The cost-effectiveness of transvaginal hydrolaparoscopy versus hysterosalpingography in the work-up for subfertility.

STUDY QUESTION: Is a strategy starting with transvaginal hydrolaparoscopy (THL) cost-effective compared to a strategy starting with hysterosalpingography (HSG) in the work-up for subfertility? SUMMARY ANSWER: A strategy starting with THL is cost-effective compared to a strategy starting with HSG in the work-up for subfertile women. WHAT IS KNOWN ALREADY: Tubal pathology is a common cause of subfertility and tubal patency testing is one of the cornerstones of the fertility work-up. Both THL and HSG are safe procedures and can be used as a first-line tubal patency test. STUDY DESIGN, SIZE, DURATION: This economic evaluation was performed alongside a randomized clinical trial comparing THL and HSG in 300 subfertile women, between May 2013 and October 2016. For comparisons of THL and HSG, the unit costs were split into three main categories: costs of the diagnostic procedure, costs of fertility treatments and the costs for pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subfertile women scheduled for tubal patency testing were eligible. Women were randomized to a strategy starting with THL or a strategy starting with HSG. The primary outcome of the study was conception leading to a live birth within 24 months after randomization. The mean costs and outcomes for each treatment group were compared. We used a non-parametric bootstrap resampling of 1000 re-samples to investigate the effect of uncertainty and we created a cost-effectiveness plane and cost-effectiveness acceptability curves. MAIN RESULTS AND THE ROLE OF CHANCE: We allocated 149 women to THL and 151 to HSG, and we were able to achieve complete follow-up of 142 versus 148 women, respectively. After the fertility work-up women were treated according to the Dutch guidelines and based on a previously published prognostic model. In the THL group, 83 women (58.4%) conceived a live born child within 24 months after randomization compared to 82 women (55.4%) in the HSG group (difference 3.0% (95% CI: -8.3 to 14.4)). The mean total costs per woman were lower in the THL group compared to the HSG group (THL group €4991 versus €5262 in the HSG group, mean cost difference = -€271 (95% CI -€273 to -€269)). Although the costs of only the diagnostic procedure were higher in the THL group, in the HSG group more women underwent diagnostic and therapeutic laparoscopies and also had higher costs for fertility treatments. LIMITATIONS, REASONS FOR CAUTION: Our trial was conducted in women with a low risk of tubal pathology; therefore, the results of our study are not generalizable to women with high risk of tubal pathology. Furthermore, this economic analysis was based on the Dutch healthcare system, and possibly our results are not generalizable to countries with different strategies or costs for fertility treatments. WIDER IMPLICATIONS OF THE FINDINGS: After 2 years of follow-up, we found a live birth rate of 58.4% in the THL group versus 55.4% in the HSG group and a lower mean cost per woman in the THL group, with a cost difference of -€271. The findings of our trial suggest that a strategy starting with THL is cost-effective compared to a strategy starting with HSG in the workup for subfertile women. However, the cost difference between the two diagnostic strategies is limited compared to the total cost per woman in our study and before implementing THL as a first-line strategy for tubal patency testing, more research in other fields, such as patient preference and acceptance, is necessary. STUDY FUNDING/COMPETING INTEREST(S): The authors received no external financial support for the research. B.W.J.M. is supported by an NHMRC Investigator Grant (GNT1176437). B.W.J.M. reports consultancy for ObsEva, Merck KGaA, Guerbet. B.W.J.M. reports receiving travel support from Merck KGaA. C.T.P. reports consultancy for Guerbet, outside of this manuscript. All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: NTR3462.

