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Abstract Background Pregnancy complications might lead to the development of autoimmune diseases in women. This review aims to summarise studies evaluating the association between pregnancy complications and the development of autoimmune diseases in women. Methods Medline, CINAHL, and Cochrane databases were searched up to January 2024. Nineteen pregnancy complications and 15 autoimmune conditions were included. Title, abstract, full-text screening, data extraction, and quality assessment were performed by two reviewers independently. Data were synthesised using narrative and quantitative methods. Results were presented using odds ratios (OR), relative risks (RR), incidence rate ratios (IRR), and 95% confidence intervals (CI). Results Thirty studies were included. One study reported composite exposure to pregnancy complications had a risk of any autoimmune disease RR 3.20 (2.90–3.51) compared to women without pregnancy complications. Women with hyperemesis gravidarum had a higher risk of developing coeliac disease (n = 1) IRR 1.98 (1.27–2.94), Crohn’s disease (n = 1) IRR 1.61 (1.25–2.04), psoriasis (n = 1) IRR 1.33 (1.01–1.71), and rheumatoid arthritis (n = 2) IRR 1.35 (1.09–1.64). Miscarriage associated with subsequent diagnosis of Sjogren syndrome (n = 2) IRR 1.33 (1.06–2.81) and rheumatoid arthritis (n = 4) OR 1.11 (1.04–1.20). Gestational hypertension/preeclampsia was linked with the development of systemic sclerosis (n = 2) IRR 2.60 (1.10–4.60) and T1DM (n = 2) IRR 2.37 (2.09–2.68). Stillbirth associated with composite autoimmune conditions (n = 2) RR 5.82 (95% CI 4.87–6.81) and aIRR 1.25 (1.12–1.40). Postpartum psychosis was associated with autoimmune thyroid disease (n = 1) aIRR2.26 (1.61–2.90). Conclusions Women with pregnancy complications subsequently had a higher risk of being diagnosed with autoimmune conditions. Whether this is due to pre-existing undiagnosed health conditions or being causally linked to pregnancy complications is not known.

Abstract Background Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. Methods All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. Discussion With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. Systematic review registration PROSPERO CRD42021272686.

Abstract Background There is a high prevalence of autoimmune conditions in women specially in the reproductive years; thus, the association with adverse pregnancy outcomes has been widely studied. However, few autoimmune conditions/adverse outcomes have been studied more than others, and this umbrella review aims to consolidate existing knowledge in this area with the aim to provide new knowledge and also identify gaps in this research area. Methods Medline, Embase, and Cochrane databases were searched from inception to December 2023. Screening, data extraction, and quality appraisal (AMSTAR 2) were done by two independent reviewers. Data were synthesised narratively and quantitatively. Relative risks (RR)/odds ratio (OR) with 95% confidence intervals were reported. Results Thirty-two reviews were included consisting of 709 primary studies. The review reported the association between 12 autoimmune conditions and 16 adverse pregnancy outcomes. Higher risk of miscarriage is reported in women with Sjögren’s syndrome RR 8.85 (95% CI 3.10–25.26) and systemic lupus erythematosus (SLE) OR 4.90 (3.10–7.69). Pre-eclampsia was reported higher in women with type 1 diabetes mellitus (T1DM) OR 4.19 (3.08–5.71) and SLE OR 3.20 (2.54–4.20). Women reported higher risk of diabetes during pregnancy with inflammatory bowel disease (IBD) OR 2.96 (1.47–5.98). There was an increased risk of intrauterine growth restriction in women with systemic sclerosis OR 3.20 (2.21–4.53) and coeliac disease OR 1.71 (1.36–2.14). Preterm birth was associated with T1DM OR 4.36 (3.72–5.12) and SLE OR 2.79 (2.07–3.77). Low birth weight babies were reported in women with women with SLE or systemic sclerosis OR 5.95 (4.54–7.80) and OR 3.80 (2.16–6.56), respectively. There was a higher risk of stillbirth in women with T1DM OR 3.97 (3.44–4.58), IBD OR 1.57 (1.03–2.38), and coeliac disease OR 1.57 (1.17–2.10). T1DM in women was associated with 32% lower odds of small for gestational age baby OR 0.68 (0.56–0.83). Conclusions Pregnant women with autoimmune conditions are at a greater risk of developing adverse pregnancy outcomes. Further research is required to develop better preconception to postnatal care for women with autoimmune conditions.

