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Read the latest articles relevant to your clinical practice, including exclusive insights from Healthed surveys and polls.

By reading selected clinical articles, you earn CPD in the Educational Activities (EA) category whenever you click the “Claim CPD” button and follow the prompts. 

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Dr Linda Calabresi
  • Clinical Articles

Green light for ginkgo

Ischaemic stroke patients are less likely to deteriorate mentally if they take ginkgo biloba extract in addition to low-dose aspirin in the acute phase, a new study suggests. “Cognitive decline after stroke can result in vascular cognitive impairment and Alzheimer’s disease,” the study authors wrote. Importantly then, this randomised controlled trial showed stroke patients who took ginkgo as well as aspirin had better memory function, executive functions, neurological function and daily life in the six months after experiencing their stroke than those patients who took aspirin alone. The Chinese study also showed that taking ginkgo was not associated with an increased incidence of adverse events. The results of the study, published in the journal, Stroke and Vascular Neurology support the long-held hypothesis that ginkgo protects against neuronal death caused by ischaemia, which had been demonstrated in animal stroke models. It has been suggested that the possible mechanism of ginkgo’s effectiveness may include anti-apoptosis and increasing cerebral blood flow. In the study, researchers randomised over 340 patients, from five hospitals who had had an ischaemic stroke in the previous seven days to receive either 450mg of ginkgo biloba extract with 100mg aspirin daily or only the 100mg of aspirin daily. Both groups were treated for six months and were various intervals over that period. From the very early assessments (at 12 days) and through until 180 days, the difference in the assessments of cognitive and executive function was statistically significant. Similarly neurological and global function was significantly better in the group that took ginkgo. “These data suggest that [ginkgo biloba extract] is effective and could be recommended in the treatment of acute ischaemic stroke,” the study authors concluded. Ref: Li S, et al. Stroke and Vascular Neurology 2017; 0:000104. doi:10.1136 /svn-2017-000104

By Dr Linda Calabresi
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Dr Jenny Robson
  • Clinical Articles

Testing options for H. pylori

Identified in 1983 by Australian Nobel prize winners Marshall and Warren, H. pylori is linked to a spectrum of disease including non-ulcer dyspepsia, peptic ulcer, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Infection is estimated to be present in about 30% of adult Australians, though not uniformly distributed in the population. Prevalence is higher in immigrants, those of lower socioeconomic status and the institutionalised. It has been conventionally treated with a standard first-line triple therapy including a proton pump inhibitor (PPI), clarithromycin and amoxicillin or metronidazole administered for seven days. However, in the past decade the effectiveness of this triple therapy, although still recommended in Therapeutic Guidelines, has declined mainly due to the development of antibiotic resistance. A recent meta-analysis1 of treatment, which reviewed 15,565 studies worldwide, highlighted the geographically localised nature of resistance profiles. It concluded that one single ‘most effective’ treatment was unlikely to be identified across the world, as the treatments needed to be tailored to regional resistance profiles. The range of tests, both non-invasive and invasive, following endoscopy are outlined below.

Pylori serology

This detects organism-specific IgG. It requires the collection of 5 mL of serum. No special preparation of the patient is required. Antibodies may take 5–10 weeks to develop after infection and may remain positive long term. A positive result may indicate present or past infection. Epidemiologic evidence now indicates that most infections are acquired during childhood, even in developed countries, and the frequency of H. pylori infection for any age group in any locality reflects that particular cohort's rate of bacterial acquisition during childhood years.

Urea breath test (UBT)

The UBT requires the patient to drink 13C-labelled or 14C-labelled urea, which is converted to labelled CO2 by the urease in H. pylori. The labelled gas is measured in a breath sample. Sullivan Nicolaides Pathology currently utilises the nonradioactive 13C-labelled isotope. The test has a sensitivity of 95% and a specificity of 98%. It is generally not suitable for children under five years because of the difficulty in following test instructions. This test has an out-of-pocket fee to the patient of $60.

Faecal antigen test

Active H. pylori infection can be detected by identifying H. pylori–specific antigens in a stool sample with the use of monoclonal antibodies. This assay has similar sensitivity and specificity to the UBT and has no additional out-of-pocket expenses for the patient.

Rapid urease test (CLO test)

If endoscopy is indicated, a biopsy specimen can be placed into a CLO tube containing urea and a pH indicator. If H. pylori is present, the urease will convert the urea to ammonia, leading to a colour change in the pH indicator. This is a reliable and cheap method for identifying H. pylori infection with reported excellent sensitivity and specificity in excess of 90%. The colour change usually occurs within minutes and the clinician can record the results the same day. If the inoculated CLO tube is forwarded to the laboratory the results can be recorded in the pathology Laboratory Information System, but must be read within 72 hours of the tube being inoculated for the result to be valid.

Histology

Histology is slightly more sensitive and specific than the rapid urease test and provides additional information on the type of gastritis, atrophy, intestinal metaplasia and malignancy. If proton pump inhibitors (PPIs) have been taken, biopsies from the gastric body in addition to the antrum can improve the diagnostic yield. The organism can be identified with conventional stains including haematoxylin and eosin and Giemsa. Immunohistochemistry increases sensitivity and specificity further and is of most use in cases of assumed low density colonisation.

