Infection prevention for immunocompromised patients: A cross-translational multicentric survey of current organization in France.

OBJECTIVES: To evaluate current organization of infection prevention for immunocompromised patients (ICP) at a countrywide level. METHODS: Nationwide cross-sectional multicenter study based on an online survey disseminated in 2022 to physicians invested with preventive healthcare missions. RESULTS: A total of 341 physicians (96% graduates, 32% infectious disease specialists), participated in the survey, with a median age of 40 [35-51] years. On-site access to infection prevention consultations for ICP was reported by 30%, dedicated pre-travel consultations for ICPs by 29%, consultations for infection prevention in solid organ transplant candidates by 16% and return-to-work consultations for ICPs by 6%. Most participants (73%) were aware of nationwide vaccination guidelines for ICP, while 50% felt comfortable using them. Tools for infection prevention advice and ICP vaccination had been developed by 10%, while 89% would have appreciated access to tools developed by others. CONCLUSIONS: Infection prevention for ICPs remains neglected. Guidelines covering all fields of prevention for ICPs would be more than welcome.

[Menopausal transition]. / De overgang.

In this educative article 10 medical questions related to the menopausal transition are answered. The questions are related to etiology, symptomatology, lab investigation, sexuality, need for contraception, hormonal and non-hormonal treatments and their risks and benefits. The purpose of this article is to assist the healthcare practitioner to understand the impact of the menopausal transition, to recognize the symptoms and to understand the risks and benefits of treatment. As women on average work and live longer, they are on average 30 percent of their lives postmenopausal. Attention should be paid to quality of life not only during menopausal transition, but also thereafter, with special awareness of the long term sequelae on women's health.

The corona pandemic and participatory governance: Responding to the vulnerabilities of secondary school students in Europe.

Adolescents in secondary schools have limited susceptibility to the SARS-COV-2 virus, but paradoxically are considered to be carrying the highest psychosocial burden during this pandemic. The aim of our European multi-country qualitative research was to investigate the COVID-19 crisis response in secondary schools and the role of national, regional, and local stakeholders in contributing to a participatory governance approach. We carried out 11 months of qualitative fieldwork, which included 90 respondents from the Netherlands, Ireland, and Finland for in-depth interviews and/or group discussions. Participant observation was conducted in four secondary schools to explore the interplay of day-to-day formal and informal practices of crisis governance. Our findings contribute to a better understanding of what efforts were made to facilitate participatory governance and where a bottom-up approach would have served useful in successfully implementing the COVID-19 mitigation strategies. Moreover, we show how these mitigation strategies have led to unintended consequences, such as students' difficulties with isolation and associated mental health problems, and the struggles of socialization when returning to a physical school environment. Our findings highlight the importance of the school environment in the socio-emotional developments of adolescents. We introduce the TAPIC-R model to analyze good governance, advancing the existing TAPIC model with an emphasis on the role of resilience in shaping participatory governance. We argue this is urgently needed during crises to strengthen engagement of the community, including vulnerable groups and achieve positive outcomes within and across policy structures and action domains.

[Deep brain stimulation as a treatment for severe multidrug-resistant obsessive compulsive disorder]. / La stimulation cérébrale profonde comme traitement du trouble obsessionnel compulsif sévère multi-résistant.

Obsessive compulsive disorder (OCD) is a common and disabling psychiatric condition. About 10 % of patients are considered to be severely affected and refractory to the usual treatments, combining antidepressants and psychotherapy. Deep brain stimulation (DBS) is a promising treatment, reserved for specialized university centers. It is based on the implantation of electrodes aimed at modulating dysfunctional cortico-striato-thalamo-cortical circuits. After studying the different targets to be used, it is now proposed to rethink DBS in terms of networks. The improvement of pathophysiological knowledge of OCD and the development of functional neuroimaging techniques should allow the design of individualized treatment protocols.

