Actus Santé

Objective: To evaluate the relationship between medications used to treat acute agitation (antipsychotics, mood stabilizers and benzodiazepines) and subsequent assault incidence in the psychiatric emergency room. Methods: Medication orders and assault incident reports were obtained from electronic health records for 17,052 visits to an urban psychiatric emergency room from 2014-2019. Assault risk was modeled longitudinally using Poisson mixed-effect regression. Results: Assaults were reported during 0.5% of visits. Intramuscular medications (IMs) were administered in 23.3% of visits overall, and predominately administered within the first 4-hours of a visit. IM administration was correlated with assault (IRR=24.2 [5.33, 110.0]), often because IM medication was administered immediately subsequent to reported assaults. Interacted with time, IMs were not significantly associated with reduction in future assaults (IRR=0.700 [0.467, 1.04]). Neither benzodiazepines nor mood stabilizers were associated with subsequent changes to the risk of reported assault. By contrast, antipsychotic medications were associated with decreased assault risk across time (IRR=0.583 [0.360, 0.942]). Conclusions: IM order rates are high relative to overall assault incident risk. Of the three major categories of medications administered commonly in the psychiatric emergency setting, only antipsychotic medications were associated with measurable decreases in subsequent assault risk. Careful weighing of the risks and benefits of medications is encouraged; antipsychotic medication can have a significant side effect burden, and other medications (IMs, benzodiazepines, mood stabilizers) were not associated with subsequent reduction in assault risk in this analysis.

Background COVID-19 is suggested to be more prevalent among ethnic minorities and individuals with low socioeconomic status. We aimed to investigate the prevalence of SARS-CoV-2 antibodies during the COVID-19 pandemic among citizens 15 years or older in Denmark living in social housing (SH) areas . Methods As part of Testing Denmark, a nationwide sero-epidemiological surveillance survey, we conducted a study between January 8th and January 31st, 2021 with recruitment in 13 selected SH areas in Denmark. Participants were offered a point-of-care rapid SARS-CoV-2 IgM and IgG antibody test and a questionnaire concerning previous testing (viral throat- and nasopharyngeal swab or antibody test), test results for COVID-19, demographics, household characteristics, employment, risk factors for SARS-CoV-2 infection and history of symptoms associated with COVID-19. Data on seroprevalence from Danish blood donors in same period using a total Ig ELISA assay were used as a proxy for the general Danish population. Findings Of the 13,279 included participants, 2,296 (17.3%) were seropositive (mean age 46.6 (SD 16.4) years, 54.2% female), which was 3 times higher than in the general Danish population (mean age 41.7 (SD 14.1) years, 48.5% female) in the same period (5.8%, risk ratios (RR) 2.96, 95% CI 2.78-3.16, p>0.001). Seropositivity was higher among males than females (RR 1.1, 95% CI 1.05-1.22%, p=0.001) and increased with age, with an OR seropositivity of 1.03 for each 10-year increase in age (95% CI 1.00-1.06, p=0.031). Close contact with COVID-19-infected individuals was associated with a higher risk of infection, especially among members of the same households (OR 5.0, 95% CI 4.1-6.2 p<0,001). Adjusted for age, gender and region living at least 4 people in a household significantly increased the OR of seropositivity (OR 1.3, 95% CI 1.1-1.6, p=0.02) as did living in a multi-generational household (OR 1.3 per generation, 95% CI 1.1-1.5, p=0.007). Only 1.6% of participants reported not following any of the national COVID-19 recommendations. Anosmia (RR 3.2 95% CI 2.8-3.7, p<0.001) and ageusia (RR 3.3, 95% CI 2.9-3.8, p<0.001) were strongest associated with seropositivity. Interpretation Danish citizens living in SH areas of low socioeconomic status had a three times higher SARS-CoV-2 seroprevalence compared to the general Danish population. The seroprevalence was significantly higher in males and increased with age. Living in multiple generations or more than four persons in a household was an independent risk factor for being seropositive. Results of this study can be used for future consideration of the need for preventive measures in the populations living in SH areas.

