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Objective: In South Asia, studies show secular trends toward slightly later women's marriage and first reproduction. However, data on related biological and social events, such as menarche and age of coresidence with husband, are often missing from these analyses. We assessed generational trends in key life events marking the transition to womanhood in rural lowland Nepal., Methods: We used data on 110 co-resident mother-in-law (MIL) and daughter-in-law (DIL) dyads. We used paired t-tests and chi-squared tests to evaluate generational trends in women's education, and mean age at menarche, marriage, cohabitation with husband, and first reproduction of MIL and DIL dyads. We examined norms held by MILs and DILs on a daughter's life opportunities., Results: On average, MIL was 29 years older than DIL (60 years vs. 31 years). Both groups experienced menarche at average age 13.8 years. MIL was married at average 12.4 years, before menarche, and cohabitated with husbands at average 14.8 years. DIL was simultaneously married and cohabitated with husbands after menarche, at average 15 years. DIL was marginally more educated than MIL but had their first child on average 0.8 years earlier (95% CI -1.4, -0.1). MIL and DIL held similar norms on daughters' education and marriage., Conclusion: While social norms remain similar, the meaning of "early marriage" and use of menarche in marriage decisions has changed in rural lowland Nepal. Compared to DIL, MIL who was married earlier transitioned to womanhood more gradually. However, DIL was still married young, and had an accelerated trajectory to childbearing., (© 2024 The Authors. American Journal of Human Biology published by Wiley Periodicals LLC.)

Objective: There is currently no consensus about managing upper airway obstruction (UAO) in infants with Robin sequence (RS), in terms of treatment efficacy or clinical outcomes. This study describes UAO management in UK/Ireland, and explores relationships between patient characteristics, UAO management, and clinical outcomes in the first 2 years of life., Methods: Active surveillance of RS throughout UK/Ireland via the British Paediatric Surveillance Unit and nationally commissioned cleft services. Clinical data were collected at initial notification and 12-month follow-up., Results: 173 infants with RS were identified, of which 47% had additional congenital anomalies or an underlying syndrome (non-isolated RS). Two-thirds (n = 119) required an airway intervention other than prone positioning: non-surgical in 84% and surgical (tracheostomy) in 16%. Nasopharyngeal airway (NPA) was the most common intervention, used in 83% (n = 99) for median 90 days (IQR 136). Surgical UAO management was associated with prolonged hospital admission, higher prevalence of neurodevelopmental delay (NDD), lower weight-for-age z-scores, and delayed oral feeding. These findings were not attributable to a higher prevalence of non-isolated RS in this group. Although more commonly associated with non-isolated RS, growth faltering was also identified in 48%, and NDD in 18%, of cases of isolated RS., Conclusions: In UK/Ireland, most infants with RS are managed with NPA, and tracheostomy is reserved for refractory severe UAO. Clinical outcomes and duration of use indicate that NPA is a safe and feasible first-line approach to UAO. Longitudinal assessment of neurodevelopment and growth is imperative, including in children with isolated RS. Current variations in practice reinforce the need for evidence-based treatment guidelines., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Reference regions are important in laboratory medicine to interpret the test results of patients, and usually given by tolerance regions. Tolerance regions of p   ( ≥ 2 ) $$ p\;\left(\ge 2\right) $$ dimensions are highly desirable when the test results contains p $$ p $$ outcome measures. Nonparametric hyperrectangular tolerance regions are attractive in real problems due to their robustness with respect to the underlying distribution of the measurements and ease of intepretation, and methods to construct them have been recently provided by Young and Mathew [Stat Methods Med Res. 2020;29:3569-3585]. However, their validity is supported by a simulation study only. In this paper, nonparametric hyperrectangular tolerance regions are constructed by using Tukey's [Ann Math Stat. 1947;18:529-539; Ann Math Stat. 1948;19:30-39] elegant results of equivalence blocks. The validity of these new tolerance regions is proven mathematically in [Ann Math Stat. 1947;18:529-539; Ann Math Stat. 1948;19:30-39] under the only assumption that the underlying distribution of the measurements is continuous. The methodology is applied to analyze the kidney function problem considered in Young and Mathew [Stat Methods Med Res. 2020;29:3569-3585]., (© 2024 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Introduction: In the context of adverse in utero environments, the fetal brain might be preserved at the expense of other tissues. This trade-off, brain sparing, has not been studied in the context of maternal infection. We investigated cases of maternal syphilis in the early 20th century and influenza during the 1918-1920 pandemic, in the Swiss city of Lausanne, a relatively high-income setting. We tested the brain sparing hypothesis, that head circumference is protected at the expense of birth weight., Methods: A total of 8530 individual birth records from 1911 to 1922 from the University Maternity Hospital of Lausanne were used. We fitted generalized linear and additive linear models to explain how neonatal size varies under disease exposure., Results: Influenza reduced head circumference and birth weight among livebirths similarly, by -0.11 and -0.14 standard deviation (SD) units respectively. Conversely, for syphilis-exposed infants, head circumference was affected more than birth weight (-0.61 SD vs. -0.46 SD). Stillborn infants exposed to syphilis experienced a much greater reduction in head circumference (-1.92 SD) than liveborn infants. After adjustment for gestational age, these findings persisted in the case of influenza, but the effects of syphilis were reduced. Furthermore, half of syphilis-exposed infants were born before term, suggesting that lower infant size was partly mediated by shorter gestation. Nevertheless, head circumference among stillbirths exposed to syphilis was still substantially reduced, even after adjustment for gestational age (-1.26 SD)., Conclusion: Our findings do not support the brain sparing hypothesis. Moreover, the substantial reduction in head circumference among syphilis-exposed fetuses might help explain why a quarter of them were stillborn., (© 2024 The Author(s). American Journal of Human Biology published by Wiley Periodicals LLC.)

