November 2022

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

October 2022

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.  

September 2022

https://anchor.fm/opotikigp/episodes/Clinical-Snippets-September-2022-e1ov3ro

Clinical Snippets September 2021 

1.  I want a blood test for cancer! 

• A recent Medscape article reported on the Galleri test which is available in the USA.  The blood test returns one of two possible results: either “positive, cancer signal detected (+ top predicted cancer signal origins)” or “negative, no cancer signal detected.”  The manufacturer claims that when a cancer signal is detected, the test predicts the origin of the cancer signal with high accuracy to help guide the next steps to diagnosis.  Currently more than 50 types of cancer can be detected.   

• The test detects abnormalities in the methylation patterns of cell-free DNA (cfDNA) that could indicate the presence of cancer by using next-generation sequencing (NGS) and machine-learning algorithms.  When a cancer signal is detected, the test identifies the origin of the signal with high accuracy to help guide the next steps to diagnosis. 

• In a large-scale validation study, the Galleri test had a specificity of 99.5% (false-positive rate of 0.5%), meaning in roughly 200 people tested without cancer, only one person received a false-positive result (ie “cancer signal detected” when cancer is not present).  The overall sensitivity of the test for any stage of cancer was 51.5%, although it was higher for later-stage cancers (77% for stage III and 90.1% for stage IV) and lower for early-stage cancers (16.8% for stage I and 40.4% for stage II).  There are multiple ongoing studied including an NHS trial in the UK attempting to validate preliminary results.  The cost of the test is around $950 US.   

2.  Recurrent UTI 

• Tools for Practice examined the evidence for efficacy of antibiotic prophylaxis for recurrent urinary tract infections (UTI) in non-pregnant women?  Recurrent UTI was defined as ≥3 episodes in 12 months, or 2 episodes in 6 months.  The conclusions were:  Antibiotic prophylaxis decreases the risk of recurrent UTIs from 66% with placebo to 12% with prophylaxis over 6-12 months. More women will experience an adverse event with antibiotics (15% versus 8% with placebo). Long-term bacterial resistance and its individual clinical impact has not been well studied.  NNT was 2-3.   

• There was no significant difference between nitrofurantoin and other antibiotics for UTI reduction; however, nitrofurantoin increased adverse events (example gastrointestinal) (~1.8x).   Rare cases of pulmonary toxicity noted with nitrofurantoin [1/5000 (acute) and 1/750-7500 (chronic)] recorded (Medsafe have published on this) and note that nitrofurantoin is contraindicated in  patients with eGFR < 60mL/min (seek specialist advice) – relates to decreased efficacy and increased risk of peripheral neuropathy.  The UK revised this contraindication to <45mL/min in 2014.   

• A recent New Zealand Doctor article examined other options for managing recurrent UTI noting there is some evidence that methenamine hippurate (Hiprex)  is non-inferior to trimethoprim and possibly other antibiotics, and NNT similar to antibiotics for use of vaginal oestrogen therapy in post-menopausal women with recurrent UTI.  The article also mentioned Uromune which is an unfunded immunostimulant against common urinary tract pathogens.  Drops are taken sublingually for three months (cost around $340 per course), a systematic review of nine small studies showed a wide range of 12- month UTI-free rates of 36-90%.  It appears to be available through some private urology clinics.  A 2021 metanalysis showed that D-mannose (available OTC) also has a weak evidence base for efficacy in UTI prevention but insufficient at this stage to recommend it routinely.   Main adverse effect was mild diarrhoea and bloating.    

3.  Viewing the body 

A recent edition of GP Pulse raised the issue of whether a video link could be considered an adequate examination prior to completing a cremation certificate, particularly if there was a risk of COVID-19 infection.  

The Ministry of Health have made the following comments:  

1. If you are the deceased patient’s doctor and you are happy to write a death certificate, there is no requirement to see or examine the patient after death.  However, if the person is to be cremated then the doctor/nurse practitioner must physically see and identify the body and certify as to whether there is a pacemaker implanted under Section 7 of the Cremation Regulations.   

2. However, there is an exemption from Section 7 if the patient has died from COVID-19 AND they live in a rest home, residential care facility, or other long-term in-patient facility.  There are several requirements if you want to use this exemption and you should read the regulations. In this case the undertaker will identify whether there is an implanted pacemaker. Importantly, this DOES NOT apply if the patient died in a hospital, a hospice or at home. 

3. There is a third situation where the body must be physically seen and examined.  This is where you are certifying death where you were not involved in the person’s care, but you are acting on behalf of the normal attending clinician.  Again you should read the relevant regulations if you find yourself in this situation.  

4.  Case of the Month 

• I have recently reviewed a complaint regarding an error in PSA monitoring over three years.  The patient had a radical prostatectomy for prostate cancer and the discharge letter from his urologist contained explicit advice to the GP requesting the GP organise six-monthly PSA monitoring for two years then annually, and to refer the patient back for consideration of salvage radiotherapy if the PSA became detectable at any stage. 

• The history of prostate cancer and prostatectomy was coded and an appropriate recall was set up.  There were several clinicians involved in ordering and reviewing the results when they came due and the patient generally enquired after the results.   

• The first six-monthly result showed a low but detectable PSA with subsequent results showing sequential rise in PSA.  Results were signed off as ‘normal’ and this was conveyed to the patient.  It was not until the PSA was noted to be outside the reference range for patient age, some three years after it first became detectable, that urology referral was made by which stage there were distant metastases present and salvage radiotherapy was not an option. 

• What might have prevented this sequence of events knowing it is not unusual for staff other than the patient’s usual GP to be reviewing results?  

• A patient alert and/or more detail under the disease classification (but ‘alert fatigue’ is a recognised issue) 
• All PSA result to be reviewed by the patient’s usual GP? 
• Greater involvement of the patient – discussion from the outset of what the tests results mean, what might be abnormal in his specific situation, and access to the results via a patient portal 

• Consider using reminder/prompts when there are results you might want to be reviewing yourself eg investigating GI symptoms – a drop in Hb from the upper limit of the reference range to the lower limit of the reference range over six months might be concerning but both results could be reported as ‘normal’   

 5.  Quickies 

(i)  Fib 4 calculator – this uses the patient age, platelet level, AST and ALT levels to determine likelihood and degree of liver fibrosis present in patients with conditions such as chronic hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD) and the cholestatic and metabolic liver diseases.  It is referred to in the HealthPathways section on NAFLD as a means of guiding when a patient should be referred for a fibroscan (the HealthPathways section on Abnormal Liver Function is a very useful resource for interpreting and acting on such results).  

(ii)  A recent Prescriber Update recommends that all NSAID prescriber information should be updated to note that NSAIDs are contraindicated in the third trimester of pregnancy.  Maternal use of NSAIDs in the third trimester of pregnancy may have adverse effects for the mother, fetus and neonate including:  

• Maternal effects: prolonged labour, post-partum haemorrhage. 
• Fetal effects: premature closure of the ductus arteriosus, fetal renal impairment, oligohydramnios. 
• Neonatal effects: respiratory distress syndrome, persistent pulmonary hypertension of the newborn (PPHN), bronchopulmonary dysplasia, renal failure, intraventricular haemorrhage, necrotising enterocolitis 

NSAIDs should not be used during the first two trimesters of pregnancy unless the expected benefits to the mother outweigh the risks to the fetus. 