Le trouble obsessionnel compulsif (TOC) est une pathologie psychiatrique fréquente et invalidante. Environ 10 % des patients sont considérés comme très sévèrement atteints et réfractaires aux traitements habituels, combinant antidépresseurs et psychothérapies. Réservée à des centres universitaires spécialisés, la stimulation cérébrale profonde (SCP) est un traitement prometteur qui repose sur l'implantation d'électrodes visant à moduler des circuits cortico-striato-thalamo-corticaux dysfonctionnels. Après l'étude des différentes cibles à utiliser, il est aujourd'hui proposé de reconsidérer la SCP en termes de réseaux. L'amélioration des connaissances physiopathologiques du TOC et le développement de techniques de neuro-imagerie fonctionnelle devraient permettre de dessiner des protocoles de traitement individualisé.

Economic evaluation of endometrial scratching before the second IVF/ICSI treatment: a cost-effectiveness analysis of a randomized controlled trial (SCRaTCH trial).

STUDY QUESTION: Is a single endometrial scratch prior to the second fresh IVF/ICSI treatment cost-effective compared to no scratch, when evaluated over a 12-month follow-up period? SUMMARY ANSWER: The incremental cost-effectiveness ratio (ICER) for an endometrial scratch was €6524 per additional live birth, but due to uncertainty regarding the increase in live birth rate this has to be interpreted with caution. WHAT IS KNOWN ALREADY: Endometrial scratching is thought to improve the chances of success in couples with previously failed embryo implantation in IVF/ICSI treatment. It has been widely implemented in daily practice, despite the lack of conclusive evidence of its effectiveness and without investigating whether scratching allows for a cost-effective method to reduce the number of IVF/ICSI cycles needed to achieve a live birth. STUDY DESIGN, SIZE, DURATION: This economic evaluation is based on a multicentre randomized controlled trial carried out in the Netherlands (SCRaTCH trial) that compared a single scratch prior to the second IVF/ICSI treatment with no scratch in couples with a failed full first IVF/ICSI cycle. Follow-up was 12 months after randomization.Economic evaluation was performed from a healthcare and societal perspective by taking both direct medical costs and lost productivity costs into account. It was performed for the primary outcome of biochemical pregnancy leading to live birth after 12 months of follow-up as well as the secondary outcome of live birth after the second fresh IVF/ICSI treatment (i.e. the first after randomization). To allow for worldwide interpretation of the data, cost level scenario analysis and sensitivity analysis was performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: From January 2016 until July 2018, 933 women with a failed first IVF/ICSI cycle were included in the trial. Data on treatment and pregnancy were recorded up until 12 months after randomization, and the resulting live birth outcomes (even if after 12 months) were also recorded.Total costs were calculated for the second fresh IVF/ICSI treatment and for the full 12 month period for each participant. We included costs of all treatments, medication, complications and lost productivity costs. Cost-effectiveness analysis was carried out by calculating ICERs for scratch compared to control. Bootstrap resampling was used to estimate the uncertainty around cost and effect differences and ICERs. In the sensitivity and scenario analyses, various unit costs for a single scratch were introduced, amongst them, unit costs as they apply for the United Kingdom (UK). MAIN RESULTS AND THE ROLE OF CHANCE: More live births occurred in the scratch group, but this also came with increased costs over a 12-month period. The estimated chance of a live birth after 12 months of follow-up was 44.1% in the scratch group compared to 39.3% in the control group (risk difference 4.8%, 95% CI -1.6% to +11.2%). The mean costs were on average €283 (95% CI: -€299 to €810) higher in the scratch group so that the point average ICER was €5846 per additional live birth. The ICER estimate was surrounded with a high level of uncertainty, as indicated by the fact that the cost-effectiveness acceptability curve (CEAC) showed that there is an 80% chance that endometrial scratching is cost-effective if society is willing to pay ∼€17 500 for each additional live birth. LIMITATIONS, REASONS FOR CAUTION: There was a high uncertainty surrounding the effects, mainly in the clinical effect, i.e. the difference in the chance of live birth, which meant that a single straightforward conclusion could not be ascertained as for now. WIDER IMPLICATIONS OF THE FINDINGS: This is the first formal cost-effectiveness analysis of endometrial scratching in women undergoing IVF/ICSI treatment. The results presented in this manuscript cannot provide a clear-cut expenditure for one additional birth, but they do allow for estimating costs per additional live birth in different scenarios once the clinical effectiveness of scratching is known. As the SCRaTCH trial was the only trial with a follow-up of 12 months, it allows for the most complete estimation of costs to date. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by ZonMW, the Dutch organization for funding healthcare research. A.E.P.C., F.J.M.B., E.R.G. and C.B. L. reported having received fees or grants during, but outside of, this trial. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL5193/NTR 5342).

