Clinical Snippets June 2023

1.  Stopping antidepressants

A recent BPAC bulletin reviewed a 2023 British Journal of General Practice article on appropriate withdrawal of SSRIs.  Key points included:

• A proportionate dose taper should be used where the dose is reduced by a proportion of the previous dose e.g. 50% of previous dose, depending on certain factors such as the patients symptoms and whether the available formulations of the SSRI allow the preferred reduction in dose.  Smaller dose reductions, e.g. 25% of previous dose, might be considered when low doses are reached and this might require alternate day dosing.

• Dose tapering should occur slowly over months to years depending on individual circumstances. Higher doses of SSRIs, longer durations of use and SSRIs with shorter half-lives, e.g. paroxetine, are generally associated with more severe symptoms of withdrawal and patients may require tapering of the dose at a slower rate.

• Monitor patients for symptoms of withdrawal and differentiate between withdrawal and relapse:  Symptoms of withdrawal include irritability, sleep disturbance, hallucination, suicidal ideation dizziness, headaches, sweating and are reported by more than half of patients when discontinuing SSRIs. Reinforce the use of coping strategies, e.g. exercise, mindfulness-based techniques, sleep hygiene and be prepared to slow the taper if withdrawal symptoms occur.  Symptoms of withdrawal are more likely to begin within days of discontinuation or reduction of the SSRI. In contrast, symptoms of relapse typically occur weeks to months after cessation of the SSRI.

• Discuss the possibility of withdrawal symptoms, including the importance of following the tapering protocol to minimise any symptoms. Advise that they should not abruptly stop taking the SSRI. A patient information sheet developed by Medsafe is available here.

Additional resources: 

• For further information on antidepressants, including switching or discontinuing, see: https://nzf.org.nz/nzf_2225
• A guide to what medications can be crushed or dissolved is available from SafeRx. 

2.   Miconazole gel and warfarin

• Miconazole oral gel inhibits the metabolism of warfarin via inhibition of CYP2C9.
• Healthcare professionals are advised to avoid miconazole oral gel in patients taking warfarin.
• If concomitant use of miconazole oral gel and warfarin is necessary, the patient’s INR should be carefully monitored.
• See the 2013 Prescriber Update on this topic. 
• The manufacturer data sheets for miconazole oral gel (and associated consumer information sheets) state it is contraindicated in children less than six months of age while NZFC  notes it is  not approved for use in children under 6 months of age (ie use in this age group is ‘off label’).  However, dosing instructions for neonates and infants under six months of age are provided in NZCF and:  For infants and young children, give oral gel in small amounts at the front of the mouth, or smear around the inside of the mouth. Do not place gel in the back of the mouth as this may cause choking. 

3.  Goodfellow Gem on lung cancer

A recent Goodfellow Gem refers to a Goodfellow Unit webinar on early detection and advances in management of lung cancer including a current study on low dose CT screening for lung cancer in high-risk Māori patients.  Lung cancer is the single biggest contributor to the difference in life expectancy between Māori and non-Māori, with lung cancer the leading cause of death for Māori women and the second leading cause of death for Māori men after cardiovascular disease. Māori women’s rates are more than four times higher and Māori men’s rates nearly three times higher than those of non-Māori.

The Gem looked at eight symptoms to consider for rapid diagnosis of lung cancer:

The persisting cough in the patient with COPD ± smoker is a common presenting symptom. The eight symptoms are:

•          Cough >3 weeks

•          Haemoptysis

•          Chest or shoulder pain

•          Dyspnoea

•          Hoarseness

•          Weight loss >10%

•          Unresolving chest infection

•          Symptoms suggestive of metastasis (liver, bone, brain, skin). In some parts of the country, if the CXR is suggestive of a curable lesion the chest CT can be bypassed but refer them to the respiratory team (refer local pathways). The e-referral should state “high suspicion of cancer”.  In those cases, the team may arrange a PET-CT scan. 

A 2021 systematic review and meta-analysis on performance of plain chest X-ray for diagnosing lung cancer in symptomatic primary care patients showed a sensitivity of around 80% with the comment: A negative chest radiograph does not exclude lung cancer, and physicians should maintain a low threshold to consider specialist referral or cross-sectional imaging.  BPAC has a comprehensive 2021 article on early detection of lung cancer in primary care. 

4.  Can PPIs help crying babies? 

A recent Tools for Practice looked at the clinical question:    In infants (≤1year) with crying/irritability attributed to feeds, do proton pump inhibitors (PPIs) improve symptoms over placebo without additional harms?  The context:

• Frequent effortless regurgitation of feeds is common in early infancy (affecting ≥40%).

• Regurgitation accompanied by distress symptoms (e.g., crying, back arching, irritability) have traditionally been attributed to gastroesophageal reflux disease. While PPIs improve oesophageal pH in infant RCTs, they do not improve symptoms.

• Guidelines recommend against empiric trials of acid-suppressing drugs for crying/distress or regurgitation.  Parents can be reassured that frequent regurgitation can be normal and frequently settles (90% have resolution at age ≤1 year).

The conclusion:  PPIs do not improve crying, fussiness, irritability, or regurgitation attributed to feeds. However, PPIs may increase the risk of serious adverse effects (e.g., respiratory tract infections) from 2.5% on placebo to 12% at 4 weeks.  Local HealthPathways state:  Use of omeprazole in infancy is not indicated in primary care as there is a lack of evidence for its effectiveness, and concerns about its safety. Evidence for the use and safety of alginates (e.g. Gaviscon Infant) is inconsistent. They may have a role in treating infants with GORD but only for an on-demand use rather than regular or long-term use.

