Gynaecology Flashcards
What was the aim of the JAMA Ovarian Ca Screening study 2011?
To evaluate the effect of screening for ovarian cancer mortality in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO)
What type of study was the JAMA 2011 Ovarian Ca Screening study?
Multicentre (USA), unblinded, RCT
What was the inclusion criteria of the JAMA 2011 Ovarian Ca Screening study?
Women aged 55y to 74y with no prior lung/ovarian/colorectal cancer
What was the intervention and comparision in the JAMA 2011 Ovarian Ca Screening study?
Intervention - Annual screening with Ca125 for 6y (abnormal >35) and TVUSS for 4y
Comparison - usual care
What were the primary and secondary outcomes the in the 2011 JAMA Ovarian Ca Screening study?
Primary - Mortality from ovarian, primary peritoneal and fallopian tube cancers
Secondary - ovarian Ca incidence, cancer stage, survival, potential harms of screening, all cause mortality
What were the main findings of the 2011 JAMA Ovarian Ca Screening study?
No difference in ovarian cancer mortality, all cause mortality, diagnosis or stage
Increase in harm from screening
- 5% of women had false positives and of those that went on to have surgeries, 15% had complications
- PPV of Ca125 + TVUSS is only 23% and only 60% of cancers detected on screening
JAMA 2011 Ovarian Ca Screening Study conclusion?
In women in the general USA population, screening with Ca125 + TVUSS for ovarian cancer did not reduce overall cancer mortality and diagnostic evaluation of false-positive screening tests were associated with complications
JAMA 2011 Ovarian Ca Screening Study - strengths
Very large numbers (68000)
RCT
Clear screening protocol
JAMA 2011 Ovarian Ca Screening Study - weaknesses
Unblinded
Screening used an invasive test (TVUSS)
Minimal contamination
What was the aim of the Scottish pregnancy intervention study: a multicentre RCT of LMWH and low dose aspirin in recurrent miscarriage (SPIN 2010 Blood Journal)?
To assess whether aspirin + LMWH + intensive pregnancy surveillance reduces rates of pregnancy loss compared with intensive pregnancy surveillance alone in women with 2+ consecutive pregnancy losses.
What sort of study was the SPIN study?
Multi-centre (11), multi-country (2) unblinded RCT
What was the inclusion criteria in the SPIN study?
2+ consecutive pregnancy loss <24/40 and presented for antenatal care <7/40
What was the intervention and comparison in the SPIN study?
Intervention - LMWH 40mg SC + aspirin 75mg PO OD until 36/40 with intense pregnancy surveillance
Comparison - intensive pregnancy surveillance
What was the primary outcome in the SPIN trial?
Primary - pregnancy loss
What was the main the main result of the SPIN trial?
No significant difference in rates of pregnancy loss in both groups (~20%)
What was the conclusion of the SPIN trial?
LMWH + aspirin does not reduce the rate of pregnancy loss in women with 2+ prior consecutive miscarriages
SPIN trial - strengths
RCT
SPIN trial - weaknesses
Small numbers (300)
Studied just 2+ previous consecutive miscarriage - did not publish effects on of 3+ previous pregnancy loss
Does not provide use of these medications from pre-conception
What was the aim of the Effect of TLH vs TAH on disease-free survival among women with stage I endometrial cancer (LACE) study?
To investigate whether TLH is equivalent to TAH in women with treatment naive endometrial cancer
What type of study is the LACE study?
Multi-country (3), multi-centre (20), RCT
What was the inclusion criteria of the LACE study?
Women with endometrioid adenocarcinoma without extrauterine disease (stage I) and uterus <8/40 size
What were the interventions in the LACE trial?
TLH vs TAH
What were the primary and secondary outcomes in the LACE trial?
Primary - disease-free survival
Secondary - disease recurrence, patterns of recurrence and overall survival
What were the main findings of the LACE trial?
No statistically significant difference in disease-free survival at 4.5y, overall survival and recurrence rates of endometrial cancer after TLH vs TAH for stage I endometrioid adenocarcinoma
LACE - strengths
RCT
Included Australia and NZ centres - generalisable
Reasonably large numbers (760)
LACE - weaknesses
Unblinded (although unlikely to affect outcomes).
