Interactive exploration of population scale pharmacoepidemiology datasets

Population-scale drug prescription data linked with adverse drug reaction (ADR) data supports the fitting of models large enough to detect drug use and ADR patterns that are not detectable using traditional methods on smaller datasets. However, detecting ADR patterns in large datasets requires tools for scalable data processing, machine learning for data analysis, and interactive visualization. To our knowledge no existing pharmacoepidemiology tool supports all three requirements. We have therefore created a tool for interactive exploration of patterns in prescription datasets with millions of samples. We use Spark to preprocess the data for machine learning and for analyses using SQL queries. We have implemented models in Keras and the scikit-learn framework. The model results are visualized and interpreted using live Python coding in Jupyter. We apply our tool to explore a 384 million prescription data set from the Norwegian Prescription Database combined with a 62 million prescriptions for elders that were hospitalized. We preprocess the data in two minutes, train models in seconds, and plot the results in milliseconds. Our results show the power of combining computational power, short computation times, and ease of use for analysis of population scale pharmacoepidemiology datasets. The code is open source and available at: https://github.com/uit-hdl/norpd_prescription_analyse

Current Global Health Impact Assessment Practice

Health impact assessment (HIA) practice has expanded across the world, since it was established more than two decades ago. This paper presents a snapshot of current global HIA practice based on the findings of an online questionnaire survey. HIA practitioners from all world regions were invited to participate. A total of 122 HIA practitioners from 29 countries completed the survey, following a broad international outreach effort. The large variety in the types of HIAs conducted, and the application of HIA in various fields reported by respondents, demonstrates that HIA practice has evolved over the past two decades. Although differences in the use of HIA were reported across world regions, an overall increasing trend in global HIA practice can be observed. In order to sustain this upward trend, efforts are needed to address the main barriers in the utilisation of HIA. The establishment of new national and international HIA teaching and training offerings seems to be an obvious strategy to pursue along with the strengthening of policies and legal frameworks that specify the circumstances, under which HIA is required, and to what extent

The important role of sponges in carbon and nitrogen cycling in a deep-sea biological hotspot

Deep-sea sponge grounds are hotspots of biodiversity, harbouring thriving ecosystems in the otherwise barren deep sea. It remains unknown how these sponge grounds survive in this food-limited environment. Here, we unravel how sponges and their associated fauna sustain themselves by identifying their food sources and food-web interactions using bulk and compound-specific stable isotope analysis of amino and fatty acids. We found that sponges with a high microbial abundance had an isotopic composition resembling organisms at the base of the food web, suggesting that they are able to use dissolved resources that are generally inaccessible to animals. In contrast, low microbial abundance sponges had a bulk isotopic composition that resembles a predator at the top of a food web, which appears to be the result of very efficient recycling pathways that are so far unknown. The compound-specific-isotope analysis, however, positioned low-microbial abundance sponges with other filter-feeding fauna. Furthermore, fatty-acid analysis confirmed transfer of sponge-derived organic material to the otherwise food-limited associated fauna. Through this subsidy, sponges are key to the sustenance of thriving deep-sea ecosystems and might have, due to their ubiquitous abundance, a global impact on biogeochemical cycles.publishedVersio

Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design

OBJECTIVETo assess whether use of specific selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in early pregnancy is associated with an increased risk of birth defects, with emphasis on cardiovascular birth defects even when accounting for lifestyle or other familial confounding.DESIGNMulticountry population based cohort study, including sibling controlled design.SETTINGNordic population (Denmark, Finland, Iceland, Norway, and Sweden) identified from nationwide health registers at different periods in 1996-2010.POPULATIONThe full study cohort included women giving birth to 2.3 million live singletons. The sibling cohort included 2288 singleton live births. The sibling controlled analyses included sibling pairs who were discordant for exposure to SSRIs or venlafaxine and birth defects.MAIN OUTCOME MEASUREPrevalence of birth defects, including subtypes of cardiac defects. Odds ratio of birth defects from logistic and conditional logistic regression.RESULTSAmong 36 772 infants exposed to any SSRI in early pregnancy, 3.7% (n=1357) had a birth defect compared with 3.1% of 2 266 875 unexposed infants, yielding a covariate adjusted odds ratio of 1.13 (95% confidence interval 1.06 to 1.20). In the sibling controlled analysis the adjusted odds ratio decreased to 1.06 (0.91 to 1.24). The odds ratios for any cardiac birth defect with use of any SSRI or venlafaxine were 1.15 (95% confidence interval 1.05 to 1.26) in the covariate adjusted analysis and 0.92 (0.72 to 1.17) in the sibling controlled analysis. For atrial and ventricular septal defects the covariate adjusted odds ratio was 1.17 (1.05 to 1.31). Exposure to any SSRI or venlafaxine increased the prevalence of right ventricular outflow tract obstruction defects, with a covariate adjusted odds ratio of 1.48 (1.15 to 1.89). In the sibling controlled analysis the adjusted odds ratio decreased to 0.56 (0.21 to 1.49) for any exposure to SSRIs or venlafaxine and right ventricular outflow tract obstruction defects.CONCLUSIONSIn this large Nordic study no substantial increase was found in prevalence of overall cardiac birth defects among infants exposed to SSRIs or venlafaxine in utero. Although the prevalence of septal defects and right ventricular outflow tract defects was higher in exposed infants, the lack of an association in the sibling controlled analyses points against a teratogenic effect of these drugs.</p

