Endometriosis risk and hormonal contraceptive usage: A nationwide cohort study.

OBJECTIVE: To investigate whether an early need of hormonal contraceptive (HC), or a failure to find a suitable method, are warning signs for endometriosis. DESIGN: A retrospective cohort study. SETTING: Sweden. POPULATION: The cohort consisted of 720 805 women aged 12-27 years during the period 2005-2017. All women, regardless of whether they received a diagnosis of endometriosis or not (reference group), were included. METHODS: We used data from Swedish national registers. Risks are expressed as crude and adjusted hazard ratios (HRs and aHRs, respectively) with 95% confidence intervals (95% CIs), adjusted for age, education level, civil status, parity, country of birth, and diagnoses of infertility, dysmenorrhea or depression. MAIN OUTCOME MEASURES: A diagnosis of endometriosis between 12 and 27 years of age. RESULTS: During this period, 3268 women were diagnosed with endometriosis (0.45%). Women who started HC at the ages of 12-14 years had a higher risk of receiving the diagnosis (aHR 2.53, 95% CI 2.21-2.90) than those who began at age 17 years or older. Having tried more types of HCs was associated with a twofold increased risk of endometriosis (more that three types of HC, aHR 2.31, 95% CI 1.71-3.12). Using HC for more than 1 year was associated with a decreased risk of endometriosis (>1 year, aHR 0.53, 95% CI 0.48-0.59). Women with endometriosis more commonly had dysmenorrhea, depression or infertility. CONCLUSIONS: The use of HCs at an early age and a failure to find a suitable HC were identified as warning signs of later receiving an endometriosis diagnosis. A longer duration of HC usage reduced the risk of receiving the diagnosis.

Clinical factors associated with quality of life among women with endometriosis: a cross-sectional study.

BACKGROUND: Endometriosis often leads to a decrease in Quality of Life (QoL), due to its impact on various aspects of women's lives, such as social life, mental health, sex life, and working capacity. Although previous studies have assessed QoL in women with endometriosis, few studies have explored the impact of different clinical variables on QoL. The aim of this study was to investigate how women with endometriosis perceive their QoL, and to analyze which clinical factors are associated with QoL. METHODS: The Endometriosis Health Profile-30 and the ENDOCARE Questionnaire were distributed to 1000 women diagnosed with endometriosis from 10 different clinics across Sweden. The responses from 476 women were included in univariate and multivariable regression analyses, where the clinical factors were correlated with overall QoL and QoL dimensions. RESULTS: The women participating in this study reported a low QoL. The clinical factors that showed a significant correlation with overall QoL were age at first onset of endometriosis symptoms (ß= -0.64, p < 0.001), having more than 10 visits to general practitioners before referral to a gynecologist (ß = 5.58, p = 0.036), current or previous mental health issues (ß = 7.98, p < 0.001) patient-centeredness (ß= -2.59, p < 0.001) and use of opioids (ß = 7.14, p = 0.002). CONCLUSIONS: This study shows that opioid use and mental health issues were associated with a worse QoL, whereas a higher degree of patient-centeredness was associated with a better QoL. The association between opioid use and a worse QoL might not entirely be caused by the opioid use itself but also by symptom severity and mental health issues. An improved patient-centeredness and more focus on taking care of mental health issues would reasonably result in a better QoL for women with endometriosis.

Demographic and clinical characteristics determining patient-centeredness in endometriosis care.

