Year: 2024

The New Zealand General Practice Podcast

opotikigp family medicine, general practice, Healthcare , , , , , , ,
Clinical Snippets February 2024

Shownotes

Clinical Snippets February 2024

1.  ACE and ARB and statin use in pregnancy – DON’T

The NZF notes that ACE inhibitors should be avoided at all stages of pregnancy. Fetal skull defects have been reported following first trimester exposure to ACE inhibitors although evidence of teratogenicity is inconclusive. In the second and third trimesters ACE inhibitors can cause abnormalities including fetal growth retardation, oligohydramnios and fetal or neonatal renal failure. Fetal death in utero has also been reported. Pregnant women who are taking an ACE inhibitor should be changed to an alternative antihypertensive as soon as possible.  Like ACE inhibitors ARBs should be avoided in pregnancy, particularly in the second and third trimesters, as similar effects to those caused by ACE inhibitors in pregnancy are expected.  

NZF notes also that Statins should be avoided in pregnancy as congenital anomalies have been reported and the decreased synthesis of cholesterol possibly affects fetal development. The individualstatin monographs state the drug is contraindicated during the first trimester and adequate contraception is required during treatment and for 1 month afterwards.  However, a 2022 metanalysis and systematic review noted there are some patients for whom there may be a significant benefit of maintaining statin therapy, in particular in the second and third trimesters. The risk and benefit of statins treatment during pregnancy need to be evaluated in an individualized approach and every trimester apart.

2.  Monitoring lithium drug interactions

A September NZ Doctor article on monitoring drug interactions with lithium is a helpful refresher on monitoring recommendations for patients on lithium therapy:

(i)  Usual monitoring: (current reference range for chronic use is 0.6-0.8 mmoL/L):

  • Three to six-monthly (depending on stability) – serum lithium level, electrolytes, eGFR.
  • Six-monthly – thyroid function, calcium, weight.
  • Annually (if over age 40 or obese) – HbA1c, lipids, consider ECG.

(ii)  When adding or removing medicines:

  • ACE inhibitors – baseline serum lithium level and renal function tests, then weekly for six weeks or until stable. For “at-risk” people (impaired renal function, volume depletion or heart failure) consider further two-weekly checks for six weeks.

20 to 35 % of people will have an increase in lithium levels if an ACE inhibitor is added to their regime, usually by around 33 %. The interaction can be delayed for up to five weeks, so it is important not to be reassured by steady lithium levels initially.  ARB interaction less likely but dose dependent (ARB) increases in lithium levels of up to 20 % after up to five weeks of treatment have been reported. 

  • Diuretics – baseline serum lithium level and renal function tests, then weekly for four weeks.

If a thiazide needs to be introduced, there may be a rapid increase in serum lithium levels by 20-25 % in 3-10 days, although this effect may also be delayed.  Loop diuretics have less impact, with potentially only up to a 20% increase in levels, and potassium-sparing diuretics appear to have no effect.

  • NSAIDs – baseline serum lithium level and renal function tests, then weekly for two weeks or until stable.

This interaction is well described for decreasing lithium clearance and increasing its toxicity, although it is unpredictable. While the average decrease in lithium clearance is usually 10-25%, there is wide variation, especially in people with impaired renal function. It is unlikely that COX-2 inhibitors would be any different to traditional NSAIDs regarding this interaction.

The risk is cumulative with concomitant use of ACE inhibitors, diuretics and NSAIDs.

3.  Shared care clozapine

The October 2023 NZ Doctor includes a refresher on shared care prescribing of clozapine.  Points include:

(i)  Clozapine can only be initiated by a psychiatrist. In some localities within Te Whatu Ora, GPs and nurse practitioners can be responsible for ongoing prescribing under the supervision of a psychiatrist. GPs can also prescribe for those with stable illness in collaboration with a community mental health team.  Patients are considered stable if they have been taking clozapine continuously for two years, had no mental-health-related hospital admissions in the last 12 months, are not taking other medications requiring close monitoring by a psychiatrist, and have been adherent to treatment and attending appointments.

(ii)  Due to the risk of agranulocytosis, all patients prescribed Clopine in New Zealand must be registered to ClopineCentral™ (the Clopine Monitoring System) or CareLink Plus (the Clozaril Monitoring System) by a registered medical practitioner.  Prescribing physicians must also register themselves onto the relevant monitoring system to access patient information. Brand swapping between clozapine products is discouraged and should occur on the advice of the initiating clinician or team. 

(iii)  The adverse effect and drug interaction profile of clozapine is wide (in particular agranulocytosis, severe constipation and cardiomyopathy/myocarditis) and there are specific requirements for pre-prescribing screening and subsequent monitoring which are critical to reduce the risk of patient harm.  There is comprehensive practical information available on HealthPathways (not yet localised for Midlands) and in publications by BPAC (2017) and SafeRx. 

