Prospective Multicenter Case-control Study Research Articles

Lens Thickness in Infants and Children with Cataracts

PurposeThe purpose of this study was to determine the association between lens thickness and cataract in subjects aged 0-5 years. DesignThis was a prospective multi-center case-control study. ParticipantsWe enrolled 118 participants (171 eyes) age 0-5 years old, mean age 14.6 ± 17.0 months, range 0 - 60 months. MethodsLens thickness was measured on 342 ultrasound biomicroscopy (UBM) images. Main Outcome MeasuresLens thickness; feasibility of lens thickness measurement from UBM images ResultsMean lens thickness among non-cataracts was 3.60 ± 0.17 mm, compared to 3.16 ± 0.61 mm among cataracts (p<0.0001). Lens thickness less than 3.5 mm was significantly associated with increased odds of cataract, adjusted OR=5.99 [2.41,14.88] (p=0.0003) among subjects age 0-7 months. Lens thickness was significantly associated with cataract laterality among subjects age 0-7 months (p<0.0001). ConclusionsQuantitative UBM can be used to evaluate lens thickness in infants and children with congenital cataracts. The lens in congenital cataract eyes was thinner than that of controls among infants. Abnormal lens thickness was significantly associated with cataract. Future longitudinal studies will examine the association between lens thickness and post-cataract surgery outcomes.

Exposome and basal cell carcinoma: a multicenter case-control study.

While ultraviolet radiation (UVR) present in sunlight is recognized as the main etiological agent of skin cancer, the most frequent form of which is basal cell carcinoma (BCC), other exposome factors like pollution, diet, and lifestyle may also contribute. This study aimed to investigate the association of BCC and exposome-related factors in the Spanish population. BCC cases (n = 119) and controls (n = 127) with no history of skin cancer were recruited between April 2020 and August 2022 by 13 dermatologists throughout Spain in this prospective multicenter case-control study. The BCC group had a higher proportion of outdoor workers, more years of UVR exposure, and a greater consumption of drugs (statins, ASA, hydrochlorothiazide, ACE inhibitors and omeprazole), P < 0.05. Avoidance of sun exposure was the most used photoprotection measure in both groups. The use of hats or caps was higher in the BCC group (P = 0.01). The solar protection factor (SPF) used 15 years previously was higher in the control group (P = 0.04). The control group had a higher daily screen time (P < 0.001), and practiced more relaxation activities (P = 0.03). Higher linolenic acid intake and lower coffee consumption were the only dietary variables associated with BCC (P < 0.05). Statistical significance for all the aforementioned variables was maintained in the multivariate analysis (P < 0.05). The study found a significant association between BCC and multiple exposome-related factors in addition to chronic sunexposure in the Spanish population. Primary prevention strategies should target specific populations, such as outdoor workers, promoting sun-safe behaviors and stress-reducing activities, and also adequate skin photoprotection in patients on certain medications associated with increased BCC risk.

Multikingdom oral microbiome interactions in early-onset cryptogenic ischemic stroke.

Although knowledge of the role of the oral microbiome in ischemic stroke is steadily increasing, little is known about the multikingdom microbiota interactions and their consequences. We enrolled participants from a prospective multicentre case-control study and investigated multikingdom microbiome differences using saliva metagenomic datasets (n = 308) from young patients diagnosed with cryptogenic ischemic stroke (CIS) and age- and sex-matched stroke-free controls. Differentially abundant taxa were identified using Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC2). Functional potential was inferred using HUMANn3. Our findings revealed significant differences in the composition and functional capacity of the oral microbiota associated with CIS. We identified 51 microbial species, including 47 bacterial, 3 viral, and one fungal species associated with CIS in the adjusted model. Co-abundance network analysis highlighted a more intricate microbial network in CIS patients, indicating potential interactions and co-occurrence patterns among microbial species across kingdoms. The results of our metagenomic analysis reflect the complexity of the oral microbiome, with high diversity and multikingdom interactions, which may play a role in health and disease.

STAR SIGN study: Evaluation of COVID-19 vaccine efficacy against the SARS-CoV-2 variants BQ.1.1 and XBB.1.5 in patients with inflammatory bowel disease.

