Penicillin Allergy De-labeling Results in Significant Changes in Outpatient Antibiotic Prescribing Patterns.

Unverified penicillin allergies are common but most patients with a penicillin allergy label can safely use penicillin antibiotics. Penicillin allergy labels are associated with poor clinical outcomes and overuse of second-line antibiotics. There is increasing focus on penicillin allergy "de-labeling" as a tool to improve antibiotic prescribing and antimicrobial stewardship. The effect of outpatient penicillin allergy de-labeling on long-term antibiotic use is uncertain. We performed a retrospective pre- and post- study of antibiotic dispensing patterns, from an electronic dispensing data repository, in patients undergoing penicillin allergy assessment at Auckland City Hospital, New Zealand. Over a mean follow-up of 4.55 years, 215/304 (70.7%) of de-labeled patients were dispensed a penicillin antibiotic. Rates of penicillin antibiotic dispensing were 0.24 (0.18-0.30) penicillin courses per year before de-labeling and 0.80 (0.67-0.93) following de-labeling with a reduction in total antibiotic use from 2.30 (2.06-2.54) to 1.79 (1.59-1.99) antibiotic courses per year. In de-labeled patients, the proportion of antibiotic courses that were penicillin antibiotics increased from 12.81 to 39.62%. Rates of macrolide, cephalosporin, trimethoprim/co-trimoxazole, fluoroquinolone, "other" non-penicillin antibiotic use, and broad-spectrum antibiotic use were all lower following de-labeling. Further, antibiotic costs were lower following de-labeling. In this study, penicillin allergy de-labeling was associated with significant changes in antibiotic dispensing patterns.

Intrauterine insemination with ovarian stimulation versus expectant management for unexplained infertility (TUI): a pragmatic, open-label, randomised, controlled, two-centre trial.

BACKGROUND: Women with unexplained infertility are often offered intrauterine insemination (IUI) with ovarian stimulation as an alternative to in-vitro fertilisation (IVF). However, little evidence exists that IUI is an effective treatment. In 2013, the UK National Institute for Health and Care Excellence recommended that IUI should not be routinely offered for couples with unexplained infertility. METHODS: For this pragmatic, open-label, randomised, controlled, two-centre study, we enrolled women attending two fertility clinics in New Zealand with unexplained infertility and an unfavourable prognosis of natural conception. Participants were randomly assigned (1:1) using a computer-generated randomisation sequence, prepared by an independent statistician, to either three cycles of IUI with ovarian stimulation (with either oral clomifene citrate [50-150 mg, days 2-6] or oral letrozole [2·5-7·5 mg, days 2-6], with choice of ovarian stimulation made by the clinic) or three cycles of expectant management (couples advised to be sexually active around the likely time of ovulation and provided with a diary to record the first day of each menstrual cycle and dates of sexual activity) in blocks of four, six, and ten, without stratification. The participating couple and the clinicians were informed of treatment allocation. The primary outcome was cumulative livebirth rate in the intention-to-treat population. The safety analyses were done in the intention-to-treat population. This study was prospectively registered with the Australian and New Zealand Clinical Trials Register, number ACTRN12612001025820. FINDINGS: Between March 12, 2013, and May 12, 2016, we randomly assigned 101 women to IUI with ovarian stimulation and 100 to expectant management, all of whom were included in the primary efficacy analysis and safety analyses. Women assigned to IUI had a higher cumulative livebirth rate than women assigned to expectant management (31 [31%] livebirths among 101 women vs nine [9%] livebirths among 100 women; risk ratio [RR] 3·41, 95% CI 1·71-6·79; p=0·0003). Of 31 livebirths in the IUI group, 23 resulted from IUI cycles and eight were conceived without assistance before or between IUI cycles. Of nine livebirths in the expectant management group, one patient was pregnant from IUI with ovarian stimulation at study entry and one had received off-protocol treatment (IVF). Two sets of twins were born, both in the IUI group (one from a cancelled cycle for over-response). INTERPRETATION: IUI with ovarian stimulation is a safe and effective treatment for women with unexplained infertility and an unfavourable prognosis for natural conception. FUNDING: Auckland Medical Research Foundation, Evelyn Bond Fund of Auckland District Health Board, Mercia Barnes Trust of Royal Australian and New Zealand College of Obstetricians and Gynaecologists, Maurice and Phyllis Paykel Trust, and The Nurture Foundation for Reproductive Research.

Time-lapse systems for embryo incubation and assessment in assisted reproduction.

