Storylines of family medicine IV: perspectives on practice-lenses of appreciation.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'IV: perspectives on practice-lenses of appreciation', authors address the following themes: 'Relational connections in the doctor-patient partnership', 'Feminism and family medicine', 'Positive family medicine', 'Mindful practice', 'The new, old ethics of family medicine', 'Public health, prevention and populations', 'Information mastery in family medicine' and 'Clinical courage.' May readers nurture their curiosity through these essays.

What is the Long-term Wear of a 5-Mrad Highly Crosslinked Polyethylene Liner? A 14-year RSA Study.

BACKGROUND: Lower doses of irradiation (≤ 5 Mrad) during the manufacture of highly crosslinked polyethylene acetabular liners may result in less crosslinking and an increased wear rate. Radiostereometric analysis (RSA) studies have found that wear of more highly irradiated highly crosslinked polyethylene liners (7 to 10 Mrad) decreases at longer-term follow-up compared with earlier reports of the same cohorts. Although wear of 5-Mrad irradiated liners appears to increase at midterm follow-up, it is unclear whether that remains true at longer follow-up. QUESTIONS/PURPOSES: We asked: (1) In patients who underwent THA with a 5-Mrad highly crosslinked polyethylene liner, what is the wear rate evaluated with RSA during the first 14 years? (2) Does the wear rate decrease after 6 years in situ? METHODS: This is a brief follow-up of prior RSA studies performed at 2 and 6 years. We prospectively reviewed the longer-term wear rate in 13 patients who underwent primary THAs with the same design of a 5-MRad irradiated crosslinked acetabular liner and a 28-mm cobalt-chromium articulation. Of the initial 30 patients who were enrolled, 13 (43%) were available at the 14-year timepoint; nine patients had died, 1 patient had withdrawn, 1 had an intraoperative fracture, 3 patients were too infirm to have radiographs, 2 had no baseline RSA radiographs, and 1 had poor-quality RSA images. Tantalum markers were inserted during surgery, and all patients had RSA radiographic examinations at 1 week, 6 months, and 1, 2, 6, and 14 years postoperatively. RESULTS: The mean ± standard deviation proximal, 2D, and 3D wear rates calculated between 1 year and 14 years were 0.019 ± 0.013 mm, 0.022 ± 0.015 mm, and 0.025 ± 0.019 mm per year, respectively. No patient had proximal 2D or 3D wear rates exceeding 0.06 mm per year. An increasing wear rate over time was measured for proximal and 2D wear rates between 6 and 14 years (0.024 and 0.030 mm per year) compared with that between 1 and 6 years (0.008 and 0.010 mm per year; p = 0.03). CONCLUSION: The proximal, 2D, and 3D wear of a highly crosslinked polyethylene liner produced using 5-Mrad radiation remains low in the longer-term. With the small numbers available in a long-term RSA study such as this, we confirmed that the wear rate did not decrease at longer-term follow-up, unlike previous RSA studies of more highly irradiated highly crosslinked polyethylene liners. Nevertheless, the wear rate remains very low and below the threshold typically associated with the development of osteolysis (0.1 mm/year of wear). This should provide assurance to orthopaedic surgeons monitoring patients with this 5-Mrad irradiated liner in situ, while providing useful information to manufacturers of future highly crosslinked polyethylene liners. LEVEL OF EVIDENCE: Level IV therapeutic study.

Large articulations do not increase wear rates of thin second-generation highly cross-linked polyethylene liners at ten years.

Aims: Radiostereometric analysis (RSA) is the most accurate radiological method to measure in vivo wear of highly cross-linked polyethylene (XLPE) acetabular components. We have previously reported very low wear rates for a sequentially irradiated and annealed X3 XLPE liner (Stryker Orthopaedics, USA) when used in conjunction with a 32 mm femoral heads at ten-year follow-up. Only two studies have reported the long-term wear rate of X3 liners used in conjunction with larger heads using plain radiographs which have poor sensitivity. The aim of this study was to measure the ten-year wear of thin X3 XLPE liners against larger 36 or 40 mm articulations with RSA. Methods: We prospectively reviewed 19 patients who underwent primary cementless THA with the XLPE acetabular liner (X3) and a 36 or 40 mm femoral head with a resultant liner thickness of at least 5.8 mm. RSA radiographs at one week, six months, and one, two, five, and ten years postoperatively and femoral head penetration within the acetabular component were measured with UmRSA software. Of the initial 19 patients, 12 were available at the ten-year time point. Results: The median proximal, 2D, and 3D wear rates calculated between one and ten years were all less than 0.005 mm/year, with no patient recording a proximal wear rate of more than 0.021 mm/year. Importantly, there was no increase in the wear rate between five and ten years. Conclusion: The very low wear rate of X3 XLPE liners with larger articulations remains encouraging for the future clinical performance of this material.

