Levodopa use in Australia: an analysis of Pharmaceutical Benefits Scheme 10% data.

Background: Levodopa remains the mainstay of treatment of Parkinson's disease, however, over time motor fluctuations and levodopa-induced dyskinesia develop, requiring add-on therapies to control emerging symptoms. To date, however, there is no clear consensus in Australia, or elsewhere, at which dose of levodopa that add-on therapies should be considered. Objectives: The purpose of this study was to examine the treatment patterns of patients with Parkinson's disease in Australia, with particular focus on levodopa doses at the time of first add-on. Methods: This was a retrospective, observational, non-interventional study of patients with Parkinson's disease within the Australian Department of Human Services Pharmaceutical Benefits Scheme (PBS) 10% sample. Data on all reimbursed prescriptions (both general and concession), prescriber type and item code were extracted for patients who were dispensed at least three PBS reimbursed prescriptions for levodopa in the previous 12 months prescription from 1 January 2007 to 31 December 2021. Results: 154 850 unique patients were included, of whom 42 330 (27%) commenced add-on therapy during the period. In the 12 months prior to add-on therapy, levodopa doses ranged from 100 mg/day to 1000 mg/day. The majority of patients were prescribed add-on therapy by a neurologist and approximately 40% of patients were prescribed levodopa doses of 600 mg/day or more prior to the first add-on therapy being initiated. Conclusions: A large proportion of patients in Australia are managed with levodopa monotherapy doses that are considered high and many of these patients may benefit from the addition of add-on therapy to their regimen.

The transition to uniportal robotic surgery in the second decade of uniportal surgery.

Uniportal robotic surgery was created by Dr. Diego Gonzalez-Rivas as a fusion of his decade of experience with uniportal video-assisted thoracoscopic surgery (VATS) and his recent experience with the Intuitive Robotic System. It represents, in his view, the natural evolution of the uniportal technique in the era of robotic surgery. In this article, we discuss some of the novel issues that this raises, including capacitive coupling, and we describe the technique in detail to help surgeons who may be interested in starting uniportal robotic surgery. We go through case selection, which should start with wedge resections and lymphadenectomy. We look at port placement, which is more posterior and lower than the usual uniportal VATS approach, and we discuss the optimal instruments and ports for the technique. We discuss the role of the assistant in uniportal robotic surgery, which is a key part of the operation as we regard this as a two-surgeon technique. We then discuss the future and other possible robotic platforms that might be suitable for uniportal robotic surgery. It is an exciting new development for robotic surgery, and we recommend that this technique is suitable for advanced surgeons who are experienced in uniportal VATS lobectomy and in multiportal robotic surgery.

Video atlas of each uniportal robotic-assisted thoracic surgery lobectomy and lymphadenectomy.

It is important when evaluating new techniques that a surgeon can see and assess all the differences and similarities between their usual technique and the novel technique. Thus, we have collated a comprehensive atlas of videos of uniportal robotic lobectomies for every lobe. Surgeons who are considering embarking on a program of uniportal robotic lobectomies can accordingly see the different views and techniques that will be required for when they perform their first procedure. We have fully narrated the videos, so that you will be taken through each procedure. Whilst these five videos are fifty-five minutes in total, our intention is not necessarily for you to watch them all from start to finish, but rather, come to this video, select the lobe that you will shortly embark on, and watch it prior to your case so that you can visualise, as closely as possible, the procedure that you will be performing. We recommend that you watch the videos with your bedside assistant as the uniportal robotic lobectomy is a joint procedure between two surgeons, rather than a single surgeon's operation with an assistant. Though we have not provided videos on segmentectomies, the uniportal robotic lobectomy is an advanced technique and we are confident that advanced surgeons will be able to gain key insights with what has been included, even if they are proceeding to a segmentectomy for their first cases. We feel for an advanced surgeon, a segmentectomy will be just as suitable an operation as a lobectomy in the initial learning phase.

