Remission and low disease activity are associated with lower healthcare costs: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

OBJECTIVES: This study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort. METHODS: Patients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity states (DAS) were defined as (1) remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone/immunosuppressants; (2) remission on-treatment: cSLEDAI-2K=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; (3) LDA-Toronto Cohort (TC): cSLEDAI-2K≤2, without prednisone/immunosuppressants; (4) modified lupus LDA state (mLLDAS): SLEDAI-2K≤4, no activity in major organs/systems, no new activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants and (5) active: all remaining assessments.At each assessment, patients were stratified into the most stringent DAS fulfilled and the proportion of time in a DAS since cohort entry was determined. Annual DCs/ICs (2021 Canadian dollars) were based on healthcare use and lost workforce/non-workforce productivity over the preceding year.The association between the proportion of time in a DAS and annual DC/IC was examined through multivariable random-effects linear regressions. RESULTS: 1692 patients were followed a mean of 9.7 years; 49.0% of assessments were active. Remission/LDA (per 25% increase in time in a remission/LDA state vs active) were associated with lower annual DC/IC: remission off-treatment (DC -$C1372; IC -$C2507), remission on-treatment (DC -$C973; IC -$C2604,) LDA-TC (DC -$C1158) and mLLDAS (DC -$C1040). There were no cost differences between remission/LDA states. CONCLUSIONS: Our data suggest that systemic lupus erythematosus patients who achieve remission, both off and on-therapy, and reductions in disease activity incur lower costs than those experiencing persistent disease activity.

High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium.

BACKGROUND: The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality. OBJECTIVE: We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Caesarean delivery and neonatal mortality: evidence from selected slums in and around Dhaka city, Bangladesh- A prospective cohort study.

BACKGROUND: This study examined the neonatal mortality for newborn of women who delivered by caesarean section or vaginally using a prospective cohort. METHODS: A total of 6,989 live births registered from 2016 to 2018, were followed for neonatal survival from the selected slums of Dhaka (North and South) and Gazipur city corporations, where icddr,b maintained the Health and Demographic Surveillance System (HDSS). Neonatal mortality was compared by maternal and newborn characteristics and mode of delivery using z-test. Logistic regression model performed for neonatal mortality by mode of delivery controlling selected covariates and reported adjusted odd ratios (aOR) with 95% confidence interval (CI). RESULTS: Out of 6,989 live births registered, 27.7% were caesarean and the rest were vaginal delivery; of these births, 265 neonatal deaths occurred during the follow-up. The neonatal mortality rate was 2.7 times higher (46 vs. 17 per 1,000 births) for vaginal than caesarean delivered. Until 3rd day of life, the mortality rate was very high for both vaginal and caesarean delivered newborn; however, the rate was 24.8 for vaginal and 6.3 per 1,000 live births for caesarean delivered on the 1st day of life. After adjusting the covariates, the odds of neonatal mortality were higher for vaginal than caesarean delivered (aOR: 2.63; 95% CI: 1.82, 3.85). Additionally, the odds were higher for adolescent than elderly adult mother (aOR: 1.60; 95% CI: 1.03, 2.48), for multiple than singleton birth (aOR: 5.40; 95% CI: 2.82, 10.33), for very/moderate (aOR: 5.13; 95% CI: 3.68, 7.15), and late preterm birth (aOR: 1.48; 95% CI: 1.05, 2.08) than term birth; while the odds were lower for girl than boy (aOR: 0.74; 95% CI: 0.58, 0.96), and for 5th wealth quintile than 1st quintile (aOR: 0.59, 95% CI: 0.38, 0.91). CONCLUSION: Our study found that caesarean delivered babies had significantly lower neonatal mortality than vaginal delivered. Therefore, a comprehensive delivery and postnatal care for vaginal births needed a special attention for the slum mothers to ensure the reduction of neonatal mortality.

Risk of chronic kidney disease in 260 patients with lupus nephritis-analysis of a nationwide multicentre cohort with up to 35 years of follow-up.