Vaccine-elicited immune responses are impaired in patients with inflammatory bowel disease (IBD) treated with anti-TNF biologics. To assess vaccination efficacy against the novel omicron sublineages BQ.1.1 and XBB.1.5 in immunosuppressed patients with IBD. This prospective multicentre case-control study included 98 biologic-treated patients with IBD and 48 healthy controls. Anti-spike IgG concentrations and surrogate neutralisation against SARS-CoV-2 wild-type, BA.1, BA.5, BQ.1.1, and XBB.1.5 were measured at two different time points (2-16 weeks and 22-40 weeks) following third dose vaccination. Surrogate neutralisation was based on antibody-mediated blockage of ACE2-spike protein-protein interaction. Primary outcome was surrogate neutralisation against tested SARS-CoV-2 sublineages. Secondary outcomes were proportions of participants with insufficient surrogate neutralisation, impact of breakthrough infection, and correlation of surrogate neutralisation with anti-spike IgG concentration. Surrogate neutralisation against all tested sublineages was reduced in patients with IBD who were treated with anti-TNF biologics compared to patients treated with non-anti-TNF biologics and healthy controls (each p ≤ 0.001) at visit 1. Anti-TNF therapy (odds ratio 0.29 [95% CI 0.19-0.46]) and time since vaccination (0.85 [0.72-1.00]) were associated with low, and mRNA-1273 vaccination (1.86 [1.12-3.08]) with high wild-type surrogate neutralisation in a β-regression model. Accordingly, higher proportions of patients treated with anti-TNF biologicshad insufficient surrogate neutralisation against omicron sublineages at visit 1 compared to patients treated with non-anti-TNF biologics and healthy controls (each p ≤ 0.015). Surrogate neutralisation against all tested sublineages decreased over time but was increased by breakthrough infection. Anti-spike IgG concentrations correlated with surrogate neutralisation. Patients with IBD who are treated with anti-TNF biologics show impaired neutralisation against novel omicron sublineages BQ.1.1 and XBB.1.5 and may benefit from prioritisation for future variant-adapted vaccines.

Vaccine effectiveness against severe COVID-19 during the Omicron wave in Germany: results from the COViK study

PurposeCOViK, a prospective hospital-based multicenter case-control study in Germany, aims to assess the effectiveness of COVID-19 vaccines against severe disease. Here, we report vaccine effectiveness (VE) against COVID-19-caused hospitalization and intensive care treatment during the Omicron wave.MethodsWe analyzed data from 276 cases with COVID-19 and 494 control patients recruited in 13 hospitals from 1 December 2021 to 5 September 2022. We calculated crude and confounder-adjusted VE estimates.Results21% of cases (57/276) were not vaccinated, compared to 5% of controls (26/494; p < 0.001). Confounder-adjusted VE against COVID-19-caused hospitalization was 55.4% (95% CI: 12–78%), 81.5% (95% CI: 68–90%) and 95.6% (95%CI: 88–99%) after two, three and four vaccine doses, respectively. VE against hospitalization due to COVID-19 remained stable up to one year after three vaccine doses.ConclusionThree vaccine doses remained highly effective in preventing severe disease and this protection was sustained; a fourth dose further increased protection.

909P A multi-cancer early detection model based on liquid biopsy of multi-omics biomarkers: A proof of concept study (PROMISE study)

Liquid biopsy is promising for cancer early detection to reduce mortality, particularly for those cancers without effective screening paradigms. The Pan-canceR early detectiOn by Multi-omIcS biomarkErs study (PROMISE, NCT04972201) is a prospective multicenter case-control study to assess the performance of the multi-cancer detection blood test (MCDBT) in the early detection of nine cancers in the lung, colorectum, liver, esophagus, pancreas, head and neck, ovary, and biliary tract.

Neutralizing Antibody Response, Safety, and Efficacy of mRNA COVID-19 Vaccines in Pediatric Patients with Inflammatory Bowel Disease: A Prospective Multicenter Case-Control Study.

The vaccination of immunocompromised children against coronavirus disease 2019 is an important public health issue. We evaluated the serological response, safety, and efficacy of the BNT162b2 vaccine in children with and without inflammatory bowel disease (IBD). A prospective, multicenter, case–control study was conducted in a pediatric population, including patients with IBD, aged 12–18 years. Clinical characteristics, safety profile, and serum samples for surrogate virus-neutralizing antibody testing pre- and post-BNT162b2 vaccination were assessed. The breakthrough infection rate during the Omicron outbreak was calculated to evaluate efficacy. Fifteen controls and twenty-three patients with IBD were enrolled. After two vaccine doses, the median level of percentage inhibition was highly increased, without significant differences between the groups (control 96.9 and IBD 96.3). However, it was significantly reduced in IBD patients receiving combination therapy (anti-tumor necrosis factor-α + immunomodulators) relative to those in other therapies and controls. Serious adverse events were not observed. The breakthrough infection rate was 42.1%, without statistical differences between the groups. Immunization with BNT162b2 in patients with IBD was comparable with that in healthy adolescents in terms of immunogenicity and safety. Nevertheless, the efficacy of BNT162b2 in preventing infection caused by the Omicron variant in the pediatric population was insufficient.

