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Dr David Palmer

The importance of eosinophils and neutrophils infiltrating oesophageal squamous epithelium as markers for reflux, eosinophilic oesophagitis, and infection are well entrenched, although traditionally less attention has been paid to lymphocytes. Small numbers of lymphocytes are normally seen in oesophageal epithelium including CD4 helper and CD8 positive cytotoxic lymphocytes. However, isolated increases in lymphocytes in the oesophageal epithelium, outside the context of entities such as lichen planus and graft versus host disease, have been less well recognised until recently. The criteria for a diagnosis of lymphocytic oesophagitis, where lymphocyte numbers are markedly increased with few or no eosinophils, is not strictly defined since this is still a reaction pattern and not a specific diagnosis per se, and thresholds vary from study to study. The strictest definition requires at least 50 intraepithelial or peripapillary lymphocytes per HPF with few or no granulocytes. The term lymphocytic oesophagitis was originally coined in 2005 by Rubio et al to describe a histological reaction pattern in the oesophagus of a series of 20 patients. The patients had a high number of peripapillary lymphocytes and a lack of neutrophils and eosinophils. The papillae are projections of lamina propria, containing capillaries, which project a short distance into the epithelium of the normal oesophagus. The pattern of lymphocytic oesophagitis showed an association with Crohn’s disease, though not a completely specific one. Of the 20 patients, 11 were age 17 or younger and of these, eight (40%) had Crohn’s disease; 20% had manifestations of reflux and the remainder a mixture of conditions including coeliac, gastroduodenitis, and Hashimoto’s thyroiditis. A similar study of 40 patients in 2008 was unable to confirm these findings. Looking at it from a different angle, Ebach et al studied 60 paediatric patients with known Crohn’s disease and control groups and found an association. Lymphocytic oesophagitis  which was found in 28% of patients with Crohn’s disease (mean age 13.3) but in only 2/30 patients with ulcerative colitis. A 2014 study of 580 paediatric patients confirms the association with Crohn’s disease, but also shows the non-specific nature of lymphocytic oesophagitis. This found 31 patients with lymphocytic oesophagitis and 49 with Crohn’s disease. Six of the 31 lymphocytic oesophagitis patients (19%) and 43 of the 514 non- lymphocytic oesophagitis patients (8.4%) had Crohn’s disease. The remaining lymphocytic oesophagitis patients had other diagnoses with no significant clinical correlates. Conversely, lymphocytic oesophagitis was identified in 12.2% of the patients with Crohn’s disease. Thus, there were still more lymphocytic oesophagitis patients without Crohn’s disease than with Crohn’s disease. In adults, the association with Crohn’s disease is not seen but there appears to be an association with oesophageal dysmotility. A 2011 study of over 129,000 patients from a large outpatient private GI pathology lab service revealed lymphocytic oesophagitis in only 119 patients, 60% female. Most patients had symptoms of oesophageal disease such as dysphagia or odynophagia, with dysphagia being the most common complaint, and around 20% complaining of reflux. Endoscopically, around a third of patients were suspected of having eosinophilic oesophagitis (including ‘feline oesophagus’ where the oesophagus has rings resembling that of a cat’s oesophagus), around 20% were normal, 18% had features suggestive of reflux, and 10% had stricture. However, none had Crohn’s disease or an association with Helicobacter gastritis. Although this study drew no firm conclusions as to the nature of lymphocytic oesophagitis in adults, the prevalence of dysphagia as a presenting complaint, and the number of patients with findings reminiscent of eosinophilic oesophagitis were noted. The association with dysmotility is enhanced by the finding that in adult patients, a lymphocytic oesophagitis with a complete absence of granulocytes was mostly seen in older female patients who presented with dysphagia and had an oesophageal motility disorder. CD4- and CD8-predominant lymphocytic oesophagitis occurs with roughly equal frequency. However, patients with CD4-predominant lymphocytic oesophagitis are more likely to be female (71%), and have a motility disorder (90% of those tested). This suggests a new entity of ‘dysmotility lymphocytic oesophagitis’. In summary, the reaction pattern of lymphocytic oesophagitis appears to be real, however, the term cannot be used as a wastebasket and true increased numbers of intraepithelial lymphocytes must be seen. Clinical and endoscopic correlations determine the significance of any pathologist comment on increased numbers of lymphocytes in the epithelium.
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.

Suzanne Dyer

A new study out today has found residents with dementia in aged-care facilities that provide a home-like model of care have a better quality of life and fewer hospitalisations than those living in more standard facilities. We also found the benefits of a home-like model were provided without an increase in running costs. Our study compared home-like models (which have up to 15 residents per unit and free access to outdoor areas) to more standard residential care, where a large number of people are housed in one building. In 2011, around half of all facilities in Australia had places for more than 60 residents, and the average size is growing. The World Health Organisation has stated smaller home-like residential care settings “hold promise for older people, family members and volunteers who provide care and support”. But Australia is lagging behind other countries in offering alternative models of residential aged care.
Read more: There's no need to lock older people into nursing homes 'for their own safety'

What is a home-like model of care?