(iii)  Pharmac informs us that supplies of Paracare 120mg/5ml are likely to run out during September. Supplies of Paracare Double Strength (250mg/5ml) are likely to begin running out during October. To cover the gap before the new contracted brands can enter the market, Avallon brand has been listed. 

Key differences of Avallon 

• Flavour is strawberry-vanilla for both strengths (previously strawberry and orange) 
• Colour is off-white for both strengths (previously pink and orange) 

• Stronger preparation is 240mg/5ml rather than 250mg/5ml 
• Patient education leaflets in a variety of languages outlining the differences are downloadable from the Pharmac website 

(iv)  Amion – this app is used by some DHBs to list names and contact details of on-call registrars and SMOS.  The access code for Te Whatu Ora Waikato is waikato.   

August 2022 – https://spotifyanchor-web.app.link/e/DJuG3C2VMsb

Shownotes

Clinical Snippets August 2022

1.  Pediatric Sepsis

• The febrile and non-specifically unwell child is a common presentation in primary care.  Sepsis is a major cause of morbidity and mortality in the paediatric population and can be very challenging to diagnose and manage.

• For every hour a child remains in septic shock the mortality risk doubles. Care delivered in the first hour after presentation or sepsis identification is crucial in ensuring the optimum outcome for the patient.

• Considering a diagnosis of sepsis and assessing for red and amber flags at triage is important.  The   Prehospital Paediatric Sepsis Screening and Action Toolprovided by Sepsis Trust NZ may be a useful resource to guide triage and assessment activity.

• Additional risk stratification tools developed by NICE are available via a BPAC article onSepsis: recognition, diagnosis and early managementpublished in 2018.   There are separate algorithms for children aged under 5 years, 5-11 years and 12 – 17 years.

• Recommendations include:  Think ‘could this be sepsis?’ if a child presents with signs or symptoms that indicate possible infection…. Assess temperature, heart rate, respiratory rate, level of consciousness, oxygen saturation and capillary refill time in children under 12 years with suspected sepsis.

• The more general NICE ‘traffic light’ system for Identifying the risk of serious illness in children with fever was published in 2007.  A recent study analysing utility of the system concluded:   The majority of children presenting to UK primary care with acute undifferentiated illness meet red or amber NICE traffic light criteria, with only 6% classified as low risk, making it unfit for use in general practice.  A second study looking at accuracy of the system for identifying children at risk of serious illness concluded the system did not accurately detect children admitted with a serious illness, nor those not seriously ill who could have been managed at home. This system is not suitable for use as a clinical tool in general practice. 

• The Pedicalc website (ED orientated) has calculators that facilitate rapid calculation of drug doses that might be required in various paediatric emergency situations.    

2.  Actinic keratoses (AK)

• A recent Dermatology Research Review article notes that the chance of any given AK evolving into invasive SCC is small (1:45 or around 2% for a mild early lesion and up to 20% for a severe or thick lesion). Efudix® is superior to imiquimod in clearing these due to its superior keratotic tissue penetration. It is not surprising that a thick lesion would require more treatment and topical treatment in that setting may not regress malignant progression. The take-home message is that patients with thicker lesions require closer more frequent monitoring and a low threshold for surgery of poorly responding lesions.

• A 2022 systematic review of use of calcipotriol with Efudix for field treatment of AK observed the combination led to greater reduction in AK, a higher percentage of patients achieving complete clearance, and less risk of progression to squamous cell carcinoma, but more burning and severe erythema.  The recommended duration of treatment is around four days (applied twice daily).  

• An older BPAC article gives recommendations (and scary images) of how to use Efudix and imiquimod for non-melanoma skin cancer in a general practice setting and is a useful resource.   It does not cover the Calcipotriol/Efudix combination however. 

3.  Assisted Dying update

The Assisted Dying Service – Ngā Ratonga Mate Whakaahuru annual report has recently been released covering the period 7 November 2021 to 31 March 2022.  Between those dates 206 people formally applied for assisted dying. As of 31 March:

• 66 people had an assisted death
• 59 people were still in the process of assessment or preparation for assisted dying
• 81 people did not continue the process (due to being ineligible, withdrawing or dying of

their condition)

• 6% of people that applied for assisted dying are Māori and 79% are NZ European/Pākehā, 55% were women, 74% were aged 65 years or older and 65% had a cancer diagnosis
• 80% of applicants for assisted dying were receiving palliative care at the time of application.
• Location of the assisted dying process was 73% at the person’s home or another private residence, 17% in aged care facilities, 6% in district health board facilities and 4% in hospice facilities
• A majority of people (85%) chose injection delivered by the attending medical or nurse practitioner
• The Secretariat received four complaints over this period, three of which were resolved and one of which was referred to HDC.  Issues include: a practitioner’s interpersonal style and

Communication; Delay in being connected with an attending medical practitioner; Disagreement with a finding of ineligibility; Poor experience of the process in a public hospital. 

4.  Change in shingles vaccination

• PHARMAC has announced that Shingrix will be replacing Zostavax on the National Immunisation Schedule and will be funded for those in their 65^th year of life. Shingrix will be available for order only once all stocks of Zostavax are exhausted. This is expected to occur in August or September.

• Shingrix is a two-dose schedule with a 2–6-month gap between doses.  As long as the person being vaccinated is 65 when they receive their first dose, both doses will be funded. At this stage, there will be no catch-up programme for this vaccine, it will simply take the place of Zostavax.

• The effectiveness of Shingrix does not decrease when given to older age groups (with an efficacy of around 90% against zoster and PHN), so those aged over 70 years will also be protected and a high level of protection (over 80%) has been shown to be maintained for more than seven years, so far.

• Per IMAC:  Shingrix may be offered to individuals who previously had Zostavax and/or has a history of zoster episodes. Allow 12 months between Zostavax or after an episode of zoster has resolved before giving Shingrix. There are no safety concerns around giving it sooner but since the immune system will have been activated against the varicella-zoster virus by these events, there is likely to be little additional short-term benefit for most people. Shingrix can be given sooner, from 3 months after a zoster episode has resolved or prior Zostavax dose, for individuals who are immunocompromised and at increased risk of zoster recurrence.

5.  Treating fever

A recent edition of the BMJ contained a meta-analysis and systematic review of 42 clinical trials looking at fever therapy in febrile adults.   The trials assessed antipyretic medicines (mainly paracetamol and ibuprofen), physical cooling and combination treatment v.s. no fever treatment or placebo, in patients with fever who were critically ill, non-critically ill, with and without infectious illness.  There was no evidence that fever therapy reduced the risk of death or the risk of serious adverse events; conversely there is no evidence that fever therapy increases these risks.  There was insufficient evidence to determine whether fever therapy influences quality of life or non-serious adverse events – we can’t even say for certain that at least it will make the patient feel better!

