Search

This study presents a systematic investigation of the characteristics and meteorological impacts of warm conveyor belts (WCBs). For this purpose, we compile a new WCB climatology (1980–2022) of trajectories calculated with the most recent reanalysis dataset ERA5 from the European Centre for Medium-Range Weather Forecasts (ECMWF). Based on this new climatology, two-dimensional masks are defined that represent the inflow, ascent, and outflow locations of WCBs. These masks are then used to objectively quantify the key characteristics (intensity, ascent rate, and ascent curvature) and meteorological impacts (precipitation and potential vorticity (PV) anomalies) of WCBs in order to (i) attribute them to different stages in the life cycle of the associated cyclones and to (ii) evaluate differences in the outflow of the cyclonic and anticyclonic branches. The approach was applied globally, but this study focuses on the North Atlantic, one of the regions where WCBs ascend most frequently. The method is first tested and illustrated through three case studies of well-documented cyclones, revealing both the similarities and the case-to-case variability in the evolution of the WCB characteristics and impacts. We then extend the analysis to about 5000 cyclones that occurred in winter between 1980–2022 in the North Atlantic. The case studies and the climatological analysis both show that WCBs are typically most intense (in terms of air mass transported, ascent rate, precipitation rate, and volume) during the intensification period of the associated cyclone. The northward displacement along the storm track and diabatic PV production lead to an increase in low-level PV in the region of WCB ascent during the cyclone life cycle. The negative PV anomaly at upper levels, associated with the WCB outflow, remains relatively constant. The investigation of the WCB branches reveals an increasing intensity of the cyclonic WCB branch with time, linked to the increasing strength of the cyclonic wind field around the cyclone. Due to a lower altitude, the outflow of the cyclonic WCB branch is associated with a weaker negative PV anomaly than the anticyclonic one, which ascends to higher altitudes. In summary, this study highlights the distinct evolution of WCB characteristics and impacts during the cyclone life cycle and the marked differences between the cyclonic and anticyclonic branches.

We present TXPipe, a modular, automated and reproducible pipeline for ingesting catalog data and performing all the calculations required to obtain quality-assured two-point measurements of lensing and clustering, and their covariances, with the metadata necessary for parameter estimation. The pipeline is developed within the Rubin Observatory Legacy Survey of Space and Time (LSST) Dark Energy Science Collaboration (DESC), and designed for cosmology analyses using LSST data. In this paper, we present the pipeline for the so-called 3x2pt analysis -- a combination of three two-point functions that measure the auto- and cross-correlation between galaxy density and shapes. We perform the analysis both in real and harmonic space using TXPipe and other LSST-DESC tools. We validate the pipeline using Gaussian simulations and show that it accurately measures data vectors and recovers the input cosmology to the accuracy level required for the first year of LSST data under this simplified scenario. We also apply the pipeline to a realistic mock galaxy sample extracted from the CosmoDC2 simulation suite (Korytov et al. 2019). TXPipe establishes a baseline framework that can be built upon as the LSST survey proceeds. Furthermore, the pipeline is designed to be easily extended to science probes beyond the 3x2pt analysis.

Competing Interests: Conflict of interest: none declared.

Introduction: The medicines information service, SafeMotherMedicine, regularly receives inquiries from breastfeeding women asking about antiemetics for nausea and vomiting during pregnancy (NVP) or hyperemesis gravidarum (HG). However, treatment guidelines for NVP or HG do not address the use of antiemetics in women who are breastfeeding while becoming pregnant again. Our objective was to characterize inquiries to describe the need for lactation risk information among women with NVP or HG and also to raise awareness of this topic. Method: We conducted a review of inquiries to the Norwegian web-based medicines information service, SafeMotherMedicine. Results: In total, 97 inquiries addressing the use of antiemetics for NVP or HG during breastfeeding were identified. The following medications were addressed in the inquiries ( n = 97): meclizine (51%), metoclopramide (33%), promethazine (16%), ondansetron (9%), and others (6%). The breastfed child was older than 6 months and 1 year in 96% and 71% of the inquiries, respectively. There was a preponderance of general inquiries (unclear motivation/double checking) (64%); however, one-third of the inquiries were generated by restrictive information from sources such as product information. Conclusion: Based on our small review of spontaneous inquiries, there seems to be an information need about the use of antiemetics during lactation among women breastfeeding an older infant whilst suffering from NVP or HG. Addressing such use in guidelines for NVP and HG and/or other easily available information sources may be considered in order to balance out the restrictive information provided by the manufacturers. This could avoid potential unnecessary weaning of breastfeeding in an otherwise challenging situation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Heitmann, Bakkebø, Havnen and Schjøtt.)

