This is the first of a continuing series of CME related posts. This rural review takes a look at the recent evidence with comment/interpretation provided by two legends who are part of the Rural Post-graduate Programme: Dr Steve Withington and Dr Garry Nixon.
Steve Withington is a rural doctor who works in Ashburton. He teaches GENA 729 Medical specialties in Rural Hospital medicine
Endovascular clot retrieval for acute ischaemic stroke in New Zealand
Burnell, A. L., Ranta, A., Wu, T., Fink, J., McGuiness, B., Caldwell, J., … Barber, P. A. (2018). Endovascular clot retrieval for acute ischaemic stroke in new zealand. The New Zealand Medical Journal (Online), 131(1484), 13–18. Retrieved from https://search-proquest-com.ezproxy.otago.ac.nz/docview/2131782948?accountid=14700
This report of New Zealand’s experience with endovascular clot retrieval (ECR) warrants serious consideration by rural generalists.
312 New Zealanders from 11 DHBs, with a mean age of 64, ranging in age from 16 to 92 have been treated with ECR since 2011, 83% with anterior and 17% with posterior circulation arterial occlusions. Most (62%) had prior intravenous alteplase. Median time from symptom onset to groin puncture was 210 minutes (3.5 hours), ranging from as little as one hour, up to 16 hours. The procedure itself took around 1 hour on average.
Around half the patients were transferred in from elsewhere, including rural locations, to the 3 tertiary centres (Auckland (77%), Christchurch (18%), Wellington (5%)) that perform ECR. Median NIHSS score at baseline was 18, indicating significant severity of stroke, decreasing to 7 by 24 hours. Good rates of recanalisation were seen in nearly 90% of patients and by 3 months 55% of the anterior and 40% of the posterior circulation patients were living independently at home (modified Rankin scores 0–2). Rates of symptomatic intracranial haemorrhage were 4% in both groups. Mortality rates were 20% and 30% respectively.
These are severe strokes, with high prior probability of disability and death, but with specific patterns of CT perfusion scanning indicating relatively small areas of infarction and recoverable ischaemic penumbra amenable to ECR, even despite relatively long delays since onset of stroke. Results are comparable with the recent DAWN (1) (49% functional independence at home with ECR vs 13% in controls; mortality 19% vs 18%) and DEFUSE 3 trials (45% vs 17% functional independence; mortality 14% vs 26%),(2) which have shown striking results in the highly selected group offered ECR.
The changing face of acute stroke treatment in NZ raises significant challenges and equity issues for rural populations and their rural health services. A few rural hospitals with available CT, such as Ashburton, Dunstan, and Thames, have been offering thrombolysis for appropriately selected ischaemic stroke patients, who are able to receive alteplase within 4.5 hours of stroke onset. Studies have showed limited benefit (especially from 3–4.5 hours post onset) in terms of increased rates of independence post stroke in thrombolysis groups. The few recent studies mentioned (but not older, pre–2015, clinical trials which used older technology) of ECR, usually in addition to thrombolysis, have shown much more impressive clinical results, over extended time periods after stroke onset. However, in many rural places there is limited or no access to urgent CT, CTA and CTP by which to identify ECR-treatable patients. Further, ECR services, will depend on the distance from and the availability and accessibility of services at the nearest tertiary centre.
It is noteworthy that the age range offered ECR has gone outside trial boundaries, and potentially other boundaries will be pushed also raising safety concerns and need for good protocols, that include the rural context. Bypass transfers are in operation in many rural areas, and Telestroke services are being proposed widely to allow remote support in decision-making.
While significant clinical benefit in the selected group seems clear, the potential costs of implementing a nationwide system that bypasses rural stroke services for the sake of a small proportion potentially benefitting from ECR, and the opportunity costs of losing access to transport options for other unwell patients needs careful consideration by clinicians and managers in rural centres, who need to be actively engaged in the planning process.
Effects of fluoxetine on functional outcomes after acute stroke
Dennis M, Mead G, Forbes J, Graham C, Hackett M, Hankey GJ, et al. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. The Lancet. 2019 Jan 19;393(10168):265–74.
This study of 3127 patients from over hospitals in the UK sought to settle the question of whether an SSRI (fluoxetine 20mg daily) given routinely to stroke patients over 18, within the first two days to two weeks of the stroke for a total of 6 months, would benefit in terms of physical stroke outcome and mental health at 6 and 12 months of follow up.