5.  Aspirin and primary prevention of CVD

A recent issue of GP Research Review commented on a recently published literature review and meta-analysis on use of aspirin with or without statin across all risk groups in patients without confirmed atherosclerotic cardiovascular disease (ASCVD).  The investigators concluded that in patients without ASVCD the risk of major bleeding associated with aspirin is greater than the reduction in MI risk across all ASCVD risk levels. Concurrent use of a statin reduces the cardiovascular benefits of aspirin without influencing bleeding risk. Therefore, in patients without ASCVD who are already taking a statin, the addition of aspirin is unlikely to achieve a meaningful CV benefit but would increase the risk of major bleeding.

Current HealthPathways recommendations are, for primary cardiovascular disease (CVD) prevention: 

• Consider aspirin only for high-risk patients younger than 70 years, taking into account the benefits and harms.
• If not high risk, aspirin and other antiplatelet agents for primary prevention alone are generally not recommended.
• If older than 70 years, the balance of benefits and harms of aspirin is not clear, so is not recommended for primary prevention alone.

6.  Winter virus action plans

As part of its ongoing commitment to antibiotic stewardship, He Ako Hiringa has developed virus action plans for adults and children which cover rationale for avoiding antibiotics and extensive modifiable management and safety netting advice.  The plans can be edited on-line and then printed and/or downloaded for electronic transmission and retention.   

7.  Sodium valproate in males

A recent Medsafe Prescriber Alert comments on the risk of neurodevelopmental disorders in children fathered by patients using valproate at the time of conception.  Information for healthcare professionals includes: 

• The Epilim data sheet and CMI have been updated to include new safety information relating to use in males of reproductive potential.
• Use of sodium valproate at the time of conception by people who are able to father children has been linked to a potential increased risk of neurodevelopmental disorders in children compared to those who took lamotrigine/levetiracetam.
• Inform patients of this potential risk and consider alternative treatment options for those wishing to father a child.
• Discuss the need for effective contraception when starting sodium valproate and periodically throughout treatment.
• The company has produced a guide which should be provided to all male patients of reproductive potential using sodium valproate.

https://podcasters.spotify.com/pod/show/opotikigp/episodes/Clinical-Snippets-May-2023-e24n5fn

Clinical Snippets May 2023

1.  Pelvic Mesh Complications

• Te Whatu Ora female pelvic mesh complications service is a national service for people born with biologically female pelvic organs, who may have been harmed by mesh implanted for the treatment of urinary stress incontinence or pelvic organ prolapse.  The Te Whatu Ora website provides comprehensive information regarding the service including downloadable GP flyer and infographic of how the process works.

• Care and support options include continence care, chronic pain management, counselling, and surgery. Care is provided by a multidisciplinary team including physiotherapists, social workers, psychology services, surgeons, pharmacist, sexual health therapist, pain medicine specialists, nurses, health navigator, and dietitian.   Services are located in Auckland and Christchurch. Transportation and accommodation assistance may be available.

• Specific referral information is available via HealthPathways (New Zealand Female Pelvic Mesh Service Requests)with more information in a recent eReferrals newsletter. 

2.  PSA Testing

GP Research Review issue 2 2023  comments on the USANZ position statement on PSA testing.      This position statement serves as an interim document for the optimised use of PSA testing in Australia and New Zealand until current guidelines on PSA testing are updated. The USANZ New Zealand section is working on new PSA guidelines to be released later this year as the 2015 guidance is now outdated and inconsistent with contemporary clinical practice.

Recommendations include:

• Ensure prostate cancer awareness amongst men and counsel them on the potential risks and benefits of PSA testing.

• Offer an individualised risk-adapted strategy for early detection of prostate cancer in men aged >50 years of age with a life expectancy of at least 10 years.

• Offer early PSA testing to men at an increased risk of prostate cancer:
  • Men >45 years of age with a family history of prostate cancer
  • Men of high-risk ethnicities (including Indigenous men) >45 years of age
  • Men carrying BRCA2 mutations >40 years of age

• Stop early diagnosis of prostate cancer based on limited life expectancy and poor performance status; for example, men with a life expectancy of <10 years are unlikely to benefit.

• For men with an initial PSA test of >3 ng/mL, the use of risk stratification (considering factors such as age, family history, digital rectal examination and PSA density) can help guide the need for further testing, including MRI and biopsy.

3.  Polypharmacy

Issue 3 of GP Research Review looked at a recent article published in the Journal of Primary Health Care with a focus on polypharmacy.

• A total of 61 indicators for inappropriate medicines prescribing in polypharmacy that are relevant to people aged over 65 years in New Zealand were identified, and form the “New Zealand Criteria”. Indicators that were considered ‘very important’ or ‘important’ in New Zealand were similar to published international criteria.

• Medicines that were identified as being of particular concern included NSAIDs, benzodiazepines, anticholinergics, antipsychotics and first-generation antihistamines. There were two indicators that reached 100% consensus: a combination of three or more CNS active medicines (e.g., antidepressants, antipsychotics, antiepileptics, benzodiazepines, zopiclone, opioids); and the use of long-acting sulfonylureas (e.g., glibenclamide). Eight out of nine experts agreed that it was very important to correct the prescribing of alpha blockers in older patients with postural hypotension and NSAIDs in older patients with stage 4 chronic kidney disease or higher.

