The New Zealand General Practice Podcast

Dr Dave Maplesden and Dr Jo Scott-Jones

Shownotes

Clinical Snippets – July 2023 

1.  Superficial venous thrombosis (thrombophlebitis) 

(i)  After reviewing a recent case of death from pulmonary embolus in a patient seen a few days previously with an apparent lower limb SVT, I have reviewed HealthPathways guidance as follows.  Superficial venous thrombosis is usually a benign self-limiting condition, when it involves the smaller tributary veins in the lower limb or in the site of an existing varicose vein.  However, when the larger veins are involved (e.g. great and small saphenous veins) or when adjacent to the sapheno-femoral junction, there is risk of a DVT. A DVT may coexist at the time of diagnosis or the clot may extend to the deep veins within 10 days. 

(ii)   The risk for VTE is the highest immediately following a diagnosis of SVT but persists over time particularly in the first three months and decreasing but still significantly higher after five years.  Diagnosis is made by clinical findings, e.g. tenderness, induration, pain, or erythema along the course of a superficial vein.  D-dimer is not considered sensitive or specific enough to predict DVT in superficial venous thrombosis. 

(iii)  Arrange an ultrasound to exclude DVT if any of: 

• There is an involved segment of vein of 5 cm or more. 
• Either the great or the small saphenous vein is involved. 
• There is asymmetrical leg swelling. 

D-dimer is not considered sensitive or specific enough to predict DVT in superficial venous thrombosis. 

(iv)  Consider full oral anticoagulation for 3 months 3 if:   

• superficial venous thrombosis is within 3 cm of the sapheno-femoral junction and/or if the length of the superficial venous thrombosis is more than 5 cm. Also seek vascular surgery advice as ligation at the sapheno-femoral junction may be recommended. 
• other risk factors for DVT (e.g. an inpatient). Also seek haematology advice. 

(v)  If no risk factors, provide local symptom relief and prevent progression to a DVT: 

• Use pain relief, e.g. NSAIDs, for 8 to 12 days if not contraindicated. 
• Treat with elevation of the leg and compression stockings for comfort and to reduce swelling. 
• Only use antibiotics if signs of infection. 
• Encourage the patient to remain ambulatory. 
• Arrange follow-up at 7 to 10 days or earlier if there is deterioration. 

• If symptoms do not resolve, arrange or repeat the ultrasound. 

2.  ACE inhibitors and angio-oedema  

(i)  The Centre for Adverse Reactions Monitoring (CARM) recently received a report of fatal angioedema with an ACE inhibitor. The patient had experienced minor tongue swelling with an ACE inhibitor previously. A different ACE inhibitor was started at a later date, and the patient developed angioedema with a fatal outcome. 

(ii)   Before prescribing an ACE inhibitor, ask patients if they have taken these medicines before and if they had any adverse reactions. Specifically ask about swelling.  Inform patients who are starting ACE inhibitors about the symptoms of angioedema and advise them to seek urgent medical attention if these occur. 

(iii)  Visceral angioedema due to ACE inhibitors has been described in a handful of case reports and reviews. Most commonly, this presents as diffuse abdominal pain and diarrhoea. In more than one-half of the case reports of visceral angioedema, symptoms began within 72 hours of starting ACE inhibitor therapy, although in other reports, angioedema developed after weeks or years of therapy.  Diagnosis is often delayed. 

(iv)  ACE inhibitors should not be prescribed to patients with a history of ACE inhibitor-induced angioedema. Educate patients who have experienced ACE inhibitor-induced angioedema about the need to avoid all ACE inhibitors in the future.  NZF also advises against use of sacubitril-valsartan (Entresto) in these patients.   Most patients can be cautiously switched to an ARB.  A proportion of patients will have recurrence of angio-oedema after stopping the culprit ACE – most commonly within the first month.    

(v)  Angioedema is thought to occur in around 0.1% to 0.7% of patients who take an ACE inhibitor. Onset is usually during the first weeks or months of therapy, but it can occur years into treatment. Angioedema has also been reported with angiotensin II receptor blockers (ARBs; eg, candesartan, losartan), but the risk is thought to be lower than with ACE inhibitors. 

3.  Ivermectin Special Authority criteria amended 

The Special Authority criteria for ivermectin were recently amended (June, 2023). Any relevant practitioner can now complete the Special Authority form for ivermectin in patients with scabies and close contacts who meet Special Authority criteria. Discussion with a dermatologist, infectious diseases specialist or clinical microbiologist is no longer required. 

For information on the management of scabies, including the role of ivermectin, there is an excellent 2022 BPAC update on the topic.   

4. Allopurinol and variable adherence 

A recent NZ Doctor article on allopurinol  prescribing for the non-adherent included some timely reminders: 

• In a person who has become non-adherent to allopurinol (even for one month), do not automatically restart at a previous dose – re-titration is required.  Titration is dependent on renal function (see 2021 BPAC article for details).  Extra caution must be made with repeat prescribing of allopurinol and assuming a person is administering the last prescribed dose when they may not be. 