Monitoring SARS-CoV-2 spread and evolution through genome sequencing is essential in handling the COVID-19 pandemic. The availability of patient hospital records is crucial for linking the genomic sequence information to virus function during the course of infections. Here, we sequenced 892 SARS-CoV-2 genomes collected from patients in Saudi Arabia from March to August 2020. From the assembled sequences, we estimate the SARS-CoV-2 effective population size and infection rate and outline the epidemiological dynamics of import and transmission events during this period in Saudi Arabia. We show that two consecutive mutations (R203K/G204R) in the SARS-CoV-2 nucleocapsid (N) protein are associated with higher viral loads in COVID-19 patients. Our comparative biochemical analysis reveals that the mutant N protein displays enhanced viral RNA binding and differential interaction with key host proteins. We found hyper-phosphorylation of the adjacent serine site (S206) in the mutant N protein by mass-spectrometry analysis. Furthermore, analysis of the host cell transcriptome suggests that the mutant N protein results in dysregulated interferon response genes. We provide crucial information in linking the R203K/G204R mutations in the N protein as a major modulator of host-virus interactions and increased viral load and underline the potential of the nucleocapsid protein as a drug target during infection.

Aim/Hypothesis: Five subgroups were described in European diabetes patients using a data driven machine learning approach on commonly measured variables. We aimed to test the applicability of this phenotyping in Indian young-onset type 2 diabetes patients. Methods: We applied the European derived centroids to the Indian type 2 diabetes patients diagnosed before 45 years of age from the WellGen (n = 1612) cohort. We also applied de novo k-means clustering to the WellGen cohort to validate the subgroups. We then compared clinical and metabolic-endocrine characteristics and the complication rates between the subgroups. We also compared characteristics of the WellGen subgroups with those of two young European cohorts ANDIS (n = 962) and DIREVA (n = 420). Subgroups were also assessed in two other Indian cohorts, Ahmedabad (n = 187) and PHENOEINDY-2 (n = 205). Results: Both Indian and European young type 2 diabetes patients were predominantly classified into severely insulin-deficient (SIDD) and mild obesity-related (MOD) subgroups, while the severely insulin-resistant (SIRD) and mild age-related (MARD) subgroups were rare. In WellGen, SIDD (53%) was more common than MOD (38%), contrary to figures in Europeans (Swedish: 26% vs 68%, Finnish: 24% vs 71% respectively). A higher proportion of SIDD compared to MOD was also seen in Ahmedabad (57% vs 33%) and in PHENOEINDY-2 (67% vs 23%). Both in Indians and Europeans, the SIDD subgroup was characterized by insulin deficiency and hyperglycemia, MOD by obesity, SIRD by severe insulin resistance and MARD by mild metabolic-endocrine disturbances. In WellGen, nephropathy and retinopathy were more prevalent in SIDD compared to MOD while the latter had higher prevalence of neuropathy. Conclusions/Interpretation: Our data identified insulin deficiency as the major driver of type 2 diabetes in young Indians, unlike in young European patients in whom obesity and insulin resistance predominate. Our results provide useful clues to pathophysiological mechanisms and susceptibility to complications in young Indian type 2 diabetes, and suggest a need to review management strategies.