Background: The World Health Organization Surgical Safety Checklist (SSC), now used by healthcare providers worldwide, has proved to be useful in the improvement of patients' health through the reduction of mortality and morbidity after surgery. In the Emilia-Romagna region in Italy the SSC is accompanied by a document that registers any non-conformity (NC) identified during SSC completion. This study aimed to investigate the association between surgical complications and checklist compliance, in terms of incompleteness and presence of NCs, using data from the Modena Local Health Unit (LHU)., Methods: We used data from surgeries performed in the Modena LHU between 2018 and 2022, with their SSC and related NC document. We estimated relative risks (RRs) of complications fitting three modified Poisson regression models. Model 1 included checklist incompleteness and NC presence, Model 2 adjusted Model 1 for patients' sex and age group, and Model 3 adjusted Model 2 for the other potential confounders. We also performed a sensitivity analysis estimating the same three models including death outcomes as complications., Results: We found an increased risk of complications for both checklist incompleteness (unadjusted RR [uRR]= 2.04; 95% confidence interval [CI]: 1.17 to 3.54) and presence of NCs (uRR = 2.35; 95% CI: 1.71 to 3.22). Results were consistent after adjustment and in the sensitivity analysis., Conclusions: Improving checklist compliance can reduce the risk of surgical complications. In particular, NCs are a risk factor that must be further investigated to better understand their relationship with complications. We believe that NCs data recording is helpful for both researchers in the scope of surgical complications, and healthcare professionals in the operating room., (© 2024 The Author(s). Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Background: A third of children born in England have at least one parent born outside the United Kingdom (UK), yet family migration history is infrequently studied as a social determinant of child health. We describe rates of hospital admissions in children aged up to 5 years by parental migration and socioeconomic group., Methods: Birth registrations linked to Hospital Episode Statistics were used to derive a cohort of 4,174,596 children born in state-funded hospitals in England between 2008 and 2014, with follow-up until age 5 years. We looked at eight maternal regions of birth, maternal country of birth for the 6 most populous groups and parental migration status for the mother and second parent (UK-born/non-UK-born). We used Index of Multiple Deprivation (IMD) quintiles to indicate socioeconomic deprivation. We fitted negative binomial/Poisson regression models to model associations between parental migration groups and the risk of hospital admissions, including interactions with IMD group., Results: Overall, children whose parents were both born abroad had lower emergency admission rates than children with parents both born in the UK. Children of UK-born (73.6% of the cohort) mothers had the highest rates of emergency admissions (171.6 per 1000 child-years, 95% confidence interval (CI) 171.4-171.9), followed by South Asia-born mothers (155.9 per 1000, 95% CI 155.1-156.7). The high rates estimated in the South Asia group were driven by children of women born in Pakistan (186.8 per 1000, 95% CI 185.4-188.2). A socioeconomic gradient in emergency admissions was present across all maternal regions of birth groups, but most pronounced among children of UK-born mothers (incidence rate ratio 1.43, 95% CI 1.42-1.44, high vs. low IMD group). Patterns of planned admissions followed a similar socioeconomic gradient and were highest among children with mothers born in Middle East and North Africa, and South Asia., Conclusions: Overall, we found the highest emergency admission rates among children of UK-born parents from the most deprived backgrounds. However, patterns differed when decomposing maternal place of birth and admission reason, highlighting the importance of a nuanced approach to research on migration and health., (© 2024. The Author(s).)

Background: Small for gestational age (SGA) is a key contributor to premature deaths and long-term complications in life. Improved characterization of maternal risk factors associated with this adverse outcome is needed to inform the development of interventions, track progress, and reduce the disease burden. This study aimed to identify socioeconomic, demographic, and clinical factors associated with SGA in Mexico.Methods: We analyzed administrative data from 1,841,477 singletons collected by the National Information Subsystem of Livebirths during 2017. Small-for-gestational-age was defined as being 12 years (aOR 0.63; 95% CI:0.6,0.66) compared with those without education. SGA was particularly likely to occur among primiparous (aOR 1.42; 95% CI: 1.39, 1.43), mothers living in very high deprivation localities (aOR 1.39; 95% CI: 1.36, 1.43), young (aOR 1.04; 95% CI: 1.02, 1.06), advanced age (aOR 1.14; 95% CI 1.09, 1.19), and mothers living in areas above 2,000 m (aOR 1.69; 95% CI: 1.65, 1.73). Antenatal care was associated with a reduced risk of SGA by 30% (aOR 0.7; 95% CI:0.67,0.73), 23% (OR 0.77; 95% CI:0.74,0.8), and 21% (OR 0.79; 95% CI:0.75,0.83), compared with those mothers who never received antenatal care, when women visited the clinic at the first, second and third trimester, respectively.Conclusion: Almost 7% of live births were found to be SGA. Parity, maternal age, education, place of residence, and social deprivation were significantly associated with this outcome. Antenatal care was protective. These findings imply that interventions focusing on early and adequate contact with health care facilities, reproductive health counseling, and maternal education should reduce SGA in Mexico.