The levonorgestrel intrauterine system versus endometrial ablation for heavy menstrual bleeding: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the costs and non-inferiority of a strategy starting with the levonorgestrel intrauterine system (LNG-IUS) compared with endometrial ablation (EA) in the treatment of heavy menstrual bleeding (HMB). DESIGN: Cost-effectiveness analysis from a societal perspective alongside a multicentre randomised non-inferiority trial. SETTING: General practices and gynaecology departments in the Netherlands. POPULATION: In all, 270 women with HMB, aged ≥34 years old, without intracavitary pathology or wish for a future child. METHODS: Randomisation to a strategy starting with the LNG-IUS (n = 132) or EA (n = 138). The incremental cost-effectiveness ratio was estimated. MAIN OUTCOME MEASURES: Direct medical costs and (in)direct non-medical costs were calculated. The primary outcome was menstrual blood loss after 24 months, measured with the mean Pictorial Blood Assessment Chart (PBAC)-score (non-inferiority margin 25 points). A secondary outcome was successful blood loss reduction (PBAC-score ≤75 points). RESULTS: Total costs per patient were €2,285 in the LNG-IUS strategy and €3,465 in the EA strategy (difference: €1,180). At 24 months, mean PBAC-scores were 64.8 in the LNG-IUS group (n = 115) and 14.2 in the EA group (n = 132); difference 50.5 points (95% CI 4.3-96.7). In the LNG-IUS group, 87% of women had a PBAC-score ≤75 points versus 94% in the EA group (relative risk [RR] 0.93, 95% CI 0.85-1.01). The ICER was €23 (95% CI €5-111) per PBAC-point. CONCLUSIONS: A strategy starting with the LNG-IUS was cheaper than starting with EA, but non-inferiority could not be demonstrated. The LNG-IUS is reversible and less invasive and can be a cost-effective treatment option, depending on the success rate women are willing to accept. TWEETABLE ABSTRACT: Treatment of heavy menstrual bleeding starting with LNG-IUS is cheaper but slightly less effective than endometrial ablation.

Is the Pictorial Blood Loss Assessment Chart (PBAC) score associated with treatment outcome after endometrial ablation for heavy menstrual bleeding? A cohort study.

OBJECTIVE: The Pictorial Blood Loss Assessment Chart (PBAC) is a validated tool that is used to diagnose heavy menstrual bleeding (HMB). Knowledge of the effect of its score and its relationship with outcome could have implications for using the PBAC as an outcome measurement in future HMB studies, and as a tool to evaluate the treatment effect in research and clinical practice. Our aim was to relate PBAC scores to other measures of success after endometrial ablation for HMB. DESIGN: Analysis of individual patient data (IPD) of randomised controlled trials studying women with HMB. SETTING: Women with HMB consulting their gynecologists. POPULATION OR SAMPLE: Individual patient data (IPD) of randomised controlled trials studying women with HMB. METHODS: We included studies if they had studied second-generation endometrial ablation techniques and had collected PBAC scores for both baseline and follow-up. The effectiveness of treatment was scored as satisfaction or re-intervention (yes/no) 12 months after treatment. We related these outcomes to the PBAC score at 12 months after treatment, and to PBAC decrease between baseline and 12 months of follow-up. RESULTS: We studied data for 900 patients included in nine studies. The median PBAC score at 12 months was 7 (0-2500). The overall satisfaction rate was 89% and the overall re-intervention rate was 7.2%. A clear association was found between absolute PBAC score at the 12-month follow-up and satisfaction (odds ratio, OR 0.16; 95% confidence interval, 95% CI 0.11-0.24) and surgical re-intervention (OR 2.3, 95% CI 1.8-2.8). A change in PBAC score was also associated with satisfaction (OR 2.0, 95% CI 1.7-2.3) and surgical re-intervention (OR 0.69, 95% CI 0.63-0.75). Both the absolute PBAC scores and the changes in score show high accuracy for both treatment outcomes. CONCLUSIONS: PBAC scores at 12 months after treatment are significantly associated with satisfaction and re-intervention rates. We propose to use the PBAC in research as a primary end point in studies on HMB, and in clinical practice as a measure to assess the effectiveness of treatment. TWEETABLE ABSTRACT: PBAC scores 12 months after treatment are significantly associated with satisfaction and reintervention rates.

Costs of non-small cell lung cancer in the Netherlands.

