A large Australian longitudinal cohort registry demonstrates sustained safety and efficacy of oral medicinal cannabis for at least two years.

INTRODUCTION: Oral medicinal cannabis (MC) has been increasingly prescribed for a wide range of clinical conditions since 2016. Despite an exponential rise in prescriptions and publications, high quality clinical efficacy and safety studies are lacking. The outcomes of a large Australian clinical electronic registry cohort are presented. METHODS: A prospective cannabis-naïve patient cohort prescribed oral MC participated in an ongoing longitudinal registry at a network of specialised clinics. Patient MC dose, safety and validated outcome data were collected regularly over two years and analysed. RESULTS: 3,961 patients (mean age 56.07 years [SD 19.08], 51.0% female) with multimorbidity (mean diagnoses 5.14 [SD 4.08]) and polypharmacy (mean 6.26 medications [SD 4.61]) were included in this analysis. Clinical indications were for: chronic pain (71.9%), psychiatric (15.4%), neurological (2.1%), and other diagnoses (10.7%). Median total oral daily dose was 10mg for Δ9-tetrahydrocannabinol (THC) and 22.5mg for cannabidiol (CBD). A stable dose was observed for over two years. 37.3% experienced treatment related adverse events. These were graded mild (67%), moderate (31%), severe (<2%, n = 23) and two (0.1%) serious adverse events. Statistically significant improvements at a p value of <0.001 across all outcomes were sustained for over two years, including: clinical global impression (CGI-E, +39%: CGI-I, +52%; p<0.001), pain interference and severity (BPI, 26.1% and 22.2%; p<0.001), mental health (DASS-21, depression 24.5%, anxiety 25.5%, stress 27.7%; p<0.001), insomnia (ISI, 35.0%; p<0.001), and health status (RAND SF36: physical function, 34.4%: emotional well-being, 37.3%; p<0.001). Mean number of concomitant medications did not significantly change over 2 years (p = 0.481). CONCLUSIONS: Oral MC was demonstrated to be safe and well-tolerated for a sustained period in a large complex cohort of cannabis-naïve, multimorbid patients with polypharmacy. There was significant improvement (p<0.001) across all measured clinical outcomes over two years. Results are subject to limitations of Real World Data (RWD) for causation and generalisability. Future high quality randomised controlled trials are awaited.

Longitudinal Relationship between the Introduction of Medicinal Cannabis and Polypharmacy: An Australian Real-World Evidence Study.

Background: Recent studies recommend medicinal cannabis (MC) as a potential treatment for chronic pain (CP) when conventional therapies are not successful; however, data from Australia is limited. This real-world evidence study explored how the introduction of MC related to concomitant medication use over time. Long-term safety also was examined. Methods: Data were collected by the Emerald Clinics (a network of seven clinics located across Australia) as part of routine practice from Jan 2020 toJan 2021. Medications were classified by group: antidepressants, benzodiazepines, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and total number of medications. Adverse events (AEs) were collected at each visit and subsequently coded using the Medical Dictionary for Regulatory Activities version 23 into the system organ class (SOC) and preferred term (PT). A total of 535 patients were analyzed. Results: The most common daily oral dose was 10 mg for delta-9-tetrahydrocannabinol (THC) and 15 mg for cannabidiol (CBD). With the introduction of MC, patients' total number of medications consumed decreased over the course of one year; significant reductions in NSAIDs, benzodiazepines, and antidepressants were observed (p < .001). However, the number of prescribed opioid medications did not differ from baseline to the end of one year (p = .49). Only 6% of patients discontinued MC treatment during the study. A total of 600 AEs were reported in 310 patients during the reporting period and 97% of them were classified as nonserious. Discussion. Though observational in nature, these findings suggest MC is generally well-tolerated, consistent with the previous literature, and may reduce concomitant use of some medications. Due to study limitations, concomitant medication reductions cannot be causally attributed to MC. Nevertheless, these data underscore early signals that warrant further exploration in randomized trials.

Participant experiences of intervention to detect and manage familial hypercholesterolaemia in Australian general practice: A qualitative descriptive study.