A 2020 systematic review and meta-analysis on use of antipyretics for preventing recurrence of febrile seizures in children concluded there was weak evidence suggesting a possible role in preventing febrile seizure recurrence within the same fever episode but there is clearly no role for antipyretic prophylaxis in preventing febrile seizures during distant fever episodes.

6.  PrEP update

• From 1 July 2022 access to emtricitabine with tenofovir disoproxil (TD/FTC) for pre-exposure prophylaxis of HIV (PrEP) was widened to allow more people access to treatment for PrEP.  The approval period was also extended and criteria that relate to monitoring and testing were removed from the SA.  This means the criteria will only require the prescriber to confirm that the patient is HIV negative, that they consider the patient is at elevated risk of HIV exposure and that use of PrEP is clinically appropriate. Pharmac estimate that initially up to an additional 3500 people per year will be able to access PrEP as a result of this change, increasing to 5500 people per year in the next five years. 

• The new SA criteria for initiation of PrEP read:

Initial application from any relevant practitioner. Approvals valid for 24 months for applications meeting the following criteria:

Both: 

1. Patient has tested HIV negative, does not have signs or symptoms of acute HIV infection and has been assessed for HIV seroconversion; and
2. The Practitioner considers the patient is at elevated risk of HIV exposure and use of PrEP is clinically appropriate. 

It is important to have a working knowledge of prescribing options, and pre-prescribing assessment and surveillance/follow-up requirements.  There are multiple useful resources available to assist with this: 

• NZ Guidelines for use of PrEP on the Australasian Society for HIV Medicine (ASHM) website
• 2019 BPAC article on prescribing PrEP
• A two page quick access guide on PrEP prescribing in NZ
• A one pager from Canterbury DHB on ongoing testing and surveillance requirements and considerations for patients taking PrEP
• Pharmac training resources on various aspects of HIV including PrEP perscribing
• Extensive on-line information resource for patients considering or taking PrEP

https://anchor.fm/opotikigp/episodes/Clinical-Snippets-July-2022-e1ma9ik

Shownotes CLINICAL SNIPPETS – JULY 2022

1.  Mild bleeding in patients on dabigatran or rivaroxaban

Pharmac and BPAC published guidelines in 2018 regarding management of bleeding in patients on dabigatran or rivaroxaban.

For mild bleeding recommended management is

• Mechanical compression
• Tranexamic acid, topically or orally, 15 mg/kg, three to four times daily – the usual adult dose is 1 g, i.e. two 500 mg tablets, per dose
• Topical application refers to gauze swabs soaked in Tranexamic acid 500mg/5mL
• Delaying the next dose of dabigatran or rivaroxaban may be sufficient when bleeding is mild or discontinue treatment as clinically appropriate (case by case basis)
• More significant bleeding in patients on DOACs requires in-hospital management

2.  Paediatric antibiotic use and vaccine induced immunity

• Issue 195 of GP Research review reports a recently published study which examined the association of antibiotic use with vaccine-induced immunity in 560 children (342 with and 218 without antibiotic prescriptions).
• Vaccine-induced antibody levels to several diphtheria-tetanus-acellular pertussis (DTaP) and pneumococcal conjugate (PCV) antigens were lower in antibiotic recipients (p < 0.05).
• Vaccine-induced antibody levels below protective levels were more common in children given antibiotics at 9 and 12 months of age (p < 0.05). Each antibiotic course reduced pre-booster antibody levels by 5.8 to 11.3% (depending on the antigen) and reduced post-booster levels by 12.2 to 21.3%
• This is the first study of this type, that I am aware of, that has demonstrated the negative impact that antibiotics have on vaccine antibody levels (to below protective levels) in very young children. This occurred across the board and has certainly now influenced my antibiotic prescribing in young children.

Reference: Pediatrics 2022;149(5):e2021052061

3.  ACC vaccine injury claims and SIRVA

• Complete an ACC2152 treatment injury claim form and an electronic or manual ACC45 injury claim form. To help with reporting, ACC needs to know the COVID-19 vaccine brand name and vaccination dose number (i.e., first, second, booster).
• You can note this on:
  • the ACC45: Tick the treatment injury box. Identify this as an adverse event in the drop-down menu. Then enter the COVID-19 vaccine brand name and vaccination dose number in the open comments section
  • the ACC2152: In Section 3 – Treatment claimed to have caused the injury.
• When lodging a claim for a physical injury, please identify the specific injury, for example ‘myocarditis’ – not just the symptoms
• Always attach the completed ACC2152 form
• For more information on treatment injury claims, read the ACC treatment injury claim lodgement guide
• Vaccines administered into the shoulder joint or bursa rather than the deltoid muscle may result in significant and disabling injury known as shoulder injury related to vaccine administration (SIRVA).  There were 359 treatment injury claims for SIRVA lodged between 2011 and 2021 of which 120 were accepted. 
• The main symptoms of SIRVA include persistent shoulder pain and a limited range of motion. The keys to distinguishing SIRVA are that the symptoms typically begin within 48 hours of vaccine administration and that they do not improve with over-the-counter analgesic medications. 

Reference:  Can Fam Physician 2019; 65(1):40-42

4. Molnupiravir and contraception advice

New Zealand Formulary states:

• Clinicians should assess a patient’s pregnancy status before initiating molnupiravir, if clinically indicated.
• Patients of childbearing potential should be counseled about abstaining from sex or using reliable contraception for the duration of therapy and for up to 4 days after receiving molnupiravir.
• Reproductive toxicity has been reported in animal studies of molnupiravir, and molnupiravir may be mutagenic during pregnancy.
• Males with sexual partners of childbearing potential should use a reliable method of contraception during treatment and for at least 3 months after the last dose 

The FDA EUA states that men of reproductive potential who are sexually active with individuals of childbearing potential should be counseled to abstain from sex or use a reliable method of contraception for the duration of treatment and for at least 3 months after the last dose of molnupiravir.

5.   Just a Thought

A recent BPAC article on OCD recommended Just a Thought as an on-line CBT resource which can be considered while awaiting access to formal psychotherapy for suitable patients. 

• Just a Thought is an on-line CBT service.  It has been through over 30 randomised clinical trials which prove its efficacy.
• It has several on-line courses that can be prescribed for your patient at no cost:  Generalised anxiety. Staying on track during Covid 19; Depression; Mixed depression and anxiety; Social anxiety; Managing insomnia.
• Each course follows the story of a fictional character (or characters) who experience the symptoms of anxiety and/or depression. Throughout the course, the stories will help the patient learn about their own symptoms and the steps required to help them recover.
• Each story takes about 20 minutes to read and will generally require the patient to take 3-4 hours in between each part to complete the suggested practice activities. The courses are self-paced, but designed to be completed within 3 months, at most. It is best to do one part every week or two to allow time to practise between.
• Access to the resource for prescribing requires clinician registration (free).  A course is prescribed via the Just a Thought website after clinician log-in.  The patient will receive an email from Just a Thought with a link and instructions on how to sign up for a course, and be supervised by the referring clinician.  The system will also send automatic reminders and alerts to the clinician and patient.
• The related Australian site is Thiswayup and has a broader range of courses available but not necessarily tailored for New Zealanders. 