OBJECTIVES: Real-world resource use and cost data on non-small cell lung cancer (NSCLC) are scarce. This data is needed to inform health-economic modelling to assess the impact of new diagnostic and/or treatment technologies. This study provides detailed insight into real-world medical resource use and costs of stage I-IV NSCLC in the Netherlands. MATERIALS AND METHODS: A random sample of patients newly diagnosed with NSCLC (2009-2011) was selected from four Dutch hospitals. Data was retrospectively collected from patient charts. This data included patient characteristics, tumour characteristics, treatment details, adverse events, survival and resource use. Resource use was multiplied by Dutch unit costs expressed in EUR 2012. Total mean costs were corrected for censoring using the Bang and Tsiatis weighted complete-case estimator. Furthermore, costs of adverse events, costs per phase of NSCLC management and costs of second opinions are presented. RESULTS: Data was collected on 1067 patients. Total mean costs for NSCLC diagnosis, treatment and follow-up are €28,468 during the study period and €33,143 when corrected for censoring. Adverse events were recorded in the patient charts for 369 patients (41%) and 82 patients (9%) experienced an adverse event of grade III or higher. For these patients, adverse event-related hospital admissions cost on average €2,091. Mean total costs are €1,725 for the diagnostic period, €17,296 for first treatment line, and €13,236 for each later treatment line. Costs of providing a second opinion are €2,580 per patient. CONCLUSIONS: Total mean hospital costs per NSCLC patient are €33,143 for the total duration of the disease. Ignoring censoring in our data underestimates these costs by 14%. Main limitations of the study relate to the short follow-up time, staging difficulties and missing data. Its main strength is that it provides highly detailed, real-world data on the costs of NSCLC.

The HysNiche trial: hysteroscopic resection of uterine caesarean scar defect (niche) in patients with abnormal bleeding, a randomised controlled trial.

BACKGROUND: A caesarean section (CS) can cause a defect or disruption of the myometrium at the site of the uterine scar, called a niche. In recent years, an association between a niche and postmenstrual spotting after a CS has been demonstrated. Hysteroscopic resection of these niches is thought to reduce spotting and menstrual pain. However, there are no randomised trials assessing the effectiveness of a hysteroscopic niche resection. METHODS/DESIGN: We planned a multicentre randomised trial comparing hysteroscopic niche resection to no intervention. We study women with postmenstrual spotting after a CS and a niche with a residual myometrium of at least 3 mm during sonohysterography. After informed consent is obtained, eligible women will be randomly allocated to hysteroscopic resection of the niche or expectant management for 6 months. The primary outcome is the number of days with postmenstrual spotting during one menstrual cycle 6 months after randomisation. Secondary outcomes are menstrual characteristics, menstruation related pain and experienced discomfort due to spotting or menstrual pain, quality of life, patient satisfaction, sexual function, urological symptoms, medical consultations, medication use, complications, lost productivity and medical costs. Measurements will be performed at baseline and at 3 and 6 months after randomisation. A cost-effectiveness analysis will be performed from a societal perspective at 6 months after randomisation. DISCUSSION: This trial will provide insight in the (cost)effectiveness of hysteroscopic resection of a niche versus expectant management in women who have postmenstrual spotting and a niche with sufficient residual myometrium to perform a hysteroscopic niche resection. TRIAL REGISTRATION: Dutch Trial Register NTR3269 . Registered 1 February 2012. ZonMw Grant number 80-82305-97-12030.

Assessment of the hepatic veins in poor contrast conditions using dual energy CT: evaluation of a novel monoenergetic extrapolation software algorithm.