• A complete list of potentially inappropriate medicines indicators is available in the full article.  A 2018 BPAC article contains useful resources for de-prescribing including a discussion on pharmacist services (eg Medicines Therapy Assessment) available in some areas. 

4.  New COPD guidance

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has published updated guidelines on chronic obstructive pulmonary disease (COPD).  The guidelines include several important changes, particularly concerning the use of long-acting bronchodilators in treatment.

• LABA/LAMA combination treatment is now recommended as first-line treatment in patients requiring a long-acting bronchodilator, including those who are more symptomatic or at high exacerbation risk. This supersedes previous guidance to use LAMA or LABA monotherapy first.

• Use of an ICS + LABA alone is now discouraged throughout COPD management unless prescribed for a concurrent diagnosis such as asthma, and a more targeted approach for ICS use is suggested.

• A revised “ABE” assessment tool for predicting patient outcomes and making treatment decisions. This recognises the clinical relevance of exacerbations, regardless of the patient’s symptom severity (i.e. categories “C” and “D” in the “ABCD” tool are now combined into a single “E” category).

• BPAC have previously provided useful COPD tools for assessment and management and note the following:  Given these significant changes, we plan to update our COPD tools. However, we will await any revision of New Zealand guidelines in accordance with the GOLD 2023 report. In addition, Special Authority approval criteria for LABA/LAMA combinations currently require patients to be stabilised on LAMA monotherapy first, making these recommendations difficult to apply equitably in practice.

5.  Type 2 diabetes

• A Dutch study reviewed in Issue 167 of the Diabetes and Obesity Research Review looked at use of SGLT-2 inhibitors in very-high cardiovascular risk patients with type 2 diabetes.  Only 10.3% of such patients were being prescribed SGLT-2 inhibitors despite being eligible under national guidelines.  Of those not prescribed the medication, there was no contraindication to prescribing in over 70% and none were on a GLP-1 agonist.  The reviewer notes SGLT-2 inhibitors have been available in the Netherlands for longer than they have here in NZ and wonders how well we are performing by comparison. 

• An excellent algorithm for management of patients with type 2 diabetes which incorporates prescribing of SGLT-2 inhibitors and GLP1 receptor agonists is available on the NZSSD website and can be downloaded as a PDF.  Further resources including interpretation and application of Special Authority criteria are available on the Pharmac website. 

• The EPIC dashboard on Te Ako Hiringa enables you to compare your prescribing for type 2 diabetes with those of your practice colleagues and national data and includes data on patient adherence to prescribed medication and tips for improving diabetes medicines equity. 

• The University of Waikato and New Zealand Society for the Study of Diabetes are running a free online diabetes management course starting 17 July 2023. The course is run over 20 weeks, made up of eight 30-minute webinars and eight 30-minute case discussion and mentoring sessions. The course is approved for 16 hours CME points.

6.  Vitamin D and diabetes

• A recent Goodfellow Gem commented on a study suggesting Vitamin D may reduce risk of diabetes in pre-diabetics.  The review and metanalysis of individual patient data from three trials reported a reduction of 3% in absolute risk of progression to diabetes. The comparable doses from two studies were 80,000 units 4 weekly and 120,000 units 4 weekly; the NZ option is 1.25 mg cholecalciferol tablet = 50,000 units once per month.

• There was an improvement with higher blood levels of Vitamin D, with the greatest reduction with a blood level of ≥ 125 nmol/l (18% absolute risk reduction). There appeared to be no adverse effects, but studies were not powered to detect these (but remember Vitamin D is fat soluble and can be toxic in overdose – usually serum levels >375 nmol/L).  The NNT to prevent diabetes is 30 (compared with 7 for intensive lifestyle and 14 with metformin). It was mainly effective in those with BMI < 31.3 Kg/m. The study ethnicities were European 50% and Asian 33%, so no Māori or Pacific patients.

• The same study was reviewed in Issue 212 of GP Research Review with the reviewer concluding:  Impressive, and I am going to be prescribing it for my prediabetics, can’t do any harm. 

7.  Topiramate in pregnancy

Medsafe have put out a further alert regarding use of topiramate in pregnancy and women of childbearing age.  Congenital malformations and neurodevelopmental disorders have been reported in children following in utero topiramate exposure.

Advice to health professionals includes: 

• Topiramate should only be used to treat epilepsy in pregnancy if the potential benefit justifies the potential risk to the mother and fetus.
• Refer epileptic women taking topiramate who become or plan to become pregnant for specialist advice.
• The use of topiramate for migraine prophylaxis is contraindicated in pregnancy.
• Perform pregnancy testing before starting treatment. Women of childbearing potential should use a highly effective contraceptive method during treatment.
• Inform women of childbearing potential about the risks of fetal harm if they become pregnant.

8.   Progestagen only contraception and risk of breast cancer

• A recent BPAC update bulletin notes previous studies have established that patients taking combined oral contraceptives are at slightly increased risk of breast cancer. Progestogen-only contraceptives have been considered an alternative option for patients where oestrogen is not recommended or contraindicated, however, the data regarding breast cancer risk and progestogen-only contraceptives has been inconsistent. A recently published study based in the United Kingdom (UK) now suggests that the risk of developing breast cancer in patients who take progestogen-only contraceptives is comparable to those taking combined hormonal contraceptives.