PURPOSE: The primary aim of this study was to assess patient-centeredness of endometriosis care in a national sample of Swedish women with endometriosis. The secondary aims were to assess the importance of different dimensions of endometriosis care and to analyze demographic and clinical determinants associated with the experience of patient-centeredness. METHODS: This cross-sectional study included 476 women with confirmed endometriosis. An invitation to participate was sent to 1000 randomly selected women aged ≥ 18 years having any endometriosis diagnosis and who had visited a gynecological clinic due to endometriosis problems any time during the past five years. Participants were recruited from ten different-sized gynecology clinics all over Sweden. The invitation letter had a link to the digital survey, which consisted of demographic and clinical questions, and the ENDOCARE questionnaire (ECQ). ECQ measures experiences, importance and patient-centeredness of ten dimensions of endometriosis care. Univariate and multiple regression analyses were used to analyze which patient-specific demographic and clinical determinants were associated with the experience of patient-centeredness. RESULTS: The response rate was 48%. The results indicate that Swedish women with endometriosis experience low patient-centeredness and rate relational aspects with healthcare professionals as the most important aspects of care. Having a gynecologist with patient responsibility was an independent predictor for high patient-centeredness. CONCLUSION: Women with endometriosis in Sweden experience low patient-centeredness, reflecting the urgent need for improvement. More effort should be given to develop the relational aspects of care. Women with endometriosis should have a responsible gynecologist to care for treatment and follow-up.

Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies.

Persistent organic pollutants (POPs) are industrial chemicals resistant to degradation and have been shown to have adverse effects on reproductive health in wildlife and humans. Although regulations have reduced their levels, they are still ubiquitously present and pose a global concern. Here, we studied a cohort of 185 women aged 21-43 years with a median of 2 years of infertility who were seeking assisted reproductive technology (ART) treatment at the Carl von Linné Clinic in Uppsala, Sweden. We analyzed the levels of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenyl ethers (PBDEs), and 8 perfluoroalkyl substances (PFASs) in the blood and follicular fluid (FF) samples collected during ovum pick-up. Impact of age on chemical transfer from blood to FF was analyzed. Associations of chemicals, both individually and as a mixture, to 10 ART endpoints were investigated using linear, logistic, and weighted quantile sum regression, adjusted for age, body mass index, parity, fatty fish intake and cause of infertility. Out of the 30 chemicals, 20 were detected in more than half of the blood samples and 15 in FF. Chemical transfer from blood to FF increased with age. Chemical groups in blood crossed the blood-follicle barrier at different rates: OCPs > PCBs > PFASs. Hexachlorobenzene, an OCP, was associated with lower anti-Müllerian hormone, clinical pregnancy, and live birth. PCBs and PFASs were associated with higher antral follicle count and ovarian response as measured by ovarian sensitivity index, but also with lower embryo quality. As a mixture, similar findings were seen for the sum of PCBs and PFASs. Our results suggest that age plays a role in the chemical transfer from blood to FF and that exposure to POPs significantly associates with ART outcomes. We strongly encourage further studies to elucidate the underlying mechanisms of reproductive effects of POPs in humans.

Junior doctors' experiences with interprofessional collaboration: Wandering the landscape.

CONTEXT: The transition from medical student to junior doctor is challenging. Junior doctors need to become part of the physician community of practice (CoP), while dealing with new responsibilities, tasks and expectations. At the same time, they need to learn how to navigate the frontiers and intersections with the other communities of practice that form the Landscape of Practice (LoP). This study aims to understand how junior doctors experience interprofessional collaboration (IPC) and what elements shape these experiences considering their transition to clinical practice. METHODS: In this multicentre qualitative study, 13 junior doctors individually drew two rich pictures of IPC experiences, one positive and one negative. A rich picture is a visual representation, a drawing of a particular situation intended to capture the complex and non-verbal elements of an experience. We used semi-structured interviews to deepen the understanding of junior doctors' depicted IPC experiences. We analysed both visual materials and interview transcripts iteratively, for which we adopted an inductive constructivist thematic analysis. RESULTS: While transitioning into a doctor, junior doctors become foremost members of the physician CoP and shape their professional identity based on perceived values in their physician community. Interprofessional learning occurs implicitly, without input from the interprofessional team. As a result, junior doctors struggle to bridge the gap between themselves and the interprofessional team, preventing IPC learning from developing into an integrative process. This professional isolation leaves junior doctors wandering the landscape of practice without understanding roles, attitudes and expectations of others. CONCLUSIONS: Learning IPC needs to become a collective endeavour and an explicit learning goal, based on multisource feedback to take advantage of the expertise already present in the LoP. Furthermore, junior doctors need a safe environment to embrace and reflect on the emotions aroused by interprofessional interactions, under the guidance of experienced facilitators.