Background: Safety information of antiseizure medication (ASM) during breastfeeding is scarce and conflicting. We aimed to identify characteristic traits of safety concerns among healthcare professionals by reviewing enquiries to the Norwegian Regional Medicines Information and Pharmacovigilance Centres (RELIS)., Method: Enquiries related to breastfeeding, epilepsy, and ASM identified by their ATC-numbers were retrieved from the RELIS database of question-and-answer pairs (QAPs) by combining indexed and Boolean database searches and manual inspection. 112 QAPs were analyzed retrospectively using descriptive statistics., Results: Hospital-employed physicians and nurses were puzzled by ambiguous or conflicting drug information advice and called for general information about the compatibility of an ASM with breastfeeding, mainly related to lamotrigine and levetiracetam. Other enquiries were related to co-medication with other drugs, mainly antidepressants. Half of the enquiries were posed after birth, 12 of these motivated by suspected adverse events in the infants., Conclusion: Healthcare professionals with acknowledged high competence in the topic were uncertain about the prevailing safety information of ASM during breastfeeding. The fear to harm the infant may lead to the decision not to recommend breastfeeding. Future information strategies should aim to reach these professions, and support their information need on this topic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Extended chemical analyses of fluvial sediments were undertaken to establish the key pollutant pressures and mixtures present across nine European Union inland waterways. A wide range of chemical components and physical parameters were investigated including substances from the EU Priority List and Watch List. The data set was examined for key indicator compounds, however it was found that a wide range of pollution pressures were present in the different sediments including organic hydrocarbons, metal(loid)s, nutrients, polycyclic aromatic hydrocarbon (PAH), polychlorinated biphenyl (PCB) compounds, perfluoroalkyl and polyfluoroalkyl substances and pesticides, some of which exceeded regulatory guidance at different sampling points. The presence of such a wide range of compounds underpins the complex chemical composition of sediments that have acted as sinks for many decades absorbing contaminants from urban, industrial and agricultural sources. This dataset has been used to describe average overall toxicity of the sediments sampled, a calculation which was based on key components identified by Principal Component Analysis (PCA) and for those that had existing freshwater sediment regulatory values. A total of 33 components were used including PCBs, PAHs, metal(iod)s and pesticides. This analysis reflected the contamination of each site, with most indicating some level of toxicity during the sampling period. Watch List chemicals triclosan (TCS) and diclofenac (DIC) were also investigated; levels were relatively low, typically 10-100's ng L -1 , however they were present at all sampling sites. The dataset is available as a resource for future chemical, and toxicological, sediment analysis comparisons., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Susanne Heise reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Samantha Richardson reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Will M. Mayes reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Sonja Faetsch reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Hanne Hetjens reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Johnny Teuchies reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Paul Walker reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Katharina Heitmann reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Kevin Welham reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Dean Moore reports were provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Lieven Bervoets reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Paul Kay reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Wayne Duffus reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Nick Smith reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Ward De Cooman reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Raf Elstj reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Els Ryken reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu. Jeanette M. Rotchell reports financial support was provided by Interreg VB North Sea Region Programme, European Regional Development Fund. www.northsearegion.eu., (Copyright © 2023. Published by Elsevier B.V.)

Background: Online information about safety of medications during pregnancy and breastfeeding is shown to be conflicting, resulting in anxiety and abstaining from use. The aim of this study was to characterize questions to SafeMotherMedicine, a web-based medicines information service for pregnant and breastfeeding women, to identify target areas that could guide subsequent development of medicines information directed at pregnant and breastfeeding women., Methods: The SafeMotherMedicine database contains all questions received through the web-based service and their corresponding answers. A retrospective database analysis of questions received from January 2016 to September 2018 was performed, using descriptive statistics., Results: A total of 11 618 questions were received including 5 985 questions (51.5%) concerning pregnancy, 4 878 questions (42.0%) concerning breastfeeding, and 755 questions (6.5%) concerning both conditions. The medications in question represented all therapeutic groups with paracetamol (7.0%), ibuprofen (4.1%), cetirizine (3.3%), desloratadine (3.2%) and meclizine (2.8%) being the top five. The 20 medications most frequently asked about for either pregnancy, breastfeeding or both pregnancy and breastfeeding, constituted half of all questions and were used to identify target areas. These included both symptomatic relief of common complaints, such as pain, nausea, and rhinitis, as well as treatment of chronic conditions such as allergy, psychiatric disorders, and asthma. Analysis of a subset of questions showed that most of these questions were asked before use of medications in a current pregnancy (49%) or during breastfeeding (72%). The questions concerned use of medications in all stages of pregnancy and breastfeeding. For 81.6% of the questions concerning pregnancy, and for 84.2% of the questions concerning breastfeeding, information of no or low risk for the foetus or the breastfed infant was provided by SafeMotherMedicine., Conclusions: We found that target areas for medicines information directed at pregnant and breastfeeding women included both symptomatic relief of common complaints as well as treatment of chronic conditions. The questions concerned a wide range of medications and involved use in all stages of pregnancy and breastfeeding. Our findings indicate that developing medicines information addressing the identified target areas will meet the information need for a large proportion of this patient group., (© 2022. The Author(s).)