Abstract Background Despite many systematic reviews and meta-analyses examining the associations of pregnancy complications with risk of type 2 diabetes mellitus (T2DM) and hypertension, previous umbrella reviews have only examined a single pregnancy complication. Here we have synthesised evidence from systematic reviews and meta-analyses on the associations of a wide range of pregnancy-related complications with risk of developing T2DM and hypertension. Methods Medline, Embase and Cochrane Database of Systematic Reviews were searched from inception until 26 September 2022 for systematic reviews and meta-analysis examining the association between pregnancy complications and risk of T2DM and hypertension. Screening of articles, data extraction and quality appraisal (AMSTAR2) were conducted independently by two reviewers using Covidence software. Data were extracted for studies that examined the risk of T2DM and hypertension in pregnant women with the pregnancy complication compared to pregnant women without the pregnancy complication. Summary estimates of each review were presented using tables, forest plots and narrative synthesis and reported following Preferred Reporting Items for Overviews of Reviews (PRIOR) guidelines. Results Ten systematic reviews were included. Two pregnancy complications were identified. Gestational diabetes mellitus (GDM): One review showed GDM was associated with a 10-fold higher risk of T2DM at least 1 year after pregnancy (relative risk (RR) 9.51 (95% confidence interval (CI) 7.14 to 12.67) and although the association differed by ethnicity (white: RR 16.28 (95% CI 15.01 to 17.66), non-white: RR 10.38 (95% CI 4.61 to 23.39), mixed: RR 8.31 (95% CI 5.44 to 12.69)), the between subgroups difference were not statistically significant at 5% significance level. Another review showed GDM was associated with higher mean blood pressure at least 3 months postpartum (mean difference in systolic blood pressure: 2.57 (95% CI 1.74 to 3.40) mmHg and mean difference in diastolic blood pressure: 1.89 (95% CI 1.32 to 2.46) mmHg). Hypertensive disorders of pregnancy (HDP): Three reviews showed women with a history of HDP were 3 to 6 times more likely to develop hypertension at least 6 weeks after pregnancy compared to women without HDP (meta-analysis with largest number of studies: odds ratio (OR) 4.33 (3.51 to 5.33)) and one review reported a higher rate of T2DM after HDP (hazard ratio (HR) 2.24 (1.95 to 2.58)) at least a year after pregnancy. One of the three reviews and five other reviews reported women with a history of preeclampsia were 3 to 7 times more likely to develop hypertension at least 6 weeks postpartum (meta-analysis with the largest number of studies: OR 3.90 (3.16 to 4.82) with one of these reviews reporting the association was greatest in women from Asia (Asia: OR 7.54 (95% CI 2.49 to 22.81), Europe: OR 2.19 (95% CI 0.30 to 16.02), North and South America: OR 3.32 (95% CI 1.26 to 8.74)). Conclusions GDM and HDP are associated with a greater risk of developing T2DM and hypertension. Common confounders adjusted for across the included studies in the reviews were maternal age, body mass index (BMI), socioeconomic status, smoking status, pre-pregnancy and current BMI, parity, family history of T2DM or cardiovascular disease, ethnicity, and time of delivery. Further research is needed to evaluate the value of embedding these pregnancy complications as part of assessment for future risk of T2DM and chronic hypertension.

Abstract Background Maternal multiple long-term conditions are associated with adverse outcomes for mother and child. We conducted a qualitative study to inform a core outcome set for studies of pregnant women with multiple long-term conditions. Methods Women with two or more pre-existing long-term physical or mental health conditions, who had been pregnant in the last five years or planning a pregnancy, their partners and health care professionals were eligible. Recruitment was through social media, patients and health care professionals’ organisations and personal contacts. Participants who contacted the study team were purposively sampled for maximum variation. Three virtual focus groups were conducted from December 2021 to March 2022 in the United Kingdom: (i) health care professionals (n = 8), (ii) women with multiple long-term conditions (n = 6), and (iii) women with multiple long-term conditions (n = 6) and partners (n = 2). There was representation from women with 20 different physical health conditions and four mental health conditions; health care professionals from obstetrics, obstetric/maternal medicine, midwifery, neonatology, perinatal psychiatry, and general practice. Participants were asked what outcomes should be reported in all studies of pregnant women with multiple long-term conditions. Inductive thematic analysis was conducted. Outcomes identified in the focus groups were mapped to those identified in a systematic literature search in the core outcome set development. Results The focus groups identified 63 outcomes, including maternal (n = 43), children’s (n = 16) and health care utilisation (n = 4) outcomes. Twenty-eight outcomes were new when mapped to the systematic literature search. Outcomes considered important were generally similar across stakeholder groups. Women emphasised outcomes related to care processes, such as information sharing when transitioning between health care teams and stages of pregnancy (continuity of care). Both women and partners wanted to be involved in care decisions and to feel informed of the risks to the pregnancy and baby. Health care professionals additionally prioritised non-clinical outcomes, including quality of life and financial implications for the women; and longer-term outcomes, such as children’s developmental outcomes. Conclusions The findings will inform the design of a core outcome set. Participants’ experiences provided useful insights of how maternity care for pregnant women with multiple long-term conditions can be improved.