Combined expression of HOXA11 and CD10 identifies endometriosis versus normal tissue and tumors.

The gold standard for diagnosing endometriosis is by laparoscopic visual demonstration of ectopic endometrial lesions outside the uterus, preferably verified by biopsy and microscopical examination. Molecular markers to facilitate the microscopical diagnosis of endometriosis and for distinguishing endometriosis from other benign and malignant lesions are lacking. Our aim was to test and validate an immunohistochemical antibody panel for improved diagnostic accuracy of endometriosis. Both CD10 and HOXA11 have been implicated in regulation of endometrial homeostasis. Here we have analyzed the expression pattern of these two proteins using immunohistochemistry on human tissues in a tissue microarray format. CD10 and HOXA11 expression in endometriosis lesions were compared to expression patterns in a range of normal tissues and in primary- and metastatic lesions of endometrial-, cervical- and ovarian cancer. HOXA11 and CD10 were expressed in 98% and 91% of endometriosis lesions and the combined double-positive expression profile of both HOXA11 and CD10 was highly sensitive for ectopic endometrial tissue (90%). The specificity and sensitivity for this double-positive signature in endometriosis was significantly different from all investigated tissues, cancers and metastases except normal, eutopic endometrial- and cervical mucosa. The combination of HOXA11 and CD10 expression profiles provides a useful tool to identify ectopic endometrial tissue and for distinguishing endometriosis from various types of gynecological malignancies and metastases.

Age-related differences in experienced patient-centred care among women with endometriosis.

Younger women with endometriosis report lower quality of life and seek more care. Patient-centeredness is a central part of quality of care. The aim of this study was to investigate if women younger than 35 years experience endometriosis care as less patient-centred than women 35 years and older. The ENDOCARE Questionnaire was sent to 1000 randomly selected women with verified endometriosis from 10 clinics in Sweden. Answers from 469 women were analysed using Mann-Whitney's U-test and Spearman's correlation. Our findings show that younger women experience care as less patient-centred regarding 'Physical comfort,' 'Continuity,' 'Access to care,' 'Technical skills,' and overall patient-centeredness score in comparison with older women. On the contrary, younger women experience more patient-centeredness in 'Emotional support'. Positive correlations were found for age and 'Access to care' and 'Technical skills', while a negative correlation was found for age and 'Emotional support'. Impact StatementWhat is already known on this subject? There is a need for improvement of quality of endometriosis care. Patient-centeredness is an important part of care improvement work. Many factors have an impact on experienced patient-centeredness in endometriosis care, whereof age is one possible determinant. Given the impact of age on QoL and care seeking behaviour, age may also have influence on the experience patient-centeredness.What do the results of this study add? Our findings show that younger women experience their endometriosis care as less patient-centred than older women.What are the implications of these findings for clinical practice and/or further research? Our results highlight the need of improvement of endometriosis care, especially for younger women. The results contribute to the understanding of the experience of patient-centeredness, which may be used as a guidance to how healthcare recourses should be allocated. Further research is needed to identify other factors contributing to the experience of patient-centeredness. Future studies could also evaluate how different interventions can improve patient-centeredness.

Comparison of vaginal self-sampling and cervical sampling by medical professionals for the detection of HPV and CIN2+: A randomized study.