The risk factors of preterm birth: A multicentre case-control survey in China in 2018.

To investigate the risk profile of preterm birth (PTB) in 2018 in China. A prospective multicentre case-control study was conducted in 15 hospitals located in seven provinces throughout three geographical areas (the Eastern, South-Central and North-Western regions) in China. A total of 3147 preterm (<37+0 weeks) and 3147 term (37+0 to 41+6 weeks) live-birth mothers were included. Designed questionnaires were used to investigate maternal and fetal information. We calculated multivariable logistic regression and population attributable risk (PAR). Iatrogenic PTB accounted for 48.1% of preterm mothers. Multivariable analysis showed PTB was significantly associated with six categories of maternal and fetal factors, adverse life-style and psychological conditions (adjusted odds ratio (aOR) 2.063, 95% confidence interval (CI) 1.601-2.657) had the highest PAR% (60.1%). High school and below education level (PAR%=25.8%), living in town or village (PAR%=24.4%), low pregnant weight gain (PAR%=16.8%), hypertensive disorders in pregnancy (aOR: 5.010, 95% CI: 4.039-6.216, PAR%=15.3%), placental abnormality (aOR: 4.242, 95% CI: 3.454-5.211, PAR%=14.1%) and multiple pregnancy (aOR: 10.990, 95% CI: 7.743-15.599, PAR%=11.8%) were significantly associated with PTB with high PAR% value. The main risk factors for PTB in China were placental abnormality, hypertensive disorders in pregnancy and multiple pregnancy. Adverse life-style and psychological conditions and socio-economic disadvantage had high public health significance.

Sulodexide in the treatment of patients with long COVID 19 symptoms and endothelial dysfunction: The results of TUN-EndCOV study

BackgroundEndothelial dysfunction is probably one of the mechanisms of long COVID-19 symptoms. Sulodexide has pleiotropic properties within the vascular endothelium that can prove beneficial in the long COVID-19 symptoms.PurposeWe aimed to evaluate the effect of sulodexide when used in patients with endothelial dysfunction and long COVID-19 symptoms.MethodsWe conducted a prospective multicenter longitudinal case-control study. Endothelial function was evaluated with DTM “E4-Diagnose” Polymath based on the Endothelium Quality Index (EQI). A group of patients with endothelial dysfunction (EQI < 2.0) received sulodexide. All the patients were followed-up 21 days after inclusion. Primary outcomes were defined as endothelial function amelioration (delta EQI) and long COVID-19 symptoms evolution during the follow-up.ResultsA total of 410 patients were included in this study. Patients were included at an average time of 1.89 ± 1.2 month after COVID-19 infection. At inclusion, 210 (51.2%) patients had an EQI < 2. The median age was 49 ± 13.8 (18–80) years. Among the patients with endothelial dysfunction, only 79 patients received sulodexide. Patients in sulodexide group had lower EQI than the non-medical intervention group (0.94 ± 0.6 vs. 1.52 ± 0.4; P < 10−3). They were more diabetic, hypertensive, had more coronary artery disease and received more long-term medications (aspirin, Bblockers and statins) than the others (P = 0.01, 0.002, 0.01, 0.009, 0.001 and 0.01, respectively). At the 21-days follow-up, patients in sulodexide group presented lower long COVID symptoms especially chest pain, palpitations, fatigue and neuro-cognitive difficulties associated to a significant amelioration of endothelial function (delta EQI 1.26 ± 1.07 vs. 0.22 ± 0.7; P < 10−3).ConclusionSulodexide in patients with long COVID-19 may be a good intervention to ameliorate chest pain, palpitations, fatigue and neuro-cognitive difficulties associated to endothelial dysfunction.

Bacterial and Viral Respiratory Tract Microbiota and Host Characteristics in Adults With Lower Respiratory Tract Infections: A Case-Control Study.