Developing conceptually sound items for a clinical courage questionnaire.

INTRODUCTION: Clinical courage can be described as a rural doctor's adaptability and willingness to undertake clinical work at the limits of their training and experience to meet the needs of their patients. This article describes the in-house development of survey items to include in a quantitative measure of clinical courage. METHODS: The questionnaire development involved two key concepts: a second-order latent factor model structure and a nominal group technique, used to develop consensus among the research team members. RESULTS: The steps taken to develop a sound clinical courage questionnaire are described in detail. The resulting initial questionnaire is presented, ready for testing with rural clinicians and refinement. CONCLUSION: This article outlines the psychometric process of questionnaire design and presents the resultant clinical courage questionnaire.

Perception of Perioperative Risk for Arthroplasty Patients: A Poll of Australian Orthopedic Surgeons.

BACKGROUND: There is growing interest in the perioperative management of patients who have indications for hip and knee arthroplasty in the setting of modifiable risk factors such as morbid obesity, poorly controlled diabetes, and smoking. A recent survey of the American Association of Hip and Knee Surgeons (AAHKS) found that 95% of respondents address modifiable risk factors prior to surgery. The aim of this study was to poll Australian arthroplasty surgeons regarding their approach to patients who have modifiable risk factors. METHODS: The survey tool used in the AAHKS study was adapted for use in the Australian context and distributed to the membership of the Arthroplasty Society of Australia via SurveyMonkey. There were 77 responses received, representing a response rate of 64%. RESULTS: The majority of respondents were experienced, high volume arthroplasty surgeons. Overall, 91% of respondents restricted access to arthroplasty for patients who have modifiable risk factors. There were 72% restricting access for excessive body mass index, 85% for poor diabetic control, and 46% for smoking. Most respondents made decisions based on personal experience or literature review rather than hospital or departmental pressures. While 49% of surgeons believed that current payment systems did not impair their ability to achieve good outcomes, 58% believed that certain arthroplasty patients would benefit from additional intervention, based on their socioeconomic status. CONCLUSION: Over 90% of surgeons who responded address modifiable risk factors prior to surgery. This finding aligns with the practice patterns of AAHKS members, despite differences in healthcare systems.

Perception of Perioperative Risk for Arthroplasty Patients: A Poll of Indian Orthopedic Surgeons.

BACKGROUND: A survey of the American Association of Hip and Knee Surgeons (AAHKS) reported that 95% of respondents attempted to modify risk factors prior to arthroplasty. This study investigated Indian arthroplasty surgeons' approach to patients who have modifiable risk factors. METHODS: The AAHKS survey tool was adapted for Indian surgeons and distributed to the membership of the Indian Society of Hip and Knee Surgeons and Indian Arthroplasty Association via a Survey Monkey. A total of 92 survey responses were received, representing a response rate of 12%. RESULTS: Overall, 87% of respondents restricted access to arthroplasty surgery for patients who have modifiable risk factors, but only 51% of respondents reported delays or restricted treatment because of risk factors. Respondents reported that financial implications were more likely to delay or restrict treatment in 97% and social/family reasons in 66%. Poor diabetic control (81%), previous infection (57%), and malnutrition/hypoalbuminemia (47%) were the most frequent modifiable risk factors. There were 82% of surgeons reporting that the patient's socioeconomic status influenced treatment including: 71% of patients who have low socioeconomic status, 57% who do not have insurance, and 45% who have limited social supports. Most surgeons (92%) reported that funding influenced the type of care provided and the choice of implants. CONCLUSION: Over 97% of Indian arthroplasty surgeons thought socioeconomic factors impaired access to orthopaedic treatment. Only half the surgeons restricted access for comorbidities and these were more often related to infection risks and diabetes. These findings contrast dramatically to the practice patterns of American AAHKS members.

A desirability of outcome ranking (DOOR) for periprosthetic joint infection - a Delphi analysis.