Objectives: To investigate the perceived risk of psychotropic and mental illness exposures (1) during pregnancy or (2) while breastfeeding on offspring neurodevelopment, and factors associated with this perception in women with past/current mental illness., Design: Cross-sectional, web-based study., Setting: Nationwide in Norway, June 2020-June 2021., Participants: Women aged 18-55 years who were pregnant, recent mothers or planning a pregnancy, and had been offered antidepressants in the last 5 years., Primary and Secondary Outcome Measures: Perceived risk of prenatal and breastmilk exposure to psychotropic medications and maternal mental illness on offspring neurodevelopmental outcomes., Results: We included 448 women: 234 pregnant, 146 mothers and 68 planning a pregnancy. On a 0-10 scale, women perceived antidepressants as least harmful both (1) in pregnancy (mean score 4.2, 95% CI 3.6 to 4.8) and (2) while breastfeeding (mean score 3.8, 95% CI 3.3 to 4.4), relative to antipsychotics, anxiety/sleeping medication or antiepileptics (mean score range: 6.3-6.5 during pregnancy, 5.5-6.2 while breastfeeding). Many participants were unfamiliar with psychotropics other than antidepressants. The perceived risk of mental illness exposure exceeded that of antidepressants (mean score range 5.6-5.9) in both exposure periods. Using general linear models, factors associated with greater antidepressant risk perception in both exposure periods included having lower education, non-Norwegian native language, and employment status (range mean score difference (β): 2.07-6.07). For pregnant women and mothers, there was an inverse association between perceived risk and the perceived antidepressant effectiveness in both exposure periods (range of β: -0.18 to -0.25)., Conclusions: In women with past/current mental illness, the perceived risk of antidepressant exposure on child neurodevelopment was lower than that for maternal mental illness. Other psychotropic medications were perceived as more harmful. As medication risk perception influences the decision-making regarding treatment of mental illness, pre- and pregnancy counselling should target women with characteristics associated with higher perceived risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Surgical replacement of the aortic root is the only intervention that can prevent aortic dissection and cardiovascular death in Marfan syndrome (MFS). However, in some individuals, MFS also causes sleep apnea. If sleep apnea predicts cardiovascular death, a new target for predictive, preventive, and personalized medicine (PPPM) may emerge for those individuals with MFS who have sleep apnea., Methods: This is an investigator-initiated study with long-term follow-up data of 105 individuals with MFS. All individuals were screened for sleep apnea regardless of symptoms. Cardiovascular death served as a primary endpoint, and aortic events as a secondary outcome., Results: Sleep apnea with an apnea-hypopnea index (AHI) > 5/h was observed in 21.0% (22/105) with mild sleep apnea in 13% (14/105) and moderate to severe sleep apnea in 7.6% (8/105). After a median follow-up of 7.76 years (interquartile range: 6.84, 8.41), 10% (10/105) had died, with cardiovascular cause of death in 80% (8/10). After adjusting for age and body mass index (BMI), the AHI score emerged as an independent risk factor for cardiovascular death (hazard ratio 1.712, 95% confidence interval [1.061-2.761], p  = 0.0276). The secondary outcome of aortic events occurred in 33% (35/105). There was no effect of the AHI score on aortic events after adjusting for age and BMI (hazard ratio 0.965, 95% confidence interval [0.617-1.509]), possibly due to a high number of patients with prior aortic surgery., Interpretation: Sleep apnea is emerging as an independent predictor of cardiovascular death in MFS. It seems mandatory to screen all individuals with MFS for sleep apnea and to include these individuals, with both MFS and sleep apnea, in further studies to evaluate the impact of preventive measures with regard to cardiovascular death., Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00291-4., Competing Interests: Competing interestsNG reports grants from Boston Scientific, grants from Medtronic, and support from Bayer Vital, outside the submitted work. SD reports institutional grants from COOK Medical and honoraria from Bayer Vital, outside the submitted work. CE reports grants and/or personal fees from Abbott, Biosense Webster, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo and Medtronic, outside the submitted work. SH reports grants from Meril Life, Boston Scientific and Spectranetics, outside the submitted work. ET reports honoraria from Abiomed and travel compensation from Bayer Vital, Edwards, and Amgen, outside the submitted work. SW reports grants and personal fees from Abbott, Boston Scientific, and Medtronic, and personal feels from Abbott, Boehringer Ingelheim, Bristol Myers Squibb, Bayer Vital, Acutus, and Daiichi Sankyo, outside the submitted work. All other authors have nothing to disclose., (© The Author(s) 2022.)

