Published: 9 June, 2023
New article: Appropriate use of tumour markers
The appropriate use of serum tumour marker testing is complex and patient harm can occur when testing is requested but not clinically indicated. This overview article covers the most frequently used tumour markers, and when they should, and should not, be requested. The main role for a tumour marker test is in the management of a patient with a known malignancy. However, there are some tumour markers that are useful in the detection of specific cancers, e.g. CA 125 in ovarian cancer.
Read the full article here
New cervical screening guidelines published
New Clinical Practice Guidelines for Cervical Screening in New Zealand (2023) have been published. These guidelines are to be used from 26th July, 2023, when HPV testing (with the option of self-testing using a vaginal swab) is introduced as the primary cervical screening test. Read the new guidelines here.
A video providing a basic overview of HPV Primary Screening has been produced by the National Cervical Screening Programme. Click here to watch.
Training modules will also be available and are expected to be online from mid-June. The first training module includes information on HPV, an overview of the cervical screening pathways and how to support decision-making by participants.
Alert Communication: sodium valproate use in males
Medsafe has issued an Alert Communication on the use of sodium valproate (Epilim) in “people who can father a child”. Evidence from a retrospective observational study in Europe revealed a potential increased risk of neurodevelopmental disorders in children after paternal use of sodium valproate at the time of conception, compared to lamotrigine or levetiracetam. The data sheets and consumer medicine information leaflets have been updated to reflect this.
Medsafe is advising healthcare professionals to inform male patients who are taking sodium valproate about this potential risk, and to consider switching those who are planning parenthood soon to an alternative treatment. At the time of prescribing sodium valproate to a male patient, discuss the need for effective contraception (if relevant), and revisit this conversation annually. A letter for healthcare professionals from the manufacturer about this risk is available here.
A guide has been produced for males taking sodium valproate, and it is recommended that this is provided to patients.
N.B. The risk of adverse effects of antiepileptic medicines for females of reproductive age is already well documented, and precautions around effective contraception for females also apply. Read more here.
Latest edition of Prescriber Update released
The June edition of Prescriber Update has been published; particular items of interest include:
- Antipsychotic-induced constipation
- Constipation is a common adverse effect of antipsychotic medicines, especially clozapine; monitor patients for constipation (which is often under-reported and can progress to be life-threatening) and initiate appropriate treatment early. Prescribe prophylactic laxatives for patients taking clozapine. For information on preventing clozapine-induced constipation, see: https://bpac.org.nz/2017/clozapine.aspx
- Ocular nonsteroidal anti-inflammatory drugs (NSAIDs) and corneal melting
- Caution is required with ocular NSAIDs, which are most commonly used after ocular surgery or injury; advise patients to urgently seek medical attention if symptoms or signs of “corneal melting” occur, e.g. eye irritation or pain, blurry or distorted vision, ocular discharge
- Autoimmune complications of immunotherapy
- Autoimmune-related adverse effects may occur during or after treatment with immune checkpoint inhibitors (e.g. nausea, diarrhoea, itching, rash, fatigue, respiratory disorders, hepatitis); be aware of this if you have any patients recently taking these medicines who develop unexplained symptoms and signs
- Quarterly summary of recent safety communications
- MARC’s remarks: March 2023 meeting
- Gathering knowledge from adverse reaction reports: June 2023
View the full edition here
ACE inhibitors and angioedema
Angiotensin-converting enzyme (ACE) inhibitors are widely prescribed in primary care. While these medicines are generally well-tolerated, rare serious adverse effects can occur in some patients, even after long periods of use without incident. A Medsafe reminder published in the latest Prescriber Update has highlighted a fatal case of ACE inhibitor-induced angioedema recently reported to The Centre for Adverse Reactions Monitoring (CARM). This involved a patient who had previously exhibited minor tongue swelling with ACE inhibitor use and was subsequently initiated on a different ACE inhibitor at a later date.
Consider the risk of angioedema whenever prescribing ACE inhibitors. Ask patients whether they have previously experienced reactions such as swelling with ACE inhibitor use and ensure they know to seek urgent medical attention if symptoms occur (and to immediately discontinue use). If airway compromise is confirmed, refer the patient immediately to the emergency department. The event should be clearly documented in the medical notes, and the patient educated that they should not take ACE inhibitors, to prevent future occurrence, e.g. if the patient changes medical providers. An alternative antihypertensive should be considered. The associated risk of angioedema is lower in patients prescribed an angiotensin receptor blocker (ARB), however, cross-reactivity can still occur in those who have previously experienced ACE inhibitor-induced angioedema.
