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.