A previous Cochrane Study had suggested benefit,(3) and similarly the FLAME study in 2011 had shown significant advantages in terms of motor recovery,(4) levels of independence and rates of depression in the 118 patients with unilateral weakness from ischaemic stroke studied. This much larger study of all eligible adult stroke patients showed no difference between fluoxetine and placebo recipients in terms of independence, as measured by a distribution of modified Rankin Scores. The fluoxetine group were somewhat less likely to develop depression (13.4% vs 17.2%; p=0.003), but they had twice as many bony fractures (2.9% vs 1.5%; p=0.007). Other potential harms such as hyponatraemia with fluoxetine were small and not significantly different between groups. The authors conclude that SSRIs are not routinely indicated post stroke, though there may be benefits in subgroups, and it was noted that the FLAME study patients did have more severe strokes on average.(4)
Stroke is common. Though an increasing number of acute strokes are transferred to base hospital stroke centres, for acute interventions and initial management, many are cared for in rural centres, either for rehabilitation only or for both acute and ongoing management. A focus on mental health post stroke is welcome. Depression post stroke is a common and doubly debilitating complication. Though data are scant and studies difficult to conduct, it would be very interesting to know whether rates and severity of diagnosis depression are different in those whose stroke treatment and rehabilitation is conducted in their own rural hospital, as opposed to those transferred centrally. The nearness of home and whanau support may potentially both decrease the onset of depression and support its diagnosis more speedily, and with greater confidence. Some have advocated a much more liberal, even routine policy of antidepressant use post stroke, apparently supported by a Cochrane review and the FLAME study.(3,4) The present study is a useful addition to the discussion, showing only a small benefit in prevention of depression, the rates of which were much lower in the placebo group, than in the FLAME study,(4) at the cost of increased fractures. Independence rates were not improved.
Antidepressants have a role post stroke, but appropriate patient selection involving regular clinical assessment for depression in a patient-centric approach, well suited to rural contexts, rather than routine administration by protocol is warranted.
Garry Nixon is a rural doctor at Dunstan Hospital. He is the Associate Dean Rural and Head of the Rural Section at the University of Otago. He teaches GENA 728 Cardiorespiratory Medicine in Rural Hospitals.
NSTEMI assessment & management in rural hospitals
Kofoed KF et al. Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome. VERDICT Randomized Controlled Trial Circulation. 2018;138:2741–2750.
The first study compares the outcomes of early PCI (within 12 hours and unrealistic in most of rural NZ) vs. PCI within 72 hours (the current ANZACS – QI NZ target). Reassuringly there was no difference in the end points (all cause mortality, all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure). This supports current practice in most of NZ, assuming we are meeting national targets for these patients (90% receiving PCI within 72 hrs.). It is still important that all our rural nonSTEMI patients are recorded on the ANZACs-QI database so that this can be monitored.
The exception was for high risk patients (GRACE score greater than 140), where there was an observed benefit of early PCI over standard management. That is patients with ST segment changes, haemodynamic instability, heart failure etc. Again, I think this is consistent with current practice, where the majority of these patients would be discussed with cardiology and transferred early.
Shah ASV, Anand A, Strachan FE, Ferry AV, Lee KK, Chapman AR, et al. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: a stepped-wedge, cluster-randomised controlled trial. The Lancet. 2018 Sep;392(10151):919–28
The second study asked the question: In patients with suspected AMI, does the use of a high-sensitivity troponin assay reduce subsequent myocardial infarction or cardiovascular death at 12 months when compared with the use of a standard assay? I.e. Are those rural sites that rely on less sensitive (point of care) troponin assays disadvantaging their patients.
In this study a stepped-wedge, cluster randomised controlled trial methodology allowed the introduction of high sensitivity troponins into 10 Scottish hospitals to be used as an experiment to evaluate the benefits of these assays. Rory Miller is considering doing a similar study when the new high sensitivity point of care Tn assay becomes available in NZ. The traditional assay in this study had cut offs similar to the new cut offs being recommended for the iSTAT Tn assay. (ref)
The bottom line:
The high-sensitivity cardiac troponin I assay resulted in the reclassification 17% of the chest pain patient as nonSTEMI. Only one-third of these were eventually given a diagnosis of type 1 myocardial infarction (most had type II MIs). The reclassification of these patients resulted in an increase in the intensity of their management (including angiography rates) but did not improve outcomes (myocardial infarction or death from cardiovascular causes within one year).
The high sensitivity assay picked up more cases of nonSTEMI but this did not result in improved patient outcomes. This supports the current practice in many NZ rural hospitals of using point of care troponins as a rule out test for AMI.