Reminder: patients currently taking cilazapril should be switched to another appropriate medicine before the end of 2023 (as reported in Bulletin 74)
For further information on prescribing ACE inhibitors, see: https://bpac.org.nz/2021/ace.aspx
SGLT-2 inhibitors and the risk of polycythaemia
As covered in the June edition of Prescriber Update, Medsafe is warning of the potential risk of polycythaemia with SGLT-2 inhibitor use (e.g. empagliflozin) based on a recent case report to CARM. SGLT-2 inhibitors are recommended not only for patients with diabetes but also in the management of other long-term conditions, e.g. chronic kidney disease, heart failure. Given their recent emergence and application in daily practice, the evidence around potential adverse effects is still evolving. In Bulletin 64 we discussed two other rare, but serious adverse effects associated with SGLT-2 inhibitors: diabetic ketoacidosis and Fournier’s gangrene.
Patients with polycythaemia (erythrocytosis) have an abnormally high concentration of red blood cells, resulting in increased haemoglobin and/or haematocrit levels.
While the mechanism and consequences of SGLT-2 inhibitor-induced polycythaemia continue to be reported and investigated in the wider literature, specific forms of polycythaemia (e.g. polycythaemia vera) have previously been associated with an increased risk of thromboembolic events.
If polycythaemia is detected on FBC during follow-up, consider SGLT-2 inhibitors as a potential cause after considering patient history and examination findings, e.g. dehydration, hypoxaemia-related conditions, renal dysfunction. In some cases, secondary care input may be necessary for guiding diagnosis and management; depending on the severity of the polycythaemia, the SGLT-2 inhibitor may need to be discontinued.
Coeliac Awareness Week
Next week (12 – 18th June) is coeliac disease awareness week. The theme for this year is “My coeliac challenge – take charge, get diagnosed and find help” which aims to encourage people with coeliac disease to think about different ways to overcome some of the challenges they encounter, which are often daily. Click here for more information.
Raising awareness of coeliac disease can prompt people with symptoms or risk factors to get tested. Coeliac Awareness Week may provide an opportunity for clinicians to refresh their knowledge about the condition and to consider whether they are testing appropriately. For your patients with known coeliac disease, it might be a chance to check how they are managing with a gluten-free diet and whether they have any new or persistent symptoms that require further investigation.
For further information on the investigation and management of coeliac disease in primary care, see: https://bpac.org.nz/2022/coeliac.aspx
Medicine supply issues
The following issues relating to medicine supply, of particular interest to primary care, have recently been announced. This information is also available in the New Zealand Formulary at the top of the individual monograph for any affected medicine and summarised here.
Paracetamol 250 mg/5 mL oral liquid
Paracetamol 250 mg/5 mL oral liquid is now out of stock with the supplier, following the shortage that was reported in Bulletin 75. New stock is expected to arrive during June. Supply of the paracetamol 120 mg/5 mL oral liquid is currently unaffected.
Amoxicillin with clavulanic acid
Amoxicillin 250 mg/5 mL with clavulanic acid 62.5 mg/5 mL oral liquid* (Curam) is out of stock due to high demand. The 125 mg/5 mL amoxicillin with 31.25 mg/5 mL clavulanic acid (Augmentin) is currently unaffected. Stock of Curam is not expected to arrive until July, 2023. Pharmac is looking for an alternative product, however, in the meantime, the lower strength of amoxicillin with clavulanic acid may need to be prescribed. Ensure parents/caregivers of children understand that a different dose measurement will be required (if they are usually prescribed the other strength). Otherwise, consider whether an alternative antibiotic could be used (there are few first-line indications for amoxicillin clavulanate).
*Amoxicillin 50 mg with clavulanic acid 12.5 mg per mL powder (grans) for oral suspension
Supply issues affecting salbutamol inhalers have been ongoing. The current situation is that:
- Respigen is now available (following a recent supply issue as reported in Bulletin 68), but supply is still constrained. It may take some time for stock to reach all pharmacies. Stock levels are expected to return to normal by August.
- SalAir is out of stock and there is a delay in getting new supply
- Ventolin is available and is a suitable alternative inhaler to Respigen or SalAir if required, but it is only partly funded
There is also currently a supply issue affecting stock of Duolin HFA inhalers (salbutamol with ipratropium bromide). For further information, click here.