[ARN COVID-19 COMIRNATY Vaccine desensitization in a case of PEG Severe Immediate Hypersensitivity]. / Induction de tolérance au vaccin à ARN COMIRNATY chez un patient avec une hypersensibilité allergique sévère au PEG.

Vaccination is the most efficient way to fight the Covid epidemic. However, suspicion of severe hypersensitivity to PEG (PolyEthylen Glycol) usually constitutes a vaccine contraindication. We report the case of a patient with a proven allergy to PEG and skin sensitization to the COMIRNATY vaccine (PEG in its composition). He was able to benefit from the vaccine under the 5-step desensitization protocol. Conclusions: Specific allergological management should be offered to patients suspected of severe hypersensitivity to PEG and other vaccine excipients. We propose a solution for Comirnaty administration for patients with a proven severe allergy to PEG.

The effects of ACE2 expression mediating pharmacotherapy in COVID-19 patients.

BACKGROUND: There has been debate on the use of angiotensin-converting enzyme­2 (ACE2) expression mediating pharmacotherapy in COVID-19 infected patients. Although it has been suggested that these drugs might lead to a higher susceptibility and severity of COVID-19 infection, experimental data suggest these agents may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation and fibrosis. METHODS: A systematic literature search was performed to answer the question: What is the effect of medications that influence ACE2 expression (ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), nonsteroidal anti-inflammatory drugs (NSAIDs) and thiazolidinediones) on the outcomes of COVID-19? Relevant outcome measures were mortality (crucial), hospital admission, length of stay, thromboembolic complications (pulmonary embolism, stroke, transient ischaemic attack), need for mechanical ventilation, acute kidney injury and use of renal replacement therapy. Medline and Embase databases were searched with relevant search terms until 24 June 2020. After systematic analysis, nine studies were included. RESULTS: The results were described for two different groups, an overall group in which all users were compared with non-users and a group in which only hypertensive patients were included. Within each group a distinction was made between results for ACEI/ARB use, ACEI use, ARB use, NSAID use and thiazolidinedione use. None of the studies demonstrated increased mortality in the two groups. Furthermore, none of the studies showed an effect on other outcome measures in COVID-19, such as ICU admission, length of hospital stay, thromboembolic complications, need for mechanical ventilation, acute kidney failure or need for renal replacement therapy. However, the level of evidence of all studies varied from 'moderate' to 'very low', according to the GRADE methodology. CONCLUSION: Analysis of the literature demonstrated that there was insufficient evidence to answer our objective on the effect of ACE2 expression mediating pharmacotherapy on outcome in COVID-19 patients, especially due to the low scientific quality of the described studies. Randomised controlled studies are needed to answer this question.

Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH).

STUDY QUESTION: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71-2.07) and RR 0.73 (95% CI 0.38-1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between -1.2% and +11.4% (95% CI). LIMITATIONS, REASONS FOR CAUTION: This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports 'other' from Ferring BV, personal fees from Up to date Hyperthecosis, 'other' from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work. TRIAL REGISTRATION NUMBER: Registered in the Netherlands Trial Register (NL5193/NTR 5342). TRIAL REGISTRATION DATE: 31 July 2015. DATE OF FIRST PATIENT'S ENROLMENT: 26 January 2016.