Culture and susceptibility testing

Culturing of the organism is available for those who fail therapy. This is done from a gastric biopsy and permits testing for sensitivity to antimicrobial agents. Specialised transport media Portagerm pylori (PORT-PYL – Item 25016) is available to improve organism viability. Susceptibility guided versus empirical antibiotic treatment for H. pylori infection has been shown to be superior to empirical 7–10 day triple therapy for first line treatment. The recent meta-analysis showed that the worst-ranking treatment is standard triple therapy (proton pump inhibitor, clarithromycin and amoxycillin or metronidazole) administered for seven days. Over the past 10 years our microbiology laboratory has cultured H. pylori from 108 endoscopic biopsies and 102 patients. Most of these cultures were performed because patients had failed therapy, introducing significant sample bias. For 24% of episodes, despite the organism being cultured, it did not remain viable to complete susceptibility testing. Susceptibility results for 76 isolates that remained viable for testing indicate that antibiotic resistance (clarithromycin – 59.7%; metronidazole – 51.3%; ampicillin – 22.4%) is a significant cause of treatment failure. Ref:
  1. Li Bao-Zhu, Threapleton DE et al Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis. BMJ 2015;351:h4052 http://www.bmj.com/content/351/bmj.h4052
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.
By Dr Jenny Robson
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Dr Linda Calabresi
  • Clinical Articles

New hope for kids with severe food allergies

One of the new class of biologics may have a pivotal role in desensitising children with severe food allergies, US researchers say. That was the conclusion after their placebo-controlled study showed that a preliminary short course of the monoclonal antibody, omalizumab (Xolair) improved the safety and efficacy of oral immunotherapy in children with multiple severe Ig-E mediated food allergies. Admittedly the study was small, involving only 48 children aged 4-15 years, and only looked at children with Ig-E mediated allergies to multiple foods but the implications, the study authors say are important. These patients are a highly atopic population who are at risk of near-fatal or fatal food allergic reactions to multiple foods. There is plenty of evidence that oral immunotherapy is effective for single food desensitisation. However there has been little proof that immunotherapy works in children with allergies to multiple foods, and these are the ones more likely to accidentally ingest a food that may trigger anaphylaxis. Children with multiple food allergies are also far more likely to be unable to tolerate the oral immunotherapy. So in this phase 2 trial, those children in the treatment group were given omalizumab for eight weeks before commencing oral immunotherapy against a range of allergens including peanuts, cows milk and several different tree nuts. Outcomes were assessed by a food challenge at week 36 that looked at the ability to tolerate 2g of the trigger food. At the 36 week mark, 83% of children could now tolerate the allergenic food in the omalizumab-primed group compared with only 33% in the placebo group.  It also appeared that omalizumab was well-tolerated with no serious or severe adverse events occurring in those who received it. The impact of these findings on the lives of affected children should not be underestimated, the researchers suggest in The Lancet Gastroenterology and Hepatology. “[The] ability to increase an individual’s threshold of food ingestion to a serving of protein [for example] is important for their nutrition and overall quality of life,” they wrote. The study had its limitations, namely it remains unknown if the desensitisation was sustained but the finding that the anti-IgE cover made the oral immunotherapy more tolerable and therefore more effective is a major though incremental advance in the management of this increasingly prevalent condition. Ref: Lancet Gastroenterology and Hepatology. Published Online Dec 11, 2017 http://dx.doi.org/10.1016/52468-1253(17)30392-8

By Dr Linda Calabresi
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Ms Sasha Petrova
  • Clinical Articles

Understanding Victoria’s new assisted dying laws

Victorians with a terminal illness will be able to request an assisted death from the middle of 2019, after the state’s parliament became the first in Australia to legalise voluntary assisted dying. Victorian residents over the age of 18, of decision making capacity, who have six months to live and are in intolerable suffering can be granted access to lethal medication to end their life. Eligibility is extended to 12 months for those with neurodegenerative conditions, such as motor neurone disease, multiple sclerosis and Alzheimer’s disease. Here are five articles in The Conversation’s coverage leading up to the passing of the bill, that will give you a better understanding of what’s in it, the issues in the debate and what drugs might be offered for those who request access to assisted dying.

1. What’s in the bill?

Victorian Premier Daniel Andrews has said the safeguards in this legislation make it the safest and most conservative model in the world. The Voluntary Assisted Dying bill was drafted after several reports based on extensive consultations with relevant stakeholders. After a parliamentary inquiry into end-of-life choices delivered recommendations in December 2016, the Victorian government responded by setting up an independent panel of experts to propose what would be in the bill. Chaired by former president of the Australian Medical Association, Professor Brian Owler, the panel’s report was delivered in July 2017. Ben White, Lindy Willmott and Andrew McGee, from Queensland University of Technology, wrote at the time:
The panel has proposed a very rigorous process - comprised of 68 safeguards – that involves three separate requests for voluntary assisted dying (one which is witnessed by two independent witnesses) and two independent medical assessments.
Read more about the panel’s recommendations that informed the final bill here: Victoria may soon have assisted dying laws for terminally ill patients

