Clinical Snippets January 2025

Clinical Snippets January 2025 

1. New prostate cancer care pathway

Te Aho o Te Kaho (Cancer Control Agency) have recently published Optimal cancer care pathway for people with prostate cancer (OCCP – publication not yet available on their website).  The pathway extends from preventative health measures through to palliative and end of life care as it relates to prostate cancer.  There are some (mostly subtle) variations from current Community Health Pathways (CHP) guidance and these changes will be incorporated into the pathway in the future.  

• Screening Recommendations

The CHP emphasizes shared decision-making for prostate cancer screening in men aged 50–70 years, and those over 40 years with a family history of prostate cancer or carrying BRCA2 mutations. The OCCP focuses on PSA testing for men aged 50–69 years and recommends screening for higher-risk groups such as positive family history, Māori or African descent (from age 45 years) and known BRCA2 carriers (from age 40 years). It advises against PSA testing in asymptomatic men older than 75 years or those with a life expectancy of less than 10 years.

• PSA Thresholds and Management

Thresholds for referral based on PSA levels differ slightly between the two guidelines. The CHP and OCCP suggest a PSA level above 4 µg/L for men younger than 70 years and above 20 µg/L for men older than 76 years as markers for referral to urology. For men aged 71-75 years the OCCP recommends a referral threshold PSA level of 6.5 ug/L compared with the current CHP recommendation of 10 ug/L.   Both pathways agree that a PSA level above 50 µg/L warrants immediate referral for a high suspicion of cancer.

• Repeat Testing and Diagnostic Pathway

Both guidelines recognize the importance of excluding transient causes of PSA elevation, such as urinary tract infections or recent ejaculation, before testing. However, the OCCP specifically recommends repeat PSA testing in six weeks to confirm an elevated result, whereas the CHP allows a window of 6–12 weeks for repeat testing. The OCCP also advocates for using adjunct diagnostic tools, such as MRI and PSA kinetics (density and velocity), to guide biopsy decisions. This is a key distinction, as the HealthPathways guidance primarily relies on PSA and digital rectal examination (DRE) findings.

• Role of Digital Rectal Examination

The Community HealthPathways considers DRE as part of the screening process but allows for PSA testing alone if men decline DRE. In contrast, the OCCP strongly emphasizes the importance of DRE, noting that abnormal findings may warrant referral even if PSA levels are normal.

• Management and Follow-Up

Both pathways provide guidance on active surveillance for low-risk cancers. The OCCP formalizes this process with regular PSA monitoring intervals based on risk level, while the Community HealthPathways recommends annual PSA and DRE for men with a family history or other high-risk factors. 

2.  FIT testing and colorectal symptoms

• Current Health Pathways on investigation of patients with colorectal symptoms note that use of faecal occult blood test (FOBT) and immunochemical faecal blood test (iFOBT) are not recommended outside of the National Bowel Screening Programme although the Canterbury version notes that patients satisfying the criteria for direct access colonoscopy or CT colonography may be asked to provide a faecal sample for FIT testing.  

• This variation relates to research being undertaken in the region with a study published in NZMJ towards the end of last year concluding that FIT based prioritisation of patients referred with symptoms concerning for CRC is feasible and reduces time to CRC diagnosis.  Participants (over 700) were 50 years or older (40 years or older for Maori) with colorectal symptoms satisfying non-urgent criteria for colonoscopy.  Depending on fHB concentration, patients were then triaged to either urgent colonoscopy, non-urgent colonoscopy or CT colonography.  Overall, 17.1% of the 715 patients returning a sample had FIT positivity ≥10mcg/g, and 2.2% of patients (n=15) were diagnosed with colorectal cancer. FIT detected colorectal cancer with sensitivity and specificity of 80.0% and 84.3%, respectively. The median time to diagnosis was 25 days, which the authors note is a reduction from what is currently seen in NZ due to long wait times for colonoscopy.

• The authors comment also that informal feedback regarding the pathway has been universally positive, albeit with some criticism that general practitioners cannot yet request the test directly. Nevertheless, we anticipate with enthusiasm a national directive on the use of FIT in patients presenting with colorectal symptoms, a work in progress under the supervision of the national bowel cancer working group, which we hope will revolutionise the assessment, referral and triage of these cases, and help obtain the greatest benefit from our colonoscopy resource.

3.  Infrequent zoledronate from early menopause

• Another New Zealand based study recently published in NEJM looked at the effect of infrequent administration of zoledronate in preventing vertebral fractures in early post-menopausal women.  The study was a 10-year, prospective, double-blind, randomized, placebo-controlled trial involving early postmenopausal women (50 to 60 years of age) with bone mineral density T scores lower than 0 and higher than −2.5 (scores of −1 or higher typically indicate normal bone mineral density) at the lumbar spine, femoral neck, or hip. 

• Participants were randomly assigned to receive an infusion of zoledronate at a dose of 5 mg at baseline and at 5 years (zoledronate–zoledronate group), zoledronate at a dose of 5 mg at baseline and placebo at 5 years (zoledronate–placebo group), or placebo at both baseline and 5 years (placebo–placebo group). Spinal X-rays were obtained at baseline, 5 years, and 10 years. The primary end point was morphometric vertebral fracture defined as at least a 20% change in vertebral height from that seen on the baseline radiograph. Secondary end points were fragility fracture, any fracture, and major osteoporotic fracture.

• Of 1054 women with a mean age of 56.0 years at baseline, 1003 (95.2%) completed 10 years of follow-up. A new vertebral fracture occurred in 6.3% in the zoledronate–zoledronate group, in 6.6% in the zoledronate–placebo group, and in 11.1% in the placebo–placebo group.  The relative risk of fragility fracture, any fracture, and major osteoporotic fracture was 0.72, 0.70 and 0.60, respectively, when zoledronate–zoledronate was compared with placebo–placebo and 0.79, 0.77, and 0.71 respectively, when zoledronate–placebo was compared with placebo–placebo.