Background: Women suffering from severe nausea and vomiting during pregnancy, hyperemesis gravidarum, have poor quality of life and increased risk of potentially fatal maternal and fetal complications. There is increasing and reassuring knowledge about safety of antiemetics in pregnancy. In 2013, the European Medical Agency (EMA) issued a warning on metoclopramide limiting treatment to maximum five days. Metoclopramide was the most used antiemetic in pregnancy at the time the warning was implemented in the Norwegian hyperemesis guidelines (2014). We aimed at describing changes in the treatment of hyperemesis over time, including changes associated with the EMA warning., Methods: Retrospective chart review of all women hospitalized for hyperemesis gravidarum with metabolic disturbances between 01/Jan/2002 and 31/Dec/2019 at a university hospital serving nearly 10% of the pregnant population in Norway. Time-series analysis described changes over time and interrupted time series analysis quantified changes in treatment and clinical outcomes related to the EMA warning., Results: In total, 1,064 women (1.2% of the birthing population) were included. The use of meclizine, prochlorperazine, and ondansetron increased during 2002-2019. This led to a yearly increase in the percentage of women using any antiemetic of 1.5% (95%CI 0.6; 2.4) pre-hospital, 0.6% (95%CI 0.2; 1.1) during hospitalization, and 2.6% (95%CI 1.3; 3.8) at discharge. Overall, only 50% of the women received antiemetics pre-hospital. Following the EMA warning, prehospital use of metoclopramide dropped by 30% (95%CI 25; 36), while use of any antiemetic pre-hospital dropped by 20% (95%CI 5.7; 34). In timely association, we observed a decrease in gestational age (-3.8 days, 98.75%CI 0.6; 7.1) at first admission, as well as indication of increased rate of termination of pregnancy with an absolute increase of 4.8% (98.75%CI 0.9; 8.7) in 2014., Conclusion: During 2002-2019, the overall use of antiemetics in treatment of hyperemesis increased. The EMA-warning on metoclopramide in 2013 temporarily limited pre-hospital antiemetic provision associated with hospitalization at lower gestational length and indication of an increase in termination of pregnancy., (© 2022. The Author(s).)

Background: Acute myocardial injury (AMJ), assessed by elevated levels of cardiac troponin, is associated with fatal outcome in coronavirus disease 2019 (COVID-19). However, the role of acute cardiovascular (CV) events defined by clinical manifestation rather than sole elevations of biomarkers is unclear in hospitalized COVID-19 patients., Objective: The aim of this study was to investigate acute clinically manifest CV events in hospitalized COVID-19 patients., Methods: From 1 March 2020 to 5 January 2021, we conducted a multicenter, prospective, epidemiological cohort study at six hospitals from Hamburg, Germany (a portion of the state-wide 45-center CORONA Germany cohort study) enrolling all hospitalized COVID-19 patients. Primary endpoint was occurrence of a clinically manifest CV-event., Results: In total, 132 CV-events occurred in 92 of 414 (22.2%) patients in the Hamburg-cohort: cardiogenic shock in 10 (2.4%), cardiopulmonary resuscitation in 12 (2.9%), acute coronary syndrome in 11 (2.7%), de-novo arrhythmia in 31 (7.5%), acute heart-failure in 43 (10.3%), myocarditis in 2 (0.5%), pulmonary-embolism in 11 (2.7%), thrombosis in 9 (2.2%) and stroke in 3 (0.7%). In the Hamburg-cohort, mortality was 46% (42/92) for patients with a CV-event and 33% (27/83) for patients with only AMJ without CV-event (OR 1.7, CI: (0.94-3.2), p = 0.077). Mortality was higher in patients with CV-events (Odds ratio(OR): 4.8, 95%-confidence-interval(CI): [2.9-8]). Age (OR 1.1, CI: (0.66-1.86)), atrial fibrillation (AF) on baseline-ECG (OR 3.4, CI: (1.74-6.8)), systolic blood-pressure (OR 0.7, CI: (0.53-0.96)), potassium (OR 1.3, CI: (0.99-1.73)) and C-reactive-protein (1.4, CI (1.04-1.76)) were associated with CV-events., Conclusion: Hospitalized COVID-19 patients with clinical manifestation of acute cardiovascular events show an almost five-fold increased mortality. In this regard, the emergence of arrhythmias is a major determinant.

