Ability to detect potentially inappropriate prescribing in older patients: comparative analysis between PIM-Check and STOPP/STARTv2.

Potentially inappropriate prescribing (PIP) is a source of preventable adverse drug events. The objective of this study was a comparative analysis (quantitative and qualitative) between two tools used to detect PIP, PIM-Check and STOPP/START. First, a qualitative analysis (QAC) was conducted to evaluate the concordance between the criteria, which constitute PIM-Check and the gold standard STOPP/START. Second, a retrospective comparative and observational study was performed on the list of treatment at the admission of 50 older patients hospitalized in an acute geriatric ward of a university hospital in Switzerland in 2016 using both tools. The QAC has shown that 50% (57 criteria) of STOPP/START criteria are fully or partially concordant with those of PIM-Check. The retrospective study was performed on 50 patients aged 87 years, suffering from 5 co-morbidities (min-max 1-11) and treated by of 8 drugs (min-max 2-16), as medians. The prevalence of the detected PIP was 80% by PIM-Check and 90% by STOPP/START. Medication review shows that 4.2 PIP per patient were detected by PIM-Check and 3.5 PIP by STOPP/START among which 1.9 PIP was commonly detected by both tools, as means. PIM-Check detected more PIP related to cardiology, angiology, nephrology, and endocrinology in older patients but missed the PIP related to geriatric syndromes (e.g., fall, dementia, Alzheimer) detected by STOPP/START. By using PIM-Check in geriatric settings, some PIP will not be detected. It is considered as a limitation for this tool in this frail population but brings a certain complementarity in other areas of therapy not covered by STOPP/START

Utility of an Algorithm to Increase the Accuracy of Medication History in an Obstetrical Setting.

BACKGROUND: In an obstetrical setting, inaccurate medication histories at hospital admission may result in failure to identify potentially harmful treatments for patients and/or their fetus(es). METHODS: This prospective study was conducted to assess average concordance rates between (1) a medication list obtained with a one-page structured medication history algorithm developed for the obstetrical setting and (2) the medication list reported in medical records and obtained by open-ended questions based on standard procedures. Both lists were converted into concordance rate using a best possible medication history approach as the reference (information obtained by patients, prescribers and community pharmacists' interviews). RESULTS: The algorithm-based method obtained a higher average concordance rate than the standard method, with respectively 90.2% [CI95% 85.8-94.3] versus 24.6% [CI95%15.3-34.4] concordance rates (p<0.01). CONCLUSION: Our algorithm-based method strongly enhanced the accuracy of the medication history in our obstetric population, without using substantial resources. Its implementation is an effective first step to the medication reconciliation process, which has been recognized as a very important component of patients' drug safety

Major malformations risk following early pregnancy exposure to metformin: a systematic review and meta-analysis.

Metformin is considered as first-line treatment for type 2 diabetes and an effective treatment for polycystic ovary syndrome (PCOS). However, evidence regarding its safety in pregnancy is limited. We conducted a systematic review and meta-analysis of major congenital malformations (MCMs) risk after first-trimester exposure to metformin in women with PCOS and pregestational diabetes mellitus (PGDM). Randomized controlled trials (RCTs) and observational cohort studies with a control group investigating risk of MCM after first-trimester pregnancy exposure to metformin were searched until December 2021. ORs and 95% CIs were calculated separately according to indications and study type using Mantel-Haenszel method; outcome data were combined using random-effects model. Eleven studies (two RCTs; nine observational cohorts) met the inclusion criteria: four included pregnant women with PCOS, four included those with PGDM and three evaluated both indications separately and were considered in both indication groups. In PCOS group, there were two RCTs (57 exposed, 52 control infants) and five observational studies (472 exposed, 1892 control infants); point estimates for MCM rates in RCTs and observational studies were OR 0.93 (95% CI 0.09 to 9.21) (I2=0%; Q test=0.31; p value=0.58) and OR 1.35 (95% CI 0.37 to 4.90) (I2=65%; Q test=9.43; p value=0.05), respectively. In PGDM group, all seven studies were observational (1122 exposed, 1851 control infants); the point estimate for MCM rates was OR 1.05 (95% CI 0.50 to 2.18) (I2=59%; Q test=16.34; p value=0.01). Metformin use in first-trimester pregnancy in women with PCOS or PGDM do not meaningfully increase the MCM risk overall. However, further studies are needed to characterize residual safety concerns

