Heritability of frontotemporal dementia

One of my side projects over the past 2 years has been research in the cognitive neurosciences under the supervision of Dr James Burrell at Neuroscience Research Australia (NeuRA). Specifically, we were looking at the heritability of frontotemporal dementia.

Preliminary results from our study were published as a poster at the Australian and New Zealand Association of Neurologists (ANZAN) Annual Scientific Meeting 2014 in Adelaide. I doubt that anyone else at a neurology conference would typeset a poster in Helvetica Neue Light!

Our poster at ANZAN ASM 2014

This culminated in a paper which was accepted in the Journal of Neurology and published in November 2014 (vol 261 no 11). The abstract is reproduced below, along with the correct author affiliations (an error was introduced by the journal subeditors – Professors Kwok, Halliday and Hodges are not affiliated with Concord Repatriation General Hospital).

Po et al. J Neurol 2014

Author Affiliations

Concord Repatriation General Hospital, Sydney, Australia – KP, JB
Sydney Medical School, The University of Sydney, Australia – KP
Neurosciences Research Australia, Sydney, Australia – FL, NG, LB, JK, GH, JH, JB
The University of New South Wales, Sydney, Australia – JK, GH, JH, JB

Abstract

Frontotemporal dementia (FTD) is reportedly highly heritable, even though a recognized genetic cause is often absent. To explain this contradiction, we explored the “strength” of family history in FTD, Alzheimer’s disease (AD), and controls. Clinical syndromes associated with heritability of FTD and AD were also examined. FTD and AD patients were recruited from an FTD-specific research clinic, and patients were further sub-classified into FTD or AD phenotypes. The strength of family history was graded using the Goldman score (GS), and GS of 1-3 was regarded as a “strong” family history. A subset of FTD patients underwent screening for the main genetic causes of FTD. In total, 307 participants were included (122 FTD, 98 AD, and 87 controls). Although reported positive family history did not differ between groups, a strong family history was more common in FTD (FTD 17.2 %, AD 5.1 %, controls 2.3 %, P < 0.001). The bvFTD and FTD-ALS groups drove heritability, but 12.2 % of atypical AD patients also had a strong family history. A pathogenic mutation was identified in 16 FTD patients (10 C9ORF72 repeat expansion, 5 GRN, 1 MAPT), but more than half of FTD patients with a strong family history had no mutation detected. FTD is a highly heritable disease, even more than AD, and patients with bvFTD and FTD-ALS drive this heritability. Atypical AD also appears to be more heritable than typical AD. These results suggest that further genetic influences await discovery in FTD.

Citation

Po K, Leslie FVC, Gracia N, Bartley L, Kwok JBJ, Halliday GM, Hodges JR, Burrell JR. Heritability in frontotemporal dementia: more missing pieces? J Neurol. 2014;261(11):2170–7.

doi: 10.1007/s00415-014-7474-9
PMID: 25156163 (PubMed)

Winter is coming… to Sydney Uni

Studying for the physicians exams in Fisher Library a few weeks ago, I was delighted to hear the Game of Thrones theme being played on the University of Sydney Carillon (pronounced /kəˈrɪljən/). Honorary carillonist Isaac Wong was the one responsible, as seen in the clip below. Hearing it in person amongst the neogothic grandeur of the Quadrangle is quite epic.

 

SMP class of 2010

After four long years of blood, sweat and tears, my Sydney Medical Program colleagues and I have finally finished medical school! Congratulations to everyone in the SMP graduating class of 2010!

I was given the honour (and burden) of organising the official year photo for the Sydney Medical Program 2010 graduating cohort during Conference Week. Equipment used: Canon EOS 7D, Canon EF-S 17-55mm f/2.8 IS USM, Manfrotto 7302YB tripod. Thanks to Mian Bi for operating the shutter-release in the Concord photo, Dana Perrignon Roth for operating the shutter release in the whole-year photo, and Andrew Caterson for his crowd management expertise.

Sydney Medical Program 2010

The farewell for Concord Clinical School was held at Tintilla Estate – the Hunter Valley winery owned by the clinical school’s Associate Dean, Professor Robert Lusby. It was a great way to finish med school – a relaxing Sunday afternoon barbecue in the leafy surrounds of the prof’s vineyard.

Concord Clinical School farewell BBQ 2010

Full-size versions of the whole-year photo and clinical school photos are available on my Flickr photostream. Congratulations again to everyone in the cohort and best wishes for the years ahead!

Coonabarabran: rural medicine

So after the previous few posts on Coonabarabran, you might be wondering whether I actually got around to doing any medicine during my placement there. Indeed I had plenty of medical practice in Coona and it was an amazing experience! (As with previous posts on Coona, the photos below and more can be found on my Flickr photostream).