BackgroundViruses and bacteria from the nasopharynx are capable of causing community-acquired pneumonia (CAP), which can be difficult to diagnose. We aimed to investigate whether shifts in the composition of these nasopharyngeal microbial communities can be used as diagnostic biomarkers for CAP in adults.MethodsWe collected nasopharyngeal swabs from adult CAP patients and controls without infection in a prospective multicenter case-control study design. We generated bacterial and viral profiles using 16S ribosomal RNA gene sequencing and multiplex polymerase chain reaction (PCR), respectively. Bacterial, viral, and clinical data were subsequently used as inputs for extremely randomized trees classification models aiming to distinguish subjects with CAP from healthy controls.ResultsWe enrolled 117 cases and 48 control subjects. Cases displayed significant beta diversity differences in nasopharyngeal microbiota (P = .016, R2 = .01) compared to healthy controls. Our extremely randomized trees classification models accurately discriminated CAP caused by bacteria (area under the curve [AUC] .83), viruses (AUC .95) or mixed origin (AUC .81) from healthy control subjects. We validated this approach using a dataset of nasopharyngeal samples from 140 influenza patients and 38 controls, which yielded highly accurate (AUC .93) separation between cases and controls.ConclusionsRelative proportions of different bacteria and viruses in the nasopharynx can be leveraged to diagnose CAP and identify etiologic agent(s) in adult patients. Such data can inform the development of a microbiota-based diagnostic panel used to identify CAP patients and causative agents from nasopharyngeal samples, potentially improving diagnostic specificity, efficiency, and antimicrobial stewardship practices.

Placental pathology in COVID-19 affected pregnant women: A prospective case-control study

IntroductionDuring pregnancy, SARS-CoV-2 infection may cause an abnormal development of the placenta, thus influencing maternal and fetal outcomes. Few studies have reported data on placental morphology and histology in infected pregnant patients, although not compared with carefully matched controls. The aim of this study is to compare placental morphology and histology of pregnant women affected by SARS-CoV-2 to non-infected controls. MethodsThis is a prospective multicenter case-control study on 64 pregnant women affected by SARS-CoV-2 who delivered at term or late-preterm. Data were collected about pregnancy course, maternal and fetal outcomes, placental biometry and macro- and microscopical morphology. 64 not-infected women were identified as controls, matched by age, body mass index and ethnicity. ResultsCases and controls had similar fetal and maternal outcomes. No significant differences were observed in placental macro- or microscopical morphology between the two groups. In the cases treated with antivirals, chloroquine, LMWH or antibiotics, placentas were heavier but not more efficient than the non-treated, since the fetal/placental weight ratio did not differ. Moreover, delayed villous maturation was more frequent in treated women, although not significantly. The newborns whose mothers received oxygen therapy as treatment had higher levels of umbilical cord pO₂ at birth. DiscussionIn this prospective case-control study, SARS-CoV-2 infection during the third trimester did not influence placental histological pattern. Pharmacological and oxygen therapy administered to women affected by this viral infection could impact maternal and fetal outcomes and be associated to placental histological alterations.

Risk of intracerebral haemorrhage from hypertension is greatest at an early age.

The risk of intracerebral haemorrhage (ICH) associated with hypertension (HTN) is well documented. While the prevalence of HTN increases with age, the greatest odds ratio (OR) for HTN as a risk for ischemic stroke is at an early age. We sought to evaluate if the risk for ICH from HTN was higher in the youngest patients of each race. The Ethnic/Racial Variations of ICH (ERICH) study is a prospective multicenter case-control study of ICH among whites, blacks, and Hispanics. Participants were divided into age groups based on race-specific quartiles. Cases in each race/age group were compared to controls using logistic regression (i.e., cases and controls unmatched). The probability of ICH among cases and controls for each race were compared against independent variables of HTN, quartile of age and interaction of quartile and age also using logistic regression. Overall, 2033 non-lobar ICH cases and 2060 controls, and 913 lobar ICH cases with 927 controls were included. ORs were highest in the youngest age quartile for non-lobar haemorrhage for blacks and Hispanics and highest in the youngest quartile for lobar haemorrhage for all races. The formal test of interaction between age and HTN was significant in all races for all locations with the exception of lobar ICH in whites (p = 0.2935). Hypertension is a strong independent risk factor for ICH irrespective of location among persons of younger age, consistent with the hypothesis that first exposure to HTN is a particularly sensitive time for all locations of ICH.

Comorbidities, anthropometric, demographic, and lifestyle risk factors for ulnar neuropathy at the elbow: A case control study

