Clinical consultations and investigations before and after discontinuation of endocrine therapy in women with primary breast cancer

Objective: Although clinical trials recommend that women with hormone-dependent primary breast cancer remain on endocrine therapy for at least 5 years, up to 60% discontinue treatment early. We determined whether these women had consulted with clinicians or had investigations for cancer recurrence or metastasis around the time they discontinued endocrine therapy, and whether clinical contact continued after discontinuation. Methods: We performed case-control and cohort studies of women from the 45 and Up Study who were diagnosed with invasive primary breast cancer between January 2003 and December 2008, and who had ≥12 months of anastrozole, exemestane, letrozole or tamoxifen subsequently dispensed. Results: Women who consulted general practitioners and surgeons/oncologists, and women who had breast ultrasound/mammogram were just as likely to discontinue endocrine therapy within 30 days as those who did not consult these clinicians or have this investigation. In the 6 months after early discontinuation, women who discontinued endocrine therapy were less likely to consult general practitioners (adjusted risk ratio [RRadj] 0.80; 95% confidence interval [CI] 0.75, 0.86) and surgeons/oncologists (RRadj 0.62; 95% CI 0.54, 0.72) than those who remained on therapy. Conclusions: For most women, endocrine therapy discontinuation did not appear to follow consultation with doctors managing their breast cancer treatment or investigations for recurrence or metastasis. However, women who discontinued endocrine therapy were less likely to consult their general practitioner or surgeon/oncologist in the 6 months following discontinuation than those who remained on therapy. Of the clinician groups studied, general practitioners are best placed to engage and support women to continue pharmacotherapy. However, mechanisms are needed to prompt clinicians to do this at every visit

Tobacco policy reform and population-wide antismoking activities in Australia: the impact on smoking during pregnancy

Publisher's version (útgefin grein)Introduction This study examined the impact of antismoking activities targeting the general population and an advertising campaign targeting smoking during pregnancy on the prevalence of smoking during pregnancy in New South Wales (NSW), Australia. Methods Monthly prevalence of smoking during pregnancy was calculated using linked health records for all pregnancies resulting in a birth (800 619) in NSW from 2003 to 2011. Segmented regression of interrupted time series data assessed the effects of the extension of the ban on smoking in enclosed public places to include licensed premises (evaluated in combination with the mandating of graphic warnings on cigarette packs), television advertisements targeting smoking in the general population, print and online magazine advertisements targeting smoking during pregnancy and increased tobacco tax. Analyses were conducted for all pregnancies, and for the population stratified by maternal age, parity and socioeconomic status. Further analyses adjusted for the effect of the Baby Bonus maternity payment. Results Prevalence of smoking during pregnancy decreased from 2003 to 2011 overall (0.39% per month), and for all strata examined. For pregnancies overall, none of the evaluated initiatives was associated with a change in the trend of smoking during pregnancy. Significant changes associated with increased tobacco tax and the extension of the smoking ban (in combination with graphic warnings) were found in some strata. Conclusions The declining prevalence of smoking during pregnancy between 2003 and 2011, while encouraging, does not appear to be directly related to general population antismoking activities or a pregnancy-specific campaign undertaken in this period.This research was supported by an Australian National Health and Medical Research Council Project Grant (#1028543) and AH is supported by a National Heart Foundation Future Leader Fellowship (#100411). The funders had no involvement in the study design; the collection, analysis or interpretation of the data; in the writing of the report or the decision to submit the report for publication.Peer Reviewe

Pioglitazone use in Australia and the United Kingdom following drug safety advisories on bladder cancer risk: An interrupted time series study