• While it is recommended that the new information is included when discussing the risks and benefits of contraceptive options with patients, the UK-based Faculty of Sexual and Reproductive Healthcare (FSRH) have not currently recommended any major changes to clinical practice in response to the study.

• Best practice tip: The absolute risk of breast cancer with progestogen-only contraceptive use is still very small, especially in younger patients with no familial breast cancer risk. The decision to prescribe any type of hormonal contraception should consider this low risk in the context of the possible benefits of use, e.g. reduced risk of an unplanned pregnancy and other non-contraceptive benefits such as reducing the risk of endometrial and ovarian cancers.

9.  Prescribing for ADHD

(i)  Pharmac has announced the General Rules of the Pharmaceutical Schedule will be amended from 1 June 2023 to allow three months of the stimulant/ADHD treatments, methylphenidate and dexamfetamine, to be funded when prescribed electronically.  While the Regulations allow electronic prescriptions for methylphenidate and dexamfetamine to be issued for three months at a time instead of one month, the frequency of dispensing for these medicines remains monthly. 

(ii)  The RANZCP has a statement on guidance for the use of stimulant medications in adults  (2015) which includes:  Specific caution, including appropriate monitoring, is required in the consideration of stimulant prescription to persons who have a history of substance abuse or dependence… Clinicians should assess and monitor the risk associated with stimulant prescription in adults with a history of hypertension, cardiovascular or cerebrovascular disorders. A baseline electrocardiogram (ECG) should be performed if there is a family history of serious cardiac disease or sudden death in young family members, or abnormal finding on cardiac examination. The patient’s blood pressure should be regularly monitored during the course of treatment with stimulant medication.

(iii)  New Zealand Formulary includes the following screening and monitoring advice for methylphenidate:

Pre-treatment screening 

• Obtain a detailed psychiatric history including family history of suicide, bipolar disorder, and depression
• Assess for risk of misuse (including family and caregivers)
• Assess for personal or family history of tics or Tourette’s syndrome
• Assess cardiovascular function including blood pressure and heart rate—seek specialist cardiac advice if history of, or current, cardiovascular disease
• Assess for family history of sudden cardiac or unexplained death or malignant arrhythmia
• Measure height and weight 

Monitoring requirements 

• Monitor for development or worsening of pre-existing psychiatric disorders, aggressive behaviour, anxiety or agitation at the start of treatment, at every dose adjustment, and at least every 6 months—consider discontinuing treatment if psychiatric disorders develop or worsen
• Monitor for emergence or worsening of tics or Tourette’s syndrome at every dose adjustment and at every clinic visit—consider discontinuing treatment if tics develop or worsen
• Monitor for misuse
• Monitor cardiovascular status including blood pressure and heart rate at least every 6 months and at every dose adjustment—seek prompt cardiac evaluation if palpitations, exertional chest pain, unexplained syncope, dyspnoea or other symptoms suggestive of cardiac disease occur
• Assess weight and appetite at least every 6 months
• Closely monitor patients at risk of acute angle-closure glaucoma
• Monitor full blood count, differential and platelet counts during prolonged therapy as clinically indicated.
• Consider de-challenge at least once yearly 

https://podcasters.spotify.com/pod/show/opotikigp/episodes/Clinical-Snippets-April-2023-e24n53a

Shownotes

Clinical Snippets April 2023

1.  Syphilis

(i)  A recent Te Whatu Ora Waikato newsletter notes here has been a sharp increase in infectious syphilis notifications during 2022. This is particularly in the upper half of the North Island including Waikato and largely due to a sharp rise in reported cases among men. Notifications among men who have sex with women (MSW) have more than doubled between 2022 Q1- 2022 Q3. Infectious syphilis notifications among Māori MSW more than tripled. Notifications among men who have sex with men (MSM) increased by 40%.

(ii) The number of infectious syphilis notifications among women of reproductive age (15-49) and pregnant women remain high. In Q3 about half of the women who have sex with men (WSM) notified were pregnant – we are not testing enough young women.  Congenital syphilis (CS) notifications remain high and individuals of Māori ethnicity continue to be overrepresented in maternal and CS cases.

(iii)  HealthPathways recommends testing for syphilis in the following situations:

• All patients having a routine sexual health check. Recommend a repeat test 3 months from the time of last sexual intercourse if particular concern.
• All pregnant women (first antenatal bloods). Offer re-screening between 28 to 38 weeks gestation for women at increased risk: who have had a new sexual partner during pregnancy; with more than one sexual partner during pregnancy; with an STI diagnosed during pregnancy; whose partner is diagnosed with an STI.
• All MSM, especially if HIV positive. Arrange serology at least annually.
• Any rash or genital symptoms in MSM
• HSV genital ulcer(s), atypical or non-healing genital ulcer(s)
• Unusual clinical presentations e.g., lymphadenopathy, unexplained abnormal liver function tests, alopecia, pyrexia of unknown origin
• Patients who have had sexual contact with a person diagnosed with syphilis (serology usually carried out by sexual health clinic)

(iv)  Syphilis can be asymptomatic. Consider syphilis testing in cases with unusual skin rashes, oral, genital or perianal ulcers, lymphadenopathy, hepatitis and/or neurological symptoms. Syphilis in its secondary stage can affect any body system and cause end organ damage, hence its reputation as the ‘Great Pretender’.   Management guidelines can be accessed through HealthPathways and the Aotearoa New Zealand STI Management Guidelines. 