Most older people with dementia want to stay at home as long as they can. When this is no longer possible, they move into residential aged-care facilities, which become their homes. These residential facilities, or nursing homes, frequently adopt a model of care that emphasises individuality. This is known as person-centred care. But delivering this model may require more staff or a different mix of staff, which may be difficult to deliver with current funding. So standard aged-care facilities in Australia often have some similarities to health facilities, with designated staff areas and centralised kitchens. Access to outdoor areas, particularly for people with dementia, may depend on the availability of staff. Despite adhering to philosophies such as person-centred care, the scheduling of this care and of meals often lacks flexibility. The problems are compounded when residential care is used for multiple purposes ranging from palliative care to providing care for people with dementia. The needs of these two groups are quite different and the lack of focus makes delivering quality care a challenge. Evidence shows the physical design of the residential aged-care environment may play an important role in the well-being of residents, particularly those living with dementia. Internationally, there is a move towards providing care in facilities that feel more like a home and promote independence. Such models of residential aged care generally have:
  • flexibility in daily routines – for example, the time people get dressed and eat
  • opportunity for residents to participate in domestic activities such as meal preparation
  • access to outdoor spaces
  • clusters of smaller living units (up to, say, 15 residents in each)
  • care staff assigned to living units for continuity of care and development of relationships between staff and residents.

Read more: God’s waiting room? Life needs to be valued in nursing homes

What we found

Our study was specifically designed to include people with dementia and their family members. People with dementia are not often included in research studies. It included 541 participants from 17 not-for-profit residential aged-care facilities in four different states in Australia. They had been residents for a year or longer. These facilities were all considered high quality. This means they had lower hospitalisation rates for potentially avoidable conditions than the national performance target. And more than 80% of residents in the standard care facilities indicated they felt as safe as they wanted and that their environment was as clean and comfortable as they wanted. Around one-quarter of people in the study lived in a facility with a home-like model of care. All of them were living with dementia. The study found residents in home-like models of care had a better quality of life, as rated by the residents themselves or their family members. They also had a 68% lower rate of being admitted to hospital and 73% lower rate of having an emergency department presentation. We have previously shown residents who lived in a home-like model were 52% less likely to be exposed to potentially inappropriate medications. These are medications where the potential harms may outweigh the benefit, such as antipsychotics or relaxants, but are still often prescribed to older people in residential care. The benefits for residents were provided with similar running costs for the home-like and the standard models of care. However, the costs excluded differences in the build of the facilities. Initial establishment costs are likely to be higher, due to the requirement for more space per resident.
Read more: There is extra funding for aged care in the budget, but not enough to meet demand

Rethinking models of care

Funding arrangements don’t incentivise Australian aged-care providers to offer variety in terms of models of care. Government funding is provided based on the assessed care needs of the residents, rather than the preferred model of care or resident outcomes. Funding supplements are available to care providers for reasons such as residents’ financial hardship or risk of homelessness and to small, rural aged-care service providers, but none are available for offering an alternative model of care. The ConversationThe Australian government plans to improve the aged-care system to offer “choice and flexibility”. This is crucial, but we also need to improve choice and variety in residential aged-care models. Suzanne Dyer, Senior Research Fellow, Flinders University and Stephanie Harrison, Postdoctoral research fellow, Flinders University This article was originally published on The Conversation. Read the original article.
Dr Vivienne Miller

Based on an interview with Melbourne urologist, Dr Caroline Dowling conducted in March, 2018 Australia was the first country to ban vaginal mesh products used surgically via transvaginal implantation for the treatment of pelvic organ prolapse. Australia was also a leader in evaluating the complications of these implant, through large scale research.1 On November 28th 2017, the Therapeutic Goods Administration withdrew implants for use in prolapse, stating it “was of the belief that the benefits of using transvaginal mesh products in the treatment of pelvic organ prolapse do not outweigh the risks these products pose to patients”. There are unique risks related to mesh use. These include mesh erosion (up to 14% of cases)1, vaginal and groin pain (up to 3% to 4%)1 and mesh exposure. These complications may be more common and more severe (requiring surgery) if the mesh is used for prolapse repair, as opposed to the treatment of stress incontinence. Reports of complications associated with transvaginal mesh products began over a decade, with the Food and Drug Administration issuing an alert about their use back in 2008. Repeated warnings were then given. In 2013, legal action began in Australia with 300 women registering for a national class action against Johnson & Johnson Medical Australia. So what do GPs tell their patients who have a vaginal mesh in situ, and what alternative managements are there for vaginal prolapse and stress incontinence? Patients who feel they have complications should be reviewed by the surgeon who operated on them, but it worth noting that most women have had no problems with these products and so, in the absence of symptoms may be reassured that they need no further management. “Women who have no problems from their transvaginal mesh implants should be reassured that they do not require them to be removed,” says Melbourne urologist Dr Caroline Dowling There is not an inherent risk with mesh as an implant, it is used widely in general surgery for inguinal hernia and abdominal wound repair. Nonetheless, it would be wise to explain the possible side-effects of the vaginal mesh in case these occur in the future. Alternatives to the vaginal mesh implant are the traditional vaginal prolapse repair using native tissue, and these are effective procedures for most women seeking surgical treatment of their prolapse. There are several alternatives to mesh for the treatment of stress incontinence that has failed conservative therapy, including an autologous fascial sling, bulking agents and Burch colposuspension. In 2015, the Cochrane Incontinence Group concluded that mid-urethral slings were highly effective in the short-term and medium-term and had a good safety profile. The mid-urethral sling remains available in its retropubic and transobturator form, but patients can no longer access mini-slings or single incision slings outside trial settings. This may change once the results of longer term studies become available. Single incisions may have a more favourable side-effect profile than full-length slings. More conservative management includes pelvic floor exercises and silicon pessaries inserted for prolapse and stress incontinence treatment. Pelvic floor exercises may be difficult to do effectively and repeatedly for many women, especially over time. They may also be less effective in cases of significant cystocoele. Silicon pessaries are particularly useful in women who are symptomatic but wish to have further pregnancies, in women who do not want surgery, in the elderly and for those in poor health.3 Patients may need help with the insertion and correct placement, but pessaries work well and may be an underutilised option.
  1. A/Prof. Christopher Maher, Explaining the Vaginal Mesh Controversy. Royal Brisbane and Women's and Wesley Hospitals Brisbane, The University of Queensland. June 17th
https://medicine.uq.edu.au/article/2017/06/explaining-vaginal-mesh-controversy
  1. Ford et al. Mid-urethral sling operations for stress urinary incontinence in women. Cochrane Incontinence Group, July 2015.
http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD006375.pub3/abstract
  1. Jones, K. Harmanli, O. Pessary Use in Pelvic Organ Prolapse and Urinary Incontinence. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2876320

