2018

The Use of Hormones in Menopausal Therapy and Contraception: Coming Full Circle

This article discusses the history of hormonal therapy in menopause and contraception.

Diabetes in the Older Adult

This article discusses the complications and considerations associated with managing older patients with type 2 diabetes and the need for an individualised approach.

Managing Diabetes in Patients with Liver Disease

This article discusses how to assess abnormal liver function in a patient with type 2 diabetes, and the importance of managing this condition to improve long-term health outcomes.

Controlling Glucose in Patients with Renal Impairment

This article discusses common co-morbidities of type 2 diabetes and poor kidney function, and how optimal management must account for the mutual effects of one condition on the other.

Antidepressants in Pregnancy

“Be patient with yourself… nothing in Nature blooms all year.” One of my favourite quotes regarding perinatal depression and anxiety which affects 10-16% of all new parents.

The importance of perinatal mental health cannot be overstated. Research has shown that an untreated perinatal mental health condition can lead to substance misuse, poor antenatal attendance as well as poor self-care.

There is also a risk of poor attachment to the infant, and a long-term risk of poor child development outcomes through neglect. Suicide is the final risk. The government have recently supported our concerns regarding this important topic by changing the MBS item numbers (16590, 16591, 16407) to include a mental health assessment.

We have a duty of care to our patients to know what is safe to prescribe or continue to use in pregnancy- remembering that pregnancy is not protective against mental illness.

Did you know that more than half of all women abruptly discontinue antidepressant medication upon confirming a pregnancy? Almost 70% of these women suffer a relapse of depression.

Currently the recommendations for a woman on an antidepressant who has been euthymic for at least 12 months include cease the medication in pregnancy, continue the current medication, change to an alternative, safer medication or cease the medication and then reintroduce it if a relapse occurs.

Antidepressant medications can cross the placenta, meaning the fetus is exposed. There are also potential pregnancy complications, but the risks to the fetus and the pregnancy are very low.

Congenital malformation may occur from exposure to some antidepressants in the first trimester. Growth restriction and neurobehavioural problems may result from exposure in the second trimester. And congenital cardiac defects have been associated with paroxetine use in pregnancy.

Postpartum haemorrhage is the only significant potential obstetric complication associated with SSRI and SNRI use. There is also a small increased risk of persistent pulmonary hypertension of the newborn associated with SSRI, SNRI and TCA use in late pregnancy.

Antidepressants taken in late pregnancy, may also cause poor neonatal adaptation syndrome (PNAS). This manifests as hypotonia, respiratory distress, hypoglycaemia, seizures and most commonly ‘jittery-ness’ in the infant. Paroxetine has the highest risk of PNAS.

Despite this, it is NOT recommended that the dose of medication be reduced in late pregnancy. Because the fetus may not clear the medication in the same way the mother does, lowering the dose might simply risk a relapse of depression in the mother while gaining little or no benefit to the infant.

RANZCOG states that SSRIs are generally considered low risk and safe to prescribe in pregnancy and breastfeeding. It is important to know that sertraline has the lowest placental exposure and the lowest excretion into breastmilk.

Other medications are listed in the table below as a quick reference guide:

Table 1. ANTIDEPRESSANT CATEGORIES FOR PREGNANCY AND BREASTFEEDING:

Compatible- an acceptably low relative infant dose or no significant plasma concentrations or no adverse effects in breastfed infants.

When managing perinatal depression is it important to consider potential risk against the known benefits of the medications and the potential detrimental effects of mental illness on the development of the infant and other children in the home.

Key References:

1. The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.  Perinatal Depression and Anxiety: C-Obs 48. East Melbourne (AU): RANZCOG; Mar 2015. 16 p. RANZCOG Cat. No.: C-Obs 48. Available from: https://www.ranzcog.edu.au/RANZCOG_SITE/media/RANZCOG-MEDIA/Women%27s%20Health/Statement%20and%20guidelines/Clinical-Obstetrics/Mental-health-care-in-the-perinatal-period-(C-Obs-48).pdf?ext=.pdf
2. White L. Antidepressants in Pregnancy. O&G Magazine. 2018; 20(3): 24-25. Available from: https://www.ogmagazine.org.au/20/3-20/antidepressants-in-pregnancy/
3. Galbally M, Lewis AJ, Snellen M. Introduction Pharmacological management of major depression in pregnancy. In: Gabally M, Snellen M, Lewis AJ, editors. Psychopharmacology and Pregnancy. Berlin: Springer; 2014. p. 67-85.

Dr Julia Marcello works at Bentley Maternity Unit which provides maternity services to low risk women in WA. The unit is staffed by GP obstetricians, specialist obstetricians and gynaecologists and midwives and offers the option of private care within a public setting. The midwife service is available to low risk women and includes antenatal care, birthing services and postnatal care through the visiting midwifery service and lactation consultant support.  GP shared care services are also available. The Unit also provides a gynaecology service led by Dr Aseel Alkiaat and specialists from King Edward Hospital. 