Purpose: National regulators in Australia and the United Kingdom issued safety advisories on the association between pioglitazone use and bladder cancer in July 2011. The Australian advisory noted that males were at higher risk of bladder cancer than females, while the UK advisory highlighted a new recommendation, suggest careful consideration in the elderly due to increasing risk with age. This study examined whether these differences in the advisories had different age- and sex-based impacts in each country. Methods: Interrupted time series analysis was used to compare pioglitazone use (prescriptions/100000 population) in Australia and the United Kingdom for the 24 months before and 11 months after the July 2011 safety advisories (study period July 2009–June 2012). Separate models were used to compare use by sex and age group (≥65 years vs. <65 years) in each country. Results: Pioglitazone use fell in Australia (17%) and the United Kingdom (24%) following the safety advisories. Use of pioglitazone fell more for males (18%) than females (16%) in Australia, and more for females (25%) than males (23%) in the United Kingdom; however, neither difference was statistically significant (Australia p = 0.445, United Kingdom p = 0.462). Pioglitazone use fell to a similar extent among older people than younger people in the United Kingdom (23% vs. 26%, p = 0.354), and did not differ between age groups in Australia (both 18%, p = 0.772). Conclusions: The results indicate that differences in the Australian and UK safety advisories resulted in substantial reductions in pioglitazone use at the population level in both countries, however, differences by sub-groups were not observed

Discovery of s-process enhanced stars in the LAMOST survey

Here we present the discovery of 895 s-process-rich candidates from 454 180 giant stars observed by the Large Sky Area Multi-Object Fibre Spectroscopic Telescope (LAMOST) using a data-driven approach. This sample constitutes the largest number of s-process enhanced stars ever discovered. Our sample includes 187 s-process-rich candidates that are enhanced in both barium and strontium, 49 stars with significant barium enhancement only and 659 stars that show only a strontium enhancement. Most of the stars in our sample are in the range of effective temperature and log g typical of red giant branch (RGB) populations, which is consistent with our observational selection bias towards finding RGB stars. We estimate that only a small fraction (∼0.5 per cent) of binary configurations are favourable for s-process enriched stars. The majority of our s-process-rich candidates (95 per cent) show strong carbon enhancements, whereas only five candidates (<3  per cent) show evidence of sodium enhancement. Our kinematic analysis reveals that 97 per cent of our sample are disc stars, with the other 3 per cent showing velocities consistent with the Galactic halo. The scaleheight of the disc is estimated to be z_h = 0.634±0.063kpc⁠, comparable with values in the literature. A comparison with yields from asymptotic giant branch (AGB) models suggests that the main neutron source responsible for the Ba and Sr enhancements is the ¹³C(α,n)¹⁶O reaction. We conclude that s-process-rich candidates may have received their overabundances via mass transfer from a previous AGB companion with an initial mass in the range 1−3M_⊙

On the discovery of K-enhanced and possibly Mg-depleted stars throughout the Milky Way

Stars with unusual elemental abundances offer clues about rare astrophysical events or nucleosynthetic pathways. Stars with significantly depleted magnesium and enhanced potassium ([Mg/Fe] 1) have to date only been found in the massive globular cluster NGC 2419 and, to a lesser extent, NGC 2808. The origin of this abundance signature remains unknown, as does the reason for its apparent exclusivity to these two globular clusters. Here we present 112 field stars, identified from 454 180 LAMOST giants, that show significantly enhanced [K/Fe] and possibly depleted [Mg/Fe] abundance ratios. Our sample spans a wide range of metallicities (−1.5 < [Fe/H] < 0.3), yet none show abundance ratios of [K/Fe] or [Mg/Fe] that are as extreme as those observed in NGC 2419. If confirmed, the identified sample of stars represents evidence that the nucleosynthetic process producing the anomalous abundances ratios of [K/Fe] and [Mg/Fe] probably occurs at a wide range of metallicities. This would suggest that pollution scenarios that are limited to early epochs (such as Population III supernovae) are an unlikely explanation, although they cannot be ruled out entirely. This sample is expected to help guide modelling attempts to explain the origin of the Mg–K abundance signature

Varenicline is More Effective than Nicotine Replacement Therapy During Pregnancy: Findings from the Smoking MUMS (Maternal Use of Medications and Safety) Study

