Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

BACKGROUND ; There is uncertainty over whether maternal smoking is associated with birth defects. We conducted the first ever comprehensive systematic review to establish which specific malformations are associated with smoking. METHODS ; Observational studies published 1959-2010 were identified (Medline), and included if they reported the odds ratio (OR) for having a non-chromosomal birth defect among women who smoked during pregnancy compared with non-smokers. ORs adjusted for potential confounders were extracted (e.g. maternal age and alcohol), otherwise unadjusted estimates were used. One hundred and seventy-two articles were used in the meta-analyses: a total of 173 687 malformed cases and 11 674 332 unaffected controls. RESULTS ; Significant positive associations with maternal smoking were found for: cardiovascular/heart defects [OR 1.09, 95% confidence interval (CI) 1.02-1.17]; musculoskeletal defects (OR 1.16, 95% CI 1.05-1.27); limb reduction defects (OR 1.26, 95% CI 1.15-1.39); missing/extra digits (OR 1.18, 95% CI 0.99-1.41); clubfoot (OR 1.28, 95% CI 1.10-1.47); craniosynostosis (OR 1.33, 95% CI 1.03-1.73); facial defects (OR 1.19, 95% CI 1.06-1.35); eye defects (OR 1.25, 95% CI 1.11-1.40); orofacial clefts (OR 1.28, 95% CI 1.20-1.36); gastrointestinal defects (OR 1.27, 95% CI 1.18-1.36); gastroschisis (OR 1.50, 95% CI 1.28-1.76); anal atresia (OR 1.20, 95% CI 1.06-1.36); hernia (OR 1.40, 95% CI 1.23-1.59); and undescended testes (OR 1.13, 95% CI 1.02-1.25). There was a reduced risk for hypospadias (OR 0.90, 95% CI 0.85-0.95) and skin defects (OR 0.82, 0.75-0.89). For all defects combined the OR was 1.01 (0.96-1.07), due to including defects with a reduced risk and those with no association (including chromosomal defects). CONCLUSIONS ; Birth defects that are positively associated with maternal smoking should now be included in public health educational materials to encourage more women to quit before or during pregnancy.

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Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls

This is a very large compilation of growth data with an extremely wide coverage of population groups, many of which will be completely unknown to all but the professional ethnographer. There is, however, a disappointingly narrow coverage of variables (length, weight, body widths, circumferences and proportions, skinfold thicknesses, and maturity). Many of the findings are relevant to an important question: should one set of growth reference data be used throughout the world, thus allowing ready comparability between groups, or should there be separate sets for each major racial group or even a multitude of local sets? The studies summarized in this volume indicate many population groups have similar potentials for growth in major body dimensions. For example, the narrower range of means among European than among African groups that range from "tribal" to well-off indicates the range of variation in growth would be reduced greatly if the environmental circumstances allowed

Worldwide Variation in Human Growth

Health care organizations are leveraging machine-learning techniques, such as artificial neural networks (ANN), to improve delivery of care at a reduced cost. Applications of ANN to diagnosis are well-known; however, ANN are increasingly used to inform health care management decisions. We provide a seminal review of the applications of ANN to health care organizational decision-making. We screened 3,397 articles from six databases with coverage of Health Administration, Computer Science and Business Administration. We extracted study characteristics, aim, methodology and context (including level of analysis) from 80 articles meeting inclusion criteria. Articles were published from 1997–2018 and originated from 24 countries, with a plurality of papers (26 articles) published by authors from the United States. Types of ANN used included ANN (36 articles), feed-forward networks (25 articles), or hybrid models (23 articles); reported accuracy varied from 50% to 100%. The majority of ANN informed decision-making at the micro level (61 articles), between patients and health care providers. Fewer ANN were deployed for intra-organizational (meso- level, 29 articles) and system, policy or inter-organizational (macro- level, 10 articles) decision-making. Our review identifies key characteristics and drivers for market uptake of ANN for health care organizational decision-making to guide further adoption of this technique.

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Applications of artificial neural networks in health care organizational decision-making: A scoping review

Although clubfoot is one of the most common congenital abnormalities affecting the lower limb, it remains a challenge not only to understand its genetic origins but also to provide effective long-term treatment. This review provides an update on the etiology of clubfoot as well as current treatment strategies. Understanding the exact genetic etiology of clubfoot may eventually be helpful in determining both prognosis and the selection of appropriate treatment methods in individual patients. The primary treatment goal is to provide long-term correction with a foot that is fully functional and pain-free. To achieve this, a combination of approaches that applies the strengths of several methods (Ponseti method and French method) may be needed. Avoidance of extensive soft-tissue release operations in the primary treatment should be a priority, and the use of surgery for clubfoot correction should be limited to an “a la carte” mode and only after failed conservative methods. Level of Evidence: Level V, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Update on clubfoot: etiology and treatment.

Genetics and epidemiology of idiopathic congenital talipes equinovarus.

