Narrative reviews

Reperfusion therapies for ischaemic stroke have transformed the prognosis for long term disability, but maximising patient benefit requires increased community recognition and faster treatment

Bruce CV Campbell

Due to the remarkable improvements in the diagnosis and management of myeloma over the past decade, we can look forward to regimens that will allow the eradication of residual disease and result in the cure of myeloma

Douglas E Joshua · Christian Bryant · Caroline Dix · John Gibson · Joy Ho

A review of the legislation may be warranted to assess the balance between professional and public interests

Leon A Simons

A low threshold for investigation and treatment of CVD in COPD and COPD in CVD is essential

Paul Leong · Martin I Macdonald · Brian S Ko · Phil G Bardin

Despite pregnancy being identified as a time of increased HIV susceptibility, with risks to both the mother and unborn infant of HIV acquisition, there is a paucity of guidelines, eligibility criteria and risk assessment tools pertaining specifically to the usage of PrEP in pregnancy and lactation. Existing local and international guidelines suggest a low threshold for the initiation of PrEP in serodiscordant HIV‐negative women. It is imperative that the needs of such patients be met through the implementation of strategies to enable appropriate and timely prescription of PrEP.Moreover, with the commencement of availability of Pharmaceutical Benefits Scheme‐subsidised PrEP, the financial and practical obstacles to PrEP provision will be reduced and a subsequent increase in patient awareness and acceptance of PrEP is anticipated. However, the logistics and responsibility of providing PrEP and subsequent necessary follow‐up for pregnant and lactating women at risk of HIV infection has not been sufficiently considered or formalised (ie, general practice versus antenatal clinic).We therefore recommend development of multidisciplinary guidelines on the prevention of mother‐to‐child transmission of HIV among Australian pregnant and lactating women. These guidelines should include information about PrEP. Development of the guidelines must also engage with clinicians treating male patients to ensure that uninfected female partners of child‐bearing potential are not forgotten. The guidelines will require multidisciplinary input including expertise in the areas of HIV, obstetrics, midwifery, general practice and paediatrics, and commitment to: outlining the appropriate circumstances for the provision of PrEP during peri‐conception, pregnancy and lactation; creation of behavioural eligibility criteria and risk assessment tools which recognise the risks specific to pregnant and lactating women; outlining the appropriate follow‐up of patients commenced on PrEP during pregnancy and lactation; defining the setting in which PrEP will be prescribed and post‐prescription surveillance will be undertaken for the pregnant and lactating patient cohort; targeted education of health professionals tasked with the provision of PrEP to the pregnant and breastfeeding patient group; and creation of patient information resources to maximise serodiscordant couple awareness of the requirement for pre‐conception counselling and treatment options available. We believe such a framework is vital to guide and empower medical professionals in the appropriate usage of PrEP in this patient cohort and ultimately provide the best patient care.

Lisa Horgan · Christopher C Blyth · Asha C Bowen · David A Nolan · Andrew P McLean‐Tooke

As a result of their widespread use, elucidating the influence of DMTs on fertility, pregnancy and breastfeeding is critical for assisting physicians and patients in weighing up the relative risks and benefits of continuing therapy. International pregnancy registries have a key role to play, and neurologists should be encouraged to contribute to these when possible. Furthermore, family planning counselling may be useful for patients with multiple sclerosis to help alleviate fears and concerns and to enable more informed decision making. A multidisciplinary approach, involving collaboration between neurologists, obstetricians, midwives, anaesthesiologists and fertility specialists (when required), is also recommended to help optimise outcomes for both the patient and the child. Decision making should be a shared experience between patient and physician, with a personalised approach developed to meet the unique needs of each individual patient.