The Importance of Culture Change Associated With Novel Surgical Approaches and Innovation: Does Perioperative Care Transcend Technical Considerations for Pulmonary Lobectomy?

Robotic thoracic surgery for pulmonary lobectomy was introduced at our unit in 2015, along with enhanced perioperative patient care pathways. We evaluated the effect of this practice change on short-term outcomes. Data on all adult patients who underwent a lobectomy in our unit between 2015 and 2019 were obtained retrospectively from our surgical database. Patients fell into three groups: conventional open surgery via thoracotomy, video-assisted thoracoscopic surgery (VATS), and robot-assisted thoracoscopic surgery (RATS). Survival was defined as survival to discharge. Our cohort included 722 patients. Three hundred and ninety-two patients (54.3%) underwent an open operation, 259 patients (35.9%) underwent VATS surgery, and 71 patients (9.8%) underwent a robotic procedure. Comparing these surgical approaches, there was no statistically significant difference in the overall incidence of post-operative complications (p = 0.15) as well as the incidence of wound infections, arrhythmias, prolonged air leaks, respiratory failure, or ICU readmissions. Additionally, there was no statistically significant difference in survival to discharge (p = 0.66). However, patients who had a VATS procedure were less likely to develop a post-operative chest infection (p = 0.01). Evaluating our practice over time, we found a decrease in the overall incidence of post-operative complications (p = 0.01) with an improvement in survival to discharge (p = 0.02). In our experience, VATS lobectomy was associated with a lower incidence of post-operative chest infections. However, the limitations of our study must be considered; factors such as patient selection that may have had a substantial impact. The culture change associated with adoption of a VATS and robotic surgical programme appears to have corresponded with an improved survival to discharge for all lobectomy patients, irrespective of surgical approach. Perioperative care may therefore have a more significant impact on outcomes than technical considerations.

Quantitative evaluation and comparison of coronary artery characteristics by 3D coronary volume reconstruction.

Non-atherosclerotic abnormalities of vessel calibre, aneurysm and ectasia, are challenging to quantify and are often overlooked in qualitative reporting. Utilising a novel 3-dimensional (3D) quantitative coronary angiography (QCA) application, we have evaluated the characteristics of normal, diabetic and aneurysmal or ectatic coronary arteries. We selected 131 individuals under 50 years-of-age, who had undergone coronary angiography for suspected myocardial ischaemia between 1st January 2011 and 31st December 2015, at the Bristol Heart Institute, Bristol, UK. This included 42 patients with angiographically normal coronary arteries, 36 diabetic patients with unobstructed coronaries, and 53 patients with abnormal coronary dilatation (aneurysm and ectasia). A total of 1105 coronary segments were analysed using QAngio XA 3D (Research Edition, Medis medical imaging systems, Leiden, The Netherlands). The combined volume of the major coronary arteries was significantly different between each group (1240 ± 476 mm3 diabetic group, 1646 ± 391 mm3 normal group, and 2072 ± 687 mm3 abnormal group). Moreover, the combined coronary artery volumes correlated with patient body surface area (r = 0.483, p < 0.01). Inter-observer variability was assessed and intraclass correlation coefficient of the total coronary artery volume demonstrated a low variability of 3D QCA (r = 0.996, p < 0.001). Dedicated 3D QCA facilitates reproducible coronary artery volume estimation and allows discrimination of normal and diseased vessels.

Three wound-dressing strategies to reduce surgical site infection after abdominal surgery: the Bluebelle feasibility study and pilot RCT.