2. Why did some oppose the bill?

After a 47-37 conscience vote in favour of the bill in the lower house on October 20, 2017, the legislation went to the upper house, where it faced some heavy opposition. The team from Australia’s Centre for Health Law Research at QUT categorised the reasons MPs voted “no” into four themes:
[…] the bill doesn’t have adequate safeguards to protect the vulnerable; legalising assisted dying presents a slippery slope; palliative care services must be improved first; and a doctor’s duty is to treat, not to kill.
Four reasons Victorian MPs say ‘no’ to assisted dying, and why they’re misleading

3. What were the amendments?

The upper house passed the legislation only after taking in some amendments. The main of these is a change to the time an eligible patient has to live, from 12 to six months. There are exceptions though, for people with neurodegenerative conditions, such as motor neurone disease and multiple sclerosis, who can apply for assistance to die up to 12 months before their expected death. Professor Colleen Cartwright argues such strict prognoses are problematic, as doctors generally struggle with predicting how long someone has to live, and many tend to overestimate the time. She writes:
A review of studies exploring predictions of survival in palliative care for patients with a range of illnesses found that doctors’ predictions were ‘frequently inaccurate’. Estimates ranged from an underestimate of 86 days to an overestimate of 93 days.
The six-month amendment could defeat the purpose of Victoria’s assisted dying bill

4. What drugs will be given?

One thing that is still unclear is what kind of drugs will be used to help end a patient’s life. The drug most commonly used in other jurisdictions, Nembutal, is not legal in Australia. Betty Chaar and Sami Isaac from the University of Sydney’s school of pharmacy explain:
While [alternative drugs] are legally available in Australia, they could cause a long, protracted death, with many more side effects that could cause distress and suffering at the end of life. Nembutal and its relatives are less likely to do so, with greater evidence from international practices than any other drugs that can end life.
Read more about the drugs that may be suitable for the purposes of assisted dying: Dying a good death: what we need from drugs that are meant to end life

5. Don’t forget palliative care

And while assisted dying is another avenue for someone with intolerable suffering to be able to relieve that suffering, the government must still ensure everyone has good end-of-life care. The Victorian Andrews government has, in line with the assisted dying bill, also pledged to spend A$62 million over five years to improve palliative care across the state. Director of the Health Program at the Grattan Institute Stephen Duckett writes:
Politicians regularly express their support for palliative care. Yet, there is often a chasm between such positive rhetoric and actual delivery.
Assisted dying is one thing, but governments must ensure palliative care is available to all who need it The ConversationThe Conversation also has a palliative care series that explains end-of-life care in Australia. You can read these articles here. Sasha Petrova, Deputy Editor: Health + Medicine, The Conversation This article was originally published on The Conversation. Read the original article.
By Ms Sasha Petrova
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Dr Linda Calabresi
  • Clinical Articles

Don’t hold back on giving patches to pregnant smokers

All pregnant women who are smokers should be offered nicotine replacement therapy (NRT) as an option to help them quit, Australian researchers say. In a review published in the MJA, authors said that even though there was a general acknowledgement that there was no firm evidence that proved NRT was safe or effective in pregnancy, all the current guidelines recommend its use for women who couldn’t quit without medication. In a nutshell, NRT is safer than smoking, and smoking during pregnancy is the most important preventable risk factor for poor maternal and infant health outcomes, they said. Despite this, there appears a reluctance among doctors, both here and around the world to prescribe the therapy to pregnant women. The researchers cited a recent survey of Australian GPs and obstetricians that found one in four said they never prescribed NRT in pregnancy. One possible reason for this reluctance, they suggest is the caveats and cautions included in many of the guidelines. Phrases such as ‘only if women are motivated’, ‘only give out two weeks’ supply’ and ‘under close supervision’ hardly inspire confidence in the safety of the therapy. “Ambiguous messages may be contributing to the low NRT prescribing rates and, therefore, it is important to provide a clear practical message to health practitioners and women,” they said. After analysing the various guidelines, the researchers suggest using the strength of the urge to smoke as well as how frequently the urge to smoke occurs to help assess when a woman needs to start or increase the dose of their NRT. “The most important guidance for NRT in pregnancy is to use the lowest possible dose that is effective. However, to be effective, women should be instructed to use as much as needed to deal with cravings,” they advised. They also recommend women be encouraged to use NRT for at least 12 weeks or longer if required to ensure they don’t relapse. All smokers who are pregnant should be told “There is nothing better for you and your baby’s health than to quit smoking.” Ref: MJA  Online first 4.12.17 doi:10.5694/mja17.00446

By Dr Linda Calabresi
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Dr Jenny Robson
  • Clinical Articles