Pharmacological treatment of attention deficit hyperactivity disorder (ADHD) is challenging due to a wide age span among patients, risk of reduced adherence, and comorbidities like psychiatric disorders and drug addiction. Drugs used for ADHD are associated with risk of interactions and adverse drug reactions due to their potent pharmacological effect. In this brief report we aimed to describe real-world problem areas concerning interactions in pharmacotherapy of ADHD. We reviewed questions to a Norwegian drug information center from physicians concerning drug-drug interactions involving ADHD drugs in the last 10-year period. Questions were retrieved by a combination of indexed and Boolean database searches, in addition to manual inspection. ADHD drugs and interacting drugs were defined according to the Anatomical Therapeutic Chemical (ATC) classification system. Interactions were classified by use of Stockley's Interactions Checker (SIC). Answers were examined with regard to whether the advice from the drug information center was more restrictive, similar or more liberal than SIC when assessing drug combinations. We retrieved 61 questions that included assessment of 96 drug combinations, and found 33 potential interactions according to SIC. Methylphenidate was involved in more than 50% of the interactions, and interacting drugs were in nearly 70% of the cases from ATC-group N (Nervous system) with antidepressants most frequently involved. Seventy percent of the interactions were pharmacodynamic, and interactions were frequently described as potentially severe although they were based on theoretical evidence. All the 33 interactions could be handled with monitoring or adjusting dose or with informative measures, and none was contraindicated according to SIC. More than 90% of the questions came from physicians in hospitals or outpatient specialist practice, and questions mainly concerned adults. In 75% of the drug combinations that involved ADHD drugs, we found similar advice from SIC and the drug information center. Our results suggest that future drug information efforts in ADHD treatment to clinicians, including specialists in the field, should focus on psychotropic interactions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Schjøtt, Heitmann, Bakkebø and Jahnsen.)

Aesthetic impairment is a crucial issue in Adolescent Idiopathic Scoliosis (AIS), but to date no objective measurements are available. The aim of the study is to evaluate the repeatability of 17 parameters measured by surface topography in a group of AIS subjects and verify their diagnostic validity. The paper is divided into three cross-sectional observational studies. We evaluated 17 selected surface topography parameters that could be good predictors of scoliosis' impact on the patients' trunk. We analysed short-term (30 seconds, 38 subjects) and medium-term (90 minutes, 14 subjects) repeatability of surface topography measures and their diagnostic validity in AIS (74 subjects, 33 AIS patients and 41 healthy subjects). All examined parameters were highly correlated as far as short and medium-term repeatability is concerned. We found a statistically significant difference between the scoliosis group and the control group in 3 surface rotation parameters, 1 shoulder parameter and 3 waist parameters. In conclusion, surface topography showed a good repeatability. Moreover, some of its parameters are correlated with AIS, enabling us to find differences between pathological and healthy subjects. Thanks to these findings, it will be possible to develop a tool that can objectively evaluate aesthetics is AIS patients., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

Purpose: Approximately 80% of pregnant women use medications. There is a need for evidence based medicines information that provide realistic risk estimates as pregnant and breastfeeding women tend to overestimate the risk of medications. The purpose of this paper is to describe the development and future perspectives of an innovative medicines information service aiming to increase empowerment among pregnant and breastfeeding women., Description: SafeMotherMedicine (SMM) (www.tryggmammamedisin.no) is a Norwegian medicines information service for pregnant and breastfeeding women. Established in 2011, the service was initially web-based only, in contrast to most teratology information services that at the time mainly operated using telephone and/or e-mail., Assessment: During the last eight years, SMM has provided close to 30,000 answers promoting appropriate medication use among pregnant and breastfeeding women. SMM launched a telephone-service in 2016, however, the annual number of questions received through the web-based service continues to increase., Conclusion: The service seems to have fulfilled a previously unmet need of evidence-based, individually tailored information about medications to pregnant and breastfeeding women in Norway. SMM empowers the women to make informed decisions regarding medication use in pregnancy and breastfeeding, thus contributing to person-centred medicine. The web-based design of the service may represent the pregnant and breastfeeding women's preferred way of communication.