We performed a prospective multicenter case-control study to explore the association between ulnar neuropathy at elbow (UNE) and body and elbow anthropometric measures, demographic and lifestyle factors, and comorbidities. Cases and controls were consecutively enrolled among subjects admitted to four electromyography labs. UNE diagnosis was made on clinical and neurographic findings. The control group included all other subjects without signs/symptoms of ulnar neuropathy and with normal ulnar nerve neurography. Anthropometric measurements included weight, height, waist, hip circumferences, and external measures of elbow using a caliper. The participants filled in a self-administered questionnaire on personal characteristics, lifestyle factors, and medical history. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by fitting unconditional logistic regression models adjusted by center and education level. We enrolled 220 cases (males 61.8%; mean age 51.7 years) and 460 controls (47.4% males; mean age 47.8 years). At multivariable analysis, UNE was associated to male gender (OR = 2.4, 95%CI = 1.6-3.7), smoking habits (>25 pack-years (OR = 2.3, 95%CI = 1.3-4.1), body mass index (OR = 1.05, 95%CI 1.01-1.10), polyneuropathies (OR = 4.1, 95%CI 1.5-11.5), and leaning with flexed elbow on a table/desk (OR = 1.5, 95%CI 1.0-2.2). Cubital groove width (CGW) turned out to be negatively associated with UNE (OR = 0.80, 95%CI = 0.74-0.85). Our study suggests that some personal factors especially anthropometric measures of the elbow may play a role in UNE pathogenesis as the measures of wrist in CTS. We demonstrated that for each millimeter of smaller CGW the risk of idiopathic UNE increases of 25%.

Risk Factors of Neonatal Immune Thrombocytopenia in Pregnant Women Previously Diagnosed with ITP: Results from a French Nationwide Prospective Study

Background : Neonatal immune thrombocytopenia (NITP) is a well described complication in newborns of women with ITP. It is reported to occur in about 15% to 30% of neonates. Previous pregnancies with NITP or ITP refractory to splenectomy have been described as associated with NITP mostly in retrospective studies. Methods: We conducted a nationwide prospective multicenter observational case-control study (ClinicalTrials.gov NCT02892630). Thirty-three centers including in the network of ITP experts in France participated in the study. Over a two years period, we enrolled 180 pregnant women with a history of ITP diagnosed before pregnancy and 171 of them were followed up until the delivery. Neonatal platelet counts were available for 136 newborns. Risk factor for developing NITP were evaluated as well as NITP treatment and complications. Results: NITP defined as a platelet count &amp;lt; 100 x 109/L was observed in 37 newborns (27.2%). More severe NITP with platelet counts &amp;lt; 50 x 109/L and &amp;lt; 30 x 109/L, were reported in 19 (14%) and 13 (9.6%) newborns respectively. Intravenous immune globulins were given to 18 newborns. Their median platelet count was 25.5 x 109/L (6; 56). Platelet transfusion was used for 8 newborns with a median platelet count of 13.5 x 109/L (6; 50). NITP was complicated by a hemorrhagic event in only 2 newborns, with a fatal bleeding in 1. Decline in disease ITP status in the mother during pregnancy and previous history of NITP were identified as predictors of NITP &amp;lt; 50 x 109/L by a univariate analysis while only previous history of NITP was confirmed in multivariate analysis (adjusted odds ratio (OR) 4.55; 95% confidence interval (CI) 1.48-13.92; p= 0.008). Decline in ITP disease status in the mother during pregnancy was the sole predictive factor for severe NITP defined as platelet &amp;lt; 30 x 109/L in multivariate analysis (adjusted OR 3.99; 95% CI 1.04-15.36; p = 0.044). Conclusion: Our study confirms that for ITP women with several pregnancies, a previous history of NITP is a risk factor for NITP. We also identify for the first time worsening of disease status during pregnancy to be a novel risk factor of severe NITP. In contrast, we did not confirm that a history of splenectomy was associated with an increased risk of NITP as suggested in retrospective studies (Loustau et al, Br J Haematol 2014; 166 929-35). Our results support that pregnancy in women with ITP is associated with an acceptable risk of severe bleeding in the newborn with NITP which is low but yet existing. Hence, close monitoring of pregnancy and delivery of mothers with ITP and their newborns is required, mainly in women who have a previous history of NITP or experienced a worsening of ITP during the pregnancy. Disclosures Haioun: Takeda: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Roche: Honoraria; Servier: Honoraria; Miltenyi: Honoraria. Mahevas:GSK: Research Funding. Michel:Rigel: Consultancy; Bioverativ: Consultancy; Alexion Pharmaceuticals: Consultancy. Godeau:Novartis: Honoraria; Amgen: Honoraria; Amgen: Research Funding; LFB: Honoraria.