Background: Women's underage marriage (<18 years) is associated with adverse maternal and child health outcomes. Poverty in the natal household has been widely considered to be a key risk factor for underage marriage, but the evidence base is unreliable. When investigating this issue, most studies use marital wealth inappropriately, as a proxy for wealth in the natal household. In contrast, we investigated whether the timing of women's marriage was associated with the wealth of the households they marry into, and how this may vary by women's education level. This approach allows us to explore a different set of research questions which help to understand the economic value placed on the timing of women's marriage., Methods: We used data on 3,102 women aged 12-34 years, surveyed within 1 year of marriage, from the cluster-randomized Low Birth Weight South Asia Trial in lowland rural Nepal. Linear mixed-effects regression models investigated independent associations of women's marriage age and education level with marital household wealth, and their interactive effects. Models adjusted for marital household traits. We analysed the full sample, and then only the uneducated women, who comprised a substantial proportion in our sample., Results: In the full sample, we found that each later year of women's marriage was associated with 1.5% lower asset score for those with primary education, and with 0.3% and 1.3% higher asset score for those with lower secondary or secondary/higher education, respectively. For uneducated women, relative to marrying ≤14 years, marrying at 15, 16, 17 and ≥18 years was associated with 1.5%, 4.4%, 2.4% and 6.2% greater marital asset score respectively., Conclusion: On average, marrying ≥18 years was associated with greater marital assets for secondary-educated women. There were only very modest benefits in terms of marital household wealth for delaying marriage beyond 16 years for uneducated women or those with low education. These findings elucidate potential trade-offs faced by families, including decisions over how much education, if any, to provide to daughters. They may help to understand the economic rationale underpinning the timing of marriage, and why early marriage remains common despite efforts to delay it., Competing Interests: The authors declare that they have no competing interests., (© 2024 Marphatia et al.)

Background: Findings from studies assessing Long Covid in children and young people (CYP) need to be assessed in light of their methodological limitations. For example, if non-response and/or attrition over time systematically differ by sub-groups of CYP, findings could be biased and any generalisation limited. The present study aimed to (i) construct survey weights for the Children and young people with Long Covid (CLoCk) study, and (ii) apply them to published CLoCk findings showing the prevalence of shortness of breath and tiredness increased over time from baseline to 12-months post-baseline in both SARS-CoV-2 Positive and Negative CYP., Methods: Logistic regression models were fitted to compute the probability of (i) Responding given envisioned to take part, (ii) Responding timely given responded, and (iii) (Re)infection given timely response. Response, timely response and (re)infection weights were generated as the reciprocal of the corresponding probability, with an overall 'envisioned population' survey weight derived as the product of these weights. Survey weights were trimmed, and an interactive tool developed to re-calibrate target population survey weights to the general population using data from the 2021 UK Census., Results: Flexible survey weights for the CLoCk study were successfully developed. In the illustrative example, re-weighted results (when accounting for selection in response, attrition, and (re)infection) were consistent with published findings., Conclusions: Flexible survey weights to address potential bias and selection issues were created for and used in the CLoCk study. Previously reported prospective findings from CLoCk are generalisable to the wider population of CYP in England. This study highlights the importance of considering selection into a sample and attrition over time when considering generalisability of findings., (© 2024. The Author(s).)

Introduction: Respiratory syncytial virus (RSV) causes a severe respiratory condition, bronchiolitis, in infants but not in adults. Bronchiolitis is characterised by neutrophilic infiltration in the airways, but whether neutrophils enhance recovery from infection or contribute to its pathology remains unknown., Methods: We used a novel in-vitro model to compare term umbilical cord blood (infant) (n=17 donors) and adult neutrophils (n=15 donors) during migration across RSV-infected differentiated human nasal airway epithelial cells (AECs) in a basolateral to apical direction., Results: Greater numbers of infant neutrophils (mean (95% CI)) (336 684 (242 352 to 431 015)) migrated across RSV-infected AECs to the apical compartment (equivalent to the airway lumen) compared with adult neutrophils (56 586 (24 954 to 88 218)) (p<0.0001). Having reached the apical compartment of infected AECs, much greater numbers of infant neutrophils (140 787 (103 117 to 178 456)) became apoptotic compared with adult (5853 (444 to 11 261)) (p=0.002). Infant neutrophils displayed much greater expression of CD11b, CD64, neutrophil elastase (NE) and myeloperoxidase (MPO) than adult neutrophils at baseline and at all points of migration. However, as adult neutrophils migrated, expression of CD11b, CD64, NE and MPO became greater than at baseline., Discussion: The high proportion of infant neutrophils migrating across RSV-infected AECs correlates with the neutrophilic infiltrate seen in infants with severe RSV bronchiolitis, with large numbers undergoing apoptosis, which may represent a protective mechanism during infection. Compared with adult neutrophils, infant neutrophils already have high expression of surface markers before contact with AECs or migration, with less capacity to increase further in response to RSV infection or migration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in infected people over 85 years of age remains high. Here we investigate differences in the cellular landscape and function of paediatric (<12 years), adult (30-50 years) and older adult (>70 years) ex vivo cultured nasal epithelial cells in response to infection with SARS-CoV-2. We show that cell tropism of SARS-CoV-2, and expression of ACE2 and TMPRSS2 in nasal epithelial cell subtypes, differ between age groups. While ciliated cells are viral replication centres across all age groups, a distinct goblet inflammatory subtype emerges in infected paediatric cultures and shows high expression of interferon-stimulated genes and incomplete viral replication. In contrast, older adult cultures infected with SARS-CoV-2 show a proportional increase in basaloid-like cells, which facilitate viral spread and are associated with altered epithelial repair pathways. We confirm age-specific induction of these cell types by integrating data from in vivo COVID-19 studies and validate that our in vitro model recapitulates early epithelial responses to SARS-CoV-2 infection., (© 2024. The Author(s).)