11% loss to follow-up
What was the aim of the Aspirin + Heparin or Aspirin Alone in Women with Recurrent Miscarriage NEJM 2010 study?
To determine whether aspirin + LMWH vs aspirin alone vs placebo improved live birth rates in women with unexplained recurrent miscarriage
What type of study was the NEJM 2010 LMWH/aspirin recurrent miscarriage study?
Multicentre (8 - Netherlands), blinded, RCT
What was the inclusion criteria in the NEJM 2010 LMWH/aspirin recurrent miscarriage study?
Women 18-42y with unexplained recurrent miscarriage (2+ <20/40), attempting to conceive or pregnant <6/40
What were the interventions and comparison in the NEJM 2010 LMWH/aspirin for recurrent miscarriage study?
Interventions:
- Aspirin 80mg/day + LMWH
- Aspirin 80mg/day alone
Comparison:
- Placebo
All from 6/40 until labour.
What were the primary and secondary outcomes int eh NEJM 2010 LMWH/aspirin recurrent miscarriage study?
Primary - rate of live births
Secondary - rates of miscarriage, IUFD (>20/40) and obstetric complications e.g. PET, HELLP, SGA, abruption, PTB
What were the main findings of the NEJM 2010 LMWH/aspirin recurrent miscarriage study?
No significant difference in live birth rates in all 3 groups.
Those receiving combination therapy delivered 1 week earlier than placebo.
What was the conclusion of the NEJM 2010 LMWH/aspirin recurrent miscarriage study?
Neither aspirin nor combined aspirin/LMWH improved live birth rates in women with unexplained miscarriage
NEJM 2010 LMWH/aspirin recurrent miscarriage study - strengths
RCT
NEJM 2010 LMWH/aspirin recurrent miscarriage study - weaknesses
Netherlands only centres - ?generalisable
Not blinded to clexane use
Small numbers (360)
Looked at 2+ miscarriage and did not publish data for 3+
Trial discontinued with 22 still in follow-up
What was the aim of the Breast cancer and HRT in the Million Women study? (Lancet 2003)
To investigate the effects of specific types of HRT on incident and fetal breast cancer
What type of study was the Million Women study?
Prospective cohort study of 1 million women
What was the inclusion criteria of the Million Women study?
Women 50-64y recruited at the time of triennial breast screening
What were the exposures in the Million Women study?
- MHT use and type
- Menopausal status
- Baseline demographic factors
What were the main findings in the Million Women study?
Statistically significant increase in breast cancer incidence (RR 1.66) and deaths (RR 1.22) in current MHT users
Statistically significant increase in breast cancer incidence in
- Combined MHT - RR 2.0
- Oestrogen only MHT - RR 1.3
- Tibolone - RR 1.45
Breast cancer deaths increased in risk with duration of use.
Increase in breast cancer incidence and deaths not seen in past users.
Endometrial cancers reduced in combined MHT users.
Million Women study conclusion?
Current MHT use associated with increased risk if incident and fatal breast cancer, with the effect substantially greater in combined MHT
Million Women study - strengths
Very large numbers
Long follow-up
Million Women study - weaknesses
Poor design
Previous estradiol use included in never used group
Average age 55.9y - higher than the average age of women taking HRT
Selection bias (only women that present for screening)
- More likely to use MHT and higher SES
What was the aim of the Ovarian Conservation at the Time of Hysterectomy for Benign Disease study? O&G 2005
To establish the optimum age at which prophylactic oophorectomy should be recommended for women at average risk of ovarian cancer
What sort of study was the O&G 2005 Ovarian Conservation study?
Prospective observation trial using a Markov decision analytic model to estimate optimal survival strategy per 9 years
What were the exposures in the O&G 2005 Ovarian Conservation study?
- Ovarian conservation +/- oestrogen therapy
- Oophorectomy +/- oestrogen therapy
What was the inclusion criteria in the O&G 2005 Ovarian Conservation study?
Healthy women 40-80y who had hysterectomy for benign disease with published data from 1990
What were the primary outcomes studied in the O&G 2005 Ovarian Conservation study?
Survival to 80 years
Ovarian cancer
Coronary heart disease
Hip fracture
Breast cancer
Stroke
What were the main findings from the 2005 Ovarian Conservation study?