OBJECTIVES: To compare proliferative (PLN) and membranous (MLN) lupus nephritis (LN) regarding clinical and laboratory presentation and long-term outcomes; To investigate predictors of progression to chronic kidney disease (CKD). METHODS: Multicentre observational study, with retrospective analysis of a prospective cohort, using data from the Rheumatic Diseases Portuguese Registry-Reuma.pt. Patients with biopsy-proven PLN, MLN and mixed LN were included. Cox regression survival analysis was used to investigate predictors of CKD. RESULTS: 260 patients were included. Median follow-up was 8 years (IQR 11; minimum 1, maximum 35 years). MLN patients presented with significantly lower serum creatinine (0.70 (IQR 0.20; minimum 0.50, maximum 1.30) mg/dl vs 0.80 (IQR 0.31; minimum 0.26, maximum 2.60) in PLN, p= 0.003). Proteinuria levels did not differ between groups (p= 0.641). Levels of complement were reduced in PLN but nearly normal in MLN patients, and there were fewer patients with positive anti-dsDNA antibodies in the MLN group (p< 0.001). One year after the beginning of treatment, 62% of the patients achieved EULAR/ERA-EDTA complete response, with further 5% achieving partial response. Patients with lower proteinuria at diagnosis were more likely to achieve a complete renal response at one year, however, proteinuria at diagnosis or at one year did not predict long term CKD. Estimated glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 at one year was the strongest predictor of progression to CKD (HR 23 [95% CI 8-62], p< 0.001). Other possible predictors included the use of azathioprine for induction of remission, older age at diagnosis and male sex. CONCLUSION: Proteinuria levels did not predict LN histologic class in our cohort. eGFR cutoff of 75 mL/min/1.73 m2 after one year of treatment was strongly predictive of progression to CKD.

Gut microbiome composition reveals the distinctiveness between the Bengali people and the Indigenous ethnicities in Bangladesh.

Ethnicity has a significant role in shaping the composition of the gut microbiome, which has implications in human physiology. This study intends to investigate the gut microbiome of Bengali people as well as several indigenous ethnicities (Chakma, Marma, Khyang, and Tripura) residing in the Chittagong Hill Tracts areas of Bangladesh. Following fecal sample collection from each population, part of the bacterial 16 s rRNA gene was amplified and sequenced using Illumina NovaSeq platform. Our findings indicated that Bangladeshi gut microbiota have a distinct diversity profile when compared to other countries. We also found out that Bangladeshi indigenous communities had a higher Firmicutes to Bacteroidetes ratio than the Bengali population. The investigation revealed an unclassified bacterium that was differentially abundant in Bengali samples while the genus Alistipes was found to be prevalent in Chakma samples. Further research on these bacteria might help understand diseases associated with these populations. Also, the current small sample-sized pilot study hindered the comprehensive understanding of the gut microbial diversity of the Bangladeshi population and its potential health implications. However, our study will help establish a basic understanding of the gut microbiome of the Bangladeshi population.

Comparing pregnancy outcomes in patients with Systemic Lupus Erythematosus (SLE) and Undifferentiated Connective Tissue Disease (UCTD): a descriptive cohort study.