Background: Anti-human leukocyte antigen (HLA)-antibody production represents a major barrier to heart transplantation, limiting recipient compatibility with potential donors and increasing the risk of complications with poor waiting-list outcomes. Currently there is no consensus to when desensitization should take place, and through what mechanism, meaning that sensitized patients must wait for a compatible donor for many months, if not years. We aimed to determine if intraoperative immunoadsorption could provide a potential desensitization methodology., Methods: Anti-HLA antibody-containing whole blood was added to a Cardiopulmonary bypass (CPB) circuit set up to mimic a 20 kg patient undergoing heart transplantation. Plasma was separated and diverted to a standalone, secondary immunoadsorption system, with antibody-depleted plasma returned to the CPB circuit. Samples for anti-HLA antibody definition were taken at baseline, when combined with the CPB prime (on bypass), and then every 20 min for the duration of treatment (total 180 min)., Results: A reduction in individual allele median fluorescence intensity (MFI) to below clinically relevant levels (<1000 MFI), and in the majority of cases below the lower positive detection limit (<500 MFI), even in alleles with a baseline MFI >4000 was demonstrated. Reduction occurred in all cases within 120 min, demonstrating efficacy in a time period usual for heart transplantation. Flowcytometric crossmatching of suitable pseudo-donor lymphocytes demonstrated a change from T cell and B cell positive channel shifts to negative, demonstrating a reduction in binding capacity., Conclusions: Intraoperative immunoadsorption in an ex vivo setting demonstrates clinically relevant reductions in anti-HLA antibodies within the normal timeframe for heart transplantation. This method represents a potential desensitization technique that could enable sensitized children to accept a donor organ earlier, even in the presence of donor-specific anti-HLA antibodies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background/aims: Evaluation of telemedicine care models has highlighted its potential for exacerbating healthcare inequalities. This study seeks to identify and characterise factors associated with non-attendance across face-to-face and telemedicine outpatient appointments., Methods: A retrospective cohort study at a tertiary-level ophthalmic institution in the UK, between 1 January 2019 and 31 October 2021. Logistic regression modelled non-attendance against sociodemographic, clinical and operational exposure variables for all new patient registrations across five delivery modes: asynchronous, synchronous telephone, synchronous audiovisual and face to face prior to the pandemic and face to face during the pandemic., Results: A total of 85 924 patients (median age 55 years, 54.4% female) were newly registered. Non-attendance differed significantly by delivery mode: (9.0% face to face prepandemic, 10.5% face to face during the pandemic, 11.7% asynchronous and 7.8%, synchronous during pandemic). Male sex, greater levels of deprivation, a previously cancelled appointment and not self-reporting ethnicity were strongly associated with non-attendance across all delivery modes. Individuals identifying as black ethnicity had worse attendance in synchronous audiovisual clinics (adjusted OR 4.24, 95% CI 1.59 to 11.28) but not asynchronous. Those not self-reporting their ethnicity were from more deprived backgrounds, had worse broadband access and had significantly higher non-attendance across all modes (all p<0.001)., Conclusion: Persistent non-attendance among underserved populations attending telemedicine appointments highlights the challenge digital transformation faces for reducing healthcare inequalities. Implementation of new programmes should be accompanied by investigation into the differential health outcomes of vulnerable populations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Evidence on the socioeconomic burden associated with childhood visual impairment, severe visual impairment and blindness (VI/SVI/BL) is needed to inform economic evaluations of existing and emerging interventions aimed at protecting or improving vision. This study aimed to evaluate the quantity and quality of literature on resource use and/or costs associated with childhood VI/SVI/BL disorders., Methods: PubMed, Web of Science (Ovid), the National Health Service (NHS) Economic Evaluation Database and grey literature were searched in November 2020. The PubMed search was rerun in February 2022. Original articles reporting unique estimates of resource use or cost data on conditions resulting in bilateral VI/SVI/BL were eligible for data extraction. Quality assessment (QA) was undertaken using the Drummond checklist adapted for cost-of-illness (COI) studies., Results: We identified 31 eligible articles, 27 from the peer-reviewed literature and four from the grey literature. Two reported on resource use, and 29 reported on costs. Cerebral visual impairment and optic nerve disorders were not examined in any included studies, whereas retinopathy of prematurity was the most frequently examined condition. The quality of studies varied, with economic evaluations having higher mean QA scores (82%) compared to COI studies (77%). Deficiencies in reporting were seen, particularly in the clinical definitions of conditions in economic evaluations and a lack of discounting and sensitivity analyses in COI studies., Conclusions: There is sparse literature on resource use or costs associated with childhood visual impairment disorders. The first step in addressing this important evidence gap is to ensure core visual impairment outcomes are measured in future randomised control trials of interventions as well as cohort studies