For further information go to www.bhs.health.wa.gov.auFor-health-professionals

Traveller’s Diarrhoea

This article discusses the latest evidence on the incidence and prevalence of Traveller’s Diarrhoea, and how it is best prevented, assessed and treated.

Omega-3 Marine Polyunsaturated Fatty Acids Post-myocardial Infarction

This article discusses the importance of supplementary intake of marine omega-3 polyunsaturated fatty acids: (EPA) and (DHA) for patients post-acute myocardial infarction.

Vitamin B12 Testing in General Practice

Introduction

Vitamin B12 testing remains the most common vitamin investigation in clinical practice and is often included in the investigation of common problems such as anaemia and dementia.
The assessment of Vitamin B12 status using blood tests is imperfect and although a variety of other tests can be used to improve assessment, this can lead to complexity and confusion. In this discussion I hope to share the insights from thousands of analyses and hundreds of clinician’s questions.

Sources of Vitamin B12

Vitamin B12 is a unique cobalt-containing molecule naturally synthesised by bacteria. Some animals, especially herbivores, absorb it from their intestinal microbiome, and build up a store.

Other animals, particularly carnivores, can obtain B12 by eating animals that store B12, or animal-based products such as eggs and milk. Vegetarians consuming milk products and eggs may have low B12 levels, as the B12 content of milk is often low (1mg/L) and even lower if ultra-heat treated. Non-animal sources of B12 are extremely limited, with Nori seaweed containing small amounts and B12 levels in mushrooms and most other plant-based sources reflecting bacterial exposure (eg manure/compost).(1)

Only strict vegetarians are considered at serious risk of dietary B12 deficiency, and even then only after some years. However, vegetarian and vegan diets are becoming increasingly popular. Similarly, breast-fed infants of vegan mothers, if not supplemented, may also be at risk of B12 deficiency.

How common is B12 deficiency?

Vitamin B12 deficiency is relatively common (4- 26%) but difficult to define accurately because of varying definitions.(2)

It is more common in the elderly and significant deficiency is present in up to 23% of elderly Australian populations.(3) Iron deficiency is similarly common, especially in young women, and since low consumption of iron from meat sources correlates with lower B12 intake, B12 deficiency should always be considered when dietary iron deficiency exists.

While pernicious anaemia is often considered as a cause of B12 deficiency, this autoimmune illness has a relatively low prevalence compared to B12 deficiency. In our experience, only 4% of our Intrinsic Factor antibody requests are positive which is a similar result to that described by others.(4) Higher prevalence has been reported when using the less specific parietal antibody test, but even then, less than 20% of B12 deficiency can be attributed to pernicious anaemia.(5)

Less than one in eight patients with positive parietal cell antibodies have pernicious anaemia and this lack of specificity increases in the elderly when the test should be avoided.

Clinical issues

Unexplained anaemia and/or macrocytosis have traditionally been the indications used for suspicion of B12 deficiency. But there are other common reasons for anaemia such as iron deficiency and the anaemia of chronic disease. There are also other common reasons for macrocytosis including liver disease and alcoholism.

Vitamin B12 levels are more likely to be low in a vegetarian (or vegan) than in a patient with anaemia or macrocytosis.(6)

We also find that symptoms of confusion and dementia are just as likely to be associated with low B12 levels as anaemia. And while this may be partly associative due to the higher prevalence of B12 deficiency, it should be concerning because of the neurological sequelae of B12 deficiency that may arise prior to anaemia.

Neurological symptoms of B12 deficiency include paraesthesia of the hands and feet, diminished perception of vibration and position, absence of reflexes, and unsteady gait and balance (ataxia). But the range of symptoms is broad and may include irritability, tiredness, and mild memory and cognitive impairment.

Severe deficiency causes subacute combined degeneration of the spinal cord. In pregnancy, B12 deficiency is associated with some increase in the risk of neural tube defects and in childhood is associated with developmental delay and failure to thrive.

Why is testing so complicated?

Cobalamine is a precious vitamin that is captured and chaperoned around the body. Saliva contains a protein that will capture B12. In the stomach, intrinsic factor is produced to capture B12 released by digestion and transport it into the body.

Within the bloodstream, there are two proteins that bind B12; haptocorrin and transcobalamin. These two proteins seem to have different functions with transcobalamin delivering B12 to the cells whereas haptocorrin correlates with storage. (This is similar to iron where transferrin transports iron to the cells and ferritin reflects storage.)

How to interpret B12 and HoloTC levels.