Placement sites

I was based at Warrumbungle Medical Centre (59 Cassilis St), with husband/wife general practitioners Drs Aniello Iannuzzi and Eve Tsironis as my principal supervisors. Warrumbungle Medical Centre is the main medical practice in Coona (there are two other medical practices in town), with Drs Iannuzzi & Tsironis, two GP registrars and two registered nurses (RNs). My role at the medical centre was mainly clinical observation and assisting with clinical procedures. I also spent some time at the co-located Orana Pathology Service collection centre (a courier does a twice-daily run to Dubbo with the samples). I learnt a lot about general practice and rural medicine from all of the doctors and nurses, to whom I’m very grateful for the experience. Dr Iannuzzi, a recent candidate for AMA national president, and I also engaged in some interesting discussions about life, politics and medicine…

Warrumbungle Medical Centre
Warrumbungle Medical Centre

The doctors at Warrumbungle Medical Centre are also visiting medical officers (VMOs) at the local hospital, as is the norm in many rural settings. Coonabarabran Health Service is a 20-bed district hospital (with a 3-bed emergency department) operated by the Greater Western Area Health Service, with the main referral hospital being Dubbo Base Hospital (c. 1.5 hours away by ambulance). At Coona hospital, I was put on-call in the emergency department (ED) for triage categories 3–5 for three 24-hour periods during my placement – in practice, this meant that I’d be called-in by the ED RN to assess the patient then report my findings and clinical impression/diagnosis to the doctor on-call (who would decide on the course of action from there). I also attended ward rounds with my supervisors, assisted in clinical procedures and with the visiting endoscopy service (see below). Incidentally, I was provided with accommodation at the hospital nurses’ quarters during my placement.

Coonabarabran Hospital ED sign
Coonabarabran Hospital ED sign

Emergency Department, Coonabarabran Hospital
Emergency Department, Coonabarabran Hospital

Nurses quarters, Coonabarabran Hospital
Nurses’ quarters, Coonabarabran Hospital (N.B. MacBook & monitor are mine)

Medical firsts

It’s almost a truism that rural general practice is where you really get to develop and practise clinical and procedural skills, and indeed this was true for my placement. There were many medical “firsts” for me, including: successful insertion of (many) IV cannulae, venesection using a 16-gauge needle (for a patient with haemochromatosis), venepuncture by needle & syringe (cf. Vacutainer/Vacuette), parenteral (SC/IM/IV) administration of medications, manually pushing IV fluids, local anaesthetic infiltration in a conscious patient, needle thoracotomy and thoracentesis of (>2 litres!) pleural effusions, suturing of a wound (using 6-0 monofilament), surgical debridement (severe tinea + MSSA cellulitis + maggot infestation!), admission of a patient, ophthalmic work-up (incl. slit-lamp exam + fluorescein), assisting in resuscitation and early management of severe trauma (motor vehicle accident), etc.

The flying doctor

When Dr Iannuzzi mentioned that one Dr Peter McInerney was flying into Coona to perform endoscopy at the hospital, I assumed that he must’ve chartered a flight to Coonabarabran Airport (which no longer has regular commercial services). It turned out that Dr McInerney was literally flying in – he piloted the plane himself, flying from his hometown of Scone (c. 175 km away). I learnt quite a bit from Dr McInerney during the day I spent assisting him in the operating theatre, including a quick tutorial on how operate the endoscope. It also turned out that his daughter and I had studied pharmacy together – it really is a small world!

School of Rural Health

One weekend my friend Nilay (on placement in Gilgandra) and I decided to visit Dubbo, which for me involved a drive of just under two hours down A39 Newell Highway. We had some friends based at the School of Rural Health (whom we hadn’t seen since the start of third-year) and also wanted to visit Taronga Western Plains Zoo. After spending several weeks in a small town, the City of Dubbo felt like being back in suburban Sydney – it was a bit of a shock to encounter the first set of traffic lights in weeks. It was great to catch-up with our friends (and interesting to observe the bountiful resources of the School of Rural Health), and the open-layout Taronga Western Plains Zoo was also well worth visiting.

School of Rural Health, The University of Sydney
School of Rural Health, The University of Sydney

Meerkat – Taronga Western Plains Zoo
Meerkat – Taronga Western Plains Zoo

The dinner

One of the traditions for students completing their placement with Drs Iannuzzi & Tsironis is that the students are expected to cook a meal for the doctors and their families at the Iannuzzi residence. I was a little trepidatious about this at first, as I’d never cooked for 13 people before… Fortunately, the other medical students (Kate and Shanela from the University of Notre Dame Australia) and I rose to the challenge, putting in a successful joint effort to cook-up an international buffet. My contributions were miso soup (味噌汁), fried rice (炒飯) and genmaicha (玄米茶) – I had some forewarning from previous students, so brought many of the ingredients (unavailable in Coona) with me from Sydney. Kate and Shanela prepared: green salad, papadums, raita, lamb rogan josh, salmon & teriyaki chicken maki-sushi, Moroccan chicken, kheer, barfi, and mango lassi.