(iv) Clozapine levels are reduced by cigarette smoking; however, it is the constituents of smoke, not nicotine itself, that is responsible.  Elevated clozapine levels, up to double baseline, may occur when patients stop smoking and this is not affected by NRT.  If patients stop smoking it is advisable to monitor plasma clozapine levels, dose reduction may be required in conjunction with mental health service advice. Conversely, if a patient starts smoking during treatment, the therapeutic effect of clozapine may be reduced. The plasma concentration of clozapine can also be increased by a high caffeine intake (more than 400mg/day – colas, tea and many energy drinks contain significant amounts of caffeine). Clozapine levels can subsequently decrease by nearly 50% after a 5-day caffeine-free period.

(v)  The article concludes:  Every time a patient comes in, there is an opportunity to query about adverse effects (with a focus on smoking status and bowel habits), check they are taking their medication appropriately, and offer lifestyle advice. Blood test results should be checked and compared with baseline. It is also important to ensure patients are aware of the need for blood tests to be done on the day they are due.  The Porirua Protocol is an evidence-based bowel management regime for patients taking clozapine.  

4.  PAD – best practice and equity

Issue 106 of the Maori Health Review reported a recent retrospective study from the Midland region on prescribing of cardioprotective medications and the impact on survival for patients with peripheral artery disease that undergo intervention.  Findings included:

  • Overall, 80.7% of patients received a prescription for antihypertensive medication, 77.4% for lipid-lowering medication and 89.9% for antithrombotic medication with prescribing of all three noted as ‘best medical therapy’.
  • Patients with concomitant ischaemic heart disease were more likely to be prescribed cardioprotective medication. Women were less likely to be prescribed lipid-lowering medication than men and younger patients were less likely to be prescribed lipid lowering medication than older patients.  Māori men were less likely to be prescribed antiplatelet medication compared with non-Māori men although were more often prescribed antihypertensive agents and no significant difference in statin prescribing.
  • Lipid-lowering and antiplatelet medication showed a survival advantage on univariate analysis, while antihypertensive and anticoagulant medication did not. Best medical therapy was associated with better survival after adjustment for age, sex, end stage renal failure and presence of chronic limb-threatening ischaemia.

On the equity theme, there is a great article from Cook Street Medical Centre in the January edition of GP Voice about their equity journey and outcomes. 

5.  Medsafe monitoring communication

In January Medsafe released a monitoring communication regarding the DPP4 inhibitor vildagliptin (Galvus, Galvumet).  The communication requested reporting to CARM of any patients on the medication being diagnosed with ileus.  While there is insufficient evidence currently to confirm any association between use of DPP4 inhibitors and ileus, the association may have biological plausibility as DPP-4 inhibitors act by inhibiting the breakdown of endogenous glucagon-like peptide-1 (GLP-1), which has a role in inhibition of gastrointestinal motility.

6.  Resource 1:  Pregnancy-related and post-natal depression and anxiety

Online mental health provider, Just a Thought, has launched CBT courses titled Pregnancy Wellbeing and Postnatal Wellbeing for women who experience depression and anxiety during their perinatal journey. The courses are evidence-based and free of charge.  You can refer your patients and follow their progress via the on-line dashboard once you are registered as a clinician with Just a Thought, or the patient can self-access.

7.  Resource 2:  Skin Cancer Symposiums

Educational provider Skin Cancer Symposiums offers a variety of on-line and in-person courses aimed at facilitating accurate and timely diagnosis of skin cancers, particularly melanoma.  They are currently offering a complimentary on-line mini-course on the basics of dermatoscopy and diagnosing melanomas (Register here)  with the goal of the course described as: to facilitate the basic understanding of the visual “red flags” of diagnosing melanoma.  In all of the cases presented, we include clinical and dermatoscopic images. In some, the diagnosis will be evident in the clinical image and reviewing the dermatoscopic image will further reinforce this. In some examples, the diagnosis is only evident in the dermatoscopic image.

8.  Covid vaccine 2024

Manatu Hauora confirmed at the end of December that a vaccine to combat the newer strains of COVID-19 has been approved by Medsafe and will be available to New Zealanders in time for winter 2024.  The COVID-19 XBB.1.5 (Comirnaty® Omicron XBB.1.5) has been approved for the 12+ age group with no plan reported for any changes in current eligibility criteria.   Eligible people are encouraged not to defer booster shots of the existing vaccine if due in view of prevalence of Covid-19 in the community.  While the most prevalent subvariant currently internationally and in NZ is JN.1, the receipt of updated SARS-CoV-2 vaccines containing the monovalent XBB.1.5 spike protein is anticipated to provide protection against JN.1[1].

