Hysterosalpingo-foam sonography versus hysterosalpingography during fertility work-up: an economic evaluation alongside a randomized controlled trial.

STUDY QUESTION: What are the costs and effects of tubal patency testing by hysterosalpingo-foam sonography (HyFoSy) compared to hysterosalpingography (HSG) in infertile women during the fertility work-up? SUMMARY ANSWER: During the fertility work-up, clinical management based on the test results of HyFoSy leads to slightly lower, though not statistically significant, live birth rates, at lower costs, compared to management based on HSG results. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during the fertility work-up is performed by HSG. The FOAM trial, formally a non-inferiority study, showed that management decisions based on the results of HyFoSy resulted in a comparable live birth rate at 12 months compared to HSG (46% versus 47%; difference -1.2%, 95% CI: -3.4% to 1.5%; P = 0.27). Compared to HSG, HyFoSy is associated with significantly less pain, it lacks ionizing radiation and exposure to iodinated contrast medium. Moreover, HyFoSy can be performed by a gynaecologist during a one-stop fertility work-up. To our knowledge, the costs of both strategies have never been compared. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation alongside the FOAM trial, a randomized multicenter study conducted in the Netherlands. Participating infertile women underwent, both HyFoSy and HSG, in a randomized order. The results of both tests were compared and women with discordant test results were randomly allocated to management based on the results of one of the tests. The follow-up period was twelve months. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1160 infertile women (18-41 years) scheduled for tubal patency testing. The primary outcome was ongoing pregnancy leading to live birth. The economic evaluation compared costs and effects of management based on either test within 12 months. We calculated incremental cost-effectiveness ratios (ICERs): the difference in total costs and chance of live birth. Data were analyzed using the intention to treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 of the 1160 women underwent both tubal tests and had data available: 747 women with concordant results (48% live births), 136 with inconclusive results (40% live births), and 143 with discordant results (41% had a live birth after management based on HyFoSy results versus 49% with live birth after management based on HSG results). When comparing the two strategies-management based on HyfoSy results versus HSG results-the estimated chance of live birth was 46% after HyFoSy versus 47% after HSG (difference -1.2%; 95% CI: -3.4% to 1.5%). For the procedures itself, HyFoSy cost €136 and HSG €280. When costs of additional fertility treatments were incorporated, the mean total costs per couple were €3307 for the HyFoSy strategy and €3427 for the HSG strategy (mean difference €-119; 95% CI: €-125 to €-114). So, while HyFoSy led to lower costs per couple, live birth rates were also slightly lower. The ICER was €10 042, meaning that by using HyFoSy instead of HSG we would save €10 042 per each additional live birth lost. LIMITATIONS, REASONS FOR CAUTION: When interpreting the results of this study, it needs to be considered that there was a considerable uncertainty around the ICER, and that the direct fertility enhancing effect of both tubal patency tests was not incorporated as women underwent both tubal patency tests in this study. WIDER IMPLICATION OF THE FINDINGS: Compared to clinical management based on HSG results, management guided by HyFoSy leads to slightly lower live birth rates (though not statistically significant) at lower costs, less pain, without ionizing radiation and iodinated contrast exposure. Further research on the comparison of the direct fertility-enhancing effect of both tubal patency tests is needed. STUDY FUNDING/COMPETING INTEREST(S): FOAM trial was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, and interpretation of the data. K.D. reports travel-and speakers fees from Guerbet and her department received research grants from Guerbet outside the submitted work. H.R.V. received consulting-and travel fee from Ferring. A.M.v.P. reports received consulting fee from DEKRA and fee for an expert meeting from Ferring, both outside the submitted work. C.H.d.K. received travel fee from Merck. F.J.M.B. received a grant from Merck and speakers fee from Besins Healthcare. F.J.M.B. is a member of the advisory board of Merck and Ferring. J.v.D. reported speakers fee from Ferring. J.S. reports a research agreement with Takeda and consultancy for Sanofi on MR of motility outside the submitted work. M.v.W. received a travel grant from Oxford Press in the role of deputy editor for Human Reproduction and participates in a DSMB as independent methodologist in obstetrics studies in which she has no other role. B.W.M. received an investigator grant from NHMRC GNT1176437. B.W.M. reports consultancy for ObsEva, Merck, Guerbet, iGenomix, and Merck KGaA and travel support from Merck KGaA. V.M. received research grants from Guerbet, Merck, and Ferring and travel and speakers fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: International Clinical Trials Registry Platform No. NTR4746.

