Using a decline in serum hCG between days 0-4 to predict ectopic pregnancy treatment success after single-dose methotrexate:a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>The current measure of treatment efficacy of single-dose methotrexate for ectopic pregnancy, is a fall in serum hCG of ≥15% between days 4–7 of treatment, which has a positive predictive value of 93% for treatment success. Two small studies have proposed a fall in serum hCG between days 0–4 after treatment confers similar, earlier prognostic information, with positive predictive values of 100% and 88% for treatment success. We sought to validate this in a large, independent cohort because of the potentially significant clinical implications.</p> <p>Methods</p> <p>We conducted a retrospective study of women (n=206) treated with single-dose methotrexate for ectopic pregnancy (pre-treatment serum hCG levels ≤3000 IU/L) at Scottish hospitals between 2006–2011. Women were divided into two cohorts based on whether their serum hCG levels rose or fell between days 0–4 after methotrexate. Treatment outcomes of women in each cohort were compared, and the test performance characteristics calculated. This methodology was repeated for the current measure (≥15% fall in serum hCG between days 4–7 of treatment) and an alternate early measure (<20% fall in serum hCG between days 0–4 of treatment), and all three measures were compared for their ability to predict medical treatment success.</p> <p>Results</p> <p>In our cohort, the positive predictive value of the current clinical measure was 89% (95% CI 84-94%) (121/136). A falling serum hCG between days 0–4 predicted treatment success in 85% (95% CI 79-92%) of cases (94/110) and a <20% fall in serum hCG between days 0–4 predicted treatment success in 94% (95% CI 88-100%) of cases (59/63). There was no significant difference in the ability of these tests to predict medical treatment success.</p> <p>Conclusions</p> <p>We have verified that a decline in serum hCG between days 0–4 after methotrexate treatment for ectopic pregnancies, with pre-treatment serum hCG levels ≤3000 IU/L, provides an early indication of likelihood of treatment success, and performs just as well as the existing measure, which only provides prognostic information on day 7.</p

A multi-centre, double-blind, placebo-controlled, randomised trial of combination methotrexate and gefitinib versus methotrexate alone to treat tubal ectopic pregnancies (GEM3): trial protocol

Background Tubal ectopic pregnancy (tEP) is the most common life-threatening condition in gynaecology. Treatment options include surgery and medical management. Stable women with tEPs with pre-treatment serum human chorionic gonadotrophin (hCG) levels  1000 IU/L can take significant time to resolve with methotrexate and require multiple outpatient monitoring visits. In pre-clinical studies, we found that tEP implantation sites express high levels of epidermal growth factor receptor. In early-phase trials, we found that combination therapy with gefitinib, an orally active epidermal growth factor receptor antagonist, and methotrexate resolved tEPs without the need for surgery in over 70% of cases, did not cause significant toxicities, and was well tolerated. We describe the protocol of a randomised trial to assess the efficacy of combination gefitinib and methotrexate, versus methotrexate alone, in reducing the need for surgical intervention for tEPs. Methods and analysis We propose to undertake a multi-centre, double-blind, placebo-controlled, randomised trial (around 70 sites across the UK) and recruit 328 women with tEPs (with pre-treatment serum hCG of 1000–5000 IU/L). Women will be randomised in a 1:1 ratio by a secure online system to receive a single dose of intramuscular methotrexate (50 mg/m2) and either oral gefitinib or matched placebo (250 mg) daily for 7 days. Participants and healthcare providers will remain blinded to treatment allocation throughout the trial. The primary outcome is the need for surgical intervention for tEP. Secondary outcomes are the need for further methotrexate treatment, time to resolution of the tEP (serum hCG ≤ 15 IU/L), number of hospital visits associated with treatment (until resolution or scheduled/emergency surgery), and the return of menses by 3 months after resolution. We will also assess adverse events and reactions until day of resolution or surgery, and participant-reported acceptability at 3 months. Discussion A medical intervention that reduces the need for surgery and resolves tEP faster would be a favourable treatment alternative. If effective, we believe that gefitinib and methotrexate could become standard care for stable tEPs

Fractional CO2 laser for treatment of stress urinary incontinence.

Objectives: To evaluate the impact of trans-vaginal fractional CO2 laser treatment on symptoms of stress urinary incontinence (SUI) in women. Study design: Women clinically diagnosed with SUI preferring non-surgical treatment were recruited to the study. Fractional CO2 laser system (MonaLisa T, DEKA) treatments were administered trans-vaginally every 4-6 weeks for a total of three treatments. Response to treatment was assessed at baseline (T1), at 3 months after treatment completion (T2) and at 12-24-month follow-up (T3) using the Australian Pelvic Floor Questionnaire (APFQ). The primary outcome was changes in reported symptoms of SUI. Secondary outcomes assessed included bladder function, urgency, urge urinary incontinence (UUI), pad usage, impact of urinary incontinence on quality of life (QOL) and degree of bothersome bladder. Results: Fifty-eight women were recruited and received the study treatment protocol. Eighty-two percent of participants reported an improvement in symptoms of SUI at completion of treatment (mild to no SUI) (p = <0.01). Treatment effect waned slightly when assessed at follow-up. Nevertheless, 71% of participants reported ongoing improvement in SUI symptoms at 12-24 months (p < 0.01). All secondary outcome measures were improved after treatment compared to baseline. Conclusions: This study suggests that fractional CO2 laser is a safe, feasible, and beneficial treatment for SUI and may have a role as a minimally-invasive alternative to surgical management

The health and educational costs of preterm birth to 18 years of age in Australia

Background Preterm birth is the greatest cause of death up to five years of age and an important contributor to lifelong disability. There is increasing evidence that a meaningful proportion of early births may be prevented, but widespread introduction of effective preventive strategies will require financial support. Aims This study estimated the economic cost to the Australian government of preterm birth, up to 18 years of age. Materials and Methods A decision-analytic model was developed to estimate the costs of preterm birth in Australia for a hypothetical cohort of 314 814 children, the number of live births in 2016. Costs to Australia’s eight jurisdictions included medical expenditures and additional costs to educational services. Results The total cost of preterm birth to the Australian government associated with the annual cohort was estimated at $1.413 billion (95% CI 1047‒1781). Two-thirds of the costs were borne by healthcare services during the newborn period and one-quarter of the costs by educational services providing special assistance. For each child, the costs were highest for those born at the earliest survivable gestational age, but the larger numbers of children born at later gestational ages contributed heavily to the overall economic burden. Conclusion Preterm birth leaves many people with lifelong disabilities and generates a significant economic burden to society. The costs extend beyond those to the healthcare system and include additional educational needs. Assessments of economic costs should inform economic evaluations of interventions aimed at the prevention or treatment of preterm birth