[1] https://www.idsociety.org/covid-19-real-time-learning-network/vaccines/will-covid-vaccines-continue-to-work-against-jn.1-and-other-new-variants#/+/0/publishedDate_na_dt/desc/

The New Zealand General Practice Podcast

opotikigp family medicine, general practice, Healthcare ,

Clinical Snippets January 2024

https://podcasters.spotify.com/pod/show/opotikigp/episodes/Clinical-Snippets-January-2024-e2g4c8q

Shownotes

Clinical Snippets January 2024

1. Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE)

The December edition of Prescriber Update includes an article on symmetrical drug-related intertriginous and flexural exanthema (SDRIFE).   This is a type 4 delayed hypersensitivity reaction presenting as a well-defined symmetrical V-shaped erythematous rash of the gluteal region or groin, hence its original name of ‘baboon syndrome’. There is often involvement of at least one other skin fold or flexural area, such as the armpit and behind the knees. 

The lack of systemic symptoms is a key characteristic of SDRIFE. Aside from the rash, the person is generally well with no other symptoms. The most common medicines associated with SDRIFE are beta-lactam antibiotics (eg, penicillins, cephalosporins), which are implicated in about 50 percent of SDRIFE cases.  SDRIFE is self-limiting and should resolve when the suspect medicine is withdrawn. Re-exposure to the suspect medicine usually causes SDRIFE to recur. Topical steroids may help to resolve the rash more quickly.

More details can be found on Dermnet (including  images and a list of known culprit drugs).

2. Sodium valproate in people who can father children

Medsafe has updated its alert information on use of sodium valproate in people who can father children following re-analysis of data from retrospective observational study.  Recommendations for health professionals are:

  • Use of sodium valproate within the 3 months prior to conception by people who are able to father children has been linked to a potential increased risk of neurodevelopmental disorders in children compared to those who took lamotrigine/levetiracetam.
  • The potential risks to children fathered more than 3 months (the time taken for new sperm to be formed) after stopping sodium valproate are unknown.
  • Inform patients of this potential risk and consider alternative treatment options for those wishing to father a child.
  • Discuss the need for effective contraception when starting sodium valproate and periodically throughout treatment. If discontinuing treatment, continue effective contraception for 3 months.
  • Inform patients to avoid donating sperm while taking sodium valproate and for 3 months after stopping treatment. The company has produced a guide which should be provided to all male patients of reproductive potential using sodium valproate.

3. Accelerated silicosis

In November, Bunnings and IKEA announced they would discontinue selling engineered stone because of the adverse effects on tradespeople working with the product.  I have previously talked about the Accelerated Silicosis Assessment Pathway and  BPAC have recently published a comprehensive article on accelerated silicosis including details of the assessment pathway.   Health Pathways also gives a helpful succinct guide to the assessment pathway and would be my go-to resource if you are dealing with an AS assessment request for the first time.   The BPAC article is an excellent resource for the background, management and prognosis of AS

All tradespeople who have worked with engineered stone for more than six months in the past 10 years are being encouraged to see their GP.  As at September 2023, 190 claims have been lodged with the Accelerated Silicosis (AS) Assessment Pathway

Very briefly, the pathway involves an initial GP assessment (which may be undertaken via telehealth) to establish exposure history, risk factors and presence of symptoms.  This includes past and current silica exposure, safety and hygiene measures used to reduce exposure, symptom history (respiratory, dermatological and rheumatological), smoking history, workplace monitoring (spirometry), respiratory examination if practical and consent for information to be provided to ACC.   If the patient is at possible risk of AS (if they have worked with engineered stone for more than 6 months in the last 10 years) an ACC claim is completed.

ACC assess the claim and direct further investigation if required.  This includes a funded 30-minute more comprehensive GP assessment including completion of the  Adapted Crystalline Silica Health Form – Medical Section , spirometry and arranging of further investigations and/or specialist referral as requested by ACC.  Psychosocial support may also be required for patients with confirmed AS.  

4. Cyanobacteria and cyanotoxin poisoning

The December Waikato Public Health Bulletin notes that during the warmer summer months Waikato’s lakes are often affected by blooms of cyanobacteria which can release a toxin harmful to animals and humans. 