For more information read the Clinician Welcome Guide and the Clinician getting started guide.

6.  Ukrainian Special Policy and TB risk

The Ukrainian Special Policy allows Ukrainian-born citizens and residents in New Zealand to sponsor a family who ordinarily reside in the Ukraine. All arrivals will be granted either a two-year working visa or two-year student visa and will have full access to publicly funded health and disability services. As of 16 June 2022, 780 visas have been approved and 213 people have arrived under this policy setting.  As part of the policy setting, all health requirements for entering New Zealand have been waived for this visa.

According to 2019 WHO estimates, Ukraine has the fourth highest Tuberculosis (TB) incidence rate among the 53 countries of the WHO European Region. Ukraine has one of the highest burdens of multidrug resistant tuberculosis (MDR-TB) in the world. 

The Ministry of Health advises the following:

• All Ukrainian arrivals should be referred for chest X-ray screening due to the high incidence of tuberculosis in the Ukrainian population.
• Ukrainian arrivals with symptoms may have active TB and should be referred with high priority.
• Chest X-rays can be arranged through DHB chest X-ray referral and the following should be annotated on the form: “Chest X-ray to exclude TB infection: high risk patient – recently arrived Ukrainian Refugee (eligible for publicly funded healthcare in NZ)”
• If a chest X-ray comes back abnormal, Public Health Units will become involved in the case, including in obtaining a sputum sample and in the follow up management required for all contacts.  Tuberculosis us a notifiable disease. 
• It is advised to offer vaccination against TB for those who are <5, are tuberculin negative and don’t have a history of BCG vaccination. Contact your local public health service to find out who can give the BCG vaccine in your area. 

7.  New ACE on the horizon

• PHARMAC is currently consulting on a proposal to fund ramipril, an ACE inhibitor that is commonly used in other countries, including Australia, for hypertension, heart failure and chronic kidney disease. If the proposal is accepted, from 1 November, 2022 ramipril will be fully funded without restriction, and available in four strengths of capsule.

• Cilazapril is due to be delisted from the pharmaceutical schedule in mid-2023; currently no new patients may be initiated on this medicine and prescriptions for current patients must be endorsed.

8.  Lorazepam (Ativan) 1 mg tab: Supply issue

• The supplier of lorazepam 1 mg tablets (Ativan) has notified Pharmac of a supply issue affecting this medicine. PHARMAC are asking that healthcare professionals avoid starting new patients on lorazepam 1 mg tablets until this medicine is resupplied and consider alternative treatment options for patients who are using lorazepam 1 mg tablets for longer periods

• Pharmac clinical advisors suggest alternative funded treatments might be suitable for some patients. These may include diazepam and clonazepam. Some clinicians may consider temporarily transitioning patients to half a 2.5 mg tablet, although this represents a 25 percent increase in dose-per-tablet. (The 2.5 mg tablets are scored for simpler halving.) This will require a new prescription. 

Listen here : https://anchor.fm/opotikigp/episodes/Clinical-Snippets-June-2022-e1kp5l2

Clinical Snippets June 2022

1.  Proton Pump Inhibitors

A recent POEM of the Week podcast discusses the small risk of gastric cancer with long-term use of PPIs.  Numbers needed to harm were 2000 users after 5 years and 1200 users over 10 years to get gastric cancer. The risk was higher in patients on higher doses. The advice was to try short periods and lower doses of PPI.

A BPAC article notes additional adverse effects associated with long-term use of PPIs including:

• Bone fractures – absolute risk increase is estimated to be 0.1% to 0.5% per year for an individual patient.
• Malabsorption of nutrients including increased risk of B12 deficiency, hypomagnesaemia and iron deficiency  
• Clostridium difficile infection. The relative risk for community-acquired C. difficile infection is increased by 50% in people taking PPIs, however, the low incidence of this bacterial infection means the absolute risk increase is estimated to be 0.09% per year.
• Community-acquired pneumonia. The acid-lowering effects of PPIs is thought to allow proliferation of bacteria in the stomach, which may then move up into the oesophagus to be aspirated and cause lower respiratory tract infection, e.g. pneumonia.
• Chronic kidney disease. PPI use has been associated with chronic kidney disease and end-stage renal disease. The estimated absolute risk increase of chronic kidney disease for an individual patient per year is 0.1% to 0.3%.  There is also an association with acute interstitial nephritis – more common in patients aged over 60 and in the first thee months of use.

The BPAC article poses some questions to consider: 

• How often do you review patients on long-term PPI treatment?
• Do you have a system or plan for reviewing PPI use in patients? Do you discuss expected duration of treatment when you initiate PPIs?
• Have you ever had reason to suspect that PPI was associated with adverse effects, e.g. oesteoporosis or acute interstitial nephritis, in any patients?
• Were you aware of the issue of rebound acid secretion and do you/will you discuss this with patients?
• Do you encounter resistance from patients to withdraw from PPIs as they prefer PPIs to lifestyle adjustments for symptom control, and if so, how do you manage this?

2.  Patients who refuse to wear a mask

The RNZCGP has published advice on managing patients who refuse to wear a mask, initially in October 2021 with a more recent update. 

• Initial advice suggested that a patient presenting without a mask should be asked to wait outside where they could be assessed (subject to privacy considerations), or they need to be offered a telehealth consult to manage their medical problems remotely.
• However, if a face-to-face consultation is deemed necessary, or the patient refuses the telehealth consult, then the patient will need to be seen by a clinician, who may or may not be their usual GP. The patient should be treated as a ‘red’ stream patient according to practice procedures and appropriate precautions taken including:  separation in the waiting room, or waiting outside the practice (e.g., in the carpark) from other patients; the use of appropriate PPE by clinical staff interacting with the patient.
• The latest advice notes there is no legal requirement for a person to carry or show their exemption card when asked. The Ministry of Health warns that anyone questioning a non-mask wearer about their eligibility may be at risk of contravening the Human Rights Act. 
• Under these circumstances the College suggests   that practices might like to place a notice in their reception area stating:

This practice respects that some people are not able to routinely wear a mask and they have an exemption for this.  However, both our practice staff and other patients are in a particularly vulnerable situation with unmasked patients entering the building. 

For those who have an exemption, it would be appreciated if you would consider wearing a mask for the short duration that you are here.

If you are unable to wear a mask, we will insist that you remain separated from other patients by at least two metres.

3.  Scabies

Delayed diagnosis of scabies, particularly in aged care facilities, is a reasonably common source of complaint to HDC

• BPAC has recently released an updated article on diagnosis and management of scabies  noting aids to diagnosis include use of dermoscopy to visualise the mite or an ink test to highlight burrows.  Microscopy to confirm a diagnosis of scabies is rarely required except in crusted scabies when a skin scraping should be considered.

• Permethrin 5% cream (Lyderm) or lotion (A-Scabies) is the recommended first-line treatment for classic scabies.  Treatment is not effective against eggs so it should be repeated seven days after the initial application to cover any newly hatched larvae.  Hands will need to be treated with cream if washed with soap within 8 hours of application.