Primary screening with human papillomavirus (HPV) test is more effective in reducing cervical cancer incidence than cytology and it also offers the opportunity to self-sample. We conducted a randomized study to compare vaginal self-sampling with cervical sampling by medical professionals for HPV testing concerning prevalence of HPV and detection of cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+) in primary screening. In total, 11 951 women aged 30-60 years were randomized into two groups, 5961 for self-sampling (SS arm) and 5990 for sampling by medical professionals (SMP arm). Sampling was performed with a RoversViba-brush in the SS arm and a cytobrush in the SMP arm. All samples were applied to an indicating FTA elute card and analyzed for HPV using a clinically validated real-time PCR test (hpVIR). All HPV-positive women performed repeated sampling about 6 months later using the same procedure as used initially. All HPV-positive women in the second sampling were referred to colposcopy. The prevalence of HPV in the first test did not differ between the SS arm (6.8%, 167/2466) and the SMP arm (7.8%, 118/1519) (P = .255). The prevalence of CIN2+ per 1000 screened women was 17 (43/2466 × 1000) (95%CI 13-24) in the SS arm and 21 (32/1519 × 1000) (95%CI 15-30) in the SMP arm. For CIN3+, the prevalence per 1000 screened women was 14 (35/2466 × 1000) (95%CI 10-20) in the SS arm and 15 (23/1519 × 1000) (95%CI 10-23) in the SMP arm. In conclusion, self-sampling and sampling by medical professionals showed the same prevalence of HPV and detection rate of CIN2+ and CIN3+ in histology.

Identification of Candidate Plasma Protein Biomarkers for Cervical Cancer Using the Multiplex Proximity Extension Assay.

Human papillomavirus (HPV) is recommended as the primary test in cervical cancer screening, with co-testing by cytology for HPV-positive women to identify cervical lesions. Cytology has low sensitivity and there is a need to identify biomarkers that could identify dysplasia that are likely to progress to cancer. We searched for plasma proteins that could identify women with cervical cancer using the multiplex proximity extension assay (PEA). The abundance of 100 proteins were measured in plasma collected at the time of diagnosis of patients with invasive cervical cancer and in population controls using the Olink Multiplex panels CVD II, INF I, and ONC II. Eighty proteins showed increased levels in cases compared with controls. We identified a signature of 11 proteins (PTX3, ITGB1BP2, AXIN1, STAMPB, SRC, SIRT2, 4E-BP1, PAPPA, HB-EGF, NEMO and IL27) that distinguished cases and controls with a sensitivity of 0.96 at a specificity of 1.0. This signature was evaluated in a prospective replication cohort with samples collected before, at or after diagnosis and achieved a sensitivity of 0.78 and a specificity 0.56 separating samples collected at the time of diagnosis of invasive cancer from samples collected prior to diagnosis. No difference in abundance was seen between samples collected prior to diagnosis or after treatment as compared with population controls, indicating that this protein signature is mainly informative close to time of diagnosis. Further studies are needed to determine the optimal window in time prior to diagnosis for these biomarker candidates.

Translation, Cross-Cultural Adaptation, and Psychometric Evaluation of the Swedish Version of ENDOCARE: An Instrument to Measure Patient Centeredness of Endometriosis Care.

OBJECTIVES: The need for quality improvement within endometriosis healthcare is widely acknowledged. The ENDOCARE questionnaire (ECQ) measures patient centeredness of endometriosis care. The aims of this study were (1) to translate and culturally adapt ECQ into Swedish, (2) to evaluate validity (construct validity), and (3) to measure reliability (internal consistency and test-retest reliability). DESIGN: This is a cross-sectional randomized study. Participants, Setting, and Methods: ECQ was first translated according to a well-established guideline and was thereafter sent to 500 randomly selected women with endometriosis, who had visited participating clinics during the past 3 years. The first 150 women who returned their questionnaires were immediately sent the same questionnaire again. The ECQ consists of 3 parts. The first part contains demographic and clinical questions, while part II has 38 items that are answered according to 2 aspects: percentage of negative experience of care and mean personal importance. A patient-centeredness score (PCS) is calculated based on these 2 aspects. The items are also divided into 10 dimensions of care. Part III is a grading of overall experience and an open-ended question on any missing aspect in the questionnaire. RESULTS: A total of 187 native Swedish-speaking women participated. Data completeness was high (>90%). The overall PCS median was 3.5. The highest median PCS was found in the dimension regarding endometriosis clinic staff and the lowest in emotional support and alleviation of fear and anxiety and the involvement of significant others. Factor analysis could roughly confirm 2 of the 10 dimensions. The Cronbach's α coefficient for PCS ranged from 0.35 to 0.73. The test-rest analysis showed acceptable reliability. LIMITATIONS: The most important limitation was the relatively low participation rate and the risk of recall bias. It is likely that women gave their answers based on their most recent experiences. CONCLUSIONS: Overall, our results indicate that the Swedish version of the ECQ is a usable instrument to measure patient centeredness in endometriosis care, but due to the unstable factor analysis, conclusions based on the dimensions should be made with caution.

Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized study.

BACKGROUND: Human papillomavirus (HPV) testing is recommended in primary cervical screening to improve cancer prevention. An advantage of HPV testing is that it can be performed on self-samples, which could increase population coverage and result in a more efficient strategy to identify women at risk of developing cervical cancer. Our objective was to assess whether repeated self-sampling for HPV testing is cost-effective in comparison with Pap smear cytology for detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) in increasing participation rate in primary cervical screening. METHODS: A cost-effectiveness analysis (CEA) was performed on data from a previously published randomized clinical study including 36,390 women aged 30-49 years. Participants were randomized either to perform repeated self-sampling of vaginal fluid for HPV testing (n = 17,997, HPV self-sampling arm) or to midwife-collected Pap smears for cytological analysis (n = 18,393, Pap smear arm). RESULTS: Self-sampling for HPV testing led to 1633 more screened women and 107 more histologically diagnosed CIN2+ at a lower cost vs. midwife-collected Pap smears (€ 229,446 vs. € 782,772). CONCLUSIONS: This study resulted in that repeated self-sampling for HPV testing increased participation and detection of CIN2+ at a lower cost than midwife-collected Pap smears in primary cervical screening. Offering women a home-based self-sampling may therefore be a more cost-effective alternative than clinic-based screening. TRIAL REGISTRATION: Not registered since this trial is a secondary analysis of an earlier published study (Gustavsson et al., British journal of cancer. 118:896-904, 2018).

Elderly women's experiences of self-sampling for HPV testing.

BACKGROUND: Self-sampling for HPV testing, as an alternative to the conventional speculum based sampling, is highly acceptable to women of screening ages. The aim of this study was to describe older women's (60 to 75 years) experiences of self-sampling. METHODS: In Sweden a descriptive study with quantitative and qualitative methods was designed to collect data from a survey of women who participated in self-sampling for HPV testing. Individual interviews were done with women who tested positive in the first self-sampling, and were either negative in their second HPV test or were positive in their second HPV test, but without precancerous lesions or cancer. RESULTS: Of 893 eligible women, 868 (97.2%) answered the survey. Among the surveyed women, 49.2% reported it was very easy to perform self-sampling, 46.8% answered it was easy and 2.0% answered it was not easy. A majority (58.9%) answered that they prefer self-sampling, 16.5% that they prefer sample collection by a healthcare provider, 23.7% did not have any preference and 0.9% did not answer the question. In the interviews, 13 of 16 invited women participated. Most of them reported that they prefer self-sampling because it was easy to perform, less embarrassing and less time consuming than a visit to a clinic. The majority of women reported that they were not worried when informed about having an HPV positive test. Overall, participating women with better knowledge about the significance of an HPV infection were more worried about having a positive HPV test. CONCLUSION: Cervical cancer remains a highly preventable disease through screening and early treatment. Our results indicated that vaginal self-sampling for HPV testing was a well-accepted method for cervical cancer prevention in this group of older women. TRIAL REGISTRATION: https://www.researchweb.org/is/en/fouckfuu/project/272587. Registered 24 June 2019-retrospectively registered. www.researchweb.org.

Temporal changes in the vaginal microbiota in self-samples and its association with persistent HPV16 infection and CIN2.