Dr Linda Calabresi

Surviving childhood cancer is a major win in anyone’s language. However, it is well-known, that even as adults these survivors are at an increased risk of dying before the age of their cancer-history-free peers. Now, it would appear, these people can do something about managing that Damocles sword. According to a recent study published in JAMA Oncology, regular vigorous exercise in early adulthood is associated with a lower risk of mortality in adult survivors of childhood cancer. And the study authors believe the finding could have a significant impact, given the numbers of children that now survive cancer. “These findings may be of importance for the large and rapidly growing population of adult survivors of childhood cancer at substantially higher risk of mortality due to multiple competing risks,” they said. The study was a multicentre cohort analysis of data from over 15,400 adults who had had cancer diagnosed at one of number of paediatric tertiary hospitals in North America before the age of 21. Interviews were conducted at baseline (median age at almost 26 years) at which, among a range of other parameters, levels of exercise were assessed. These patients were then followed for up to 15 years (median follow-up 9.6 years). Overall, after adjusting for chronic health conditions and treatment exposures the researchers found an inverse association between exercise and all-cause mortality. More compelling was the analysis of a subset of almost 5700 survivors, which showed that increased exercise over an eight-year period was associated with a 40% reduction in all-cause mortality compared with low levels of exercise. Of course, the critical question is what constitutes vigorous or increased exercise? How much exercise does a person need to do to qualify for this benefit? The question these patients were asked was ‘on how many of the past seven days did you exercise or do a sport that made you sweat or breathe hard?’ This was considered vigorous exercise, and the mortality benefit was seen in people who exercised to this level for at least 60 minutes a week. But the benefit was not entirely dose-dependent.  It appeared that vigorously exercising for about an hour a day, five days a week (eg a brisk 60 min walk) was the most advantageous in terms of mortality, beyond that the benefit was attenuated. It is well known that, in the general population, regular exercise reduces all-cause and cause-specific mortality, however there are much fewer studies looking at its benefit among cancer survivors, especially younger-age cancer survivors. “To this end, our findings….significantly extend the current evidence base and arguably provide the best available epidemiological evidence to support the endorsement of exercise for cancer survivors,” the study authors said. Ref: JAMA Oncology doi10:1001/jamaoncol.2018.2254

Dr Trevor W. Beer

Melanoma is rare in childhood, representing no more than 2% of all skin melanomas. Diagnosis is often delayed because melanoma is unsuspected, partly due to differences in presentation and its rarity. The diagnosis is made with trepidation by pathologists, since the vast majority of childhood skin lesions are benign. Establishing the true prevalence of juvenile melanoma is complicated by a number of factors, one being the definition of childhood or juvenile. Many studies use a cut-off age of 19 years, but this is not consistent. Cancer registry data may also be unreliable due to misclassified Spitz naevi, for example.

ABCDE + ABCDD

ABCDE criteria help to identify adult melanoma clinically (Asymmetry, Border irregularity, Colour variation, Diameter >6mm, Evolution). Many melanomas in childhood are non-pigmented (> 50% of 65 recent cases from Victoria). Additional ABCD criteria have been suggested in children: Amelanotic, Bleeding bump, Colour uniformity, De novo, any Diameter to facilitate earlier recognition. Children more often present with advanced disease due to diagnostic delay, reported in 50-60% of patients.

Childhood Melanoma in WA

A recent WA study with the WA Melanoma Advisory Service (WAMAS) identified 95 melanomas in patients 19 years or younger over a 14-year period. Three patients died from melanoma. The majority of tumours, 75%, occurred between ages 13 and 19 years, similar to other studies. In all populations, juvenile melanoma is much less common before puberty. Delayed diagnosis was evident with 21 of 23 patients presenting with Clark level 4 or 5 melanomas with Breslow thickness >1mm in 65%. A family history of melanoma was seen in 17%. A study this year in Victoria revealed 65 melanomas during a 19-year period, with seven fatalities. A decrease in juvenile melanoma has been seen in WA despite an increasing population. In Queensland, a substantial decline occurred between 1997 and 2010, attributed to safer sun exposure practices since the 1980s.