BACKGROUND AND OBJECTIVES: General practitioners (GPs) are ideally placed to have a much larger role in detection and management of familial hypercholesterolaemia (FH) among their patients. The aim of this study was to seek the reflections of practice staff and newly diagnosed patients with FH on the implementation of an FH model of care in the general practice setting. METHOD: Qualitative descriptive methodology was used. Interviews were conducted with 36 practice staff and 51 patients from 15 practices participating in the study. RESULTS: Data were analysed thematically and coded into themes - efficacy of GP training, screening for FH, model of care, patient awareness and cascade testing. DISCUSSION: Findings reflect the real-world clinical experience of Australian general practice and the acceptability of the model of care for both patients with FH and practice staff. Patient health literacy is a barrier to both management of FH and cascade testing. A systematic approach to cascade testing is required.

Cost impact of undertaking detection and management of familial hypercholesterolaemia in Australian general practice.

BACKGROUND AND OBJECTIVES: Familial hypercholesterolaemia (FH) can be effectively detected and managed in primary care, but the health economic evidence for this is scarce. The aim of this study was to examine management pathways and cost implications of FH screening and management in Australian general practice. METHOD: Cost-effectiveness outcomes were projected using a life table model. Data was used from 133 patients in 15 Australian general practice clinics from an earlier screening and management study. Costing and mortality data were sourced from governmental sources and published literature. RESULTS: Most patients had a regular general practice consultation at baseline (82%), though the proportion seen under a chronic disease management item at follow-up increased to 23%. The median cost of management was $275 per annum in the first year of management. Managing patients with statins up to the age of 60 years yielded an increase of 248,954 life-years at a cost of $759 million, representing a cost per life-year gained of $3047. DISCUSSION: Screening and management of FH in general practice has the potential for substantial health benefits while requiring relatively modest investments from the health system.

Awareness of familial hypercholesterolaemia in Australian primary care: A qualitative descriptive study.

BACKGROUND AND OBJECTIVES: A lack of public and health professional awareness about familial hypercholesterolaemia (FH) leads to an estimated 90,000 Australians remaining undiagnosed. The aim of this study was to establish the level of knowledge and awareness of FH in Australian general practices. METHOD: A qualitative descriptive methodology was used to explore baseline knowledge and perceptions of practice staff about diagnosing and managing FH. Overall, 63 interviews were conducted with general practice staff at 15 practices taking part in a National Health and Medical Research Council partnership grant study (GNT1142883). RESULTS: Data were analysed thematically and coded into themes - knowledge/awareness/recall, management, use of guidelines/referrals, and contacting family members. Most general practitioners treated the high cholesterol component as their primary focus. Guidelines and referrals were rarely used. DISCUSSION: This research reflected a lack of knowledge, awareness and use of guidelines similar to that shown in other published studies. Improved primary care infrastructure, knowledge and awareness of FH need to be addressed.

Improving detection and management of familial hypercholesterolaemia in Australian general practice.

OBJECTIVE: Familial hypercholesterolaemia (FH) is characterised by elevated low-density lipoprotein (LDL)-cholesterol and increased risk of cardiovascular disease. However, FH remains substantially underdiagnosed and undertreated. We employed a two-stage pragmatic approach to identify and manage patients with FH in primary healthcare. METHODS: Medical records for 232 139 patients who attended 15 general practices at least once in the previous 2 years across five Australian States were first screened for potential risk of FH using an electronic tool (TARB-Ex) and confirmed by general practitioner (GP) clinical assessment based on phenotypic Dutch Lipid Clinic Network Criteria (DLCNC) score. Follow-up GP consultation and management was provided for patients with phenotypic FH. RESULTS: A total of 1843 patients were identified by TARB-Ex as at potential risk of FH (DLCNC score ≥5). After GP medical record review, 900 of these patients (49%) were confirmed with DLCNC score ≥5 and classified as high-risk of FH. From 556 patients subsequently clinically assessed by GPs, 147 (26%) were diagnosed with phenotypic FH (DLCNC score >6). Follow-up GP consultation and management for 77 patients resulted in a significant reduction in LDL-cholesterol (-16%, p<0.01). A higher proportion of these patients attained the treatment target of 50% reduction in LDL-cholesterol (74% vs 62%, p<0.001) and absolute levels of LDL-cholesterol goals compared with baseline (26% vs 12%, p<0.05). CONCLUSIONS: A pragmatic approach integrating electronic medical record tools and clinical GP follow-up consultation is a feasible method to identify and better manage patients with FH in the primary healthcare setting. TRIAL REGISTRATION NUMBER: 12616000630415.

Cannabis: are there any benefits?