ABSTRACT Importance: Despite its high prevalence and poor outcomes, research on peripheral artery disease (PAD) remains limited due to the poor accuracy of billing codes for identifying PAD in health systems. Objective: Design a natural language processing (NLP) system that can extract ankle brachial index (ABI) and toe brachial index (TBI) values and evaluate the performance of extracted ABI/TBI values to identify patients with PAD in the Veterans Health Administration (VHA). Design, Setting, Participants: From a corpus of 392,244 ABI test reports at 94 VHA facilities during 2015-2017, we selected a random sample of 800 documents for NLP development. Using machine learning, we designed the NLP system to extract ABI and TBI values and laterality (right or left). Performance was optimized through sequential iterations of 10-fold cross validation and error analysis on 3 sets of 200 documents each, and tested on a final, independent set of 200 documents. Performance of NLP-extracted ABI and TBI values to identify PAD in a random sample of Veterans undergoing ABI testing was compared to structured chart review. Exposure: ABI <0.9, or TBI <0.7 in either right or left limb used to define PAD at the patient-level Main Outcome: Precision (or positive predictive value), recall (or sensitivity), F-1 measure (overall measure of accuracy, defined as harmonic mean of precision and recall) Results: The NLP system had an overall precision of 0.85, recall of 0.93 and F1-measure of 0.89. The F-1 measure was similar for both ABI and TBI (0.88 to 0.91). Recall was higher for ABI (0.95 to 0.97) while precision was higher for TBI (0.94 to 0.95). Among 261 patients with ABI testing (49% with PAD), the NLP system was able to extract ABI and TBI values in 238 (91.2%) patients. The NLP system had a positive predictive value of 92.3%, sensitivity of 89.3% and specificity of 92.3% to identify PAD. Conclusion: We have successfully developed and validated an NLP system to extract ABI and TBI values which can be used to accurately identify PAD within the VHA. Our findings have broad implications for PAD research and quality improvement efforts in large health systems.

Background: In early January 2021, an outbreak of nosocomial cases of COVID 19 emerged in Western France, with RT PCR tests repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole genome sequencing (WGS) revealed a new variant, currently defining a novel SARS CoV 2 lineage: B.1.616. In March, WHO classified this variant as "under investigation" (VUI). We analyzed the characteristics and outcomes of COVID 19 cases related to this new variant. Methods: Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled patients with at least one of the following: i) positive SARS CoV 2 RT PCR on a respiratory sample; ii) seroconversion with anti SARS CoV 2 IgG/IgM; iii) suggestive symptoms and typical features of COVID 19 on chest CT scan. Cases were categorized as either: i) B.1.616; ii) variant of concern (VOC); iii) unknown. Findings: From January 1st to March 24th, 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n=34), VOC (n=32), and unknown (n=48). B.1.616 related cases were older than VOC related cases (81 years [73-88], vs 73 years [67-82], P<0.05) and their first RT PCR tests were less often positive (5/34, 15% vs 31/32, 97%, P<0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.2 [1.3 , 13.5], P=0.018), and increased lethality (logrank test P=0.01): 28day mortality 15/34 (44%) with B.1.616, vs. 5/32 (16%) for VOC, P=0.036. Interpretation: We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, poorly detected by RT PCR on nasopharyngeal samples, with high lethality.

The uncontrolled spread of the COVID-19 pandemic has led to the emergence of different SARS-CoV-2 variants across the globe. The ongoing global vaccination strategy to curtail the COVID-19 juggernaut, is threatened by the rapidly spreading Variants of Concern (VOC) and other regional mutants, which are less responsive to neutralization by infection or vaccine derived antibodies. We have previously developed the hiVNT system which detects SARS-CoV-2 neutralizing antibodies in sera in less than three hours. In this study, we modify the hiVNT for rapid qualitative screening of neutralizing antibodies (nAb) to multiple variants of concern (VOC) of SARS-CoV-2, and assess the neutralizing efficacy of the BNT162b2 mRNA vaccine on seven epidemiologically relevant SARS-CoV-2 variants. Here we show that the BNT162b2 mRNA vaccine can activate humoral immunity against the major SARS-CoV-2 mutants that are currently in circulation. Albeit a small sample size, we observed that one dose of vaccine was sufficient to elicit a protective humoral response in previously infected people. Using a panel of seven SARS-CoV-2 variants and a single prototype virus, our modified hiVNT would be useful for large-scale community wide testing to detect protective immunity that may confer vaccine/immune passport in the ongoing COVID-19 pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has been mutating and thus variants emerged. This suggests that SARS-CoV-2 could mutate at an unsteady pace. Supportive evidence comes from the accelerated evolution which was revealed by tracking mutation rates of the genomic location of Spike protein. This process is sponsored by a small portion of the virus population but not the largest viral clades. Moreover, it generally took one to six months for current variants that caused peaks of COVID-19 cases and deaths to survive selection pressure. Based on this statistic result and the above speedy Spike evolution, another upcoming peak would come around July 2021 and disastrously attack Africa, Asia, Europe, and North America. This is the prediction generated by a mathematical model on evolutionary spread. The reliability of this model and future trends out of it comes from the comprehensive consideration of factors mainly including mutation rate, selection course, and spreading speed. Notably, if the prophecy is true, then the new wave will be the first determined by accelerated Spike evolution.