Prognosis

The outlook for childhood melanoma mirrors that in adults being primarily based on stage and Breslow thickness. The exceptions are tumours with spitzoid features. These show appearances resembling Spitz naevi and, although often metastasising to local nodes, are less frequently lethal. Prognostication is complicated by the fact that occasional examples behave aggressively and some spitzoid melanomas in case series may be misdiagnosed Spitz naevi.

Treatment

Complete excision, as in adults, is required. Further investigations and treatment should be decided in conjunction with expert advice. Treatment of advanced melanoma is progressing rapidly and possible eligibility for clinical trials means that patients will get the best opportunities for positive outcomes with personally tailored, up-to-date guidance. It is recommended that all melanoma diagnoses in childhood are reviewed by pathologists with expertise in melanocytic lesions. Referral to a multidisciplinary team is valuable to ensure correct diagnosis and to optimise treatment and advice to patients and families.

Sophie Spitz’s ‘Juvenile Melanoma’

Pathologist Sophie Spitz described 12 unusual ‘juvenile melanomas’ in 1948. Follow-up showed benign behaviour, despite microscopy suggesting melanoma. These lesions are now called Spitz naevi. Although typically childhood lesions, they can occur in adults, reducing in frequency with age. Diagnosis clinically and microscopically can be challenging. Lesions may clinically resemble pyogenic granulomas, haemangioma or dermatofibroma. While most are correctly identified pathologically, some are misdiagnosed as melanoma. Conversely, a leading cause of litigation in pathology is underdiagnosis of melanoma as Spitz naevus. Distinction between Spitz naevi and melanoma may be extremely difficult or even impossible. In these histologically ambiguous tumours inter-observer agreement is notoriously poor. There is now a move away from traditional benign versus malignant divisions with suggestions that a histological continuum exists between Spitz naevi at one end and Spitzoid melanoma at the other. Indeterminate lesions may be labelled Spitzoid tumours of uncertain malignant potential (STUMP) with a guarded prognosis.

Improving pathological diagnostic accuracy

Treatment and prognostication of childhood melanoma requires accurate diagnosis which can be enhanced by experience and consultation between pathologists. Molecular studies such as FISH and aCGH may assist in ambiguous cases, but such methods are still in development and not uniformly available. However, molecular techniques will ultimately lead to more accurate diagnosis, prognostication and tailored treatment for children with melanoma. References available on request
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.
Dr Linda Calabresi

Almost three quarters of men with low grade prostate cancer may not be being adequately monitored, a recent Victorian study suggests. According to data from the Prostate Cancer Outcomes Registry – Victoria, only 26.5% of over 1600 men who had low risk prostate cancer had follow-up investigations consistent with standard active surveillance protocols in the two years after their diagnosis. Specifically, researchers were investigating whether these men adhered to the schedule that consisted of at least three PSA measures and at least one biopsy in the two years post diagnosis. While the study authors concede the clinical consequences of this shortcoming are yet unknown, the finding is still of concern. “If [these men] are not being followed appropriately according to [Active Surveillance] protocols, men may miss the opportunity to be treated with curative intent,” they wrote in the MJA. Active surveillance is increasingly the management of choice for men with low risk prostate cancer. In Victoria, 60% of men diagnosed with this grade of cancer are now managed with active surveillance, the study authors said. A major issue with active surveillance as a management option, is that the optimal timing of follow-up investigations has not been strictly defined, resulting in several different protocols and guidelines being developed worldwide.  This, in part was the impetus for the development of the Victorian prostate cancer registry, which was established in 2009 ‘to improve knowledge of patterns of care and outcomes for men diagnosed with prostate cancer.’ Currently the Australian protocol for active surveillance is based on the consensus opinion, and the three PSA tests and repeat biopsy within two years has been widely accepted as standard care. The finding that 73.5% did not receive monitoring in accordance with thisprotocol, reflected adherence levels that were among the worst when compared to similar studies around the world, and the study authors suggested the reason was likely to be multifactorial. The reasons for the non-compliance ‘may reflect patient-, clinician- and health service-related factors,” they wrote. Patients may avoid biopsy because of pain, clinicians may delay testing based on a patient’s comorbidities or health services may have fewer resources for sending reminders or pursuing patients who miss appointments, the study authors suggested. Nonetheless, efforts needed to be made to ensure men with low grade prostate cancer are not disadvantaged in terms of health outcomes if they opt to accept active surveillance as their management strategy. “To improve adherence, a multifaceted approach may be required, including an education campaign that highlights the need for men to undergo regular PSA assessment and prostate biopsy,” they concluded. Ref: MJA doi:10.5694/mja17.00559

