Theresa A Lawrie

Adjuvant Radiotherapy for Stage I Endometrial Cancer: An Updated Cochrane Systematic Review and Meta-analysis

BACKGROUND The role of adjuvant radiotherapy in stage I endometrial cancer has changed in recent years. This updated Cochrane systematic review aimed to reexamine the efficacy and toxicity of adjuvant radiotherapy vs no treatment in stage I endometrial cancer. METHODS We searched various databases including The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and the Specialised Register of the Cochrane Gynaecological Cancer Review Group (CGCRG) for randomized controlled trials that met the predefined inclusion criteria. The primary outcome was overall survival (OS); secondary outcomes were endometrial cancer-specific survival, locoregional recurrence, distant recurrence, and toxicity. Hazard ratios (HRs) were estimated and pooled if possible; otherwise, dichotomous data were extracted. All statistical tests were two-sided. RESULTS Of the eight included trials, seven trials (3628 women) compared external beam radiotherapy (EBRT) and no EBRT (or vaginal brachytherapy [VBT]), and one trial (645 women) compared VBT and no additional treatment. EBRT statistically significantly reduced locoregional recurrence compared with no EBRT (or VBT alone) (HR = 0.36, 95% confidence Interval [CI] = 0.25 to 0.52; P < .001), but this did not translate into an improvement in OS (HR = 0.99, 95% CI = 0.82 to 1.20; P = .95), endometrial cancer-specific survival (HR = 0.96, 95% CI = 0.72 to 1.28; P = .80), or distant recurrence rates (risk ratio = 1.04, 95% CI = 0.80 to 1.35; P = .77). EBRT was associated with an increased risk of severe acute toxicity, severe late toxicity, and reduced quality of life scores. CONCLUSIONS EBRT reduces the risk of locoregional recurrence but has no statistically significant impact on cancer-related deaths or OS. However, EBRT is associated with clinically and statistically significant morbidity and a reduction in quality of life.

Maternal and perinatal health research priorities beyond 2015: an international survey and prioritization exercise.

BackgroundMaternal mortality has declined by nearly half since 1990, but over a quarter million women still die every year of causes related to pregnancy and childbirth. Maternal-health related targets are falling short of the 2015 Millennium Development Goals and a post-2015 Development Agenda is emerging. In connection with this, setting global research priorities for the next decade is now required.MethodsWe adapted the methods of the Child Health and Nutrition Research Initiative (CHNRI) to identify and set global research priorities for maternal and perinatal health for the period 2015 to 2025. Priority research questions were received from various international stakeholders constituting a large reference group, and consolidated into a final list of research questions by a technical working group. Questions on this list were then scored by the reference working group according to five independent and equally weighted criteria. Normalized research priority scores (NRPS) were calculated, and research priority questions were ranked accordingly.ResultsA list of 190 priority research questions for improving maternal and perinatal health was scored by 140 stakeholders. Most priority research questions (89%) were concerned with the evaluation of implementation and delivery of existing interventions, with research subthemes frequently concerned with training and/or awareness interventions (11%), and access to interventions and/or services (14%). Twenty-one questions (11%) involved the discovery of new interventions or technologies.ConclusionsKey research priorities in maternal and perinatal health were identified. The resulting ranked list of research questions provides a valuable resource for health research investors, researchers and other stakeholders. We are hopeful that this exercise will inform the post-2015 Development Agenda and assist donors, research-policy decision makers and researchers to invest in research that will ultimately make the most significant difference in the lives of mothers and babies.

The effect of depot medroxyprogesterone acetate on postnatal depression: a randomised controlled trial.

Background Depot medroxyprogesterone acetate (DMPA) is the most commonly used hormonal contraceptive method in South Africa. It is frequently administered in the immediate postnatal period, yet it is unclear whether it affects the risk of postnatal depression (PND). Aim To determine whether DMPA increases the risk of PND compared with the copper-containing intrauterine device (IUD) when administered after delivery. Design and setting A single-blind randomised controlled trial conducted at two teaching hospitals in East London, South Africa. Methods Eligible, consenting women (N=242) requiring postnatal contraception were randomised to receive DMPA or an IUD within 48 hours of childbirth and interviewed at 1 and 3 months postpartum. Depression was measured using the Beck Depression Inventory (BDI-II) and the Edinburgh Postnatal Depression Scale (EPDS). Resumption of sexual intercourse, menstrual symptoms and breastfeeding rates were also assessed. Results One-month EPDS depression scores were statistically significantly higher in the DMPA arm compared with IUD arm (p=0.04). Three-month BDI-II scores were significantly higher in the DMPA arm than in the IUD arm (p=0.002) and, according to the BDI-II but not the EPDS, more women in the DMPA arm had major depression at this time-point (8 vs 2; p=0.05). There were no statistically significant differences in other outcome measures except that fewer women had resumed sexual activity by 1 month postpartum in the DMPA arm (13% vs 26%; p=0.02). Conclusions The possibility that immediate postnatal DMPA use is associated with depression cannot be excluded. These findings justify further research with longer follow-up. Clinical trial number PACTR201209000419241.