Abstract Background Heterogeneity in reported outcomes can limit the synthesis of research evidence. A core outcome set informs what outcomes are important and should be measured as a minimum in all future studies. We report the development of a core outcome set applicable to observational and interventional studies of pregnant women with multimorbidity. Methods We developed the core outcome set in four stages: (i) a systematic literature search, (ii) three focus groups with UK stakeholders, (iii) two rounds of Delphi surveys with international stakeholders and (iv) two international virtual consensus meetings. Stakeholders included women with multimorbidity and experience of pregnancy in the last 5 years, or are planning a pregnancy, their partners, health or social care professionals and researchers. Study adverts were shared through stakeholder charities and organisations. Results Twenty-six studies were included in the systematic literature search (2017 to 2021) reporting 185 outcomes. Thematic analysis of the focus groups added a further 28 outcomes. Two hundred and nine stakeholders completed the first Delphi survey. One hundred and sixteen stakeholders completed the second Delphi survey where 45 outcomes reached Consensus In (≥70% of all participants rating an outcome as Critically Important). Thirteen stakeholders reviewed 15 Borderline outcomes in the first consensus meeting and included seven additional outcomes. Seventeen stakeholders reviewed these 52 outcomes in a second consensus meeting, the threshold was ≥80% of all participants voting for inclusion. The final core outcome set included 11 outcomes. The five maternal outcomes were as follows: maternal death, severe maternal morbidity, change in existing long-term conditions (physical and mental), quality and experience of care and development of new mental health conditions. The six child outcomes were as follows: survival of baby, gestational age at birth, neurodevelopmental conditions/impairment, quality of life, birth weight and separation of baby from mother for health care needs. Conclusions Multimorbidity in pregnancy is a new and complex clinical research area. Following a rigorous process, this complexity was meaningfully reduced to a core outcome set that balances the views of a diverse stakeholder group.

Abstract Background Screening programmes aim to identify individuals at higher risk of developing a disease or condition. While globally, there is agreement that people who attend screening should be fully informed, there is no consensus about how this should be achieved. We conducted a mixed methods study across eight different countries to understand how countries address informed choice across two screening programmes: breast cancer and fetal trisomy anomaly screening. Methods Fourteen senior level employees from organisations who produce and deliver decision aids to assist informed choice were interviewed, and their decision aids (n = 15) were evaluated using documentary analysis. Results We discovered that attempts to achieve informed choice via decision aids generate two key tensions (i) between improving informed choice and increasing uptake and (ii) between improving informed choice and comprehensibility of the information presented. Comprehensibility is fundamentally at tension with an aim of being fully informed. These tensions emerged in both the interviews and documentary analysis. Conclusion We conclude that organisations need to decide whether their overarching aim is ensuring high levels of uptake or maximising informed choice to participate in screening programmes. Consideration must then be given to all levels of development and distribution of information produced to reflect each organisation’s aim. The comprehensibility of the DA must also be considered, as this may be reduced when informed choice is prioritised.

Introduction Considering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk–benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing. In this study, we aim to detect adverse and protective effect signals of exposure to individual and pairwise combinations of medications during pregnancy.Methods and analysis Using a range of real-world data sources from the UK, we aim to conduct a pharmacovigilance study to assess the safety of medications prescribed during the preconception period (3 months prior to conception) and first trimester of pregnancy. Women aged between 15 and 49 years with a record of pregnancy within the Clinical Practice Research Datalink (CPRD) Pregnancy Register, the Welsh Secure Anonymised Information Linkage (SAIL), the Scottish Morbidity Record (SMR) data sets and the Northern Ireland Maternity System (NIMATS) will be included. A series of case control studies will be conducted to estimate measures of disproportionality, detecting signals of association between a range of pregnancy outcomes and exposure to individual and combinations of medications. A multidisciplinary expert team will be invited to a signal detection workshop. By employing a structured framework, signals will be transparently assessed by each member of the team using a questionnaire appraising the signals on aspects of temporality, selection, time and measurement-related biases and confounding by underlying disease or comedications. Through group discussion, the expert team will reach consensus on each of the medication exposure–outcome signal, thereby excluding spurious signals, leaving signals suggestive of causal associations for further evaluation.Ethics and dissemination Ethical approval has been obtained from the Independent Scientific Advisory Committee, SAIL Information Governance Review Panel, University of St. Andrews Teaching and Research Ethics Committee and Office for Research Ethics Committees Northern Ireland (ORECNI) for access and use of CPRD, SAIL, SMR and NIMATS data, respectively.