Ovarian conservation until age 65y benefits overall survival
- BSO <55y - 8.6% excess mortality by 80y
- BSO <59y - 4% excess mortality
Oestrogen replacement reduces the risk of mortality from CHD and hip fracture in women with oophorectomy
What was the conclusion of the 2005 Ovarian Conservation study?
Ovarian conservation until at least 65y benefits long term survival for women at average risk of ovarian cancer when undergoing hysterectomy for benign disease
2005 O&G Ovarian Conservation study - strengths
Large numbers
2005 O&G Ovarian Conservation study - weaknesses
Probability estimates are derived mostly from case-controls studies - inherent possibility of selection bias, chance and reporting bias
Most women in studies caucasian 0 limited generalisability
Insufficient date on QoL
Definition of “average risk” of ovarian cancer was not provided
What was the aim of the WHI combined MHT RCT? (JAMA 2002)
To assess the major health benefits and risks of oestrogen and progesterone in healthy post-menopausal women
What type of study was the Risks and Benefits of Estrogen + Progestin in Healthy Postmenopausal Women (WHI) study? (JAMA 2002)
Multicentre (40, USA), placebo-controlled, RCT
What was the inclusion criteria or the WHI combined MHT RCT?
Healthy postmenopausal women aged 50-79y with intact uterus
What was the intervention and comparison in the WHI combined MHT RCT?
Intervention - Combined MHT in 1 daily tablet with 0.625mg conjugated equine estrogen and 2.5mg MPA
Comparison - matching placebo
What were the primary outcomes in the WHI combined MHT RCT?
Coronary heart disease (MI or CHD death)
Invasive breast cancer
What were the secondary outcomes of the WHI combined MHT RCT?
Global index of risks and benefits
- 2 primary outcomes plus stroke, PE, endometrial Ca, CRC, hip #, death due to other causes
What were the main findings of the WHI combined MHT RCT?
Overall significant increase in primary outcomes
- CHD +7/10,000 women years
- Breast cancer +8/10,000 women years (significant after 5y use)
Overall extra 19 risk events/10,000 women years
- Increase in stroke and PE
- Reduction in CRC and hip #
What was the conclusion of the WHI combined MHT study?
Overall risks exceeded benefits from use of combined oral MHT for an average of 5.2y follow-up
WHI combined MHT RCT - strengths
Large numbers (16000)
6y follow-up
WHI combined MHT RCT - weaknesses
Majority of study population age 60-69y - not reflective of population most likely to use MHT (50s)
Only tests 1x drug regimen (oral combined)
- data may not apply to transdermal/intrauterine formulations
42% discontinuation in active treatment arm and 10% cross over from placebo to active arm
No appropriate screening for co-morbidities
What was the aim of the NEJM 2014 LARC teenage pregnancy study?
To assess whether removal of barriers to LARC (information lack, limited access, cost) reduces unintended pregnancy and birth rates among high-risk, sexually active teens.
What type of study was the Provision of No-cost LARC and Teenage Pregnancy Study? (NEJM 2014)
Prospective cohort study
What was the inclusion criteria in the LARC teen pregnancy NEJM 2014 study?
Adolescents 14-19y enrolled in the Contraceptive CHOICE project (counselling and free LARC or other contraceptive)
LARC teen pregnancy NEJM 2014 study primary outcomes?
Rates of pregnancy, live birth and abortion at age 15-19y
What were the main findings of the NEJM 2014 LARC teen pregnancy study?
Significant reduction in pregnancy, live birth and abortion rates in teens enrolled in CHOICE
- Pregnancy 34 vs 158 per 1000
- Live birth 19 vs 94 per 1000
- Abortion 10 vs 41 per 1000
NEJM 2014 LARC teen pregnancy study conclusion?
Teenage girls/women who were provided contraception at no cost and educated about reversible contraception and the benefits of LARC had much lower rates of pregnancy, birth and abortion
NEJM LARC teen pregnancy study - strengths
Large numbers (1400)
Baseline characteristics of study population similar to source population
NEJM LARC teen pregnancy study - weaknesses
USA - ?generalisability
Outcomes were self reported - possible bias
Teens surveyed regularly about contraceptive use - ?affected compliance
What was the aim of the 2004 JAMA WHI oestrogen for PM women with hysterectomy study?