Acute febrile patients presenting at hospitals in Douala, Cameroon between July and December 2020, were screened for dengue infections using RT-PCR on fragments of the 5 and 3 UTR genomic regions. In total, 12.8% (41/320) of cases examined were positive for dengue. Dengue virus 3 (DENV-3) was the most common serotype found (68.3%), followed by DENV-2 (19.5%) and DENV-1 (4.9%). Co-infections of DENV-3 and DENV-2 were found in 3 cases. Jaundice and headache were the most frequent clinical signs associated with infection and 176 cases (55%) were co-infections with malaria. Phylogenetic analysis of the envelope gene identified DENV-1 as belonging to genotype V, DENV-2 to genotype II and DENV-3 to genotype III. The simultaneous occurrence of three serotypes in Douala reveals dengue as a serious public health threat for Cameroon and highlights the need for further epidemiological studies in the major cities of this region.

Background Social network-based HIV self-testing (HIVST) is useful to promote HIV testing. Secondary distribution is one social network-based method whereby individuals (indexes) access multiple HIVST kits and distribute them to their social networks (alters). This quasi-experimental study compared the effectiveness and cost of two social network-based HIV testing strategies (HIVST secondary distribution and HIV testing card referral) in promoting HIV testing among Chinese men who have sex with men (MSM). Methods MSM aged 18 years or older were recruited in Guangzhou, Guangdong Province. From May to September 2019, indexes recruited during that period could distribute HIVST kits to people within their social network. Indexes recruited from October 2019 to January 2020 could refer HIV testing cards to people within their social network for free facility-based tests. Participants could access 1-5 HIVST kits or testing referral cards for distribution. Alters were encouraged to upload a picture of their test results and complete an online survey. Indexes and alters received an incentive to report test results. Results Two hundred thirty-nine potential participants were assessed for eligibility and 208/245 (84.9%) were eligible. Among those who completed baseline assessment, 154/208 (74.0%) completed one month of follow-up. Overall,106 indexes were recruited in the HIVST arm and 102 in the testing card arm. The two arms had similar socio-demographic characteristics. At the one-month follow-up, 92 indexes in the HIVST arm self-reported having distributed self-test kits to 179 unique alters, and 62 in the testing card arm self-reported having distributed testing referral cards to 26 unique alters. Additionally, 69/92 (75%) in the HIVST arm distributed any test to friends or sexual partners compared to 18/62 (29%) in the testing card arm, with a risk difference of 46% (95% CI 31%, 61%). Indexes in the HIVST arm distributed an average of 1.95 (SD=1.90) tests, compared to 0.42 (SD=0.78) in the testing card arm, with a risk difference of 1.53 (95% CI 1.09, 1.96). Subgroup analysis suggested that indexes in the HIVST arm who self-identified as gay (p = 0.007) or were previously tested for HIV (p = 0.02) were more likely to distribute. The HIVST arm had a higher total cost and higher testing coverage compared to the testing card referral arm. The ICER per alter tested was $52.78. Conclusions Secondary distribution of HIVST engaged more MSM to distribute tests to their social network and reached more MSM for test. MSM who self-identify as gay or who have previously tested for HIV were more effective in distributing tests. Future testing approaches should include HIVST kits in voluntary counselling and testing settings and incorporate digital strategies for secondary distribution.