BACKGROUND: Females diagnosed with systemic lupus erythematosus (SLE) face an elevated risk of adverse pregnancy outcomes (APOs). However, the evidence regarding whether a similar association exists in patients with undifferentiated connective tissue disease (UCTD) is inconclusive. METHODS: We conducted a retrospective review (2006-2019) of pregnancy outcomes among patients with SLE (n = 51) and UCTD (n = 20) within our institution. We examined the occurrence of various APOs, encompassing miscarriage, stillbirth, termination, preterm birth, pre-eclampsia, eclampsia, HELLP syndrome, intrauterine growth restriction, abruption placentae, congenital heart block, or other cardiac abnormalities. RESULTS: The mean age at pregnancy was 35 ±â€¯7.0 years for patients with SLE and 35 ±â€¯6.8 years for those with UCTD (p = 0.349). The proportion of Caucasian women was 47% in SLE and 80% in UCTD. Pregnancies in both groups were planned (81% in SLE and 77% in UCTD), and patients presented with inactive disease at conception (96% in SLE and 89% in UCTD). Hydroxychloroquine at conception was utilized by 86% of women with SLE, in contrast to 36% in the UCTD group. Both, SLE and UCTD cohorts exhibited low rates of disease flares during pregnancy and/or puerperium (14% vs. 10%). The incidence of APOs was 15.6% in SLE patients compared to 5% in those with UCTD (Risk difference 19.5%; 95% confidence interval: -3.9 to 43.1; p = 0.4237). CONCLUSION: Our study underscores the importance of strategic pregnancy planning and the maintenance of appropriate treatment throughout pregnancy to ensure optimal disease management and minimize adverse outcomes in both SLE and UCTD pregnancies.

Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus.

BACKGROUND: Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort. METHODS: Individuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up. RESULTS: Of the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1). CONCLUSION: Anti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis.

Effect of a parenting and nutrition education programme on development and growth of children using a social safety-net platform in urban Bangladesh: a cluster randomized controlled trial.

Background: Although sustainable development goals mandate for quality early childhood development (ECD) interventions for children <8 years, little occurs for children <3 years, especially in urban settings in low-and-middle-income countries (LMICs). Our primary objective was to measure the effect of an ECD-focused parenting and nutrition education on children's development through home visits using a social safety net platform of urban Bangladesh. Methods: A cluster randomized controlled trial was conducted with mothers of children aged 6-16 months in 20 clusters across the Rangpur city, Bangladesh. The intervention group received fortnightly ECD-focused parenting and nutrition education at homes by local Community Health Workers (CHWs) for one year. Bayley-III was used to measure children's cognitive, language and motor development. Data were analyzed using intention to treat. ClinicalTrials.gov Identifier: NCT03753646. Findings: Out of 599 mother-child dyads, 56.6% mothers were aged ≤ 25 years old. After one year, the intervened children had higher cognitive [Effect size Cohen's d; 0.42 SD (95% CI: 0.58-0.25)], language (0.38 SD, 95% CI: 0.55-0.22) and motor (0.17 SD, 95% CI: 0.01-0.34) development. In the intervention group, mothers experienced less violence [Odds ratio; 0.6 (95% CI: 0.4-1.0)] and fathers engaged more (0.23 SD, CI: 0.39-0.06) in ECD activities with their children compared to the comparison group. Total home stimulation and mothers' knowledge on child care were also improved in the intervention. But the children's growth was not improved. Interpretation: This ECD programme improves the development of children of young mothers in urban settings using a social safety-net platform. The evidence may help in increasing ECD coverage in urban areas in LMICs. Funding: Grand Challenges Canada, Saving Brains Programme Grant Number: SB-1810-20176.

Long-Term Kinetics of SARS-CoV-2 Neutralizing and Anti-Receptor Binding Domain Antibodies among Laboratory-Confirmed COVID-19 Cases in Delhi National Capital Region, India: A Prospective, One-Year Follow-Up Study.

Background: This study was conducted with the objective of measuring the neutralizing and anti-receptor binding domain antibody levels against SARS-CoV-2 among laboratory-confirmed COVID-19 cases and exploring its long-term kinetics over a period of 1 year. Methods: One hundred laboratory-confirmed COVID-19 cases were recruited. Serum samples of the participants were collected within three months from the date of the positive COVID-19 report. The participants were prospectively followed up every three months for symptoms and the collection of blood samples for three additional rounds. The presence of anti-SARS-CoV-2 antibodies (IgA, IgG, and IgM antibodies), anti-receptor binding domain antibodies (anti-RBD), and neutralizing antibodies were measured. Findings: Median plaque reduction neutralization test (PRNT) titers showed a rising trend in the first three rounds of follow-up. The quantitative anti-receptor binding domain ELISA (QRBD) values showed a declining trend in the initial three rounds. However, both the PRNT titers and QRBD values showed significantly higher values for the fourth round of follow-up. Total antibody (WANTAI) levels showed an increasing trend in the initial three rounds (statistically significant). Interpretation: Neutralizing antibodies showed an increasing trend. The anti-receptor binding domain antibodies showed a decreasing trend. Neutralizing antibodies and anti-RBD antibodies persisted in the majority.