Objective: Hyperemesis gravidarum (HG) affects 0.3-3% of pregnant women and is a leading cause of hospitalization in early pregnancy. The aim of the study was to investigate women's treatment and management of HG, as well as the consequences of HG on women's daily life., Design and Setting: A cross-sectional study based on a structured telephone interview and an online questionnaire. Participants were recruited by social media and by the Norwegian patient's organization for HG., Subjects: Norwegian women that experienced HG., Main Outcome Measure: Women's perspectives on management and consequences of HG., Results: The study included 107 women. Maternal morbidity was profound; about 3/4 of participants were hospitalized due to HG, and the majority showed clinical signs of dehydration (79%), ketonuria (75%), and >5% weight loss (84%). Antiemetics were used by >90% and frequently prescribed "as needed". Metoclopramide (71%) and meclozine (51%) were most commonly used. Participants described HG as having severe psychosocial consequences and profound impact on daily activities. Almost two out of five reported thoughts of elective abortion, and 8 women had at least one elective pregnancy termination due to HG. Overall, 20 women (19%) changed GPs due to dissatisfaction with HG management., Conclusion: Despite the high psychosocial burden and major impact on daily activities, many women with HG reported a lack of support from healthcare professionals and suboptimal management. Greater awareness and knowledge among healthcare professionals is needed to improve care for women with HG. Key Points There is a paucity of studies on management and the consequences of HG on women's daily lives and psychosocial burden. We found that: • Many women described HG as one of their worst life experiences with profound morbidity. • Many women reported suboptimal management of HG and lack of support from healthcare professionals. • Greater understanding of patient perspectives among healthcare professionals is important to improve care and management for HG patients.

Background: Though nausea and vomiting is very common during pregnancy, no studies have investigated the impact of this condition on the women's daily lives in a Scandinavian population. The aim of this study was to describe the burden of nausea and vomiting during pregnancy (NVP) on global quality of life, daily life functioning and willingness to become pregnant again according to the severity of NVP symptoms., Methods: This study is a cross-sectional population-based study conducted in Norway. Pregnant women and mothers with children <1 year of age with current or prior NVP were eligible to participate. Data were collected through an anonymous on-line questionnaire accessible from November 10 th , 2014 to January 31 st , 2015. Severity of NVP was measured using the 24-h Pregnancy Unique Quantification of Emesis Scale (PUQE). Associations between severity of NVP, daily life functioning and willingness to become pregnant again were tested using chi-square tests. Associations with global quality of life measured in terms of the Quality of Life Scale (QOLS) were estimated using generalized linear models and reported as unstandardized regression coefficients (β) with 95% confidence intervals (CI)., Results: 712 women with NVP were included in the study. NVP was significantly associated with several characteristics, including daily life functioning, quality of life and willingness to become pregnant again. The negative impact was greater the more severe the symptoms were, although considerable adverse effects were also seen among women with mild and moderate NVP symptoms. Over one fourth of the women with severe NVP considered terminating the pregnancy due to NVP, and three in four considered not to get pregnant again. Severity of NVP remained significantly associated with reduced global quality of life when adjusting for maternal characteristics and illnesses with β (95% CI) = -10.9 (-16.9, -4.9) for severe versus mild NVP., Conclusions: NVP as measured by PUQE had a major impact on various aspects of the women's lives, including global quality of life and willingness to become pregnant again.

Objectives: To describe, compare and evaluate whether pharmacists in two European countries, Serbia and Norway, give appropriate counselling for common ailments in pregnancy., Design: A cross sectional, web-based study., Participants and Settings: A study was conducted among Serbian and Norwegian pharmacists during two four-month study periods in 2012 respectively 2014. Participants were recruited through postal and electronic invitation facilitated by several pharmacy chains. Participation in the study was anonymous and voluntary., Measurement Instrument: Pharmacists were presented with the questionnaire that included five scenarios (back pain, heavy legs, nausea, cold and constipation in pregnancy) and were asked to give their advice about use of medicines, supplements (e.g. herbal products, vitamins, minerals), non-pharmacological treatment and referral to physician in each condition., Findings: In total, 276 pharmacists, 119 in Serbia and 157 in Norway, accepted to participate in the study. Recommendation about medicines use ranged from 32% (heavy legs) to 71% (back pain) in Serbia and from 3% (heavy legs) to 92% (constipation) in Norway. Several pharmacists' recommendations on medicines and supplements use were inappropriate. Recommendation about non-pharmacological treatments ranged from 11% (nausea) to 50% (heavy legs) in Serbia and from 12% (constipation) to 63% (cold) in Norway. Approximately 12% of the Norwegian and Serbian pharmacists offered referral to a physician as only advice for nausea in pregnancy, indicating a lack of confidence in or knowledge about this common ailment in pregnancy., Key Conclusions and Implications for Practice: Large differences in counselling of pregnant women by pharmacists in Serbia and Norway were observed. Enhancement of pharmacists' knowledge about treatment of common ailments in pregnancy is needed and will enhance pharmacists' role in improving maternal health., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Previous studies have shown that echinacea is among the most widely used herbal medicines during pregnancy in Western countries. Despite its frequent use, we know little about the safety of this herbal medicine during pregnancy. The primary aim of this study was to study the consequences of the use of echinacea on malformations and common adverse pregnancy outcomes. Secondly, we aimed to characterize women using this herb in pregnancy., Method: This study is based on the Norwegian Mother and Child Cohort Study (MoBa) and included 68,522 women and their children. Information was retrieved from three self-administered questionnaires completed by the women in pregnancy weeks 17 and 30 and 6 months after birth. Information on pregnancy outcomes was retrieved from the Medical Birth Registry of Norway. Generalized estimating equations analyses were performed to assess the association between exposure to echinacea and pregnancy outcomes. Pearson's chi-square test was used to assess factors related to use of echinacea in pregnancy., Results: Among 68,522 women, 363 (0.5 %) reported the use of echinacea during pregnancy. These women were characterized by high age and delivery before 2002 and were to a less extent smoking in pregnancy. The use of echinacea was not associated with an increased risk of malformations or adverse pregnancy outcomes., Conclusion: This study revealed no increased risk of malformations or adverse pregnancy outcomes after the use of echinacea in pregnancy. Studies on the safety of commonly used herbal medications are important to identify herbals that should be avoided in pregnancy.