Prof Adam Watkins

ON THE PILL: In this seven-part series we explore the history, myths, side-effects and alternatives of the pill, and why it’s the most popular form of contraception in Australia.
The female contraceptive pill has helped millions of women take control of their fertility and reproductive health since it became available in 1961. Yet a male equivalent has yet to be fully developed. This effectively leaves men with only two viable contraceptive options: condoms or a vasectomy. The idea of creating a male contraceptive has been around almost as long as the female contraceptive. In theory, targeting the production of sperm should be a simple process. The biology of sperm production and how they swim towards the egg are well understood. Yet, studies aimed at developing an effective male pill have been dogged by issues such as severe side effects. Most recently, a study that injected men with the hormones testosterone and progestogen – similar to hormones found in the female pill – had to be stopped early.
Read more: Why the male 'pill' is still so hard to swallow
The study, from 2016, showed pregnancy rates for female partners of men receiving the injections fell below that typically seen for women on the pill. But the study was cut short due to reports of adverse side effects including acne, mood disorders and raised libido. For the men taking part, these side effects proved too severe for them to continue, despite the desired drop in sperm production. However, many people may see these side effects as relatively minor compared to those suffered by women on the pill, which include anxiety, weight gain, nausea, headaches, reduced libido and blood clots. Male contraceptives have been under development for at least 50 years. However, the drive to bring a male contraceptive onto the market has stalled for two main reasons. First, there is a general pessimism of men towards taking a contraceptive pill, especially in countries such as India. Second, the global success of the female pill provides little incentive for pharmaceuticals to invest in a male pill. Globally, the female pill is the third most-used form of contraception, with a projected market value of nearly US$23 billion by 2023. Despite these setbacks, a new way of thinking about male contraception is taking shape. Here, the focus has shifted from stopping sperm production to stopping the sperm being able to fertilise the egg.

The clean sheet pill

The clean sheet pill effectively works as its name suggests: preventing the release of sperm. The clean sheet pill has two main selling points. First, by preventing the release of sperm and the fluid they are carried in, the clean sheet pill simultaneously prevents unwanted pregnancy and the spread of sexually-transmitted infections. Second, because the pill does not affect the feeling of orgasm, there is no reduction in male sexual pleasure. Unfortunately, the clean sheet pill has so far only been tested in animals. As such, a version for human use is probably ten years away from being developed.

Vasalgel

One of the downsides of a vasectomy is that it can render a man permanently sterile. However, the recent development of a product call Vasalgel may offer men a serious alternative to a vasectomy. Vasalgel is a long-term, non-hormonal yet reversible form of contraception. This offers benefits over both hormonal contraceptives with their side effects as well as the permanency of a vasectomy. Vasalgel is polymer that is injected into the vas deferens, the tube that carries sperm from the testes. This allows the movement of fluid, but stops the passage of sperm.
Read more: A new male contraceptive could help men bear the family planning burden
In a trial in monkeys, Vasagel was found to be 100% effective at preventing conception. In separate studies in animals, the effect of Vasagel was easily reversed with a simple second injection to dissolve the polymer. If these effects are replicated in men, this could offer a low-cost, minimally invasive and effective contraceptive that is also reversible.

Heart-stopping poisons

A deadly, heart-stopping poison might not sound like a good starting point for a new male contraceptive. However, researchers have shown that a toxic compound call oubain can be be used to slow down the swimming of sperm. Researchers already knew that oubain could affect male fertility. But the cardio toxic effects of oubain prevented scientists from exploring its effects on male reproduction in any detail. By modifying the structure of the oubain molecule, researchers showed it can be used to reduce the motility (ability to swim) of rat sperm while being non-toxic to the heart.

Research and development

While research into male contraceptives have been ongoing for nearly 50 years, we still seem to be at least “five to ten years away” from an effective male pill.
Read more: We won't have a male contraceptive until we change our understanding of risk
Potential new targets for male contraceptives are being developed and tested scientifically all the time. However, without the significant input and push from big pharmaceutical companies, these discoveries may never see the light of day. The ConversationWith the cost of developing a new drug to market estimated at US$2.6 billion, the burden of family planning looks to remain firmly on the shoulders of women for now. Adam Watkins, Assistant Professor, University of Nottingham This article was originally published on The Conversation. Read the original article.
Dr Linda Calabresi

In what will be seen as a blow to cryptic crossword compilers the world over, it appears wealth is a better determinant of whether you keep your marbles than education. In a UK prospective study of over 6000 adults aged over 65 years, researchers found those people in the lowest quintile in terms of socioeconomic status were almost 70% more likely to get dementia than those categorised to be in the top fifth, over a 12 year follow-up period. Depressingly, this finding held true regardless of education level. “This longitudinal cohort study found that wealth in late life, but not education, was associated with increased risk of dementia, suggesting people with fewer financial resources were at higher risk,” the study authors said. On further analysis, researchers found the association between wealth, or the lack thereof and dementia was even more pronounced in the younger participants in the cohort. So what did the researchers think was the reason behind the link between poverty and dementia? One explanation was that having money allowed one to access more mentally stimulating environments including cultural resources (reading, theatre etc) and increased social networks that might help preserve cognitive function. While on the flip side, poverty (or ‘persistent socioeconomic disadvantage’ as the authors describe it) affects physiological functioning, increasing the risk of depression, vascular disease and stroke – all known risk factors for dementia. Other factors such as poor diet and lack of exercise also appear to more common among poorer people in the community. All this seems fairly logical, but what of the lack of a protective effect of education? Well, the researchers think this might be a particularly British phenomenon in this age group. “This might be a specific cohort effect in the English population born and educated in the period surrounding the World War II,” they suggested. A number of other studies have shown other results, with some, including the well-respected Canadian Study of Health and Aging-  showing the complete opposite – education protects against dementia. Consequently, the authors of this study, published in JAMA Psychiatry, hypothesise that perhaps this cohort of patients may have been unable to access higher education because of military service or financial restrictions but were able to access intellectually challenging jobs after the war. All in all, the study is an observational one and it is possible there are a number of confounding factors from smoking to availability of medical care that play a role in why poorer people are at greater risk of dementia. And while the researchers are not advocating older people give up their Bridge game and just buy lottery tickets, it would seem money is useful, if not for happiness, then at least for preserving brain power. Ref: JAMA Psychiatry doi:10.1001/jamapsychiatry.2018.1012

Dr Paul Glendenning

Markers of bone turnover, measured in blood or urine, correlate with changes in the metabolic activity of bone. The rate of bone remodelling is important. With ageing, the quantum of bone removed/ resorbed and the amount replaced/ formed becomes increasingly imbalanced. Consequently, the more bone remodelling units that are active at any one time, or the greater the activity of individual units, the greater the overall rate of bone loss. Bone turnover markers are probably predictive of the rate of bone loss and could help determine the efficacy of treatment.