Schistosomiasis

Schistosomiasis, also known as bilharzia, is the second most prevalent tropical disease after malaria and is a leading cause of morbidity in many parts of the world. It is not uncommon in Australia because of the many travellers who visit endemic areas and swim or bathe in freshwater lakes and streams. Places commonly implicated include Lake Kariba and Lake Malawi in Africa. Immigrants and refugees from bilharzia endemic countries are also likely to present with untreated infection. With increasing travel to and migration from Africa and the Americas knowledge of the dangers and means of avoiding schistosomiasis is essential. Schistosomiasis is caused by trematodes of the genus Schistosoma. The principal schistosomes of medical importance, S japonicum, S mansoni, S mekongi (intestinal schistosomiasis) and S haematobium (urinary schistosomiasis), infect people who enter water in which infected snails (intermediate hosts) are living. The larval cercariae shed by the snail actively penetrate unbroken skin and develop into schistosomulae that migrate through the lungs to the liver where they mature into adults. Female worms lay eggs that pass through the vessels and tissues to the lumen of the gut or bladder (depending on localisation of worms). A proportion of eggs escape from the host and may be found in faeces or urine. The host's immune response to eggs that become lodged in the tissues is largely responsible for disease, Figure 1.  

Geographic distribution

This is governed by the distribution of the intermediate host snail. S haematobium                         Africa, Middle East, India (only Maharashtra) S japonicum                               Philippines, Indonesia (only Sulawesi), parts of China S mansoni                                   Africa, Middle East, some Caribbean Islands, parts of South America (Brazil, Surinam, Venezuela) S mekongi                                   Laos and Cambodia S intercalatum                           10 countries within the rainforest belt of West Africa.

At-risk groups

Owing to the absence of suitable snail hosts, transmission cannot occur in Australia. A history of overseas travel or residence is essential for this diagnosis. Chronic schistosomiasis is more likely to be seen in migrants and refugees from endemic areas. In Australia, where the definitive host is freshwater and marine birds, non-human trematodes may cause schistosomal dermatitis (cercarial dermatitis, swimmer's itch). Onset is usually within 15 minutes of skin contact with cercariae.

Clinical presentation

Disease due to schistosomiasis depends on the infecting species and the intensity of infection. Acute schistosomiasis occurs two to 12 weeks post infection and symptoms last for periods varying from one day to a month or more; recurrence of symptoms 2-3 weeks later is common. Between 40-95% of individuals, not previously exposed to infection, develop symptoms which include fever, malaise, headache, abdominal pain, diarrhoea and urticaria. Many have eosinophilia. After the initial acute onset, most become asymptomatic, although those with S haematobium infections may develop microscopic or macroscopic haematuria. Rare complications result from ectopic deposition of eggs in the spinal cord and brain. Most travellers are only mildly infected and are therefore often asymptomatic and unlikely to develop the severe manifestations of chronic schistosomiasis. Severe disease occurs in patients with heavy and prolonged infection. Hepatosplenomegaly, portal hypertension, ascites and oesophageal varices may result from intestinal schistosomiasis. And frank haematuria with varying degrees of impairment of the urinary bladder and ureters may occur with S haematobium infections.

Diagnosis

The prepatent period of S japonicum, S mansoni and S mekongi is 6-8 weeks, and for S. haematobium 10-12 weeks. Examination of faeces or urine before this time often yields false negative results. Similarly, with serology, testing too early may result in false negative results. Antibody development occurs slightly before eggs are detected. Eosinophilia (greater than 0.60 x103/mL) is present in up to 80% of patients with infections; however, its absence does not exclude infection.

Parasitologic examination

Diagnosis is by demonstration of eggs of S japonicum, S mansoni and S mekongi  in faeces, or eggs of S haematobium in urine. At least two stool or urine specimens should be submitted for examination over a period of 10 days. Whilst eggs may be found in all specimens of urine, there is some evidence of a diurnal periodicity with a peak of excretion around midday. Collection of the terminal portion of urine collected between noon and 2 pm is therefore recommended. Schistosome eggs can also be demonstrated in rectal snips or bladder biopsies. Viability of eggs can be assessed if the biopsies are received fresh.

Serologic examination

At our laboratory, antibodies are detected by enzyme immunoassay (EIA) using purified egg S mansoni antigen. Antibodies to this antigen may be undetectable in the pre-patent period lasting 8-10 weeks. The test detects genus specific antibodies. In the absence of a diagnosis based on egg identification, travel history provides the best assessment of likely species.

Interpretation

Parasitologic Faeces is concentrated (modified formalin-ethyl acetate) and urine either centrifuged or filtered; all of the concentrate or sediment is examined. Because of the low sensitivity of these techniques, a negative faecal or urine examination does not exclude schistosomiasis. Microscopic examination of eggs enables the species of parasite to be determined. At least two examinations on different days are recommended. Serologic Schistosome serology cannot distinguish between past or current infection nor differentiate the species of infection. Clinical history and further investigations should be considered when establishing the diagnosis. Recent infections may be serologically negative.

Preventative measures

Cercariae can burrow through the mucosa of the mouth as well as through unbroken skin. All fresh water in endemic areas should be considered suspect, although snails tend to live in slow-flowing and stagnant waters, rather than in rapids and fast-flowing waters. If freshwater contact is unavoidable, bathing water should be heated to 50°C for five minutes or treated with iodine or chlorine as for the treatment of drinking water. Water can also be strained through paper filters, or allowed to stand for 2-3 days before use. This exceeds the usual life span of the cercariae. Of course, the container must be kept free of snails. High waterproof boots or hip waders are recommended if wading through streams or swamps. It is wise to carry a pair of rubber gloves to protect hands when contact with fresh water is anticipated. Vigorous towel drying, and rubbing alcohol on exposed skin immediately after contact with untreated water, may also help reduce cercarial penetration. Vegetables should be well cooked and salads avoided as these may have been washed in infected water, allowing cercariae to attach themselves to the leaves.