Introduction: Mistreatment by healthcare providers disproportionately affects people of color in the United States (US). The goal of this study is to adapt the global Person-Centered Maternity Care (PCMC) scale to the experiences of people of color in the US using a community-engaged approach. Methods: We conducted expert reviews to improve content validity and cognitive interviews with potential respondents were conducted to assess relevance, comprehension, and comprehensiveness. Surveys of 297 postpartum people, 82% of whom identified as Black, were used for psychometric analysis in which we assessed construct and criterion validity and reliability. The University of California, San Francisco, California Preterm Birth Initiative Community Advisory Board (CAB), which consists of community members, community-based health workers, and social service providers in Northern California, provided input during all stages of the project. Results: Through an iterative process of factor analysis, discussions with the CAB, and a prioritization survey, we eliminated items that performed poorly in psychometric analysis, yielding a 35-item PCMC-US scale with sub-scales for dignity and respect, communication and autonomy, and responsive and supportive care. The Cronbach alpha for the full scale is 0.95 and for the sub-scales is 0.87. Standardized summative scores range from 0 to 100, with higher scores indicating higher PCMC. Correlations with related measures indicated high criterion validity. Conclusions: The 35-item PCMC-US scale and its sub-scales have high validity and reliability in a sample of predominantly Black women. This scale provides a tool to support efforts to reduce the disparities in birth outcomes among people of color.

Objectives To investigate the impact of targeted vaccination strategies on morbidity and mortality due to COVID-19, as well as on the incidence of SARS-CoV-2, in India. Design Mathematical modelling. Settings Indian epidemic of COVID-19 and vulnerable population. Data sources Country specific and age-segregated pattern of social contact, case fatality rate and demographic data obtained from peer-reviewed literature and public domain. Model An age-structured dynamical model describing SARS-CoV-2 transmission in India incorporating uncertainty in natural history parameters was constructed. Interventions Comparison of different vaccine strategies by targeting priority groups such as key workers including health care professionals, individuals with comorbidities (24 - 60 year), and all above 60. Main outcome measures Incidence reduction and averted deaths in different scenarios, assuming that the current restrictions are fully lifted as vaccination is implemented. Results The priority groups together account for about 18% of India's population. An infection preventing vaccine with 60% efficacy covering all these groups would reduce peak symptomatic incidence by 20.6% (95% uncertainty intervals (CrI) 16.7 - 25.4), and cumulative mortality by 29.7% (95% CrI 25.8- 33.8). A similar vaccine with ability to prevent symptoms (but not infection) will reduce peak incidence of symptomatic cases by 10.4% (95% CrI 8.4 - 13.0), and cumulative mortality by 32.9% (95% CrI 28.6 - 37.3). In the event of insufficient vaccine supply to cover all priority groups, model projections suggest that after keyworkers, vaccine strategy should prioritise all who are > 60, and subsequently individuals with comorbidities. In settings with weakest transmission, such as sparsely-populated rural areas, those with comorbidities should be prioritised after keyworkers. Conclusions An appropriately targeted vaccination strategy would witness substantial mitigation of impact of COVID-19 in a country like India with wide heterogenity. 'Smart vaccination', based on public health considerations, rather than mass vaccination, appears prudent.

Genome-wide association studies (GWAS) of proxy-phenotypes using family history of disease (GWAX) substantially boost power for genetic discovery when combined with direct case-control GWAS, most prominently in the context of Alzheimer's Disease (AD). However, despite twin study heritability estimates of approximately 60%, recent SNP-based estimates of common variant heritability of AD from meta-analyzed GWAS-GWAX data have been particularly low (2.5%), calling into question the prospects of continued progress in AD genetics. We demonstrate that commonly used approaches for combining GWAX and GWAS data produce dramatic underestimates of heritability, and we introduce a multivariate method for estimating individual SNP effects and recovering unbiased estimates of SNP heritability when combining GWAS and GWAX summary data. We estimate the SNP heritability of Clinical AD diagnoses excluding the APOE region at ~6-10%, with the corresponding estimate for biological AD (based on prevalence rate estimates from recently published molecular imaging data) as high as ~20%. Common variant risk for AD appears to represent a very strong effect of APOE superimposed upon a relatively diffuse polygenic signal that is distributed across the genome.