• The manufacturer recommends application to the body but to exclude head and neck. However, application should be extended to the scalp, neck, face, and ears according to NZF.  Larger patients may require up to 2 x 30 g packs for adequate treatment.

• Second line treatment for classic scabies (if permethrin ineffective) or first line if crusted scabies is oral ivermectin stat dose repeated after 7-10 days (not to be used in children weighing under 15kg). 

4.  Clinical Pearl – Suturing

When suturing a wound on the back of the hand and other areas in the elderly where the skin is like tissue paper first stick a piece of narrow Micropore tape or a wide steristrip along the wound edge and suture through it to close the wound.  The tape can be removed at the time of suture removal or left in place to separate over a longer period.  The technique is described in more detail with references and accompanying video on the laceration.com website.  

5.  Phentermine and serotonin syndrome risk

In the latest NZF update, serotonin syndrome has been added as a precaution to phentermine (Duromine) prescribing information when phentermine is prescribed with other serotonergic drugs. 

• Serotonin syndrome diagnosis is based on ingestion of a serotonergic agent(s), presence of a combination of different symptoms and exclusion of other causes.
• Symptoms may include alterations to mental status (eg, confusion, anxiety and agitation), autonomic changes (eg, hyperthermia, hypertension, tachypnoea, diaphoresis, diarrhoea and tachycardia) and neuromuscular effects (eg, clonus, tremors, hyperreflexia and hypertonia). The cardinal sign is clonus.
• Symptoms of serotonin syndrome usually occur within hours to days of taking the medicine.
• Treatment involves stopping the serotonergic agent and providing supportive care.

A non-exhaustive list of serotonergic agents is available in a 2015 Prescriber Update article with phentermine having been added since that time. 

An older BPAC article reviewed several cases of serotonin syndrome notified to CARM with clinical details:

• Fluoxetine added within the previous week to low dose amitriptyline taken for several months.
• Venlafaxine taken in increasing doses to 325 mg daily over five days.
• The patient was also taking nortriptyline.
• A single dose of citalopram added to tramadol which had been taken for three days.
• Paroxetine taken for less than one month, with a recent dose increase, in addition to long term clomipramine.
• Low dose phenelzine commenced. Citalopram had been discontinued five days previously with a dose reduction to 10 mg daily two weeks prior.

6.  Antivirals Access Criteria assessment tool

An electronic guide developed by Pharmac is intended to help clinicians assess whether their patient is eligible for funded COVID-19 antiviral treatments under section 4 of the access criteria.

7.  Post-Covid-19 Syndrome

There is evolving evidence regarding diagnosis and management of this condition summarised in a recent NZ Doctor article.   A similar guidance article from the UK reiterates some of the principles of management

• The illness is characterised by an unpredictable, relapsing–remitting pattern with fluctuating symptoms (dubbed the ‘corona coaster’). Significant associated conditions can often appear weeks to months into the disease course. Without effective treatment, recovery is typically very slow; in fact, many patients remain symptomatic up to 2 years after the initial infection.

• Barriers to recovery include stress, poor sleep, poor gut health, and menstrual hormone imbalance in women. Overexertion (both mental and physical) may cause an exacerbation of symptoms, termed the ‘boom-and-bust’ phenomenon.  Intercurrent infection can also trigger symptom flares.

• There is considerable overlap between some symptoms of long COVID and those of mast cell activation syndrome. A significant reduction in symptom burden was evident in up to 72% of patients with long COVID treated for up to 16 weeks with a combination of H1 and H2 antihistamines in an ongoing UK study.  Their standard antihistamine protocol is to recommend a therapeutic trial of the oral H1 antihistamine loratadine (10 mg twice daily), in combination with the H2 antihistamine famotidine (40 mg once daily), in all patients with long COVID. This treatment typically needs to be taken for a minimum of 3 months.

• Coding is important to monitor the burden of disease.

April 2022

Clinical Snippets April 2022

1.  Eating disorders

Some useful resources for parents while they wait include (Goodfellow Gem):

• F.E.A.S.T info for parents
• EDANZ 
• Eating disorders. Mental Health Foundation
• Eating disorders. Health Navigator NZ
• Centre for Clinical Interventions   https://www.cci.health.wa.gov.au/  

For clinicians: Regional clinical pathways.   Also links to multiple resources for patients and whanau together with advice on management and monitoring. 

Private options include:

New Zealand Eating Disorders Clinic (NZEDC)

2.  BPAC update on weight loss

BPAC has recently released an update on weight loss: the options and the evidence.   Some key practice points include:

• The overriding principle of weight loss is that energy intake needs to be less than energy expenditure; there is no consistent evidence that any one calorie-restricted diet is better than another at achieving weight loss
• At least 2.5 hours of moderate intensity physical activity per week should be included in all weight loss interventions
• Contrary to popular belief, rapid weight loss is not associated with an increased risk of weight regain compared to gradual weight loss
• Pharmacological interventions may be considered only after dietary, exercise and behavioural approaches have been initiated and evaluated for people who are obese or as an adjunct to diet and lifestyle interventions, after the potential harms and benefits of treatment have been reviewed

There are two new pharmacological interventions approved in New Zealand (but not funded) for weight management:

Liraglutide (a GLP 1 receptor agonist – Saxenda) – daily SC injection, cost about $500 per month

Naltrexone + bupropion (Contrave) – tablet uptitrated over 3 weeks, cost about $220 per month

Cost comparison:  phentermine Duromine (30mg caps) $100/month;  orlistat (Xenical)  $180/month

Indication:  BMI ≥30 or 27-30 if at least one weight-related co-morbidity

Recent Tools for Practice question:  Is naltrexone/bupropion (Contrave^®) effective for weight loss?

Bottom line:  Over 28-56 weeks, at best, ~50% of patients taking naltrexone/bupropion achieved a >5% loss in body weight, compared to ~20% in control. Naltrexone/bupropion adverse events (examples nausea, constipation) lead to withdrawal in 23% of patients versus 12% on placebo.

3.  Depo-Provera dose interval update

In the April 2022 NZF update a change to dosing recommendation for Depo-Provera is noted as: 

• Individuals should be advised to return every 13 weeks for a repeat injection of intramuscular DMPA (outside the product licence for intramuscular DMPA). Health practitioners should be aware that this is an evidence-based recommendation and signals a change in practice in New Zealand. This recommendation may differ from the Manufacturer data sheet.

• Good practice points:  An injection of DMPA can be administered up to 7 days late (up to 14 weeks after the last injection) without the need for additional contraceptive precautions (outside the product licence for intramuscular DMPA). If necessary, an early repeat injection of DMPA can be administered from 10 weeks. 

4.  Supply issues with smoking cessation treatments

All patients who smoke should be encouraged to stop and provided with cessation support, including both behavioural and pharmacological treatment. Currently, the options for pharmacological support are limited due to supply constraints.

•  Varenicline has been unavailable for almost 12 months due to a manufacturing safety issue, and bupropion supply is now being managed in New Zealand due to increased global demand and manufacturing constraints.
• This leaves nicotine replacement therapy (patches, gum or lozenges) as the remaining funded pharmacological option; note that this is usually the first-line recommended treatment for smoking cessation. Nortriptyline (funded) may also be an option for some patients. Read more about smoking cessation treatments here.
• Vaping is not an approved smoking cessation method, but health care professionals can provide information to help smokers make an informed choice: read more here.

