The New Zealand General Practice Podcast

November 2022

https://anchor.fm/opotikigp/embed/episodes/Clinical-Snippets-November-2022-e1ri4u9

Clinical Snippets November 2022
 
1.  Hepatitis C update
A recent NZ Doctor update reviewed the current state of Hepatitis C testing and treatment in NZ and includes the following points:
·       Glecaprevir and pibrentasvir (Maviret) is a combined drug pill that is 98 to 99 per cent effective after an eight-week course (equally effective for all genotypes; therefore, testing for genotype or viral load is not required).  The combination is generally very well tolerated.
 
·       Ideally, all patients should have a FibroScan – to test for fibrosis and cirrhosis. An AST-to-platelet ratio index (APRI) is a less accurate but useful score if the patient is considered low risk. APRI calculators can be found online.  People under 35 are generally regarded as low risk.
 
·       A PCR test should be checked 12 weeks after completing treatment. Annual HCV RNA assays or HCV core antigen assays are recommended for patients with ongoing risk factors (eg, people who inject drugs [PWID]) as previous infection does not confer immunity. The 1 to 2 per cent of people who are treatment failures require different treatment at specialist clinics and those with cirrhosis require specialist input and long-term surveillance for HCC.
 
·       It is estimated approximately 35 to 40 per cent of New Zealanders with chronic HCV infection are undiagnosed.  Overall, only 20 per cent of the original estimated cohort have been treated to date.  this brings the number still infected and needing treatment down to approximately 40,000 in 2022.
 
·       Hepatitis C is responsible for more than 200 deaths per annum and is now the leading indication for liver transplantation in New Zealand. The incidence of hepatitis C-related hepatocellular carcinoma (HCC) remains at 80 to 90 cases per year.
 
·       Testing all patients with unexplained elevation of ALT beyond three months is essential. Anyone with a history of intravenous drug use, even if they have normal liver function tests, needs to have an HCV antibody test then confirmatory PCR test. Screening of the general population (average risk) will find one case in 100–200 individuals, but 50 to 80 per cent of PWID are infected.
 
·       Strategies proposed to improve case detection and treatment include: point-of care-testing (especially in prisons) using PCR machine no longer required for Covid detection; Increasing access to FibroScans at community clinics; loosening prescriber criteria to include pharmacists and nurse prescribers. 
 
·       Details regarding pre-treatment assessment and the treatment itself are available in the ‘Chronic Hepatitis-C’ section of Healthpathways. 
 
 
2.  Lithium (again) 
A pharmacotherapy case study in NZ Doctor looked at a relatively common scenario of a patient stable on lithium requiring additional treatment for a comorbid condition.   Key points include: 
 With appropriate monitoring, ACE inhibitors, angiotensin II receptor blockers, diuretics and NSAIDs can be safely used with lithium.
Discontinuation of interacting medicines also requires laboratory monitoring.
·       Usual monitoring:
o   Three to six-monthly (depending on stability) – serum lithium, electrolytes, eGFR.
o   Six-monthly – thyroid function, calcium, weight.
o   Annually (if over age 40 or obese) – HbA1c, lipids, consider ECG.
 
·       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, consider further two-weekly checks for six weeks. [20 to 35 % of people will have an increase in lithium levels with addition of an ACE inhibitor, usually by approximately 33 %. The interaction can be delayed for up to five weeks, so it is important not to be reassured by steady lithium levels initially.  The interaction appears less likely with angiotensin II receptor blockers (ARBs).  However, there have been reports of serum lithium level increases of up to 20 per cent after up to five weeks of treatment, with it being an ARB dose-dependent interaction].
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 to 25 per cent in three to 10 days, although this effect may also be delayed. Loop diuretics have less impact, with potentially only up to a 20 per cent increase in serum lithium 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 to 25 per cent, there is wide variation, especially in people with impaired renal function. It is unlikely that celecoxib or other cyclooxygenase-2 inhibitors would be any different to traditional NSAIDs regarding this interaction.
 