• The researchers concluded:  Ten years after trial initiation, zoledronate administered at baseline and 5 years was effective in preventing morphometric vertebral fracture in early postmenopausal women.

4.  Isotretinoin prescribing reminder

A recent issue of RNZCGP Pulse included a letter from Te Whatu Ora regarding isotretinoin prescribing.  This followed a coronial case relating to death by suicide of a young patient taking isotretinoin.  Prescribing advice includes:

• Please refamiliarise yourself with the appropriate use of isotretinoin. Local information can also be found at Community HealthPathways, bpacnz, and New Zealand Formulary. 

• Allow sufficient time to discuss the benefits and risks of isotretinoin and other treatment options with the patient (and their whānau/caregiver where appropriate). Although not every patient will experience adverse effects, every patient should know about them and what to do if they occur. We recommend discussing both common and potentially serious but rarer adverse effects and the pre-treatment screening and monitoring required to manage these risks. 

• Document discussions and decisions. Please ensure that your records accurately reflect the information that was discussed/provided during the informed consent process. We recommend providing written information to supplement discussions. Printable patient information is available online from several trusted sources such as Healthify. 

• Schedule follow-up appointments to monitor treatment effect and adverse effects. Regular follow-up is needed for all patients taking isotretinoin to ensure the treatment is working as intended and is being tolerated with no unacceptable adverse effects. 

• Psychiatric adverse effects have been reported in people treated with isotretinoin. Successful treatment of acne can improve psychological wellbeing. However, serious mood and behavioural disorders have been reported in some patients taking isotretinoin. While a causal association has not been definitively established, mental health should be assessed before prescribing isotretinoin and during treatment. 

• Isotretinoin is highly teratogenic. Isotretinoin is contraindicated in people who are pregnant or people at risk of becoming pregnant due to the rate of severe birth defects (25-40%) even with a short duration of exposure. Patients must be able to comply with the necessary contraceptive measures and pregnancy must be excluded before starting treatment and, periodically during treatment. 

• Isotretinoin can cause liver function and lipid abnormalities. These effects are common (up to 25% of patients) and while usually mild, rare cases of hepatitis and pancreatitis have been reported. Serum lipids and hepatic function should be checked prior to starting isotretinoin and periodically during treatment.

5.  Plug for This Way Up

In this time of constrained mental health resources this is a reminder of the This Way Up resources summarised in a recent newsletter to primary care health providers.  Of note is a new on-line education and CBT programme designed for patients with health anxiety issues described as being suitable for patients who:  

• tend to worry a lot about their health and the possibility of having or developing an illness
• check their body frequently for signs and symptoms of disease or illness
• feel compelled to research their symptoms or try to avoid health-related information or content entirely
• seem to be stuck in the way they feel and would love to learn how to get out of this cycle
• are ready and willing to learn new skills to change the way they feel

This is one of many on-line CBT programmes the site offers for a variety of psychological issues, all evidence based.  The programmes are offered at no charge to the patient if prescribed by you (provider registration required) and this facilitates patient support and monitoring.  

6.  Equity in H Pylori testing

• The January issue of Helicobacter includes a New Zealand study on ethnic inequity in the current approach to H. pylori testing and treatment in Aotearoa New Zealand.  There are up to sixfold differences in gastric cancer mortality by ethnicity in this country, and H. pylori is the major modifiable risk factor. 
• The study design was a retrospective cohort analysis of linked administrative health data. Laboratory testing data and pharmacy dispensing were linked to the Northern region health user population dataset (1.9 million) from 2015 to 2018 with an individual’s first test for H. pylori investigated. Ethnic differences in rates of H. pylori testing, infection, treatment, and retesting, adjusted for age, sex, and calendar year were analysed.
• Ethnic inequities were present across the clinical pathway. Compared to sole-European, testing rates were lowest in Māori (OR 0.69) and Pacific (OR 0.81) and highest in Middle-Eastern/Latin-American/African (MELAA) (OR 2.21) and Asian (OR 2.02). Positivity rates were highest in MELAA (RR 2.96, 39%) and Pacific (RR 2.84, 38%) followed by Asian (RR 1.93, 26%) and Māori (RR 1.71, 23%). Treatment rates were similar for Asian (HR 1.05), MELAA (HR 1.03), and Māori (HR 0.98) compared to sole-European but lower in Pacific (HR 0.90). Māori and Pacific were half as likely to be retested as sole-European.
• The investigators concluded:  Despite the higher prevalence of H. pylori and gastric cancer, Māori and Pacific are relatively underserved with lower rates of testing and treatment than sole-European. Improved guidelines and the consistent application of these along with an equity-focused test and treat program are likely to be particularly beneficial for Māori and Pacific in addressing inequities.
• The local Health Pathways (Dyspepsia and Reflux) notes gastric cancer tends to occur a decade earlier in Māori or Pacific people, or immigrants from high-risk countries (defined as East Asia, Central and South America, Southern and Eastern Europe, the Caribbean, Middle Eastern, Latin American, African (MELAA)).  Recommended investigations include H pylori testing noting the faecal antigen test is the only test available in primary care and recommendation:
  • Advise the patient to only do the test when they have:
    • had no antibiotics for at least 1 month before the test
    • had no omeprazole or pantoprazole (PPIs) for at least 1 week before the test (even better 2 weeks)

• For further information see the 2022 BPAC article H pylori: who to test and how to treat.

7.  Resources and brief updates

• BPAC Peer Group discussion points on drug misuse, best preceded by review of an earlier BPAC article on unintentional misuse of prescription medicines.  
• One pager from Manatu Hauora summarising practical aspects of use of the Mental Health (Compulsory Assessment and Treatment) Act 1992 ( The Mental Health Act).  Further online training on application of the Act is available on the Te Pou website.  
• Avoiding triple whammy handout from Healthify.  Consider supplying to all patients on an ACE/ARB (including valsartan)and diuretic.  
• BPAC Best Practice bulletin 112 refers to availability of a new guide: Continence management for people with dementia mate wareware published by researchers from the University of Auckland.  The two-part guide provides practical information and advice for people with dementia mate wareware and their carers about how to navigate through the system, e.g. how to access disability support services, allied health professionals or specialist community support groups, and possible solutions to commonly encountered continence problems, e.g. locating, accessing and using public toilets, personal continence products.