BACKGROUND: Surgical site infection (SSI) affects up to 20% of people with a primary closed wound after surgery. Wound dressings may reduce SSI. OBJECTIVE: To assess the feasibility of a multicentre randomised controlled trial (RCT) to evaluate the effectiveness and cost-effectiveness of dressing types or no dressing to reduce SSI in primary surgical wounds. DESIGN: Phase A - semistructured interviews, outcome measure development, practice survey, literature reviews and value-of-information analysis. Phase B - pilot RCT with qualitative research and questionnaire validation. Patients and the public were involved. SETTING: Usual NHS care. PARTICIPANTS: Patients undergoing elective/non-elective abdominal surgery, including caesarean section. INTERVENTIONS: Phase A - none. Phase B - simple dressing, glue-as-a-dressing (tissue adhesive) or 'no dressing'. MAIN OUTCOME MEASURES: Phase A - pilot RCT design; SSI, patient experience and wound management questionnaires; dressing practices; and value-of-information of a RCT. Phase B - participants screened, proportions consented/randomised; acceptability of interventions; adherence; retention; validity and reliability of SSI measure; and cost drivers. DATA SOURCES: Phase A - interviews with patients and health-care professionals (HCPs), narrative data from published RCTs and data about dressing practices. Phase B - participants and HCPs in five hospitals. RESULTS: Phase A - we interviewed 102 participants. HCPs interpreted 'dressing' variably and reported using available products. HCPs suggested practical/clinical reasons for dressing use, acknowledged the weak evidence base and felt that a RCT including a 'no dressing' group was acceptable. A survey showed that 68% of 1769 wounds (727 participants) had simple dressings and 27% had glue-as-a-dressing. Dressings were used similarly in elective and non-elective surgery. The SSI questionnaire was developed from a content analysis of existing SSI tools and interviews, yielding 19 domains and 16 items. A main RCT would be valuable to the NHS at a willingness to pay of £20,000 per quality-adjusted life-year. Phase B - from 4 March 2016 to 30 November 2016, we approached 862 patients for the pilot RCT; 81.1% were eligible, 59.4% consented and 394 were randomised (simple, n = 133; glue, n = 129; no dressing, n = 132); non-adherence was 3 out of 133, 8 out of 129 and 20 out of 132, respectively. SSI occurred in 51 out of 281 participants. We interviewed 55 participants. All dressing strategies were acceptable to stakeholders, with no indication that adherence was problematic. Adherence aids and patients' understanding of their allocated dressing appeared to be key. The SSI questionnaire response rate overall was 67.2%. Items in the SSI questionnaire fitted a single scale, which had good reliability (test-retest and Cronbach's alpha of > 0.7) and diagnostic accuracy (c-statistic = 0.906). The key cost drivers were hospital appointments, dressings and redressings, use of new medicines and primary care appointments. LIMITATIONS: Multiple activities, often in parallel, were challenging to co-ordinate. An amendment took 4 months, restricting recruitment to the pilot RCT. Only 67% of participants completed the SSI questionnaire. We could not implement photography in theatres. CONCLUSIONS: A main RCT of dressing strategies is feasible and would be valuable to the NHS. The SSI questionnaire is sufficiently accurate to be used as the primary outcome. A main trial with three groups (as in the pilot) would be valuable to the NHS, using a primary outcome of SSI at discharge and patient-reported SSI symptoms at 4-8 weeks. TRIAL REGISTRATION: Phase A - Current Controlled Trials ISRCTN06792113; Phase B - Current Controlled Trials ISRCTN49328913. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 39. See the NIHR Journals Library website for further project information. Funding was also provided by the Medical Research Council ConDuCT-II Hub (reference number MR/K025643/1).

Wound infections are common after surgery. Some are cured with simple treatment, but others may lead to serious problems. Reducing the risk of a wound infection is important. We do not know if the type of dressing, or not using a dressing, influences the risk of infection. A study that allocated patients to receive different dressings (or no dressing) would answer this question. We did preliminary research to explore whether or not such a study is possible. We interviewed doctors, nurses and patients about their views on dressings and a future study. We also described dressings currently being used in the NHS and found that simple dressings and tissue adhesive (glue) 'as-a-dressing' are used most frequently. We studied existing evidence and interviewed experts to develop a questionnaire, completed by patients, to identify wound infections after patients leave hospital and tested its accuracy. We also explored taking photographs of wounds. We investigated whether or not a major study would be worth the cost and designed a pilot study to test its feasibility. The pilot study recruited 394 patients undergoing abdominal operations in five NHS hospitals. These patients were allocated to have a simple dressing, glue-as-a-dressing or no dressing, and 92% received the allocated dressing method. Patients and their doctors and nurses found the dressing methods to be acceptable. We showed that the new patient questionnaire accurately identified infections. Patients or their carers also found it acceptable to photograph their wounds. Our research suggests that a future large study would be worth the investment and is possible.