The amount of B12 attached to transcobalamin (ie holo-transcobalamin or HoloTC) therefore reflects the Vitamin B12 level available to cells.

When there is a cellular deficiency of B12, the reactions dependent on B12 are obstructed and precursors such as homocysteine and methyl-malonic acid (MMA) build up and can be measured as indicators of functional B12 deficiency.

HoloTC correlates better with homocysteine and MMA than the total B12 level of the blood. When total B12 levels are low or equivocal, it is appropriate to follow up with the more specific HoloTC test to help ascertain if there is a functional deficiency.

Pregnant women often deplete their B12 stores during pregnancy, but they uncommonly have B12 deficiency evidenced by their normal HoloTC levels. Conversely, patients with some haematological malignancies may have high B12 stores (eg by tumours producing haptocorrin) but may not mobilise those stores evidenced by a low HoloTC and macrocytic anaemia.

Summary

Vitamin B12 deficiency is common and can be associated with neurological symptoms and haematological signs especially in vegetarians, and uncommonly in pernicious anaemia.
HoloTC is more specific for clinical B12 deficiency than total B12 and that is why laboratories reflex test for HoloTC whenever the total B12 is low or equivocal.

General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs. The authors provide this editorial free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.

References

1. Watanabe F, Yabuta Y, Bito T, Teng F. Vitamin B12-Containing Plant Food Sources for Vegetarians. Nutrients. 2014 May; 6(5): 1861-73.
2. Moore E, Pasco J, Mander A, Sanders K, Carne R, Jenkins N, et al. The prevalence of vitamin B12 deficiency in a random sample from the Australian population. Journal of Investigational Biochemistry. 2014 Oct 2; 3(3): 95-100.
3. Flood VM, Smith WT, Webb KL, Rochtchina E, Anderson VE, Mitchell P. Prevalence of low serum folate and vitamin B12 in an older Australian population. Aust N Z J Public Health. 2006 Feb; 30(1): 38-41.
4. Aa A, Ah A, Ap S, Fh A, Pernicious anemia in patients with macrocytic anemia and low serum B12.  Pak J Med Sci. 2014 Nov-Dec; 30(6): 1218-22.
5. Sun A, Chang JY, Wang YP, Cheng SJ, Chen HM, Chiang CP. Do all the patients with vitamin B12 deficiency have pernicious anemia? J Oral Pathol Med. 2016 Jan; 45(1): 23-7.
6. Botros M, Lu ZX, McNeil AM, Sikaris KA. Clinical notes as indicators for Vitamin B12 levels via text data mining. Pathology. 2014; 46 Suppl 1: S84.

Gastro-oesophageal Reflux in Infants

This article discusses the General Practice management of gastro-oesophageal reflux in infants.

Infantile Colic

This article discusses the diagnosis and management of infantile colic.

Infection Risk in Asplenia and Hyposplenism

It is estimated that up to 25,000 Australians are affected by asplenia or hyposplenism.¹  Many are unaware of the fact, and its potential consequences.

The spleen plays an important role in immune function, in particular the prevention of infection due to some specific organisms (Table 1).

Infection Risk

Infection is a relatively common occurrence in those without a functioning spleen. Overwhelming post-splenectomy infection (OPSI), occurs in up to 5% of asplenic patients and has a mortality rate of over 50%. The risk is particularly high in children aged under five, and in the first three years post-splenectomy. However, the risk is lifelong.¹

Organisms of Concern

Table 1:     Organisms of Concern

Causes of Asplenia and Hyposplenism

Asplenia maybe congenital but is more often acquired as a result of trauma or the surgical removal of the spleen due to haematological conditions, or after incidental splenic damage incurred during intra-abdominal surgery.

Functional hyposplenism also confers an increased risk of infection and may occur as a result of a number of medical conditions (Table 2).

Table 2:    Medical conditions associated with hyposplenism

Detection of Asplenia and Hyposplenism

The presence of Howell-Jolly bodies in a blood film may be a clue to the presence of unrecognised asplenia or hyposplenism.  Other investigations that may be of assistance in suspected cases are imaging studies such as ultrasound or CT.

Prevention of Infection

Evidence suggests it is possible to significantly decrease the incidence of infection in asplenic and or hyposplenic patients. Spleen Australia has recently demonstrated a 69% reduction in serious infections in patients on their registry.²

The key strategies utilised by Spleen Australia include;

1. Education

• Informing patients and their families of the risk of infection, signs and symptoms of sepsis and the need to develop a management plan should these occur:
  • Importance of seeking urgent medical attention if symptomatic.
  • Maintaining a standby supply of antibiotics for emergency use.
• Provision of advice regarding travel and other potential exposure risks e.g. animal contact.
• Encouraging the wearing of a Medical Alert bracelet.

