The Patterns of Antipsychotic Use for Pregnant Women Over a 16-year Timeframe in an Australian Principal Referral and Specialist Women and Newborn Hospital.

The purpose of the study is to analyse the patterns of antipsychotic use for pregnant women in an Australian Principal Referral and Specialist Women and Newborn Hospital. This retrospective, observational study involved an analysis of dispensing data of antipsychotics from 1998 to 2014 extracted from the pharmacy dispensing systems. The study included 282 antipsychotic dispensings in the years 1999 to 2006 and 3041 dispensings in the years 2007 to 2014. Second-generation antipsychotic use during pregnancy increased over time, while first-generation-antipsychotics showed declining trend. The use of quetiapine has increased from 2.9% of total antipsychotic dispensings in 2002 up to 77.9% of total antipsychotic dispensings in 2008. Olanzapine use decreased from 78.1% in 2003 to around 20% since 2006. When comparing the age distribution, there was an increased proportion of patients receiving antipsychotics in the 30-39 age range in the second period of 2007 to 2014 compared to 1999 to 2006. The proportion of women on more than one antipsychotic increased from 5% (n = 8) to 9.8% (n = 81) when comparing between 1999 and 2006 and between 2007 and 2014. Our findings indicate a significant shift in prescribing patterns over the study period, with the increased use of antipsychotics, particularly the emergence of SGAs from 2007, changing trends in the use of specific medications as published findings on their safety profiles becomes evident, and more polypharmacy prescribing.

Dominant negative ATM mutations in breast cancer families.

BACKGROUND: The ATM gene encoding a putative protein kinase is mutated in ataxia-telangiectasia (A-T), an autosomal recessive disorder with a predisposition for cancer. Studies of A-T families suggest that female heterozygotes have an increased risk of breast cancer compared with noncarriers. However, neither linkage analyses nor mutation studies have provided supporting evidence for a role of ATM in breast cancer predisposition. Nevertheless, two recurrent ATM mutations, T7271G and IVS10-6T-->G, reportedly increase the risk of breast cancer. We examined these two ATM mutations in a population-based, case-control series of breast cancer families and multiple-case breast cancer families. METHODS: Five hundred twenty-five or 262 case patients with breast cancer and 381 or 68 control subjects, respectively, were genotyped for the T7271G and IVS10-6T-->G ATM mutations, as were index patients from 76 non-BRCA1/2 multiple-case breast cancer families. Linkage and penetrance were analyzed. ATM protein expression and kinase activity were analyzed in lymphoblastoid cell lines from mutation carriers. All statistical tests were two-sided. RESULTS: In case and control subjects unselected for family history of breast cancer, one case patient had the T7271G mutation, and none had the IVS10-6T-->G mutation. In three multiple-case families, one of these two mutations segregated with breast cancer. The estimated average penetrance of the mutations was 60% (95% confidence interval [CI] = 32% to 90%) to age 70 years, equivalent to a 15.7-fold (95% CI = 6.4-fold to 38.0-fold) increased relative risk compared with that of the general population. Expression and activity analyses of ATM in heterozygous cell lines indicated that both mutations are dominant negative. CONCLUSION: At least two ATM mutations are associated with a sufficiently high risk of breast cancer to be found in multiple-case breast cancer families. Full mutation analysis of the ATM gene in such families could help clarify the role of ATM in breast cancer susceptibility.