Retrospective study of the impact of unrecognised Kawasaki disease, coronary aneurysm and ectasia.

BACKGROUND: Coronary artery aneurysms resulting from unrecognised or untreated Kawasaki Disease (KD) have thrombotic and stenotic potential leading to myocardial infarction. We aimed to characterise the prevalence and outcomes of patients presenting to a UK-based adult tertiary cardiology service with angiographic evidence of aneurysm or ectasia. METHODS: Retrospective review was undertaken of reports and original coronary angiograms in all patients under 50years old undergoing coronary angiography between 2011 and 2015. Aneurysm/ectasia were defined by calibre discrepancy >1.5× and the number of segments involved. Aneurysms were categorised as being probable, or unlikely to represent unrecognised KD. RESULTS: Aneurysm or ectasia was observed in 49 of 1578 patients (3.7%). Eleven patients had angiographic findings consistent with probable antecedent KD (0.8%), a further 18 patients had evidence of coronary artery aneurysm (1.4%) and ectasia was observed in 20 patients (1.5%). The commonest mode of presentation was ST elevation myocardial infarction, observed in 71.4% of patients. Review of angiogram written reports demonstrated a spurious application of the terms aneurysm and ectasia, with a sensitivity of 10.3% & 55.0%, and a positive predictive value of reporting of 50.0% & 52.4%, respectively. CONCLUSIONS: As the first UK study to characterise the angiographic prevalence of Kawasaki Disease, both aneurysm and ectasia were observed with a relatively low frequency. However, their presence is associated with high-risk acute ischaemic presentations. Furthermore, we demonstrated a poor level of reporting of coronary abnormalities and advocate an increased awareness of Kawasaki disease and coronary aneurysm/ectasia amongst adult cardiologists.

Medium- to long-term persistence with non-vitamin-K oral anticoagulants in patients with atrial fibrillation: Australian experience.

OBJECTIVE: Long-term anticoagulant therapy with non-valvular atrial fibrillation (AF) is essential to prevent thromboembolic complications, especially ischemic stroke. This study examines medium-term persistence in AF patients using a non-vitamin-K antagonist oral anticoagulant drug (NOAC). RESEARCH DESIGN AND METHODS: We assessed national Pharmaceutical Benefit Scheme records December 2013 through September 2016 for initial prescription of a NOAC in a 10% random sample of concessional patients. Key outcome measures were: (a) proportions filling first repeat prescription, (b) proportions persisting with NOAC over 12 and 30 months and (c) proportions switching to another NOAC or warfarin. RESULTS: A total of 8656 patients with AF initiated a NOAC (3352 apixaban, 1340 dabigatran, 3964 rivaroxaban). Mean age was 77 years, 53% male; 91% collected the first repeat prescription for any NOAC, 70% and 57% collected any NOAC or subsequent warfarin prescription over 12 months and 30 months respectively; 8.9% had switched to warfarin. The proportions switching from apixaban, dabigatran and rivaroxaban to a different NOAC were 14%, 31% and 17% respectively. In a regression model adjusting for age, gender and comorbidity, apixaban-initiated patients over 30 months were 28% more likely to persist with any anticoagulant therapy compared with dabigatran-initiated patients (hazard ratio [95% CI] 1.28 [1.16-1.42]) and 15% more likely to persist compared with rivaroxaban-initiated (1.15 [1.06-1.24]). Rivaroxaban-initiated patients were 12% more likely to persist compared with dabigatran-initiated patients (1.12 [1.02-1.24]). CONCLUSIONS: Long-term persistence with anticoagulation in patients with AF remains a concern, even with NOACs. Patients initiated to apixaban appear to experience better medium-term persistence compared with rivaroxaban or dabigatran.