Telehealth as a Means of Enabling Health Equity.

OBJECTIVE: The goal of this paper is to provide a consensus review on telehealth delivery prior to and during the COVID-19 pandemic to develop a set of recommendations for designing telehealth services and tools that contribute to system resilience and equitable health. METHODS: The IMIA-Telehealth Working Group (WG) members conducted a two-step approach to understand the role of telehealth in enabling global health equity. We first conducted a consensus review on the topic followed by a modified Delphi process to respond to four questions related to the role telehealth can play in developing a resilient and equitable health system. RESULTS: Fifteen WG members from eight countries participated in the Delphi process to share their views. The experts agreed that while telehealth services before and during COVID-19 pandemic have enhanced the delivery of and access to healthcare services, they were also concerned that global telehealth delivery has not been equal for everyone. The group came to a consensus that health system concepts including technology, financing, access to medical supplies and equipment, and governance capacity can all impact the delivery of telehealth services. CONCLUSION: Telehealth played a significant role in delivering healthcare services during the pandemic. However, telehealth delivery has also led to unintended consequences (UICs) including inequity issues and an increase in the digital divide. Telehealth practitioners, professionals and system designers therefore need to purposely design for equity as part of achieving broader health system goals.

Can hysterosalpingo-foam sonography replace hysterosalpingography as first-choice tubal patency test? A randomized non-inferiority trial.