Treatment

Praziquantel (Biltricide) 20 mg/kg bodyweight every four hours for 2-3 doses depending upon the species is recommended. In travellers, this is likely to achieve cure rates in the order of 90%. Tablets are scored and available as a 600mg dose dispensed six per pack. In patients at risk of chronic disease, such as refugees and migrants, it is important to be aware of complications that may arise from chronic infection: liver fibrosis, portal hypertension and its sequelae, and colorectal malignancy in the intestinal forms; obstructive uropathy, superimposed bacterial infection, infertility and possibly bladder cancer.

Follow-up

Follow-up schistosomiasis serology is recommended in 12 to 36 months after treatment. Follow-up serology may differ between immigrants and returned travellers. Travellers may show a more rapid serological decline post-treatment due to a shorter duration of infection and lower parasite burden. Immigrants may even show a rise in titre within the first 6-12 months post-treatment. Persisting titres should not automatically justify retreatment, this should be based on symptoms, parasite identification or eosinophilia. Viable eggs may continue to be excreted for up to one month after successful treatment. Non-viable and degenerate eggs can be found in tissue biopsies for years after infection has occurred.
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.
By Dr Jenny Robson
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Dr Linda Calabresi
  • Clinical Articles

Unprecedented Rise In Scarlet Fever In England And Asia

Scarlet fever is on the rise. According to the latest issue of The Lancet Infectious Diseases, cases of scarlet fever in the UK reached a 50 year high last year with a seven fold increase in new cases in the last five years. In addition, similar increases having been reported in a number of Asian countries including Vietnam, China, South Korea and Hong Kong. But public health authorities remain perplexed as to why the disease appears to be making a comeback. Detailed analysis of the causative organism shows different strains of the strep bacteria have been responsible for the UK and Asian outbreaks, so they are unsure if they are linked at all or whether the resurgence has to do with external factors such as the immune status of the population or environmental factors. So far it would seem that Australia is yet to be affected by this increased incidence however experts are warning we should not be complacent. Unlike in England, scarlet fever is not a notifiable disease in this country except in WA. And even in the UK, data suggests marked under-reporting. Scarlet fever is highly contagious and usually affects children under the age of 10, although it can occur in adults as well. While the bacterial infection, caused by Streptococcus pyogenes or group A Streptococcus (GAS) was a common cause of death in the 1800s, these days it is readily treated with antibiotics usually penicillin. However, failure to recognise the condition and treat it appropriately can lead to complications such as pneumonia, and liver and kidney damage. Children with the infection typically experience sore throat, headache and fever along with the characteristic popular pink-red rash that feels like sandpaper and the so-called strawberry tongue. Diagnosis is usually made via a throat swab. In an accompanying comment, Australian infectious diseases researchers Professor Mark Walker and Stephan Brouwer from the University of Queensland said, “Scarlet fever epidemics have yet to abate in the UK and northeast Asia. Thus, heightened global surveillance for the dissemination of scarlet fever is warranted.” In other words, be alert, people! Ref: Lancet Infect Dis 2017 Published Online November 27, 2017 http://dx.doi.org/10.1016/ S1473-3099(17)30693-X Online/Comment http://dx.doi.org/10.1016/ S1473-3099(17)30694-1

By Dr Linda Calabresi
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Dr Perminder Sachdev
  • Clinical Articles

Can lithium prevent dementia?

When people think of lithium, it’s usually to do with batteries, but lithium also has a long history in medicine. Lithium carbonate, or lithium salt, is mainly used to treat and prevent bipolar disorder. This is a condition in which a person experiences significant mood swings from highs that can tip into mania to lows that can plunge into depression. More recently, though, lithium has been explored as a potential preventive therapy for dementia. A recent paper even led some to question whether we should start putting lithium in drinking water to lower population dementia rates.
But despite early studies linking lithium to better cognitive function, there is currently not enough evidence to start using it as a preventive dementia strategy.

Lithium’s medical history

Lithium is a soft, light-silver metal present in many water systems, which means humans have always been exposed to it. Its concentrations in water range from undetectable to very high, especially in geothermal waters and oil-gas field brines. The high concentration of lithium in some natural springs led to it being related to healing. In the 19th century, lithium water was used to treat gout and rheumatism. Of course this was with little objective evidence of any benefit. Early attempts to treat diseases such as kidney stones with higher doses of lithium often led to lithium toxicity – potentially irreversible damage to the kidneys and brain. The landmark event in the medical history of lithium was a 1949 paper by Australian psychiatrist John Cade in the Medical Journal of Australia. This demonstrated its benefit in bipolar disorder, then known as manic-depressive illness. The psychiatric community took some time to absorb this finding – the US regulator the Food and Drug Administration only approved lithium for use in 1970. After that, lithium as a drug transformed psychiatric practice, especially in the treatment and prevention of bipolar disorder. This led to extensive research into the mechanisms of lithium in the brain.
Read more: What is bipolar disorder?