Scarcity of ecosystem services: an experimental manipulation of declining pollination rates and its economic consequences for agriculture.

Ecosystem services (ES) such as pollination are vital for the continuous supply of food to a growing human population, but the decline in populations of insect pollinators worldwide poses a threat to food and nutritional security. Using a pollinator (honeybee) exclusion approach, we evaluated the impact of pollinator scarcity on production in four brassica fields, two producing hybrid seeds and two producing open-pollinated ones. There was a clear reduction in seed yield as pollination rates declined. Open-pollinated crops produced significantly higher yields than did the hybrid ones at all pollination rates. The hybrid crops required at least 0.50 of background pollination rates to achieve maximum yield, whereas in open-pollinated crops, 0.25 pollination rates were necessary for maximum yield. The total estimated economic value of pollination services provided by honeybees to the agricultural industry in New Zealand is NZD $1.96 billion annually. This study indicates that loss of pollination services can result in significant declines in production and have serious implications for the market economy in New Zealand. Depending on the extent of honeybee population decline, and assuming that results in declining pollination services, the estimated economic loss to New Zealand agriculture could be in the range of NZD $295-728 million annually.

Improved persistence with non-vitamin-K oral anticoagulants compared with warfarin in patients with atrial fibrillation: recent Australian experience.

OBJECTIVE: Long-term anticoagulant therapy in patients with non-valvular atrial fibrillation (AF) is essential to prevent thromboembolic complications, especially ischemic stroke, but treatment persistence with warfarin is poor. This study examines Australian nationwide persistence in AF patients using a non-vitamin-K oral anticoagulant (NOAC) drug. RESEARCH DESIGN AND METHODS: We assessed national Pharmaceutical Benefit Scheme records November-December 2013 through March 2015 for prescription of NOAC drugs in a 10% random sample of long-term concession card holders. An historical comparison was made with patients prescribed warfarin in 2008. Key outcome measures were (i) the proportion not filling first repeat prescription and (ii) discontinuation within 12 months. RESULTS: A total of 1471 patients with AF were new users of a NOAC drug (228 apixaban, 645 dabigatran, 598 rivaroxaban) and 1348 were new users of warfarin. Mean age on a NOAC was 76 years (58% male), on warfarin 74 years (54% male). Only 9% (95% CI 7-10) failed to collect the first repeat prescription on a NOAC, 30% (27-32) discontinued within 12 months; corresponding proportions on warfarin were 14% (12-16) and 62% (60-65). In a regression model adjusted for age, gender, heart failure, hypertension and diabetes, warfarin-treated patients were 2.5 times more likely to discontinue over 12 months than those who were NOAC treated (hazard ratio =2.47 [95% CI 2.19-2.79]). CONCLUSIONS: Persistence with NOAC drugs in patients with AF appears to be superior to warfarin. If continued long-term, this alone will be of clinical importance in the prevention of stroke and death.

Can ecosystem-scale translocations mitigate the impact of climate change on terrestrial biodiversity? Promises, pitfalls, and possibilities: Ecosystem-scale translocations.

Because ecological interactions are the first components of the ecosystem to be impacted by climate change, future forms of threatened-species and ecosystem management should aim at conserving complete, functioning communities rather than single charismatic species. A possible way forward is the deployment of ecosystem-scale translocation (EST), where above- and below-ground elements of a functioning terrestrial ecosystem (including vegetation and topsoil) are carefully collected and moved together. Small-scale attempts at such practice have been made for the purpose of ecological restoration. By moving larger subsets of functioning ecosystems from climatically unstable regions to more stable ones, EST could provide a practical means to conserve mature and complex ecosystems threatened by climate change. However, there are a number of challenges associated with EST in the context of climate change mitigation, in particular the choice of donor and receptor sites. With the aim of fostering discussion and debate about the EST concept, we  1) outline the possible promises and pitfalls of EST in mitigating the impact of climate change on terrestrial biodiversity and 2) use a GIS-based approach to illustrate how  potential source and receptor sites, where EST could be trialed and evaluated globally, could be identified.