Medication use in pregnancy: a cross-sectional, multinational web-based study

Objectives: Intercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. his study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use. Design: Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire. Setting: Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia. Participants: Pregnant women and new mothers with children less than 1 year of age. Primary and secondary outcome measures: Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use. Results: The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of ute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than nonimmigrants. Conclusions: In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used

COVID-19-related medicine utilization study in pregnancy: The COVI-PREG cohort

AIM The objective of this study was to describe the use of COVID-19-related medicines during pregnancy and their evolution between the early/late periods of the pandemic. METHODS Pregnant women who tested positive for SARS-CoV-2 from March 2020 to July 2021 were included using the COVI-PREG registry. Exposure to the following COVID-19-related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti-interleukin-6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID-19 severity level and early/late period of the pandemic (before and after 1 July 2020). FINDINGS We included 1964 pregnant patients who tested positive for SARS-CoV-2. Overall, 10.4% (205/1964) received at least one COVID-19-related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti-interleukin-6 (0.3%; 5/1964). The use of at least one COVID-19-related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID-19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period. CONCLUSION Medicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID-19-related medicines in pregnancy

Quantitative Mass Spectrometry Analysis Using PAcIFIC for the Identification of Plasma Diagnostic Biomarkers for Abdominal Aortic Aneurysm

BACKGROUND: Abdominal aortic aneurysm (AAA) is characterized by increased aortic vessel wall diameter (>1.5 times normal) and loss of parallelism. This disease is responsible for 1-4% mortality occurring on rupture in males older than 65 years. Due to its asymptomatic nature, proteomic techniques were used to search for diagnostic biomarkers that might allow surgical intervention under nonlife threatening conditions. METHODOLOGY/PRINCIPAL FINDINGS: Pooled human plasma samples of 17 AAA and 17 control patients were depleted of the most abundant proteins and compared using a data-independent shotgun proteomic strategy, Precursor Acquisition Independent From Ion Count (PAcIFIC), combined with spectral counting and isobaric tandem mass tags. Both quantitative methods collectively identified 80 proteins as statistically differentially abundant between AAA and control patients. Among differentially abundant proteins, a subgroup of 19 was selected according to Gene Ontology classification and implication in AAA for verification by Western blot (WB) in the same 34 individual plasma samples that comprised the pools. From the 19 proteins, 12 were detected by WB. Five of them were verified to be differentially up-regulated in individual plasma of AAA patients: adiponectin, extracellular superoxide dismutase, protein AMBP, kallistatin and carboxypeptidase B2. CONCLUSIONS/SIGNIFICANCE: Plasma depletion of high abundance proteins combined with quantitative PAcIFIC analysis offered an efficient and sensitive tool for the screening of new potential biomarkers of AAA. However, WB analysis to verify the 19 PAcIFIC identified proteins of interest proved inconclusive save for five proteins. We discuss these five in terms of their potential relevance as biological markers for use in AAA screening of population at risk

Genetic dissection of early endosomal recycling highlights a TORC1-independent role for Rag GTPases

Endocytosed cell surface membrane proteins rely on recycling pathways for their return to the plasma membrane. Although endosome-to-plasma membrane recycling is critical for many cellular processes, much of the required machinery is unknown. We discovered that yeast has a recycling route from endosomes to the cell surface that functions efficiently after inactivation of the sec7-1 allele of Sec7, which controls transit through the Golgi. A genetic screen based on an engineered synthetic reporter that exclusively follows this pathway revealed that recycling was subject to metabolic control through the Rag GTPases Gtr1 and Gtr2, which work downstream of the exchange factor Vam6. Gtr1 and Gtr2 control the recycling pathway independently of TORC1 regulation through the Gtr1 interactor Ltv1. We further show that the early-endosome recycling route and its control though the Vam6 > Gtr1/Gtr2 > Ltv1 pathway plays a physiological role in regulating the abundance of amino acid transporters at the cell surface