Targeted elimination of species-rich larval habitats can rapidly collapse arbovirus vector mosquito populations at hotel compounds in Zanzibar

Understanding the dynamics of larval habitat utilization by mosquito communities is crucial for the design of efficient environmental control strategies. The authors investigated the structure of mosquito communities found at hotel compounds in Zanzibar, networks of mosquito interactions with larval habitats and robustness of mosquito communities to elimination of larval habitats. A total of 23 698 mosquitoes comprising 26 species in six genera were found. Aedes aegypti (n = 16 207), Aedes bromeliae/Aedes lillie (n = 1340), Culex quinquefasciatus (n = 1300) and Eretmapodites quinquevitattus (n = 659) were the most dominant species. Ecological network analyses revealed the presence of dominant, larval habitat generalist species (e.g., A. aegypti), exploiting virtually all types of water holding containers and few larval habitat specialist species (e.g., Aedes natalensis, Orthopodomyia spp). Simulations of mosquito community robustness to systematic elimination of larval habitats indicate that mosquito populations are highly sensitive to elimination of larval habitats sustaining higher mosquito species diversity. This study provides insights on potential foci of future mosquito-borne arboviral disease outbreaks in Zanzibar and underscores the need for detailed knowledge on the ecological function of larval habitats for effective mosquito control by larval sources management.Danida Fellowship Centrehttp://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-2915am2022Zoology and Entomolog

Anti-asthma medication prescribing to children in the Lombardy Region of Italy: chronic versus new users

<p>Abstract</p> <p>Background</p> <p>Although anti-asthma medications are amongst those most frequently under or over prescribed it is generally accepted that prescriptions for such agents can be used as a proxy for disease prevalence. The aims of this study were to estimate prevalence and incidence of childhood asthma in a representative Italian area by analysing three years of anti-asthmatic prescriptions and hospitalizations of subjects with chronic or first time treatment, and to underline appropriateness of therapeutic choices.</p> <p>Methods</p> <p>The analysis involved prescriptions given to 6-17 year olds between 2003 and 2005 in Italy's Lombardy Region. The youths were classified as potential asthmatics, based on the different degree of drug utilization: occasional, low or high users, and grouped as 'new onset' or 'chronic' cases based on the duration of therapy dispensed. The analysis of prescriptions and hospitalization rate of these groups provided an estimate of the 2005 asthma prevalence and incidence and allowed an estimation of the level of appropriateness of treatments.</p> <p>Results</p> <p>During 2005, the estimated incidence of potential asthmatics was 0.8% and the estimated prevalence was 3.5%. When viewed retrospectively for two years, records showed that 47% of potential asthmatics received prescriptions also during 2004 and 30% also during 2003. During the three years considered, 7.5%, 2.8%, and 1.5% of high, low, and occasional users, respectively, were hospitalized for asthma. The most important inappropriateness found was the prescription of long acting beta adrenergics as first time treatment.</p> <p>Conclusions</p> <p>This study allowed a proxy of asthma incidence, prevalence, and severity. The analyses highlighted a low compliance with the guidelines, suggesting that educational interventions are needed to obtain a more rational management of childhood asthma, especially in subjects starting therapy.</p

Co-prescription of medication for bipolar disorder and diabetes mellitus : a nationwide population based study with focus on gender differences