3.  Access to medical abortion
(i)  From 1 November 2022 both Misoprostol and Mifepristone, the two medicines needed for a medical abortion, can be prescribed by a health practitioner and dispensed through a pharmacy.  This change in access coincides with the final phase of the national abortion telehealth service DECIDE.        Details of the evolution of this programme are on the Ministry of Health website
(ii)  DECIDE is provided by Family Planning and Magma Healthcare (Womens Clinic), contracted to the Ministry of Health. Alongside DHBs, both organisations are recognised experts in abortion care and have experience in providing sexual and reproductive health and abortion services via telemedicine.  The service is free for patients eligible for publicly funded health services (apart from pharmacy dispensing fees) and is currently $950 for those not eligible for publicly funded health care. 
(iii)  The services provided include (but are not limited to) direct access (by the patient) to medical abortion services up to 10 weeks gestation without the need for face-to-face consultation.  The provider website includes details of the service provided and implies the service will: order and manage all appropriate investigations; undertake counselling when requested (pre decision, pre-procedure and post-procedure); provide access to medication required including post-procedure contraception if requested; post-procedure pregnancy test (day 21).  Importantly, the site notes:
·       During the entire procedure, you will be supported by our team, 24 hours a day, via phone
·       We’ll call you the day after you have taken the misoprostol tablets to check in and see if it sounds like you have miscarried
·       Your notes will only be shared with your GP or family doctor if you agree
(iv) DECIDE has access to interpreters and the NZ Relay service (for patients with vision, hearing or speech issues). 
 
4.  Assisted Dying reminder
The EOLC Act is now a year old.  Even if you do not wish to participate in the process, it is important to be aware of the details of the legislation and your responsibility as a medical practitioner.  I recommend the learning modules on Learnonline and the Ministry of Health website also has useful written supporting information including the ‘Assisted dying care pathways for health practitioners’.  This has a section and flow chart specifically for GPs not wishing or able to be involved with the service including the following advice:
·       Medical practitioners who lack the appropriate skills or experience to provide assisted dying services (reasons of competency) are advised to tell the person the reason they do not provide the service and inform them of the SCENZ Group as a minimum.
 
·       Medical practitioners following this care pathway are advised not to discuss a person’s eligibility for assisted dying. There is a formal process for this that is outlined in the Care pathway for medical and nurse practitioners providing assisted dying services.
 
·       Medical practitioners may consider it appropriate to discuss eligibility if the person raising assisted dying is clearly not eligible, ie, is under 18 years old, is not a New Zealand citizen, or does not have a terminal illness. Medical practitioners should only discuss eligibility if they are competent and confident to do so.
 
5.  Pancreatic cancer study
A recent NZ Doctor article reviewed a large UK study that examined the link between weight loss, high blood sugar and diabetes in relation to pancreatic cancer diagnosis.   Some findings included:
·       At the time of diagnosis, the average BMI of people with pancreatic cancer was nearly three units lower than people who did not have cancer. Raised glucose levels were detected even earlier – from three years before the diagnosis.
·       Their analysis revealed that weight loss in people with diabetes was associated with a higher risk of developing pancreatic cancer than in people without diabetes. And increasing glucose levels in people without diabetes was associated with a higher risk of pancreatic cancer than in people with diabetes.
·       The results suggest that unexplained weight loss, mainly in people with diabetes (but not exclusively) should be treated with suspicion. Also, increasing glucose levels, especially in people without weight gain, should be considered a potential red flag for pancreatic cancer.
Conversely, Uptodate[1] includes the following statements:
·       At least some data suggest that the risk of pancreatic cancer is especially elevated in older adults with new-onset diabetes and a previously healthy weight with otherwise unexplained unintentional weight loss but whether these patients have a high enough risk of pancreatic cancer to justify screening is not established.
·       Thus, screening for pancreatic cancer is not warranted in older, otherwise asymptomatic adults with new-onset atypical diabetes. This recommendation is consistent with guidelines from the United States Preventive Services Task Force, which specifically recommend against screening for pancreatic cancer in asymptomatic adults not known to be at high risk because of family history or inherited genetic syndromes, including those with pre-existing or new-onset diabetes. 
 
6.  Quetiapine
·       Due to metabolic adverse effects, quetiapine and some other atypical antipsychotics can increase the risk of gestational diabetes if used during pregnancy. This issue was discussed at the most recent meeting of the Medicines Adverse Reactions Committee (MARC) in September, where it was recommended that the pregnancy section of the quetiapine data sheet should be updated to reflect this risk.
·       MARC also discussed the results from a 2018 study in New Zealand which suggested that quetiapine is widely prescribed for unapproved uses including sleep and anxiety, and use is increasing over time. This is a concern as prescribing quetiapine for an unapproved indication, without evidence of effectiveness and safety data, impacts the risk-benefit balance, particularly in pregnant women. Prescribers should take this into consideration when discussing treatment choices.
·       The study showed 72% of quetiapine prescribing was ‘off-label’, 56% initiated in primary care, 11% had a patient note indicating ‘off label’ use was discussed and 2.3% underwent recommended metabolic monitoring.  There is some evidence (one review and two data papers) that the known adverse metabolic effects of quetiapine can occur at low doses.  Conclusions included:  prescribers should be aware of the currently available risk-benefit profile for the relevant non-approved indication in each patient, noting the rationale behind their decision to use this drug at this dose. Even when ‘off-label low doses’ are being prescribed, the prescriber should be aware that the dose equivalent for the elderly patient (especially the female elderly patient) is about half that used for the younger patient and that the elderly are at increased risk of the adverse effects.  