The Factors Associated With COVID-19 Infection Among Healthcare Workers at a Tertiary Care Institution in North India: A Case-Control Study.

Background and objective Healthcare workers (HCWs) are at a higher risk of contracting coronavirus disease 2019 (COVID-19) since they regularly come into direct contact with infected patients and their surroundings. In light of this, it is critical to study the potential risk factors for SARS-CoV-2 infection among HCWs to help determine its transmission patterns and prevent infections among HCWs, as well as healthcare-associated COVID-19. Methods We conducted a case-control study at a tertiary healthcare center from December 2020 to August 2021. HCWs who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, by RT-PCR were included as cases and those who tested negative for RT-PCR and SARS-CoV-2 antibodies were recruited as controls. We interviewed 316 HCWs (187 cases and 129 controls) by using the WHO questionnaire titled "Protocol for assessment of potential risk factors for coronavirus disease 2019 among health workers in a health care setting" to assess infection prevention and control (IPC) knowledge and practices, including the use of personal protective equipment (PPE). The odds ratio (OR) for factors associated with infection was determined by multivariable logistic regression. Results The majority (87.2%) of the cases were symptomatic. Adherence to IPC measures was higher among controls as compared to cases. A significantly higher number of controls used PPE compared to cases. The proportions of HCWs involved in cleaning, patient transport, reception, and catering were higher among cases (37.9%) compared to controls (19.1%). In multivariable analysis, undergoing training on care for COVID-19 patients was associated with a lower risk of infection (OR: 0.40, 95% CI: 0.24-0.69). Conclusions Adherence to IPC and use of PPE were significantly higher among controls as compared to cases. Receiving training in COVID-19 patient care and compliance with IPC measures were associated with a lower risk of COVID-19 infection among HCWs in this study.

The impact of antiphospholipid antibodies/antiphospholipid syndrome on systemic lupus erythematosus.

aPLs are a major determinant of the increased cardiovascular risk in patients with SLE. They adversely affect clinical manifestations, damage accrual and prognosis. Apart from the antibodies included in the 2006 revised classification criteria for APS, other non-classical aPLs might help in identifying SLE patients at increased risk of thrombotic events. The best studied are IgA anti-ß2-glycoprotein I, anti-domain I ß2-glycoprotein I and aPS-PT. Major organ involvement includes kidney and neuropsychiatric systems. aPL/APS severely impacts pregnancy outcomes. Due to increased thrombotic risk, these patients require aggressive cardiovascular risk factor control. Primary prophylaxis is based on low-dose aspirin in high-risk patients. Warfarin is the gold-standard drug for secondary prophylaxis.

Preterm birth and neonatal mortality in selected slums in and around Dhaka City of Bangladesh: A cohort study.