and are reported as a discrete health outcome., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Boys with haemophilia (BwH) have improved health outcomes. Measures of physical function in haemophilia are not challenging or sensitive enough to reflect physical limitations or guide rehabilitation. To identify meaningful tests, we aimed to: evaluate the performance of BwH on two physical performance measures: iSTEP and 10 m-ISWT; identify factors which predict performance and compare BwH to their unaffected peers., Methods: BwH completed both iSTEP and 10 m-ISWT. Disease severity, age, BMI, HJHS, lower limb muscle torque, time spent in moderate to vigorous physical activity, sedentary time, were included as factors to predict performance. Results were compared to unaffected peers., Results: 43 boys median age 10 (10 mild/moderate, 26 severe, 7 inhibitors) were recruited. BwH were less likely to complete the iSTEP and performed less well on the 10 m-ISWT than age matched peers. Ceiling effects were apparent for iSTEP, but not the 10 m-ISWT test. Age was the only significant predictor for performance in the iSTEP, with older boys being more likely to achieve a higher level or complete the test. Greater age, lower BMI, milder disease severity and more time spent in MVPA all predicted better performance on the 10 m-ISWT, with BMI and habitual physical activity a potential rehabilitation focus for underperforming individuals. HJHS and muscle strength did not predict performance on either test., Conclusion: Despite the space need to conduct the 10 m-ISWT, it appears to be a superior performance measure than the iSTEP in BwH and provides clinically meaningful information, which can be interpreted using age-specific normative reference equations., (© 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

SARS-CoV-2 initially infects cells in the nasopharynx and oral cavity. The immune system at these mucosal sites plays a crucial role in minimizing viral transmission and infection. To develop new strategies for preventing SARS-CoV-2 infection, this study aimed to identify proteins that protect against viral infection in saliva. We collected 551 saliva samples from 290 healthcare workers who had tested positive for COVID-19, before vaccination, between June and December 2020. The samples were categorized based on their ability to block or enhance infection using in vitro assays. Mass spectrometry and enzyme-linked immunosorbent assay experiments were used to identify and measure the abundance of proteins that specifically bind to SARS-CoV-2 antigens. Immunoglobulin (Ig)A specific to SARS-CoV-2 antigens was detectable in over 83% of the convalescent saliva samples. We found that concentrations of anti-receptor-binding domain IgA >500 pg/µg total protein in saliva correlate with reduced viral infectivity in vitro. However, there is a dissociation between the salivary IgA response to SARS-CoV-2, and systemic IgG titers in convalescent COVID-19 patients. Then, using an innovative technique known as spike-baited mass spectrometry, we identified novel spike-binding proteins in saliva, most notably vimentin, which correlated with increased viral infectivity in vitro and could serve as a therapeutic target against COVID-19., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Periodontitis, a ubiquitous severe gum disease affecting the teeth and surrounding alveolar bone, can heighten systemic inflammation. We investigated the association between very severe periodontitis and early biomarkers of age-related macular degeneration (AMD), in individuals with no eye disease., Design: Cross-sectional analysis of the prospective community-based cohort United Kingdom (UK) Biobank., Participants: Sixty-seven thousand three hundred eleven UK residents aged 40 to 70 years recruited between 2006 and 2010 underwent retinal imaging., Methods: Macular-centered OCT images acquired at the baseline visit were segmented for retinal sublayer thicknesses. Very severe periodontitis was ascertained through a touchscreen questionnaire. Linear mixed effects regression modeled the association between very severe periodontitis and retinal sublayer thicknesses, adjusting for age, sex, ethnicity, socioeconomic status, alcohol consumption, smoking status, diabetes mellitus, hypertension, refractive error, and previous cataract surgery., Main Outcome Measures: Photoreceptor layer (PRL) and retinal pigment epithelium-Bruch's membrane (RPE-BM) thicknesses., Results: Among 36 897 participants included in the analysis, 1571 (4.3%) reported very severe periodontitis. Affected individuals were older, lived in areas of greater socioeconomic deprivation, and were more likely to be hypertensive, diabetic, and current smokers (all P < 0.001). On average, those with very severe periodontitis were hyperopic (0.05 ± 2.27 diopters) while those unaffected were myopic (-0.29 ± 2.40 diopters, P < 0.001). Following adjusted analysis, very severe periodontitis was associated with thinner PRL (-0.55 μm, 95% confidence interval [CI], -0.97 to -0.12; P  = 0.022) but there was no difference in RPE-BM thickness (0.00 μm, 95% CI, -0.12 to 0.13; P  = 0.97). The association between PRL thickness and very severe periodontitis was modified by age ( P < 0.001). Stratifying individuals by age, thinner PRL was seen among those aged 60 to 69 years with disease (-1.19 μm, 95% CI, -1.85 to -0.53; P < 0.001) but not among those aged < 60 years., Conclusions: Among those with no known eye disease, very severe periodontitis is statistically associated with a thinner PRL, consistent with incipient AMD. Optimizing oral hygiene may hold additional relevance for people at risk of degenerative retinal disease., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 by the American Academy of Ophthalmology.)