Background: Treatment outcomes in studies on prosthetic joint infection are generally assessed using a dichotomous outcome relating to treatment success or failure. These outcome measures neither include patient-centred outcome measures including joint function and quality of life, nor do they account for adverse effects of treatment. A desirability of outcome ranking (DOOR) measure can include these factors and has previously been proposed and validated for other serious infections. We aimed to develop a novel DOOR for prosthetic joint infections (PJIs). Methods: The Delphi method was used to develop a DOOR for PJI research. An international working group of 18 clinicians (orthopaedic surgeons and infectious disease specialists) completed the Delphi process. The final DOOR comprised the dimensions established to be most important by consensus with > 75  % of participant agreement. Results: The consensus DOOR comprised four main dimensions. The primary dimension was patient-reported joint function. The secondary dimensions were infection cure and mortality. The final dimension of quality of life was selected as a tie-breaker. Discussion: A desirability of outcome ranking for periprosthetic joint infection has been proposed. It focuses on patient-centric outcome measures of joint function, cure and quality of life. This DOOR provides a multidimensional assessment to comprehensively rank outcomes when comparing treatments for prosthetic joint infection.

Differential roles and regulation of the protein kinases PAK4, PAK5 and PAK6 in melanoma cells.

The protein kinases PAK4, PAK5 and PAK6 comprise a family of ohnologues. In multiple cancers including melanomas PAK5 most frequently carries non-synonymous mutations; PAK6 and PAK4 have fewer; and PAK4 is often amplified. To help interpret these genomic data, initially we compared the cellular regulation of the sister kinases and their roles in melanoma cells. In common with many ohnologue protein kinases, PAK4, PAK5 and PAK6 each have two 14-3-3-binding phosphosites of which phosphoSer99 is conserved. PAK4 localises to the leading edge of cells in response to phorbol ester-stimulated binding of 14-3-3 to phosphoSer99 and phosphoSer181, which are phosphorylated by two different PKCs or PKDs. These phosphorylations of PAK4 are essential for its phorbol ester-stimulated phosphorylation of downstream substrates. In contrast, 14-3-3 interacts with PAK5 in response to phorbol ester-stimulated phosphorylation of Ser99 and epidermal growth factor-stimulated phosphorylation of Ser288; whereas PAK6 docks onto 14-3-3 and is prevented from localising to cell-cell junctions when Ser133 is phosphorylated in response to cAMP-elevating agents via PKA and insulin-like growth factor 1 via PKB/Akt. Silencing of PAK4 impairs viability, migration and invasive behaviour of melanoma cells carrying BRAFV600E or NRASQ61K mutations. These defects are rescued by ectopic expression of PAK4, more so by a 14-3-3-binding deficient PAK4, and barely by PAK5 or PAK6. Together these genomic, biochemical and cellular data suggest that the oncogenic properties of PAK4 are regulated by PKC-PKD signalling in melanoma, while PAK5 and PAK6 are dispensable in this cancer.

Highly Crosslinked Polyethylene Liners Have Negligible Wear at 10 Years: A Radiostereometric Analysis Study.

BACKGROUND: The introduction of crosslinked ultra-high molecular weight polyethylene (XLPE) acetabular liners has been very successful, with decreased wear and reduction in the rates of revision hip arthroplasties. XLPE is the preferred articulation for most surgeons; however, there are concerns about the long-term performance of XLPE liners created with different manufacturing processes, which may lead to time-dependent failure, including accelerated wear, after several years. QUESTIONS/PURPOSES: (1) What is the amount and rate of wear during the first 10 years using radiostereometric analysis (RSA) measurements of patients who had THAs that included a second-generation XLPE bearing? (2) Does the rate of wear change after 5 years in situ? METHODS: This is a brief follow-up of a previous RSA study. In that study, we prospectively enrolled 21 patients with osteoarthritis who underwent primary cementless THA with an XLPE acetabular liner (three cycles of 3Mrad annealed) and 32-mm articulation. That group represented 44% of the 48 THAs performed by the surgeon at the hospital where RSA was available; 16 had cemented hips, leaving 32 who were invited to participate in this study. Of those, 11 lived rurally and declined to participate, leaving 21 patients who were included in the initial study. Since then, three patients died, one developed dementia and could not participate, and one had revision THA for reasons other than wear, leaving 16 patients available for analysis at 10 years. Tantalum markers were inserted during surgery, and all patients had RSA radiographs taken at 1 week, 6 months, and 1, 2, 5, and 10 years postoperatively. Femoral head penetration into the acetabular component was measured with RSA, including bedding-in during the first year and annual wear thereafter. RESULTS: The median medial, proximal, anterior, two-dimensional (2D), and three-dimensional (3D) wear rates between 1 and 10 years were -0.001, 0.004, -0.012, 0.000, and 0.002 mm/year, respectively. No patient in this cohort had a proximal or 2D wear rate greater than 0.025 mm/year. The median proximal wear rate between 5 and 10 years (0.002 mm/year) was not greater than wear at 1 to 5 years (0.004 mm/year). CONCLUSION: Femoral head penetration in this second-generation XLPE liner remained very low at 10 years and accelerated wear after 5 years in situ did not occur. Concerns about late-onset wear from oxidation of irradiated-annealed XLPE were not observed. The low level of wear remains encouraging for the future clinical performance of this material. LEVEL OF EVIDENCE: Level II, therapeutic study.