A Pharmac press release last month notes that consultation is currently underway regarding a proposal to increase patient access to ADHD medications.  To quote the release:  The Ministry of Health is proposing to change the approval notices for these medicines, so that more doctors and nurse practitioners are able to prescribe them… Pharmac is proposing to change its Special Authority criteria for ADHD medicines to align with the changes the Ministry of Health is making.  This will mean more doctors and nurse practitioners will be able to submit Special Authority applications for people starting funded ADHD stimulant medicines…If this proposal is approved, the Ministry of Health will change the approval notices on 1 July 2025. Pharmac will update its Special Authority Criteria at the same time.  There is an ADHD update: Assessment, management, and care pathways webinar day being run by the Goodfellow Unit on Saturday 22 February 2025 (registration required, cost $320).  

Clinical Snippets

December 2024

Clinical Snippets December 2024

1. Empagliflozin and ketoacidosis

The December 2024 Prescriber Update includes a reminder on the risk of ketoacidosis associated with use of SGLT2 inhibitors (empagliflozin in NZ) whether or not they are being used for treatment of diabetes.  Key messages and prescribing considerations include:

• Patients taking SGLT-2 inhibitors are more likely to develop ketoacidosis when other risk factors are present, including acute illness, infections, surgery, pancreatic disorders, insulin dose reduction, insulin insufficiency, severe dehydration, reduced caloric intake, low carbohydrate diet, heavy alcohol use and a history of ketoacidosis.
• Inform patients taking SGLT-2 inhibitors about ketoacidosis risk factors, signs and symptoms. Blood glucose levels may be normal or only mildly elevated. Symptoms may be non-specific and include nausea, vomiting, malaise, anorexia, abdominal pain, excessive thirst, shortness of breath, dizziness or confusion. Advise patients to seek medical attention immediately if they experience ketoacidosis symptoms, irrespective of blood glucose levels.
• Consider monitoring ketones and temporarily discontinuing SGLT-2 inhibitors in clinical situations known to predispose patients to ketoacidosis. Refer to local clinical guidelines for further advice, including management before surgery/procedures and during acute illness.
• Ketoacidosis may be prolonged in patients with T2DM, despite stopping SGLT-2 inhibitors.

Healthify has excellent resources for users of empagliflozin including a printable information sheet in a variety of languages that covers risks of ketoacidosis. 

2.  Decision to fund fosfomycin in the community

Pharmac has decided to fund fosfomycin (branded as UroFos) in the community from 1 November 2024. This decision will allow New Zealanders to access funded fosfomycin treatment in the community, reducing the need for people to be treated for urinary tract infections (UTIs) in the hospital.  Dose for an adult is 3 as a single dose – comes as a sachet which the patient mixes with water (see NZF).  Special authority is required with initial application from any relevant practitioner. Approvals are valid for 2 months for applications meeting the following criteria:

Both:

• Patient has an acute, symptomatic, bacteriologically-proven uncomplicated urinary tract infection (UTI)/cystitis with Escherichia coli; and

Either:

• Microbiological testing confirms the pathogen is resistant to all of: trimethoprim, nitrofurantoin, amoxicillin, cefaclor, cefalexin, amoxicillin with clavulanic acid, and norfloxacin; or
• The patient has a contraindication or intolerance to all of: trimethoprim, nitrofurantoin, amoxicillin, cefaclor, cefalexin, amoxicillin with clavulanic acid, and norfloxacin that the pathogen is susceptible to.

3.  Latent autoimmune diabetes

I have received a complaint recently regarding delayed diagnosis of latent autoimmune diabetes of adults (LADA) in a patient in his 40’s with history of Graves disease who was diagnosed with type two diabetes and had two years of poor glycaemic control despite metformin and SGLT2 inhibitors before the correct diagnosis was made and insulin therapy commenced.  A BPAC article on management of type 2 diabetes notes at least 5-10% of adult-onset diabetes is not type 2 and this can result in suboptimal treatment.   LADA occurs when there is progressive autoimmune-mediated destruction of pancreatic beta cells commencing in adulthood, and has feature of both type 1 and type 2 diabetes (sometimes called type 1.5 diabetes).  Features that might raise suspicion of the condition include:

• Symptoms of insulin deficiency at diagnosis e.g. polyuria, polydipsia, weight loss
• Rapid deterioration in glucose levels/HbA1c
• Ketoacidosis (NB: Ketoanaemia or ketonuria without acidosis are weak discriminators between the types of diabetes)
• Normal or low BMI at diagnosis
• Personal or family history of autoimmune disease
• Family history of type 1 diabetes

Most cases of LADA are associated with positive anti-GAD antibodies and reduced C-peptide levels.  HealthPathways recommends if both are anti-GAD and anti-IA2 antibodies are negative and you still suspect a type 1 diabetes picture, seek specialist diabetes advice about arranging anti-ZnT8 antibodies.  Management principles are similar to that for general diabetes management although use of sulfonylureas is thought to accelerate beta cell loss and earlier progression to insulin therapy. The linked reference notes the main challenge is to distinguish patients with LADA from those with T2DM. By definition, patients with T2DM have absent autoantibodies to islet cell antigens, normal or elevated fasting, and stimulated C-peptide and usually do not require insulin for an extended period. Clinicians should consider screening for LADA in patients with T2DM who do not achieve adequate glycemic control within a reasonable period after compliance with therapy. This is particularly true if they are not obese, lack the features of the MetS, or they, or their first-degree relatives, have other autoimmune disorders, including Hashimoto thyroiditis, Graves disease, celiac disease, rheumatoid arthritis, or pernicious anemia.