BACKGROUND: The vaginal microbiota has been reported to be associated with HPV infection and cervical cancer. This study was performed to compare the vaginal microbiota at two timepoints in women performing self-sampling and had a persistent or transient HPV16 infection. The women were tested for 12 high-risk HPV (hrHPV) types but only women with single type (HPV16) were included to reduce confounding variables. METHODS: In total 96 women were included in this study. Of these, 26 were single positive for HPV16 in the baseline test and HPV negative in the follow-up test and 38 were single positive for HPV16 in both tests and diagnosed with CIN2+ in histology. In addition, 32 women that were negative for all 12 HPV tested were included. The samples of vaginal fluid were analyzed with the Ion 16S™ Metagenomics Kit and Ion 16S™ metagenomics module within the Ion Reporter™ software. RESULTS: K-means clustering resulted in two Lactobacillus-dominated groups, one with Lactobacillus sp. and the other specifically with Lactobacillus iners. The two remaining clusters were dominated by a mixed non-Lactobacillus microbiota. HPV negative women had lower prevalence (28%) of the non-Lactobacill dominant cluster in the baseline test, as compared to women with HPV16 infection (42%) (p value = 0.0173). Transition between clusters were more frequent in women with persistent HPV16 infection (34%) as compared in women who cleared the HPV16 infection (19%) (p value = 0.036). CONCLUSIONS: The vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.

Pregnancy in metabolic healthy and unhealthy obese women.

INTRODUCTION: Obesity-associated adverse obstetric outcomes are well-known but still relatively rare and difficult to predict. Not all obese individuals are unhealthy; some have metabolically healthy obesity (MHO) and others have metabolic unhealthy obesity (MUO). Our aim was to investigate whether the MHO and MUO classification could be used for prediction of obesity-associated complications in pregnancy. MATERIAL AND METHODS: We included 547 pregnant women with obesity, 2302 pregnant women with overweight and 5852 normal weight pregnant women. The women with obesity were classified as MUO (n = 181, 33.1%) or MHO (n = 366, 66.9%) based on first trimester blood pressure, lipoprotein levels and nonfasting glucose levels. The risk of obstetric outcomes was evaluated by multivariable logistic regression. We compared cardiovascular risk markers in blood between obese pregnant women with MUO and MHO. RESULTS: Overall, 45.9% of women with MUO developed at least one adverse obesity-associated obstetric outcome, whereas corresponding proportions in women with MHO, overweight and normal weight were 35.0%, 27.6% and 21.2%, respectively. Following adjustment, the overall risk of at least one obesity-associated obstetric or perinatal complication in women with MUO, vs women with MHO, was increased (adjusted odds ratio 1.49, 95% confidence interval 1.03-2.15), but the predictive value of the model was low. Women with MUO had altered levels of cardiovascular risk markers such as cathepsin S, adiponectin, and cystatin C in comparison with women with MHO. CONCLUSIONS: Women with MUO had an overall increased risk of adverse obstetric outcomes in comparison to women with MHO, but the classification had little relevance for risk prediction beyond that of body mass index.

Psychometric evaluation of the Swedish version of the 30-item endometriosis health profile (EHP-30).

BACKGROUND: The 30-Item Endometriosis Health Profile (EHP-30) is a specific instrument measuring quality of life among women with endometriosis. Although the Swedish version of EHP-30 is widely used in research and clinical settings, it has not yet been evaluated psychometrically. Ensuring validity and reliability is of most importance when using translated instruments. Therefore, the aim of the study was to evaluate the psychometric properties of the Swedish version of the EHP-30. METHODS: This study was conducted at a Swedish referral university hospital specializing in endometriosis. Data collection was performed in January 2013. The EHP-30 was sent to 369 randomly selected women with a laparoscopy-verified endometriosis diagnosis. The psychometric evaluation included evaluation of data completeness, score distributions, floor and ceiling effects, internal consistency, factor analysis and test-retest reliability. RESULTS: Out of the 211 women with endometriosis who answered the questionnaire, 128 were native Swedish speakers who had experienced symptoms of endometriosis during the past 4 weeks, and were included in the psychometric evaluation. Data completeness was 99.5%. The highest median score was found in the Control and Powerlessness subscale, and lowest in Pain. Distributions towards ill health were found in all subscales except for the pain subscale, but there were no noteworthy floor or ceiling effects. Internal consistency was good (Cronbach's α 0.83-0.96). Factor analysis could roughly confirm three of the five subscales. The test-rest analysis showed good reliability. Scores were systematically lower during the second measurement. CONCLUSIONS: We conclude that the Swedish version of EHP-30 is a valid and reliable instrument to measure health-related quality of life in women with endometriosis. It is understandable, acceptable and usable and can be recommended for use in clinical daily routines and for research purposes.