Background: Catatonia is a neuropsychiatric syndrome associated with both psychiatric disorders and medical conditions. Understanding of the pathophysiology of catatonia remains limited, and the role of the environment is unclear. Although seasonal variations have been shown for many of the disorders underlying catatonia, the seasonality of this syndrome has not yet been adequately explored., Methods: Clinical records were screened to identify a cohort of patients suffering from catatonia and a control group of psychiatric inpatients, from 2007 to 2016 in South London. In a cohort study, the seasonality of presentation was explored fitting regression models with harmonic terms, while the effect of season of birth on subsequent development of catatonia was analyzed using regression models for count data. In a case-control study, the association between month of birth and catatonia was studied fitting logistic regression models., Results: In total, 955 patients suffering from catatonia and 23,409 controls were included. The number of catatonic episodes increased during winter, with a peak in February. Similarly, an increasing number of cases was observed during summer, with a second peak in August. However, no evidence for an association between month of birth and catatonia was found., Conclusions: The presentation of catatonia showed seasonal variation in accordance with patterns described for many of the disorders underlying catatonia, such as mood disorders and infections. We found no evidence for an association between season of birth and risk of developing catatonia. This may imply that recent triggers may underpin catatonia, rather than distal events., Competing Interests: Declaration of competing interest MSZ declares honoraria for a lecture from Eisai Co., Ltd. All other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Two-thirds of the 2.4 million newborn deaths that occurred in 2020 within the first 28 days of life might have been avoided by implementing existing low-cost evidence-based interventions for all sick and small newborns. An open-source digital quality improvement tool (Neotree) combining data capture with education and clinical decision support is a promising solution for this implementation gap., Objective: We present results from a cost analysis of a pilot implementation of Neotree in 3 hospitals in Malawi and Zimbabwe., Methods: We combined activity-based costing and expenditure approaches to estimate the development and implementation cost of a Neotree pilot in 1 hospital in Malawi, Kamuzu Central Hospital (KCH), and 2 hospitals in Zimbabwe, Sally Mugabe Central Hospital (SMCH) and Chinhoyi Provincial Hospital (CPH). We estimated the costs from a provider perspective over 12 months. Data were collected through expenditure reports, monthly staff time-use surveys, and project staff interviews. Sensitivity and scenario analyses were conducted to assess the impact of uncertainties on the results or estimate potential costs at scale. A pilot time-motion survey was conducted at KCH and a comparable hospital where Neotree was not implemented., Results: Total cost of pilot implementation of Neotree at KCH, SMCH, and CPH was US $37,748, US $52,331, and US $41,764, respectively. Average monthly cost per admitted child was US $15, US $15, and US $58, respectively. Staff costs were the main cost component (average 73% of total costs, ranging from 63% to 79%). The results from the sensitivity analysis showed that uncertainty around the number of admissions had a significant impact on the costs in all hospitals. In Malawi, replacing monthly web hosting with a server also had a significant impact on the costs. Under routine (nonresearch) conditions and at scale, total costs are estimated to fall substantially, up to 76%, reducing cost per admitted child to as low as US $5 in KCH, US $4 in SMCH, and US $14 in CPH. Median time to admit a baby was 27 (IQR 20-40) minutes using Neotree (n=250) compared to 26 (IQR 21-30) minutes using paper-based systems (n=34), and the median time to discharge a baby was 9 (IQR 7-13) minutes for Neotree (n=246) compared to 3 (IQR 2-4) minutes for paper-based systems (n=50)., Conclusions: Neotree is a time- and cost-efficient tool, comparable with the results from limited similar mHealth decision-support tools in low- and middle-income countries. Implementation costs of Neotree varied substantially between the hospitals, mainly due to hospital size. The implementation costs could be substantially reduced at scale due to economies of scale because of integration to the health systems and reductions in cost items such as staff and overhead. More studies assessing the impact and cost-effectiveness of large-scale mHealth decision-support tools are needed., (© Hassan Haghparast-Bidgoli, Tim Hull-Bailey, Deliwe Nkhoma, Tarisai Chiyaka, Emma Wilson, Felicity Fitzgerald, Gwendoline Chimhini, Nushrat Khan, Hannah Gannon, Rekha Batura, Mario Cortina-Borja, Leyla Larsson, Msandeni Chiume, Yali Sassoon, Simbarashe Chimhuya, Michelle Heys. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org).)

Background/aims: To investigate if impaired vision adversely impacts the intentions/ambitions of adolescents concerning their future education, careers and social outcomes., Methods: Population-based birth cohort study in the UK comprising 9273 participants from the Millennium Cohort Study who were followed up to age 17 years. Children were classified as having normal vision or unilateral or bilateral impaired vision caused by significant eye conditions based on detailed parental-structured questionnaire data on sight problems and treatment coded by clinicians. Ten domains covering education, career and social outcomes by age 30 were investigated., Results: Adjusted regression models showed few differences by vision status. Bilateral impaired vision was associated with increased odds of intending to remain in full-time education after statutory school age (adjusted OR (aOR) 2.00, 95% CI 1.08 to 3.68) and of home ownership at age 30 (aOR 1.83, 95% CI 1.01 to 3.32). Impaired vision was not associated with intending to attend university. A significantly higher proportion of parents of children with bilateral or unilateral impaired vision thought that their child would not get the exam grades required to go to university than parents of those with normal vision (29% or 26% vs 16%, p= 0.026)., Conclusion: Adolescents with impaired vision have broadly the same intentions/ambitions regarding future education, careers and social outcomes as their peers with normal vision. The known significant gaps in attainment in these domains among young adults with vision impairment are therefore likely to be due to barriers that they face in achieving their ambitions. Improved implementation of existing interventions is necessary to ensure equality of opportunities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Childhood vision impairment (VI) can