2.  Verifying death

(i)  The Ministry of Health Guidelines for Verifying Death note that medical practitioners, nurse practitioners, registered nurses, enrolled nurses, midwives, emergency medical technicians, paramedics and intensive care paramedics are authorised by the Chief Coroner to verify death, including deaths which meet the criteria for reporting to the Coroner.  

(ii)  A health practitioner can verify death when:

• the body shows signs of rigor mortis incompatible with life, or
• the body has visible injuries incompatible with life, or
• the body shows signs of decomposition incompatible with life.

Alternatively, health practitioners can verify death once they have undertaken two assessments (a minimum of 10 minutes apart) to establish death. The health practitioner must confirm the following:

• no signs of breathing for one minute (requires exposure of entire chest and abdomen)
• no palpable central pulse (femoral, carotid or brachial). In most circumstances this will

require palpation for 5–10 seconds

• no audible heart sounds
• pupils dilated and unreactive to light (requires a focal light source eg a torch)
• where available, a cardiac monitor or defibrillator is used and shows asystole

The reason given for the second assessment is that the person may be in asystole for 5–10 minutes and then spontaneously develop return of a beating heart. This is sometimes called auto-resuscitation or the Lazarus reflex.

(iii)  Medical practitioners and nurse practitioners can now use Death Documents to report deaths to the coroner. This new function asks a series of screening questions to guide the practitioner through the reporting requirements then provides a firm recommendation to either complete and submit a Coroner Report or complete a medical certificate of cause of death (because the death does not need to be reported to the coroner).  GPs have previously phoned the coroner to report a death. They are now encouraged to report the death using Death Documents.  The coroner’s office (NIIO) is notified immediately, and the death is reported to Te Whatu Ora so that the NHI record can be updated with the date of death.  NIIO will register the report and contact the practitioner by phone within 2 hours to confirm whether they have taken the case.  If the coroner decides to investigate the death, you must notify the police of the death if they are not already involved.

3.  Opioid prescribing

A recent BPAC article on opioid prescribing (Quick reference here) includes some potentially useful resources related to the prescribing recommendations, and an oxycodone prescribing audit which can be used for Te Whanake CPD credits.  There is a link to the Live Well with Pain website which is an initiative developed by clinicians in the United Kingdom. It includes a comprehensive suite of freely available resources designed to inform and support health professionals working with patients who have persistent pain and to help guide the appropriate use of opioid medicines.  Free registration is required. 

Key recommendations in the BPAC article include:

• Establish a treatment plan when initiating an opioid, including measurable goals and the timeframes for achieving these, information about adverse effects and a plan to stop use. This jointly agreed plan can be verbal, but it should be documented in the patient notes. BPAC has provided an editable pain management plan template.

• In some cases, a formal written and signed opioid contract may be suitable to ensure safe and effective opioid use.  BPAC has provided an example opioid contract if you think it might be suitable for a specific patient.

• Ideally select an immediate release formulation due to the lower risk of sedation, respiratory depression and overdose (particularly during initiation). Modified-release opioids are a strong risk factor for opioid dependence. N.B. modified-release formulations may still be considered in certain scenarios depending on clinical judgement.

• Use the lowest potency and dose possible to effectively manage pain. Reassess the benefits and risks of treatment when considering each dose increase if pain is insufficiently controlled. Prescribe in combination with non-opioid analgesics and/or adjuvant medicines as this may reduce the dose of opioid required to achieve pain relief.  Be alert for potential signs of misuse and dependence, e.g. requests for early repeats or escalating doses

• If initiation of a strong opioid is being considered in primary care, ensure morphine is trialled first before prescribing oxycodone (unless the patient has a documented allergy or intolerance)

• Prescribe for the shortest possible duration (ideally three days or less). If this is not practical and longer-term use is required, advise intermittent dosing (i.e. as-needed within the daily dosing limits), rather than continuous use. Intermittent dosing reduces the risks of dependence without compromising potential benefits.

• Prescribe a laxative if use will exceed 2 – 3 days duration and advise patients to remain hydrated. 

• If longer-term use is required, check in with the patient at each new prescription to assess the need for continued use. The opioid dose or potency should be gradually titrated down as pain improves (as per treatment plan).  A link is provided to the Te Pou publication Substance withdrawal management: Guidelines for medical and nursing practitioners 

4.  Drug Driving

(i)  The Land Transport (Drug Driving) Amendment Act 2022 was introduced on 11 March, 2023.  The key changes, recommendations and resources are included in a recent Medsafe Alert.

(ii)  The key changes are the addition of Schedule 5 and new blood tests to measure the amount (concentration) of drugs in the blood.

• Schedule 5 contains 25 ‘listed qualifying drugs’ (4 illicit drugs and 21 prescription medicines). These drugs have been identified as having the highest risk to road safety.
• Police will continue to stop drivers at random to check for alcohol or drug driving. If a person fails a Compulsory Impairment Test (a behavioural test to check for impairment), they will be required to take a blood test to check for the presence of drugs. With the law change, blood concentration levels will also be measured for Schedule 5 drugs. The blood concentration determines the type of offence, which may be a fine, demerit points, licence disqualification, or a criminal conviction.

(iii)  If a qualifying drug is identified, a medical defence is available for the use of prescription medicines for drug driving offences:

• if the driver can demonstrate that they took the medicine according to a current and valid prescription from health practitioner, and
• they have followed any instructions from a health practitioner or manufacturer of the medicine.

