Effects on heavy menstrual bleeding and pregnancy of uterine artery embolization (UAE) or myomectomy for women with uterine fibroids wishing to avoid hysterectomy: The FEMME randomized controlled trial.

OBJECTIVE: To determine treatment options (myomectomy vs. uterine artery embolization (UAE)) for women wishing to avoid hysterectomy. METHODS: A multicenter randomized controlled trial was conducted on 254 women and data were collected on fibroid-specific quality of life (UFS-QOL), loss of menstrual blood, and pregnancy. RESULTS: At 4 years, the mean difference in the UFS-QOL was 5.0 points (95% confidence interval (CI) -1.4 to 11.5; P = 0.13) in favor of myomectomy. This was not statistically significant as it was at 2 years. There were no differences in bleeding scores, rates of amenorrhea, or heavy bleeding. Of those who were still menstruating, the majority reported regular or fairly regular periods: 36 of 48 (75%) in the UAE group and 30 of 39 (77%) in the myomectomy group. Twelve women after UAE and six women after myomectomy became pregnant (4 years) with seven and five live births, respectively (hazard ratio 0.48, 95% CI 0.18-1.28). There was no difference between the levels of hormones associated with the uterine reserve in each group. CONCLUSION: Leiomyoma are common in reproductive-aged women, causing heavy menses and subfertility. Among women with uterine fibroids, myomectomy resulted in better fibroid-related quality of life at 4 years, compared with UAE but the treatments decreased menstrual bleeding equally. There was also no significant difference in the impact of treatment on ovarian reserve.

Uterine artery embolisation versus myomectomy for premenopausal women with uterine fibroids wishing to avoid hysterectomy: the FEMME RCT.

BACKGROUND: Uterine fibroids are the most common tumour in women of reproductive age and are associated with heavy menstrual bleeding, abdominal discomfort, subfertility and reduced quality of life. For women wishing to retain their uterus and who do not respond to medical treatment, myomectomy and uterine artery embolisation are therapeutic options. OBJECTIVES: We examined the clinical effectiveness and cost-effectiveness of uterine artery embolisation compared with myomectomy in the treatment of symptomatic fibroids. DESIGN: A multicentre, open, randomised trial with a parallel economic evaluation. SETTING: Twenty-nine UK hospitals. PARTICIPANTS: Premenopausal women who had symptomatic uterine fibroids amenable to myomectomy or uterine artery embolisation were recruited. Women were excluded if they had significant adenomyosis, any malignancy or pelvic inflammatory disease or if they had already had a previous open myomectomy or uterine artery embolisation. INTERVENTIONS: Participants were randomised to myomectomy or embolisation in a 1 : 1 ratio using a minimisation algorithm. Myomectomy could be open abdominal, laparoscopic or hysteroscopic. Embolisation of the uterine arteries was performed under fluoroscopic guidance. MAIN OUTCOME MEASURES: The primary outcome was the Uterine Fibroid Symptom Quality of Life questionnaire (with scores ranging from 0 to 100 and a higher score indicating better quality of life) at 2 years, adjusted for baseline score. The economic evaluation estimated quality-adjusted life-years (derived from EuroQol-5 Dimensions, three-level version, and costs from the NHS perspective). RESULTS: A total of 254 women were randomised - 127 to myomectomy (105 underwent myomectomy) and 127 to uterine artery embolisation (98 underwent embolisation). Information on the primary outcome at 2 years was available for 81% (n = 206) of women. Primary outcome scores at 2 years were 84.6 (standard deviation 21.5) in the myomectomy group and 80.0 (standard deviation 22.0) in the uterine artery embolisation group (intention-to-treat complete-case analysis mean adjusted difference 8.0, 95% confidence interval 1.8 to 14.1, p = 0.01; mean adjusted difference using multiple imputation for missing responses 6.5, 95% confidence interval 1.1 to 11.9). The mean difference in the primary outcome at the 4-year follow-up time point was 5.0 (95% CI -1.4 to 11.5; p = 0.13) in favour of myomectomy. Perioperative and postoperative complications from all initial procedures occurred in similar percentages of women in both groups (29% in the myomectomy group vs. 24% in the UAE group). Twelve women in the uterine embolisation group and six women in the myomectomy group reported pregnancies over 4 years, resulting in seven and five live births, respectively (hazard ratio 0.48, 95% confidence interval 0.18 to 1.28). Over a 2-year time horizon, uterine artery embolisation was associated with higher costs than myomectomy (mean cost £7958, 95% confidence interval £6304 to £9612, vs. mean cost £7314, 95% confidence interval £5854 to £8773), but with fewer quality-adjusted life-years gained (0.74, 95% confidence interval 0.70 to 0.78, vs. 0.83, 95% confidence interval 0.79 to 0.87). The differences in costs (difference £645, 95% confidence interval -£1381 to £2580) and quality-adjusted life-years (difference -0.09, 95% confidence interval -0.11 to -0.04) were small. Similar results were observed over the 4-year time horizon. At a threshold of willingness to pay for a gain of 1 QALY of £20,000, the probability of myomectomy being cost-effective is 98% at 2 years and 96% at 4 years. LIMITATIONS: There were a substantial number of women who were not recruited because of their preference for a particular treatment option. CONCLUSIONS: Among women with symptomatic uterine fibroids, myomectomy resulted in greater improvement in quality of life than did uterine artery embolisation. The differences in costs and quality-adjusted life-years are very small. Future research should involve women who are desiring pregnancy. TRIAL REGISTRATION: This trial is registered as ISRCTN70772394. FUNDING: This study was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme, and will be published in full in Health Technology Assessment; Vol. 26, No. 22. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Uterine fibroids are the most common non-cancerous tumour in women of childbearing age. Uterine fibroids are associated with heavy bleeding, lower chances of having children and reduced quality of life. Traditional surgical options were either to remove the fibroids (via myomectomy) or to completely remove the womb. A newer approach, known as uterine artery embolisation, involves blocking the blood supply to the fibroids in the womb. WHAT DID WE PLAN TO DO?: We compared myomectomy with uterine artery embolisation in women with fibroids who wanted to keep their womb. We wanted to see which treatment improved quality of life, was associated with the fewest complications and was the best value for money for the NHS. We also wanted to see if either treatment had an impact on women's ability to get pregnant and give birth. We included 254 women in a clinical trial. Women were assigned to have myomectomy or uterine artery embolisation at random to ensure a fair comparison. Women completed questionnaires about their symptoms and quality of life at intervals up to 4 years after treatment. WHAT DID WE FIND?: We found that myomectomy improved women's quality of life more than uterine artery embolisation. Complications from the treatments occurred in a similar proportion of women. There appeared to be no difference on reproductive hormone levels between treatments. Too few women in the trial got pregnant for any difference in the numbers of women having children to be seen. The differences in costs and overall disease burden were small. WHAT DOES THIS MEAN?: Both treatments improve quality of life and cost about the same to the NHS but, on average, myomectomy will provide greater benefit to women. There is no evidence to suggest that either treatment is unsuitable for women wanting to get pregnant, but more research is needed in younger women.