5.  Chronic pain guideline for primary care 

A recent Goodfellow Gem looked at the work of a Canadian panel that filtered 74,000 papers to get a summary for chronic pain management of osteoarthritis, low back pain, and neuropathic pain.  The findings are summarised in a table that might be useful for discussion with patients.

Some findings of note include:

• Placebo is fairly effective 29% to 40%.
• Physical activity is essential for OA and back pain.
• For OA (NZ available drugs) – steroid injections, oral and topical NSAIDs are effective.
• Glucosamine and chondroitin are of uncertain benefit as the publicly funded trials found no benefit while the industry-sponsored ones did show benefit.
• For low back pain – spinal manipulation, oral NSAIDs, and TCAs.
• The authors felt cannabinoids and opiates showed that harms exceeded benefits.

6.  The dangers of psychosis induced violence

Findings of a recent Coronial inquest into the deaths of five people who were killed in 2015 and 2016 by patients who were in a florid psychotic state have been summarised in GP Pulse with learnings for GPs documented as:

• When you are concerned about a patient and refer them, be ASSERTIVE. Say what you think and if it is a phone call, identify exactly who you are talking to. 
• Insist on talking to a consultant psychiatrist if you have concerns.  
• If you have an expectation about the type of care required, you need to state it clearly. You should also state that if your recommendation is not to be acted upon, then you should be contacted (leave your contact number) and you may wish to speak to a more senior member of the mental health team.
  • These cases are monumentally complicated, and a peer-to-peer discussion is the safest form of communication. You may well be the person who has the greatest insight into the case.
• Once you have made a referral, document it carefully.
  • If something goes wrong, you may find that other health professionals have a very different interpretation of what you said/documented.
• Keep clinical antennae up with patients who are guarded in their communication. Despite being psychotic, some patients can be wary of health professionals who may insist on treatments that they find intolerable.
• When family members or indeed other members of the public report abnormal behaviour you need to talk to and listen to them. This is not breaking patient confidentiality and may be critical to everyone’s welfare. You need to interview these people often without the patient present.
• We have a duty of care to our patients and their families and better outcomes for both should be paramount in our thinking.

Clinical Snippets May 2022

Clinical Snippets – May 2022

1.  ACC Treatment Injury

• Refusal to provide or delays in lodging a Treatment Injury claim with ACC is not an uncommon source of patient complaints.  However, on average a third of Treatment Injury claims are declined each year

• ACC has a provider resource (to which a patient could also be referred) clarifying the process

• The principles of a claim are:
  • An injury has occurred that has resulted in physical harm or damage to the patient
  • The injury has been caused by the treatment (probability rather than possibility considered)
  • The injury is not a necessary part or an ordinary consequence of treatment, having regard to the clinical knowledge at the time of treatment and the underlying health condition of the patient

• A precipitating event can include when treatment has not been given by mistake or has been given unreasonably late

• Lack of evidence of physical injury caused by treatment is the most common reason for a claim to be declined

• If review of an ACC Treatment Injury claim results in concern there is a risk to the public, the details may be forwarded to HDC

2.  Concussion

BPAC has recently published a comprehensive overview of concussion management for primary healthcare professionals – audiovisual and written resources including a summary sheet.  Key practice points include:

• Recognising concussion in primary care can be challenging as symptoms and signs are often subtle, non-specific, and can progress over time.  Initial loss of consciousness only occurs in one in ten people with concussion
• The Brain Injury Screening Tool (BIST) is a standardised and validated assessment tool to evaluate patients with suspected concussion; this is specifically tailored for use in time-limited clinical consultations (takes 5-6 minutes to complete)
• Initial management of patients with concussion involves physical and mental rest for 24 – 48 hours; in most cases patients should then progressively re-engage in normal activities after this rest period, assuming the degree of engagement does not significantly worsen symptoms – excessive rest can prolong recovery.
• Patients who have sustained a sports-related concussion should be immediately removed from play, and not return until they have been medically cleared after completing a graduated return-to-play protocol
• Patients can be reassured that most people who experience a concussion will fully recover within two to four weeks. However, recovery is strongly influenced by the timeliness of clinical review and follow-up, effective education delivered at an appropriate level of health literacy (and whether the advice given is culturally appropriate/relevant), as well as other patient-specific factors, e.g. initial symptom burden, ‘yellow flags’
• On-line educational resources are available from ACC for adult patients (English and Te Reo Maori) and for carers of an affected child
• Post-concussion syndrome is no longer a recognised as a diagnosis in DSM-5. ICD-11 or by ACC.  The preferred term is ‘persistent concussion symptoms’ (beyond three months). 

The article covers all aspects of assessment, education, recovery and rehabilitation,  complications, return to work and sport advice etc. 

3.  Calcium for hypertension?

A recent PEARL published in NZ Doctor referenced a Cochrane review noting several studies have shown an inverse association between calcium intake and blood pressure, and small reductions in blood pressure have been shown to produce rapid reductions in cardiovascular disease risk even in individuals with normal blood pressure. A 2 mmHg lower systolic blood pressure is predicted to produce about 10% lower stroke mortality and about 7% lower mortality from ischaemic heart disease.

An increase in calcium intake slightly reduced both systolic and diastolic blood pressure in normotensive people. The effect was confirmed in multiple prespecified subgroups, including a possible dose–response effect (1500mg per day being more efficacious than 1000mg), reinforcing the efficacy of the intervention. The effects were observed after only 3.5 months of intervention and were more pronounced in younger patients.

Most of the studies used calcium supplements and there is some suggestion that the effect might be lost over time in populations with adequate calcium intake.

Conversely, a 2021 meta-analysis in the journal Nutrients reported that dietary calcium intake of 700–1000 mg per day or supplementary calcium intake of 1000 mg per day increased the risk of CVD by about 15% in healthy postmenopausal women.

4.  Dog bites

Starship Hospital has updated its guidance on management of dog bite injuries which are increasing in frequency.  Practice points include:

• In serious incidents police or animal management may require photos or DNA collection from the wound prior to washout or closure. Encourage patients to take their own photos of injuries to keep for future reference.

