Hidden in plain sight:Using administrative data to conduct a longitudinal cohort study of children exposed to opioids in pregnancy

Objectives: Children of women who use substances are difficult to research at a population-level using traditional research methods due to the complexity of their lives. Resultingly, we have little robust evidence on their outcomes. This study developed an administrative data cohort of children exposed to opioids and explored health outcomes.Methods: Using data from birth records, antenatal records, prescription data, hospital/psychiatric hospital admissions, and drug and alcohol service data, we identified 6,408 children (born 2009-2019) in Scotland who were exposed to opioids through illicit use and/or medication assisted treatment (i.e. methadone/buprenorphine). A control group (n. 19,089) of children not exposed to opioids were matched on age of mother and Scottish Index of Multiple Deprivation. Data were described and linear and logistic regression models were used to examine the relationship between risk factors (such as drug and alcohol use in pregnancy, gestation at booking and at birth), and key early outcomes.Results: Although the majority of women had their substance use recorded in antenatal records, 28.9\% did not, demonstrating the importance of using multiple administrative datasets to form the cohort. Children in the cohort were more likely to experience a range of adverse outcomes including being born early (17\% born prematurely, compared with 6.5\% in control group), having a below normal Apgar score (the scoring system used to assess newborns shortly after birth) (2.9\% in cohort vs. 1.5\% in controls), having significantly lower birthweight, length and head circumference, and more likely to be removed from their mother prior hospital discharge. Differences between the cohorts remained after controlling for other risk factors including alcohol use, and gestation.Conclusion: This feasibility study brought together a cohort of children usually excluded from traditional forms of research. The research demonstrated early differences in outcomes between exposed children and others from similar socio-economic groups. The next stage of this research is exploring health and development outcomes in the preschool period

Measuring the impact of maternal critical care admission on short- and longer-term maternal and birth outcomes

PurposeFactors increasing the risk of maternal critical illness are rising in prevalence in maternity populations. Studies of general critical care populations highlight that severe illness is associated with longer-term physical and psychological morbidity. We aimed to compare short- and longer-term outcomes between women who required critical care admission during pregnancy/puerperium and those who did not. MethodsA cohort study including all women delivering in Scottish hospitals between 01/01/2005-31/12/2018, using national healthcare databases. The primary exposure was Intensive Care Unit (ICU) admission, whilst secondary exposures included High Dependency Unit admission. Outcomes included hospital readmission (1-year post-hospital discharge, 1-year mortality, psychiatric hospital admission, stillbirth and neonatal critical care admission). Multivariable Cox and logistic regression were used to report hazard ratios (HR) and odds ratios (OR) of association between ICU admission and outcomes. ResultsOf 762,918 deliveries, 1,449 (0.18%) women were admitted to ICU, most commonly due to post-partum haemorrhage (225, 15.5%) followed by eclampsia/pre-eclampsia (133, 9.2%). Over-half (53.8%) required mechanical ventilation. One-year hospital readmission was more frequent in women admitted to ICU compared with non-ICU populations (24.5% (n=299) vs 8.9% (n=68,029)). This association persisted after confounder adjustment (HR=1.93, 95%CI 1.33, 2.81, p&lt;0.001). Furthermore, maternal ICU admission was associated with increased 1-year mortality (HR=40.06, 95%CI 24.04,66.76, p&lt;0.001, stillbirth (OR=12.31, 95%CI 7.95,19.08,p&lt;0.001) and neonatal critical care admission (OR=6.99, 95%CI 5.64 ,8.67, p&lt;0.001) after confounder adjustment. ConclusionCritical care admission increases the risk of adverse short-term and long-term maternal, pregnancy and neonatal outcomes. Optimising long-term post-partum care may benefit maternal critical illness survivors.<br/

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

The role of ixazomib as an augmented conditioning therapy in salvage autologous stem cell transplant (ASCT) and as a post-ASCT consolidation and maintenance strategy in patients with relapsed multiple myeloma (ACCoRd [UK-MRA Myeloma XII] trial): study protocol for a Phase III randomised controlled trial

Background: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed disease management (salvage ASCT), has been shown to prolong the progression-free survival and overall survival following a proteasome inhibitor-containing re-induction regimen, in the Cancer Research UK-funded National Cancer Research Institute Myeloma X (Intensive) study. It is now recommended that salvage ASCT be considered for suitable patients by the International Myeloma Working Group and the National Institute for Health and Care Excellence NG35 guidance. Methods/design: ACCoRd (Myeloma XII) is a UK-nationwide, individually randomised, multi-centre, multiple randomisation, open-label phase III trial with an initial single intervention registration phase aimed at relapsing MM patients who have received ASCT in first-line treatment. We will register 406 participants into the trial to allow 284 and 248 participants to be randomised at the first and second randomisations, respectively. All participants will receive re-induction therapy until maximal response (four to six cycles of ixazomib, thalidomide and dexamethasone). Participants who achieve at least stable disease will be randomised (1:1) to receive either ASCTCon, using high-dose melphalan, or ASCTAug, using high-dose melphalan with ixazomib. All participants achieving or maintaining a minimal response or better, following salvage ASCT, will undergo a second randomisation (1:1) to consolidation and maintenance or observation. Participants randomised to consolidation and maintenance will receive consolidation with two cycles of ixazomib, thalidomide and dexamethasone, and maintenance with ixazomib until disease progression. Discussion: The question of how best to maximise the durability of response to salvage ASCT warrants clinical investigation. Given the expanding scope of oral therapeutic agents, patient engagement with long-term maintenance strategies is a real opportunity. This study will provide evidence to better define post-relapse treatment in MM

A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms

We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms ( SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds ( a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines - in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases

Lower Cancer Incidence in Amsterdam-I Criteria Families Without Mismatch Repair Deficiency: Familial Colorectal Cancer Type X

Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown

Author Correction: Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

Correction to: Nature Communications https://doi.org/10.1038/s41467-023-42320-4, published online 22 December 202

Association between lifestyle factors and headache

Modification of lifestyle habits is a key preventive strategy for many diseases. The role of lifestyle for the onset of headache in general and for specific headache types, such as migraine and tension-type headache (TTH), has been discussed for many years. Most results, however, were inconsistent and data on the association between lifestyle factors and probable headache forms are completely lacking. We evaluated the cross-sectional association between different lifestyle factors and headache subtypes using data from three different German cohorts. Information was assessed by standardized face-to-face interviews. Lifestyle factors included alcohol consumption, smoking status, physical activity and body mass index. According to the 2004 diagnostic criteria, we distinguished the following headache types: migraine, TTH and their probable forms. Regional variations of lifestyle factors were observed. In the age- and gender-adjusted logistic regression models, none of the lifestyle factors was statistically significant associated with migraine, TTH, and their probable headache forms. In addition, we found no association between headache subtypes and the health index representing the sum of individual lifestyle factors. The lifestyle factors such as alcohol consumption, smoking, physical activity and overweight seem to be unrelated to migraine and TTH prevalence. For a judgement on their role in the onset of new or first attacks of migraine or TTH (incident cases), prospective cohort studies are required

Phylogenetically Widespread Polyembryony in Cyclostome Bryozoans and the Protracted Asynchronous Release of Clonal Brood-Mates

The file attached is the Published/publisher’s pdf version of the articl