4.  HINTS Test for vertigo

One reasonably common are of complaints I see is missed or delayed diagnosis of posterior circulation stroke, with a contributing factor being assessment of central vertigo as peripheral.  While most vertebrobasilar strokes are also accompanied by other signs (such as diplopia, dysarthria, dysphagia, motor and sensory deficits) a proportion of cerebellar strokes present only with vertigo and subtle incoordination on examination. A positive HINTS exam has been reported to have a high sensitivity and specificity for the presence of a central cause of vertigo.

The HINTS exam is only used on a subset of the patients who present with:

• Persistent vertigo over hours or days
• Nystagmus
• A normal full neurological exam

HINTS is comprised of three core components: head impulse test, evaluation of nystagmus, and a test of skew.  An excellent 8-minute video that illustrates the tests including abnormal results is available on Youtube.

5.  Treating yourself and those close to you

MCNZ has updated their statement on treating yourself and those close to you.  

• Allowance made for one-off management of minor ailments
• Accommodating the challenges faced by doctors in rural, remote and under-served communities
• Emergency situations

The statement notes that in those circumstances when treatment is provided, you must inform the patient’s general practitioner (with the patient’s consent).  There are some situations where you must not treat yourself or those close to you:

• Issuing medical certificates, death certificates and conducting third party medical assessments
• Providing psychotherapy
• Providing recurring treatment or ongoing management of an illness or condition
• Performing complex procedures
• Performing sensitive examinations
• Prescribing medication with a risk of or misuse, controlled drugs, and psychotropic drugs (except in an emergency) 

6.  ADHD changes

The ADHD landscapes is changing.  From 1 December 2024, Pharmac removed the renewal criteria for methylphenidate, dexamfetamine and modafinil, medicines used to treat ADHD and narcolepsy. This means that once an initial special authority approval for stimulant medicines has been granted, a doctor or nurse practitioner can continue to prescribe it.  From the same date, lisdexamfetamine will be funded when prescribed for people with ADHD who meet certain eligibility criteria, outlined in the Pharmac information page.  The Goodfellow Unit has scheduled a half-day online webinar event on 22 February 2025 that aims to provide an in-depth exploration of ADHD care, from initial assessment to long-term management – you can register here.  The Unit also has multiple existing podcasts/webinars on various aspects of ADHD diagnosis and management via their searchable database. 

7.  Pertussis

A whooping cough epidemic has recently been declared in NZ and it is timely to review our part in supporting pregnant patients/hapu mama to receive pertussis and influenza vaccines during pregnancy.  An interactive Geohealth Tool allows you to examine vaccination rates in your region by year, vaccine and ethnicity up to 2021.  For Hamilton City in 2021, pertussis vaccination rates for hapu mama were 46% for NZE, 13% for Maori, 27% for Pacifika and 49.4% for Asian ethnicity.  IMAC includes the following additional pertussis advice: 

• Advise pregnant people of the current increase in pertussis cases and strongly recommend the free Boostrix vaccination with every pregnancy. The vaccine is funded from the second trimester of pregnancy and recommended from 16 weeks. Vaccination during pregnancy is 92% protective against infant death from pertussis.
• Encourage all members of the extended whānau, including infants, children and older people to check they are up to date with all immunisations, especially their pertussis boosters – funded for people aged 4 years (Infanrix-IPV), 11 years, 45 years and 65 years (Boostrix). Some whānau may wish to privately purchase a booster (Adacel/Boostrix) if a newborn baby is expected to join the household.
• Ensure all babies receive on-time 6-week immunisations.
• Ensure pathways are in place to identify, diagnose and notify cases as well as seek public health advice for vaccinating close contacts, as recommended.
• Encourage all staff, including reception, administrative and retail, to ensure they are up to date with immunisations (in particular pertussis and measles). Booster vaccinations of Boostrix every 5 years are recommended for all lead maternity carers and healthcare workers who are in regular contact with infants.
• Notify the Medical Officer of Health as soon as you suspect a case of pertussis.

8.  Medical Aspects of Fitness to Drive

On 25 November 2024, Waka Kotahi published the 2024 edition of MAFTD.  A summary of changes is available and worth reviewing (15 pages).   Legal and other obligations to which the health practitioner undertaking the driver’s examination and completing certification are subject to include:

• To use the guide when doing a medical examination
• To give NZTA medical reports as soon as practicable of persons unfit to drive, or who should only drive subject to conditions, and are likely to continue to drive after being advised not to. Delays in sending or not giving enough information can create a road safety risk.
• When issuing a medical certificate, to give NZTA written notice as soon as practicable that the applicant isn’t medically fit to drive. Delays in sending or not giving enough information can create a road safety risk.
• Always advise your patient about the impact their medical condition, disability or treatment, may have on their ability to drive. Give this advice to them in writing as well as verbally.
• Recommend any temporary driving restrictions to the patient where appropriate. This could be not driving for a specific amount of time or not driving at night.
• Discuss with your patients any recommendations you’ll make to NZTA around their fitness to drive, including licence conditions, potential suspension, or revocation of their licence.
• Advise patients on their responsibility to report their condition to NZTA if their long-term or permanent injury or illness may affect their ability to drive safely.
• Include ongoing consideration of their fitness to drive while you treat, monitor, and manage the patient’s medical condition.