Being mindful of one of the registrar’s preferences, this was also the first time any of us had prepared halal food. I had to email one of my friends in Sydney to clarify which foods were permissible, and we were fortunately able to source some halal chicken meat from Coona Food Suppliers (35 Timor St). Being careful during preparation of the food to avoid any contamination, we were able to make many of our dishes above halal (including both of mine).

Miso soup
Miso soup (味噌汁)

Fried rice
Fried rice (炒飯)

MedSoc logo refresh

The Sydney University Medical Society (MedSoc) has a historic logo designed by Professor Sir Thomas Anderson Stuart, which has remained in use since the late 1880s. Perhaps the reason this design has endured over a century is the strong symbolism featured on it: the caduceus*, lion passant guardant (USyd, NSW, UK), waratah (NSW), and abbreviation for ‘University of Sydney Faculty of Medicine’.

Unfortunately, the original plates were lost over time and the only digital images we had to work with were two low-detail JPEG files (see images below). Even some on the MedSoc Council didn’t realise that our logo featured a lion and waratah on it.

As part of preliminary work for the Sydney University Medical Journal (SUMJ) 2010, I decided to create a detailed vector version of our logo. I looked through our Journal archives to cross-reference the general design and decided to base my new artwork on a print I found on the cover of SUMJ 1965 (vol. 54)…

Sydney University Medical Society logos – old and new

The vector logos were created using Adobe Illustrator CS4. From a design perpsective, my primary aim was to modernise the appearance whilst remaining true to the original design. Thus my 2009 version employs cleaner lines and revised geometries, which help to emphasise the symbolic elements. For example, text was set in Univers 73 Black Extended after the style of the 1965 version’s sans-serif type.

The 1965 colour scheme was very eye-catching, dominated by scarlet and jungle green, to the point of being described as ‘Christmassy’ by some. I’m not sure whether this was a true representation of Anderson Stuart’s original colour scheme, but in any case I decided that a more subdued palette was preferable for my 21st century refresh.

The new logos were officially adopted at the 2nd meeting of the 124th MedSoc Council.

*Whilst the caduceus is traditionally the symbol for messengers and commerce (the traditional symbol for medicine being the rod of Asclepius), I suspect that Anderson Stuart chose it deliberately to represent the Royal College of Physicians.

Peer-reviewed and published!

Over a four-month period in summer 2007/08, I was involved in public health research at the National Centre for Immunisation Research and Surveillance (NCIRS) on a Faculty of Medicine Summer Research Scholarship. The results from that work have now been published in the journal BMC Health Services Research, which means that I now have my first peer-reviewed journal article to my name. The full text of our article (open access) is available from BioMed Central.

Seale, et al. BMC Health Serv Res 2009.

Abstract

Background: There is a general consensus that another influenza pandemic is inevitable. Although health care workers (HCWs) are essential to the health system response, there are few studies exploring HCW attitudes to pandemic influenza. The aim of this study was to explore HCWs knowledge, attitudes and intended behaviour towards pandemic influenza.

Methods: Cross-sectional investigation of a convenience sample of clinical and non-clinical HCWs from two tertiary-referral teaching hospitals in Sydney, Australia was conducted between June 4 and October 19, 2007. The self-administered questionnaire was distributed to hospital personal from 40 different wards and departments. The main outcome measures were intentions regarding work attendance and quarantine, antiviral use and perceived preparation.

Results: Respondents were categorized into four main groups by occupation: Nursing (47.5%), Medical (26.0%), Allied (15.3%) and Ancillary (11.2%). Our study found that most HCWs perceived pandemic influenza to be very serious (80.9%, n = 873) but less than half were able to correctly define it (43.9%, n = 473). Only 24.8% of respondents believed their department to be prepared for a pandemic, but nonetheless most were willing to work during a pandemic if a patient or colleague had influenza. The main determinants of variation in our study were occupational factors, demographics and health beliefs. Non-clinical staff were significantly most likely to be unsure of their intentions (OR 1.43, p < 0.001). Only 42.5% (n = 459) of respondents considered that neuraminidase inhibitor antiviral medications (oseltamivir/zanamivir) would protect them against pandemic influenza, whereas 77.5% (n = 836) believed that vaccination would be of benefit.

Conclusion: We identified two issues that could undermine the best of pandemic plans – the first, a low level of confidence in antivirals as an effective measure; secondly, that non-clinical workers are an overlooked group whose lack of knowledge and awareness could undermine pandemic plans. Other issues included a high level of confidence in dietary measures to protect against influenza, and a belief among ancillary workers that antibiotics would be protective. All health care worker strategies should include non clinical and ancillary staff to ensure adequate business continuity for hospitals. HCW education, psychosocial support and staff communication could improve knowledge of appropriate pandemic interventions and confidence in antivirals.

Citation/identifiers

Seale H, Leask J, Po K, MacIntyre CR. “Will they just pack up and leave?” – attitudes and intended behaviour of hospital health care workers during an influenza pandemic. BMC Health Serv Res. 2009;9:30.

doi:10.1186/1472-6963-9-30
PMID: 19216792 (PubMed)