Effects of injectable progestogen contraception versus the copper intrauterine device on HIV acquisition: sub-study of a pragmatic randomised controlled trial

Background Evidence from observational studies suggests an increased risk of HIV acquisition among women using depot medroxyprogesterone acetate (DMPA) contraception. Methods Within the context of a South African programme to increase womens access to the intrauterine contraceptive device (IUD), we conducted a pragmatic, open-label, parallel-arm, randomised controlled trial (RCT) of the IUD versus injectable progestogen contraception (IPC) at two South African hospitals. The primary outcome was pregnancy; secondary outcomes included HIV acquisition. Consenting women attending termination of pregnancy services were randomised after pregnancy termination between July 2009 and November 2012. Condoms were promoted for the prevention of sexually transmitted infections. Voluntary HIV testing was offered at baseline and at 12 or more months later. Findings on HIV acquisition are reported in this article. Results HIV acquisition data were available for 1290 initially HIV-negative women who underwent a final study interview at a median of 20 months after randomisation to IPC or an IUD. Baseline group characteristics were comparable. In the IPC group, 545/656 (83%) of participants received DMPA, 96 (15%) received injectable norethisterone enanthate, 14 (2%) received the IUD and one received oral contraception. In the IUD group 609 (96%) received the IUD, 20 (3%) received IPC and 5 (1%) had missing data. According to intention-to-treat analysis, HIV acquisition occurred in 20/656 (3.0%) women in the IPC arm and 22/634 (3.5%) women in the IUD arm (IPC vs IUD, risk ratio 0.88; 95% confidence interval 0.48–1.59; p=0.7). Conclusions This sub-study was underpowered to rule out moderate differences in HIV risk, but confirms the feasibility of randomised trial methodology to address this question. Larger RCTs are needed to determine the relative risks of various contraceptive methods on HIV acquisition with greater precision. Trial registration number Pan African Clinical Trials Registry number PACTR201409000880157 (04-09-2014).

Medical and Surgical Treatments for Usual-Type Vulvar Intraepithelial Neoplasia

Clinical Question Which interventions are the most effective and tolerable for treating usual-type vulvar intraepithelial neoplasia? Bottom Line Provided cancer is not suspected, usual-type vulvar intraepithelial neoplasia treatment, including medical and surgical options, can be individualized to take into account the site, extent of disease, and a womans preferences, with a commitment to long-term follow-up.

Integrated person-centered health care for all women during pregnancy: implementing World Health Organization recommendations on antenatal care for a positive pregnancy experience.

The 2016 WHO guideline on routine antenatal care (ANC) recommends several health systems interventions to improve quality of care and increase use of services including: Midwife-led continuity of care throughout the antenatal, intrapartum, and postnatal periods Task shifting components of ANC, including promotion of health-related behaviors and distribution of nutrition supplements Recruitment and retention of health workers in rural and remote areas Community mobilization to improve communication and support to pregnant women Women-held case notes A model with a minimum of 8 antenatal care contacts The 2016 WHO guideline on routine antenatal care (ANC) recommends several health systems interventions to improve quality of care and increase use of services including: Midwife-led continuity of care throughout the antenatal, intrapartum, and postnatal periods Task shifting components of ANC, including promotion of health-related behaviors and distribution of nutrition supplements Recruitment and retention of health workers in rural and remote areas Community mobilization to improve communication and support to pregnant women Women-held case notes A model with a minimum of 8 antenatal care contacts

Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine which prophylactic interventions reduce the incidence, severity, or both of adverse gastrointestinal effects among adults receiving radiotherapy to treat primary pelvic cancers.

Authors' response to ’Comment on ’Effects of injectable progestogen contraception versus the copper intrauterine device on HIV acquisition: sub-study of a pragmatic randomised controlled trial' '

We thank Quispe Calla and colleagues for their insightful comments1 on our article.2 We agree that basic science evidence showing that various progestogens increase HIV susceptibility is compelling. We also agree that randomised clinical trials (RCTs) are informative regarding the relative risks of HIV between contraceptive alternatives, but not the absolute risks …