9.  Unexpected weight loss

Issue 247 of GP Research Review included a recently published paper in the BMJ looking at the predictive value that unexpected weight loss had for cancer, according to patient age, sex and clinical features.  The study population included 326,240 adults who presented to primary care with unexpected weight loss in England, between 2000-19. Within 6 months of presentation, 4.8% of all patients were diagnosed with cancer, of whom 98.9% were aged ≥40 years, and 96.3% ≥50 years. The most common malignancies were lung cancer (22.8%), bowel cancer (15.6%) and gastro-oesophageal cancer (12.4%). It was concluded that for men aged ≥50 years and women aged ≥60 years, the presence of unexpected weight loss alone warrants referral for invasive investigation, as the positive predictive values for cancer were above the recommended NICE threshold of 3%. Invasive investigation was also recommended for younger patients who presented with unexpected weight loss and concurrent clinical features (various symptoms and signs listed in the paper). Some of the concurrent clinical features with strongest associations with malignancy were bloating, dysphagia, chest signs, abdominal or rectal mass, VTE, pelvic mass (women) and iron deficiency anaemia (men). The blood test results associated with cancer included raised platelets (positive likelihood ratio 3.48), low albumin (3.24), raised CRP (3.13) and raised total white cell count (3.01).  Reviewer’s comment: It is the doctor’s dilemma! A patient presents with unexplained weight loss, a few non-specific blood results just outside normal parameters, and nothing else. How often do we as GPs see that?

10.  Quickies

• A recent Medscape article looked at evidence for pharmacological agents used in post-Covid syndrome and listed the most promising (with cited references) as:  low dose naltrexone; SSRIs; modafinil; antihistamines.  
• Goodfellow Unit has a learning module on Doxy-PEP to reduce chlamydia and syphilis risk, completion of which is eligible for professional development points. 
• A reminder from Medsafe (Prescriber Update) that aciclovir and valaciclovir can accumulate in the presence of renal impairment and cause neurotoxicity (confusion, agitation, hallucinations or seizure).  NZ Formulary gives specific dosing instructions for various eGFR ranges.
• The October issue of GP Voice  included links to a one-page summary regarding management of patient with possible MS relapse.  The MS Health Pathways section has more comprehensive advice including links to patient resources.  Both refer to use of methylprednisolone, not prednisone, if treatment of a relapse is required with dose recommendation differing between the two resources.  New Zealand Formulary recommends a dose of 1000mg once daily for three days or 500mg once daily for five days.  Tablets are available in 100mg strength. 

Clinical Snippets November 2024

Clinical Snippets November 2024
 
1.  Eyesore
I have recently looked at a complaint regarding delayed diagnosis and treatment of acanthamoeba keratitis.  The patient presented with an irritated red right eye after showering in a residence on tank water and with her contact lenses in place.  The patient was treated initially as a bacterial conjunctivitis with chloromycetin drops changed to fucithalmic and Maxitrol ointment (steroid/antibiotic combination) when the symptoms worsened.  An optometrist detected severe keratitis when the patient presented for a second opinion and urgent referral was made to an ophthalmologist.  There were further delays waiting for results of PCR testing on a corneal swab before appropriate treatment was commenced and after many months of treatment including corneal transplant the patient was left with a nonfunctional phthisical eye. 
A referenced resource notes that up to 93% of cases occur in contact lens wearers, and approximately 5% of cases of contact lens associated keratitis are secondary to AK.  While the condition is rare (reported rates ranging from 1-33 per million contact lens wearers), early detection and treatment offers the best chance of recovery.  Several risk factors contribute to the occurrence of AK, including inadequate contact lens hygiene, overnight wear, prolonged use, lens use during activities like swimming and showering, exposure to contaminated water, trauma, the use of contaminated contact lens solution and orthokeratology.
 
AK typically manifests unilaterally, although it may rarely occur in both eyes. A defining characteristic of AK, even in its early stages, is severe pain disproportionate to the clinical findings believed to be triggered by the activity of trophozoite-derived proteases. Patients commonly complain of reduced vision, eye redness, a foreign body sensation, photophobia, tearing, and discharge. Symptoms may fluctuate in intensity, ranging from mild to severe.  Alarmingly, 75% to 90% of patients with early AK are initially misdiagnosed, underscoring the importance of considering AK in patients where symptoms persist for several weeks without improvement despite strict adherence to a daily regimen of topical antibiotics or antivirals. Approximately 39% of patients with AK do not respond to initial therapy. Individuals with more severe clinical presentations or a history of corticosteroid use before diagnosis face a higher likelihood of treatment failure.
 
Health Pathways section on the red eye emphasises the importance of an adequate eye examination including visual acuity and corneal staining when the history might suggest keratitis.  Keratitis red flags include painful, red eye in a contact lens wearer and severe pain that is inconsistent with clinical signs in a contact lens wearer.  The initiation of topical ocular steroids in primary care is open to discussion. 
 
2.  Syphilis again
The September Waikato Public Health Bulletin included a reminder regarding the increasing prevalence of syphilis in the community.  The 2023 STI Annual 2023 Dashboard and supplementary report demonstrate a 45% increase in syphilis cases in Aotearoa since 2022. In Waikato, there were 98 cases reported throughout 2023, an increase from 57 in 2022. The highest number of cases continue to be reported in men who have sex with men (MSM), and the 30-39 and 40+ year age group. There are increasing case numbers reported in men who have sex with women (MSW), particularly in Waikato.
Untreated syphilis in pregnancy can lead to adverse outcomes including stillbirth, premature birth, and neonatal death. The incidence of congenital syphilis is inequitable, with Māori and Pacific whānau disproportionately impacted.  Access to timely antenatal care is important to ensure early identification and treatment of syphilis in pregnancy.  
 
Consider testing for syphilis in patients with unusual skin rashes, oral, genital or perianal ulcers, lymphadenopathy, hepatitis and/or neurological symptoms. Syphilis can affect any body system and cause end organ damage in its secondary stage.
 
The NZSHS has produced a statement on the use of doxy-PEP (postexposure doxycycline prophylaxis).  Three randomised controlled trials among cisgender men who have sex with men and transgender women who have sex with men at risk of bacterial STIs have shown a relative risk reduction of 70 to 80% for syphilis and 70 to 90% for chlamydia in those randomised to take a single dose of 200mg doxycycline within 72 hours after a possible exposure.  Efficacy against gonorrhoea is highly variable (0-50%) dependent on local resistance patterns.   The statement outlines those situations where you might consider prescribing doxy-PEP including relevant precautions.   
 