Healthcare Consumption and Cost Estimates Concerning Swedish Women with Endometriosis.

INTRODUCTION: Endometriosis is known for its substantial effect on women's wellbeing and quality of life. In order to evaluate disease burden, treatments and health services, assessments of healthcare consumption and cost estimates are necessary. OBJECTIVES: The aim of this study was to estimate healthcare consumption and annual cost per woman with endometriosis in Sweden and to examine healthcare consumption and costs in different age groups. METHODS: A questionnaire was distributed to 400 members of the Endometriosis Association and to 400 randomly selected women with surgically confirmed endometriosis. Official statistics were obtained via correspondence, publications, and database searches. RESULTS: Analysis of the 431 returned questionnaires showed that women under 30 years utilized more inpatient and outpatient care than older women. The mean annual cost among all women was EUR 8,768/woman. The direct healthcare cost of managing the disease was EUR 4,282, while the indirect cost was EUR 4,486. Absence from work was reported by 32% of the women, while 36% reported reduced time at work because of endometriosis. CONCLUSION: Our results confirm the substantial negative effect of endometriosis upon women's lives and their relatively high healthcare consumption.

Cross-cultural adaptation of the Swedish version of Endometriosis Health Profile-30.

The Endometriosis Health Profile-30 (EHP-30) is focusing on the effect of endometriosis symptoms upon health-related quality of life. The aim of this study was to pre-test and culturally adapt the Swedish version of EHP-30. Eighteen Swedish-speaking women with laparoscopically verified diagnosis of endometriosis answered the questionnaire and 17 were interviewed regarding their interpretations of the questionnaire. Demographics, distribution of answers, roof-ceiling effects and missing answers were analysed. The interviews were analysed using the qualitative approach proposed by Beaton et al. The Swedish version of EHP-30 was experienced as accessible with 100% data completeness and a roof effect (11%) in one dimension. Some women had difficulties with the instructions and one word should be replaced in order to culturally adapt the questionnaire. In conclusion, the Swedish version of EHP-30 is a useful and well-accepted questionnaire for women with endometriosis in Sweden, but a minor change of wording is recommended. Impact statementWhat is already known on this subject? Cross-cultural adaptation and psychometric testing are crucial when introducing translated questionnaires. Cross-cultural adaptation is a process that looks at both translational and cultural issues when a questionnaire is being prepared for use in another country than the original. EHP-30 has been translated into Swedish but has not yet been cross-culturally adapted.What do the results of this study add? The Swedish version of EHP-30 was experienced as a useful and well-accepted questionnaire for women with endometriosis, but a minor change of wording is recommended in one question to make the questionnaire convergent with the original version.What are the implications of these findings for clinical practice and/or further research? The Swedish version of EHP-30 is user friendly and can be used in clinical practice after a minor change of wording. Then, it should also undergo psychometric testing.

Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.