Purpose: The purposes of this study were to investigate the treatments used for nausea and vomiting of pregnancy (NVP) according to NVP severity among Norwegian women and to assess whether maternal characteristics and attitudes were related to the use of pharmacological treatment of NVP., Methods: This is a cross-sectional Web-based study. Pregnant women and mothers with children ≤1 year of age were eligible to participate. Data were collected through an anonymous online questionnaire accessible from November 10th, 2014 to January 31st, 2015., Results: In total, 712 women were included in the study, of which 62 (8.7 %), 439 (61.7 %) and 210 (29.5 %) had mild, moderate and severe NVP, respectively, according to the Pregnancy-Unique Quantification of Emesis (PUQE) classification. A total of 277 (38.9 %) women had used one or more antiemetics, of which meclizine, closely followed by metoclopramide, was the most commonly used. Different drug utilisation patterns were found between the groups of women with mild, moderate and severe NVP. Many with moderate or severe symptoms did not use any pharmacological treatment (70.2 and 32.9 %, respectively). Sick leave was given without initiating medical treatment in 266 (62.1 %) women. The women's beliefs about medicines had an important impact on their use of medicines for NVP., Conclusions: A large proportion of women suffered from moderate to severe symptoms of NVP, many of whom did not receive any pharmacological treatment. Many women, who had been on sick leave due to NVP, were not prescribed medicines.

Objective: Nausea and vomiting during pregnancy (NVP) is very common, and may have great impact on a woman's life. The aim of this study was to explore thoughts and attitudes among Norwegian pregnant women and GPs on treatment of NVP and pregnancy care., Design: Focus-group study., Setting and Subjects: Separate focus-group discussions were conducted with pregnant women and GPs., Results: Two focus-group discussions were conducted with pregnant women and two with GPs. The GPs thought it was important to normalize NVP symptoms. However, the women felt their distress due to NVP was trivialized by the GPs. The women were sceptical towards the use of medicines while pregnant, and avoidance was sought despite being ill. The GPs appeared uncertain with respect to medical treatment of NVP, which was stated to be considered only after progression to quite severe symptoms. Sick leave seemed to be an important part of the treatment regime applied by the GPs. The women had good experiences with graded sick leave., Conclusion: This Norwegian study identifies attitudes among GPs and pregnant women that may act as obstacles to appropriate care for women with NVP. The pregnant women and the GPs seemed to talk at cross-purposes; GPs' normalization of the symptoms made the women feel that their distress due to NVP was trivialized by the GPs. Our results indicate that pregnant women with NVP requiring medical treatment probably need comprehensive and reassuring information about treatment options before considering using any medicines., Key Points: Nausea and vomiting during pregnancy (NVP) is very common, and considered to be of clinical significance for 35% of women. While the GPs agreed on the importance of normalizing the symptoms, the women felt their distress was trivialized, and missed being properly evaluated. Both the GPs and the women showed a reluctant attitude to medical treatment of NVP. The GPs gave the impression of considering medical treatment only after progression of symptoms to becoming quite severe.

Background: The factors related to the treatment of nausea during pregnancy have not yet been investigated in several countries simultaneously. The present study aimed to describe differences in self-reported nausea during pregnancy and the patterns of use for both conventional and herbal medicines across countries. The factors related to nausea and its treatment and the relationships between different self-reported co-morbidities and nausea were also investigated., Methods: This cross-sectional study used data collected by a web-based questionnaire distributed between October 2011 and February 2012 in several countries within five regions: Western, Northern, and Eastern Europe, North America, and Australia. Women who were pregnant or had a child less than one year old were eligible to participate., Results: A total of 9113 women were included in the study, whereof 6701 (73.5%) had experienced nausea during pregnancy. Among respondents with nausea, conventional medicines were used by 1201 (17.9%) women and herbal medicines by 556 (8.3%) women. The extent of self-reported nausea and its treatment varied by country. Education, working status, and folic acid use were significantly associated with the use of conventional medicines against nausea. Respondents who had nausea also had a high burden of co-morbidity., Conclusion: The prevalence of nausea was high across all participating countries but its treatment varied, possibly due to cultural differences and differences in attitudes towards medicines. A high degree of co-morbidity was found among respondents with nausea.