Uterine artery embolization or myomectomy for women with uterine fibroids: Four-year follow-up of a randomised controlled trial.

OBJECTIVE: To examine the quality of life experienced by women with symptomatic uterine fibroids who had been treated with UAE in comparison to myomectomy. We report the four-year follow-up of the FEMME randomised trial. Two-year follow-up data has been previously reported. STUDY DESIGN: Premenopausal women who had symptomatic uterine fibroids amenable to myomectomy or uterine artery embolization were recruited from 29 UK hospitals. Women were excluded if they had significant adenomyosis, any malignancy, pelvic inflammatory disease or had had a previous open myomectomy or uterine artery embolization.Participants were randomised to myomectomy or embolization in a 1:1 ratio using a minimisation algorithm. Myomectomy could be open abdominal, laparoscopic or hysteroscopic, according to clinician preference. Embolization of the uterine arteries was performed according to local practice, under fluoroscopic guidance.The primary outcome measure was the Uterine Fibroid Symptom Quality of Life questionnaire, adjusted for baseline score and reported here at four years post-randomisation. Subsequent procedures for fibroids, pregnancy and outcome were amongst secondary outcomes.Trial registration ISRCTN70772394 https://doi.org/10.1186/ISRCTN70772394. RESULTS: 254 women were randomized, 127 to myomectomy (105 underwent myomectomy) and 127 to uterine artery embolization (98 underwent embolization). At four years, 67 (53%) and 81 (64%) completed UFS-QoL quality of life scores. Mean difference in the UFS-QoL at 4 years was 5.0 points (95% CI -1.4 to 11.5; p = 0.13) in favour of myomectomy. There were 15 pregnancies in the UAE group and 7 in the myomectomy group, with a cumulative pregnancy rate to four years of 15% and 6% respectively (hazard ratio: 0.48; 95% CI 0.18-1.28). The cumulative repeat procedure rate to four years was 24% in the UAE group and 13% in the myomectomy group (hazard ratio: 0.53; 95% CI 0.27-1.05). CONCLUSIONS: Myomectomy resulted in greater improvement in quality of life compared with uterine artery embolization, although by four years, this difference was not statistically significant. Missing data may limit the generalisability of this result. The numbers of women becoming pregnant were too small draw a conclusion on the effect of the procedures on fertility.