3.  B12 and metformin
AI have recently reviewed a case of late diagnosis of symptomatic Vitamin B12 deficiency in a patient with T2DM on metformin.  A 2022 UK drug safety update gives useful information on the topic including:
 metformin can commonly reduce vitamin B12 levels in patients, which may lead to vitamin B12 deficiency
the risk of low vitamin B12 levels increases with higher metformin dose, longer treatment duration, and in patients with risk factors for vitamin B12 deficiency
Existing low B12 levels (lower end normal range)
People at risk of decreased absorption (elderly, inflammatory bowel disease, gastric resection or autoimmune conditions)
Strict vegan and some vegetarian diets
Concomitant use of medications known to decrease B12 absorption (proton pump inhibitors, colchicine)
test vitamin B12 serum levels if deficiency is suspected (for example, in patients presenting with megaloblastic anaemia or new-onset neuropathy) and follow current clinical guidelines on investigation and management of vitamin B12 deficiency (eg Health Pathways).
Other symptoms of low vitamin B12 levels may include mental disturbance (depression, irritability, cognitive impairment), glossitis (swollen and inflamed tongue), mouth ulcers, and visual and motor disturbances.
consider periodic vitamin B12 monitoring in patients with risk factors for vitamin B12 deficiency
administer corrective treatment for vitamin B12 deficiency in line with current clinical guidelines (oral vs IM – debated); continue metformin therapy for as long as it is tolerated and not contraindicated
 
4.  Itraconazole and heart failure
Another recent case I have reviewed involved a patient with heart failure secondary to cardiomyopathy being prescribed itraconazole for severe tinea corporis and developing a marked exacerbation of his heart failure.  He was not warned of the risk of exacerbation and the prescriber was not aware. 
NZF presents a ‘blue box’ precaution:

The MCNZ statement on Good prescribing practice (revised Feb 2024) includes:  Be familiar with the indications, adverse effects, contraindications, major drug interactions, appropriate dosages, monitoring requirements, effectiveness and cost-effectiveness of the medicines that you prescribe.  How is this requirement s best achieved in a time constrained environment?
 
5.  BP cuff position
A recent Medscape article reviewed a crossover, randomized trial published in JAMA last month looking at the effect of arm position on blood pressure readings.  Guidelines for BP measurement recommend arm support on a desk with the mid-cuff at heart level. The study found that supporting the arm on the lap overestimated systolic BP (SBP) by 3.9 mm Hg and diastolic BP (DBP) by 4.0 mm Hg. When the arm hung at the side, readings overestimated SBP by 6.5 mm Hg and DBP by 4.4 mm Hg, with consistent results across subgroups.  The conclusion:  Commonly used, nonstandard arm positions during BP measurements substantially overestimate BP, highlighting the need for standardized positioning.
 
6.  Low dose naltrexone
A September NZ Doctor article reviewed the use of low dose naltrexone in post-Covid syndrome and some other conditions.  Key points were: 
In low doses (typically 3–4.5mg daily), naltrexone appears to modulate neuroinflammation and increase endorphin production, resulting in improved immune system modulation.
Low-dose naltrexone has shown promising results in fibromyalgia/chronic fatigue syndrome, chronic pain, Crohn disease, multiple sclerosis and long COVID, although the quality of evidence is generally low.
While further research is needed, given the limited choice of effective therapies for functional syndromes, LDN is a relatively safe and, in many cases, effective treatment when first-line options fail.
The article examines the evidence base for use of LDN in the various conditions described.  Note: Naltrexone is produced as a 50mg tablet and LDN requires compounding by a pharmacy or compounding laboratory.  Cost is around $115 for 100 days’ supply direct from CompoundLabs (compoundlabs.co.nz); if ordered via a local pharmacy, they may add an extra charge.  The drug is only subsidised if prescribed through and alcohol and drug service for management of alcohol dependence (SA1408) and  note is being used of label outside the indications of opioid and alcohol dependence management. 
 
7.  Endometriosis and ovarian cancer risk
Issue 243 of GP Research Review reported a large population-based study published in JAMA looking at the relative risk of ovarian cancer in women with endometriosis (n=78,893) versus a control group without.
Overall, 597 women had ovarian cancer, and the mean age at first diagnosis was 36 years. Compared to women without endometriosis, those with endometriosis had a 4.2-fold increased risk of ovarian cancer even after adjustments for sociodemographic factors, gynaecologic surgical history and reproductive history.  The risk was most marked for type 1 cancers (aHR[1] 7.48).  Women with ovarian endometriomas and/or deep infiltrating endometriosis had a near 9.7-fold increased risk for all ovarian cancers, with aHR of almost 19 for type 1 cancers. 
Type 1 cancers are composed of low-grade serous cancers, endometrioid and clear cell cancers, and mucinous cancers. This group tends to grow locally, metastasize late, and behave in a more indolent fashion. Type 2 cancers are composed of high-grade serous cancers, carcinosarcomas, and undifferentiated carcinomas. These are highly aggressive malignancies that generally present at an advanced stage.
 
8.  ACC claim numbers
In early September 2024 ACC announced an improvement to their claim approval notification process. Most kiritaki/clients will receive a text message from ACC confirming a claim approval decision, date of injury and ACC45 claim number. They will no longer receive a posted letter. Kiritaki can use their claim number straight away when seeking treatment.  Those under 16 years or without a mobile contact number will continue to receive claim details by mail. 
 
9.  Goodfellow Gems
Gem 225 – Twenty Winks Sleep Questionnaire.  This questionnaire asks about sleep patterns and provides personalised recommendations to help improve your patient’s sleep. There are 20 questions about sleep habits, lifestyle and health.
 
