The Western Australian Family Connections Genealogical Project: Detection of familial occurrences of single gene and chromosomal disorders

Aim: To investigate using a Western Australian (WA) genealogical database for the identification of single gene and chromosome disorders among families. Method: Hospital admissions for single gene and chromosome disorders recorded during 2000–2006 were identified from the WA Hospital Morbidity Data System. The proportion of these conditions occurring in family groups was then identified using genealogical links created through the WA Family Connections Genealogical Project. Results: There were 216 family clusters among 11,303 people who were recorded as having a genetic or chromosomal disorder on their hospital admission record. The most common single gene conditions found to occur in multiple family members included blood clotting disorders such as Factor VIII deficiency and Von Willebrand’s disease, followed by cystic fibrosis, myotonic dystrophies, neurofibromatosis, tuberous sclerosis, and osteogenesis imperfecta. Discussion: Single gene disorders most commonly occurring in multiple family members have been identified using the WA Family Connections Genealogical Project. These disorders reflect the most common single gene disorders requiring hospital admission, but which are not fatal before reproductive age and do not result in a loss of fertility. They are also restricted to disorders with earlier onset, as the WA Family Connections Genealogical Project currently covers 2–3 of the most recent generations. This study demonstrates the utility of record linkage genealogies to identify kindred with genetic disorders, offering a rich resource of information for focused genetic epidemiological research

How have advances in CT dosimetry software impacted estimates of CT radiation dose and cancer incidence? A comparison of CT dosimetry software: Implications for past and future research

Objective: Organ radiation dose from a CT scan, calculated by CT dosimetry software, can be combined with cancer risk data to estimate cancer incidence resulting from CT exposure. We aim to determine to what extent the use of improved anatomical representation of the adult human body “phantom” in CT dosimetry software impacts estimates of radiation dose and cancer incidence, to inform comparison of past and future research. Methods: We collected 20 adult cases for each of three CT protocols (abdomen/pelvis, chest and head) from each of five public hospitals (random sample) (January-April inclusive 2010) and three private clinics (self-report). Organ equivalent and effective dose were calculated using both ImPACT (mathematical phantom) and NCICT (voxelised phantom) software. Bland- Altman plots demonstrate agreement and Passing-Bablok regression reports systematic, proportional or random differences between results. We modelled the estimated lifetime attributable risk of cancer from a single exposure for each protocol, using age-sex specific risk-coefficients from the Biologic Effects of Ionizing Radiation VII report. Results: For the majority of organs used in epidemiological studies of cancer incidence, the NCICT software (voxelised) provided higher dose estimates. Across the lifespan NCICT resulted in cancer estimates 2.9%-6.6% and 14.8%-16.3% higher in males and females (abdomen/pelvis) and 7.6%-19.7% and 12.9%-26.5% higher in males and females respectively (chest protocol). For the head protocol overall cancer estimates were lower for NCICT, but with greatest disparity, \u3e30% at times. Conclusion: When the results of previous studies estimating CT dose and cancer incidence are compared to more recent, or future, studies the dosimetry software must be considered. Any change in radiation dose or cancer risk may be attributable to the software and phantom used, rather than—or in addition to—changes in scanning practice. Studies using dosimetry software to estimate radiation dose should describe software comprehensively to facilitate comparison with past and future research

The increase in cancer prevalence and hospital burden in Western Australia, 1992-2011

Purpose - To describe cancer prevalence and hospital service utilization by prevalent cancer patients in Western Australia from 1992 to 2011. Methods - This study was a population-based cohort study using the Western Australia (WA) Cancer Registry (1982 to 2011) as the source of incident cancer cases. These data were linked to mortality (1982 to 2011) and hospital morbidity (1998 to 2011) records via the WA Data Linkage System to ascertain complete and limited-duration prevalence and cancer-related hospitalizations over time. Prevalence rates were calculated using estimated residential population data from the Australian Bureau of Statistics. Results - In 2011, one in every 27 people living in WA had been diagnosed with cancer at some time in their lifetime, and one in 68 had been diagnosed within the previous five years. Between 1992 and 2011, complete cancer prevalence in Western Australia increased by a magnitude of 2.5-fold. Forty-five and 44% of the increase in complete cancer prevalence in males and females between 1992 and 2011 can be attributed to prostate and breast cancer, respectively. The absolute number of cancer-related bed days increased 81 and 74% in males and females, respectively, diagnosed within one year, between 1998 and 2011. Conclusions - The prevalence of cancer and the burden it places on hospitals continues to rise, demanding ongoing efforts to prevent cancer through modifiable risk factors and better, more efficient use of health resources. Steps should to be taken to understand and address overdiagnosis and overtreatmen