Idiopathic Pulmonary Fibrosis (IPF) is a rare disease with poor prognosis. By contrast, cancer is common in any elderly population and a leading killer, but is now often curable. Of note, whereas IPF is driven by cellular senescence, cancer is characterized by uncontrolled cell division. Using data available from two large biobank-based studies (Finnish FinnGen study and UK biobank), we conducted a comprehensive analysis of the shared genetic background of IPF and cancer. In a population sample of 218,792 Finns with complete longitudinal health histories, we estimated the effect of individual genetic variants to the lifetime risk of IPF and cancer. We extend the analysis from IPF-GWAS to pan-cancer meta-analysis over FinnGen and UK Biobank and finally to the identification of genetic drivers of somatic chromosomal alterations. We detected six loci (SPDL1, MAD1L1, MAP2K1, RTEL1-STMN3, TERC-ACTRT3, OBFC1) associated with both IPF and cancer, all closely related to cellular division. However, each individual signal is found with opposite effects over the two diseases, termed as antagonistic pleiotropy. Several of these loci (TERC-ACTRT3, RTEL1-STMN3, OBFC1) are among the strongest inherited factors for constitutive telomere length variation and consistently indicate that shorter telomere length would increase the risk for IPF but protect from malignancy. However, a Finnish enriched SPDL1 missense variant and a common MAD1L1 intronic variant had no effect on telomere length but were shown to protect individuals from accumulation of somatic mutations. The decreased risk of cancer in SPDL1 and MAD1L1 variant carriers might result from a lower number of chromosomal alterations accumulated over time, conversely leading to fibrosis in the lung due to cellular senescence-induced inflammation. We hypothesize that the SPDL1 missense variant functions as gain-of-function mutation, leading to cellular senescence, a barrier to cancer and a driver of fibrosis in IPF. If translated to therapy, these findings might not only be able to offer relief to individuals with IPF, but also to protect from onset of cancer.

People with hearing loss experience fatigue, and it is unknown whether this is alleviated by treatment with hearing aids. The objective of this study was to address this issue, and to investigate the possible concomitant effect of hearing-aid fitting on activity levels. An intervention group (n=53) who were due to be fitted with their first ever hearing aid(s) and a control group (n=53) who had hearing loss but no change in hearing aid status completed a battery of self-report outcome measures four times: once before fitting, and at two weeks, three months and six months post fitting. Self-report outcome measures at each assessment captured fatigue, listening effort, hearing handicap, auditory lifestyle, social participation restrictions and work, social and physical activity levels. Hearing-aid fitting led to a significant reduction in listening-related fatigue, but not general fatigue, in the intervention group compared to the control group. Additionally, social activity level increased and social participation restriction decreased significantly after hearing aid fitting in the intervention group compared to the control group. No significant interaction was found between working status and change in listening-related fatigue score. This study is the first to make longitudinal measurement of fatigue before and after first-ever hearing aid fitting and to identify an increase in social activity level after hearing aid fitting. These findings have important implications for future research and the clinical practice of hearing aid fitting.

Background context Traumatic thoracolumbar (TL) fractures are frequently encountered in emergency rooms. Sagittal and anteroposterior radiographs are the first step in the trauma routine imaging. Up to 30% of TL fractures are missed in this imaging modality, thus requiring a CT and/or MRI to confirm the diagnosis. A delay in treatment leads to increased morbidity, mortality, exposure to ionizing radiation and financial burden. Fracture detection with Machine Learning models has achieved expert level performance in previous studies. Reliably detecting vertebral fractures in simple radiographic projections would have a significant clinical and financial impact. Purpose To develop a deep learning model that detects traumatic fractures on sagittal radiographs of the TL spine. Study design/setting Retrospective Cohort study. Methods We collected sagittal radiographs, CT and MRI scans of the TL spine of 362 patients exhibiting traumatic vertebral fractures. Cases were excluded when CT and/or MRI where not available. The reference standard was set by an expert group of three spine surgeons who conjointly annotated the sagittal radiographs of 171 cases. CT and/or MRI were reviewed to confirm the presence and type of the fracture in all cases. 302 cropped vertebral images were labelled -fracture- and 328 -no fracture-. After augmentation, this dataset was then used to train, validate, and test deep learning classifiers based on ResNet18 and VGG16 architectures. To ensure that the prediction of the model was based on the correct identification of the fracture zone, an Activation Map analysis was conducted. Results Vertebras T12 to L2 were the most frequently involved, accounting for 48% of the fractures. A4, A3 and A1 were the most frequent AO Spine fracture types. Accuracies of 88% and 84% were obtained with ResNet18 and VGG16 respectively. The sensitivity was 89% with both architectures but ResNet18 showed a higher specificity (88%) compared to VGG16 (79%). The fracture zone was precisely identified in 81% of the heatmaps. Conclusions Our AI model can accurately identify anomalies suggestive of vertebral fractures in sagittal radiographs by precisely identifying the fracture zone within the vertebral body. Clinical significance Clinical implementation of a diagnosis aid tool specifically trained for TL fracture identification is anticipated to reduce the rate of missed vertebral fractures in emergency rooms.

