Brain damage and maternal medication

Michael E. O’Callaghan, Alastair H. MacLenna

Seminars may increase recruitment to randomised controlled trials: lessons learned from WISDOM

Background: Recruiting patients to large randomised controlled trials (RCTs) in the primary care setting can be challenging. Research teams need to identify and utilise strategies that both maximise the efficiency of recruitment and minimise the burden on general practitioners. Purpose: To describe our methods for identifying, approaching and recruiting female patients aged 50–69 years to a long-term double-blind RCT of hormone therapy (HT) – the Women's International Study of long Duration Oestrogen after Menopause (WISDOM). The effectiveness of conducting group seminars with patients prior to one-to-one screening is discussed. Methods: Female patients aged between 50 and 69 years were sent letters from participating general practitioners in Adelaide inviting them to participate in WISDOM and attend an initial seminar providing information about HT and the trial prior to a screening interview with a trial nurse. Recruitment rates for those who did or did not attend group seminars were compared. Results: Women who attended a group seminar conducted by the research team were twice as likely to attend an initial screening visit and enrol to participate in WISDOM than women who did not attend a seminar (p < 0.001). In addition, it was estimated that the time required to randomise a woman in the trial, and the number and duration of telephone calls to screen out uninterested women, was reduced for the seminar group. Conclusion: Conducting group seminars with potential participants may be a useful strategy for maximising recruitment from general practice, by increasing patient information and reducing a research team's workload.Bronwen J. Paine, Nigel P. Stocks and Alastair H. MacLenna

The antenatal causes of cerebral palsy - Genetic and viral associations

Cerebral palsy is the most common neurological disorder in children. Epidemiological evidence suggests that antenatal origins are a major cause. Currently there is no antenatal test for cerebral palsy, no proven preventable measures in late pregnancy, and no known cure. Cerebral palsy affects not only the diagnosed child, but also their family and the community, requiring considerable social and financial resources to assist these children in their daily lives.Catherine S. Gibson, Alastair H. MacLennan, Paul N. Goldwater, and Gustaaf A. Dekker for The South Australian Cerebral Palsy Research Grou

NKX2-1 mutation in a family diagnosed with ataxic dyskinetic cerebral palsy

Benign hereditary chorea caused by mutations in the NK2 homeobox 1 gene (NKX2-1), shares clinical features with ataxic and dyskinetic cerebral palsy (CP), resulting in the possibility of misdiagnosis. A father and his two children were considered to have ataxic CP until a possible diagnosis of benign familial chorea was made in the children in early teenage. The father's neurological condition had not been appreciated prior to examination of the affected son. Whole exome sequencing of blood derived DNA and bioinformatics analysis were performed. A 7 bp deletion in exon 1 of NKX2-1, resulting in a frame shift and creation of a premature termination codon, was identified in all affected individuals. Screening of 60 unrelated individuals with a diagnosis of dyskinetic or ataxic CP did not identify NKX2-1 mutations. BHC can be confused with ataxic and dyskinetic CP. Occasionally these children have a mutation in NKX2-1.Gai McMichael, Eric Haan, Alison Gardner, Tzu Ying Yap, Suzanna Thompson, Robert Ouvrier, Russell C. Dale, Jozef Gecz, Alastair H. MacLenna

Single-nucleotide polymorphism associations with preterm delivery: a case-control replication study and meta-analysis

BackgroundThe aim of this study was to replicate single-nucleotide polymorphism (SNP) associations with preterm birth (PTB; birth at MethodsSpontaneous PTB cases and controls were selected from an existing cohort. Candidate SNPs were taken from an existing genotype panel. A systematic review was conducted for each SNP in the panel to determine suitability as a PTB candidate. Those with significant associations previously reported in Caucasians were selected for replication. Candidate SNPs were already genotyped in cases and controls and clinical data were accessed from state perinatal and cerebral palsy databases. Association analysis was conducted between each SNP and PTB, and meta-analysis was conducted if there were ≥ 3 studies in the literature. Maternal and fetal SNPs were considered as separate candidates.ResultsA cohort of 170 cases and 583 controls was formed. Eight SNPs from the original panel of genotyped SNPs were selected as PTB candidates and for replication on the basis of systematic literature review results. In our cohort, fetal factor V Leiden (FVL) was significantly associated with PTB (odds ratio (OR): 2.6, 95% confidence interval (CI): 1.31-5.17), and meta-analysis confirmed this association (OR: 2.71, 95% CI: 1.15-6.4).ConclusionReplication and meta-analysis support an increased risk of PTB in Caucasians with the fetal FVL mutation.Michael E. O’Callaghan, Alastair H. MacLennan, Gai L. McMichael, Eric A. Haan and Gustaaf A. Dekke

Identifying the quality of life effects of urinary incontinence with depression in an Australian population

Background: To explore the additive effect of urinary incontinence, in people with comorbid depression, on health related quality of life. Methods: Males and females, 15 to 95 years (n = 3010, response rate 70.2%) were interviewed face to face in the 1998 Autumn South Australian Health Omnibus Survey. Results: Self-reported urinary incontinence was found in 20.3% (n=610), and depression as defined by the PRIME-MD in 15.2% (n=459) of the survey population. Urinary incontinence with comorbid depression was found in 4.3% of the overall population. Univariate analysis showed that respondents with urinary incontinence and comorbid depression were more likely to be aged between 15 and 34 years and never married when compared to those with incontinence only. Multivariate analysis demonstrated that in people with incontinence, the risk of having comorbid depression was increased by an overall health status of Fair or Poor, or the perception that their incontinence was moderately or very serious. Respondents reporting that they experienced incontinence with comorbid depression scored significantly lower than those experiencing incontinence without depression on all dimensions of the SF-36. The interaction of the presence of incontinence and the presence of depression was significantly associated with the dimensions of physical functioning. Conclusions: Depression and incontinence both reduce QOL. When they occur together there appears to be an additive effect which affects both physical and mental health, perhaps by increasing a person’s negative perceptions of their illness. Clinicians should identify and manage comorbid depression when treating patients who have incontinence to improve their overall QOL.Jodie C Avery, Nigel P Stocks, Paul Duggan, Annette J Braunack-Mayer, Anne W Taylor, Robert D Goldney and Alastair H MacLenna

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer