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.