PURPOSE: To evaluate a novel monoenergetic post-processing algorithm (MEI+) in patients with poor intrahepatic contrast enhancement. MATERIALS AND METHODS: 25 patients were retrospectively included in this study. Late-phase imaging of the upper abdomen, which was acquired in dual-energy mode (100/140 kV), was used as a model for poor intrahepatic contrast enhancement. Traditional monoenergetic images (MEI), linearly weighted mixed images with different mixing ratios (MI), sole 100 and 140 kV and MEI+ images were calculated. MEI+ is a novel technique which applies frequency-based mixing of the low keV images and an image of optimal keV from a noise perspective to combine the benefits of both image stacks. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the intrahepatic vasculature (IHV) and liver parenchyma (LP) were objectively measured and depiction of IHV was subjectively rated and correlated with portal venous imaging by two readers in consensus. RESULTS: MEI+ was able to increase the SNR of the IHV (5.7 ±â€Š0.4 at 40keV) and LP (4.9 ±â€Š1.0 at 90keV) and CNR (2.1 ±â€Š0.6 at 40keV) greatly compared to MEI (5.1 ±â€Š1.1 at 80keV, 4.7 ±â€Š1.0 at 80keV, 1.0 ±â€Š0.4 at 70keV), MI (5.2 ±â€Š1.1 M5:5, 4.8 ±â€Š1.0 M5:5, 1.0 ±â€Š3.5 M9:1), sole 100 kV images (4.4 ±â€Š1.0, 3.7 ±â€Š0.8, 1.0 ±â€Š0.3) and 140 kV images (2.8 ±â€Š0.5, 3.1 ±â€Š0.6, 0.1 ±â€Š0.2). Subjective assessment rated MEI+ of virtual 40 keV superior to all other images. CONCLUSION: MEI+ is a very promising algorithm for monoenergetic extrapolation which is able to overcome noise limitations associated with traditional monoenergetic techniques at low virtual keV levels and consequently does not suffer from a decline of SNR and CNR at low keV values. This algorithm allows an improvement of IHV depiction in the presence of poor contrast. KEY POINTS: • The evaluated new image-based algorithm for virtual monoenergetic imaging allows calculating low virtual keV images from dual energy datasets with significantly improved contrast-to-noise ratios. • The image based novel monoenergetic extrapolation algorithm applies frequency-based mixing of the low keV images and an image of optimal keV from a noise perspective to combine the benefits of both image stacks.• When compared to traditional monoenergetic images, the novel monoenergetic algorithm has improved contrast-to-noise ratios for both low and high virtual keV images.• Contrast-enhanced dual energy images with poor contrast conditions can be significantly improved, e.g. late phase imaging of the liver.

Hysterectomy, endometrial ablation and Mirena® for heavy menstrual bleeding: a systematic review of clinical effectiveness and cost-effectiveness analysis.

OBJECTIVE: The aim of this project was to determine the clinical effectiveness and cost-effectiveness of hysterectomy, first- and second-generation endometrial ablation (EA), and Mirena® (Bayer Healthcare Pharmaceuticals, Pittsburgh, PA, USA) for the treatment of heavy menstrual bleeding. DESIGN: Individual patient data (IPD) meta-analysis of existing randomised controlled trials to determine the short- to medium-term effects of hysterectomy, EA and Mirena. A population-based retrospective cohort study based on record linkage to investigate the long-term effects of ablative techniques and hysterectomy in terms of failure rates and complications. Cost-effectiveness analysis of hysterectomy versus first- and second-generation ablative techniques and Mirena. SETTING: Data from women treated for heavy menstrual bleeding were obtained from national and international trials. Scottish national data were obtained from the Scottish Information Services Division. PARTICIPANTS: Women who were undergoing treatment for heavy menstrual bleeding were included. INTERVENTIONS: Hysterectomy, first- and second-generation EA, and Mirena. MAIN OUTCOME MEASURES: Satisfaction, recurrence of symptoms, further surgery and costs. RESULTS: Data from randomised trials indicated that at 12 months more women were dissatisfied with first-generation EA than hysterectomy [odds ratio (OR): 2.46, 95% confidence interval (CI) 1.54 to 3.93; p = 0.0002), but hospital stay [WMD (weighted mean difference) 3.0 days, 95% CI 2.9 to 3.1 days; p < 0.00001] and time to resumption of normal activities (WMD 5.2 days, 95% CI 4.7 to 5.7 days; p < 0.00001) were longer for hysterectomy. Unsatisfactory outcomes associated with first- and second-generation techniques were comparable [12.2% (123/1006) vs 10.6% (110/1034); OR 1.20, 95% CI 0.88 to 1.62; p = 0.2). Rates of dissatisfaction with Mirena and second-generation EA were similar [18.1% (17/94) vs 22.5% (23/102); OR 0.76, 95% CI 0.38 to 1.53; p = 0.4]. Indirect estimates suggested that hysterectomy was also preferable to second-generation EA (OR 2.32, 95% CI 1.27 to 4.24; p = 0.006) in terms of patient dissatisfaction. The evidence to suggest that hysterectomy is preferable to Mirena was weaker (OR 2.22, 95% CI 0.94 to 5.29; p = 0.07). In women treated by EA or hysterectomy and followed up for a median [interquartile range (IQR)] duration of 6.2 (2.7-10.8) and 11.6 (7.9-14.8) years, respectively, 962/11,299 (8.5%) women originally treated by EA underwent further gynaecological surgery. While the risk of adnexal surgery was similar in both groups [adjusted hazards ratio 0.80 (95% CI 0.56 to 1.15)], women who had undergone ablation were less likely to need pelvic floor repair [adjusted hazards ratio 0.62 (95% CI 0.50 to 0.77)] and tension-free vaginal tape surgery for stress urinary incontinence [adjusted hazards ratio 0.55 (95% CI 0.41 to 0.74)]. Abdominal hysterectomy led to a lower chance of pelvic floor repair surgery [hazards ratio 0.54 (95% CI 0.45 to 0.64)] than vaginal hysterectomy. The incidence of endometrial cancer following EA was 0.02%. Hysterectomy was the most cost-effective treatment. It dominated first-generation EA and, although more expensive, produced more quality-adjusted life-years (QALYs) than second-generation EA and Mirena. The incremental cost-effectiveness ratios for hysterectomy compared with Mirena and hysterectomy compared with second-generation ablation were £1440 per additional QALY and £970 per additional QALY, respectively. CONCLUSIONS: Despite longer hospital stay and time to resumption of normal activities, more women were satisfied after hysterectomy than after EA. The few data available suggest that Mirena is potentially cheaper and more effective than first-generation ablation techniques, with rates of satisfaction that are similar to second-generation techniques. Owing to a paucity of trials, there is limited evidence to suggest that hysterectomy is preferable to Mirena. The risk of pelvic floor surgery is higher in women treated by hysterectomy than by ablation. Although the most cost-effective strategy, hysterectomy may not be considered an initial option owing to its invasive nature and higher risk of complications. Future research should focus on evaluation of the clinical effectivesness and cost-effectiveness of the best second-generation EA technique under local anaesthetic versus Mirena and types of hysterectomy such as laparoscopic supracervical hysterectomy versus conventional hysterectomy and second-generation EA. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Should endometrial polyps be removed in patients with postmenopausal bleeding?-an assessment of study designs and report of a failed randomised controlled trial (ISRCTN73825127).