Anneke Van Der Walt · Ai‐Lan Nguyen · Vilija Jokubaitis

The peak incidence of IBD overlaps with the prime childbearing years; thus, the issue of medication use and disease control in pregnancy is of particular relevance for both patient wellbeing and all treating physicians.The most important factor in optimising pregnancy outcomes for women with IBD is to ensure their disease is in remission before and during pregnancy. Patients should be encouraged to continue their IBD medications in order to maintain disease remission. Patients with IBD require clinician‐initiated pre‐conception counselling and a consistent message regarding these factors. It is recommended that patients are reviewed regularly by their gastroenterologist during pregnancy and assessment of disease activity is performed in the form of objective, non‐invasive markers, such as faecal calprotectin. In the event of a disease flare during pregnancy, the patient's gastroenterologist should be contacted promptly and appropriate escalation of therapy should be arranged.

Sally J Bell · Emma K Flanagan

Glaucoma management varies depending on the underlying causative mechanism, with options trending towards earlier surgical intervention for both open‐angle and angle closure glaucoma. While the increased acceptance of SLT and the introduction of MIGS devices have started to change the face of glaucoma management, IOP‐lowering eye drops remain the foundation of treatment. Adherence is an ongoing treatment limitation and future therapies are being designed to diminish this.

Jed Lusthaus · Ivan Goldberg

The minimum requirement for TKA must be prolonged clinically important symptoms in the presence of clinical signs that allow attribution of those symptoms to local pathology affecting articular surfaces and knee alignment. If, after reasonable attempts at non‐operative treatment, symptoms are sufficiently severe to justify the risks, a person is considered suitable for surgery. Optimisation to attenuate surgical risks should be attempted in all TKA candidates, although high level evidence is lacking for certain important factors. Pre‐operative interventional trials, with the aim of improving post‐operative TKA outcomes, are particularly needed in the areas of patient expectation, diabetes, obesity and vascular disease.

Sam Adie · Ian Harris · Alwin Chuan · Peter Lewis · Justine M Naylor

The incidence of cerebral palsy is decreasing and early identification is not only important for families but may help to target treatment. Early interventions with targeted therapies are showing promising results in altering the natural history of cerebral palsy as well as enhancing patient activities. There remain many challenges in the management of a child with cerebral palsy, but there exist a number of interventions with a good evidence base. A child's ability should be viewed in context of their development and current evidence used to guide treatment with what is important for the child and their family. The six Fs framework provides a guide to developing shared goals with families.

David Graham · Simon P Paget · Neil Wimalasundera

Recent international consensus guidelines provide a more rigorous approach to diagnosis, introducing a system of major and minor criteria to facilitate early and accurate diagnosis and to guide diagnostic food challenge. They highlight the need for rapid fluid resuscitation in emergency presentations and the increasing evidence for the use of ondansetron in acute management. Diagnostic challenges should be performed in settings with suitable resuscitation facilities. Action plans and dietary information consistent with this guideline are available via ASCIA.10It is likely that improved understanding of the immunological basis of FPIES will, in the future, facilitate the development of a sensitive and specific biomarker. Until that time, use of standardised diagnostic criteria, improved recognition, timely fluid resuscitation, avoidance of trigger foods, and education form current best practice.