How lithium affects the brain

We don’t know exactly how lithium works, but we know it helps the way brain cell connections remodel themselves, usually referred to as synaptic plasticity. It also protects brain neurons by controlling cellular pathways, such as those involved in oxidative stress (where the brain struggles to control toxins) and inflammation. Animal studies have shown that long-term treatment with lithium leads to improvement in memory and learning. These observations led to studies of lithium’s protective effects on brain neurons in bipolar patients who had been taking it for a long time. One of these was a review of more than 20 studies, seven of which examined dementia rates in patients with mood disorders (such as bipolar) being treated with standard therapeutic doses of lithium. Five of these studies showed lithium treatment was related to low dementia rates. The review looked at four randomised controlled trials (comparing one group of patients on lithium with a group taking a placebo). These examined lithium’s effects on cognitive impairment (such as memory loss) or dementia over six to 15 months. One study did not show a statistically significant benefit on cognition but showed a biologically positive effect on the levels of a protein that promotes nerve cell growth. The other three showed statistically significant, albeit modest, beneficial effects of lithium on cognitive decline.
Read more: How we can protect our brains from memory loss and dementia

Lithium in water

A number of epidemiological studies – which track patterns and causes of diseases in populations – have linked lithium concentrations in drinking water with rates of psychiatric disease. In the above-mentioned review, nine out of 11 studies found an association between trace-dose lithium (low doses in drinking water but not detectable in blood of the people consuming it) and low rates of suicide and, less commonly, homicide, mortality and crime. More recently, researchers in Denmark conducted a nation-wide study linking dementia rates based on hospital records for people aged 50-90 with their likely exposure to lithium. This was based on the lithium levels in the waterworks predominantly supplying the region where they lived. Those with higher dementia rates came from regions with lower mean levels of lithium in the water than those without. This was 11.5 micrograms (µg) per litre compared to 12.2µg per litre. The Danish population is geographically stable and the health record linkage is excellent for such studies. The reliability and validity of dementia diagnosis in Danish health registers is also high. But the study had a number of limitations. The lithium intake was based on sampling of waterworks that provide water to only 42% of the population. The sampling was done for only four years (2009-2013) and extrapolated to a lifetime. Many potential, additional variables were not considered. For instance, a major source of lithium is diet, and some bottled water contains lithium. The study did not take this into account. An intriguing aspect of the results, for which no explanation was given, was that the relationship wasn’t linear. That is, lower doses (5.1-10µg per litre) increased the risk of dementia by about 20%, whereas exposure to levels over 15µg/L reduced the risk by about the same amount.

We’re not there yet

Observational studies (which make educated assumptions by observing a sample of the population) have considerable merit in the epidemiology of dementia, but have sometimes led to blind alleys. Aluminium is a useful example, with its preventive role in dementia still unclear after several decades of observations. A concern is lithium may take the same path.
Read more – In defence of observational science: randomised experiments aren’t the only way to the truth
Lithium was once widely used as an elixir and even as a salt substitute, but was discredited because of lack of effectiveness, marked toxicity and early death. We must wait for more observational studies with the rigour such studies warrant before we start clinical tests of its effects in drinking water. The ConversationWe must also study the potential harmful effects of lithium on the thyroid and the kidney, as these organs bear the brunt of long-term harms of lithium. For now, there is insufficient evidence to add lithium to the drinking water. Perminder Sachdev, Scientia Professor of Neuropsychiatry, Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW This article was originally published on The Conversation. Read the original article.
By Dr Perminder Sachdev
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Dr Linda Calabresi
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Pressure increased on hypertension treatment

New US guidelines are the most aggressive yet in terms of targets for blood pressure control. Put out by the American College of Cardiology and the American Heart Association, and published in JAMA, the guidelines recommend we now consider anyone with a BP of 120/80 mmHg or above as having abnormal blood pressure. People who have a systolic between 120 and 130 mmHg but whose diastolic is still below 80 mmHg are to be considered to have elevated BP. But those who have both a systolic up to 10mmHg above target (120-130mmHg) and a diastolic between 80 and 90 mmHg should now be classified as having stage 1 hypertension. An accompanying editorial estimates that this reclassification will result in a 14% increase in the US population who should be recognised as having hypertension. But before clinicians start reaching for the script pad, the guidelines recommend this stage 1 hypertension be initially treated with non-pharmacological therapies – basically addressing the factors that most likely pushed their blood pressure up to start with – lose weight, exercise more, reduce salt intake, cut down on alcohol. The exception to this, is that group of patients whose absolute 10 year CVD risk predictor has them with a 10% or more chance of having a major CV event. In these cases, it’s gloves off. The less than 130/80 target for high risk patients is very similar to Australian guidelines. What’s different is that this is now a recommended target for everyone. The new US guidelines recommend everyone with a BP over 140/90 mmHg be treated with medication (preferably two agents) regardless of their absolute CV risk. Our Heart Foundation says try other lifestyle changes in people with a very low CV risk and no other comorbidities until we reach the 160/100 mmHg mark. The other new development in the US guidelines is the recommendation to use BP measurements from ambulatory or home BP monitoring to both confirm a diagnosis of hypertension and titrate therapy. This is in keeping with Australian recommended practice. The US guidelines were developed by an expert committee after examining all the current evidence and conducting a series of systematic reviews looking at some key clinical questions. “From a public health perspective, considering the high population-attributable risk of CVD associated with hypertension, the potential benefits of tighter control of hypertension are substantial,” the guideline authors wrote. However, they do acknowledge that such an aggressive approach does carry risks, especially in the elderly. “Although studies do suggest that lower BP is better for most patients, including those older than 75 years, the balance of the potential benefits of hypertension management and medication costs, adverse effects, and polypharmacy must be considered for each individual patient,” they said. Ref: JAMA. Published online November 20, 2017. doi:10.1001/jama.2017.18706