NZF updates for June
Significant changes to the NZF in the June, 2023, release include:
- New contraindication added to ACE inhibitor monographs: concomitant use of sacubitril + valsartan
- Caution added to the cephalosporin monographs: concomitant nephrotoxic medicines, e.g. aminoglycosides (high dose cephalosporins may potentiate nephrotoxic effect). Reversible neurotoxicity (including seizures, myoclonus, agitation, delirium) has also been added as an adverse effect. For further information on the risk of neurotoxicity with cephalosporins, see Bulletin 70
- Cautions, pre-treatment screening and monitoring requirements updated in the pamidronate disodium monograph
- New indication added to the secukinumab monograph: non-radiographic axial spondylarthritis that is unresponsive to, or where there is intolerance of non-steroidal anti-inflammatory treatment
- Medsafe Monitoring Communication: interleukin inhibitors and the possible risk of pancreatitis has been added to the interleukin inhibitor monographs. See Bulletin 74 for further details.
You can read about all the changes in the June release here. Also read about any significant changes to the NZF for Children (NZFC), here.
GP CME Conference Rotorua: It’s on!
If you are attending the GP CME conference in Rotorua this weekend, come see our colleagues on the South Link Education Trust stand. The South Link Education Trust is the Diamond Sponsor of the GP CME conferences, and is home to South Link Health Services, BPAC Clinical Solutions, bpacnz Publications and the New Zealand Medicines Formulary (NZF and NZFC). The team will be presenting the new Smart Care products, along with showcasing the full range of activities and services.
Grab yourself a copy of the special conference edition Best Practice Journal or The Little Book of Thinking: a guide to peer group discussions. We would love to hear your feedback on our resources.
Paper of the Week: "Is laughter really the best medicine?"
Everyone has heard the phrase “laughter is the best medicine” but whether this statement counts as evidence-based medicine is up for debate. Previous studies have shown the potentially beneficial effects of laughter on cardiovascular health and type 2 diabetes, but there is limited evidence that laughing reduces endogenous cortisol levels. Given that everyday life is becoming more stressful for a lot of people, could taking some time out of the day to laugh really make a difference?
A 2023 systematic review and meta-analysis was carried out with the aim of determining the impact of spontaneous laughter on endogenous cortisol levels. The study found an approximately 32% reduction in cortisol levels for participants who took part in a laughing intervention such as watching a humorous video or receiving laughter therapy. This suggests there may be a therapeutic role for spontaneous laughter alongside established management interventions to improve patient outcomes.
Could you incorporate these findings into “behavioural activation” recommendations in your practice? By encouraging patients to regularly make time for an activity they enjoy, specifically something that makes them laugh or even just smile, whether it be watching a comedy, playing a game/sport, interacting with a pet, hanging out with friends or family, there is the potential to reduce ruminating negative emotions and make sustained improvements to their mood and resilience.
- Eight studies (four randomised controlled trials [RCTs] and four quasi-experimental studies) met inclusion criteria
- Studies that evaluated a laughter intervention alongside physical activity were excluded as exercise is known to reduce endogenous cortisol levels
- Data from a total of 315 participants were included. Participants had a mean age of 39 years (range: 24 – 69 years) and varied from healthy individuals to people with obesity, diabetes or receiving haemodialysis.
- Laughter interventions included watching humorous videos (five of the studies), participating in a self-administered laughing programme (one study) or receiving “laughter sessions” supervised by a trained laughter therapist (two of the studies)
- Interventions were either administered as a single session or during multiple sessions over a period of four to six weeks
- The duration of individual laughter interventions ranged from 9 – 60 minutes
- Laughter interventions were administered in both individual and group settings
- The biological effect of laughter was assessed by measuring changes in either serum or salivary cortisol levels. The time of day samples were collected varied between studies.
- The meta-analysis found an approximately 32% reduction in cortisol levels for participants who took part in laughter interventions, compared to those who did not
- This result was independent of the type of laughing intervention used; participants who watched a humorous video had a 37% reduction in cortisol levels while participants who received laughter therapy had a 19% reduction
- Sensitivity analysis showed that even just a single laughing intervention session reduced cortisol levels by 37%, however, the duration of the laughter intervention had little effect on the overall reduction in cortisol levels
- Also, when the four RCTs were analysed alone, laughter interventions showed a 37% reduction in cortisol levels compared to placebo (listed as watching “neutral” videos, reading a book or sitting quietly)
- The authors highlighted that the small sample sizes of the included studies and intervention heterogeneity, e.g. duration of intervention, were unlikely to influence their results as the effect of laughter on cortisol levels was shown over a range of interventions and the duration of intervention had no effect
- A potential source of bias acknowledged by the authors is the impact of social interaction on the laughter interventions delivered in the group settings
Kramer CK, Leitao CB. Laughter as medicine: a systematic review and meta-analysis of interventional studies evaluating the impact of spontaneous laughter on cortisol levels. PLoS ONE 2023;18:e0286260. doi:10.1371/journal.pone.0286260.
This Bulletin is supported by the South Link Education Trust
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