Cannabis has been used as a medicine for millennia. Prohibition in the mid-20th century precluded early scientific investigation. 'Cannabis' describes three separate forms - herbal cannabis, 'hemp' products, pharmaceutical-grade regulated cannabinoid-based medical products (CBMP). In Australia, CBMP became available for prescription in November 2016. Herbal cannabis with Δ9-tetrahydrocannabinol (THC), which is illegal, and cannabidiol (CBD) in herbal extracts, are both unregulated and unreliable sources of cannabinoids. The endocannabinoid system (ECS), delineated in the late 1990s, has increased the understanding and interest in research for appropriate clinical indications. The ubiquitous ECS has homeostatic and anti-inflammatory effects and comprises cannabinoid receptors, endocannabinoids and degrading enzymes. Phytocannabinoids are partial agonists of the ECS. In pre-clinical studies, THC and CBD produce beneficial effects in chronic pain, anxiety, sleep and inflammation. Systematic reviews often conflate herbal cannabis and CBMP, confusing the evidence. Currently large randomised controlled trials are unlikely to be achieved. Other methodologies with quality end-points are required. Rich, valuable high-quality real-world evidence for the safe and effective use of CBMP provides an opportunity to examine benefits and potential harms. Evidence demonstrates benefit of CBMP in multiple sclerosis, chronic neuropathic pain, chemotherapy induced nausea and vomiting, resistant paediatric epilepsy, anxiety and insomnia. CBMP are well tolerated with few serious adverse events. Additional clinical benefits are promising in many other resistant chronic conditions. Pharmaceutical grade prescribed CBMP has proven clinical benefits and provides another clinical option in the physician's pharmacopeia.

Identifying Perceptions and Preferences of the General Public Concerning Universal Screening of Children for Familial Hypercholesterolaemia.

BACKGROUND/AIMS: Familial hypercholesterolaemia (FH) is a common genetic disorder that, if untreated, predisposes individuals to premature coronary heart disease. As most individuals with FH remain undiagnosed, new approaches to detection are needed and should be considered a priority in public health genomics. Universal screening of children for FH has been proposed, and this study explores public perspectives on the acceptability of this approach. METHODS: A one-day deliberative public forum was held in Perth, WA, Australia. Thirty randomly selected individuals were recruited, with self-reported sociodemographic characteristics used to obtain discursive representation. Participants were presented with information from a variety of perspectives and asked to discuss the information provided to identify points of consensus and disagreement. The data collected were analysed using thematic analysis. RESULTS: Of the 17 participants at the forum, 16 deemed universal screening of children for FH to be acceptable. Fifteen of these 16 believed this was best performed at the time of an immunisation. Participants proposed a number of conditions that should be met to reduce the likelihood of unintended harm resulting from the screening process. DISCUSSION/CONCLUSION: The outcomes of the forum suggest that establishing a universal screening programme for FH in childhood is acceptable to the general public in WA.

Burden of primary care-type emergency department presentations using clinical assessment by general practitioners: A cross-sectional study.

OBJECTIVE: To compare methods of assessment of the burden of primary care-type ED (PCTED) presentations against clinical assessment by general practitioners (GPs) in ED. METHODS: A cross-sectional study involving clinical assessment of patients presenting to four EDs in Western Australia. The GPs assessed patients who were likely to be discharged home from ED, and considered whether they could be managed in general practice. Patient presentations were defined by the GPs as: PCTED; PCTED if additional primary care resources were available; or not PCTED. RESULTS: GP researchers determined that 80% of patients assessed were PCTED presentations, with one-third of these considered PCTED presentations if additional resources were available. A high proportion of identified PCTED presentations included categories excluded by previous methods. Analysis of linked data found the cohort assessed to be of lower urgency, younger, and with a shorter length of stay than the average patient being discharged from ED. After accounting for potential bias, it is suggested that 20-40% of all ED presentations could be PCTED presentations. CONCLUSIONS: Previous methods determining the burden of PCTED presentations have not been validated. Many presentations excluded by previous methods were identified as manageable in general practice by GPs clinically assessing patients in ED. Improved validation of criteria used to identify PCTED presentations will enable appropriately designed interventions to reduce such events.

Increasing the Detection of Familial Hypercholesterolaemia Using General Practice Electronic Databases.

