Zopiclone misuse: an update from Dublin

The prevalence of zopiclone misuse in clients attending a methadone maintenance programme in Dublin through detection of its degradation product, 2-amino-5-chloropyridine (ACP) on urinalysis is outlined. Urine samples from all 158 clients were tested for the presence of ACP, opiates, benzodiazepines, cocaine, alcohol and cannabis. Of the 37 (23%) clients who tested positive for ACP, 23 (62%) were interviewed. A profile of zopiclone misusers is outlined, including details of demographics, drug history, viral status, recent urinalysis results and opinions on zopiclone. Of the 14 (38%) clients who were not interviewed, information was obtained from their clinical casenotes and documented urinalysis results. The prevalence of zopiclone misuse was reported as 23%. Benzodiazepines were the most popular drug of misuse with zopiclone followed by heroin/opiates. Zopiclone is being misused by drug users in Dublin in the context of many other drugs. Prescribing of zopiclone should be restricted, especially among drug misusers. [Bannan N, Rooney S, O'Connor J. Zopiclone misuse: an update from Dublin. Drug Alcohol Rev 2007;26:83 - 85]     

Bilirubin influences the clinical presentation of pre-eclampsia

Objectives

Pre-eclampsia is a placental, inflammatory disease modified by maternal anti-oxidant status to give a syndrome. In its most severe forms pre-eclampsia is followed by maternal and neonatal mortality and morbidity. Bilirubin is a known antioxidant and as such is associated with a reduced risk of cardiovascular and respiratory disease. Hence we aimed to find an association between maternal bilirubin levels and the clinical severity of the disease.

Study design

A retrospective observational study of 50,712 pregnancies, 925 of which had pre-eclampsia (1999–2010), to examine the association between bilirubin level and perinatal outcome.

Results

In women with pre-eclampsia, those with bilirubin levels in the lowest quintile were more likely to require caesarean section (p = 0.001, aOR 2.59 (1.52–5.72)). The lowest quintile of bilirubin levels is associated with an increased risk of poor maternal (p = 0.002, aOR 3.52 (95%CI 1.6–7.7)) and infant/fetal (p = 0.001, OR = 3.05 (95%CI = 1.63–5.72)) outcome.

Conclusions

Low levels of bilirubin were associated with poor maternal and infant outcomes in women diagnosed with pre-eclampsia. Bilirubin may act as an anti-oxidant in this condition and thus modify the disease.     

Population‐based identity‐by‐descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia

Genome‐wide association studies (GWASs) are highly effective at identifying common risk variants for schizophrenia. Rare risk variants are also important contributors to schizophrenia etiology but, with the exception of large copy number variants, are difficult to detect with GWAS. Exome and genome sequencing, which have accelerated the study of rare variants, are expensive so alternative methods are needed to aid detection of rare variants. Here we re‐analyze an Irish schizophrenia GWAS dataset (n = 3,473) by performing identity‐by‐descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow‐up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.     

Trichomonosis and subsequent risk of prostate cancer in the Prostate Cancer Prevention Trial

We previously observed a positive association between a history of trichomonosis, a sexually transmitted infection caused by the protozoan, Trichomonas vaginalis, and prostate cancer risk in the Health Professionals Follow‐up Study. To determine the reproducibility of this finding, we conducted a second, prospective investigation of trichomonosis and prostate cancer in the Prostate Cancer Prevention Trial. Participants were men (≥55 years of age) with no evidence of prostate cancer at enrollment (n = 18,882). Men were screened annually for prostate cancer, and if not diagnosed during the trial, were offered an end‐of‐study prostate biopsy. Cases were a sample of men diagnosed with prostate cancer on any biopsy after visit 2 or on their end‐of‐study biopsy (n = 616). Controls were men not diagnosed with prostate cancer during the trial or on their end‐of‐study biopsy (n = 616). Controls were frequency‐matched to cases by age, treatment arm, and family history of prostate cancer. Serum from visit 2 was tested for anti‐T. vaginalis IgG antibodies. No association was observed between T. vaginalis serostatus and prostate cancer. 21.5% of cases and 24.8% of controls had low seropositivity, and 15.2% and 15.0% had high seropositivity. Compared to seronegative men, the odds ratio of prostate cancer for men with low seropositivity was 0.83 [95% confidence interval (CI): 0.63–1.09), and that for men with high seropositivity was 0.97 (95% CI: 0.70–1.34). Given the original strong biologic rationale and potential for prevention, additional studies are warranted to help resolve discrepancies between study findings and to further investigate this hypothesis from a variety of different approaches. © 2008 Wiley‐Liss, Inc.