Mammographic Screening in the Occupied Palestinian Territory: A Critical Analysis of Its Promotion, Claimed Benefits, and Safety in Palestinian Health Research.

PURPOSE: To critically review the evidence and opinions expressed about mammographic screening (MS) in research reports on breast cancer in the occupied Palestinian territory (oPt) and to assess whether benefits and harms in MS are presented in a balanced way. METHODS: Searches of PubMed, Cochrane, MEDLINE, EMBASE, CINAHL, and gray literature identified 14 eligible research reports relating to the oPt. We reviewed these documents and then used a thematic analysis to describe and analyze the evidence and the opinions about MS expressed in them. RESULTS: All 14 research reports mentioned that MS would improve survival rates in the oPt. Only three gave information on major harmful effects, and only two emphasized that MS must be accompanied by effective treatment to have any beneficial effects on population mortality. There was no consistency in the recommended frequency of MS. CONCLUSION: Most information presented by Palestinian health researchers was selective and failed to address the important established harms of MS. Thus, calls to support MS in the oPt are not based on a measured discussion of the risks and benefits for women or grounded in the systemic readiness of health care necessary for its effectiveness. As long as diagnostic and treatment facilities remain deficient, screening cannot lead to reduced mortality from breast cancer.

Weekly COVID-19 testing with household quarantine and contact tracing is feasible and would probably end the epidemic.

The COVID-19 epidemic can probably be ended and normal life restored, perhaps quite quickly, by weekly SARS-CoV-2 RNA testing together with household quarantine and systematic contact tracing. Isolated outbreaks could then be contained by contact tracing, supplemented if necessary by temporary local reintroduction of population testing or lockdown. Leading public health experts have recommended that this should be tried in a demonstration project in which a medium-sized city introduces weekly testing and lifts lockdown completely. The idea was not considered by the groups whose predictions have guided UK policy, so we have examined the statistical case for such a study. The combination of regular testing with strict household quarantine, which was not analysed in their models, has remarkable power to reduce transmission to the community from other household members as well as providing earlier diagnosis and facilitating rapid contact tracing.

Uterine-Artery Embolization or Myomectomy for Uterine Fibroids.

BACKGROUND: Uterine fibroids, the most common type of tumor among women of reproductive age, are associated with heavy menstrual bleeding, abdominal discomfort, subfertility, and a reduced quality of life. For women who wish to preserve their uterus and who have not had a response to medical treatment, myomectomy and uterine-artery embolization are therapeutic options. METHODS: We conducted a multicenter, randomized, open-label trial to evaluate myomectomy, as compared with uterine-artery embolization, in women who had symptomatic uterine fibroids and did not want to undergo hysterectomy. Procedural options included open abdominal, laparoscopic, or hysteroscopic myomectomy. The primary outcome was fibroid-related quality of life, as assessed by the score on the health-related quality-of-life domain of the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire (scores range from 0 to 100, with higher scores indicating a better quality of life) at 2 years; adjustment was made for the baseline score. RESULTS: A total of 254 women, recruited at 29 hospitals in the United Kingdom, were randomly assigned: 127 to the myomectomy group (of whom 105 underwent myomectomy) and 127 to the uterine-artery embolization group (of whom 98 underwent embolization). Data on the primary outcome were available for 206 women (81%). In the intention-to-treat analysis, the mean (±SD) score on the health-related quality-of-life domain of the UFS-QOL questionnaire at 2 years was 84.6±21.5 in the myomectomy group and 80.0±22.0 in the uterine-artery embolization group (mean adjusted difference with complete case analysis, 8.0 points; 95% confidence interval [CI], 1.8 to 14.1; P = 0.01; mean adjusted difference with missing responses imputed, 6.5 points; 95% CI, 1.1 to 11.9). Perioperative and postoperative complications from all initial procedures, irrespective of adherence to the assigned procedure, occurred in 29% of the women in the myomectomy group and in 24% of the women in the uterine-artery embolization group. CONCLUSIONS: Among women with symptomatic uterine fibroids, those who underwent myomectomy had a better fibroid-related quality of life at 2 years than those who underwent uterine-artery embolization. (Funded by the National Institute for Health Research Health Technology Assessment program; FEMME Current Controlled Trials number, ISRCTN70772394.).