(iv)  Advice for healthcare professionals

• Please discuss with your patients whether their medicines (both prescription and over the counter) could impair driving.
• Advise patients to check whether they have any side effects that could impair driving, and not to drive if these occur.
• Check section 4.7 of the medicine data sheet for the effects of a medicine on driving.
• Find the prescription medicines currently included in Schedule 5, for which blood concentration levels will be measured.

(v)  Points to consider

• MCNZ statement on good prescribing practice:  Ensure that the patient … is fully informed and consents to the proposed treatment and that he or she receives appropriate information, in a way they can understand, about the options available; including an assessment of the expected risks, adverse effects, benefits and costs of each option.

• Use of NZ Formulary Patient Information section and Patient Information Leaflets

• NZ Formulary Caution Advisory Labels (CALs) which are promoted by the NZ Pharmaceutical Society but do not appear to be a mandatory requirement

(vi) Additional resources

• Health Navigator Driving and medicines – contains both general and medicine-specific information for consumers including which medicines are most likely to affect driving, symptoms of impairment, when and how long to avoid driving  There is a special ‘Heavy transport and medication’ section included.
• NZ Police site explaining the new legislation from a consumer perspective
• Waka Kotahi information for consumers and  health professionals regarding substance impaired driving including a link to a substance impaired driving health professional CME online course

5. Phenobarbitone brand change

• Pharmac has notified the funded brand of phenobarbitone tablets (15 mg & 30 mg) is changing because a supplier is leaving the market.  Approximately 400 people in New Zealand take the drug.  Current stock is expected to run out in July.

• Patients taking phenobarbitone tablets for epilepsy require alerting to the impending brand change and required actions.  Two appointments with a healthcare provider are needed: at one month before (June 2023) and one month after the brand change.

• Serum phenobarbital testing is required to check that concentrations remain at the same level before and after the brand change. Testing is recommended:

• three weeks prior to the change
• within the week prior to the change
• within the first week of the change
• one month after the change

Laboratory reference ranges are for trough levels with test taken shortly before the scheduled dose.

• The brand change necessity may provide health professionals with an opportunity to review patient clinical management.  Funding is available from Pharmac to cover the patient co-payment for the two visits associated with this change.

• Waka Kotahi recommends that patients consider a voluntary driving stand-down period of eight weeks following an antiepileptic medication brand change.

• Detailed guidance on the brand change is available on the He Ako Hiringa website

6.   Take a breath

A recent Goodfellow Gem looked at two ways of breathing to improve mood/anxiety based on research from Stanford University which reported how the breathing exercises for 5 minutes per day were better for mood and anxiety than mindfulness meditation, where the breathing is just watched.   

• ‘Sighing’, characterized by deep breaths (a large breath and an extra inhalation) followed by extended, relatively longer exhales, has been associated with psychological relief, shifts in autonomic states, and a resetting of respiratory rate.
• ‘Box breathing’ or ‘tactical breathing’, which military members have used for stress regulation and performance improvement, is inhaling for a count of 4, holding for a count of 4, exhaling for a count of 4 and holding again for a count of 4. The researchers asked participants to breathe in through their noses and out through their mouths.

March 2023

Shownotes

Clinical Snippets March 2023  

1. Prescribing and equity resource – practice improvement 

• The He Ako Hiringa agency’s mission is to contribute to creating equitable access to funded medicines, by providing education and updates to primary care clinicians.  You can register with the agency and access a variety of educational resources related to equitable and best practice prescribing.   

• This includes your own EPiC dashboard which facilitates learning and reflective activities comparing your personal, practice and national prescribing data on an increasing number of themes such as equitable prescribing of cardiovascular medications for patients with CVD, antibiotic stewardship, asthma and diabetes prescribing.  Highly recommended!   

2.   Kiwifruit for constipation 

• Kiwifruit is a commonly suggested treatment for constipation in New Zealand and previous studies (here and here) examining the effects of kiwifruit on patients with constipation have demonstrated potential benefit. However, clinical guidelines favour the use of soluble fibre bulking agents as first line management options for patients with constipation.  

• With New Zealand currently experiencing ongoing supply issues with funded psyllium husk powder and other laxative products, patients need more options for symptom relief.  A 2023 paper published in the American Journal of Gastroenterology examined the effects of daily kiwifruit consumption on gastrointestinal function and comfort. This randomised controlled trial provides evidence that consumption of kiwifruit is beneficial for people with constipation and may have greater benefit than psyllium husk. 

• For further information on the management of constipation, see: https://bpac.org.nz/2019/constipation.aspx 
• For further information on the management of irritable bowel syndrome in adults, see: https://bpac.org.nz/BPJ/2014/February/ibs.aspx 

3.  New Zealand-based online CBT course for OCD released 

• Just a Thought is a New Zealand organisation that offers free online cognitive behavioural therapy (CBT) courses and hosts other resources for a range of mental health conditions. A new online CBT course has now been released for people with obsessive compulsive disorder (OCD). The course has been adapted for New Zealand from an Australian online CBT course for OCD. The Australian course by This Way Up has been evaluated in a randomised controlled trial showing good efficacy. 

• In many areas across New Zealand, there are significant wait times to access publicly funded psychological or psychiatric services, or even sometimes private services. Online therapy courses for OCD may have a role in supporting patients while they await access to secondary care services.  The course can either be completed by the patient in a self-guided manner or through prescription by a clinician. Adherence rates are higher when a clinician prescribes the course and incorporates it into their follow-up consultations. 