• Consider imaging (Xray/CT) in even seemingly simple dog-bite injuries. Significant force (>1000N) can be involved, with deep penetration or crush injuries not initially obvious.
• Examination and copious irrigation should be done if the dermis has been penetrated or if the wound is in the proximity of joints
• Primary wound closure is recommended if early presentation (<4-6hours) AND absence of non-viable/heavily damaged tissue/contamination.  Delayed wound closure or healing by secondary intention is recommended for all other wounds.
• There is evidence that prophylactic antibiotics are associated with a statistically significant reduction in infection in dog-bites to hands.  There is conflicting evidence for other wounds. Antibiotics are also indicated for any infected wound, or as prophylaxis for puncture wounds, bite-injuries to hands, feet, face or genitalia, immunocompromised patients, those requiring surgery or who have an underlying structural injury, or if presenting >8 hours after the bite. 
• Amoxicillin/clavulanic acid is the antibiotic of choice with alternative for penicillin allergic patients being metronidazole plus co-trimoxazole (≥1 month – 11 years) or metronidazole plus doxycycline ( ≥ 12 years)
• It is strongly recommended that health professionals notify all dog-bite and serious non-bite dog-related injuries to the Animal Management Service of the council where the dog bite occurred, and do not require patient consent. Dogs pose a serious health risk to vulnerable people, including children, who are more likely to receive serious bites to the head/face/neck, and the potential for significant psychological harm in any age group
•   Any serious risk to a child or the public also needs to be referred to Social Work, Oranga Tamariki and/or Police. Animal Management Officers have limitations on what they can do in situations where a dog has bitten a family member, and may require further input from these services to ensure safety measures are put in place.
• Offer psychological support to all victims, and to whānau who have witnessed an attack. ACC can provide support with counselling or therapy sessions. 
• The Starship website has a printable information sheet for carers of affected children which includes reference to notification to Animal Control Officers, and a Council Notification form (currently Auckland specific – Hamilton details are Ph 07 8386632, email: animalweb@hcc.govt.nz  ) 

5.  Avocados

• A recent BPAC update references a recent paper published in the Journal of the American Heart Association that has found higher avocado intake is associated with a significantly lower risk of cardiovascular disease (CVD) and coronary heart disease.

• In a study of almost 70,000 women and over 40,000 men who did not have a history of cancer, coronary heart disease or stroke at baseline, followed up for thirty years, it was found that those who had two or more servings of avocado per week had a 16% lower risk of CVD and 21% lower risk of coronary heart disease. There was no significant association with a lower risk of stroke.

• The authors concluded that CVD risk could be lowered by 16 – 22% by replacing half a serving per day of high fat content foods such as margarine, butter, egg, yoghurt, cheese or processed meat with the equivalent amount of avocado.

Clinical Snippets March 2022

https://anchor.fm/opotikigp/episodes/Clinical-Snippets-March-2022-e1i6ir6

Show notes :

Clinical Snippets March 2022

1.  Naloxone and non-intentional opioid overdose

• A recent NZ Doctor article noted concern from the NZ Drug Foundation at the limited availability of naloxone to selected patients with opioid dependence as a means of decreasing fatalities from accidental overdose (around 50 per year).

• In 2020, an emergency kit containing two naloxone (Nyxoid) nasal sprays was approved for sale without a prescription. However, because it is not funded, at $92 it is out of reach for many people. It is also difficult to source with few pharmacies contacted in the article actually stocking the kit and is not subsidised if prescribed.
• Naloxone ampoules (for injection) continue to be available by prescription-only (PSO – maximum of 5 ampoules) but are available as an emergency kit in some countries. 
• Health Navigator has resources regarding community initiated use of naloxone including pamphlets developed by Waitemata DHB for use of intramuscular and intranasal naloxone.
• The incidence of iatrogenic opioid use disorder is around 3% over 2 years but causation is uncertain.  The Prescription Opioid Misuse Index (POMI), a 6-point questionnaire with strong predictive ability for OUD, may be a reasonable case-finding tool.  Medsafe have recently published a pamphlet outlining the risks of opioid medications.
• The HQSC Atlas of Healthcare Variation (large PHO comparison) shows that in 2019 2.0 people/1000 enrolled with practices in the MHN Waikato PHO region were dispensed a strong opioid for more than six weeks – slightly below the national average of 2.1.  Rates ranged from 1.5 (Procare) to 2.9 (WellSouth PHO).

2.  COC and VTE

Medsafe have recently published a Prescriber Update following reports of a fatal PE in a young woman taking a COC.  Points include:

• Prescribers are reminded to counsel patients about the symptoms and signs of venous thromboembolism (VTE) when prescribing combined oral contraceptives (COCs).
• VTE may occur at any time during use of a COC. However, the risk of VTE is highest during the first year after starting a COC and when restarting after a break of four weeks or more.
• Ensure COC users know to seek medical attention if they experience symptoms or signs of VTE.
• COC use is associated with a 3- to 3.5-fold increase in the risk of VTE compared with non-use although absolute risk is low.  Reassess the risk of VTE periodically during COC use as risk factors may change over time.
• Consider the possibility of VTE in COC users who present with non-specific symptoms.  Patients with VTE may be asymptomatic or present with non-specific symptoms such as calf tightness, chest pain or cough. Always be mindful of the possibility of VTE in COC users and follow local guidelines for the investigation and management of suspected VTE as necessary.

3.  Rosuvastatin funding

• From the end of last year the very high potency statin rosuvastatin has been funded using SA for selected patient groups: 

LDL-C level eligibility for rosuvastatin funding

• Note the NZ Guidelines give an LDL-C target of < 1.4 mmol/L in people at high risk
• Use the Dutch Lipid Clinic Network Score (DLCNS) to determine the likelihood of familial hypercholesterolaemia diagnosis if suspected
• Further information on rosuvastatin dosing, contraindications and precautions can be found in a recent BPAC article  

4.  Ovarian cancer

A recent NZ Doctor article included the following points regarding ovarian cancer: 

• Ovarian cancer is a significant health issue in New Zealand – incidence and mortality rates are higher in Pacific and Māori women and compared with Australia, 16 per cent fewer women survive five years in New Zealand.
• GPs have an essential role to rule out ovarian cancer in symptomatic women and diagnose those with cancer in a timely manner.  Practitioners in countries with better survival are more willing to order an ultrasound at first visit for the following scenario: a 53-year-old woman who had her last period six months ago and has experienced abdominal pain for the past three weeks; she has had no other symptoms and the same sexual partner for 20 years.
• On average, a GP with 2000 patients will see one patient with ovarian cancer every four and a half years.
• Ovarian cancer is much more common in the postmenopausal population. However, in New Zealand, it is worth noting that one in eight cases occur in women younger than 45 years, and in the 20–44 age group, ovarian cancer remains the fifth most common cause of female cancer death. Younger age is a risk factor for delayed diagnosis.
• The symptoms women present with are variable but can include one or more of: bloating/distension, early satiety, urinary frequency/urgency, abdominal/pelvic/back pain and bowel habit changes. Other symptoms are also possible, including indigestion, nausea, fatigue, abnormal vaginal bleeding/discharge, unexplained weight changes and painful intercourse.  While it’s true these symptoms are very common in general practice, in women without ovarian cancer, they are usually mild and occur on five or fewer days a month.  In contrast, symptoms in ovarian cancer occur more frequently.
• Investigation for ovarian cancer usually includes a pelvic exam, cancer antigen 125 (CA-125) blood test and transvaginal ultrasound (TVUS).  Though pelvic exam has a low sensitivity when used as screening, it remains an important part of assessment in symptomatic patients. DHBs report decreased wait times for TVUS when pelvic exam is positive.
• Further detail on local recommendations regarding interpretation of CA-125 levels and referral for ultrasound and gynaecological assessment or advice can be found in HealthPathways.   A downloadable symptom diary can be found here. 