Bone turnover markers:

  • May predict fracture risk independently of bone mineral density, according to some studies.
  • A drop in bone resorption is an early predictor of response to all anti-resorptive osteoporosis treatments initiated in general practice (bisphosphonates, denosumab or raloxifene), with these markers changing earlier than comparable markers of bone formation.
  • They may be predictive of later changes in bone mineral density (BMD), and can be measured before BMD changes can be evaluated.

Which bone resorption marker?

Markers measuring the rate of bone loss are degradation products of type 1 collagen cleaved during bone resorption. Cross-linking telopeptides of collagen can be measured by immunoassays that are specific for the beginning (N terminal- called NTX) or end (C terminal- called CTX) of type 1 collagen. While measuring urinary NTX and serum CTX provide comparable information there are some advantages of CTX over NTX. Consequently, serum CTX has been proposed as a reference method. The measurand in the CTX assay is clearly defined, allowing this 8 amino acid oligopeptide to become the reference method.
  • Most serum CTX is from osteoclastic bone resorption (indicating high specificity).
  • The assay can be performed manually or by automated methods and is only provided by one manufacturer (obviating the need for harmonisation)
  • The biological and analytical variability for CTX is well documented in the literature.

Uses and limitations

Serum CTX is a potentially useful test when investigating the cause of increased alkaline phosphatase, verifying compliance with osteoporosis treatment, improving persistence with that treatment or identifying occult secondary causes of osteoporosis such as apathetic hyperthyroidism or other metabolic bone disorders such as Paget’s disease. Samples collected fasting in the morning minimise intra-individual variation and requests ideally should include the reason for testing. Medicare currently provides a rebate for tests of bone resorption in patients with known bone disease taking treatment.
  1. Not all anti-resorptive treatments suppress bone resorption to the same degree. Provision of the type of anti-resorptive agent used and the duration of treatment is not only helpful for billing but allows us to report more specifically - whether the rate of bone resorption is typical or higher than expected for a particular anti-resorptive agent. For example, denosumab suppresses bone resorption earlier and to a greater degree than a bisphosphonate.
  2. Bone resorption is not predictive of future fracture risk in individuals. CTX can provide complementary information to bone mineral density in subpopulations but this measurement has not been currently adopted into fracture risk alogrithm calculators such as FRAX or the Garvan risk calculator for individuals.
  3. The measurement of serum CTX cannot be used to select treatment. This is because the baseline rate of bone remodelling is not predictive of the rate of change of bone remodelling or rate of change of bone density while on treatment.
  4. Measurement of bone formation and bone resorption do not provide additive information. While bone remodelling is a coupled process wherein bone formation and bone resorption are linked, the measurement of bone resorption or bone formation markers provide comparable information regarding the rate of bone remodelling. Measurements of both bone formation and bone resorption markers in individual patients do not help determine the degree of imbalance in bone remodelling and is therefore unnecessary. Understanding these limitations and the potential value of measuring bone remodelling markers can be useful when making decisions regarding individual patient management in those taking treatment for osteoporosis.
Reproduced with permission from Medical Forum magazine Oct 2017 edition
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.
Dr Linda Calabresi

Resistance exercise training significantly reduces depressive symptoms, a new meta-analysis has found. According to international researchers who looked at over 30 randomised clinical trials on the subject, resistance exercise training including activities such as weight lifting reduced depressive symptoms by an average of a third. In fact, the meta-analysis findings suggested that resistance exercise training may be particularly helpful for reducing symptoms in patients with more severe depression. The study results, published in JAMA Psychiatry, concluded that only four people needed to be treated in order to have one to show significant benefit from the intervention. And the improvement inn depressive symptoms occurred regardless of the patient’s overall health status, the volume of resistance training exercise the patient undertook or any improvements in strength the patient experienced. And while the study authors made sure to point out their analysis was not comparing this exercise program with other treatments for depression, reducing symptoms by an average of a third certainly compares with other treatments currently available for this condition. “The available empirical evidence supports [resistance exercise training) as an alternative or adjuvant therapy for depressive symptoms,” the researchers said. What we still don’t know, apparently is exactly what sort of exercise, at what intensity, how frequently and for how long is required until a significant improvement in the depression is achieved. Many of the randomised controlled trials included in the meta-analysis did not measure all these parameters. What the researchers did find was that supervised training programs appeared more effective than non-supervised, which may reflect adherence to the exercise regimen. They also said the most common frequency of resistance exercise training was three times a week. The study authors suggested the limitations of the studies included in this analysis should help direct further research. “Future trials, matching different exercise modes on relevant features of the exercise stimulus, will allow more rigorous and controlled comparisons between exercise modalities, and the examination of interactions between factors such as frequency, intensity, duration and exercise modality,” they said. But regardless of the lack of fine print, the results of this moderate-sized effect of resistance exercise training reported in this study and the complete lack of adverse effects, would seem sufficient to justify recommending it to patients with depression, at least as an adjunctive treatment for one of Australia’s most common mental illnesses. Ref: JAMA Psychiatry doi:10.1001/jamapsychiatry.2018.0572