Geographical Narcissism in Psychotherapy
Fors M. Geographical narcissism in psychotherapy: Countermapping urban assumptions about power, space, and time. Psychoanalytic Psychology. 2018;35(4):446–53.
When this paper was recently passed around (by Prof. Roger Strassser), it came with a one line commentary, ‘food for thought’. The sensible thing would be to pass on with a similarly brief and noncommittal comment. But the article is hard ignore, despite being long, from the other side of the globe and written by a psychologist, in their language.
Its largely a viewpoint paper, that examines the relationship between rural and urban health care providers.
It pulls no punches in describing what it sees as urban privilege and frequently uses the language of power politics and colonisation to describe the relationship between the urban and rural parts of the health sector.
During my postgraduate education in Tromsø, I encountered attitudes that I was in a big city where they really know better, and that my rurally based clinic had a lot to learn from the Tromsø professionals. They never asked how our clinic operated or what they could learn from us.
The attractiveness of rural areas may raise real estate prices beyond the ability of locals to afford. Exploitation and colonization of the rural may also include work opportunities: People from urban areas come “with knowledge” to work for short contracts in rural areas—not to take part fully in such societies but take advantage of them. Visiting urban professionals: Colonizers or rescuers? Many health professionals come here as secular missionaries: They earn money on lucrative short contracts and then leave. Hospital personnel who live here permanently, in contrast, work for a normal salary and must train the transient newcomers.
The most interesting insights might be what the rural urban-divide tells us about ourselves:
A challenge when working in rural areas is the demand to be a good generalist, diving into new arenas and doing as well as possible. The down-side is that one is in constant touch with one’s deficits and limitations. Urban specialization can mean a narrowing of one’s gaze. It may give professionals a false impression that they are doing demonstrably superior interventions, in contrast to the practice of rural clinicians, who are always trying to do what they have not mastered. It is arguable, however, that flexibility, the capacity to learn whatever one has to learn, is a skill in itself.
And perhaps the insight we should be most aware of:
Oppression makes people introject a version of both the oppressor and the oppressed, a complicated mix of feelings of inferiority and resistance.
It won’t be everyone’s cut of tea but if you’ve at it for a while you may appreciate reading the full paper, you may recognise the experiences, others and yourself.
Rory Miller is a rural doctor at Thames Hospital. He teaches GENA 724 Context of rural hospital medicine
Redipred for pre-school wheeze?
Foster SJ, Cooper MN, Oosterhof S, Borland ML. Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine. 2018 Feb 1;6(2):97–106. EZProxy link
Preschool wheeze is a common problem encountered in any clinical practice and there is uncertainty about whether bronchodilaters and corticosteroids are beneficial, given the different aetiology compared with school-aged or older wheezers.
This 2018 Australian (n=605) double-blind study done in an single urban tertiary paediatric emergency department randomised children between 2 and 5 years to receive placebo or prednisolone (1mg/kg) for 3 days if they presented with wheeze plus symptoms/signs of upper respiratory tract infection. Very sick (sepsis, silent chest, ICU) kids were excluded. Children were also excluded if they had had prednisolone in the last 14days. The placebo and prednisolone were designed to look and smell/taste the same.
Length of stay was significantly increased in the placebo group (540 min) versus the prednioslone group (370 min). Although there was no difference between the two therapies in the number of children able to be discharged within 4 hours, there were singificantly more children that had to stay >12 hours in the placebo arm.
Interestingly post-hoc subgroup analysis shows the difference between the two arms was only seen in those children who had received salbutamol before attending the emergency department. No serious adverse events were reported.
Several changes to the methodology were made once the trial commenced, however these are very unlikely to affect the validity of the study.
Oral prednisolone had a clear benefit over placebo at reducing the length of stay in children presenting to a paediatric emergency department with virus-associated wheeze and was well tolerated.
In rural areas, the administration of oral corticosteroids to children aged 2–5 with viral wheeze may enable the child to be kept locally having short stays in assessment/emergency rooms, rather than transfer to base hospital. Overall I think this study reflects that pre-school wheezers are a heterogenous group with a spectrum between responders and non-responders to bronchodilaters, which we see clinically. A study that attempts to identify these children and treat the two groups differently is required. Previous studies of children that included children less than 2 have shown no benefit of prednisolone.