BACKGROUND: Although under-five mortality has declined appreciably in Bangladesh over the last few decades, neonatal mortality still remains high. The objective of the study is to assess the level and determinants of preterm birth and the contribution of preterm birth to neonatal mortality. METHODS: Data for this study came from selected slums in and around Dhaka city, where; since 2015, icddr,b has been maintaining the Health and Demographic Surveillance System (HDSS). The HDSS data were collected by female Field Workers by visiting each household every three months; however, during the visit, data on the Last Menstrual Period (LMP) were also collected by asking each eligible woman to ascertain the date of conception. Gestational age was estimated in complete weeks by subtracting LMP from the date of the pregnancy outcome. In this study, 6,989 livebirths were recorded by HDSS during 2016-2018, and these births were followed for neonatal survival; both bivariate and multivariate analyses were performed. RESULTS: Out of total births, 21.7% were born preterm (before 37 weeks of gestation), and sub-categories were: 2.19% for very preterm (28 to 31 weeks), 3.81% for moderate preterm (32 to 33 weeks), and 15.71% for late preterm (34 to 36 weeks). The study revealed that preterm babies contributed to 39.6% of neonatal deaths; however, the probability of death was very high on the 1st day of birth (0.124 for very preterm, 0.048 for moderate preterm, 0.024 for late preterm, and 0.013 for term birth), and continued until the 3rd day. In the regression analysis, compared to the term neonates, the odds of neonatal mortality were 8.66 (CI: 5.63, 13.32, p<0.01), 4.13 (CI: 2.69, 6.34, p<0.01) and 1.48 (CI: 1.05, 2.08, p<0.05) respectively for very, moderate, and late preterm birth categories. The population attributable fraction for neonatal mortality was 23%, and sub-categories were 14% for very preterm, 10% for moderate preterm, and 6% for late preterm. CONCLUSIONS: Although urban slums are in proximity to many health facilities, a substantial proportion of preterm births contribute to neonatal deaths. So, pregnant women should be targeted, to ensure timely care during pregnancy, delivery, and post-partum periods to improve the survival of new-borns in general and preterm birth in particular.

SARS-CoV-2 infection and seropositivity among household contacts of laboratory confirmed cases of COVID-19 in residents of Delhi, India.

The transmission of respiratory pathogens, including SARS-CoV-2, is often facilitated through household contact. To better understand the transmission rate of COVID-19 among households and factors that affect viral clearance and seroconversion, a case-ascertained community-based prospective study was conducted between December 2020 and June 2021 on the urban population of the national capital region of India. The study collected nasopharyngeal swabs for SARS-CoV-2 RT-PCR on the 1st, 7th, 14th, and 28th day, and blood samples for antibody detection on the 1st, 14th, and 28th day from household contacts (HCs) of laboratory-confirmed COVID-19 cases. The study monitored the demographic data, symptoms, and outcomes of 417 participants, including 99 index cases and 318 contacts, for a period of 28 days. The results of the study showed that SARS-CoV-2 was easily spread within households, with a secondary infection rate of 44.3 %. In fact, almost 70 % of the contacts got infected within 1-2 days of identification of the index case, while 34 % remained asymptomatic. Sero-conversion was found in 35.6 % of the participants while 22.9 % did not produce antibodies after 28 days of infection. The study also revealed that females, spouses, older members, and primary care providers were at higher risk of getting infected in a home setting. However, approximately one-third of individuals in the younger age group managed to avoid infection. The study demonstrated that most infected individuals became RT-PCR negative within two weeks, although viral clearance was delayed in older patients and those with lower cycle threshold values in RT-PCR.

Trends and risk of recurrent preterm birth in pregnancy cohorts in rural Bangladesh, 1990-2019.

INTRODUCTION: A history of preterm birth reportedly increases the risk of subsequent preterm birth. This association has primarily been studied in high-income countries and not in low-income settings in transition with rapidly descending preterm birth figures. We evaluated the population-based trends of preterm births and recurrent preterm births and the risk of preterm birth recurrence in the second pregnancy based on prospectively studied pregnancy cohorts over three decades in Matlab, Bangladesh. METHODS: A population-based cohort included 72 160 live births from 1990 to 2019. We calculated preterm birth and recurrent preterm birth trends. We assessed the odds of preterm birth recurrence based on a subsample of 14 567 women with live-born singletons in their first and second pregnancies. We used logistic regression and presented the associations by OR with a 95% CI. RESULTS: The proportion of preterm births decreased from 25% in 1990 to 13% in 2019. The recurrent preterm births had a similar, falling pattern from 7.4% to 3.1% across the same period, contributing 27% of the total number of preterm births in the population. The odds of second pregnancy preterm birth were doubled (OR 2.18; 95% CI 1.96 to 2.43) in women with preterm birth compared with the women with term birth in their first pregnancies, remaining similar over the study period. The lower the gestational age at the first birth, the higher the odds of preterm birth in the subsequent pregnancy (test for trend p<0.001). CONCLUSION: In this rural Bangladeshi setting, recurrent preterm births contributed a sizeable proportion of the total number of preterm births at the population level. The increased risk of recurrence remained similar across three decades when the total proportion of preterm births was reduced from 25% to 13%.