Histone deacetylase (HDAC) inhibitors (HDACis) are well-characterized anti-cancer agents with promising results in clinical trials. However, mechanistically little is known regarding their selectivity in killing malignant cells while sparing normal cells. Gene expression-based chemical genomics identified HDACis as being particularly potent against Down syndrome-associated myeloid leukemia (DS-AMKL) blasts. Investigating the antileukemic function of HDACis revealed their transcriptional and post-translational regulation of key autophagic proteins, including ATG7. This leads to suppression of autophagy, a lysosomal degradation process that can protect cells against damaged or unnecessary organelles and protein aggregates. DS-AMKL cells exhibit low baseline autophagy due to mammalian target of rapamycin (mTOR) activation. Consequently, HDAC inhibition repressed autophagy below a critical threshold, which resulted in accumulation of mitochondria, production of reactive oxygen species, DNA damage and apoptosis. Those HDACi-mediated effects could be reverted upon autophagy activation or aggravated upon further pharmacological or genetic inhibition. Our findings were further extended to other major acute myeloid leukemia subgroups with low basal level autophagy. The constitutive suppression of autophagy due to mTOR activation represents an inherent difference between cancer and normal cells. Thus, via autophagy suppression, HDACis deprive cells of an essential pro-survival mechanism, which translates into an attractive strategy to specifically target cancer cells.

Background: Cranberry is one of the most commonly used herbs during pregnancy. The herb has been used traditionally against urinary tract infections. No studies are found that specifically address the risk of malformations after use of cranberry during pregnancy. The aim of the study was to investigate the safety of cranberry use during pregnancy, including any effects on congenital malformations and selected pregnancy outcomes., Methods: The study is based on data from The Norwegian Mother and Child Cohort Study including more than 100,000 pregnancies from 1999 to 2008. Information on use of cranberry and socio-demographic factors was retrieved from three self-administered questionnaires completed by the women in pregnancy weeks 17 and 30, and 6 months after birth. Information on pregnancy outcomes was retrieved from the Medical Birth Registry of Norway., Results: Among the 68,522 women in the study, 919 (1.3%) women had used cranberry while pregnant. We did not detect any increased risk of congenital malformations after use of cranberry. Furthermore, the use of cranberry was also not associated with increased risk for stillbirth/neonatal death, low birth weight, small for gestational age, preterm birth, low Apgar score (<7), neonatal infections or maternal vaginal bleeding in early pregnancy. Although an association was found between use of cranberry in late pregnancy and vaginal bleeding after pregnancy week 17, further sub-analyses of more severe bleeding outcomes did not support a significant risk., Conclusions: The findings of this study, revealing no increased risk of malformations nor any of the following pregnancy outcomes; stillbirth/neonatal death, preterm delivery, low birth weight, small for gestational age, low Apgar score and neonatal infections are reassuring. However, maternal vaginal bleeding should be investigated further before any firm conclusion can be drawn. Treatment guidelines on asymptomatic bacteriuria in pregnancy recommend antimicrobial therapy as the first line treatment. According to our data and the outcomes studied, cranberry does not appear to be a harmful adjunctive self-treatment.

Purpose: The objective of the study was to examine the safety of ginger use during pregnancy on congenital malformations and selected pregnancy outcomes., Methods: The Norwegian Mother and Child Cohort study, a large population-based cohort, provided the data used in this study. Our study population consisted of 68,522 women. Data on ginger use and socio-demographic factors were retrieved from three self-administered questionnaires completed by the women during weeks 17 and 30 of the pregnancy and when their child was 6 months old. Data on pregnancy outcomes were provided by the Medical Birth Registry of Norway., Results: Among the 68,522 women in the study, 1,020 (1.5 %) women reported using ginger during pregnancy. The use of ginger during pregnancy was not associated with any increased risk of congenital malformations. No increased risk for stillbirth/perinatal death, preterm birth, low birth weight, or low Apgar score was detected for the women exposed to ginger during pregnancy compared to women who had not been exposed., Conclusion: Use of ginger during pregnancy does not seem to increase the risk of congenital malformations, stillbirth/perinatal death, preterm birth, low birth weight, or low Apgar score. This finding is clinically important for health care professionals giving advice to pregnant women with NPV.