5.  Methotrexate and trimethoprim

Key points in a recent Medsafe Prescriber Update following a death associated with co-prescribing of methotrexate and trimethoprim include: 

• Severe bone marrow suppression has been reported in patients on methotrexate who have received trimethoprim or co-trimoxazole (trimethoprim with sulfamethoxazole). Some cases have been fatal.
• Trimethoprim and co-trimoxazole should be avoided in patients taking methotrexate.
• If this drug combination cannot be avoided, warn patients about the symptoms of bone marrow suppression. Advise them to seek immediate medical attention should these symptoms occur.

6.  Supply issues affecting FundaPen2 rollout

EpiPen® auto-injectors have been available through the FundaPen2 initiative from Wednesday 9 February 2022.  However, Allergy New Zealand has hit supply issues with 300mg adult EpiPens® due to global COVID freight delays. To ensure as many people as possible benefit from FundaPen2, it is important to keep prescribing under the FundaPen2 protocols. Patients will receive their free EpiPen® as soon as the stock is available, April 2022 at the earliest.

A reminder of the process:

1. The GP establishes that the patient is clinically eligible for FundaPen (doctor-diagnosed with an allergy that puts them at risk of anaphylaxis, and needing an EpiPen® as per prescribing guidelines)

2. The GP completes the patient’s prescription for ONE EpiPen® as usual and e-mails to Allergy Pharmacy info@queenstownpharmacy.co.nz .  Please include the patient’s weight on the prescription so that the correct Epipen® is dispensed. (As per ASCIA guidelines more than 20kg qualifies the patient for an Adult Epipen® auto-injector regardless of age).

3.  Additional Pharmacy details are:  Fax 03 441 0591;    Allergy Pharmacy, PO Box 157, Queenstown.

4.   Allergy Pharmacy assesses that the prescription meets the FundaPen qualification criteria and dispenses the EpiPen® to the prescribing GP. 

5. GP receives the EpiPen® and contacts the patient to return for training (if required) and dispensing. 

6. Only one FREE EpiPen® is available per eligible patient.  Once the available subsidised supply (fixed funding) has been exhausted, normal fees and charges will apply. 

February 2022

Clinical Snippets February 2022

1.  Peripheral artery disease and walking

From a recent Tools for Practice:  In patients with PAD, exercise therapy improves maximum walking distance and pain-free walking distance by up to ~200 meters over 2 to 78 weeks compared to usual care. No benefit has been demonstrated for amputation or mortality. The most commonly studied exercise is supervised walking 2-3 times per week for 30-60 minutes, although other supervised activities (example resistance training) may be beneficial in those who cannot tolerate walking.

• Patient understanding of physical activity for PAD should be explored:
• 63% identified walking as the primary aetiology for their pain, 90% thought walking would worsen symptoms.

2.  Electronic communication and the internet

Last year MCNZ released an updated statement on Use of the internet and electronic communication  which includes the following points (and I recommend reviewing the whole document):

• Inappropriate communication, including use of social media, can be considered unprofessional, whether this is directly related to a doctor’s work or not.
• Patients who get information from the internet may wish to discuss this with you. You should use this as an opportunity to talk about how sometimes the information obtained from these sources may be of poor quality, incorrect, or create unrealistic expectations. Provide sound reasons for the views you express and, where possible, provide documentation, to support the alternative advice or treatment that you are recommending.
• There are security issues specific to the use of email. It is difficult to verify a person’s identity from an email; some families and groups share a common email address; and computers (particularly family computers) may be accessed by a number of different people. For these reasons, check with the patient before sending them sensitive information by email.

3.  Aotearoa New Zealand STI Management Guidelines – Chlamydia

• There is growing evidence that sexually transmitted Chlamydia trachomatis establishes a persistent rectal reservoir that is refractory to treatment with azithromycin stat.
• The evidence is very strong for men who have sex with men, but is growing for women too.
• Contemporary guidelines are abandoning azithromycin stat and reverting to doxycycline 100mg BD for seven days with stat azithromycin only if doxycycline contraindicated or patient is highly likely to be non-adherent.
• Symptomatic anorectal infection generally requires specialist advice as further testing and management is complex

4.  Recurrent Bacterial Vaginosis (BV)

A recent article in NZ Doctor includes the following key points on recurrent BV:

• There have been no major advances in the treatment and cure of bacterial vaginosis, perhaps because the pathophysiology is complex, multifactorial and not fully understood.
• Standard therapy is seven days of twice-daily metronidazole, but many women are looking for alternative treatments that may provide longer duration between recurrences.
• Intravaginal boric acid capsules have been used historically and may be considered an alternative, though unfunded, treatment to use in conjunction with antibiotic therapy.

DermnetNZ lists a number of alternative treatments including gels to reduce vaginal pH and a vaginal antiseptic dequalinium.  It does not appear any of the recommended products are in NZF but Aci-Jel is available OTC (around $30 per 100g tube).    Boric acid vaginal pessaries can be bought on-line – eg pHD $199 for 72 caps (about five courses)

A 2009 Cochrane review concluded that research at that time research did not provide conclusive evidence that probiotics are superior to or enhance the effectiveness of antibiotics in the treatment of BV.  However, a 2019 meta-analysis concluded that probiotic regimes are safe and may exhibit a short-term and long-term beneficial effect for BV treatment.  There are many OTC preparations available.  Probiotics do not form part of HealthPathways or Aotearoa New Zealand STI Management Guidelines recommendations for management of BV. 

DermnetNZ also discusses cytolytic vaginosis as a cause of possible of persistent vaginal discharge.  This is the result of a hyperacidic vaginal environment due to overgrowth of lactic acid producing bacilli, with management aiming to reduce vaginal pH (baking soda douching). 

5.  Extended use of intrauterine devices

Tools for Practice examined the evidence around effectiveness of intrauterine devices for prevention of pregnancy when used beyond the manufacturer recommended use period.  The conclusion was:

If it is not possible or desirable to replace a levonorgestrel 52mg or copper-T380A intrauterine device (IUD) at the end of the approved duration of use, small observational studies demonstrated similar efficacy and safety for up to two additional years, with little evidence afterwards. Guidelines suggest that with patient-informed discussion, deferral of IUD replacement for up to twelve months is reasonable.

6.  Antipsychotic switching tool

A useful tool is available from NPS Australia that assists prescribers when changing a patient’s antipsychotic treatment. Using the interactive tool, the prescriber enters the formulation (oral or depot), the current medicine the patient is prescribed and the medicine they want to switch the patient to. This then generates prescribing information about how to stop one medicine and start the next, along with key clinical issues to be aware of. All antipsychotic medicines currently funded in New Zealand are included in the tool.

7.  Serotonin syndrome – a reminder

A relatively common prescribing complaint I see relates to patients concerned they were not warned of the risk of serotonin syndrome, or that they experienced serotonin syndrome, usually secondary to co-prescribing of two serotonergic agents.  The most common combinations I see are tramadol and SSRI, SNRI or TCA, or when a TCA is added to an existing antidepressant regime.  A 2015 communication from Medsafe discusses the issue in more detail and is worth a quick review.