and personality factors; health and psychological factors; cognitive factors; and socio‐emotional factors. While a number of factors play a role in determining whether or not a person establishes an EPOA, the factor most malleable to change is the awareness and knowledge of older adults and their families regarding the utility of EPOAs.     

Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease.Motor neuron diseases (MNDs), including ALS and spastic paraplegia (SP), are characterized by the progressive, length-dependent degeneration of motor neurons, leading to muscle atrophy, paralysis, and, in some cases, premature death. There are both inherited and sporadic forms of MNDs, which can affect upper motor neurons, lower motor neurons, or both. Although the molecular and cellular causes of most MNDs are unknown, many are associated with defects in axonal transport of cellular components required for neuron function and maintenance (1–6).A subset of MNDs is associated with impaired mitochondrial respiration and mitochondrial distribution. This observation has led to the hypothesis that neurodegeneration results from defects in mitochondrial motility and distribution, which, in turn, cause subcellular ATP depletion and interfere with mitochondrial calcium ([Ca²⁺]_m) buffering at sites of high synaptic activity (reviewed in ref. 7). It is not known, however, whether mitochondrial motility defects are a primary cause or a secondary consequence of MND progression. In addition, it has been difficult to isolate the primary effect of mitochondrial motility defects in MNDs because most mutations that impair mitochondrial motility in neurons also affect transport of other organelles and vesicles (1, 8–11).In mammals, the movement of neuronal mitochondria between the cell body and the synapse is controlled by adaptors called trafficking kinesin proteins (Trak1 and Trak2) and molecular motors (kinesin heavy chain and dynein), which transport the organelle in the anterograde or retrograde direction along axonal microtubule tracks (7, 12–24). Mitochondrial Rho (Miro) GTPase proteins are critical for transport because they are the only known surface receptors that attach mitochondria to these adaptors and motors (12–15, 18, 25, 26). Miro proteins are tail-anchored in the outer mitochondrial membrane with two GTPase domains and two predicted calcium-binding embryonic fibroblast (EF) hand motifs facing the cytoplasm (12, 13, 25, 27, 28). A recent Miro structure revealed two additional EF hands that were not predicted from the primary sequence (29). Studies in cultured cells suggest that Miro proteins also function as calcium sensors (via their EF hands) to regulate kinesin-mediated mitochondrial “stopping” in axons (15, 16, 26). Miro-mediated movement appears to be inhibited when cytoplasmic calcium is elevated in active synapses, effectively recruiting mitochondria to regions where calcium buffering and energy are needed. Despite this progress, the physiological relevance of these findings has not yet been tested in a mammalian animal model. In addition, mammals ubiquitously express two Miro orthologs, Miro1 and Miro2, which are 60% identical (12, 13). However, the individual roles of Miro1 and Miro2 in neuronal development, maintenance, and survival have no been evaluated.We describe two new mouse models that establish the importance of Miro1-mediated mitochondrial motility and distribution in mammalian neuronal function and maintenance. We show that Miro1 is essential for development/maintenance of specific cranial neurons, function of postmitotic motor neurons, and retrograde mitochondrial motility in axons. Loss of Miro1-directed retrograde mitochondrial transport is sufficient to cause MND phenotypes in mice without abrogating mitochondrial respiratory function. Furthermore, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or [Ca²⁺]_m buffering. These findings have an impact on current models for Miro1 function and introduce a specific and rapidly progressing mouse model for MND.     

Variable temporoinsular cortex neuroanatomy in primates suggests a bottleneck effect in eastern gorillas

We describe an atypical neuroanatomical feature present in several primate species that involves a fusion between the temporal lobe (often including Heschl's gyrus in great apes) and the posterior dorsal insula, such that a portion of insular cortex forms an isolated pocket medial to the Sylvian fissure. We assessed the frequency of this fusion in 56 primate species (including apes, Old World monkeys, New World monkeys, and strepsirrhines) by using either magnetic resonance images or histological sections. A fusion between temporal cortex and posterior insula was present in 22 species (seven apes, two Old World monkeys, four New World monkeys, and nine strepsirrhines). The temporoinsular fusion was observed in most eastern gorilla (Gorilla beringei beringei and G. b. graueri) specimens (62% and 100% of cases, respectively) but was seen less frequently in other great apes and was never found in humans. We further explored the histology of this fusion in eastern gorillas by examining the cyto‐ and myeloarchitecture within this region and observed that the degree to which deep cortical layers and white matter are incorporated into the fusion varies among individuals within a species. We suggest that fusion between temporal and insular cortex is an example of a relatively rare neuroanatomical feature that has become more common in eastern gorillas, possibly as the result of a population bottleneck effect. Characterizing the phylogenetic distribution of this morphology highlights a derived feature of these great apes. J. Comp. Neurol. 522:844–860, 2014. © 2013 Wiley Periodicals, Inc.     

Target‐ and input‐dependent organization of AMPA and NMDA receptors in synaptic connections of the cochlear nucleus

We examined the synaptic structure, quantity, and distribution of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA)‐ and N‐methyl‐D‐aspartate (NMDA)‐type glutamate receptors (AMPARs and NMDARs, respectively) in rat cochlear nuclei by a highly sensitive freeze‐fracture replica labeling technique. Four excitatory synapses formed by two distinct inputs, auditory nerve (AN) and parallel fibers (PF), on different cell types were analyzed. These excitatory synapse types included AN synapses on bushy cells (AN‐BC synapses) and fusiform cells (AN‐FC synapses) and PF synapses on FC (PF‐FC synapses) and cartwheel cell spines (PF‐CwC synapses). Immunogold labeling revealed differences in synaptic structure as well as AMPAR and NMDAR number and/or density in both AN and PF synapses, indicating a target‐dependent organization. The immunogold receptor labeling also identified differences in the synaptic organization of FCs based on AN or PF connections, indicating an input‐dependent organization in FCs. Among the four excitatory synapse types, the AN‐BC synapses were the smallest and had the most densely packed intramembrane particles (IMPs), whereas the PF‐CwC synapses were the largest and had sparsely packed IMPs. All four synapse types showed positive correlations between the IMP‐cluster area and the AMPAR number, indicating a common intrasynapse‐type relationship for glutamatergic synapses. Immunogold particles for AMPARs were distributed over the entire area of individual AN synapses; PF synapses often showed synaptic areas devoid of labeling. The gold‐labeling for NMDARs occurred in a mosaic fashion, with less positive correlations between the IMP‐cluster area and the NMDAR number. Our observations reveal target‐ and input‐dependent features in the structure, number, and organization of AMPARs and NMDARs in AN and PF synapses. J. Comp. Neurol. 522:4023–4042, 2014. © 2014 Wiley Periodicals, Inc.