Dr Kees Van Gool

The winners of this year’s health budget are aged care, rural health and medical research. The government has announced A$1.6 billion over four years to allow 14,000 more older Australians to remain in their home for longer through more high-level home care places. For those in aged care, an additional A$82.5 million will be directed to improve mental health services in the facilities. The budget includes A$83.3 million over five years for a rural health strategy, which aims to place more doctors and nurses in the bush and train 100 additional GPs. There’s A$1.3 billion over ten years for a National Health and Medical Industry Growth Plan, which includes A$500 million for new research in the field of genomics. Other key announcements include: - A$1.4 billion for new and amended listings on PBS - A$302.6 million in savings over forward estimates by encouraging greater use of generic and bio similar medicines - A$253.8 million for a new Aged Care Quality and Safety Commission.
Read more:Infographic: Budget 2018 at a glance

Aged care

Helen Dickinson, Associate Professor, Public Service Research Group at UNSW It was well foreshadowed that this budget would bring with it significant provisions for aged care. It has been widely reported that reforms to pension and superannuation tax have resulted in disaffection in the Coalition within older age groups. Making older Australians the cornerstone of budget measures is a calculated political tactic in a budget that in the short term makes only limited tax cuts for low- and middle-income earners. The A$1.6 billion for 14,000 new places for home-care recipients will be welcome, but are a drop in the ocean, given there are currently more than 100,000 people on the national priority list for support. Additional commitments around trials for physical activities for older people, initiatives to improve connections to communities and protections for older people against abuse will bolster those remaining in homes and communities. Commitments made for specific initiatives for Aboriginal and Torres Strait Islander people and aged care facilities in rural and remote Australia will be welcomed, although their size and scope will likely result in little to address older age groups with complex needs. While investment in aged care services will be welcome, it remains to be seen whether this multi-million-dollar commitment will succeed in clawing back support from older voters. Recent years have seen around A$2 billion of cuts made to the sector through adjustments to the residential care funding formula. The current financial commitments go some way to restoring spending, but do not significantly advance spending beyond previous levels in an area of the population we know is expanding substantially in volume and level of need and expectation. A number of new budget commitments have been announced in relation to mental health services for older people in residential aged care facilities, for a national mental health commission, and for Lifeline Australia. However, given the current turbulence in mental health services, it’s unclear whether these will impact on the types of issues that are being felt currently or whether this will further disaggregate an already complex and often unconnected system.

Equity, prevention and Indigenous health

Lesley Russell, Adjunct Associate Professor, Menzies Centre for Health Policy at the University of Sydney The government states its desire for a stronger economy and to limit economic imposts on future generations, but this budget highlights a continued failure to invest in the areas that will deliver more sustainable health care spending, reduce health disparities, and improve health outcomes and productivity for all Australians. We know what the best buys in primary prevention are. But despite the fact that obesity is a heavy and costly burden on the health care system, and the broad agreement from experts on a suite of solutions, this can is once again kicked down the road. There is nothing new to address the harms caused by excessive alcohol use or opioid abuse. The crackdown on illegal tobacco is about lost taxes rather than smoking prevention. There is A$20.9 million over five years to improve the health of women and children – an assorted collection of small programs which could conceivably be claimed as preventive health. There is nothing in this budget to address growing out-of-pocket costs that limit the ability of many to access needed care. Additional funding (given in budget papers as A$83.3 million over five years but more accurately described as A$122.4 million over 2018-19 and 2019-20, with savings of A$55.6 million taken in 2020-21 and 2021-22) is provided for rural health that should help improve health equity for country Australians. Continued funding is provided for the Indigenous Australians’ Health Program (A$3.9 billion over four years); there is new money for ear, eye and scabies programs and also for a new Medicare item for remote dialysis services. There are promises for a new funding model for primary care provided through Aboriginal Community Controlled Health Services (but no details) and better access for Indigenous people to aged care. The renewal of the Remote Indigenous Housing Agreement with the Northern Territory will assist with improved health outcomes for those communities.

PBS, medicines and research

Rosalie Viney, Professor of Health Economics at the University of Technology Sydney The budget includes a notable increase in net expenditure on the Pharmaceutical Benefits Scheme (PBS) of A$1.4 billion for new and amended listings of drugs, although most of these have already been anticipated by positive recommendations by the Pharmaceutical Benefits Advisory Committee (PBAC). Access to a number of new medicines has been announced. The new and amended medicine listings are clearly funded through savings in PBS expenditure from greater use of generic and bio-similar medicines, given the net increase in expenditure over the five year outlook is around A$0.7 billion. In terms of medical research, there is an encouraging announcement of significant further investments through the Medical Research Futures Fund. This will be welcomed by health and medical researchers across Australia. What is notable is the focus on the capacity of health and medical research to generate new jobs through new technology. While this is certainly important, it is as much about boosting the local medical technology and innovation industry than on improving health system performance. And the announcements in the budget are as much about the potential job growth from medical innovation as on providing more or improved health services. There is new funding for medical research, development of diagnostic tools and medical technologies, and clinical trials of new drugs. The focus on a 21st century medical industry plan recognises that health is big business as well as being important for all Australians. All of this is welcome, but it will be absolutely critical that there are rigorous processes for evaluating this research and ensuring the funding is allocated based on scientific merit. This can represent a major challenge when industry development objectives are given similar standing in determining priorities as health outcomes and scientific quality.