Using sound waves in pneumonia
Lissaman C, Kanjanauptom P, Ong C, Tessaro M, Long E, O’Brien A. Prospective observational study of point-of-care ultrasound for diagnosing pneumonia. Archives of Disease in Childhood. 2018 Jun 7;archdischild–2017–314496. EZProxy link
This study in an Australian tertiary Paediatric ED included children aged 1mo to 18 years who were going to have a chest XRay (CXR) for suspected pneumonia.
There is an emphasis on a clinical diagnosis of pneumonia, however this may increase unnecessary antibiotic use. CXR is often used to support clinical suspicion, although CXR lack sensitivity and may not alter patient outcomes. Lung ultrasound (LUS) may offer a low cost, radiation free and increasingly available option cf. CXR. This study “aimed to contribute evidence for the accuracy of point-of-care LUS in the diagnosis of pneumonia, using CR as the reference standard, and guide future research that may reduce CR rates and improve antibiotic stewardship.
This was a prospective observational cohort study (n=97) that included patients were aged 1mo to 18yo who received a CXR for possible pneumonia. Children with prior CXR for same illness or requiring ‘life support’ were excluded. All children received a single AP CXR. Clinicians interpreted the film using a standardised form and were blinded from the LUS findings. The CXR was then read by radiologist who was also blinded from the LUS findings.
LUS was performed within 12 hours of presentation by a first year paediatric medicine fellow and a final year medical student, both without prior ultrasound experience. LUS included upper and lower zones of anterior, lateral, posterior lungs in longitudinal and oblique orientations using a linear transducer (L14–5w Zonare).
Sonographic diagnosis= lung consolidation with air bronchograms. Subpleural consolidation depth was measured to allow sub-analysis if depth >1cm. The sonologists didn’t read clinical notes and scans ‘double-read’ by an ED physician with extensive USS training.
97 patients with suspected pneumonia were included in the study. CXR was positive in 45% and LUS positive in 59% of patients. IPU admission occurred in 52% with positive CXR. Consolidation was identified in 85% of these patients by the reviewing sonologist and 79% had air bronchograms. B lines were present in 72% of positive scans and 78% of negative scans.
Sensitivity and specificity compared to CXR was 91% (78–98%) and 68%(54%–80%) respectively. (NPV = 90%, PPV 70%). If >1cm of subpleural consolidation used sensitivity decreased to 71% (55–83%) and specificity increased to 85% (72–93%). (NPV = 78%, PPV 80%)
When consolidation >1cm, 87% had clinical diagnosis of pneumonia and were treated with antibiotics. When consolidation <1cm, 56% had a clinical diagnosis of pneumonia and received antibiotics. The remaining patients improved without antibiotics.
Point-of-care LUS appears promising for the diagnosis of pneumonia in the hands of sonologists with focused training in the paediatric ED. LUS may be an appropriate first-line imaging modality in patients with possible pneumonia. A positive finding of >1 cm of lung consolidation may rule-in pneumonia without requiring CXR confirmation. Subsequent studies with a greater sample size could confirm these findings, better clarify whether the size of consolidation has clinical significance and evaluate the role of LUS in decision-making regarding antibiotics.”
Many of us have ready access to POCUS and limited access to plain film radiology, especially after-hours. This study shows that POCUS may have the ability to identify pneumonic consolidation (especially if subpleural consolidation >1cm) nearly as well as CXR in children and confirm clinical suspicions without needing to call in the radiographer or subject the child to unnecessary radiation. It is important to note to note that sub-pleural consolidation and air-bronchograms are required and not the presence of b-lines alone.
However, this study assumed that CXR is the gold standard in the diagnosis of pneumonia and doesn’t really determine which children need antibiotics, which is the more relevant question. It appears that if the consolidation is <1cm or without air bronchograms then you are probably ok without but this is begging for a nice trial.(5)
1. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. New England Journal of Medicine. 2018 Jan;378(1):11–21.
2. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. New England Journal of Medicine. 2018 Feb;378(8):708–18.
3. Mead GE, Hsieh C-F, Lee R, Kutlubaev MA, Claxton A, Hankey GJ, et al. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database of Systematic Reviews. 2012;(11).
4. Chollet F, Tardy J, Albucher J-F, Thalamas C, Berard E, Lamy C, et al. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): A randomised placebo-controlled trial. The Lancet Neurology. 2011 Feb;10(2):123–30.
5. Milliner BHA, Tsung JW. Lung Consolidation Locations for Optimal Lung Ultrasound Scanning in Diagnosing Pediatric Pneumonia. Journal of Ultrasound in Medicine. 2017;36(11):2325–8.