To identify the malignancy in human breast, hand-held optical probes are simulated using the Monte Carlo method. These devices were used to scan different tissue equivalent numerical breast phantoms to detect the embedded cancerous tissues in them. The phantoms were simulated with glandular tissues embedded with ductal carcinoma of size 5 mm and 2 mm diameter at various depths. Two optical probes namely dual side detector (DSD) probe and a single side detector (SSD) probe are designed through which one million light photons of wavelengths 600 nm and 800 nm respectively were passed into the numerical phantoms. The photons that were backscattered from the phantoms were received by the detectors in both probes. They were measured as signals and both probes were able to detect the presence of the embedded cancerous tissues at different depths. The results indicate that the probes with a light source at 800 nm could detect deep-seated inhomogeneities. The absolute value of Peak Intensity (|PI|) and Full Width at Half Maximum (FWHM) would be indicative of their location and approximate size of the embedded tissues. The |PI| decreases with the size and depth of the embedded tissue, and the FWHM increases with depth. The results show that the designed probes are capable of detecting small variations in tissues.

Objectives The aim of this systematic overview of reviews was to synthesise available evidence on inequalities in infectious disease based on three dimensions of inequalities; inclusion health groups, protected characteristics and socioeconomic inequalities.Methods We searched MEDLINE, Embase, Web of Science and OpenGrey databases in November 2021. We included reviews published from the year 2000 which examined inequalities in the incidence, prevalence or consequences of infectious diseases based on the dimensions of interest. Our search focused on tuberculosis, HIV, sexually transmitted infections, hepatitis C, vaccination and antimicrobial resistance. However, we also included eligible reviews of any other infectious diseases. We appraised the quality of reviews using the Assessment of Multiple Systematic Reviews V.2 (AMSTAR2) checklist. We conducted a narrative data synthesis.Results We included 108 reviews in our synthesis covering all the dimensions of inequalities for most of the infectious disease topics of interest, however the quality and volume of review evidence and consistency of their findings varied. The existing literature reviews provide strong evidence that people in inclusion health groups and lower socioeconomic status are consistently at higher risk of infectious diseases, antimicrobial resistance and incomplete/delayed vaccination. In the protected characteristics dimension, ethnicity, and sexual orientation are important factors contributing to inequalities across the various infectious disease topics included in this overview of reviews.Conclusion We identified many reviews that provide evidence of various types of health inequalities in different infectious diseases, vaccination, and antimicrobial resistance. We also highlight areas where reviews may be lacking. The commonalities in the associations and their directions suggest it might be worth targeting interventions for some high risk-groups that may have benefits across multiple infectious disease outcomes rather than operating purely in infectious disease siloes.

Introduction One in five pregnant women has multiple pre-existing long-term conditions in the UK. Studies have shown that maternal multiple long-term conditions are associated with adverse outcomes. This observational study aims to compare maternal and child outcomes for pregnant women with multiple long-term conditions to those without multiple long-term conditions (0 or 1 long-term conditions).Methods and analysis Pregnant women aged 15–49 years old with a conception date between 2000 and 2019 in the UK will be included with follow-up till 2019. The data source will be routine health records from all four UK nations (Clinical Practice Research Datalink (England), Secure Anonymised Information Linkage (Wales), Scotland routine health records and Northern Ireland Maternity System) and the Born in Bradford birth cohort. The exposure of two or more pre-existing, long-term physical or mental health conditions will be defined from a list of health conditions predetermined by women and clinicians. The association of maternal multiple long-term conditions with (a) antenatal, (b) peripartum, (c) postnatal and long-term and (d) mental health outcomes, for both women and their children will be examined. Outcomes of interest will be guided by a core outcome set. Comparisons will be made between pregnant women with and without multiple long-term conditions using modified Poisson and Cox regression. Generalised estimating equation will account for the clustering effect of women who had more than one pregnancy episode. Where appropriate, multiple imputation with chained equation will be used for missing data. Federated analysis will be conducted for each dataset and results will be pooled using random-effects meta-analyses.Ethics and dissemination Approval has been obtained from the respective data sources in each UK nation. Study findings will be submitted for publications in peer-reviewed journals and presented at key conferences.