2.  Provision of advice regarding appropriate antibiotic therapy (as per Therapeutic Guidelines)

• Consider antibiotic prophylaxis, particular in first three years post-splenectomy (With either penicillin or roxithromycin).
• Maintain a standby emergency supply of antibiotics in case of sepsis (usually Amoxil 3g).

3.  Provision of current, detailed, practical guidelines for vaccination (As per Immunisation Handbook)

• Pneumococcal, Meningococcal, Haemophilus influenza type B vaccines – initial course and ongoing boosters as required.
• Annual influenza vaccine – to minimise the chance of post-influenza bacterial infection.

Currently, persons resident in Victoria, Queensland and Tasmania are able to register with Spleen Australia and will then receive regular newsletters and reminders when vaccines are due. It is hoped that this service will be extended to other states. See www.spleen.org.au for details.

Key Messages

• Infection is a significant, life-long risk in asplenic and hyposplenic patients.
• The risks can be mitigated by:
  • The early recognition of the underlying condition,
  • Comprehensive patient education,
  • Appropriate use of use of prophylactic and empirical antibiotics, and
  • Ensuring that patients receive recommended initial and ongoing vaccinations.

Spleen Australia provides an excellent range of resources and is happy to assist in the management of these patients if required.

References

1. Spleen Australia. Welcome to Spleen Australia: a clinical service and registry for people with a non-functioning spleen. Melbourne VIC: Diabetes Australia. Available from: www.spleen.org.au
2. Arnott A, Jones P, Franklin LJ, Spelman D, Leder K, Cheng AC. A Registry for Patients With Asplenia/Hyposplenism Reduces the Risk of Infections With Encapsulated Organisms. Clin Infect Dis. 2018 Aug 1; 67(4): 557-61. Available from: https://doi.org/10.1093/cid/ciy141

General Practice Pathology is a new regular column each authored by an Australian expert pathologist on a topic of particular relevance and interest to practising GPs.

The authors provide this editorial, free of charge as part of an educational initiative developed and coordinated by Sonic Pathology.

The Vit D Story Now a Fairytale

It wasn’t that long ago that vitamin D appeared to be the panacea for everything from preventing MS to reducing the risk of diabetes.

But the one area where we thought the benefit of this vitamin was not up for debate was bone health.

It has been proven – lack of vitamin D causes rickets. It has been proven that vitamin D is important in bone metabolism and turnover. And it has been proven the people with low bone density are more likely to experience fractures. Therefore add vitamin D and improve bones, right? Wrong!

The latest meta-analysis of more than 80 randomised controlled trials shows that vitamin D supplementation does not prevent fractures or falls, and does not have any consistently clinically relevant effects on bone mineral density. This comes as a bit of a surprise, to say the least.

According to the systematic review, vitamin D had no effect on total fractures, hip fractures, or falls among the 53,000 participants in the pooled analysis.

And it didn’t matter if higher or lower doses of vitamin D were used, the New Zealand researchers reported in The Lancet.

In looking for a reason for the lack of an effect from supplementation, previous explanations such as baseline 25OHD of trial participants being too high, or the supplement dose being too low, or the trial being done in the wrong population just don’t hold water. The sheer number and variety of trials included in this meta-analysis has meant all of these possible confounders have been accounted for.

“The trials we included have a broad range of study designs and populations, but there are consistently neutral results for all endpoints, including the surrogate endpoint of bone mineral density,” they said.

Consequently, the researchers said future trials were unlikely to alter these conclusions.

“There is little justification to use Vitamin D supplements to maintain or improve musculoskeletal health,” they stated.

And while they acknowledge the clear exception to this is in the case of the prevention or treatment of rickets and osteomalacia, in general clinical guidelines should not be recommending vitamin D supplementation for bone health.

The conclusion appears quite emphatic and definitive, and it is supported in an accompanying commentary by a leading US endocrinologist.

“The authors should be complimented on an important updated analysis on musculoskeletal health,” said Dr Chris Gallagher from Creighton University Medical Centre, Omaha in the US.

But he suggests many Vitamin D supporters will still be flying the flag for supplementation, pointing to the multiple potential non-bony benefits.

“Within three years, we might have that answer because there are approximately 100,000 participants currently enrolled in randomised, placebo-controlled trials of vitamin D supplementation,” he said.

“I look forward to those studies giving us the last word on vitamin D.”

References

Bolland MJ, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol. 2018 Oct 4. Available from: http://dx.doi.org/10.1016/S2213-8587(18)30265-1 [epub ahead of print]

Gallagher JC. Vitamin D and bone density, fractures, and falls: the end of the story? Lancet Diabetes Endocrinol. 2018 Oct 4. Available from: http://dx.doi.org/10.1016/S2213-8587(18)30269-9 [epub ahead of print]