We conducted a randomised study to compare vaginal self-sampling with assisted sampling by medical personnel on the cervix for HPV testing in primary screening. The first aim was to determine if the HPV prevalence is independent of sampling location (vagina versus cervix) and the person performing the sampling. The second aim was to evaluate if the two sampling strategies differed in the detection rate of CIN2+. In total, 19,523 women were randomised into two groups, with 9926 invited to perform self-sampling (SS arm) using the Rover VIBA-brush and 9597 offered assisted sampling using the cytobrush (AS arm). All samples were applied to the indicating FTA elute card and analysed for high-risk HPV using the hpVIR real-time PCR assay. The outcome for the first aim was HPV prevalence and for the second aim the number of CIN2+ based on histology. In the SS arm, 52.7% of invited women participated in the study, as compared to 34.2% in the AS arm. All samples contained sufficient amount of nuclear DNA for a valid HPV result, with vaginal samples having a higher DNA amount than cervical samples (p < 4.62 × 10-11 ). HPV prevalence was 4.6% in the SS arm and 4.1% in the AS arm (p = 5.5 × 10-2 ), and the distribution of HPV types similar between arms. There was no difference in the prevalence of CIN2+ per 1000 women screened between arms (p = 0.86). The results show that vaginal self-sampling is an equivalent alternative to sampling by medical personnel for HPV typing and identification of CIN2+.

Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia.

BACKGROUND: The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is elevated in pregnant women before the clinical onset of preeclampsia, but its predictive value in women with suspected preeclampsia is unclear. METHODS: We performed a prospective, multicenter, observational study to derive and validate a ratio of serum sFlt-1 to PlGF that would be predictive of the absence or presence of preeclampsia in the short term in women with singleton pregnancies in whom preeclampsia was suspected (24 weeks 0 days to 36 weeks 6 days of gestation). Primary objectives were to assess whether low sFlt-1:PlGF ratios (at or below a derived cutoff) predict the absence of preeclampsia within 1 week after the first visit and whether high ratios (above the cutoff) predict the presence of preeclampsia within 4 weeks. RESULTS: In the development cohort (500 women), we identified an sFlt-1:PlGF ratio cutoff of 38 as having important predictive value. In a subsequent validation study among an additional 550 women, an sFlt-1:PlGF ratio of 38 or lower had a negative predictive value (i.e., no preeclampsia in the subsequent week) of 99.3% (95% confidence interval [CI], 97.9 to 99.9), with 80.0% sensitivity (95% CI, 51.9 to 95.7) and 78.3% specificity (95% CI, 74.6 to 81.7). The positive predictive value of an sFlt-1:PlGF ratio above 38 for a diagnosis of preeclampsia within 4 weeks was 36.7% (95% CI, 28.4 to 45.7), with 66.2% sensitivity (95% CI, 54.0 to 77.0) and 83.1% specificity (95% CI, 79.4 to 86.3). CONCLUSIONS: An sFlt-1:PlGF ratio of 38 or lower can be used to predict the short-term absence of preeclampsia in women in whom the syndrome is suspected clinically. (Funded by Roche Diagnostics.).

HPV viral load in self-collected vaginal fluid samples as predictor for presence of cervical intraepithelial neoplasia.

OBJECTIVE: This study was performed to evaluate the use of high-risk HPV (hrHPV) viral load in screening tests for cervical cancer to predict persistent infection and presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). METHODS: We followed women between 30 and 60 years of age who performed self-sampling of vaginal fluid and subsequently a hrHPV test. Women who were hrHPV positive in their screening test repeated the hrHPV test 3-6 months later and were included in the present study. RESULTS: Our results show that women with a persistent HPV16 infection had higher HPV viral load in their primary screening test than women with transient infections (p = 5.33e-03). This was also true for sum of viral load for all hrHPV types in the primary screening test (p = 3.88e-07). 48% of women with persistent HPV16 infection and CIN2+ had an increase in HPV16 titer in the follow-up test, as compared to only 20% of women with persistent infection but without CIN2+ lesions. For the sum of all hrHPV types, 41% of women with persistent infection and CIN2+ had an increase in titer as compared to 26% of women without CIN2 + . CONCLUSIONS: The results show that hrHPV viral load in the primary screening HPV test is associated with the presence of CIN2+ and could be used in triaging hrHPV positive women for different follow-up strategies or recall times. Serial testing of hrHPV viral load has the potential to distinguish women with CIN2+ lesions from women with persistent infection but without CIN2+ lesions.