Introduction With good medical care, most pregnancy complications like pre-eclampsia, gestational diabetes, etc resolve after childbirth. However, pregnancy complications are known to be associated with an increased risk of new long-term health conditions for women later in life, such as cardiovascular disease. These umbrella reviews aim to summarise systematic reviews evaluating the association between pregnancy complications and five groups of long-term health conditions: autoimmune conditions, cancers, functional disorders, mental health conditions and metabolic health conditions (diabetes and hypertension).Methods and analysis We will conduct searches in Medline, Embase and the Cochrane database of systematic reviews without any language restrictions. We will include systematic reviews with or without meta-analyses that studied the association between pregnancy complications and the future risk of the five groups of long-term health conditions in women. Pregnancy complications were identified from existing core outcome sets for pregnancy and after consultation with experts. Two reviewers will independently screen the articles. Data will be synthesised with both narrative and quantitative methods. Where a meta-analysis has been carried out, we will report the combined effect size from individual studies. For binary data, pooled ORs with 95% CIs will be presented. For continuous data, we will use the mean difference with 95% CIs. The findings will be presented in forest plots to assess heterogeneity. The methodological quality of the studies will be evaluated with the AMSTAR 2 tool or the Cochrane risk of bias tool. The corrected covered area method will be used to assess the impact of overlap in reviews. The findings will be used to inform the design of prediction models, which will predict the risk of women developing these five group of health conditions following a pregnancy complication.Ethics and dissemination No ethical approvals required. Findings will be disseminated through publications in peer-reviewed journals and conference presentations.

Background: Histopathological diagnosis of lesions arising from the intake of tobacco is based on subjective evaluation of morphological alterations within the lesional tissue. Oral exfoliative cytology is a non-invasive diagnostic technique for early detection of oral premalignant and malignant lesions. Morphometric techniques have been advocated as objective and reproducible methods of detecting changes before they are visible by routine microscopy and can facilitate differentiation of normal and abnormal epithelium. This study was conducted to assess the morphometric parameters (cell diameter, nuclear diameter and nuclear cytoplasmic ratio [N:C ratio]) in tobacco smokers and chewers and to evaluate the variations, if any. Materials and Methods: The study was conducted on cytological smears obtained from oral lesions of patients with habit of tobacco smoking (Group B) and tobacco chewing (Group C). Group A comprised of subjects free from oral lesions and not using tobacco in any form. Patients with both the habits were excluded. The smears were stained using Papanicoloaou staining method. For morphometric analysis, Microimage 3.0 image analysis software was employed. The statistical test employed was an analysis of variance and P < 0.05 was considered as significant. Results: The results of this study showed that the cellular diameter was progressively reduced and nuclear diameter progressively increased from Group A to Group B to Group C. The N:C ratio also showed a progressive increase from Group A to Group C. Conclusion: The results confirmed that tobacco chewing and smoking influenced the cytomorphology of normal appearing buccal mucosa and the degree of these changes were found to be greater in chewers as compared to smokers.

In this report, the role of oxygen plasma on oxidation of vanadium (V) metal and the volatilization of its oxides has been studied as a function of source (V metal strip) temperature (Tss) and oxygen partial pressure (PO2). The presence of O2-plasma not only enhances the oxidation rate but also ficilitates in transport of oxide molecules from metal to substrate, as confirmed by the simultanous deposition of oxide film onto substrate. Both the oxidized metal strips and oxide films deposited on substrates are characterized separately. The structural and vibrational results evidence the presence of two different oxide phases (i.e. orthorhombic V2O5 and monocilinic V O2) in oxide layers formed on V metal strips, whereas the oxide films deposited on substrates exhibit only orthorhombic phase (i.e. V2O5). The decrease in peak intensities recorded from heated V metal strips on increasing Tss points out the increment in the rate of oxide volatilization, which also confirms by the oxide layer thickness measurements. The SEM results show the noticeable surface changes on V-strips as the function of Tss and PO2 and their optimum values are recorded to be 500 ˚ C and 7.5 × 10−2 Torr, respectively to deposit maximum thick oxide film on substrate. The formation of microcracks on oxidized V-strips, those responsible to countinue oxidation is also confirmed by SEM results. The compositional study of oxide layers formed on V-strips, corroborates their pureness and further assures about the existence of mixed oxide phases. The effect of oxygen partial pressure on oxidation of V-metal has also been discussed in the present report. All the results are well in agreement to each other.