Compared to Normal-Weight Pregnant Women, Overweight Pregnant Women Fail to Upregulate Iron Absorption in the Third Trimester Despite Iron Deficiency and Their Infants Are Born with Lower Body Iron Stores

Introduction: Overweight/obesity (OWOB) causes low-grade systemic inflammation which induces hepcidin and a reduces fractional iron absorption (FIA) even when iron stores are low. Pregnancy increases iron needs because of the expansion of maternal blood volume and fetal needs. It is unclear whether and/or to what extent OWOB during pregnancy influences FIA, iron supply of the fetus and risk of iron deficiency in mother and newborn. In this study, we (1) determined the impact of maternal OWOB on FIA in pregnancy and on the transfer of iron to the fetus and newborn iron status; (2) confirmed the relationship between BMI, hepcidin, serum ferritin (SF) and inflammatory markers. Methods: In this prospective experimental multi-center case-control study (normal-weight (NW) n=40; OWOB n=37) we administered labeled [57Fe]- or [58Fe]-FeSO4 to women during the 2nd and 3rd trimester of pregnancy. We measured FIA by determining erythrocyte incorporation of iron stable isotopes 14 days after administration. From pregnancy week (PW) 12 until PW 36, iron-, inflammation and hepcidin were monitored. Iron transfer to the fetus was determined isotopically as the concentration of circulating iron in the infant aged three days. We assessed iron status in infants born to NW (n=29) and OWOB (n=31) at age three days, three months and six months. Results: Subject characteristics in PW 12 for the NW/OWOB were: mean (±SD) age: 29±6/ 30±6 years, median (IQR) pre-pregnancy BMI: 21.6 (20.3-23.7)/ 31.6 (28.4-35.9) kg/m2 (p&amp;lt;0.001), mean (±SD) hemoglobin: 12.3±1.1/ 12.4±0.9 g/dL, median (IQR) SF: 27.7 (17.3-48.2)/ 30.6 (16.6-64.4) µg/L and median (IQR) interleukin-6: 1.41 (1.03-1.95)/ 2.37 (1.91-3.85) pg/ml (p&amp;lt;0.001). Independent sample t-test showed no difference in FIA between NW and OWOB in the 2nd trimester with median FIA (IQR) 12.3 (7.2-20.6) and 10.1 (6.9-17.2) % (p=0.788). Despite the OWOB had ≈30% lower body iron stores (BIS) and comparable hepcidin concentrations to the NW in the 3rd trimester, FIA was significantly higher in the NW compared to the OWOB with median FIA (IQR) 22.3 (10.6-33.8) and 12.7 (10.4-18.1) % (p=0.042). In the NW, FIA was upregulated by 80% in the 3rd trimester compared to the 2nd trimester, whereas in the OWOB FIA, it was only upregulated by 25%. Linear mixed effect model analysis (LMM) showed a significant group-effects on weight, IL-6 and CRP throughout pregnancy (all p&amp;lt;0.05), but surprisingly no group-effect on hepcidin. In multiple regression analysis, the main predictor of hepcidin throughout pregnancy was BIS, not inflammation. Iron transfer to the newborn was non-significantly higher in the NW compared to the OWOB with mean (±SD) circulating iron in the newborn at age three days 136.6 ± 42.7 and 126.3 ± 32.4 mg. LMM on infant BIS and on infant serum transferrin receptor (sTfR) over the first six months showed significant group (p=0.024, p=0.046) and time-effects (both p&amp;lt;0.001) with lower BIS and higher sTfR in infants born to OWOB. Median (IQR) BIS at age six months were 7.7 (6.3-8.8) and 6.6 (4.6-9.2) mg/kg bodyweight in infants born to NW and OWOB. Conclusion: In normal pregnancy, FIA increases over time to support increased iron needs of mother and fetus. Our data show a dramatically reduced increase in FIA in OWOB pregnant women in the 3rd trimester, despite low BIS and low hepcidin, and this results in less iron transfer to the fetus. Future molecular studies are needed to clarify the mechanism of reduced FIA and fetal iron transfer in OWOB. To our knowledge, this is the first study assessing the impact of maternal OWOB on infant iron status at multiple time points over the first six months. Our findings strongly argue for careful monitoring of iron status in OWOB pregnancy and for defining a more effective iron supplementation regimen for this population group. Prevalence of anemia in pregnancy and infancy is high, especially in low and middle income countries and is often associated with severe health consequences. If iron status of OWOB pregnant women and their infants could be improved by optimizing iron supplementation guidelines for OWOB, this could have major benefits. Disclosures No relevant conflicts of interest to declare.