By Dr Linda Calabresi
Just Checking people with an intellectual disability
Dr Lee Price
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Measuring Troponin In General Practice

High sensitivity(HS) troponin measurement in the emergency room/hospital setting is now widely established in Australia and is now being recommended for widespread implementation in the USA. Lower cut-offs into the normal range may find value as a single determinant for exclusion purposes in the acute emergency ward setting, however, because HS troponin may be elevated in a number of noncoronary cardiac conditions, a rise and/or fall in the level is usually required for diagnosis of a coronary infarct1. In unstable angina pectoris, a troponin level may be normal, as may an ECG recording if the patient is pain free at the time. Two articles in the Medical Journal of Australia published in the past three years have addressed the issues/problems surrounding ordering of the test in general practice 1,2. In both articles the authors agree that there are times when a single measurement of HS troponin can be useful clinically; however, there are times when it can be counterproductive. Firstly, it is agreed that a patient with classical features of the acute coronary syndrome (ACS) plus or minus ECG findings who has had pain in the 24 hours prior to assessment should be referred urgently to an emergency centre without troponin measurement. The turnaround time for an urgent troponin in most acute hospitals is of the order of 60 minutes or less. In the community private pathology scenario, turnaround time for a troponin result, even when treated as urgent, could take anywhere from four to 12 hours. That usually means that the result is only available after hours. Frequently, the ordering clinician is unavailable to receive or act on the result. A troponin can be useful in the general practice setting if the patient has had atypical chest pain with a low but not negligible likelihood of ACS; or if the patient has been pain and symptom free for 24 hours with a normal ECG. After an infarct, troponin can remain elevated for over a week. For the laboratory, an abnormal troponin requires phoning the result if it is an urgent request from the clinician. This may be after hours – even after midnight. Usually the context of the result is only known by the requesting clinician. If a requesting clinician is unavailable to receive the result after hours, the patient will usually be contacted by a pathologist or emergency services. After-hours doctor services often are uninterested in receiving or acting on critical results such as troponin. In summary, there is a place for troponin measurement in general practice. Elevated levels are not uncommon due to causes other than the ACS. Turnaround time for a result may take much longer when collected in a collection centre than in the hospital setting. When ordering an urgent troponin please ensure that the laboratory has a valid contact number for after hours. References 1. Aroney CA, Cullen L. Appropriate use of serum troponin testing in general practice: a narrative review. MJA 2016; 205:(2) 91-94. 2. Marshall GA, Wijeratne NG, Thomas D. Should general practitioners order troponin tests? MJA 2014; 201: 155-157.
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.

By Dr Lee Price
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Dr Linda Calabresi
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Antibiotics Still Best For Suspected UTI

At a time when there is increasing pressure on GPs not to prescribe antibiotics, a new primary care study endorsing their role in the early treatment of uncomplicated UTI makes a welcome change. The trial, recently published in the BMJ showed that not only did early antibiotic treatment for a lower UTI significantly shorten the duration of symptoms, it also reduced the risk of the patient developing pyelonephritis. However, the researchers stopped short of recommending all women with lower UTI symptoms commence antibiotics at first presentation. In deference to the rising rates of antibiotic resistance against UTI-causing bacteria, and the fact that little harm came to the women who were originally in the NSAID group but were eventually put on antibiotics, they effectively suggest a ‘just in case’ script. “[A] strategy of selectively deferring rather than completely withholding antibiotic treatment may be preferable for uncomplicated lower UTI,” they said. The only caveat they suggested to this strategy, was for women who had lower UTI symptoms and a CRP greater than 10mg/L who appeared, in post hoc analysis to have a greater likelihood of developing pyelonephritis and might therefore benefit from immediate antibiotics. But this would need further research they suggested. The Swiss study, a randomised, double blind trial involved more than 250 women who presented to their GP with symptoms of an uncomplicated lower UTI, and were found to have either leucocytes or nitrite or both on a urine dipstick test. The women were randomised to receive either norfloxacin or the NSAID, diclofenac. The choice of norfloxacin as the antibiotic, which does seem a little like using a hammer to crack a nut, was based on pre-determined high susceptibility rates in this Swiss population and diclofenac was the NSAID chosen because it had the same dosing regimen as the norfloxacin. Overall, symptoms were gone after a median of two days in the antibiotic group but lasted twice as long in the NSAID group, with the majority of NSAID women eventually needing antibiotics. Also of note was that 5% of women in the NSAID group developed pyelonephritis compared with none in the antibiotic group. So even though research suggests we can safely withhold antibiotics in a number of self-limiting bacterial diseases such as acute otitis media, sinusitis and traveller’s diarrhoea – we should perhaps reconsider that strategy for treating UTIs, the study authors suggest. BMJ 2017; 359: j4784. http://dx.doi.org/10.1136/bmj.j4784