Laparoscopic Colorectal Surgery Outcomes Improved After National Training Program (LAPCO) for Specialists in England

OBJECTIVE: To examine the impact of The National Training Programme for Laparoscopic Colorectal Surgery (Lapco) on the rate of laparoscopic surgery and clinical outcomes of cases performed by Lapco surgeons after completion of training.SUMMERY BACKGROUND DATA: Lapco provided competency-based supervised clinical training for specialist colorectal surgeons in England.METHODS: We compared the rate of laparoscopic surgery, mortality and morbidity for colorectal cancer resections by Lapco delegates and non-Lapco surgeons in 3-year periods preceding and following Lapco using difference in differences analysis. The changes in the rate of post-Lapco laparoscopic surgery with the Lapco sign-off competency assessment and in-training global assessment scores were examined using risk-adjusted cumulative sum to determine their predictive clinical validity with predefined competent scores of 3 and 5 respectively.RESULTS: 108 Lapco delegates performed 4586 elective colorectal resections pre-Lapco and 5115 post-Lapco while non-Lapco surgeons performed 72930 matched cases. Lapco delegates had a 37.8% increase in laparoscopic surgery which was greater than non-Lapco surgeons by 20.9% (95% CI, 18.5 to 23.3, p [less than] 0.001) with a relative decrease in 30-day mortality by -1.6% (95% CI, -3.4 to -0.2, p = 0.039) and 90-day mortality by -2.3% (95% CI, -4.3 to -0.4, p = 0.018). The change point of risk-adjusted cumulative sum was 3.12 for competency assessment tool and 4.74 for global assessment score whereas laparoscopic rate increased from 44% to 66% and 40% to 56% respectively.CONCLUSIONS: Lapco increased the rate of laparoscopic colorectal cancer surgery and reduced mortality and morbidity in England. In-training competency assessment tools predicted clinical performance after training

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Diagnosing Fetal Aneuploidy in Australia: The Impact of Prenatal Screening and the Integration of New Technology

This thesis explores the historical uptake, impact, performance and outcomes of prenatal screening for fetal aneuploidy in Western Australia. New models were developed to evaluate the economic and clinical impact of new non-invasive cell free DNA (NIPT cfDNA) testing. NIPT can improve the detection of fetal Down syndrome and reduce invasive diagnostic testing and procedure related loss. These studies provide evidence to support the translation of NIPT into national public health policy

Newborn bloodspot screening policy framework for Australia

Background: The aim of newborn bloodspot screening (NBS) is to identify rare genetic and non - genetic conditions in children soon after birth in order to commence therapies that prevent the development of progressive, serious, and irreversible disabilities. Universal NBS program me s have been implemented in most countries, with minor adaptations to target conditions most relevant to the local healthcare environment. Aims: In this article, we describe the initiative s of international and Australian governments to develop policies to address the expansion of NBS in their healthcare systems. Methods: We have reviewed published public policies and literature to formulate recommendations based on clinical, social, legal, and ethical principles to inform a national governance and policy framework for Australia. Results: Australia n policy makers have been slow to develop a coordinated plan. While the experience from other governments can guide our national policy, there are specific areas that require further consideration by Australian health experts. Key reforms involve the separation of policy and operational activities, multidisciplinary decision - making and oversight by the Australian Health Ministers’ Advisory Council for policy direction. Conclusion: A formal national policy framework will guide the coordination of NBS service s that can adapt to the needs of Australian children and families