• The important point around dosing is to commence allopurinol according to renal function using clinical pathways or 1.5mg of allopurinol per eGFR unit as a guide. Note that renal function is used to guide starting doses, but once a person is stabilised on a dose of allopurinol, the dose should not be routinely decreased if renal function deteriorates. 

• Remember anti-inflammatory prophylaxis (and remember to stop this when stable).  This may be low dose NSAID or colchicine (or prednisone if alternatives not tolerated) 

• To mitigate treatment failure, people must be forewarned of the increased risk of flares when initiating allopurinol. It is also necessary to plan for the eventual cessation of anti-inflammatory prophylaxis. Usually, only three to six months is required, although this may be much longer in people with a high urate burden with tophi. 

• For patients with gout and hypertension, losartan or calcium channel blockers are the antihypertensive medicines of choice as they reportedly have mild uricosuric (urate-excreting) properties. Patients who are taking diuretics for hypertension, for reasons other than heart failure, should be switched to an alternative antihypertensive, if possible. 

• Always advise people that if a rash (especially extensive) occurs, they must cease allopurinol and seek medical assistance promptly.  Rash affects around 2% of people taking allopurinol but could be a symptom of allopurinol hypersensitivity syndrome (includes DRESS, Steven-Johnson syndrome and toxic epidermal necrolysis – affects about 1-4:1000 patients prescribed allopurinol and has a mortality rate of up to 27%). Risk factors for AHS include: higher starting dose of allopurinol and rapid titration; recent commencement (6-8 weeks) of allopurinol; coadministration of diuretics (especially thiazide) and amoxicillin; comorbidities of CKD and cardiovascular disease; risk of AHS is nearly 100-fold higher in carriers of the HLA-B*58:01 allele than in noncarriers. Populations with high allele frequency include people of Han Chinese (6%–8%), Korean (12%) and Thai (6%–8%) descent and NZF recommends genetic testing in these high-risk patients and avoiding allopurinol in confirmed carriers unless there is no suitable alternative.  See SaferRx for more details.   

• Māori and Pacific peoples are inequitably burdened by gout. There is also evidence demonstrating Māori and Pacific peoples are less likely to receive regular allopurinol prescriptions.  You can analyse your gout prescribing on the Epic dashboard in He Ako Hiringa including percentage of patients being prescribed urate lowering therapy irregularly, and there are tips for improving gout prescribing equity.    

5.  Topical anaesthesia for chronic painful leg ulcers 

Prilocaine-lidocaine (EMLA) cream has a listed indication of topical anaesthesia of leg ulcers to facilitate mechanical cleansing or debridement with instruction to apply under an occlusive dressing 30–60 minutes before procedure.  Cost:  Around $45 for the Numit brand (30g) from the Chemist warehouse.  The cream has also been studied as a primary dressing for painful leg ulcers and has proved effective.   

 The NZ Palliative Care Handbook also notes use of topical morphine as local pain relief for palliative patients with fungating wounds or ulcers with instructions:   morphine injection added to a gel in a clean environment and used topically may help (0.05 to 0.1% morphine [i.e. 0.5 to 1 mg/mL] in IntrasiteTM gel, metronidazole gel or KY JellyTM).  More detailed instructions including precautions are available as NHS guidance and note this is off-label use of morphine.   Some systemic absorption will occur, and it is most effective for superficial ulcers.  Some studies have shown reduced healing rates in wounds treated with topical morphine.   

6.  Dense breasts 

GP Research Review Issue 216  summarised a 2023 meta-analysis of MRI imaging in screening women at high risk of breast cancer which showed that  MRI alone increased the detection rate of breast cancer versus mammography alone by 8 per 1000 women screened while MRI plus mammography had a better detection rate versus MRI alone by 1 per 1000 women screened.  The article reviewer noted there is conflicting evidence of the impact of ionising radiation from repeated mammography related to repeated mammographic breast screening in women at high risk of malignancy and taking this into account MRI alone may be considered as best choice in such high-risk women. 

This raises the issues of informed choice and equity, particularly if private screening is the only way MRI imaging can be accessed in this situation.  The issue of reporting of breast density and management of women with extremely dense breasts within the Breast Screen Aotearoa (BSA) national screening programme is ongoing with formal reporting of breast density not currently part of BSA reporting requirements (see BSA information sheet) or planned as part of a recent quality improvement review of clinical quality and safety of the programme.  Discussion was stimulated following publication of European Society of Breast Imaging (EUSOBI) recommendations last year which included that women should be informed of their individual breast density and the diagnostic and prognostic implications of having dense breasts, and that supplemental or standalone MRI screening is offered to women with extremely dense breasts, from age 50-70, preferably every 2-3 years.    