[Severe epigastric pain in a 59-year-old patient]. / Massivste epigastrische Schmerzen bei einem 59-jährigen Patienten.

Abdominal pain is a frequent cause of consultation to doctors' offices and emergency rooms. The most common differential diagnoses can be confirmed with readily available, cost-effective, and low-risk diagnostic tools such as laboratory tests, ultrasound, or gastroscopy. Additional diagnostic tests are required to exclude rare causes such as small, solid, or hematological malignancies, metabolic disorders, or polyneuropathies of varying origin. In the following, we present the case of a patient with severe epigastric pain due to neuroborreliosis, and recapitulate the diagnostic steps for clarifying abdominal pain using this example.

Risks of floating microplastic in the global ocean.

Despite the ubiquitous and persistent presence of microplastic (MP) in marine ecosystems, knowledge of its potential harmful ecological effects is low. In this work, we assessed the risk of floating MP (1 µm-5 mm) to marine ecosystems by comparing ambient concentrations in the global ocean with available ecotoxicity data. The integration of twenty-three species-specific effect threshold concentration data in a species sensitivity distribution yielded a median unacceptable level of 1.21 ∗ 105 MP m-³ (95% CI: 7.99 ∗ 103-1.49 ∗ 106 MP m-³). We found that in 2010 for 0.17% of the surface layer (0-5 m) of the global ocean a threatening risk would occur. By 2050 and 2100, this fraction increases to 0.52% and 1.62%, respectively, according to the worst-case predicted future plastic discharge into the ocean. Our results reveal a spatial and multidecadal variability of MP-related risk at the global ocean surface. For example, we have identified the Mediterranean Sea and the Yellow Sea as hotspots of marine microplastic risks already now and even more pronounced in future decades.

Monoculture-based consumer-resource models predict species dominance in mixed batch cultures of dinoflagellates.

Global change will disturb the frequency, scale and distribution of harmful algal blooms (HABs), but we are unable to predict future HABs due to our limited understanding of how physicochemical changes in the environment affect interspecific competition between dinoflagellates. Trait-based mechanistic modelling is an important tool to unravel and quantify various direct and indirect interactions between species. The present study explores whether MacArthur's consumer-resource model can be used as a viable base model to predict dinoflagellate growth in closed multispecies systems. To this end, two batch culture experiments (294 cultures in total) with monocultures and multispecies cultures of Alexandrium minutum, Prorocentrum lima, P. micans, Protoceratium reticulatum and Scrippsiella trochoidea were performed. Despite changes to the relative (different nitrate concentrations) and absolute nutrient availability (dilutions of L1 medium), P. micans outcompeted all other species in mixed cultures. Consumer-resource modelling parameterized using monoculture growth correctly predicted this species dominance (R² between 0.80 and 0.95). Parameter estimates revealed that P. micans had a faster uptake of nitrogen when compared to its competitors, but did not differ in resource efficiency and natural mortality rate. Yet, while the model accurately predicted community dynamics during the growth phase, it was not able to predict their dynamics beyond the point of quiescence. Consumer-resource modelling was shown to differentiate the roles of resource assimilation, resource efficiency, and natural mortality rates in batch culture experiments with minimal data requirements beyond common measurements. The results suggest that consumer-resource models provide a promising basis for trait-based modelling of interspecific competition between (harmful) algae.

Septum resection in women with a septate uterus: a cohort study.