Introduction Studies in the general population suggest that varenicline is more effective than nicotine replacement therapy (NRT) for smoking cessation. However, clinical guidelines recommend against the use of varenicline during pregnancy and suggest NRT be used when the expected benefits outweigh the potential risks. Objectives and Approach We evaluated whether varenicline was more effective than NRT for smoking cessation when used during pregnancy. Routinely-collected records of all births (01/01/2011-12/31/2012) in New South Wales and Western Australia were used to identify a cohort of women who smoked during the first 20 weeks of pregnancy. Pharmaceutical dispensing data were then linked to identify varenicline or NRT dispensing in the first 20 weeks of pregnancy. Smoking cessation was defined as women reported not smoking after the first 20 weeks of pregnancy. Inverse probability of treatment weighting with propensity scores were used to account for differences between the two treatment groups. Results Overall, 117 women used varenicline and 135 NRT in the first 20 weeks of pregnancy. In the unweighted sample, more women who used varenicline quit smoking after the first 20 weeks than women using NRT (28.2% vs. 11.1%, crude rate difference:17.1%, 95% confidence intervals[CI]:7.4-26.8%). In the weighted sample, quitting rate was 12.7% (95%CI:0.8-24.6%) higher in pregnant smokers who used varenicline (27.4% vs. 14.7%) when compared to those who used NRT. Conclusion/Implications Pregnant smokers using varenicline were more likely to quit smoking than those using NRT. This information will assist healthcare providers to make informed recommendations, but data regarding safety of varenicline in pregnancy are also urgently needed. Future studies with greater statistical power are required to confirm our results

On the discovery of K-enhanced and possibly Mg-depleted stars throughout the Milky Way

Stars with unusual elemental abundances offer clues about rare astrophysical events or nucleosynthetic pathways. Stars with significantly depleted magnesium and enhanced potassium ([Mg/Fe] 1) have to date only been found in the massive globular cluster NGC 2419 and, to a lesser extent, NGC 2808. The origin of this abundance signature remains unknown, as does the reason for its apparent exclusivity to these two globular clusters. Here we present 112 field stars, identified from 454 180 LAMOST giants, that show significantly enhanced [K/Fe] and possibly depleted [Mg/Fe] abundance ratios. Our sample spans a wide range of metallicities (−1.5 < [Fe/H] < 0.3), yet none show abundance ratios of [K/Fe] or [Mg/Fe] that are as extreme as those observed in NGC 2419. If confirmed, the identified sample of stars represents evidence that the nucleosynthetic process producing the anomalous abundances ratios of [K/Fe] and [Mg/Fe] probably occurs at a wide range of metallicities. This would suggest that pollution scenarios that are limited to early epochs (such as Population III supernovae) are an unlikely explanation, although they cannot be ruled out entirely. This sample is expected to help guide modelling attempts to explain the origin of the Mg–K abundance signature

Influence of drug safety advisories on drug utilisation: an international interrupted time series and meta-analysis

OBJECTIVE: To evaluate the association between regulatory drug safety advisories and changes in drug utilisation. DESIGN: We conducted controlled, interrupted times series analyses with administrative prescription claims data to estimate changes in drug utilisation following advisories. We used random-effects meta-analysis with inverse-variance weighting to estimate the average postadvisory change in drug utilisation across advisories. STUDY POPULATION: We included advisories issued in Canada, Denmark, the UK and the USA during 2009-2015, mainly concerning drugs in common use in primary care. We excluded advisories related to over-the-counter drugs, drug-drug interactions, vaccines, drugs used primarily in hospital and advisories with co-interventions within ±6 months. MAIN OUTCOME MEASURES: Change in drug utilisation, defined as actual versus predicted percentage change in the number of prescriptions (for advisories without dose-related advice), or in the number of defined daily doses (for dose-related advisories), per 100 000 population. RESULTS: Among advisories without dose-related advice (n=20), the average change in drug utilisation was -5.83% (95% CI -10.93 to -0.73; p=0.03). Advisories with dose-related advice (n=4) were not associated with a statistically significant change in drug utilisation (-1.93%; 95% CI -17.10 to 13.23; p=0.80). In a post hoc subgroup analysis of advisories without dose-related advice, we observed no statistically significant difference between the change in drug utilisation following advisories with explicit prescribing advice, such as a recommendation to consider the risk of a drug when prescribing, and the change in drug utilisation following advisories without such advice. CONCLUSIONS: Among safety advisories issued on a wide range of drugs during 2009-2015 in 4 countries (Canada, Denmark, the UK and the USA), the association of advisories with changes in drug utilisation was variable, and the average association was modest