Utilization of antidepressants, anxiolytics, and hypnotics during the COVID-19 pandemic in Scandinavia

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A unified earthquake catalogue for the North Sea to derisk European CCS operations

Carbon capture and storage (CCS) technology is essential to European decarbonisation efforts, and several offshore CO2 storage projects are being developed in the North Sea. Understanding the geomechanical response to CO2 injection is key to both the pre-characterisation and operation of a storage reservoir. A thorough assessment of seismicity gives critical insights into the stress field and faulting around reservoirs, both key controls on the geomechanical response to injection. Seismicity also illuminates potential hydraulic pathways for leakage, be it directly by revealing the extent of faults, or indirectly through fractures imaged by measurements of seismic anisotropy. High quality seismicity data is critical to underpin all of these methods of analysis. This paper presents the most complete catalogue of seismicity in the North Sea to date. The combined data are enabling revised assessments of seismic hazard and leakage risk in the North Sea, as well as a better understanding of faulting and stress. This study shows the value of unifying disparate seismicity data, allowing for more accurate seismological analyses. These lay the foundation for better management of risks for not only geologic CO2 storage, but other offshore industries and infrastructure

Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

Background: Hypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP). Methods and Findings: Three population-based EUROCAT congenital anomaly registries- Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010)—were linked to the electronic healthcare databases holding prospectively collected prescription information for all pregnancies in the timeframes available. We included 519,117 deliveries, including foetuses terminated for congenital anomalies, with data covering pregnancy and the preceding quarter, including 462,641 with data covering pregnancy and one year either side. For SSRI exposures 91 days either side of LMP, separately and together, odds ratios with 95% confidence intervals (ORs, 95%CI) for all major anomalies were estimated. We also explored: pausing or discontinuing SSRIs preconception, confounding, high dose regimens, and, in Wales, diagnosis of depression. Results were combined in meta-analyses. SSRI prescription 91 days either side of LMP was associated with increased prevalence of severe congenital heart defects (CHD) (as defined by EUROCAT guide 1.3, 2005) (34/12,962 [0.26%] vs. 865/506,155 [0.17%] OR 1.50, 1.06–2.11), and the composite adverse outcome of 'anomaly or stillbirth' (473/12962, 3.65% vs. 15829/506,155, 3.13%, OR 1.13, 1.03–1.24). The increased prevalence of all major anomalies combined did not reach statistical significance (3.09% [400/12,962] vs. 2.67% [13,536/506,155] OR 1.09, 0.99–1.21). Adjusting for socio-economic status left ORs largely unchanged. The prevalence of anomalies and severe CHD was reduced when SSRI prescriptions were stopped or paused preconception, and increased when >1 prescription was recorded, but differences were not statistically significant. The dose-response relationship between severe CHD and SSRI dose (meta-regression OR 1.49, 1.12–1.97) was consistent with SSRI-exposure related risk. Analyses in Wales suggested no associations between anomalies and diagnosed depression. Conclusion: The additional absolute risk of teratogenesis associated with SSRIs, if causal, is small. However, the high prevalence of SSRI use augments its public health importance, justifying modifications to preconception care

Integrated study of water Sr isotopes and carbonate Sr-C-O isotopes reveals long-lived fluid compartments in the Langfjellet oil discovery, Norwegian North Sea

Routine measurements of reservoir pressure variation with depth can detect pressure discontinuities indicative of barriers to vertical fluid movement. This study investigates how pressure data can be augmented by detailed profiles of formation water 87Sr/86Sr ratio to determine the precise location and cause of such barriers, and by C–O–Sr isotope analysis of carbonate cements to determine the duration over which the barrier has persisted. The study focuses on the clastic Hugin Formation reservoir in the Langfjellet Oil Discovery (Norwegian North Sea). Here, pressure data indicated a barrier somewhere within a 25 m depth interval. Formation water 87Sr/86Sr was measured with high spatial resolution by extraction from core samples using the residual salt analysis (RSA) method. This revealed three homogeneous populations of water separated by a small step in 87Sr/86Sr over a 7 m interval containing coal and shale layers, and a very large step in 87Sr/86Sr over a 1.2 m interval corresponding to a thin coal and shale layer situated below a major flooding surface. The latter is the main candidate for the pressure barrier. Modelling confirmed that this inferred pressure barrier also greatly retards Sr diffusion. Carbonate cements occur disseminated throughout the reservoir and in several heavily-cemented zones. Oxygen isotope-derived temperatures indicate that these formed in two episodes: (1) Pre-compactional, precipitated shortly after deposition in the zone of bacterial methanogenesis (~30 °C, ~200 m depth, ~162 Ma); (2) Post-compactional incorporating thermal decarboxylation-derived carbon (~90 °C, ~2500 m depth, ~46 Ma). Carbonate 87Sr/86Sr data reveal the same compositional populations present in the current formation water to be present in both cement generations. The water compositional stratification must thus have been present when the early and late cements precipitated, down till today. The persistence of a compositional step for most of the geological history of the rocks confirms the presence of a major fluid communication barrier. The Sr RSA data show invariant water composition across the heavily carbonate cemented intervals, implying no barrier effect. The combination of pressure data (to identify pressure barriers), Sr RSA (to add spatial resolution) and Sr–C–O isotopes of carbonates of different ages (to add a time dimension) is useful for identifying major long-term fluid communication barriers and differentiating them from smaller, less effective or shorter-term features. The method has applications for identifying seals in exploitation of petroleum and water resources, and underground storage of CO2 and radioactive waste

Association of prenatal exposure to benzodiazepines and child internalizing problems: A sibling-controlled cohort study