The overestimation and the inappropriate promotion of the benefits of mammographic screening in breast cancer research and interventions in the Gaza Strip.

BACKGROUND: There has been extensive debate about whether mammographic screening has done more good than harm. Recent reviews showed that women who undergo mammographic screening are more likely to have a tumour that was an overdiagnosis and therefore would not cause them problems. In the Gaza Strip, a strong forum of people advocate an increase in mammographic screening, and the aim of this study was to establish the evidence for this view. METHODS: Research papers that have focused on breast screening in the Gaza Strip or elsewhere in the occupied Palestinian territory were reviewed. Published educational material, including brochures, booklets, and short videos on mammographic screening, were also reviewed. A thematic analysis was done to document the opinions of authors on the effect of mammography. FINDINGS: 11 studies and 20 sets of educational material were identified. Results of six cross-sectional studies showed that about 70% of Palestinian women had never had a mammogram, whereas data from one study showed that 90% of women in the Gaza Strip were willing to undergo diagnostic mammography, but around 30% of them were willing to undergo mammographic screening. Some investigators argued that mammographic screening programmes would improve survival by more than 20% in the Gaza Strip. The authors of two retrospective cohort studies concluded that Palestinian women have low survival rates because of the poor availability of mammography. Only three study groups mentioned harmful effects of mammographic screening. All educational materials had clear information on the benefits of mammographic screening but minimal information on its harms. INTERPRETATION: Research in the Gaza Strip overestimated the reduction in breast cancer mortality that can be attributable to mammographic screening, and this would encourage women to undergo screening without knowing that it could harm them. The content of breast cancer educational material was misleading. This study shows that the information and advice given to women in the Gaza Strip is one-sided. FUNDING: None.

Economic evaluation of type 2 diabetes prevention programmes: Markov model of low- and high-intensity lifestyle programmes and metformin in participants with different categories of intermediate hyperglycaemia.

BACKGROUND: National guidance on preventing type 2 diabetes mellitus (T2DM) in the UK recommends low-intensity lifestyle interventions for individuals with intermediate categories of hyperglycaemia defined in terms of impaired fasting glucose (IFG) or 'at-risk' levels of HbA1c. In a recent systematic review of economic evaluations of such interventions, most studies had evaluated intensive trial-based lifestyle programmes in participants with impaired glucose tolerance (IGT). This study examines the costs and effects of different intensity lifestyle programmes and metformin in participants with different categories of intermediate hyperglycaemia. METHODS: We developed a decision tree and Markov model (50-year horizon) to compare four approaches, namely (1) a low-intensity lifestyle programme based on current NICE guidance, (2) a high-intensity lifestyle programme based on the US Diabetes Prevention Program, (3) metformin, and (4) no intervention, modelled for three different types of intermediate hyperglycaemia (IFG, IGT and HbA1c). A health system perspective was adopted and incremental analysis undertaken at an individual and population-wide level, taking England as a case study. RESULTS: Low-intensity lifestyle programmes were the most cost-effective (£44/QALY, £195/QALY and £186/QALY compared to no intervention in IGT, IFG and HbA1c, respectively). Intensive lifestyle interventions were also cost-effective compared to no intervention (£2775/QALY, £6820/QALY and £7376/QALY, respectively, in IGT, IFG and HbA1c). Metformin was cost-effective relative to no intervention (£5224/QALY, £6842/QALY and £372/QALY in IGT, IFG and HbA1c, respectively), but was only cost-effective relative to other treatments in participants identified with HbA1c. At a willingness-to-pay threshold of £20,000/QALY, low- and high-intensity lifestyle programmes were cost-effective 98%, 99% and 98% and 81%, 81% and 71% of the time in IGT, IFG and HbA1c, respectively. An England-wide programme for 50-59 year olds could reduce T2DM incidence by < 3.5% over 50 years and would cost 0.2-5.2% of the current diabetes budget for 2-9 years. DISCUSSION: This analysis suggests that current English national policy of low-intensity lifestyle programmes in participants with IFG or HbA1c will be cost-effective and have the most favourable budget impact, but will prevent only a fraction of cases of T2DM. Additional approaches to prevention need to be investigated urgently.

Child and adolescent obesity: part of a bigger picture.