Primary Total Knee Arthroplasty Revised for Instability: A Detailed Registry Analysis.

BACKGROUND: Instability after total knee arthroplasty is a common but poorly understood complication. METHODS: Data from a large national registry was used to study patient and prosthesis characteristics of 2605 total knee arthroplasty revisions for instability. The cumulative percent revision was calculated using Kaplan-Meier estimates, and Cox proportional models used to compare revision rates. The rate of further revision was analyzed with regard to prostheses used in the first revision. RESULTS: Instability increased from 6% of all first revision procedures in 2003 to 13% in 2019. The revision risk was lower for minimally stabilized prostheses, males, and patients aged ≥65 years. Polyethylene insert exchange was used for 55% of revision procedures, using a thicker insert in 93% and a change in insert conformity in 24% of cruciate-retaining knees. The increase in either thickness or conformity had no effect on the rate of further revision. After a revision for instability, 24% had a second revision by 14 years. Recurrent instability accounted for 32% of further revisions. A lower second revision rate was seen after revision of both femoral and tibial components, and where constrained components were used. CONCLUSION: Revision for instability is increasing. Revising both femoral and tibial components led to a lower rate of second revision compared to a change in insert alone. Recurrent instability was common.

The impact of interpersonal relationships on rural doctors' clinical courage.

INTRODUCTION: Clinical courage occurs when rural doctors push themselves to the limits of their scope of practice to provide the medical care needed by patients in their community. This mental strength to venture, persevere and act out of concern for one's patient, despite a lack of formally recognised expertise, becomes necessary for doctors who work in relative professional isolation. Previous research by the authors suggested that the clinical courage of rural doctors relies on the relationships around them. This article explores in more depth how relationships with others can impact on clinical courage. METHODS: At an international rural medicine conference in 2017, doctors who practised rural/remote medicine were invited to participate in the study. Twenty-seven semistructured interviews were conducted exploring experiences of clinical courage. Initial analysis of the material, using a hermeneutic phenomenological frame, sought to understand the meaning of clinical courage. In the original analysis, an emic question arose: 'How do interpersonal relationships impact on clinical courage'. The material was re-analysed to explore this question, using Wenger's community of practice as a theoretical framework. RESULTS: This study found that clinical courage was affected by the relationships rural doctors had with their communities and patients, with each other, with the local members of their healthcare team and with other colleagues and health leaders outside their immediate community of practice. CONCLUSION: As a collective, rural doctors can learn, use and strengthen clinical courage and support its development in new members of the discipline. Relationships with rural communities, rural patients and urban colleagues can support the clinical courage of rural doctors. When detractors challenge the value of clinical courage, it requires individual rural doctors and their community of practice to champion rural doctors' way of working.

Acetabular screws do not improve early revision rates in primary total hip arthroplasty. An instrumented registry analysis.