• For further information on the recognition and management of a patient with OCD, see: https://bpac.org.nz/2022/ocd.aspx 

4.  CRP and paediatric abdominal pain 

• A recent issue of NZ GP Research Review commented on a Dutch retrospective study looking at the added value of CRP to clinical features when assessing appendicitis in children with acute abdominal pain in primary care.  The study showed the sensitivity and specificity of a CRP cut-off ≥10 mg/L were 0.87 and 0.77 respectively. When symptoms lasted > 48 h, this sensitivity increased to 1.00. Positive predictive values for CRP alone were low (0.18–0.38) for all cut-off values.   

• The reviewer noted:  Point-of-care CRP testing is very common in the Netherlands. It is used in identifying viral versus bacterial infection especially for acute respiratory symptoms in children and this study demonstrates that it is valuable in diagnosing acute appendicitis versus mesenteric lymphadenitis, which can have very similar symptoms and signs.  If CRP is <10 mg/L along with non-progressive symptoms over a 48-hour time span, appendicitis is unlikely. 

5.  Croup and steroids 

• A recent PEARL in NZ Doctor  looked at the question:  Are glucocorticoids effective and safe for treating croup in children aged 18 years and under?  Citing a Cochrane systematic review, the bottom line is that compared with placebo, budesonide (2mg per nebuliser) and dexamethasone reduced the symptoms of croup within 2 hours of treatment, with the effect lasting at least 24 hours. One trial showed that prednisolone reduced the symptoms of croup within 6 hours, with the effect lasting at least 12 hours. One trial showed that fluticasone did not reduce the symptoms of croup after 2, 6 or 24 hours compared with placebo. 

• There was little to no difference between dexamethasone and prednisolone for reduction in croup symptoms 2 hours following treatment, and likely no difference after 6 hours. However, dexamethasone probably reduced the rate of return visits and/or (re)admissions for croup by almost half.   A smaller dose of 0.15 mg/kg of dexamethasone may be as effective as the standard dose of 0.60 mg/kg but more studies are needed to confirm this.  

• Starship Hospital croup guidelines include the following recommendation:  Oral dexamethasone 0.15mg/kg/dose and oral prednisolone 1mg/kg/dose are both as effective as oral dexamethasone 0.6mg/kg/dose. In the community, where oral dexamethasone may not be available, community providers can prescribe oral prednisolone at 1mg/kg/dose once daily for 2 days. 

• It is important to differentiate the steroid advice for croup ad asthma from that for bronchiolitis where Starship Hospital and BPAC guidance advises:   

• Do not administer beta-agonists 
• Do not administer corticosteroids (systemic or nebulised) 
• Do not administer adrenaline (except in peri-arrest/arrest) 
• Do not administer hypertonic saline 

• Antibiotics and antivirals are not indicated in bronchiolitis 

6.  Prescriber Update 

The March 2023 Medsafe Prescriber Update included the following updates and reminders: 

(i)  Risk of neurotoxicity with cephalosporins 

• There have been reports of neurotoxicity with cephalosporins, including encephalopathy, seizures and/or myoclonus.  Risk factors include older age groups, renal impairment, underlying central nervous system disorders and intravenous administration.    
• Consider cephalosporins as a potential cause of neurotoxicity in patients with these risk factors and an unexplained, new onset neurological condition.  Symptoms of neurotoxicity have been reported to develop within several days after starting treatment and to resolve following discontinuation.  NB maximum doses dependent on eGFR are listed in NZF and drug data sheets. 

(ii)  Lithium and new diabetes agents 

• Sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as empagliflozin and dapagliflozin, may increase the renal excretion of lithium and lead to decreased serum lithium levels. 

• Monitor the patient’s serum lithium levels more frequently when a SGLT2 inhibitor is initiated or following dose changes. Adjust the lithium dose if necessary. 

(iii)  Metoclopramide in children and young adults 

• Due to the risk of dystonic side effects, metoclopramide use in children and young adults (aged 1 to 19 years, inclusive) is limited   to certain conditions and for second-line therapy.  NZF states:  Patients under 20 years:  Use restricted to severe intractable vomiting of known cause, vomiting of radiotherapy and cytotoxics, aid to gastro-intestinal intubation, premedication; dose should be determined on the basis of body-weight. 
• Dystonia can occur after a single dose of metoclopramide and occurs more frequently in children and young adults, and in females. 
• Do not use in people under 20 years of age unless absolutely necessary, and then strictly follow the dose recommendations in the metoclopramide data sheets to reduce the risk of dystonic side effects. 

January 2023

Clinical Snippets – January 2023 – Shownotes

1.  Goodfellow Gem – Diagnosing sleep conditions 

A recent Goodfellow Gem includes a straightforward screening tool for common sleep conditions:  the Goodfellow Unit Short Sleep Questionnaire.¹

Two lesser-known issues are:

• Primary insomnia (chronic insomnia), when patients spend more time in bed than they need to. The Australian Sleep Association² has tools for how to diagnose and treat this and other sleep conditions.
• Delayed sleep phase disorder – those who prefer to go to bed late [after midnight] and get up late in the morning is the other less common issue; this is a teenage sleep pattern seen in 25% of University students. This group need melatonin at night and light boxes or sunlight early in the morning.
  