7.  On a lighter note… 

Two more fascinating studies summarised in GP Research Review Issue 216 

1.  A randomized controlled trial on the effects of light music played by piano on satisfaction, anxiety, and pain in patients undergoing colonoscopy showed, in the group with piano music, significantly lower anxiety scores and higher overall satisfaction scores, including satisfaction with pain management, following the procedure than the group with no music.  The reviewer notes the results appear to be perfectly tailored to a GP’s waiting room – less anxiety, more satisfaction and less pain. And at no cost! Probably worth swapping the blaring radio ads/music in the waiting room for something soothing like Mozart. 

2.  A randomized trial on the effects of a topical hop extract gel versus topical oestradiol cream for treatment of postmenopausal sexual dysfunction showed no significant differences in the total Female Sexual Function Index (FSFI) or sub-scores (sexual desire, sexual arousal, vaginal lubrication, satisfaction, orgasm, sexual pain) between the two groups. There were no adverse events. Humulus lupulus L. (hop) has been recognised as having antioxidant, anti-inflammatory, anticancer, and oestrogenic properties.  I could not find any vaginal hop creams currently commercially available on line, and the hopeful sounding Tired Hands Hop Cream turned out to be a beer! 

Clinical Snippets February 2023

Clinical Snippets February 2023

1.  Post-partum screening for diabetes

• A NZ retrospective study published recently sought to estimate the proportion of women with a first episode of gestational diabetes who received post-partum type 2 diabetes screening in accordance with local guidance. 
• The study showed only 40% of women were screened within 3 months post-partum and that only improved to 61% after 12 months. Additional findings included that Māori women and those with higher deprivation were less likely to be screened, and there was extreme variation by postcode (15.3–67.5% screened by 12 months). 
• HealthPathways notes the Increased risk of patients with gestational diabetes developing type 2 diabetes following the pregnancy:

• The cumulative risk has been estimated to be as high as 50% within 5 years postpartum, depending on ethnicity and time from index pregnancy.
• There is good evidence that the risk of developing type 2 diabetes can be reduced by either lifestyle or pharmacological interventions (e.g., metformin) in the non-pregnant population
• Post-partum screening advice for women who developed gestational diabetes is to check HbA1c at 3 months and annually thereafter

2.  Referral guidelines and unmet need

The end of year BPAC bulletin commented on some criticism the agency had received that some referral criteria and advice documented in various articles aren’t realistic, there is no way that patient will be seen…”. 

The comments noted BPAC is presenting what should happen, based on clinical trial data and consensus guidelines to improve patient outcomes. If we don’t refer based on the presumption that the referral will be declined due to resource constraints, the health system cannot measure unmet need. Te Whatu Ora in the October, 2022 “Planned Care Taskforce – Reset and Restore Plan” acknowledges that there is “no current effective measure of unmet need” and there is also no ability to measure the “not to refer” decisions that are based on a presumption that the outcome of the referral will be a denial of access. “Decline rates” are the simplest measure of unmet need, until other tools are developed to assess this.

3.  EpiPen funded from February, 2023

A recent Pharmac decision means that EpiPen and EpiPen Jr will be funded from 1 February, 2023, for people who have previously experienced anaphylaxis or who are at high risk.

• Funding restrictions include a maximum of two devices per prescription, and replacement of up to two devices prior to expiry or after a device is used
• Special Authority eligibility criteria include previous anaphylactic reaction which has resulted in presentation to an emergency department, or assessed by a relevant practitioner (including general practitioners, nurse practitioners and pharmacist prescribers) as being at significant risk of anaphylaxis; renewals of approval are not required
• Patients being prescribed an Epipen can register on the supplier’s website (Mylan EpiClub ) to order a free training pack and practice pen. There are also videos on how to use the pen and other resources.

4.  Meningococcal B vaccination wider funded access

Access to the meningococcal B vaccine, Bexsero, will be widened from 1 March, 2023, to include all children aged up to 12 months and people aged 13 to 25 years in their first year of a specified close-living situation.

• Pharmac eligibility criteria for the 13-to-25-year age group are: 

Either:

• Two doses for individuals who are entering within the next three months, or in their first year of living in boarding school hostels, tertiary education halls of residence, military barracks, or prisons; or
  • Two doses for individuals who are currently living in boarding school hostels, tertiary education halls of residence, military barracks, or prisons, from 1 March 2023 to 28 February 2024. 