BACKGROUND: Initial stability of uncemented acetabular components in total hip arthroplasty (THA) is important for osseointegration and potentially enhanced by screw fixation. We used Australian Orthopaedic Association National Joint Replacement Registry data to determine whether screw usage influences uncemented acetabular component survival. METHODS: Primary THA with uncemented acetabular components performed for osteoarthritis from 1999 to 2018 was included. Survivorship was calculated using Kaplan-Meier estimates of cumulative percent revision (CPR). Comparisons used Cox proportional hazards method. An instrumental variable analysis adjusted for surgeon preference for screws as a confounding factor was used. RESULTS: Three hundred thirty thousand one hundred ninety-two THAs were included (31.8% with screws, 68.2% without). Two hundred twenty thousand six hundred seven were included in the instrumental variable analysis. Revision rate of acetabular components (all causes) was higher with screws during the first six years (hazard ratio (HR) = 1.45 (95% CI 1.34, 1.57), p < 0.001) and lower thereafter (HR = 0.81 (95% CI 0.67, 0.98), p = 0.027). Revision rate of acetabular components for loosening was higher with screws over the entire study period (HR = 1.73 (95% CI 1.51, 1.98), p < 0.001). Overall THA revision rate was higher with screws during the first six years (HR = 1.20 (95% CI 1.15, 1.26), p < 0.001) but lower thereafter (HR = 0.89 (95% CI 0.81, 0.98), p = 0.020). Revision rate for dislocation was higher with screws over the entire period (HR = 1.16 (95% CI 1.06, 1.26), p < 0.001). Instrumental variable analysis revealed higher revision rates with acetabular screws in the first six years. (HR = 1.18 (95% CI 1.09-1.29), p < 0.001). CONCLUSION: Screws did not confer a protective effect against acetabular loosening and were not associated with long-term negative consequences.

A PKB-SPEG signaling nexus links insulin resistance with diabetic cardiomyopathy by regulating calcium homeostasis.

Diabetic cardiomyopathy is a progressive disease in diabetic patients, and myocardial insulin resistance contributes to its pathogenesis through incompletely-defined mechanisms. Striated muscle preferentially expressed protein kinase (SPEG) has two kinase-domains and is a critical cardiac regulator. Here we show that SPEG is phosphorylated on Ser2461/Ser2462/Thr2463 by protein kinase B (PKB) in response to insulin. PKB-mediated phosphorylation of SPEG activates its second kinase-domain, which in turn phosphorylates sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a (SERCA2a) and accelerates calcium re-uptake into the SR. Cardiac-specific deletion of PKBα/ß or a high fat diet inhibits insulin-induced phosphorylation of SPEG and SERCA2a, prolongs SR re-uptake of calcium, and impairs cardiac function. Mice bearing a Speg3A mutation to prevent its phosphorylation by PKB display cardiac dysfunction. Importantly, the Speg3A mutation impairs SERCA2a phosphorylation and calcium re-uptake into the SR. Collectively, these data demonstrate that insulin resistance impairs this PKB-SPEG-SERCA2a signal axis, which contributes to the development of diabetic cardiomyopathy.

Does Knee Prosthesis Survivorship Improve When Implant Designs Change? Findings from the Australian Orthopaedic Association National Joint Replacement Registry.

BACKGROUND: TKA generally has excellent long-term survivorship. When a new knee system supersedes a previous model, increased survivorship, improved functional performance, or both may be expected, because key areas of design modification are often targeted to address wear, stability, and the patellofemoral articulation. However, not all design changes are beneficial, and to our knowledge, knee arthroplasty has not been systematically evaluated in the context of design changes that occur during the development of new knee arthroplasty systems. QUESTIONS/PURPOSES: Using the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) we performed multiple old-to-new comparisons of frequently used contemporary knee implants to ask: (1) does overall prosthesis survivorship free from revision increase when a new knee prosthesis system is introduced to replace a prior prosthesis system? (2) Has survivorship free from revision improved for the revision indications of wear, instability, and patellofemoral articulation issues, where development efforts have been concentrated? METHODS: Data from the AOANJRR from September 1999 to December 2017 were used to compare the survivorship of prostheses free from revision at a maximum of 17 years in procedures where a new design model was introduced to replace a prior knee system from the same manufacturer. Only prosthesis systems used in a minimum of 2000 primary TKA procedures for osteoarthritis that had a minimum of 5 years of follow-up were included. Varus-valgus constrained and hinge TKA designs were excluded. Cruciate-retaining, posterior-stabilized, and medial pivot-design knees were considered separately. The new and old prosthesis systems were paired for analysis. Survivorship was calculated with Kaplan Meier estimates and comparisons were performed using the Cox proportional hazards method. Subanalyses according to the three main revision indications were performed, and where possible, analyses were performed based on polyethylene types (highly cross-linked polyethylene and ultra-high-molecular-weight polyethylene), combined and separated. Revision was defined as a reoperation of a previous knee arthroplasty in which one or more of the components was removed, replaced, or added. There were 323,955 TKA procedures and 11 new prosthesis system designs that were introduced to replace an earlier knee system from the same manufacturer. Of these prosthesis system pairs, six were cruciate-retaining prostheses, four were posterior-stabilized designs, and one was a medial pivot design. RESULTS: Six of the 11 knee system pairs showed improved survivorship with the new design, three were no different, and in two, the newer prosthesis systems had a higher rate of revision than the old one did. When revision for wear was analyzed, five prosthesis systems showed improvement, five were no different, and one had a higher rate of revision than the previous system did. There was no improvement in the rate of revision for instability; seven new prosthesis systems showed no difference from the previous system and four new prosthesis systems had a higher rate of revision than the previous system did. A subanalysis of revision for patellofemoral complications showed improvement in two comparisons, no difference in six, and a higher revision rate in two; one could not be calculated because of an insufficient number of revisions for this reason. CONCLUSIONS: It is difficult to predict whether a new system will demonstrate better survival than a previous one, and widespread uptake of a new design before a benefit is shown in robust clinical studies is unwise. Similarly, adoption of a new system for which there is no difference in survivorship from a previous model may be premature because a new device may have associated unknown and unintended consequences. Healthcare policy makers and therapeutic device regulators should similarly be guided by results and seek out peer-reviewed evidence before accepting change to established practice. Surgeons must be aware that implant changes may not translate into better survivorship and must seek compelling evidence of improvement in survival and/or function before changing systems. LEVEL OF EVIDENCE: Level III, therapeutic study.