BACKGROUND: Embryo incubation and assessment is a vital step in assisted reproductive technology (ART). Traditionally, embryo assessment has been achieved by removing embryos from a conventional incubator daily for assessment of quality by an embryologist, under a light microscope. Over recent years time-lapse systems (TLSs) have been developed which can take digital images of embryos at frequent time intervals. This allows embryologists, with or without the assistance of computer algorithms, to assess the quality of the embryos without physically removing them from the incubator.The potential advantages of a TLS include the ability to maintain a stable culture environment, therefore limiting the exposure of embryos to changes in gas composition, temperature and movement. Additionally a TLS has the potential advantage of improving embryo selection for ART treatment by utilising additional information gained through monitoring embryo development. OBJECTIVES: To determine the effect of a TLS compared to conventional embryo incubation and assessment on clinical outcomes in couples undergoing ART. SEARCH METHODS: A comprehensive search of all the major electronic databases, including grey literature, was undertaken in co-ordination with the Trials Search Co-ordinator of the Cochrane Menstrual Disorders and Subfertility Group in July 2014 and repeated in November 2014 to confirm that the review is up to date. SELECTION CRITERIA: Two authors (SA and NA) independently scanned the titles and abstracts of the articles retrieved by the search. Full texts of potentially eligible randomised controlled trials (RCTs) were obtained and examined independently by the authors for their suitability according to the review inclusion criteria. In the case of doubt between the two authors, a third author (LC) was consulted to gain consensus. The selection process is documented with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart. DATA COLLECTION AND ANALYSIS: Data were obtained and extracted by two authors. Disagreement was resolved by consensus. Trial authors were contacted by e-mail to obtain further study information and data. All extracted data were dichotomous outcomes and odds ratios (OR) were calculated on an intention-to-treat basis. Where enough data were available, meta-analysis was undertaken. MAIN RESULTS: Three studies involving 994 women were found for inclusion. Data from all three studies were used to address comparison one, TLS with or without cell-tracking algorithms versus conventional incubation. No studies were found to address comparison two, TLS utilising cell-tracking algorithms versus TLS not utilising cell-tracking algorithms.There was only one study which reported live birth (n = 76). The results demonstrated no conclusive evidence of a difference in live birth rate per couple randomly assigned to the TLS and conventional incubation arms of the study (OR 1.1, 95% CI 0.45 to 2.73, 1 RCT, n = 76, moderate quality evidence).All three studies reported miscarriage (n = 994). There was no conclusive evidence of a difference in miscarriage rates per couple randomly assigned to the TLS and conventional incubation arms (OR 0.70, 95% CI 0.47 to 1.04, 3 RCTs, n = 994, I(2) = 0%, low quality evidence).Only one study reported stillbirth rates (n = 76). There were equal numbers of stillbirths in both the TLS and conventional incubation arms of the study. Therefore, there was no evidence of a difference in the stillbirth rate per couple randomly assigned to TLS and conventional incubation (OR 1.0, 95% CI 0.13 to 7.49, 1 RCT, moderate quality evidence).All three studies reported clinical pregnancy rates (n = 994). There was no conclusive evidence of a difference in clinical pregnancy rate per couple randomly assigned to the TLS and conventional incubation arms (OR 1.23, 95% CI 0.96 to 1.59, 3 RCTs, n = 994, I(2) = 0%, low quality evidence). None of the included studies reported cumulative clinical pregnancy rates. AUTHORS' CONCLUSIONS: There is insufficient evidence of differences in live birth, miscarriage, stillbirth or clinical pregnancy to choose between TLS and conventional incubation. Further data explicitly comparing the incubation environment, the algorithm for embryo selection, or both, are required before recommendations for a change of routine practice can be justified.

Can we improve the prevention and detection of congenital abnormalities? An audit of early pregnancy care in New Zealand.

AIM: To determine whether there were "quality gaps" in the provision of care during pregnancies that resulted in a perinatal death due to congenital abnormality. METHOD: Perinatal deaths from congenital cardiovascular, central nervous system or chromosomal abnormality in 2010 were identified retrospectively. Data were extracted by retrospective clinical note review and obtained by independent review of ultrasound scans. RESULTS: There were 137 perinatal deaths due to a congenital cardiovascular (35), central nervous system (29) or chromosomal abnormality (73). First contact with a health professional during pregnancy was predominantly with a general practitioner. First contact occurred within 14 weeks in 85% of pregnancies and there was often a significant delay before booking. Folate supplements were taken by 7% pre-conceptually and 54% of women in the antenatal period. There were 20 perinatal deaths from neural tube defects that could potentially have been prevented through the use of pre-conceptual folate. Antenatal screening was offered to 75% of the women who presented prior to 20 weeks and 84% of these undertook at least one of the available antenatal screening tests. Review of ultrasound images found five abnormalities could have been detected earlier. CONCLUSION: Delay in booking or failure to offer screening early were the most common reasons for delay in diagnosis of screen detectable abnormalities. The preventative value and timing of (pre-conceptual) folate needs emphasis.