STUDY QUESTION: Does septum resection improve reproductive outcomes in women with a septate uterus? SUMMARY ANSWER: In women with a septate uterus, septum resection does not increase live birth rate nor does it decrease the rates of pregnancy loss or preterm birth, compared with expectant management. WHAT IS KNOWN ALREADY: The septate uterus is the most common uterine anomaly with an estimated prevalence of 0.2-2.3% in women of reproductive age, depending on the classification system. The definition of the septate uterus has been a long-lasting and ongoing subject of debate, and currently two classification systems are used worldwide. Women with a septate uterus may be at increased risk of subfertility, pregnancy loss, preterm birth and foetal malpresentation. Based on low quality evidence, current guidelines recommend removal of the intrauterine septum or, more cautiously, state that the procedure should be evaluated in future studies. STUDY DESIGN, SIZE, DURATION: We performed an international multicentre cohort study in which we identified women mainly retrospectively by searching in electronic patient files, medical records and databases within the time frame of January 2000 until August 2018. Searching of the databases, files and records took place between January 2016 and July 2018. By doing so, we collected data on 257 women with a septate uterus in 21 centres in the Netherlands, USA and UK. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included women with a septate uterus, defined by the treating physician, according to the classification system at that time. The women were ascertained among those with a history of subfertility, pregnancy loss, preterm birth or foetal malpresentation or during a routine diagnostic procedure. Allocation to septum resection or expectant management was dependent on the reproductive history and severity of the disease. We excluded women who did not have a wish to conceive at time of diagnosis. The primary outcome was live birth. Secondary outcomes included pregnancy loss, preterm birth and foetal malpresentation. All conceptions during follow-up were registered but for the comparative analyses, only the first live birth or ongoing pregnancy was included. To evaluate differences in live birth and ongoing pregnancy, we used Cox proportional regression to calculate hazard rates (HRs) and 95% CI. To evaluate differences in pregnancy loss, preterm birth and foetal malpresentation, we used logistic regression to calculate odds ratios (OR) with corresponding 95% CI. We adjusted all reproductive outcomes for possible confounders. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 257 women were included in the cohort. Of these, 151 women underwent a septum resection and 106 women had expectant management. The median follow-up time was 46 months. During this time, live birth occurred in 80 women following a septum resection (53.0%) compared to 76 women following expectant management (71.7%) (HR 0.71 95% CI 0.49-1.02) and ongoing pregnancy occurred in 89 women who underwent septum resection (58.9%), compared to 80 women who had expectant management (75.5%) (HR 0.74 (95% CI 0.52-1.06)). Pregnancy loss occurred in 51 women who underwent septum resection (46.8%) versus 31 women who had expectant management (34.4%) (OR 1.58 (0.81-3.09)), while preterm birth occurred in 26 women who underwent septum resection (29.2%) versus 13 women who had expectant management (16.7%) (OR 1.26 (95% CI 0.52-3.04)) and foetal malpresentation occurred in 17 women who underwent septum resection (19.1%) versus 27 women who had expectant management (34.6%) (OR 0.56 (95% CI 0.24-1.33)). LIMITATIONS, REASONS FOR CAUTION: Our retrospective study has a less robust design compared with a randomized controlled trial. Over the years, the ideas about the definition of the septate uterus has changed, but since the 257 women with a septate uterus included in this study had been diagnosed by their treating physician according to the leading classification system at that time, the data of this study reflect the daily practice of recent decades. Despite correcting for the most relevant patient characteristics, our estimates might not be free of residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that septum resection, a procedure that is widely offered and associated with financial costs for society, healthcare systems or individuals, does not lead to improved reproductive outcomes compared to expectant management for women with a septate uterus. The results of this study need to be confirmed in randomized clinical trials. STUDY FUNDING/COMPETING INTEREST(S): A travel for JFWR to Chicago was supported by the Jo Kolk Studyfund. Otherwise, no specific funding was received for this study. The Department of Obstetrics and Gynaecology, University Medical Centre, Groningen, received an unrestricted educational grant from Ferring Pharmaceutical Company unrelated to the present study. BWM reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck, personal fees from Guerbet, other payment from Guerbet and grants from Merck, outside the submitted work. The other authors declare no conficts of interest. TRIAL REGISTRATION NUMBER: N/A.

Immune profile at HIV infection diagnosis: Evolution in the French Alps area over the last 20 years.