Human osteocyte expression of Nerve Growth Factor: The effect of Pentosan Polysulphate Sodium (PPS) and implications for pain associated with knee osteoarthritis.

Pentosan polysulphate sodium (PPS) is a promising therapeutic agent for blocking knee pain in individuals with knee osteoarthritis (KOA). The mode of action of PPS in this context is unknown. We hypothesised that the osteocyte, being the principal cell type in the sub-chondral bone, was capable of expressing the pain mediator Nerve Growth Factor (NGF), and that this may be altered in the presence of PPS. We tested the expression of NGF and the response to PPS in the presence or absence of the proinflammatory cytokine tumour necrosis factor-alpha (TNFα), in human osteocytes. For this we differentiated human primary osteoblasts grown from subchondral bone obtained at primary knee arthroplasty for KOA to an osteocyte-like stage over 28d. We also tested NGF expression in fresh osteocytes obtained by sequential digestion from KOA bone and by immunofluorescence in KOA bone sections. We demonstrate for the first time the production and secretion of NGF/proNGF by this cell type derived from patients with KOA, implicating osteocytes in the pain response in this pathological condition and possibly others. PPS inhibited TNFα-induced levels of proNGF secretion and TNFα induced NGF mRNA expression. Together, this provides evidence that PPS may act to suppress the release of NGF in the subchondral bone to ameliorate pain associated with knee osteoarthritis.

FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning.

The concerted action of many protein kinases helps orchestrate the error-free progression through mitosis of mammalian cells. The roles and regulation of some prominent mitotic kinases, such as cyclin-dependent kinases, are well established. However, these and other known mitotic kinases alone cannot account for the extent of protein phosphorylation that has been reported during mammalian mitosis. Here we demonstrate that CK1α, of the casein kinase 1 family of protein kinases, localises to the spindle and is required for proper spindle positioning and timely cell division. CK1α is recruited to the spindle by FAM83D, and cells devoid of FAM83D, or those harbouring CK1α-binding-deficient FAM83DF283A/F283A knockin mutations, display pronounced spindle positioning defects, and a prolonged mitosis. Restoring FAM83D at the endogenous locus in FAM83D-/- cells, or artificially delivering CK1α to the spindle in FAM83DF283A/F283A cells, rescues these defects. These findings implicate CK1α as new mitotic kinase that orchestrates the kinetics and orientation of cell division.

Outcomes of a 1-year longitudinal integrated medical clerkship in small rural Victorian communities.