Background: During pregnancy, many women experience sleep problems and anxiety that require treatment. The long-term safety for the child of maternal benzodiazepine (BZD) and z-hypnotic use during pregnancy remains controversial. Method We conducted a cohort and a sibling control study using data from the Norwegian Mother and Child Cohort Study. Data on use of BZD and z-hypnotics, internalizing and externalizing outcomes, and covariates were collected from mothers at gestational weeks 17 and 30 and when children were 0.5, 1.5, and 3 years of age. The total sample consisted of 71,996 children (19,297 siblings) at 1.5 years and 55,081 children (13,779 siblings) at 3 years. Short-term use was defined as use in one pregnancy period only. Long-term use was defined as use in two or more pregnancy periods. Linear full cohort random-effect and sibling-matched fixed-effect regression models were used to compare internalizing and externalizing behavior in children prenatally exposed compared to those unexposed in the full cohort of pregnancies accounting for family clusters, as well as within sibling clusters comparing pregnancies with discordant exposures. Propensity score (PS) adjustment included variables on indication for use (sleep problems, symptoms of anxiety and depression) and other potential confounding factors. Results: Long-term prenatal exposure to BZD or z-hypnotics was associated with increased internalizing behavior in crude cohort analyses and at age 1.5 years after PS adjustment in sibling-matched fixed-effect models [β 0.60, 95% confidence interval 0.17–0.95]. Analyses on specific drug groups showed that prenatal exposure to BZD-anxiolytics was associated with increased internalizing problems at both 1.5 years [β 0.25, 0.01–0.49] and 3 years [β 0.26, 0.002–0.52] while exposure to z-hypnotics was not associated with any adverse outcomes after adjustment. Conclusion: The findings suggest a moderate association between BZD-anxiolytic exposure and child internalizing problems that is not likely due to stable familial confounding factors

Substance abuse and psychiatric co-morbidity as predictors of premature mortality in Swedish drug abusers a prospective longitudinal study 1970 - 2006

<p>Abstract</p> <p>Background</p> <p>Few longitudinal cohort studies have focused on the impact of substances abused and psychiatric disorders on premature mortality. The aim of the present study was to identify predictors of increased risk of drug related death and non drug related death in substance abusers of opiates, stimulants, cannabis, sedatives/hypnotics, hallucinogens and alcohol over several decades.</p> <p>Methods</p> <p>Follow-up study of a consecutive cohort of 561 substance abusers, admitted to a detoxification unit January 1970 to February 1978 in southern Sweden, and followed up in 2006. Demographic and clinical data, substance diagnoses and three groups of psychiatric diagnoses were identified at first admission. Causes of death were coded according to ICD-10 and classified as drug related deaths or non drug related deaths. To identify the incidence of some probable risk factors of drug related premature death, the data were subjected to a competing risks Cox regression analysis.</p> <p>Results</p> <p>Of 561 patients in the cohort, 11 individuals had either emigrated or could not be located, and 204/561 patients (36.4%) were deceased by 2006. The cumulative risk of drug related death increased more in the first 15 years and leveled out later on when non drug related causes of death had a similar incidence. In the final model, male gender, regular use of opiates or barbiturates at first admission, and neurosis were associated with an increased risk of drug related premature death, while cannabis use and psychosis were associated with a decreased risk. Neurosis, mainly depression and/or anxiety disorders, predicted drug related premature death while chronic psychosis and personality disorders did not. Chronic alcohol addiction was associated with increased risk of non drug related death.</p> <p>Conclusions</p> <p>The cohort of drug abusers had an increased risk of premature death to the age of 69. Drug related premature death was predicted by male gender, the use of opiates or barbiturates and depression and anxiety disorders at first admission. The predicted cumulative incidence of drug related death was significantly higher in opiate and barbiturate abusers over the observed period of 37 years, while stimulant abuse did not have any impact. Alcohol contributed to non drug related death.</p

Selective serotonin reuptake inhibitor antidepressant use in first trimester pregnancy and risk of specific congenital anomalies: A European register-based study

Evidence of an association between early pregnancy exposure to selective serotonin reuptake inhibitors (SSRI) and congenital heart defects (CHD) has contributed to recommendations to weigh benefits and risks carefully. The objective of this study was to determine the specificity of association between first trimester exposure to SSRIs and specific CHD and other congenital anomalies (CA) associated with SSRI exposure in the literature (signals). A population-based case-malformed control study was conducted in 12 EUROCAT CA registries covering 2.1 million births 1995-2009 including livebirths, fetal deaths from 20 weeks gestation and terminations of pregnancy for fetal anomaly. Babies/fetuses with specific CHD (n = 12,876) and non-CHD signal CA (n = 13,024), were compared with malformed controls whose diagnosed CA have not been associated with SSRI in the literature (n = 17,083). SSRI exposure in first trimester pregnancy was associated with CHD overall (OR adjusted for registry 1.41, 95% CI 1.07-1.86, fluoxetine adjOR 1.43 95% CI 0.85-2.40, paroxetine adjOR 1.53, 95% CI 0.91-2.58) and with severe CHD (adjOR 1.56, 95% CI 1.02-2.39), particularly Tetralogy of Fallot (adjOR 3.16, 95% CI 1.52-6.58) and Ebstein's anomaly (adjOR 8.23, 95% CI 2.92-23.16). Significant associations with SSRI exposure were also found for ano-rectal atresia/stenosis (adjOR 2.46, 95% CI 1.06-5.68), gastroschisis (adjOR 2.42, 95% CI 1.10-5.29), renal dysplasia (adjOR 3.01, 95% CI 1.61-5.61), and clubfoot (adjOR 2.41, 95% CI 1.59-3.65). These data support a teratogenic effect of SSRIs specific to certain anomalies, but cannot exclude confounding by indication or associated factors