We describe the design of a randomised controlled trial to evaluate the efficacy of endometrial polyp removal in women with postmenopausal bleeding. We designed a trial in which patients with postmenopausal bleeding and endometrial thickness >4 mm undergo hysteroscopy. If during hysteroscopy an endometrial polyp was diagnosed, patients were asked to participate in this trial and after informed consent allocated to immediate removal of the polyp or expectant management. This trial suffered from lack of recruitment related both to doctors seeking for informed consent as well as to patients' unwillingness to participate in this trial. However, a randomised controlled trial on this subject is still necessary to evaluate the efficacy of uterine cavity evaluation in the diagnostic work-up of women with postmenopausal bleeding, focussing on benign pathology. Therefore, we propose an alternative design, which might be more feasible.

Cost-effectiveness of transvaginal sonography and saline infused sonography in the evaluation of menorrhagia.

OBJECTIVES: To assess the cost-effectiveness of transvaginal sonography (TVS) and saline infused sonography (SIS) in the diagnostic work-up of women with menorrhagia. METHODS: We performed a decision analysis in which we compared the percentage of patients treated successfully and cost of six strategies for the evaluation of menorrhagia: (0) hormonal treatment, (I) treatment of all patients with balloon ablation, (II) TVS and therapeutic hysteroscopy, (III) TVS, SIS and therapeutic hysteroscopy, (IV) SIS and therapeutic hysteroscopy, and (V) diagnostic hysteroscopy and therapeutic hysteroscopy. Hormonal treatment was considered to be the reference strategy to which the five strategies were compared. Data were obtained from the published literature. In order to evaluate the robustness of our results, we performed extensive sensitivity analyses, in which we varied sensitivity and specificity of TVS and hysteroscopy, the prevalence of intracavitary abnormalities, as well as costs of TVS and SIS. RESULTS: We found that the strategy starting with SIS (IV) and the strategy with diagnostic hysteroscopy (V) revealed the highest number of patients treated successfully for menorrhagia. In terms of cost-effectiveness, SIS for all patients was superior over immediate diagnostic hysteroscopy for all patients. Strategies starting with TVS were less effective than the strategy starting with SIS. CONCLUSIONS: We recommend SIS as the procedure of first choice in the work-up for women with menorrhagia.