Abstract Objective On the basis of retrospectively analysis the trans-cerebellar section showing the Sylvian fissure of normal fetus is better than trans-thalamic section in middle and late trimester, we prospectively established the normal reference range of developmental parameters related to the Sylvian fissure of normal fetus in the trans-cerebellar section in order to provide valuable information for the diagnosis of fetal cerebral cortical dysplasia. Methods A prospective cross-sectional study was conducted on 845 normal fetuses at 21 to 32 weeks of gestation from January 2019 to September 2020. The depth and width of the Sylvian fissure was measured respectively, and regression analysis was performed according to different gestational age groups. Results The depth of Sylvian fissure was positively correlated with gestational weeks, and the width of Sylvian fissure was negatively correlated with gestational weeks, with correlation coefficients 0.751 and 0.825 respectively (all P < 0.001).Taking gestational weeks as the independent variable, and the depth and width of Sylvian fissure of fetus as the dependent variables, linear regression analysis showed that there was a linear relationship between the independent variables and the dependent variables. The obtained equation was simplified to a formula: Fetal Sylvian fissure depth (mm)=7+0.6X(gestational weeks-21), Sylvian fissure width (mm)=8-0.6X(gestational weeks-21). Conclusion The reference range of the depth and width of Sylvian fissure of normal fetus at 21 to 32 weeks of pregnancy through the trans-cerebellar section was established, which could provide valuable information for the evaluation of the normal development of the lateral fissure of fetus and the prenatal diagnosis of fetal cortical hypoplasia. Key words Fetus; Sylvian fissure; depth; width; trans-cerebellar section

Introduction: Gestational hypertension (GH)/Pre-eclampsia (PEC) is an important cause of direct maternal deaths in Sri Lanka. GH/PEC and threatened miscarriage (TM) share common pathophysiological mechanisms. This study was conducted to determine the association between TM and development of GH/PEC. Methodology: A case control study was conducted at Castle Street Hospital for Women, Sri Lanka from April 2015 to October 2015. Cases consisted of patients with GH/PEC and compared with age and parity matched controls. A systematic random sampling method was used. Similar number of cases and controls were compared while each group consisted of 245 subjects. Data was obtained from medical records. It is also important to note that mothers aged 20-35 years were included and medical disorders other than GH/PEC was excluded. Results: There were 245 subjects in each group of the study. Among the cases, 56% had GH and the rest had PEC. There were 25 patients with TM in the study population and 64% of them subsequently developed GH or PEC. There is also a significant risk of developing PEC in a patient who had a history of threatened miscarriage (OR 3.31, 95% CI 1.35-8.11). Moreover the patients who had a history of TM tend to develop GH or PEC early, within 20-32 weeks of gestation (OR 11.49, 95% CI 3.88-33.99). As we identified, 62% of patients who had TM developed GH/PEC early (from 20 to 32 weeks) but among the cases who had no history of TM, only 12% developed GH/PEC between 20 to 32 weeks of gestation (O.R. 20.7 (5.66 to 91.96). There is a significant risk of developing severe GH/PEC in the group of patients who had a history of TM (OR 8.59, 95% CI 2.87- 25.66). Eighty one percent (81%) of the cases, who had a history of TM, developed severe and moderate GH/PEC rather than mild. But the majority (63%) of the cases, who had no history of TM, developed mild GH/PEC (O.R. 7.6 (2.00 to 42.55).