Pyrosequencing of prey DNA in faeces of carnivorous land snails to facilitate ecological restoration and relocation programmes.

Identifying and understanding predator diets is of high importance in biological conservation. This is particularly true for the introduction, establishment and maintenance of predator populations in newly created or modified ecological communities, such as translocation sites or restored habitats. Conservation status of predators may not permit captive feeding trials or intrusive gut-content methods, so non-intrusive diet assessment is required, such as faecal analysis. However, prey such as earthworms leave no morphological clues suitable for accurately discriminating between species consumed through visual faecal analysis. This study uses non-intrusive molecular methods on earthworm DNA extracted from the faeces of the carnivorous land snail Powelliphanta patrickensis to identify its earthworm diet and any seasonal trends. Data from 454-pyrosequencing revealed earthworm DNA in all samples (n = 60). Sequences were compared to a DNA library created from published and unpublished studies of New Zealand's endemic earthworms and online databases. Unidentified earthworm sequences were clustered into molecular operational taxonomic units (MOTUs). Twenty-six MOTUs were identified, 17 of which matched the library, whereas nine did not. Similarity indices indicate that there were seasonal differences (P < 0.05) in the earthworm communities represented in the summer and the winter diets. This study highlights the importance of utilising the vast body of data generated by pyrosequencing to investigate potential temporal diet shifts in protected species. The method described here is widely applicable to a wide range of predatory species of conservation interest and can further inform habitat restoration and relocation programmes to optimize the long-term survival of the target species.

Assessment of EGFR/HER2 dimerization by FRET-FLIM utilizing Alexa-conjugated secondary antibodies in relation to targeted therapies in cancers.

The expression level of the HER family is unreliable as a predictive marker for targeted therapies in cancer. Thus, there is a need to develop other biomarkers, which can be used to accurately select responsive patients for targeted therapies. The HER dimerization status may be more important than HER receptor expression per se in determining sensitivity or resistance to a given therapeutic agent. The aim of the study is to develop a FRET assay using dye conjugated secondary antibodies to assess HER receptor dimerization. Using primary antibodies from different species in conjunction with Alexa488 and Alexa546 conjugated secondary antibodies, we validated our EGFR/HER2 dimerization assay in three cell lines, EGFR positive A431 cells as well as HER2 positive breast cell lines BT474 and SKBR3 cells. Finally, we applied our assay to assess EGFR/HER2 dimerization in paraffin embedded cell pellets. Our results show promise for the assay to be applied to tumor samples in order to assess the prognostic significance and predictive value of HER receptor dimerization in various cancers.

Pacing strategy from high-frequency field data: more evidence for neural regulation?

INTRODUCTION: We demonstrate a methodology that uncovers an athlete's true pacing strategy from high-frequency (≤1 km) split field data, even if affected by high gradient variation on course. The method thus opens up the analysis of many previously opaque but popular undulating professional and amateur races to scientific scrutiny. METHODS: The method is relatively simple to use in any standard statistical package, and execution only requires the addition of the altitude-distance trace of the event to a runner's split times (e.g., as automatically collected by a modern Global Positioning System-enabled wristwatch). In addition, as opposed to assuming a pacing function (e.g., "J shaped," "U shaped," "all-out") and testing this function on the data, the method uses a preliminary discovery step to suggest the most appropriate pacing function(s) to test on the data (if any). RESULTS: The method is demonstrated with two novel case studies: Gebrselassie's world-record Berlin marathon (September 2008) and a unique data set taken from several years of the Six Foot Track Ultramarathon (45 km, Sydney, Australia). CONCLUSIONS: In both cases, the method reveals highly variable pacing strategies on a microscale despite remarkable symmetry on a macroscale in one case adding weight to the recent complex system perspective of the neural regulator.