STUDY QUESTION: Does hysterosalpingo-foam sonography (HyFoSy) lead to similar pregnancy outcomes, compared with hysterosalpingography (HSG), as first-choice tubal patency test in infertile couples? SUMMARY ANSWER: HyFoSy and HSG produce similar findings in a majority of patients and clinical management based on the results of either HyFoSy or HSG, leads to comparable pregnancy outcomes. HyFoSy is experienced as significantly less painful. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during fertility work-up is performed by HSG. HyFoSy is an alternative imaging technique lacking ionizing radiation and iodinated contrast medium exposure which is less expensive than HSG. Globally, there is a shift towards the use of office-based diagnostic methods, such as HyFoSy. STUDY DESIGN, SIZE, DURATION: This multicentre, prospective, comparative study with a randomized design was conducted in 26 hospitals in The Netherlands. Participating women underwent both HyFoSy and HSG in randomized order. In case of discordant results, women were randomly allocated to either a management strategy based on HyFoSy or one based on HSG. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included infertile women between 18 and 41 years old who were scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male infertility or a known iodine contrast allergy were excluded. The primary outcome for the comparison of the HyFoSy- and HSG-based strategies was ongoing pregnancy leading to live birth within 12 months after inclusion in an intention-to-treat analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 women underwent HyFoSy and HSG. HyFoSy was inconclusive in 97 of them (9.5%), HSG was inconclusive in 30 (2.9%) and both were inconclusive in 9 (0.9%). In 747 women (73%) conclusive tests results were concordant. Of the 143/1026 (14%) with discordant results, 105 were randomized to clinical management based on the results of either HyFoSy or HSG. In this group, 22 of the 54 women (41%) allocated to management based on HyFoSy and 25 of 51 women (49%) allocated to management based on HSG had an ongoing pregnancy leading to live birth (Difference -8%; 95% CI: -27% to 10%). In total, clinical management based on the results of HyFoSy was estimated to lead to a live birth in 474 of 1026 women (46%) versus 486 of 1026 (47%) for management based on HSG (Difference -1.2%; 95% CI: -3.4% to 1.5%). Given the pre-defined margin of -2%, statistically significant non-inferiority of HyFoSy relative to HSG could not be demonstrated (P = 0.27). The mean pain score for HyFoSy on the 1-10 Visual Analogue Scale (VAS) was 3.1 (SD 2.2) and the mean VAS pain score for HSG was 5.4 (SD 2.5; P for difference < 0.001). LIMITATIONS, REASONS FOR CAUTION: Since all women underwent both tubal patency tests, no conclusions on a direct therapeutic effect of tubal flushing could be drawn. WIDER IMPLICATIONS OF THE FINDINGS: HyFoSy or HSG produce similar tubal pathology findings in a majority of infertile couples and, where they differ, a difference in findings does not lead to substantial difference in pregnancy outcome, while HyFoSy is associated with significantly less pain. STUDY FUNDING/COMPETING INTEREST(S): The FOAM study was an investigator-initiated study funded by ZonMw, The Netherlands organization for Health Research and Development (project number 837001504). ZonMw funded the whole project. IQ Medical Ventures provided the ExEm-foam® kits free of charge. The funders had no role in study design, collection, analysis and interpretation of the data. K.D. reports travel and speaker fees from Guerbet. F.J.M.B. reports personal fees as a member of the external advisory board for Merck Serono, The Netherlands, and a research support grant from Merck Serono, outside the submitted work. C.B.L. reports speakers' fee from Ferring in the past, and his department receives research grants from Ferring, Merck and Guerbet. J.S. reports a research agreement with Takeda on MR of motility outside the submitted work. M.V.W. reports leading The Netherlands Satellite of the Cochrane Gynaecology and Fertility Group. B.W.J.M. is supported by an NHMRC Investigator grant (GNT1176437). B.W.J.M. reports consultancy for Guerbet and research funding from Merck and Guerbet. V.M. reports non-financial support from IQ medicals ventures, during the conduct of the study; grants and personal fees from Guerbet, outside the submitted work. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: NTR4746/NL4587 (https://www.trialregister.nl). TRIAL REGISTRATION DATE: 19 August 2014. DATE OF FIRST PATIENT'S ENROLMENT: 7 May 2015.

PREsurgery thoughts - thoughts on prehabilitation in oncologic gynecologic surgery, a qualitative template analysis in older adults and their healthcare professionals.

PURPOSE: This study aimed to reveal information that can be used for composing a prehabilitation program tailored to elderly gynecological oncological patients and is applicable to healthcare professionals. We investigated possible content and indications for prehabilitation, and what potential barriers might exist. MATERIALS AND METHODS: Because of the primary exploratory study aim, inductive thematic template analysis on semi-structured interviews with gynecologic oncological patients aged ≥60 years and healthcare professionals were used. RESULTS: 16 patients and 20 healthcare professionals were interviewed. Three themes important for prehabilitation were found: (1) "Motivation," (2) "Practical issues and facilitators," and (3) "Patient-related factors." A short time interval between diagnosis and surgery was reported as a potential barrier for prehabilitation. Given components for a tailor-made prehabilitation program are: (1) The first contact with a nurse who screens the patients, gives tailor-made advice on prehabilitation and keeps patients motivated and supports them mentally; (2) If patients are referred to a more extensive/supervised program, this should preferably be arranged close to a patients' home. CONCLUSION: Based on our findings, an outline of a patient-tailored prehabilitation program was developed. The main important themes for prehabilitation were "Motivation," "Practical issues and facilitators," and "Patient-related factors."IMPLICATIONS FOR REHABILITATIONPatients and healthcare professionals are positive about prehabilitation.Main themes for designing a prehabilitation program are "Motivation," "Practical issues and facilitators," and "Patient-related factors."Nursing staff can play a key role in prehabilitation.It is important to screen patients for specific impairments to obtain a tailor-made prehabilitation program.For some patients, general advice on prehabilitation might be sufficient, while others may need more supervision.The time interval between diagnosis and surgery is often short and is perceived as a potentially significant barrier for an effective prehabilitation program.