Gem 226 – This looks at the 2024 update on modifiable risk factors for dementia published by the Lancet Commission on dementia prevention.  Two new factors (LDL cholesterol (7% contribution) and visual loss in later life (2%)) have been added since the 2020 update.  The accompanying infographic might be useful when discussing lifestyle improvements with your patients.
 
10.  Health Equity
Issue 111 of Maori Health Review looked at a study published in the NZMJ on the impact of continuous glucose monitors in reducing disparities in glycaemic metrics for Maori Tamariki with recently diagnosed type 1 diabetes.   At the time of the study of 206 children diagnosed over 12 months 2020-2021, CGM use was 56.7% for Māori and 77.2% for European children. At 12 months post-diagnosis, HbA1c was 10.8 mmol/mol (95% CI 2.3-19.4 mmol/mol; p = 0.013) higher in Māori vs European children without CGM, but was similar between ethnic groups in those using CGM.  Hopefully the disparity in numbers accessing CGM will reduce since the devices have become funded. 


[1] Adjusted hazard ratio

Clinical Snippets August 2024

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Clinical Snippets August 2024

1.  Diverticulitis

A recent Tools for Practice from the College of Family Physicians of Canada looked at the question:   Do antibiotics change clinical outcomes for patients with acute uncomplicated diverticulitis?  The bottom line based on current evidence is that for non-septic immunocompetent patients with acute uncomplicated diverticulitis, antibiotics do not alter early complication or recurrence rates.

This approach is emphasised in a 2023 BPAC article on diverticular disease which contains detailed diagnostic and management advice including the following practice points:

• Patients with red flag symptoms indicative of complicated diverticulitis, e.g. abscess, perforation, obstruction or fistula, significant immune suppression or relevant uncontrolled co-morbidities likely to worsen their condition, e.g. diabetes, liver or renal disease, require referral to secondary care (where a CT scan can be performed to confirm the diagnosis)
• For patients with less severe symptoms, a clinical diagnosis of uncomplicated diverticulitis can be made after reasonable exclusion of other causes, and conservative treatment initiated in the community, including paracetamol (NSAIDs or weak opioids can be considered if no contraindications). Patients should be ideally followed up in 48 hours, or earlier depending on their clinical condition.

• Antibiotics are no longer routinely recommended for most patients with suspected acute uncomplicated diverticulitis; oral antibiotics may be considered for some patients who are at higher risk of complications (e.g. due to co-morbidities), but who do not meet criteria for secondary care referral.  Antibiotics can also be considered for patients managed conservatively who do not show improvement within 48 hours of their first presentation.

• While conventional advice has recommended short-term diet modification for patients with acute uncomplicated diverticulitis, i.e. two to three days of clear liquids before slowly reintroducing dietary fibre, there is a lack of clinical evidence to support this. If tolerated, an unmodified diet may be more appropriate. It is now accepted that obstruction in acute diverticulitis is rare and diets high in nuts, seeds and corn do not increase this risk of developing diverticulitis, suggesting there are other mechanisms involved.

2a.  New Free Resources available through Healthpathways. 

• Health New Zealand Te Whatu Ora has provided all Healthpathways users with access to two free “evidence-based medicine” tools – BMJ Best Practice, and EBSCO Dynamed.  
• Just follow the links on your Health Pathways home page to sign up for your free profiles and have a look around.  
• Both sites give access to up to the minute evidence-based guidance and information on a huge range of medical topics, medical calculators, clinical updates and medical news. Each have different flavours and styles. 

As an example, there was reference in a recent GPs for GPs Facebook post to changes in recommendations for first line drug therapy for patients with persistent restless legs syndrome (RLS).  The BMJ Best Practice site takes a practical approach through diagnosis and what tests to order to treatment algorithms with recommendations changing depending on severity of RLS (intermittent, chronic, refractory) and pregnancy status.  For non-pregnant patients with chronic RLS gabapentinoids (e.g., pregabalin, gabapentin) are the first-line pharmacological option with dopamine agonists now regarded as second line. 

2b.  WINZ Resource

WINZ have produced a downloadable one-page summary of main and supplementary financial benefits available to eligible patients which may be of assistance when advising patients in need.   

3.  Type 2 diabetes

A UK-based cohort study recently published in the BMJ and reviewed in Issue 13 of GP Practice Review found that, the GLP-1 receptor agonist-SGLT-2 inhibitor combination was associated with a lower risk of major adverse cardiovascular events and serious renal events compared with either drug class alone. The reviewer noted the study provides evidence that after initiating lifestyle change and pharmacotherapy with metformin and either a SGLT-2 inhibitor or a GLP-1 receptor agonist, stepping up to triple therapy by adding either a SGLT-2 inhibitor or a GLP-1 receptor agonist is an effective method of intensifying treatment to reduce cardiovascular risk and potentially improve renal outcomes. However, in New Zealand this would require patients to self- fund at least one of these medicines with Pharmac special authority criteria as they currently stand.

Related to this – Pharmac’s procurement process for continuous glucose monitoring (CGM) devices, insulin pumps and insulin pump consumables is progressing but it appears funding for these products will be limited to those with type 1 diabetes.  The Aotearoa Diabetes Collective has created a useful guide with templates for letters to support WINZ Disability Allowance applications for CGM and empagliflozin (for those already prescribed a GLP1 receptor agonist) for people living with type 2 diabetes.

4.  COVID-19 technology support changes

Health New Zealand Te Whatu Ora have provided an update on two COVID-19 technology products that are being decommissioned from 1 August 2024.

• GP notifications: The technology supporting notifications to GPs is being decommissioned and you will no longer receive notifications of self-reported RAT results. This change aligns COVID-19 with other ‘point of care’ tests where patients self-test and proactively contact their healthcare provider for treatment if needed.  The text message that a person receives when they self-report a positive RAT result has been updated and they are taken through a questionnaire to assess if they are eligible for antiviral medicines. If they are unwell or if it appears they’re eligible they are recommended to contact their healthcare provider or a participating community pharmacy. The GP will not be aware of a self-reported RAT result, so will not contact them.
• COVID-19 Clinical Care Module (CCCM): The CCCM will be decommissioned. GPs should continue to report COVID-19 cases via Healthlink as COVID remains a notifiable disease and this test result will automatically flow through to the Notifiable Disease Management System.