INTRODUCTION: Access to medical services for rural communities is poorer than for metropolitan communities in many parts of the world. One of the strategies to improve rural medical workforce has been rural clinical placements for undergraduate medical students. This study explores the workforce outcomes of one model of such placements - the longitudinal integrated clerkship (LIC) - delivered in year 4, the penultimate year of the medical course, as part of the rural programs delivered by a medical school in Victoria, Australia. The LIC involved student supervision under a parallel consulting model with experienced rural generalist doctors for a whole year in small community rural general practices. METHODS: This study aimed to compare the work locations (regional or more rural), following registration as a medical practitioner, of medical students who had completed 1 year of the LIC, with, first, students who had other types of rural training of comparable duration elsewhere, and second, students who had no rural training. Study participants commenced their medical degree after 2004 and had graduated between 2008 and 2016 and thus were in postgraduate year 1-9 in 2017 when evaluated. Information about the student training location(s), and duration, type and timing of training, was prospectively collected from university administrative systems. The outcome of interest was the main work location in 2017, obtained from the Australian Health Practitioner Regulation Agency's public website. RESULTS: Students who had undertaken the year 4 LIC along with additional rural training in years 3 and/or 5 were more likely than all other groups to be working in smaller regional or rural towns, where workforce need is greatest (relative risk ratio (RRR) 5.62, 95% confidence interval (CI) 2.81-11.20, compared with those having metropolitan training only). Non-LIC training of similar duration in rural areas was also significantly associated, but more weakly, with smaller regional work location (RRR 2.99, 95%CI 1.87-4.77). Students whose only rural training was the year 4 LIC were not significantly associated with smaller regional work location (RRR 1.72, 95%CI 0.59-5.04). Overall, after accounting for both LIC and non-LIC rural training exposure, rural work after graduation was also consistently positively associated with rural background, being an international student and having a return of service obligation under a bonded program as a student. CONCLUSION: This study demonstrates the value of rural LICs, coupled with additional rural training, in contributing to improving Australia's medical workforce distribution. Whilst other evidence has already demonstrated positive educational outcomes for doctors who participate in rural LIC placements, this is the first known study of work location outcomes. The study provides evidence that expanding this model of rural undergraduate education may lead to a better geographically distributed medical workforce.

Post-diagnosis skin cancer follow-up in rural general practice: A mixed-method study.

BACKGROUND AND OBJECTIVES: The literature reveals a lack of consensus on recommendations for follow-up of skin cancer in general practice for all types of skin cancer. The objective of this paper was to evaluate post-treatment surveillance practices for both melanotic and non-melanotic skin cancers (NMSC) by general practitioners (GPs) in regional Victoria, and to identify challenges in follow-up for skin cancers in rural areas. METHOD: A mixed-method study involving a survey and semi-structured interviews with GPs and registrars in Gippsland was carried out in 2015. RESULTS: The survey of 65 participants showed that 69% (45/65) followed up NMSC opportunistically, while 66% (43/65) reported using a structured follow-up practice for melanoma. Six practitioners from the interviews identified the patient's level of education, time constraints, practitioner accessibility and specialists' availability as some common challenges in follow-up. DISCUSSION: We recommend that rural GPs review follow-up strategies for all skin cancers, through the establishment of guidelines and a recall system.

Rates and outcomes of total knee replacement for rheumatoid arthritis compared to osteoarthritis.

BACKGROUND: Total knee replacement (TKR) has been shown to perform differently in patients with rheumatoid arthritis (RA) when compared to osteoarthritis (OA). In this study, we compare the survivorship between these two groups and examine patient and prosthesis factors that impact the revision rate. METHODS: All RA and OA patients undergoing TKR in Australia from 1 September 1999 to 31 December 2016 were included. Revision rates were assessed using Kaplan-Meier estimates of survivorship. The cumulative percent revision analysed age, gender, prosthesis constraint and revision for infection. RESULTS: There were 541 744 TKR procedures performed including 7542 patients with RA. RA declined as the primary diagnosis from 2.4% of all TKR in 2003 to 0.9% in 2016. Male sex was an independent revision risk in RA patients (hazard ratio (HR) = 1.66, P < 0.001) and OA patients (3.5 years+: HR = 1.09 (1.04-1.15), P < 0.001). Male RA patients had a higher revision rate for infection than females (HR = 3.14, P < 0.001). Females with RA had a lower cumulative percent revision compared to OA females, but males showed no difference between diagnoses. Revision in RA patients was not influenced by age. Compared to OA, RA patients had a decreased revision rate for those aged <65 years, but not for patients aged ≥65 years. CONCLUSION: The rate of revision after TKR in RA patients is lower than those with OA, but patients with RA are at increased risk of infection, particularly the male group. Prosthesis constraint had no influence on revision rate. Mortality in those undergoing TKR with RA was higher than in those with OA.