Transmissibility of severe acute respiratory syndrome coronavirus 2 among household contacts of coronavirus disease 2019-positive patients: A community-based study in India.

BACKGROUND: This study identified the risk factors for severe acute respiratory syndrome coronavirus 2 infection among household contacts of index patients and determined the incubation period (IP), serial interval, and estimates of secondary infection rate in Kerala, India. METHODS: We conducted a cohort study in three districts of Kerala among the inhabitants of households of reverse transcriptase polymerase chain reaction-positive coronavirus disease 2019 patients between January and July 2021. About 147 index patients and 362 household contacts were followed up for 28 days to determine reverse transcriptase polymerase chain reaction positivity and the presence of total antibodies against SARS-CoV-2 on days 1, 7, 14, and 28. RESULTS: The mean IP, serial interval, and generation time were 1.6, 3, and 3.9 days, respectively. The secondary infection rate at 14 days was 43.0%. According to multivariable regression analysis persons who worked outside the home were protected (adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.24-0.85), whereas those who had kissed the coronavirus disease 2019-positive patients during illness were more than twice at risk of infection (aOR, 2.23; 95% CI, 1.01-5.2) than those who had not kissed the patients. Sharing a toilet with the index patient increased the risk by more than twice (aOR, 2.5; 95% CI, 1.42-4.64) than not sharing a toilet. However, the contacts who reported using masks (aOR, 2.5; 95% CI, 1.4-4.4) were at a higher risk of infection in household settings. CONCLUSIONS: Household settings have a high secondary infection rate and the changing transmissibility dynamics such as IP, serial interval should be considered in the prevention and control of SARS-CoV-2.

Household transmission investigation for Corona Virus Disease 2019 (COVID-19) in a rural and urban population of north India.

BACKGROUND: Transmissibility within closed settings, such as households, can provide a strategic way to characterize the virus transmission patterns because the denominator can be well defined. We aimed to characterize the household transmission of Severe Acute Respiratory Syndrome Coronavirus (SARS CoV-2) and its associated risk factors. METHODS: This prospective case-ascertained study was conducted among the household contacts of laboratory-confirmed SARS CoV-2 cases residing in Ballabgarh, Haryana. We enrolled 148 index cases and their 645 household contacts between December 16, 2020 and June 24, 2021. We defined household contact as any person who had resided in the same household as a confirmed COVID-19 case. Baseline data collection and sample collection for real time- reverse transcriptase polymerase chain reaction (RT-PCR) and IgM/IgG against SARS CoV-2 were done on day 1 visit, and followed for a period of 28 days. RT-PCR was repeated on day 14 or whenever the contact is symptomatic and blood sample for serology was repeated on day 28. We estimated household secondary infection rate (SIR) and other epidemiological indicators-median incubation period and serial interval. We employed binomial logistic regression to quantify risk factors associated with infection. RESULTS: The household SIR was 30.5% (95% CI: 27.1-34.1%). The secondary clinical attack rate was 9.3% (95% CI: 7.2-11.8). The risk factors that showed higher susceptibility to infection were household contacts who were the primary care giver of the case, whose index cases were symptomatic, those with underlying medical conditions, those living in overcrowded households, who were sharing toilet with the index cases and also who were not wearing a mask when coming in contact with the case. The median (IQR) incubation period was 4 days (4, 5), mean (SD) serial interval 6.4 (±2.2) days, and median (IQR) serial interval 5 days (5, 7). CONCLUSION: Households favour secondary transmission of SARS CoV- 2, hence, index cases are recommended to self-isolate and wear masks; and household contacts to follow strict COVID infection control measures within households when a family member is infected.