Risk assessment for postoperative outcomes in a mixed hospitalized gynecological population by the Dutch safety management system (Veiligheidsmanagementsysteem, VMS) screening tool 'frail elderly'.

PURPOSE: Frailty is associated with a higher risk for negative postoperative outcomes. This study aimed to determine the association between the screening tool of the Dutch safety management system, Veiligheidsmanagementsysteem (VMS) 'frail elderly' and postoperative complications in a gynecological population. METHODS: This cohort study included women aged 70 years or older, who were scheduled for any kind of gynecological surgery. VMS screening data (including risk for delirium, falling, malnutrition, and functional impairment) were extracted from the electronic patient records. VMS score could range between 0 and 4 patients with a VMS score of one or more were considered frail. Data on possible confounding factors and complications within 30 days after surgery, classified with the Clavien-Dindo classification, were collected. Regression analysis was performed. RESULTS: 157 women were included with a median age of 74 years (inter quartile range 71-79). Most patients underwent prolapse surgery (52%) or hysterectomy (31%). Forty-one patients (26%) experienced any postoperative complication. Sixty-two patients (39%) were considered frail preoperatively by the VMS screening tool. Frailty measured with the VMS screening tool was not independently associated with postoperative complications in multivariable analysis (Odds ratio 1.18; 95% CI 0.49-2.82). However, a recent fall in the last 6 months (n = 208) was associated with postoperative complications (Odds ratio 3.90; 95% CI 1.57-9.66). CONCLUSION: An independent association between frailty, determined by the VMS screening tool 'Frail elderly', and postoperative complications in gynecological surgery patients could not be confirmed. A recent fall in the last 6 months seems associated with postoperative complications.

The Needs of Dutch Women During Decision-Making About Treatment for Miscarriage.

OBJECTIVE: To explore the needs of women during decision-making about treatment for miscarriage. DESIGN: Descriptive qualitative design. SETTINGS: University and teaching hospitals in the Netherlands. PARTICIPANTS: We selected a purposive sample of 16 women who needed treatment for miscarriage from an electronic patient file system. We ensured maximum variation by sampling in different hospitals and selecting women with different ages, numbers of children, miscarriage histories, treatment types, and educational levels. METHODS: We conducted face-to-face individual, semistructured interviews and used thematic analysis to identify, analyze, and describe themes. RESULTS: We identified one overarching theme, Decision Based on Reason and Emotion, and three related subthemes: Certainty, Information, and SupportFrom Environment. CONCLUSION: Health care professionals should be aware of how women's decision-making is structured in the context of treatment choices for miscarriage, and discussion regarding treatment should address reason and emotion.

The FOAM study: is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial.

BACKGROUND: Tubal pathology is a causative factor in 20% of subfertile couples. Traditionally, tubal testing during fertility work-up is performed by hysterosalpingography (HSG). Hysterosalpingo-foam sonography (HyFoSy) is a new technique that is thought to have comparable accuracy as HSG, while it is less expensive and more patient friendly. HyFoSy would be an acceptable alternative for HSG, provided it has similar effectiveness in terms of patient outcomes. METHODS/DESIGN: We aim to compare the effectiveness and costs of management guided by HyFoSy or by HSG. Consenting women will undergo tubal testing by both HyFoSy and HSG in a randomized order during fertility work-up. The study group will consist of 1163 subfertile women between 18 and 41 years old who are scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male subfertility or a known contrast (iodine) allergy will be excluded. We anticipate that 7 % (N = 82) of the participants will have discordant test results for HyFoSy and HSG. These participants will be randomly allocated to either a management strategy based on HyFoSy or a management strategy based on HSG, resulting in either a diagnostic laparoscopy with chromopertubation or a strategy that assumes tubal patency (intrauterine insemination or expectant management). The primary outcome is ongoing pregnancy leading to live birth within 12 months after randomization. Secondary outcomes are patient pain scores, time to pregnancy, clinical pregnancy, miscarriage rate, multiple pregnancy rate, preterm birth rate and number of additional treatments. Costs will be estimated by counting resource use and calculating unit prices. DISCUSSION: This trial will compare the effectiveness and costs of HyFoSy versus HSG in assessing tubal patency in subfertile women. TRIAL REGISTRATION: Dutch Trial Register (NTR 4746, http://www.trialregister.nl ). Date of registration: 19 August 2014.