By Dr Linda Calabresi
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Diana Lucia
  • Clinical Articles

Alcohol A Risk For Fathers-To-Be

Abstaining from alcohol during preconception and pregnancy is usually considered to be the woman’s responsibility. The main concern surrounding alcohol exposure during pregnancy often relates to well-established evidence of newborns developing a range of behavioural, physical and cognitive disabilities later in life. But recent research is also pointing to a link between alcohol and poor sperm development, meaning the onus is on expectant fathers too. A myriad of studies are showing biological fathers who drink alcohol may have a significant role in causing health problems in their children. Studies are showing paternal alcohol consumption has negative effects at all levels of the male reproductive system. This is as well as altered neurological, behavioural and biochemical outcomes in subsequent generations.
Read more: Hey dad, your health affects your baby’s well-being too

Men and risky drinking

In Australia, men consume alcohol at high or risky levels on a regular basis. National health guidelines recommend no more than two standard drinks on any day. According to the National Alcohol and Drug Knowledgebase, Australian men usually drink more alcohol than women. Data has shown males are twice more likely than females to consume more than two standard drinks per day on average over a 12-month period (24% compared with 9.8%). And about a third of males said they exceeded the guideline not to drink more than five standard drinks on a single occasion on a monthly basis.

Booze and swimmers

These figures are alarming given the compelling evidence about the impact of excessive, chronic or binge alcohol consumption on sperm, semen quality, fertility and child health.
Read more: Dads get postnatal depression too
Animal studies have shown a single dose of ethanol into the stomach lining (equivalent to a human binge drinking) induces damage to the testis, damaging the cells essential for sperm formation. In another experimental study, sperm health and fertility was assessed in male rats after administration of alcohol into the stomach for ten weeks. The results confirmed alcohol significantly reduced sperm concentration and the ability of the sperm to move properly. And none of the rats exposed to alcohol fertilised the females, despite confirmation of successful mating. A myriad of other non-human studies have also shown similar results, suggesting ethanol has the ability to damage sperm and fertility. Studies in humans have also supported these findings. A recent study of 1,221 young Danish men (18-28 years of age) tracked alcohol consumption in the week preceding the study to determine its effects on semen quality (volume, concentration, total count, and shape). The results showed sperm concentration, total sperm count and percentage of sperm with normal shape got worse the more the men drank. This association was observed in men reporting at least five units of alcohol in a typical week, but was most pronounced for men with a typical intake of more than 25 units a week. This suggests even modest habitual alcohol consumption of more than five units a week can negatively affect semen quality.
Read more: Mother knows best? Fathers missing in research about kids
A recent review of studies and meta-analysis of population data replicated many of these findings. The main results showed daily alcohol intake at moderate to high levels had a detrimental effect on semen volume and normal shape.

The effects on children

Limited studies have tracked the drinking patterns of fathers around the time of conception and subsequent health outcomes of the child. But rodent models have shown changes in offspring weight and development, learning and activity, anxiety related behaviours and molecular and physiological effects. A study also reported the women whose partners consumed ten or more drinks per week prior to conception had two to five times increased risk of miscarriage compared to those whose partners did not drink during preconception. Other studies provide some preliminary evidence that paternal preconception alcohol use is associated with acute leukemia at high-level use, heart malformation with daily use, microcephaly with low to moderate use, and effects in relation to fetal growth and mild cognitive impairments.

How can alcohol affect kids before they’re born?

The exact mechanism of how alcohol alters developing sperm and the later health outcomes of the foetus is still not yet fully understood. It’s been suggested alcohol can change the micro-environment within the testes, altering the development and maturation of the sperm. It’s also been suggested alcohol can influence sperm by creating genetic alterations and epigenetic marks. This means changes to gene expression occur without changes to the underlying DNA sequence. These epigenetic marks can be transferred at the time of fertilisation. This can subsequently alter the molecular makeup of the early embryo, leading to alterations in foetal development and the potential to impair offspring health. The biggest hurdle for researchers now is continuing to translate findings from the basic sciences to more sophisticated research in humans. The next stage is to identify patterns of alcohol use by men during the preconception period on foetal and childhood outcomes in the Australian context. The ConversationBut most importantly we need to realise decisions about alcohol use during the preconception period are not the sole responsibility of women. We need to be talking to men about these issues to ensure healthy outcomes for the baby. Diana Lucia, PhD candidate, Neuroscience, School of Biomedical Sciences, The University of Queensland and Karen Moritz, Professor, The Univeristy of Queensland, The University of Queensland This article was originally published on The Conversation. Read the original article.
By Diana Lucia, Prof Karen Moritz

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