Outcome of Immune Thrombocytopenia in Pregnancy: A French Nationwide Prospective Multicenter Observational Case-Control Study

Background: Adult immune thrombocytopenia (ITP) is a rare autoimmune disease that can affect women of childbearing age. The effect of pregnancy on women with a pregestational diagnosis of ITP is still unclear and has never been prospectively studied. Objective: Investigate the effect of pregnancy on the course of ITP. Methods: We conducted a nationwide prospective multicenter observational case-control study (ClinicalTrials.gov NCT02892630). Thirty-three centers from the French ITP reference center network participated in the study. Over a two years period, we enrolled 131 pregnant women with a pregestational diagnosis of ITP and 131 non pregnant women of childbearing age with ITP who served as controls. Matching criteria included: history of splenectomy, disease status (defined as non-responder, responder or complete responder depending on platelet count and the need of treatment modification in the last 2 months) and ITP duration (i.e; persistent (&amp;lt;1 year) or chronic). Cases and controls were followed up for 15 months and platelets counts, hemorrhagic complications and treatment initiation or intensification for ITP were recorded. We defined ITP worsening by a combined score including the occurrence of bleeding and/or occurrence of severe thrombocytopenia (i.e. &amp;lt; 30 G/L) and/or changes in ITP disease status. Results: ITP worsening was significantly increased in pregnant women with ITP when compared to matched controls, affecting respectively 52.7% versus 38.2% (p= 0.05) of patients (figure 1). It occurred mainly during the second and third trimesters. However, the frequency of severe thrombocytopenia (28.2% vs 25.2%, p= 0.69) and incidence of bleeding (22.9% vs 15.3%, p= 0.15) were similar in both groups, even when considering severe bleeding only (Khellaf's bleeding score &amp;gt;7) (16% vs 9.2%, p= 0.11).In contrast, initiation and intensification of therapy were significantly increased in pregnant women compared to matched controls, respectively 32.1% versus 20.6% (p = 0.01) of patients. Importantly, this increased need for therapy did not lead to an increase in maternal and obstetrical complications. In particular, we found no increase of complications that could have been exacerbated by corticosteroid and intravenous immunoglobulins use such as gestational diabetes or high blood pressure. Also compared to pre-gestational period, at 6 months post-partum, only 16.8% of pregnant women showed disease worsening. This frequency was comparable in the control group after 15 months follow-up (16.8%, p = 0.57). Conclusion: The current guidelines on therapy for pregnant women with pregestational ITP are mostly based on expert opinions and retrospective studies that mainly recommend treatment for pregnant women with a platelet count &amp;lt; 30 x 109/L. This prospective observational study investigating ITP progression during pregnancy shows that women with ITP were more intensively treated during pregnancy compared with matched controls. Paradoxically, this does not coincide with an increased of clinical or biological worsening in pregnant womenwhich raises questions of the relevance of this therapeutic conduct although we cannot exclude that these therapies may have prevented disease progression during pregnancy. Finally in late post-partum period, disease worsening was low and seems to be link to the natural course of the disease. Disclosures Haioun: Celgene: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Roche: Honoraria; Servier: Honoraria; Amgen: Honoraria; Miltenyi: Honoraria. Mahevas:GSK: Research Funding. Michel:Rigel: Consultancy; Alexion Pharmaceuticals: Consultancy; Bioverativ: Consultancy. Godeau:Novartis: Honoraria; LFB: Honoraria; Amgen: Honoraria; Amgen: Research Funding.

Suicidal behaviour recurrence in psychiatric emergency departments of patients without a prior suicide attempt, index and reattempters: A prospective study

IntroductionThere has been little change in the incidence of suicidal behaviour and reattempts in recent years. Evidence is needed on the incidence of suicidal behaviour in the psychiatric population and its follow-up. Material and methodA prospective multi-centre case–control study. The sample covered the cases of 440 patients seen as psychiatric emergencies. For this purpose, we used the Vital Adverse Event Scale by Brugha and screening with the Columbia Scale. The sample was divided into three groups: patients without prior suicide attempts, patients with an index attempt and patients with more than one attempt. At two years, the clinical histories of these patients were reviewed, assessing for suicidal behaviour. ResultsA total of 49.1% (n=216) of the patients required urgent psychiatric care during the follow-up period, and 2.7% eventually committed suicide. The data shows a differential profile between the three groups analysed. Among them, the group of reattempters required the highest number of interventions regarding suicide behaviour (11.0%; χ2=30.3; d.f.=2; p<.001). Eventually, 6.1% of the patients without prior suicide attempts tried to commit suicide for the first time, and 21.7% (n=60) of the remaining sample repeated their prior attempts. The highest risk of attempt was in the thirty days following the urgent intervention. After this period, risk distribution varied for each group. Three items from the Columbia Scale predict suicide behaviour. ConclusionsThe results show the need for assessing suicidal behaviour for all patients who receive psychiatric urgent care, including during the follow-up period. A more thorough control should be performed during the first months for patients without prior suicide attempts, and longer periods for those patients who have already tried to commit suicide.