BACKGROUND: Familial hypercholesterolaemia (FH) is a common autosomal co-dominant condition that causes premature cardiovascular disease. Awareness of FH is poor and only 10-15% of the affected population is identified. Electronic health records provide an opportunity to increase detection and awareness in general practice OBJECTIVE: To determine whether a simple electronic extraction tool can increase detection of FH in general practice. METHOD: An extraction tool applied to general practice electronic health records (EHR) to screen for FH, total cholesterol and low density lipoprotein cholesterol (LDL-c) levels in association with entered diagnostic criteria and demographic data in five general practices. RESULTS: Of 157,290 active patients examined, 0.7% (n=1081) had an LDL-c>5.0 mmol/L representing 1 in 146 of active patients. An additional 0.8% (n=1276) patients were at possible risk of FH. Of those with an LDL-c>5.0 mmol/L 43.7% of patients had no record of being prescribed statins. Twenty patients (0.013%) had a clinical diagnosis of FH entered in the EHR. CONCLUSIONS: Patients at high risk of FH can be identified by a simple electronic screening method in general practice. Clinical data entry is variable in general practice. Targeted screening enables clinical assessment of patients at risk of cardiovascular disease and using the DLCNS will enable primary care to increase identification of FH. Approximately one in five patients extracted using this method, are likely to have phenotypically probable FH, making it a useful screening tool.

Cardiac troponin testing for diagnosis of acute coronary syndromes in primary care.

OBJECTIVE: To examine the use of cardiac troponin (cTn) testing for acute coronary syndrome (ACS) diagnosis in primary care. DESIGN AND SETTING: Prospective cohort study; general practitioner-initiated cTn tests conducted from 24 September 2009 to 3 September 2010 in Perth, Western Australia. Patient outcomes were obtained from linked data sources for up to 12 months after the final test. Clinical information and outcomes were compared with data from emergency department patients with ACS symptoms. PARTICIPANTS: 369 patients with samples collected at community laboratories. Requesting GPs provided the clinical context for testing. MAIN OUTCOME MEASURES: Cardiovascular risk status, symptoms prompting cTn testing; estimated ACS likelihood and referral decision before and after testing; result turnaround time; hospital presentations, procedures and mortality. RESULTS: Of the 328 GPs who received a survey request, 124 (37.8%) responded. 122 of 124 test results (98.4%) were negative. Based on clinical risk factors, 71 of 104 patients (68.2%) were at high or intermediate risk of ACS. 69 of 124 patients (55.6%) had typical ischaemic pain and 62 of 124 patients (50.0%) were tested within 48 hours of symptom onset (23.4% within 12 hours, with no serial testing). Test results affected GPs' estimation of ACS likelihood (P < 0.01) but not their referral decisions (P = 0.23). 94 of 355 patients (26.5%) presented to hospital with cardiovascular symptoms or diagnoses during follow-up; 27 of 355 patients (7.6%) had at least one ACS, 13 of 255 (3.7%) within 30 days of testing. CONCLUSIONS: GP-initiated cTn testing involves patients at high risk of ACS. ACS and associated adverse outcomes can occur in patients undergoing testing, even when the cTn test result is negative. Potential gaps exist in physicians' understanding of the limitations of cTn testing, and cTn test results have minimal influence on their management of patients. GPs may benefit from guidance about ordering cTn testing.

Challenges in the care of familial hypercholesterolemia: a community care perspective.

Familial hyperchoelsterolaemia (FH) remains under-diagnosed and under-treated in the community setting. Earlier evidence suggested a prevalence of 1:500 worldwide but newer evidence suggests it is more common. Less than 15% of FH patients are ever diagnosed, with children and young adults rarely tested despite having the most to gain given their lifetime exposure. Increasing awareness among primary care teams is critical to improve the detection profile for FH. Cascade testing in the community setting needs a sustainable approach to be developed to facilitate family tracing of index cases. The use of the Dutch Lipid Clinic Network Criteria score to facilitate a phenotypic diagnosis is the preferred approach adopted in Australia and eliminates the need to undertake genetic testing for all suspected FH cases.

Systematic detection of familial hypercholesterolaemia in primary health care: a community based prospective study of three methods.