Background and purpose In response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, self-isolation practices aimed to curb the spread of COVID-19 have severely complicated the medical management of patients suffering from endometriosis and their physical and mental well- being. Endometriosis, the main cause for chronic pelvic pain (CPP), is a highly prevalent disease characterized by the presence of endometrial tissue in locations outside the uterine cavity that affects up to 10% of women in their reproductive age. This study aimed to explore the effects of the global COVID-19 pandemic on patients suffering from endometriosis across multiple countries, and to investigate the different approaches to the medical management of these patients based on their self- reported experiences. Methods A cross-sectional survey, partially based on validated quality of life questionnaires for endometriosis patients, was initially created in English, which was then reviewed by experts. Through the process of assessing face and content validity, the questionnaire was then translated to fifteen different languages following the WHO recommendations for medical translation. After evaluation, the questionnaire was converted into a web form and distributed across different platforms. An analysis of 2964 responses of participants from 59 countries suffering from self-reported endometriosis was then conducted. Results The data shows an association between COVID-19 imposed compromises with the reported worsening of the mental state of the participants, as well as with the aggravation of their symptoms. For the 1174 participants who had their medical appointments cancelled, 43.7% (n=513) reported that their symptoms had been aggravated, and 49.3% (n=579) reported that their mental state had worsened. In comparison, of the 1180 participants who kept their appointments, only 29.4% (n=347) stated that their symptoms had been aggravated, and 27.5% (n=325) stated their mental health had worsened. 610 participants did not have medical appointments scheduled, and these participants follow a similar pattern as the participants who kept their appointments, with 29.0% (n=177) reporting aggravation of symptoms and 28.2% (n=172) reporting that their mental state had worsened. Conclusions These findings suggest that COVID-19 pandemic has had a clinically significant negative effect on the mental and physical well-being of participants suffering from endometriosis based on their self-reported experiences. Thus, they show the importance of further assessment and reevaluation of the current and future management of this condition in medical practices worldwide. Keywords Endometriosis, COVID-19, questionnaire, Quality of life, Mental health, Physical health

Objective On the basis of retrospectively analysis the trans-cerebellar section showing the Sylvian fissure of normal fetus is better than trans-thalamic section in middle and late trimester, we prospectively studied the morphological changes of the Sylvian fissure of normal fetus on the trans-cerebellar section in order to provide valuable information for the diagnosis of fetal cerebral cortical dysplasia. Methods A prospective cross-sectional study was conducted on 845 normal fetuses at 21 to 32 weeks of gestation from January 2019 to September 2020. The angle of the posterosuperior horn of the Sylvian fissure was measured. Based on the angle, the morphology of the Sylvian fissure was divided into four shapes included trapezoid shape (Angle >90), square shape (Angle=90); T shape (Angle <90) and I shape (Angl=0). Results The angle of the posterosuperior horn of the Sylvian fissure was negatively correlated with gestational age which correlation coefficient was 0.966 (P < 0.001). Taking gestational age as the independent variable and the angle of posterosuperior horn of the Sylvian fissure as the dependent variable, it showed that there was a linear relationship between the gestational age and the angle of posterosuperior horn of the Sylvian fissure. We got a simple correlation formula that the angle of posterosuperior horn of the Sylvian fissure =140-13X(gestational weeks-21). It was found that the morphological changes of the Sylvian fissure were related to the gestational age. The morphology of the Sylvian fissure was trapezoid shaped at 21 to 24 weeks of gestation, square shaped at 25 to 26 weeks of gestation, T shaped at 26 to 30 weeks of gestation, and the Sylvian fissure was almost closed and appeared I shaped after 31 to 32 weeks of gestation. Conclusion This study preliminarily elucidates that the morphological changes of the posterosuperior horn of the Sylvian fissure of normal fetuses at 21 to 32 weeks of gestation through the trans-cerebellar section, which could provide valuable information for the evaluation of the normal development of the Sylvian fissure and the prenatal diagnosis of cerebral cortical hypoplasia of fetuses. Key words Fetus; Sylvian fissure; posterosuperior horn; morphology; trans-cerebellar section