Acute influenza virus-associated encephalitis and encephalopathy in adults: a challenging diagnosis.

Background: Acute influenza-associated encephalopathy/encephalitis (IAE) in adults is a rare but well-known complication of influenza virus infection. The diagnosis is difficult to make due to the absence of distinctive clinical symptoms and validated diagnostic criteria. We present an illustrative case and a case review on acute IAE in adults. Methods: We performed a Medline search of the English literature using the terms influenz*, encephal* and adult, and constructed a database of detailed descriptions of patients with influenza virus infection with influenza-like symptoms at the onset of neurological symptoms. Results: A total of 44 patients were included. Confusion and seizures were the most prevalent neurological symptoms, present in 12 (27 %) and 10 (23 %) patients, respectively. Magnetic resonance imaging (MRI) was performed in 21 patients and anomalies were found in 13 (62 %), with lesions located throughout the brain. Influenza virus RNA was detected in cerebrospinal fluid (CSF) in 5 (16 %) of 32 patients. Eight (18 %) of the forty-four patients died. The benefits of antiviral and immunomodulatory therapy have not been well studied. Discussion: Our results show that many different neurological symptoms can be present in patients with acute onset IAE. Therefore, the diagnosis should be considered in patients with fever and neurological symptoms, especially during the influenza season. Laboratory diagnosis consists of demonstration of influenza virus RNA in brain tissue, CSF or respiratory samples, and demonstration of intrathecal antibody production against influenza virus. The presence of brain lesions in MRI and influenza virus in CSF appear to be of prognostic value.

Treatment of Immunocompromised, Critically Ill Patients with Influenza A H1N1 Infection with a Combination of Oseltamivir, Amantadine, and Zanamivir.

Immunocompromised patients are at increased risk of complications of influenza virus infection. We report on two critically ill patients on immunosuppressive medication with influenza pneumonia. In both patients, oseltamivir monotherapy did not result in clearance of the virus after 18 and five days, respectively. After adding zanamivir and amantadine to the treatment, PCRs on pharyngeal and/or plasma specimens turned negative in both patients after four and three days, respectively. We suggest, that in critically ill patients with influenza A H1N1 infection, treatment efficacy should be monitored closely and treatment with a combination of antiviral drugs should be considered.

Influenza virus infection in pregnancy: a review.

BACKGROUND: Influenza virus infection is very common and a significant cause of morbidity and mortality in specific populations like pregnant women. Following the 2009 pandemic, several reports on the effects of influenza virus infection on maternal health and pregnancy outcome have been published. Also the safety and efficacy of antiviral treatment and vaccination of pregnant women have been studied. In this review, we have analyzed and summarized these data. OBJECTIVE: To provide information on the influence of influenza virus infection during pregnancy on maternal health and pregnancy outcome and on the effect of treatment and vaccination. DATA SOURCES: We have searched Medline, Embase and the Cochrane Library. We used influenza, influenz*, pregnancy and pregnan* as search terms. STUDY SELECTION: In total, 294 reports were reviewed and judged according to the STROBE guidelines or CONSORT statement. In all, 100 studies, published between 1961 and 2015, were included. RESULTS: Compared to the general population, pregnant women are more often hospitalized and admitted to an intensive care unit due to influenza virus infection. For hospitalized patients, increased rates of preterm birth and fetal/neonatal death are reported. Early treatment with oseltamivir is associated with a reduced risk of severe disease. Vaccination of pregnant women is safe and reduces maternal and neonatal morbidity. CONCLUSIONS: There is level 2b evidence that maternal health and pregnancy outcome can be severely affected by influenza virus infection. Antiviral treatment may diminish these effects and vaccination protects pregnant women and neonates from infection (level of evidence 2b and 1b, respectively).