[1] Fernandez-del Castillo c et Jimenez R.  Epidemiology and nonfamilial risk factors for exocrine pancreatic cancer.  Uptodate.  http://www.uptodate.com 
 

The New Zealand General Practice Podcast

October 2022

https://spotifyanchor-web.app.link/e/Ty9jBmyXVub
Podcast Link

Clinical Snippets – October 2022

1.  Heavy Menstrual Bleeding
A Research Review educational article on Heavy Menstrual Bleeding was published last month.  This includes helpful management algorithms and advice and is well worth downloading for easy reference.  
Take home messages include:
•	HMB is an under-diagnosed and under-treated condition occurring in approximately one in four women of reproductive age; ask all women of reproductive age about their periods.
•	Māori and Pacific women have higher rates of endometrial cancer and worse outcomes compared to other ethnic groups.  One review of social and cultural beliefs concluded that norms and practices in Pacific Island communities make it hard for some women to manage menstrual health with dignity due to the association of menstruation with taboos and shame. This highlights the importance of proactively asking Pacific women about their periods whilst remembering to be culturally sensitive to any beliefs they may have towards investigation and treatment.
•	Most patients with HMB can be effectively managed in primary care.  For all patients with HMB, discuss the impact the condition is having and their goals of treatment. Ask to perform a pelvic examination and test for iron deficiency and anaemia.
•	In patients with HMB and risk factors for endometrial cancer, prompt investigation (including a pipelle biopsy) is recommended, particularly in women of Māori or Pacific ethnicity
•	A pelvic ultrasound performed on day 5-10 of the menstrual cycle is the first-line investigation for patients with suspected structural uterine abnormalities
•	Patients with HMB need to understand the benefits and risks of their treatment options to enable them to make the best choice
•	A LNG-IUD (MIRENA®) is the first-line treatment for HMB once underlying pathology has been excluded; this should be offered to all patients, where clinically appropriate
•	Referral for consideration of surgical options is appropriate at patient’ request, when pathology is identified or when medical treatment fails

A recent Tools for Practice compared levonorgestrel intrauterine systems for heavy menstrual bleeding compared with standard oral treatments (NSAID, TXA. COC and progestagen only pills)
The review concluded:  Compared to other treatments (example oral contraceptives), blood loss with an IUD is reduced ~80% versus 25%, more women with an IUD are satisfied (75% versus 60%), and more remain on treatment at 2 years (64% versus 38%).

2.  Case of the month
(i)  A patient in his mid-50s presented with a five-month history of a left submandibular lump which he felt may be slowly growing.  Examination unremarkable other than a firm painless 3cm lump in the submandibular region diagnosed as possible reactive lymph node and patient advised to return if it persisted beyond another three months or grew.  Returned in four months as lump unchanged.  Noted to have likely dental infection/poor dental hygiene treated with antibiotics and lump attributed to this.  Similar return advice provided.  Patient reviewed in another medical centre six months later because the lump had grown further – immediately referred and diagnosed with adenoid cystic carcinoma with pulmonary metastases.    
(ii)  HealthPathways section ‘Neck Lumps in Adults’  refers to the MoH neck lump ‘HSCAN’ criteria as:
Unexplained neck or salivary mass and 1 or more of:
•	mass larger than 1 cm and persisting longer than 3 weeks.
•	mass is increasing in size.
•	previous head and neck cancer including skin cancer.
•	facial palsy.
•	any new unexplained upper respiratory tract symptoms, e.g. hoarseness, dysphagia, throat or ear pain, blocked nose or ear.
(iii)  Management advice includes:  
•	If a lump is likely to have an infective cause, treat with broad spectrum antibiotics. Recheck in 1 to 2 weeks for resolution, although complete disappearance may take a couple of months.
•	If lump is suspicious, as well as arranging FNA, request ORL assessment.
•	If FNA result is not consistent with clinical findings, discuss with pathologist or await specialist opinion.
•	A reactive node on FNA can be observed for 1 to 2 months. If it does not settle, consider a repeat FNA or request ORL assessment.
(iv)  There are several Mercy Ascot Learning Modules on neck lumps and related topics that are a useful refresher on the subject.  