Preservation of whole antibodies within ancient teeth.

Archaeological remains can preserve some proteins into deep time, offering remarkable opportunities for probing past events in human history. Recovering functional proteins from skeletal tissues could uncover a molecular memory related to the life-history of the associated remains. We demonstrate affinity purification of whole antibody molecules from medieval human teeth, dating to the 13th-15th centuries, from skeletons with different putative pathologies. Purified antibodies are intact retaining disulphide-linkages, are amenable to primary sequences analysis, and demonstrate apparent immunoreactivity against contemporary EBV antigen on western blot. Our observations highlight the potential of ancient antibodies to provide insights into the long-term association between host immune factors and ancient microbes, and more broadly retain a molecular memory related to the natural history of human health and immunity.

Benchmarking the Effects of Water Demand Management During Water Crisis in a Regional City.

Regional cities are having their unique water security challenges due to regional urban water contexts, regional socio-economic structure, and climate conditions. Regional urban community's perceptions of water usage are expected to be different from the communities in large metropolitan cities. The city of Townsville is the largest regional city in the northern tropical region of the state of Queensland in Australia, and it is known to have its unique dry tropic climate condition. The city faced a water crisis due to a prolonged drought in 2013-2018. As part of this research, at first, a literature review was conducted to understand what water demand management (WDM) tools worked well during urban water crisis in different parts of the world. This paper then investigates how residential water usage changed with the changes in drought measures in the city of Townsville in the last decade. A minimum per capita residential water requirement is established for the study region to benchmark the effects of tools implemented in the region. The paper investigates the WDM policies implemented in the city of Townsville including when the policies were applied and the impacts and efficacy of these policies before water crisis, during water crisis and after water crisis. The most effective WDM tools identified are water restrictions, public awareness raising and education programmes. The impacts of water restriction policies and the perceptions of local water professionals on their success elements are also studied. The results are compared and the reasons behind the findings are investigated.

Comparative predictive power of serum vs plasma proteomic signatures in feto-maternal medicine.

BACKGROUND: Blood proteins are frequently measured in serum or plasma, because they provide a wealth of information. Differences in the ex vivo processing of serum and plasma raise concerns that proteomic health and disease signatures derived from serum or plasma differ in content and quality. However, little is known about their respective power to predict feto-maternal health outcomes. Predictive power is a sentinel characteristic to determine the clinical use of biosignatures. OBJECTIVE: This study aimed to compare the power of serum and plasma proteomic signatures to predict a physiological pregnancy outcome. STUDY DESIGN: Paired serum and plasma samples from 73 women were obtained from biorepositories of a multinational prospective cohort study on pregnancy outcomes. Gestational age at the time of sampling was the predicted outcome, because the proteomic signatures have been validated for such a prediction. Multivariate and cross-validated models were independently derived for serum and plasma proteins. RESULTS: A total of 1116 proteins were measured in 88 paired samples from 73 women with a highly multiplexed platform using proximity extension technology (Olink Proteomics Inc, Watertown, MA). The plasma proteomic signature showed a higher predictive power (R=0.64; confidence interval, 0.42-0.79; P=3.5×10-6) than the serum signature (R=0.45; confidence interval, 0.18-0.66; P=2.2×10-3). The serum signature was validated in plasma with a similar predictive power (R=0.58; confidence interval, 0.34-0.75; P=4.8×10-5), whereas the plasma signature was validated in serum with reduced predictive power (R=0.53; confidence interval, 0.27-0.72; P=2.6×10-4). Signature proteins largely overlapped in the serum and plasma, but the strength of association with gestational age was weaker for serum proteins. CONCLUSION: Findings suggest that serum proteomics are less informative than plasma proteomics. They are compatible with the view that the partial ex-vivo degradation and modification of serum proteins during sample processing are an underlying reason. The rationale for collecting and analyzing serum and plasma samples should be carefully considered when deriving proteomic biosignatures to ascertain that specimens of the highest scientific and clinical yield are processed. Findings suggest that plasma is the preferred matrix.