High rate of chronic villitis in placentas of pregnancies complicated by influenza A/H1N1 infection.

INTRODUCTION: Pandemic influenza A/H1N1 infection during pregnancy has a negative impact on several aspects of pregnancy outcome. As yet, no elucidating mechanism has been revealed for these effects. We investigated whether placentas of pregnancies complicated by 2009 influenza A/H1N1 infection demonstrated an increased rate of chronic villitis and whether this villitis was caused by influenza virus. METHODS: We performed a cohort study on 145 pregnant outpatients during the 2009-2010 influenza A H1N1 pandemic. The placentas of patients with influenza infection were examined for histologic signs of chronic villitis. In case of villitis, polymerase chain reaction (PCR) on influenza virus was performed on placental tissue. RESULTS: 29 patients had influenza infection. Placentas of 15 of these patients were collected and examined. In 7 cases (47%) chronic villitis was detected. Placental weight and birth weight of the neonates did not differ between cases with and without chronic villitis. In all cases PCR was negative for influenza. CONCLUSION: In our series, chronic villitis was present in a high proportion of placentas of pregnancies complicated by 2009 influenza A/H1N1 infection. We could not demonstrate the presence of influenza virus in placental tissue.

The patient's perspective in the Dutch National Technical Agreement on Telemedicine.

In 2007, the Dutch National Technical Agreement (NTA) for Telemedicine was established. Telemedicine deals with care processes. The goals of Telemedicine were defined broadly, including quality of life in non-medical terms as seen from the patient's perspective: 1) independence, 2) self-reliance; 3) participation in society and social life and 4) self-determination (autonomy through freedom of choice) for the care consumer and his environment. Quality aspects were defined at three levels:1) patient level Telemedicine must be in line with his needs. 2) level of information provision, such as: patient's rights in information control were also defined in the NTA: the care consumer has ultimate control over his own data. The care consumer decides who, in which functional capacity within the care process, is entitled to access which data at which level (reading) and is entitled to process it in some way: making additions, changes or possibly deleting (writing). On request, the healthcare provider must allow the care consumer access to his own data as quickly as possible and/or provide a copy of (part of) the record.3) level of business processes, e.g.it is important that the care process is designed on the basis of statutory requirements for the allocation and registration of the roles, rights and obligations of all actors concerned. For quality assurance, the processes must be defined on the basis of the function that they perform in the achievement of the goals (intended outcome), from the starting situation (input). The intended outcome means that the needs or requirements of the involved parties are fulfilled. The quality of the Telemedicine service must be assured in a cyclical and ongoing process. This can best be done by developing a quality management system based on indicators and criteria for quality.

Empowering the patient with ICT-tools: the unfulfilled promise.

For the patient, ICT is a resource that helps the individual to cope with illness. On the basis of in depth interviews with diabetic patients, their desired coping strategies that relate to communication and information were identified. The strategies fall into the following categories: Contact with fellow-patients, Care (choice of care, control of care and control of information) and social environment. Patient empowerment by ICT means that ICT enables the patient to cope with illness. A number of ICT-tools currently available for patients were analyzed on the aspect of patient empowerment. Findings are that most tools provide little support for patients' coping behaviour in choice (of treatment and caregiver), control of care and control of information (by the patient). This lack of effective instrumental support for a patient's coping and empowerment is not explained by technical restraints, but by the dominance on the supply side in healthcare. To meet the neglected needs of patients, caregivers would have to adapt the organisation of their work. Examples of success in applying ICT/Telemedicine are given. The structural impediments for patient empowerment must be further clarified and removed or minimised.