3.  Fever in children under 2 months of age
A recent Research Review speakers series on management of fever in children include reference to the 2022 Starship Hospital guidance on management of fever in children under two months of age.  Recommendations are summarised as:
•	Fever in the guideline is defined as temperature of > 38° C rectally, in the hospital or in the community.  Aural temperature can be unreliable in this age group.  
•	Risk of serious bacterial infection is stratified by age – highest under 21 days, intermediate in the 21-28-day group and decreases progressively in the older age groups.  
•	Refer all unwell infants 
•	Refer well infants <28 days - clinical appearance cannot be relied upon to “rule out” invasive bacterial infections and septic screen is required
•	Well appearing 29 to 60 days - clean urine sample as a minimum; observation +/- other investigations.  Techniques for obtaining a clean catch urine sample in neonates and infants are described in the Starship Hospital guidance on urinary tract infection.  

4.  End of life care
A recent GP Pulse included an opinion piece on the inequitable state of palliative care in New Zealand, largely due to under-resourcing and lack of central planning.  The report noted a recent case of a woman in her 90s is an all-too-common scenario. Her daughter had set up her home to care for her mother until she died, as was her wish. Sadly, towards the end she developed some pain and required morphine. There were no doctors available at that time of night to make a house call, so she had to go to the Emergency Department to have it administered. She died in an ED cubicle a while later – not at all what she and her family had hoped for. 
For GPs wanting to take a more active and proactive role in end of life care of their patients, the Ministry of Health resource Te Ara Whakapiri Toolkit is worth downloading and gives very practical advice on proactive assessment and planning to ensure the patient’s needs are established and met, recognising the dying patient and specific symptom control strategies.  

5.  Update from the National Cervical Screening Programme  
From July, 2023, the primary method for cervical screening will test for human papillomavirus (HPV), the cause of over 95% of cervical cancers. Self-testing will be an option for everyone.
•	Participants can choose how to have their screening test performed - they can opt for:
o	Self-testing using a swab, in a location of their choice (including at home)
o	A clinician to take the HPV test using a swab
o	A clinician to take a liquid-based cytology sample (using a speculum) which can be used for HPV testing, and cytology if required
•	Clinical oversight is required in order to explain the test, manage results and arrange follow up. The NCSP website notes:  When HPV primary screening is introduced it is likely participants will still access their health care provider for the cervical screening, even when undertaking self-testing. The Ministry of Health will be looking at ways to make screening even more accessible in the future, which may include a future approach of a national mail-out of self-testing kits, if they are found to work safely and well for participants.
•	A GP Pulse article further defines clinical oversight for self-testing as:  for every self-test sample, there is a health professional who signs the laboratory request form and who is responsible for: 
o	providing advice and obtaining informed consent  
o	providing the test kit to the participant/coordinating getting it back (tests won’t be sent out centrally) 
o	ensuring the correct lab request information is provided on the request form and that the request form is signed by them
o	ensuring the participant is told of the test result and the result is followed up and the next steps/referrals are completed as needed
•	Protocols to manage results will be formalised before the programme starts, based on this guidance: 
o	HPV not detected -> five-year screening interval. 
o	HPV 16/18 detected -> option of returning to primary care for a cytology sample or direct referral to colposcopy, where cytology will be taken. 
o	HPV other (non 16/18) detected -> Cytology sample required: Normal / Low-grade cytology -> repeat HPV Test in 12 months; High-grade cytology – referral to colposcopy
•	In the meantime, the key message is “keep screening”. We don’t want anyone holding off on screening until HPV Primary Screening becomes available next year because the time lag will make a difference for some people - cytology screening needs to continue while we prepare for the new programme.

6.  Out of interest…

Spironolactone and binge drinking:  A group of American researchers found that spironolactone reduced binge drinking in mice and reduced self-administration of alcohol in rats without adversely affecting food or water intake or causing motor or coordination problems.  They then retrospectively analysed electronic health records of patients drawn from the United States Veterans Affairs healthcare system to explore potential changes in alcohol use after spironolactone treatment was initiated for other conditions and found a significant link between spironolactone treatment and reduction in self-reported alcohol consumption, with the largest effects observed among those who reported hazardous/heavy episodic alcohol use prior to starting spironolactone treatment.  The action may relate to spironolactone’s mineralocorticoid blocking effect on the amygdala.