To assess the effects of oestrogen MHT after hysterectomy on major disease incidence in healthy postmenopausal women
What sort of study was the WHI: Effects of Conjugated Equine Estrogen in Postmenopausal Women with Hysterectomy?
Double-blinded placebo-controlled RCT
What was the inclusion criteria of the WHI oestrogen hysterectomy trial?
Healthy postmenopausal 50-79 who had undergone hysterectomy
What was the intervention and comparison in the WHI oestrogen hysterectomy trial?
Intervention - 0.625mg/day conjugated equine oestrogen
Comparison - matching placebo
What were the primary outcomes of the WHI oestrogen hysterectomy trial?
Coronary heart disease (MI or CHD death)
Invasive breast cancer
What were the secondary outcomes of the WHI oestrogen hysterectomy trial?
Global index of risks and benefits
- 2 primary outcomes plus stroke, PE, endometrial Ca, CRC, hip #, death due to other causes
What were the main findings of the WHI oestrogen hysterectomy trial?
No significant difference in the primary outcomes (breast cancer, CHD)
No significant difference in overall global index
Significant increase in stroke (+12 per 10,000 women years and DVT
Significant decrease in hip fracture (-6 per 10,000 women years)
What was the conclusion of the WHI oestrogen hysterectomy study?
Conjugated equine estrogen did not change the risk of CHD or breast cancer or mortality, but did reduce fracture risk and increase stroke/DVT risk
WHI oestrogen hysterectomy study - strengths
RCT
Large numbers (10,000)
WHI oestrogen hysterectomy study - weaknesses
Tested only oral conjugated equine estrogen, did not test other types/preparations e.g. transdermal
High rates of discontinuation of study medications and crossover (Only 53% adherence to study protocol)
- can dilute effects
Study terminated early due to breast and CHD risk with combined MHT
Average age was 63y - higher than usual age of MHT use
What was the aim of the NEJM 2005 medical vs surgical management for early pregnancy failure study?
To evaluate the safety, efficacy and acceptability of medical management of early pregnancy failure with misoprostol vs surgical management
What type of study was A Comparison of Medical Management with Misoprostol and Surgical Management for Early Pregnancy Failure NEJM 2005?
Multi-centre (6), unblinded RCT
What was the inclusion criteria of the 2005 NEJM medical vs surgical miscarriage study?
Early pregnancy loss
- Anembryonic gestation MSD 16-45mm
- Missed miscarriage CRL 5-40mm no FHR
- GS growth <2mm over 5d, <3mm over 7d
- Rise of HCG <15% of 2d with yolk sac seen
- Incomplete miscarriage >30mm RPOC
- Inevitable miscarriage <45mm GS, <40mm CRL
What were the intervention and comparison in the 2005 NEJM medical vs surgical miscarriage study?
Intervention - 800mcg PV misoprostol, second dose if no POC passed by day 3
Comparison - MVAC
What was the primary outcome of the 2005 NEJM medical vs surgical miscarriage study?
Treatment failure = MVAC within 30 days for unsuccessful firstline treatment
What were the secondary outcomes in the 2005 NEJM medical vs surgical miscarriage study?
Adverse outcomes (e.g. fever, ED visit, haemorrhage, Hb drop, endometritis, N or V, diarrhoea, abdo pain, pain score) and acceptability
What were the main findings of the 2005 NEJM medical vs surgical miscarriage study?
Statistically significant higher rates of treatment failure in misoprostol group 16% vs 3%
Miso
- 70% expulsion by day 3
- 84% expulsion by day 8
- more pain, nausea, vomiting, diarrhoea
- Lower success in anembryonic pregnancy
No difference in:
- pelvic infection
- haemorrhage
- ED visits <24h
What was the conclusion of the 2005 NEJM medical vs surgical miscarriage study?
Treatment of early miscarriage with 800mcg PV misoprostol and safe and acceptable with 84% success rate
2005 NEJM medical vs surgical miscarriage study -strengths
RCT, high powered
Strict inclusion criteria and well defined end points
Low loss to follow-up
2005 NEJM medical vs surgical miscarriage study - weaknesses
Small numbers (600)
Unblinded
Heterogenous group of miscarriage type
4 centres in one country ?generalisable