BACKGROUND: Familial hypercholesterolaemia (FH), a co-dominantly inherited disease of cholesterol that markedly increases risk of premature coronary artery disease (CAD), is significantly under-diagnosed. Primary health care is increasingly seen as a setting in which to increase the detection rate of index cases. We report a prospective study of three methods of case detection using pre-existing primary health care services in one community. METHODS: Three methods of case detection were tested: pathology laboratory database search, workplace health checks and general practice database search. People identified at risk by each of the three screening methods were offered detailed assessment for FH using the Dutch Lipid Clinic Network Criteria score (DLCNCS). RESULTS: 1316 participants underwent detailed assessment for FH. The proportion of at risk people identified for further assessment was in decreasing order: GP (659 of 2494, 26.4%), workplace assessment (60 of 268, 22.4%) and pathology database (597 of 4517, 13.2%) p<0.001. Eight-six (6.5%) were identified as clinical FH (DLCNCS>5) of which 59 had genetic testing and 11 of 59, 18.6%, were confirmed to have a mutation causing FH. Pathology database detected the greatest number of clinical FH (51 of 86, 59.3%) and mutation positive participants (8 of 11, 72.7%). CONCLUSION: Screening within primary health care was successful in detecting participants with FH. An integrated case detection model combining screening of pathology and GP databases is proposed.

Optimising the detection and management of familial hypercholesterolaemia: central role of primary care and its integration with specialist services.

Familial hypercholesterolaemia (FH) is the most common monogenic lipid disorder associated with premature coronary heart disease (CHD). However, the majority of people with FH are undiagnosed or undertreated. Early cholesterol lowering therapy reduces cardiovascular disease mortality in FH. Low awareness and knowledge of FH in specialty and general practice highlights the need for strategies to improve the detection and management of FH. We present an algorithm describing a multidisciplinary approach to FH detection and management. We highlight the role of primary care, and where GPs can work with preventive cardiologists to improve care of FH. Novel strategies to detect index cases with FH are presented including the community laboratory, highlighting patients at high risk of FH, and targeted FH detection through searching the general practice database. General practitioners request over 90% of LDL cholesterol measurements in the community. Once an individual with FH is detected only a small proportion of patients require specialty management with the majority of patients suitably managed in primary care. However, it is crucial to screen family members, as 50% of first-degree family members are expected to have FH due to the autosomal dominant inheritance.

Future models of general practice training in Australia.

Current proposals for significant primary health care reform in Australia create a timely opportunity to reflect on the education and training requirements of future general practitioners. Australian general practice will become increasingly team-based, with growing emphasis on coordinated care, chronic disease management, and disease prevention and self-management, while maintaining its focus on delivering high-quality, patient-centred care. This will require cost-effective application of new technologies and information management systems within new models of delivering health care. Future models of general practice training must respond to these new ways of working to ensure general practice remains an attractive career choice and training programs graduate doctors who are equipped to meet the health needs of Australians. This article discusses potential development of new general practice vocational training models in Australia. This includes hospital rotations that are more directly integrated with general practice placements and have greater emphasis on the needs of the future general practice workforce; and an extension of the training program to 4 years with a final year tailored to future career plans including development of expertise in practice management, specific clinical disciplines or academic skills.

General Practice Super Clinics--how will they meet their educational objectives?

The Australian Government will provide $275 million over 4 years to general practice infrastructure across Australia with the rollout of 31 General Practice Super Clinics. One of the core objectives of these Super Clinics is to support medical education. Several studies have demonstrated that the major barriers to teaching in general practice are time, space and money. We argue that General Practice Super Clinics can provide a responsive, flexible work culture; and improved payment and targeted resources to support the need for increased teaching capacity, and to attract and retain workforce for general practice and primary care.

Hospital grand rounds in Australia.

OBJECTIVE: To determine whether grand rounds are becoming less common in Australian hospitals. DESIGN AND PARTICIPANTS: Between November 2003 and April 2004, we surveyed 88 clinicians with educational responsibilities in Australian hospitals. A written questionnaire evaluated whether grand rounds were held and how frequently; the structure and percentage of attendees; and the perceived value of grand rounds with regard to education, professional development and general characteristics. RESULTS: Clinicians in 73/88 hospitals completed the survey (83% response rate). Of the 73 respondents, 63 reported that their hospitals continued to hold grand rounds, and most considered them to be valuable in the areas surveyed. Grand rounds were more common in larger hospitals, public hospitals, and those having junior medical officers. The proportion of clinical staff regularly attending grand rounds was estimated to be 10%-50% by most respondents. CONCLUSION: Grand rounds continue in the majority of hospitals and are considered valuable for educational and professional reasons. There may be scope for improving attendance at grand rounds by greater emphasis on the specific needs of attendees.