Sam Mehr · Dianne E Campbell

At present, high level evidence for the safety and efficacy of radiotherapy and immunotherapy still need to be demonstrated clinically; therefore, the combination cannot be recommended outside of clinical trials. It is also currently unclear which patients will benefit from the combination. However, due to the increased number of clinical trials investigating radiotherapy as a mean to antitumour immunity, it is likely that the evidence will emerge shortly.40,41 In 2016, a study presented a list of 93 active trials combining radiotherapy with an antibody inhibiting CTLA‐4, PD‐1 and PD‐L1, transforming growth factor β‐cytokine, or other immune molecules.40 ClinicalTrials.gov now reports at least 200 completed or recruiting trials evaluating the new combination. Box 1 lists investigator‐initiated clinical trials combining radiotherapy and immunotherapy in Australia. If positive, the results of these trials are likely to lead to a paradigm shift in the use of radiotherapy, which would certainly be a cost‐effective and low toxicity mean to enhance the response to immune agents in addition to its well established role of killing tumour cells. 3 Trial name (trial registration no.) Phase Disease (stage) Radiotherapy dose Immunotherapy Question SABRSeq (NCT03307759) 1b (randomised) NSCLC (IV) 18–20 Gy/1 fraction to 1–3 metastases, 7 days before ICIs 18–20 Gy/1 fraction to 1–3 metastases, 7 days after ICIs Pembrolizumab Safety profile of SABR with ICIs when given before or after SABR RAPPORT (NCT02855203) 1b/2 (single arm) RCC (oligometastatic IV) 18–20 Gy/1 fraction to 1–5 metastases, 5 days before ICIs Pembrolizumab Safety profile of SABR with pembrolizumab BOSTON‐II (closed) (NCT02303366) 1b (single arm) Breast (oligometastatic IV) 20 Gy/1 fraction to 1–5 metastases Pembrolizumab Safety profile of SABR with pembrolizumab AZTEC (TROG 17.05) 2 (randomised) Breast triple negative (IV with ≥ 2 metastases) 20 Gy/1 fraction to 1–4 metastases 24 Gy/3 fractions to 1–4 metastases Delivered before ICIs Atezolizumab Efficacy and safety of two SABR fractionation with atezolizumab ICE‐PAC (ACTRN12618000954224) 2 (single arm) Prostate (mCRPC) (IV) 18–20 Gy/1 fraction to 2–3 metastases, 5 days before ICIs Avelumab rPFS at 24 weeks NIVORAD (TROG 16.01) 2 (randomised) NSCLC (IV) 18–20 Gy/1 fraction to ≥ 1 metastases 14 days after ICIs No radiotherapy Nivolumab PFS at 6 months SABR‐IMPACT I (ACTRN12616001064493) (U1111‐1185‐5624) 1 (multilevel) Melanoma (non‐oligometastatic IV) 10–30 Gy/1 fraction to single metastasis, before or during ICIs Ipilimumab, nivolumab or pembrolizumab Maximum tolerated dose of SABR with ICIs PCR‐MIB (NCT02662062) 2 (single arm) Bladder (II–III post‐TURBT) 64 Gy/32 fractions + concurrent cisplatin + ICIs Pembrolizumab Grade 3 or 4 acute toxicities (excluding urinary) ABC‐X Study (NCT03340129) 2 (single arm) Melanoma (brain metastasis IV) SRS: 16–22 Gy/1 fraction or 30 Gy/10 fractions whole brain Ipilimumab and nivolumab Intracranial response to immunotherapy Ave‐Rec (NCT03299660) 2 (single arm) Rectal carcinoma (III) 50.4 Gy/28 fractions + 5FU, before ICIs Avelumab Pathological response rate ICIs = immune checkpoint inhibitors. 5FU = fluorouracil. mCRPC = metastatic castration‐resistant prostate cancer. NSCLC = non‐small cell lung cancer. PFS = progression‐free‐survival. RCC = renal cell carcinoma. rPFS = radiological progression‐free survival. SABR = stereotactic ablative radiotherapy. TURBT = transurethral resection of bladder tumour. ◆ Much needs to be understood to optimise the complex immunological effect of radiotherapy and its interaction with ICIs. Histological subtype, target organ (bone, visceral, brain), immunotherapy molecule, volume of irradiation, radiotherapy dose and sequence are hypothesised to have different effects. Radiotherapy pulsing, in which doses of radiation are delivered regularly (eg, monthly) throughout the ICI therapy, has also been proposed.64In conclusion, ICIs result in impressive clinical responses in select groups of patients, but optimal results in larger populations will require combination with other therapies. Radiotherapy will certainly be part of this arsenal, but fundamental questions about mechanisms of treatment non‐redundancy, tumour resistance and patients’ tolerance are to be answered. Preclinical studies to direct informed clinical trial design are needed to determine how best to integrate these modalities and optimise their synergistic effect.