• Existing eligibility criteria for patients over one year of age are: 
  • up to two doses and a booster every five years for patients pre- and post-splenectomy and for patients with functional or anatomic asplenia, HIV, complement deficiency (acquired or inherited), or pre- or post-solid organ transplant; or
  • up to two doses for close contacts of meningococcal cases of any group; or
  • up to two doses for person who has previously had meningococcal disease of any group; or
  • up to two doses for bone marrow transplant patients; or
  • up to two doses for person pre- and post-immunosuppression (Immunosuppression due to corticosteroid or other immunosuppressive therapy must be for a period of greater than 28 days)

5.  Soft tissue ultrasound

(i)  A recent Te Whatu Ora Waikato newsletter commented on the significant volume of requests being received for non-specific soft tissue mass USS.  There is reference to national imaging guidelines which include standard indications for community imaging referral as:

• Soft tissue mass with red flags; however, specialist assessment is preferred, so only request imaging if there is likely to be a delay before the patient is seen
• suspicion of a foreign body where not covered by ACC.

(ii)  Red flags include a soft tissue mass with any of the following characteristics:

• growing
• >5 cm in size
• deep to deep fascia (limited mobility, less mobile with muscle flexion)
• painful (most malignant lumps are painless; pain suggests nerve or bone involvement)
• recurring after a previous excision.

(iii)  Additional guidance is:

• Apply caution in the use of ultrasound, as its ability to characterise solid mass lesions is limited and incorrect diagnosis can lead to significant treatment delays.
• Consider requesting a plain X-ray as well.
• If a sarcoma is suspected, reserve biopsy for an orthopaedic or sarcoma specialist.

(iv)  A localised HealthPathway for Soft Tissue Lumps and Sarcoma has been recently published.  The pathway reiterates the limitations of ultrasound in determining whether or not a mass is likely to be malignant although it can determine  if a mass is present, superficial or deep to fascia, and solid or cystic.     

(v)  If a lump is not being investigated or referred:

• advise the patient to report any changes promptly.
  • reassess at 3 months if any concern.
  • consider discussing with a general practitioner colleague for a second opinion.

6.  Ramadan and Diabetes

• Ramadan 2023 is expected to run from the evening of Wednesday 22 March to the evening of Thursday 20 April.  The Research Review series has published an excellent guide on diabetes management during Ramadan.

• Many Muslims with diabetes have a strong desire to participate in the Ramadan fast, even though they may be exempted due to their underlying condition.  Be proactive about asking Muslim patients about their intention to fast as they may not volunteer this information. A pre-Ramadan assessment is essential for patients with diabetes who wish to fast.

• Individualised risk stratification forms the basis for shared-decision making and recommendations regarding lifestyle, blood glucose monitoring and dose adjustments for glucose-lowering therapies. Patients at low risk should be able to fast safely, while those at moderate risk may be able to fast safely with appropriate education and monitoring. Patients at high risk should be discouraged from fasting.

• Reassure patients who are at high risk that there are alternatives ways of obtaining spiritual rewards if they do not fast; consider engaging with a local Iman if the patient is uncertain about any of the medical recommendations provided.

• Education about the risks associated with fasting and the provision of individualised strategies to preventing adverse outcomes are essential for the safety of patients with diabetes. Avoiding dehydration by drinking adequate quantities between Iftar and Suhoor is important.

• SMBG is important for all patients with diabetes who are fasting and doing so does not break the fast. Patients at low risk should SMBG at least once during the day and following Iftar, as well as whenever they feel unwell or have symptoms of hypoglycaemia or hyperglycaemia. Patients at higher risk should test more frequently.

• All patients with diabetes should break the fast if at any stage:
  • Blood glucose <3.9 mmol/L
  • Blood glucose >16.6 mmol/L
  • Symptoms of hypoglycaemia or acute illness develop.

• Information about dosing and/or timing adjustments should be provided to all patients taking glucose-lowering therapies, especially those using insulin.  It is recommended that patients be on a stable treatment regimen before beginning the Ramadan fast.

• A post-Ramadan follow-up is recommended to review what went well for the patient and to discuss challenges to make any future fasts safer and more rewarding.

7.  Asymptomatic bacteriuria in the elderly

A recent Tools for Practice summary looked at the question:  In elderly, does asymptomatic bacteriuria (ASB) cause altered mental state and will treating ASB improve clinical outcomes?

The context:  Ordering urine culture is associated with antibiotic use.  ASB is common in elderly: 5-20% in community age>80 (females>males) and institutionalization (25-50% women/15-40% men).

ASB guidelines recommend:

• Avoiding ASB treatment in elderly without clear infection signs/symptoms. 
• Assessment for other causes; careful observation; attention to contributing factors like dehydration.

BOTTOM LINE:   Due to important evidence limitations, it is not confirmed that ASB, or even Urinary Tract Infection (UTI), is clearly associated with altered mental state. Treating ASB does not improve clinical outcomes (including altered mental state) but may increase adverse events from 1% to 7%. In elderly patients with ASB and altered mental state, antibiotics should be avoided without clear signs/symptoms of infection, and alternative reasons for altered mental state should be considered.