BackgroundStudies have shown a correlation between bipolar disorder and diabetes mellitus. It is unclear if this correlation is a part of common pathophysiological pathways, or if medication for bipolar disorder has negative effects on blood sugar regulation.MethodsThe Norwegian prescription database was analyzed. Prescriptions for lithium, lamotrigine, carbamazepine and valproate were used as proxies for bipolar disorder. Prescriptions for insulin and oral anti-diabetic agents were used as proxies for diabetes mellitus. We explored the association between medication for bipolar disorder and diabetes medication by logistic regressionResultsWe found a strong association between concomitant use of medication to treat diabetes mellitus and mood stabilizers for the treatment of bipolar disorder. Females had a 30% higher risk compared to men of being treated for both disorders. Persons using oral anti-diabetic agents had higher odds of receiving valproate than either lithium or lamotrigine. Use of insulin as monotherapy seemed to have lower odds than oral anti-diabetic agents of co-prescription of mood stabilizers, compared to the general population.ConclusionsThis study showed a strong association between the use of mood stabilizers and anti-diabetic agents. The association was stronger among women than men

Does present use of cardiovascular medication reflect elevated cardiovascular risk scores estimated ten years ago? A population based longitudinal observational study

Background It is desirable that those at highest risk of cardiovascular disease should have priority for preventive measures, eg. treatment with prescription drugs to modify their risk. We wanted to investigate to what extent present use of cardiovascular medication (CVM) correlates with cardiovascular risk estimated by three different risk scores (Framingham, SCORE and NORRISK) ten years ago. Methods Prospective logitudinal observational study of 20 252 participants in The Hordaland Health Study born 1950-57, not using CVM in 1997-99. Prescription data obtained from The Norwegian Prescription Database in 2008. Results 26% of men and 22% of women aged 51-58 years had started to use some CVM during the previous decade. As a group, persons using CVM scored significantly higher on the risk algorithms Framingham, SCORE and NORRISK compared to those not treated. 16-20% of men and 20-22% of women with risk scores below the high-risk thresholds for the three risk scores were treated with CVM, while 60-65% of men and 25-45% of women with scores above the high-risk thresholds received no treatment. Among women using CVM, only 2.2% (NORRISK), 4.4% (SCORE) and 14.5% (Framingham) had risk scores above the high-risk values. Low education, poor self-reported general health, muscular pains, mental distress (in females only) and a family history of premature cardiovascular disease correlated with use of CVM. Elevated blood pressure was the single factor most strongly predictive of CVM treatment. Conclusion Prescription of CVM to middle-aged individuals by large seems to occur independently of estimated total cardiovascular risk, and this applies especially to females

Publisher Correction: Biodiversity, environmental drivers, and sustainability of the global deep-sea sponge microbiome

The original version of the Description of Additional Supplementary Files associated with this Article contained errors in the legends of Supplementary Data 5–8 and omitted legends for the Source Data. The HTML has been updated to include a corrected version of the Description of Additional Supplementary Files; the original incorrect version of this file can be found as Supplementary Information associated with this Correction

Antipsychotic drug use in pregnancy: A multinational study from ten countries

Aim: To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents. Methods: Individually linked health data in Denmark (2000−2012), Finland (2005–2014), Iceland (2004–2017), Norway (2005–2015), Sweden (2006–2015), Germany (2006–2015), Australia (New South Wales, 2004–2012), Hong Kong (2001–2015), UK (2006–2016), and the US (Medicaid, 2000–2013, and IBM MarketScan, 2012–2015) were used. Using a uniformed approach, we estimated the prevalence of antipsychotic use as the proportion of pregnancies where a woman filled at least one antipsychotic prescription within three months before pregnancy until birth. For the Nordic countries, data were meta-analyzed to investigate maternal characteristics associated with the use of antipsychotics. Results: We included 8,394,343 pregnancies. Typical antipsychotic use was highest in the UK (4.4%) whereas atypical antipsychotic use was highest in the US Medicaid (1.5%). Atypical antipsychotic use increased over time in most populations, reaching 2% in Australia (2012) and US Medicaid (2013). In most countries, prochlorperazine was the most commonly used typical antipsychotic and quetiapine the most commonly used atypical antipsychotic. Use of antipsychotics decreased across the trimesters of pregnancy in all populations except Finland. Antipsychotic use was elevated among smokers and those with parity ≥4 in the Nordic countries. Conclusion: Antipsychotic use during pregnancy varied considerably between populations, partly explained by varying use of the typical antipsychotic prochlorperazine, which is often used for nausea and vomiting in early pregnancy. Increasing usage of atypical antipsychotics among pregnant women reflects the pattern that was previously reported for the general population