  References:

1. Short Sleep questionnaire View
2. Australian Sleep Association Website

2.  Topiramate and pregnancy

A BPAC bulletin refers to a recently published study in JAMA Neurology which has identified an increased risk of neurodevelopmental disorders in children exposed in utero to topiramate.  The results of this study suggest that topiramate poses a similar risk of neurodevelopmental adverse effects as sodium valproate (or potentially higher) and the same level of caution should therefore be applied. In New Zealand, topiramate is indicated for epilepsy and migraine prophylaxis in adults and is also used off-label in restless leg syndrome, as a mood stabiliser (BPAD, PTSD) and neuropathic pain. 

Key points for prescribing any anti-epileptic medicines to females of child-bearing potential include:

• Women of child-bearing age should be made aware of the potential risks of anti-epileptic medicines, but also of the risk of seizures during pregnancy, i.e. if an appropriate anti-epileptic medicine is not taken
• Two forms of effective contraception should be used by women of child-bearing age who are taking an anti-epileptic medicine; N.B. Some hormonal contraceptives interact with enzyme-inducing anti-epileptic medicines
• Pregnancy should be planned so that an anti-epileptic medicine regimen with the lowest risk, while balancing treatment efficacy, can be put in place
• If an anti-epileptic medicine is being considered for a condition such as migraine prophylaxis or neuropathic pain, consider other suitable treatment options first in a woman of child-bearing age

3.  New ACE inhibitor available from December: ramipril

Ramipril (Tryzan), an angiotensin-converting enzyme (ACE) inhibitor, will be funded from 1 December, 2022, without restrictions. Ramipril is indicated for people with hypertension, heart failure, progressive kidney disease and for the prevention of cardiovascular events in people with heart disease. Ramipril will be available in 1.25 mg, 2.5 mg, 5 mg and 10 mg capsules (see dosing information on NZF).

4.  Cellulitis Pathway updated on HealthPathways

Important assessment points include checking for signs of sepsis and determining the severity of cellulitis which in turn guides therapy. 

Wound swabs are not usually necessary.  If you are taking a sample, do not swab skin, wound ooze or wound surfaces. Send only aspirate or swab of pus from a drained or draining abscess for microbiology.  Chronic wound swabs should never be taken.

For mild to moderate cellulitis, start oral antibiotics according to the presentation and the patient’s sensitivity to penicillin (see your local Healthpathway for details)

Monitor the patient and consider changing antibiotics only when necessary:

• Be aware that the natural history of cellulitis shows increasing redness and swelling within the first 48 hours.
• If the patient is improving overall at 48 to 72 hours after initiation of oral therapy, do not start intravenous therapy solely due the persistence of redness or swelling.
• Consider intravenous (IV) antibiotics with probenecid if the patient has moderate cellulitis and you have concerns about adherence or absorption. (This may need approval in your district by an infectious diseases specialist, or to be prescribed in the emergency department.)

5.  Removal of funding restrictions for zoledronic acid

Pharmac is removing all Special Authority funding restrictions from zoledronic acid from 1 March, 2023, e.g. there will no longer be a requirement for bone mineral density scanning. The bisphosphonate zoledronic acid is indicated for people with osteoporosis and Paget disease, as well as some cancer-related indications. It is given as an intravenous infusion over 15 minutes and can be administered by health professionals as part of the community-based infusion service.

A reminder there are pre-screening and monitoring requirements associated with zoledronic acid infusion and these are summarised on your local HealthPathways under the headings:   Zoledronic Acid Infusion and Zoledronic Infusion Checklist 

6.  UTI in ACF

 The Health Quality and Safety Commission have developed this guide to support aged residential care multidisciplinary teams in implementing strategies to:

• improve symptom recognition and communication in the diagnosis of urinary tract infections (UTI) including use of a decision support tool to ensure clinical criteria for treatment are met.  Dipstick urinalysis is recommended only to rule out UTI. 
• reduce the rate of urinary antibiotic prescriptions for residents whose symptoms do not meet clinical criteria for UTI
• improve systems for review of antibiotic treatment following results of laboratory testing: urine microscopy, sensitivity and culture.

The guide has been written for aged residential care teams, but it’s also relevant to general practice.

7.  Legionellosis season

• The Waikato December Public Health Bulletin notes that  an increase in the rate of legionellosis is expected at this time of year due to increased exposure to compost and potting mix as part of gardening activities.
• Legionella bacteria are ubiquitous in New Zealand environments, with L. pneumophilia being mostly associated with warm-water systems and L. longbeachae with compost/potting mix.
• Nationally, there were 34 cases in the 3 weeks to 29 November 2022. This is 1.89 times higher than the same period in 2021. In Waikato we had 4 cases notified in November, up from 1 case in October.
• Symptoms are less helpful than risk factors in assessing risk for Legionella, but may include:
  • dry coughing.
  • high fever, chills.
  • shortness of breath, chest pains.
  • headaches, excessive sweating, nausea, vomiting.
  • abdominal pain.
  • diarrhoea, which is more common than with other forms of community-acquired pneumonia.
• Send sputum for PCR and culture noting risk factors on request form.  Urine antigen test is positive only for Legionella pneumophila serogroup 1, so not helpful after exposure to potting mix.  Treatment for possible or suspected Legionellosis is addition of roxithromycin orally 300 mg once daily for 10 to 14 days to standard CAP treatment.

8.  Cyber Incident Response planning hui

 Te Whatu Ora – Health New Zealand is hosting a cyber incident and response hui for general practices on 25 January 2023, 12-1pm.  The workshop will cover:

• the importance of incident response planning
• possible scenarios
• incident response checklist
• support and resources available

 Please email: Nancy.Taneja@health.govt.nz if you would like to attend

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