OBJECTIVES: Health of HIV-infected people relies on early antiretroviral therapy, i.e. early diagnosis. We aimed to determine whether the characteristics at HIV diagnosis in two French medical centres changed over the last 20 years. PATIENTS AND METHODS: All individuals diagnosed with HIV infection in Grenoble University Hospital (N=814) and Annecy Hospital (N=246) between 1997 and 2015 were included. We collected age, country of birth, mode of transmission, CD4T cell count, CD4/CD8 ratio, and HIV viral load. RESULTS: Among the 1060 patients (mean age 37.4±11 years, 70.2% of men), 42.5% were men having sex with men (MSM); 65.2% were born in France, and 24.4% were born in Africa. Mean CD4T cell count at diagnosis was 396±288/mm3 and was stable over the study period when considering all patients; when considering the MSM group, a significant increase over time was observed, with a mean increase of 7.3 CD4/mm3 per year (P<0.001). A higher CD4 count at diagnosis was observed after 2005 (400±289 vs 468±271/mm3, P=0.005). The proportion of MSM patients with a CD4 count<200/mm3 at diagnosis was lower after 2005 (14.7% after 2005 and 25.6% before, P=0.028) This was not observed in heterosexual patients (born in Africa or not). CONCLUSION: In the MSM population, CD4 count at diagnosis is higher after 2005, suggesting that screening campaigns have become more efficient. This was not observed in other populations, who should be better targeted in future strategies.

Ab initio predictions and laboratory validation for consistent ozone intensities in the MW, 10 and 5 µm ranges.

Reliable ozone spectral data consistent over several spectral ranges are a challenge for both experiment and theory. We present ab initio calculations for strong lines that lead to consistent results from the microwave to mid-infrared regions. The results agree well with established microwave line lists and our new measurements in the fundamental and first overtone regions of ozone at 5 and 10 µm. The calculations and their agreement to within 1% with measurements provide an important step toward consistent and accurate spectroscopic ozone data. The results imply that actual databases need to be corrected by about 3% in the corresponding mid-infrared spectral intervals. Appropriate recommendations for the consistency of strong line intensities of the ozone molecule in microwave, 10 and 5 µm ranges, in HITRAN (HIgh-resolution TRANsmittance and molecular apbsorption) and GEISA (Gestion et Etude des Informations Spectroscopiques Atmosphériques) databases are suggested.

Prognostic factors associated with early gout flare recurrence in patients initiating urate-lowering therapy during an acute gout flare.

Lowering serum urate levels below the threshold for crystal formation with urate-lowering therapy (ULT) has been associated with a lower risk for gout flare reoccurrences. However, gout patients on ULT still commonly suffer from recurring gout flares. The purpose of this study was to explore prognostic factors associated with gout flare recurrence within the first 3 months, in gout patients starting ULT during an acute gout flare. Post-hoc analysis of trial data on acute gout patients randomized to either gout flare standard of care or anakinra treatment were used, including baseline demographic, laboratory, clinical, and patient-reported variables, as well as 3-month follow-up data on gout flare recurrences. Only patients starting ULT at baseline were included. Using variable selection based on clinical relevance, univariate, and multivariate binary logistic regression analyses were done to examine predictors of gout flare reoccurrence. A total of 75 patients were included in this study, of which 36 (48%) experienced a gout flare ≤ 3 months post baseline. The multivariate regression analysis revealed that CRP levels > 30 mg/L (OR 9.47) and lack of prophylaxis when starting ULT (OR 11.56) were independently associated with gout flare recurrence. Similar results were found for the univariate regression analyses. Our results show that CRP levels > 30 mg/L and lack of prophylaxis when starting ULT were prognostic factors for early gout flare reoccurrence in patients starting ULT during an acute gout flare. KEY POINTS: • Gout flare recurrences were common within the first 3 months after starting urate-lowering therapy in gout patients. • Intake of prophylaxis when starting ULT had a strong protective effect on gout flare recurrences. • C-reactive protein level > 30 mg/L was an additional prognostic factor for early (≤ 3 months) gout flare reoccurrence in patients starting ULT during an acute gout flare.

Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial.

BACKGROUND: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. METHODS: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. TRIAL REGISTRATION: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.