adversely impact health and social outcomes and limit life chances. We investigated whether its adverse impacts into adult life changed during a period in which legislation, policy and services to address inequalities relating to disability were implemented., Methods: Cross-cohort study comprising 14 247 participants from the 1946, 1958 and 1970 British birth cohorts (BC). Participants dichotomized as VI at age 15/16 (distance visual acuity was 6/12 or worse in the better-seeing eye) or normally sighted. Associations of childhood VI with health, well-being, socioeconomic and social participation outcomes in mid-adult life were investigated using regression models adjusted for participants' early life socioeconomic markers and sex. Change in adjusted odds ratios of >10% in the same direction in successive cohorts, or a > 20% difference between 1970BC and one older cohort were considered meaningful., Results: Trends over time in impacts of childhood onset VI into mid-adult life were complex. This included worsening of odds of poorer physical health (odds ratio 1.47; 95% confidence interval 1.02-2.14), living in unsatisfactory (1.54; 1.03-2.29) or overcrowded (2.34; 1.26-4.06) households, being unemployed (2.19; 1.19-3.97) and not gaining additional educational qualifications during mid-adult life (1.61; 1.08-2.47). By contrast the odds of not participating in some social activities (e.g. seeing friends) improved over time. Associations with other outcomes were unchanged., Conclusions: Many adverse impacts of childhood VI do not appear ameliorated over time by legislation, policies and provision that would have been expected to reduce inequalities. Moreover, some were increased. Childhood VI continues to cast a life-long shadow., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

Robin sequence (RS), a congenital disorder of jaw maldevelopment and glossoptosis, poses a substantial healthcare burden and has long-term health implications if airway obstruction is suboptimally treated. This study describes the global birth prevalence of RS and investigates whether prevalence estimates differ by geographical location, ethnicity or study data source (registry versus non-registry data). The protocol was prospectively registered with PROSPERO.Databases were searched using keywords and subject terms for "Robin sequence", "epidemiology", "incidence" and "birth prevalence". Meta-analysis was performed fitting random effects models with arcsine transformation.From 34 eligible studies (n=2722 RS cases), pooled birth prevalence was 9.5 per 100 000 live births (95% CI 7.1-12.1) with statistical heterogeneity. One third of studies provided a case definition for RS and numerous definitions were used. A total of 22 countries were represented, predominantly from European populations (53% of studies). There was a trend towards higher birth prevalence in European populations and lower prevalence from registry-based studies. Only two studies reported ethnicity.This study indicates that RS occurs globally. To investigate geographical differences in prevalence, additional studies from non-European populations and reporting of ethnicity are needed. Heterogeneity of estimates may be due to variable diagnostic criteria and ascertainment methods. Recently published consensus diagnostic criteria may reduce heterogeneity among future studies., Competing Interests: Conflict of interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Bioelectrical impedance analysis (BIA) is a technique widely used for estimating body composition and health-related parameters. The technology is relatively simple, quick, and non-invasive, and is currently used globally in diverse settings, including private clinicians' offices, sports and health clubs, and hospitals, and across a spectrum of age, body weight, and disease states. BIA parameters can be used to estimate body composition (fat, fat-free mass, total-body water and its compartments). Moreover, raw measurements including resistance, reactance, phase angle, and impedance vector length can also be used to track health-related markers, including hydration and malnutrition, and disease-prognostic, athletic and general health status. Body composition shows profound variability in association with age, sex, race and ethnicity, geographic ancestry, lifestyle, and health status. To advance understanding of this variability, we propose to develop a large and diverse multi-country dataset of BIA raw measures and derived body components. The aim of this paper is to describe the 'BIA International Database' project and encourage researchers to join the consortium., Methods: The Exercise and Health Laboratory of the Faculty of Human Kinetics, University of Lisbon has agreed to host the database using an online portal. At present, the database contains 277,922 measures from individuals ranging from 11 months to 102 years, along with additional data on these participants., Conclusion: The BIA International Database represents a key resource for research on body composition., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: On average, boys grow faster than girls in early life but appear more susceptible to undernutrition. We investigated sex differences in early child growth, and whether maternal nutritional status and diet differed by offspring sex during and after pregnancy in an undernourished population., Methods: We analyzed longitudinal data from a cluster-randomized trial from plains Nepal, stratifying results by child or gestational age. Children's outcomes (0-20 months) were weight, length, and head circumference and their z-scores relative to WHO reference data in 2-monthly intervals (n range: 24837 to 25 946). Maternal outcomes were mid-upper arm circumference (MUAC), and body mass index (BMI) during pregnancy (12-40 weeks) (n = 5550 and n = 5519) and postpartum (n = 15 710 and n = 15 356), and diet in pregnancy. We fitted unadjusted and adjusted mixed-effects linear and logistic regression models comparing boys with girls., Results: Boys were larger than girls, however relative to their sex-specific reference they had lower length and head circumference z-scores from birth to 12 months, but higher weight-for-length z-scores from 0 to 6 months. Mothers of sons had higher MUAC and BMI around 36 weeks gestation but no other differences in pregnancy diets or pregnancy/postpartum maternal anthropometry were detected. Larger sex differences in children's size in the food supplementation study arm suggest that food restriction in pregnancy may limit fetal growth of boys more than girls., Conclusions: Generally, mothers' anthropometry and dietary intake do not differ according to offspring sex. As boys are consistently larger, we expect that poor maternal nutritional status may compromise their growth more than girls. Copyright © 2021 John Wiley & Sons, Ltd., (© 2021 The Authors. American Journal of Human Biology published by Wiley Periodicals LLC.)