Reduced incidence of type 2 diabetes in patients with chronic hepatitis C virus infection cleared by direct-acting antiviral therapy: A prospective study.

To assess the effect of hepatitis C virus (HCV) eradication on type 2 diabetes mellitus (T2DM). incidence. A prospective multicentre case-control study was performed, which included 2426 patients with HCV, 42% of whom had liver fibrosis stage F0-F2 and 58% of whom had liver fibrosis stage F3-F4. The study population consisted of a control group including 1099 untreated patients and 1327 cases treated with direct-acting antivirals (DAAs). T2DM incidence was assessed during a median (interquartile range) follow-up period of 30 (28-42) months. Risk factors for T2DM were assessed using a Cox regression model (relative risk [RR], hazard ratio [HR], Kaplan-Meier analysis). Insulin sensitivity was evaluated by homeostatic model assessment (HOMA) and changes by repeated-measures ANOVA. Factors independently associated with T2DM were assessed by multivariate analysis. The absolute incidence of T2DM for controls and cases was 28 and 7/1000 person-years, respectively (P = 0.001). In cases compared to controls, HCV clearance reduced the RR and HR of T2DM by 81% and 75% to 93%, respectively (P = 0.001). It was calculated that, for every 15 patients who obtained HCV clearance, one case of T2DM was saved. HCV clearance was associated with significant reductions in HOMA-insulin resistance and HOMA-β-cell function and an increase in HOMA-insulin sensitivity, as assessed in 384 patients before and after HCV clearance. At multivariate analysis, HCV clearance emerged as independently associated with a reduced T2DM risk. The results showed that HCV clearance by DAA treatment reduces T2DM incidence probably by restoring the HCV-induced alteration of glucose homeostasis mechanisms.

Osteoporosis: risk factor for implants?

Many, mostly older patients suffer from osteoporosis: a chronic skeletal disease causing bone to become more porous and less strong. 2 recent systematic reviews and one long-term prospective multicentre case-control study showed that placing implants in osteoporosis patients is not contraindicated. From these studies it can be concluded that results comparable to those with patients who do not suffer from osteoporosis can be reached. Osseointegration, implant survival rate, marginal bone loss and mucosal parameters do not behave differently than they do in the healthy group of patients.

Sexual Function in Women With Polycystic Ovary Syndrome: Design of an Observational Prospective Multicenter Case Control Study.

IntroductionThe prevalence of polycystic ovary syndrome (PCOS) is 10–15% in women of reproductive age. Its characteristics are (i) clinical or biochemical hyperandrogenism, (ii) oligomenorrhea or amenorrhea, and (iii) polycystic ovaries on ultrasound. PCOS is associated with lower quality of life, depression, anxiety, diabetes, and cardiovascular disease. Treatment commonly entails oral contraceptive use to lower endogenous androgen levels. Androgen levels and comorbidities may affect sexual function. Previous studies have addressed a limited range of possible contributing factors. We will assess sexual function as well as genital and self-reported sexual arousal in a laboratory setting in women with PCOS compared to an age-matched healthy control group. Modulation by biopsychosocial factors mentioned will be studied.MethodsThis is a multicenter prospective case control study. The study population includes healthy women with and without PCOS, aged 18–40 years, in a stable heterosexual relationship for at least 6 months. Power is calculated at 67 participants in each group. Anticipating a drop out of 10%, 150 participants will be recruited.Main outcome measuresThe main outcomes measured are sexual function using the Female Sexual Function Index, Sexual Desire Inventory, and Female Sexual Distress Scale-Revised; genital sexual arousal measured as vaginal pulse amplitude; and self-reported sexual arousal in response to erotic stimuli in a laboratory setting. The mediators that will be investigated include testosterone, free androgen levels, oral contraceptive use, sensitivity to androgens (using CAG repeat length), body mass index, body image, mental health, and self-esteem.ConclusionStrengths of this study are the inclusion of a broad range of biopsychosocial outcome measures including DNA analysis, a healthy control group, and standardized assessment of genital and self-reported sexual arousal in a laboratory setting. With the design of this study we aim to provide an insight into which biopsychosocial factors associated with PCOS are related to sexual function, and how sexual function may be affected by treatment. These new insights may help to improve clinical management of PCOS while improving the quality of life.Pastoor H, Both S, Timman R, et al. Sexual Function in Women With Polycystic Ovary Syndrome: Design of an Observational Prospective Multicenter Case Control Study. Sex Med 2020;8:718–729.