5.  Perinatal depression

A Recent issue of NZ Doctor contained an excellent article on management of perinatal depression.  Important practice points included:

• Antidepressants are not risk free. However, given the adverse outcomes associated with uncontrolled depression for both the birthing parent and their baby, most antidepressants have a favourable risk–benefit ratio for moderate to severe depression during pregnancy and breastfeeding.

• Routine discontinuation or switching of antidepressants during pregnancy and breastfeeding is discouraged without consideration and discussion of the specific risks (including the risks of relapse) and benefits for that individual. If the decision is made to discontinue, the antidepressant should be slowly tapered, not stopped abruptly.

• If the patient has not had antidepressants before, selective serotonin reuptake inhibitors (SSRIs) are generally recommended for first-line treatment with Sertraline being the preferred SSRI in pregnancy. It is thought to have the lowest placental transfer of any SSRI and may have the lowest risk of neonatal persistent pulmonary hypertension.  Additionally, if breastfeeding is desired, it has low infant exposure via milk.

• Escitalopram or citalopram are also relatively safe in pregnancy and breastfeeding and are reasonable alternatives. Fluoxetine, while having a reasonable safety profile during pregnancy, is least preferred during breastfeeding as it has a long half-life and may accumulate in milk. Paroxetine may have an increased risk of congenital heart defects, although this has not been conclusively proven. Paroxetine also has an increased risk of neonatal adaptation syndrome (NAS) compared with other SSRIs. For these reasons, some guidelines recommend avoiding paroxetine during pregnancy, if possible, although it has low infant exposure via milk for those who wish to breastfeed.

The article reviews use of all classes of antidepressants and current evidence base for risks versus benefits.   There are links to a variety of support and self-help resources including:

• Perinatal Anxiety & Depression Aotearoa provides screening tools, factsheets on antenatal and postnatal anxiety and depression, and locally available support services and helplines
• Mothers Helpers offers support for mothers with antenatal and postnatal anxiety and depression, including an online perinatal depression recovery course
• Healthifyhas information on perinatal depression and anxiety, how it is treated, and a list of available support services
• Beating the Blues provides free online cognitive behavioural therapy
• Just a Thought offers two free specialised online perinatal CBT courses
• Tuku Iho is a bilingual app that focuses on te ao Māori maternal and tamariki wellbeing

The article also includes links to two sites that provide consumer-oriented information on risks and benefits of various drugs that may be used in pregnancy:

• Organization of Teratology Information Specialists (US) MothertoBaby factsheets
• UK Teratology Information Service, Best Use of Medicine in Pregnancy leaflets

6.  Patient information sheets available from bpac^nz

The following information sheets are especially designed to support primary care consultations, and can be downloaded and printed, or the link sent to patients via text or email.

• Advice if you are prescribed an antibiotic 
• Advice if your child is prescribed an antibiotic
• Information for managing seasonal viral illness (“Cold & Flu”)
• Information for managing at home with COVID-19

7.  HPV priority group funding

Funding for HPV screening and follow-up priority groups has been extended until 30th June, 2025.  Details of the process are available on the Heath NZ Te Whatu Ora website and includes two algorithms aimed at simplifying determination of eligibility for funding.

8.  Weird but wonderful

Preliminary studies have shown a significant decrease in severity of obstructive sleep apnea (OSA) with the use of a combination of atomoxetine and oxybutynin, with patients having moderate pharyngeal collapsibility during sleep (a higher proportion of hypopneas to apnea and mild degree of oxygen desaturation) more likely to respond. A 2022 study evaluated the efficacy and safety of atomoxetine 80 mg and oxybutynin 5 mg in the treatment of OSA confirming findings of previous studies.  The most common adverse events (insomnia (12%) and nausea) were consistent with the expected profile of the individual drugs.  A 2024 study adding acetazolamide to the combination found no increase in efficacy with this addition. 

9.  Why I don’t sleep at night…

I have recently reviewed the case of an older child assessed in primary care after running in to a barrier pipe (waist level) with subsequent abdominal pain.  There were no findings of an acute abdomen and the child was discharged after responding to simple analgaesia but collapsed and died at home about 36hrs later.  Post-mortem findings revealed a jejeunal rupture.    Children are more vulnerable to blunt abdominal injury than adults because they have relatively compact torsos with smaller anterior-posterior diameters, which provide a smaller area over which the force of injury can be dissipated; larger viscera, especially liver and spleen, which extend below the costal margin; and less overlying fat, and weaker abdominal musculature to cushion intra-abdominal structures.  Uptodate[1] notes that repeated, serial examinations are necessary in children with abdominal trauma because serious intra-abdominal injury (IAI) may not be apparent upon the initial examination. Abdominal tenderness may be especially difficult to determine in young children who are frightened and cannot clearly communicate and in older children who are uncooperative or neurologically impaired.  The message is to have a high index of suspicion for possible IAI in children presenting with blunt force abdominal trauma.   

Coincidentally, Issue 28 of Child Health Research Review reviewed the recently published Pediatric Emergency Care Applied Research Network (PECARN) prediction rules to reduce inappropriate use of computed tomography (CT) in children with abdominal or head trauma. The rules were validated with a high degree of accuracy: the intra-abdominal injury rule had a sensitivity of 100.0% and a negative predictive value (NPV) of 100.0% but has not been validated for use in primary care and given presence of abdominal pain is a ‘not very low risk’ criterion I’m not sure how practical it would be. 

[1] Saladino R et Conti K.  Pediatric blunt abdominal trauma: Initial evaluation and stabilization.  Uptodate.  www.uptodate.com  Accessed 1 August 2024