Childhood visual impairment can have a significant impact on an individual's development. To improve clinical care and develop appropriate psychosocial interventions of these patients, it is necessary to understand the contributing and modifiable factors that both identify individuals in greater need and could be targeted in interventions. Here we investigate the broader individual, family, and environmental factors associated with vision-related quality of life (VQoL) of children and young people with visual impairment (CYP-VI). Data for this cross-sectional study were collected from September 2014 to May 2017 to develop and validate two vision-specific patient-reported outcome measures (PROMs) for CYP-VI. Patients were recruited from 22 hospitals in the United Kingdom and were aged 7-18 years with visual impairment as per WHO criteria. Participants self-completed the two PROMs, VQoL and Functional Vision Questionnaires. Clinical characteristics were extracted from medical records. Their carers provided information on family sociodemographic backgrounds. Associations between the VQoL scores and other factors were examined using Spearman's correlation, Kruskal-Wallis, Wilcoxon rank-sum tests, and quantile regression models. The sample consisted of 152 CYP-VI (67 females). Better VQoL was significantly associated with better functional vision overall (rSpearman = -0.52), parent-reported absence of additional chronic conditions (dCohen = 0.46), attending mainstream (versus other) school (dCohen = 0.44), higher socio-economic status (rSpearman = 0.17) and higher parental education level (rSpearman = 0.20). No other investigated factors were significantly associated with VQoL. The final quantile regression model included functional vision scores and the presence of additional health condition. Variation in self-reported VQoL in CYP-VI can be partly accounted for by factors relating to the clinical status of the affected child and, more importantly, by non-health-related factors. This needs to be considered in clinical practice when assessing vision-specific outcomes and providing support to CYP-VI, as well as in the development of future interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Šemrov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: Cadaveric studies have shown disease-related neurodegeneration and other morphological abnormalities in the retina of individuals with Parkinson disease (PD); however, it remains unclear whether this can be reliably detected with in vivo imaging. We investigated inner retinal anatomy, measured using optical coherence tomography (OCT), in prevalent PD and subsequently assessed the association of these markers with the development of PD using a prospective research cohort., Methods: This cross-sectional analysis used data from 2 studies. For the detection of retinal markers in prevalent PD, we used data from AlzEye, a retrospective cohort of 154,830 patients aged 40 years and older attending secondary care ophthalmic hospitals in London, United Kingdom, between 2008 and 2018. For the evaluation of retinal markers in incident PD, we used data from UK Biobank, a prospective population-based cohort where 67,311 volunteers aged 40-69 years were recruited between 2006 and 2010 and underwent retinal imaging. Macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL), and inner nuclear layer (INL) thicknesses were extracted from fovea-centered OCT. Linear mixed-effects models were fitted to examine the association between prevalent PD and retinal thicknesses. Hazard ratios for the association between time to PD diagnosis and retinal thicknesses were estimated using frailty models., Results: Within the AlzEye cohort, there were 700 individuals with prevalent PD and 105,770 controls (mean age 65.5 ± 13.5 years, 51.7% female). Individuals with prevalent PD had thinner GCIPL (-2.12 μm, 95% CI -3.17 to -1.07, p = 8.2 × 10 -5 ) and INL (-0.99 μm, 95% CI -1.52 to -0.47, p = 2.1 × 10 -4 ). The UK Biobank included 50,405 participants (mean age 56.1 ± 8.2 years, 54.7% female), of whom 53 developed PD at a mean of 2,653 ± 851 days. Thinner GCIPL (hazard ratio [HR] 0.62 per SD increase, 95% CI 0.46-0.84, p = 0.002) and thinner INL (HR 0.70, 95% CI 0.51-0.96, p = 0.026) were also associated with incident PD., Discussion: Individuals with PD have reduced thickness of the INL and GCIPL of the retina. Involvement of these layers several years before clinical presentation highlight a potential role for retinal imaging for at-risk stratification of PD., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Birth prevalence of Robin sequence (RS) is commonly reported as 1 case per 8000-14 000 live births. These estimates are based on single-source case ascertainment and may miss infants who did not require hospital admission or those without overt upper airway obstruction at birth., Objectives: To identify the true birth prevalence of RS with cleft palate in the UK and Ireland from a population-based birth cohort with high case ascertainment., Methods: Active surveillance of RS with cleft palate was carried out in the UK/Ireland using dual sources of case ascertainment: British Paediatric Surveillance Unit (BPSU) reporting card and nationally commissioned cleft services. Clinical data were collected from notifying clinicians at two time points., Results: 173 live-born infants met the surveillance case definition, giving a birth prevalence of 1 case per 5250 live births (19.1 per 100 000 (95% CI 16.2 to 21.9)), and 1:2690 in Scotland. 47% had non-isolated RS, with Stickler syndrome the most common genetic diagnosis (12% RS cases). Birth prevalence derived from the combined data sources was significantly higher than from BPSU surveillance alone., Conclusions: Birth prevalence of RS in the UK/Ireland derived from active surveillance is higher than reported by epidemiological studies from several other countries, and from UK-based anomaly registries, but consistent with published retrospective data from Scotland. Dual case ascertainment sources enabled identification of cases with mild or late-onset airway obstruction that were managed without hospital admission. Studies of aetiology and equivalent well-designed epidemiological studies from other populations are needed to investigate the identified geographical variability in birth prevalence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Evolutionary perspectives on human childbirth have primarily focused on characteristics of our species in general, rather than variability within and between contemporary populations. We use an evolutionary framework to explore how physical and demographic characteristics of mothers shape the risks of childbirth complications in rural lowland Nepal, where childbearing typically commences in adolescence and chronic undernutrition is widespread, though maternal overweight is increasing in association with nutrition transition., Methods: We conducted secondary analyses of data from a cluster-randomized trial. Women aged 14-35 years were categorized by age, number of previous pregnancies, height, body mass index (BMI), husband's education, and household wealth. Multivariable logistic regression models tested whether these characteristics independently predicted risks of episiotomy and cesarean section (CS, n = 14 261), and obstructed labor (OL, n = 5185)., Results: Risks were greatest among first-time adolescent mothers, though associations with age varied by outcome. Independent of age and parity, short stature and high BMI increased risks of CS and OL, whereas associations were weaker for episiotomy. Male offspring had increased risk of CS and OL but not episiotomy. Wealth was not associated with OL, but lower wealth and lower husband's education were associated with lower likelihood of episiotomy and CS., Conclusions: At the individual level, the risk childbirth complications is shaped by trade-offs between fertility, growth, and survival. Some biological markers of disadvantage (early childbearing, short stature) increased the risk, whereas low socio-economic status was associated with lower risk, indicating reduced access to relevant facilities. Independent of these associations, maternal age showed complex effects., (© 2021 The Authors. American Journal of Human Biology published by Wiley Periodicals LLC.)