Congenital talipes equinovarus (CTEV) is a common developmental disorder of the foot, affecting between 1 and 4.5 per 1000 live births. The aetiology is not well elucidated. While both genetic and environmental factors are implicated, no specific genes have been identified and little is known about environmental risk factors. We conducted a case-control study of idiopathic congenital talipes equinovarus (ICTEV) in the United Kingdom. 194 cases and 60 controls were recruited. Pedigrees were obtained for 167 cases. The rank of the index pregnancy, maternal education and caesarean delivery were significantly associated with ICTEV risk in a multivariate model. There were suggestions that maternal use of folic acid supplements in the three months before the pregnancy decreased ICTEV risk, and that parental smoking during the pregnancy increased risk, although the associations were not statistically significant. One quarter of pedigrees showed a family history of CTEV, and autosomal dominant inheritance was suggested in some of these. Uterine restriction did not appear to have a strong influence on ICTEV development in our study. Large population-based studies are needed to clarify the aetiology of this common developmental disorder.

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Pedigree analysis and epidemiological features of idiopathic congenital talipes equinovarus in the United Kingdom: a case-control study

Outcome following management of congenital talipes equinovarus (clubfoot) can be assessed in a number of ways. Bjonness stated simply that "the patient is the final judge of whether he has a good foot"; a purely subjective assessment. Others have employed objective measures. Combining subjective evaluation with a more objective assessment of movement and position of the foot, is likely to give a more comprehensive picture of the final result of clubfoot. The purpose of this study was to compare subjective and objective outcome following management of clubfoot, and evaluate sex differences in outcome. We used a patient-administered subjective assessment of outcome following treatment of clubfoot and compared it with objective anthropometry and range of movement of the ankle to assess and compare subjective and objective outcome in clubfoot. Statistical analysis was performed using Pearson correlation coefficients. Significance was tested using Student's t-test test. Objective outcome can be assessed using length of the foot, calf circumference and range of movement at the ankle. These are easy to measure, reproducible, and correlate well with subjective outcome. Objective outcome is comparable for boys and girls. However, subjectively, female patients and their parents are less happy with the results of management of clubfoot. There is a correlation between the anthropometric measures and the subjective outcome and an objective grading can be designed using foot length, calf muscle bulk and range of movement at the ankle.

https://link.springer.com/content/pdf/10.1186%2F1471-2474-8-53.pdf

Subjective and objective outcome in congenital clubfoot; a comparative study of 204 children.

Background: One proposed etiology of idiopathic talipes equinovarus is an in utero enterovirus infection. Enterovirus infections demonstrate seasonal variation in temperate climates.

Methods: We collected data on 1202 children with idiopathic talipes equinovarus born in the Northeastern United States, Midwestern United States, and the United Kingdom to investigate a seasonal variation in this congenital deformity. Birth date, gestational age at the time of delivery, gender, race, and laterality were tabulated and subjected to univariate and bivariate analyses.

Results: There were 774 boys and 428 girls with idiopathic talipes equinovarus. The birth location was the United Kingdom (458 children), the Midwestern United States (426 children), and the Northeastern United States (318 children). No significant differences were detected among the geographic groups with respect to gender, race, or laterality, and no variation in month of birth or month of conception was noted.

Conclusions: This study does not support an in utero enterovirus infection as an etiology of idiopathic talipes equinovarus in industrialized populations.

Lack of seasonal variation in idiopathic talipes equinovarus.

Worldwide, 1-4 per 1,000 births are affected by clubfoot. Clubfoot etiology is unclear, but both genetic and environmental factors are thought to be involved. Low folate status in pregnant women has been implicated in several congenital malformations, and folate metabolism may be affected by polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR). Using a case-parent-triad design, the authors investigated whether the MTHFR C677T polymorphism, and maternal periconceptional folic acid supplement use, influenced risk of isolated clubfoot. Three hundred seventy-five United Kingdom case-parent triads were recruited in 1998-1999. Among the children, there was a significant trend of decreasing clubfoot risk with increasing number of T alleles: relative risk for CT vs. CC = 0.75, 95% confidence interval: 0.57, 0.97; relative risk for TT vs. CC = 0.57, 95% confidence interval: 0.35, 0.91; p trend = 0.006. This association was not modified by maternal folic acid use. Maternal MTHFR genotype did not influence clubfoot risk for the offspring overall, although a possible interaction with folic acid use was found. This is the first known report of a specific genetic polymorphism associated with clubfoot. The direction of the association is intriguing and suggests that DNA synthesis may be relevant in clubfoot development. However, clubfoot mechanisms are poorly understood, and the folate metabolism pathway is complex. Further research is needed to elucidate these relations.

The C677T Polymorphism in the Methylenetetrahydrofolate Reductase Gene (MTHFR), Maternal Use of Folic Acid Supplements, and Risk of Isolated Clubfoot: A Case-Parent-Triad Analysis

David Chesney

Papers

Genetics and epidemiology of idiopathic congenital talipes equinovarus.

Pedigree analysis and epidemiological features of idiopathic congenital talipes equinovarus in the United Kingdom: a case-control study

Subjective and objective outcome in congenital clubfoot; a comparative study of 204 children.

Lack of seasonal variation in idiopathic talipes equinovarus.

The C677T Polymorphism in the Methylenetetrahydrofolate Reductase Gene (MTHFR), Maternal Use of Folic Acid Supplements, and Risk of Isolated Clubfoot: A Case-Parent-Triad Analysis