Rural health

Andrew Wilson, Co-Director, Menzies Centre for Health Policy at the University of Sydney Rural Australians experience a range of health disadvantages including higher rates of smoking and obesity, poorer survival rates from cancer and lower life expectancy, and this is not solely due to the poor health of the Aboriginal community. The government has committed to improving rural health services through the Stronger Rural Health Strategy and the budget has some funding to underpin this. The pressure to fund another medical school in rural NSW and Victoria has been sensibly addressed by enhancing and networking existing rural clinical schools through the Murray Darling Medical Schools network. This will provide more opportunities for all medical students to spend a large proportion of their studentship in a rural setting while not increasing the number of Commonwealth supported places. There is a major need to match this increased student capacity with a greater investment in specialist training positions in regional hospitals to ensure the retention of that workforce in country areas. Hopefully the new workforce incentive program will start to address this.

Hospitals and private health insurance

Peter Sivey, Associate Professor, School of Economics, Finance and Marketing, RMIT University There was no new money in today’s budget for Australia’s beleaguered public hospitals. The government is still locked in a deadlock with Queensland and Victoria, which have refused to agree to the proposed 6.5% cap on yearly funding increases from the Commonwealth. With health inflation of about 4% and population growth close to 2% the cap doesn’t allow much room for increased use due to ageing or new technology. There is no change in the government’s private health insurance policy announced last year and nothing to slow the continuing above-inflation premium rises. The ConversationOn the savings side, there was also no move yet on the private health insurance rebate which some experts think could be scrapped. Kees Van Gool, Health economist, University of Technology Sydney; Andrew Wilson, Co-Director, Menzies Centre for Health Policy, University of Sydney; Helen Dickinson, Associate Professor, Public Service Research Group, UNSW; Lesley Russell, Adjunct Associate Professor, Menzies Centre for Health Policy, University of Sydney; Peter Sivey, Associate Professor, School of Economics, Finance and Marketing, RMIT University, and Rosalie Viney, Professor of Health Economics, University of Technology Sydney This article was originally published on The Conversation. Read the original article.
Dr Linda Calabresi

In the last few months of 2017, over 200 Australian infants were hospitalised due to infection with the little known human parechovirus, say Australian public health experts in the latest issue of the MJA. The infected infants were admitted with conditions such as severe sepsis and meningoencephalitis. Less common presentations included acute abdomen from intussusception, pseudo-appendicitis and even bowel perforation. According to the MJA review, parechovirus was originally included under the echovirus umbrella back in the 1960’s, but became an entity in its own right, in the 90’s. There are close to 20 genotypes of the virus, but to date only three (genotypes 1,3 and 6) are thought to cause human disease. For the most part parechovirus causes mild gastro or respiratory tract infections. However, one of the genotypes – genotype 3  - has been found to be considerably more dangerous, especially in babies. “It is now recognised as a leading cause of sepsis-like illness and central nervous system infection, particularly in young infants,” the review authors wrote. The first ‘epidemic’ in Australia of this parechovirus genotype occurred in spring-summer of 2013-2014. Another outbreak occurred two years later – the spring-summer of 2015-2016. This most recent ‘epidemic’ appeared to start in Victoria last August and has now spread nationwide with over 200 infants hospitalised to December. For GPs, the key presenting features to be on the lookout for are fever, irritability and sepsis-like illness – which aren’t very specific. More helpfully - while not all infected children will have a rash, if the presenting infant is ‘red, hot and angry’ -think parechovirus, the authors recommend. Infants younger than three months are most likely to be hospitalised and, of course, really young infants (less than a month old) are at greatest risk of complications so should be sent to hospital earlier rather than later. To diagnose this infection, specific PCR testing needs to be requested of either stool or CSF. Just testing for enteroviruses will not be sufficient. Unfortunately, as yet there is no specific treatment for parechovirus. Given the presentation is the same as that of bacterial sepsis, the review authors suggest antibiotics be commenced until cultures come back negative and bacterial infection is excluded. But other than that, the treatment is mainly supportive and close monitoring and perhaps hospitalisation is required. Of particular concern are a number of studies that suggest infection that is severe enough to require the child be hospitalised is associated with high risk of neurological sequelae. As a consequence, the authors recommend that all children hospitalised with parechovirus be followed up with a paediatrician – at least until they start school- ‘to monitor development and learning, and manage complications including seizures.’ In terms of a vaccine, there is not one yet developed against parechovirus. They suggest research efforts should focus on developing vaccines that target the most pathogenic genotypes of a virus rather than trying to eradicate the entire genus such as has occurred in China with the vaccine against EV71 – a specific enterovirus that causes a complicated hand, foot and mouth disease. Regardless the need to find a vaccine is a priority. “The high morbidity in young children provides a strong case for prevention,” they concluded. Ref: MJA doi: 10.5694/mja18.00149