The prevalence of childhood overweight and obesity has risen substantially worldwide in less than one generation. In the USA, the average weight of a child has risen by more than 5 kg within three decades, to a point where a third of the country's children are overweight or obese. Some low-income and middle-income countries have reported similar or more rapid rises in child obesity, despite continuing high levels of undernutrition. Nutrition policies to tackle child obesity need to promote healthy growth and household nutrition security and protect children from inducements to be inactive or to overconsume foods of poor nutritional quality. The promotion of energy-rich and nutrient-poor products will encourage rapid weight gain in early childhood and exacerbate risk factors for chronic disease in all children, especially those showing poor linear growth. Whereas much public health effort has been expended to restrict the adverse marketing of breastmilk substitutes, similar effort now needs to be expanded and strengthened to protect older children from increasingly sophisticated marketing of sedentary activities and energy-dense, nutrient-poor foods and beverages. To meet this challenge, the governance of food supply and food markets should be improved and commercial activities subordinated to protect and promote children's health.

A randomised trial of treating fibroids with either embolisation or myomectomy to measure the effect on quality of life among women wishing to avoid hysterectomy (the FEMME study): study protocol for a randomised controlled trial.

BACKGROUND: Uterine fibroids are the most common tumour in women of reproductive age. By the time they are 50-years-old around 80% of women will have developed one. Of these, around half will experience symptoms which will impact negatively on their quality of life. Hysterectomy is the traditional treatment for women with symptomatic fibroids. For women who do not wish to undergo a hysterectomy, two invasive treatments are commonly available: myomectomy or uterine artery embolization (UAE). DESIGN: FEMME is a pragmatic, randomised, open, multi-centre trial examining the quality of life menstruating women with symptomatic fibroids experience after treatment with UAE or myomectomy. METHODS: After providing informed consent, 216 women with symptomatic fibroids from 43 NHS Hospital Trusts and Health Boards across the United Kingdom will undergo randomisation by a centralised computer system to treatment by either UAE or myomectomy. A minimisation algorithm will be used in order to balance the groups with respect to the following three parameters: the longest dimension of the largest fibroid, the number of fibroids present, and whether the woman currently desires pregnancy.Using validated questionnaires the women's quality of life will be compared between groups at six months, one year, two years and four years post-procedure, taking into account pre-procedure scores. An economic evaluation will be conducted alongside the trial to determine the cost-effectiveness of UAE compared with myomectomy.Validated diaries will also be used to compare menstrual blood loss at the same time-points. The plasma concentration of Anti-Müllerian hormone (AMH), which will act as a proxy measurement of ovarian reserve, will be recorded before the woman has her procedure and then again at six weeks, six months, and twelve months afterwards. Re-intervention rates will be recorded. DISCUSSION: The FEMME trial's primary outcome is the quality of life women with symptomatic uterine fibroids experience two years after they have been treated with either UAE or myomectomy, as measured by the disease-specific Uterine Fibroid Symptom Quality-of-Life (UFS-QoL) questionnaire. TRIAL REGISTRATION: Current Controlled Trials registration number: ISRCTN70772394, registered on 2 March 2013.

The future burden of obesity-related diseases in the 53 WHO European-Region countries and the impact of effective interventions: a modelling study.

OBJECTIVE: Non-communicable diseases (NCDs) are the biggest cause of death in Europe putting an unsustainable burden on already struggling health systems. Increases in obesity are a major cause of NCDs. This paper projects the future burden of coronary heart disease (CHD), stroke, type 2 diabetes and seven cancers by 2030 in 53 WHO European Region countries based on current and past body mass index (BMI) trends. It also tests the impact of obesity interventions on the future disease burden. SETTING AND PARTICIPANTS: Secondary data analysis of country-specific epidemiological data using a microsimulation modelling process. INTERVENTIONS: The effect of three hypothetical scenarios on the future burden of disease in 2030 was tested: baseline scenario, BMI trends go unchecked; intervention 1, population BMI decreases by 1%; intervention 2, BMI decreases by 5%. PRIMARY AND SECONDARY OUTCOME MEASURES: Quantifying the future burden of major NCDs and the impact of interventions on this future disease burden. RESULTS: By 2030 in the whole of the European region, the prevalence of diabetes, CHD and stroke and cancers was projected to reach an average of 3990, 4672 and 2046 cases/100 000, respectively. The highest prevalence of diabetes was predicted in Slovakia (10 870), CHD and stroke-in Greece (11 292) and cancers-in Finland (5615 cases/100 000). A 5% fall in population BMI was projected to significantly reduce cumulative incidence of diseases. The largest reduction in diabetes and CHD and stroke was observed in Slovakia (3054 and 3369 cases/100 000, respectively), and in cancers was predicted in Germany (331/100 000). CONCLUSIONS: Modelling future disease trends is a useful tool for policymakers so that they can allocate resources effectively and implement policies to prevent NCDs. Future research will allow real policy interventions to be tested; however, better surveillance data on NCDs and their risk factors are essential for research and policy.