Guy‐Anne Turgeon · Andrew Weickhardt · Arun A Azad · Benjamin Solomon · Shankar Siva

A new PBS indication for goserelin aims to reduce infertility and other health issues for young Australian women who receive chemotherapy

Wanyuan Cui · Catharyn Stern · Martha Hickey · Fiona Goldblatt · Antoinette Anazodo · William S Stevenson · Kelly-Anne Phillips

Prompt evaluation and immediate empiric therapy are essential for averting fatal outcomes and chronic neurological sequelae

Miles H Beaman

The gut microbiota is a key cause, and potential cure, of modern gut disorders including inflammatory bowel disease, liver diseases, metabolic syndrome and obesity

Lauren S White · Johan Van den Bogaerde · Michael Kamm

The emphasis on prompt diagnosis and treatment of irritable bowel disease offers the possibility of altering the natural history of disease and reducing disability

Emily K Wright · Nik S Ding · Ola Niewiadomski

Curbing the problem of obesity is achievable and can be realised through a combination of smart governance, community initiatives, the support of individual efforts, and clinical leadership

Seema Mihrshahi · Megan L Gow · Louise A Baur

Optimal care to patients with end-stage kidney disease involves timely referral to a nephrologist and a patient-centred decision to start dialysis

Titi Chen · Vincent WS Lee · David C Harris

We need to reduce the barriers to primary care access for people experiencing homelessness to stop the costly revolving door between homelessness and the hospital system

Andrew Davies · Lisa J Wood

Bronchiectasis is gaining recognition as an important chronic lung disease of increasing prevalence

Simone K Visser · Peter Bye · Lucy Morgan

The introduction of TAVI has revolutionised the management of aortic valve disease in Australia

Adam J Nelson · Nicholas J Montarello · Claudia S Cosgrove · Ross L Roberts-Thomson · Sinny Delacroix · Ramesh G Chokka · Joseph K Montarello · Stephen G Worthley

Chronic idiopathic constipation (CIC) is one of the most common gastrointestinal disorders, with a global prevalence of 14%. It is commoner in women and its prevalence increases with age. There are three subtypes of CIC: dyssynergic defaecation, slow transit constipation and normal transit constipation, which is the most common subtype. Clinical assessment of the patient with constipation requires careful history taking, in order to identify any red flag symptoms that would necessitate further investigation with colonoscopy to exclude colorectal malignancy. Screening for hypercalcaemia, hypothyroidism and coeliac disease with appropriate blood tests should be considered. A digital rectal examination should be performed to assess for evidence of dyssynergic defaecation. If this is suspected, further investigation with high resolution anorectal manometry should be undertaken. Anorectal biofeedback can be offered to patients with dyssynergic defaecation as a means of correcting the associated impairment of pelvic floor, abdominal wall and rectal functioning. Lifestyle modifications, such as increasing dietary fibre, are the first step in managing other causes of CIC. If patients do not respond to these simple changes, then treatment with osmotic and stimulant laxatives should be trialled. Patients not responding to traditional laxatives should be offered treatment with prosecretory agents such as lubiprostone, linaclotide and plecanatide, or the 5-HT4 receptor agonist prucalopride, where available. If there is no response to pharmacological treatment, surgical intervention can be considered, but it is only suitable for a carefully selected subset of patients with proven slow transit constipation.

Christopher J Black · Alexander C Ford

Consideration of the clinical context, expert evaluation of thyroid sonography, careful selection of nodules for fine-needle aspiration, and standardised cytology reporting are important components in thyroid nodules assessment

Rosemary Wong · Stephen G Farrell · Mathis Grossmann

From its early infancy in 1986, it continues to evolve and is internationally recognised as demonstrating worldÕs best practices

Miranda A Paraskeva · Kovi C Levin · Glen P Westall · Gregory I Snell

Key advances include the development of validated tools for holistic measurement and grading of non-motor symptoms, and a focus on multi-modal biomarkers to define non-motor subtypes

Nataliya Titova · K Ray Chaudhuri