Detail on identification and management of cyanotoxin poisoning can be found in a helpful 2020 BPAC article.  Points include:

  • There is no test available to confirm cyanotoxin poisoning; diagnosis is based on clinical symptoms and signs in association with a history of exposure (e.g. swimming or boating on a river or lake with a current toxic cyanobacterial bloom) and exclusion of other causes.  Non-specific laboratory tests or investigations that may be indicated based on the patient’s symptoms and signs
  • Symptoms are related to type of exposure eg Urticaria, dermatitis, perioral and perinasal blisters, other types of rashes with skin contact.  Bronchospasm, rhinitis, sore throat, pneumonia and occasionally severe allergic reactions with inhalation.  Gastroenteritis, malaise, elevated liver enzymes and neurological symptoms (dizziness, vertigo, hearing loss, visual disturbance, seizures) with ingestion (contaminated water, shellfish, algae-based supplements).
  • The time to onset and duration of symptoms is highly variable; typically, symptom onset will be within 24 hours of exposure and can last several days.
  • There are no antidotes to cyanotoxins; treatment is symptomatic/supportive and based on the type and severity of symptoms.  Boiling contaminated water or cooking contaminated fish or shellfish will not inactivate cyanotoxins; in some instances, heating can result in higher concentrations of cyanotoxins as the cyanobacteria break down. Cyanotoxins are also not removed by normal water filtration systems.
  • A reminder that any case of suspected cyanotoxin poisoning should be notified to the Medical Officer of Health. This can be done using the Hazardous Substances Disease and Injury Reporting Tool (HSDIRT) [incorporated into some PMS or via e-referral] or by contacting the Public Health Service directly.   

5.  Respiratory Resources 

(i)  The Asthma and Respiratory Foundation NZ launched a new COPD handbook to help those living with a severe respiratory condition. This handbook provides information about COPD, from the various symptoms patients may experience, to the different types of treatment and medication. It includes tips and advice about self-management and general lifestyle management. 

(ii)  The foundation has also released a reference guide to support rangitahi to quit vaping. This guide aims to help health professionals who work with adolescents and young adults (AYA) to tackle vaping and e-cigarette addiction through five important steps: screening, assessment, behavioural support, pharmacotherapy, and follow-up.

6.  Coroner’s advice regarding metoclopramide requests 

The RNZCGP E-pulse December edition includes a note from College Medical Director Dr Luke Bradford referring to a recent coroner’s finding into the use of sodium nitrite being used in six suicides in New Zealand.

  • The use of sodium nitrite has been promoted on several suicide and euthanasia websites, with people being advised to see their GP first to get a prescription for metoclopramide to take alongside it to prevent nausea and vomiting. Four of the six cases did just this.   A Canadian man has recently been charged with 14 counts of second-degree murder in relation to deaths in Ontario province associated with sodium nitrite suicide kits he was selling on-line, and 90 similar deaths in the UK are being investigated.  He had apparently distributed over 1200 kits to people in 40 countries including NZ. 
  • For GPs, these findings come as a timely reminder to have awareness around patients who specifically request a prescription for metoclopramide, especially patients with a history of mental health disorders, or patients who are known to be going through trauma or having suicidal ideation. These requests should trigger further exploration by the GP.
  • The chemical causes methaemoglobinemia and is actually available in injectable form to treat cyanide poisoning.   It is also used orally in powder form in food preservation and animal control, and in car care products (rust inhibitor) and is available commercially in NZ.

7.  Court of Appeal ruling

In a recent Court of Appeal ruling, ACC has failed in an attempt to reject an earlier High Court ruling that a 20-year-old patient (known as AZ) with spina bifida should be eligible for ACC cover as the congenital defect was not detected at the mother’s 20-week scan and, had it been detected, the mother states she would have terminated the pregnancy.

The misdiagnosis and failure to terminate was a treatment injury that caused AZ’s personal injury, spina bifida, the court determined.  “The only option to prevent the birth of a child with spina bifida was termination of the pregnancy,” the decision said. “Therefore, termination of the pregnancy would have been treatment of AZ which operated to prevent the continuation of spina bifida even though the outcome of the termination would have been to prevent AZ’s birth”.

The lawyer for ACC had argued that said the High Court was incorrect in applying the Accident Compensation Act because the treatment — the 20-week scan — did not cause the injury and that the proposed treatment, a termination of AZ in utero, was not a medical treatment of the condition, “it just ends the life”.

8.  An eye to the future

A single injection of the investigational antihypertensive agent zilebesiran effectively lowered blood pressure in adults with mild to moderate hypertension for up to 6 months, with what appeared to be an encouraging side-effect profile, in the phase 2 dose-ranging KARDIA-1 study.  Ambulatory systolic blood pressure measured over 24 hours was significantly decreased with all zilebesiran regimens being studied, with a mean reduction in systolic BP from baseline to month 6 of around 10 mm Hg

Zilebesiran is a subcutaneous injectable that targets hepatic angiotensinogen (AGT) synthesis by RNA interference. There were four nonserious adverse reactions leading to discontinuation in the zilebesiran groups: two instances of orthostatic hypotension, one of blood pressure elevation, and one of injection site reaction.