Improving Data Collection in Pregnancy Safety Studies: Towards Standardisation of Data Elements in Pregnancy Reports from Public and Private Partners, A Contribution from the ConcePTION Project

\ua9 2023, The Author(s).Introduction and Objective: The ConcePTION project aims to improve the way medication use during pregnancy is studied. This includes exploring the possibility of developing a distributed data processing and analysis infrastructure using a common data model that could form a foundational platform for future surveillance and research. A prerequisite would be that data from various data access providers (DAPs) can be harmonised according to an agreed set of standard rules concerning the structure and content of the data. To do so, a reference framework of core data elements (CDEs) recommended for primary data studies on drug safety during pregnancy was previously developed. The aim of this study was to assess the ability of several public and private DAPs using different primary data sources focusing on multiple sclerosis, as a pilot, to map their respective data variables and definitions with the CDE recommendations framework. Methods: Four pregnancy registries (Gilenya, Novartis; Aubagio, Sanofi; the Organization of Teratology Information Specialists [OTIS]; Aubagio, Sanofi; the Dutch Pregnancy Drug Register, Lareb), two enhanced pharmacovigilance programmes (Gilenya PRIM, Novartis; MAPLE-MS, Merck Healthcare KGaA) and four Teratology Information Services (UK TIS, Jerusalem TIS, Zerifin TIS, Swiss TIS) participated in the study. The ConcePTION primary data source CDE includes 51 items covering administrative functions, the description of pregnancy, maternal medical history, maternal illnesses arising in pregnancy, delivery details, and pregnancy and infant outcomes. For each variable in the CDE, the DAPs identified whether their variables were: identical to the one mentioned in the CDE; derived; similar but with a divergent definition; or not available. Results: The majority of the DAP data variables were either directly taken (85%, n = 305/357, range 73–94% between DAPs) or derived by combining different variables (12%, n = 42/357, range 0–24% between DAPs) to conform to the CDE variables and definitions. For very few of the DAP variables, alignment with the CDE items was not possible, either because of divergent definitions (1%, n = 3/357, range 0–2% between DAPs) or because the variables were not available (2%, n = 7/357, range 0–4% between DAPs). Conclusions: Data access providers participating in this study presented a very high proportion of variables matching the CDE items, indicating that alignment of definitions and harmonisation of data analysis by different stakeholders to accelerate and strengthen pregnancy pharmacovigilance safety data analyses could be feasible

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

The socio-demographic patterning of sexual risk behaviour: a survey of young men in Finland and Estonia

<p>Abstract</p> <p>Background</p> <p>Sexually transmitted infections (STIs) among the youth are an increasing challenge for public health in Europe. This study provided estimates of men's (18–25 years) sexual risk behaviour and self-reported STIs and their socio-demographic patterning in Finland and Estonia; two countries that are geographically close, but have very different STI epidemics.</p> <p>Method</p> <p>Nationally representative cross-sectional population surveys with comparable survey questions were used. Data from self-administered questionnaires for 1765 men aged 18–25 years in Finland (85% of the age cohort was included in the sampling frame, 95% of the sample responded) and 748 in Estonia, with a response rate of 43% respectively, were analysed. Socio-demographic patterning of multiple partners, condom use and self-reported STIs are presented was studied using multiple logistic regression analysis.</p> <p>Results</p> <p>The main findings focus on associations found within each country. In Finland, higher age, low education and to a lesser extent relationship with a non-steady partner increased the likelihood of reporting multiple lifetime-partners, while in Estonia only higher age and low education revealed this effect. In relation to unprotected intercourse, in Finland, higher age, low education and relationship status with a steady partner increased the likelihood of reporting unprotected intercourse. In Estonia, the same was observed only for relationship status. In Finland the likelihood of self-reported STIs increased by older age and lower education and decreased by being with a non-steady partner, while in Estonia, a non-significant increase in self-reported STIs was observed only in the older age group.</p> <p>Conclusion</p> <p>A clear socio-demographic patterning for sexual behaviour and self-reported STIs was revealed in Finland, but a less consistent trend was seen in Estonia. The findings of this study suggest that prevention strategies should focus in Finland on less educated singles and in Estonia on young men generally.</p