bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interventional pharmacoepdemiology: design and evaluation of interventions to improve prescribing
Authors: Alexander G Caleb , Grant Aileen , Hughes Carmel , Dreischulte Tobias 
Published: June 2024

Abstract
Despite the value of modern therapeutics, many obstacles prevent their optimal use. Overuse, underuse, and misuse are common, resulting in morbidity and mortality affecting billions of individuals across the world. Pharmacoepidemiology provides important insights into drug utilization, safety, and effectiveness in large populations, and it is an important method to identify opportunities to improve the value of therapeutics in clinical practice. However, for these opportunities to be realized, interventions to improve prescribing must be developed, evaluated, and implemented in the real world. We provide an overview of this process, focusing especially on how such interventions can be designed and deployed to maximize scalability, adoption, and impact. Prescribing represents a complex behavior with barriers and enablers, and interventions to improve prescribing will be most successful when developed, piloted and refined to maximize provider and patient acceptability. Carefully developed evaluations of interventions are also critical, and varied methods are available to empirically evaluate the intended and potential unintended consequences of interventions. With illustrative examples from the peer-reviewed literature, we provide readers with an overview of approaches to the essential and growing field of interventional pharmacoepidemiology.
This article is part of a Special Collection on Pharmacoepidemiology.
Induction of in vivo-like ciliation in confluent monolayers of re-differentiated equine oviduct epithelial cells
Authors: Leemans Bart , Gadella Bart M , Marchand Josephine H E A M , Van Soom Ann , Stout Tom A E 
Published: June 2024

Abstract
We recently developed re-differentiated equine oviduct epithelial cell (REOEC) monolayers demonstrating various in vivo morphological characteristics, but lacking secondary ciliation. In this study, we evaluated the effects of fetal bovine serum, reproductive steroid hormones, Wnt- and Notch ligands and inhibitors, and different EOEC seeding densities, in both conventional wells and on microporous membranes, on EOEC morphology and, in particular, secondary ciliation. REOEC monolayers were assessed by confocal microscopy after combined staining of nuclei, cilia, and the cytoskeleton. Only Wnt ligands, Notch inhibitors and oviduct explant cell concentration affected EOEC morphology. Undesirable epithelial-mesenchymal transition was observed in REOEC monolayers exposed to Wnt3a containing medium and Wnt ligand CHIR 99021. With respect to secondary ciliation, only the combined effect of oviduct explant cell concentration and Notch inhibition steered REOEC monolayers to in vivo-like ciliation patterns. De-differentiated EOECs, formed 10 days after oviduct explant cell seeding, were reseeded on inserts; only at initial oviduct explant cell concentrations of 1 and 5 × 106 cells per well was the formation of REOEC monolayers with a high rate of diffuse ciliation supported. Within 1 month after air-liquid interface introduction, &gt;40% and &gt;20% of the REOECs showed secondary cilia, respectively. At higher oviduct explant cell seeding densities secondary ciliation was not supported after re-differentiation. Additionally, Notch inhibition helped boost secondary ciliation rates to &gt;60% in REOEC monolayers with diffuse ciliation only. These monolayers demonstrated higher clathrin expression under follicular phase conditions. Overall, the ciliated REOEC monolayers better resemble in vivo oviduct epithelial cells than previous models.
The role of CT-assessed sarcopenia and visceral adipose tissue in predicting long-term survival in patients undergoing elective endovascular infrarenal aortic repair
Authors: Vaccarino Roberta , Wachtmeister Melker , Karelis Angelos , Marinko Elisabet , Sun Jianming , Resch Timothy , Sonesson Björn , Dias Nuno V 
Published: June 2024

Abstract

Objectives
To evaluate if ileo-psoas muscle size and visceral adipose tissue (VAT) can predict long-term survival after endovascular aneurysm repair (EVAR).

Methods
Patients who underwent EVAR between 2004 and 2012 in a single centre were included. Total psoas muscle area (TPA), abdominal VAT area, subcutaneous adipose tissue (SAT), and total adipose tissue were measured on the preoperative CT. Primary endpoint was all-cause mortality. Values are presented as median and interquartile range or absolute number and percentage. Cox regression analyses were performed to assess the associations with mortality.

Results
Two hundred and eighty-four patients could be included in the study. During a median follow-up of 8 (4-11) years, 223 (79.9%) patients died. Age (P ≤ .001), cardiovascular (P = .041), cerebrovascular (P = .009), renal diseases (P = .002), and chronic obstructive pulmonary disease (P ≤ .001) were independently associated with mortality. TPA was associated with mortality in a univariate (P = .040), but not in a multivariate regression model (P = .764). No significant association was found between mortality and TPA index (P = .103) or any of the adiposity measurements with the exception of SAT (P = .040). However, SAT area loss in a multivariate analysis (P = .875).

Conclusions
Assessment of core muscle size and VAT did not contribute to improving the prediction of long-term survival after EVAR.

Advances in knowledge
The finding of this study contradicts the previously claimed utility of core muscle size and VAT in predicting long-term survival after EVAR.
Propionic acid promotes neurite recovery in damaged multiple sclerosis neurons
Authors: Gisevius Barbara , Duscha Alexander , Poschmann Gereon , Stühler Kai , Motte Jeremias , Fisse Anna Lena , Augustyniak Sanja , Rehm Adriana , Renk Pia , Böse Celina , Hubert Diana , Peters Kathrin , Jagst Michelle , Gömer André , Todt Daniel , Bader Verian , Tokic Marianne , Hirschberg Sarah , Krogias Christos , Trampe Nadine , Coutourier Charlotta , Winnesberg Carmen , Steinmann Eike , Winklhofer Konstanze , Gold Ralf , Haghikia Aiden 
Published: June 2024

Abstract
Neurodegeneration in the autoimmune disease multiple sclerosis still poses a major therapeutic challenge. Effective drugs that target the inflammation can only partially reduce accumulation of neurological deficits and conversion to progressive disease forms. Diet and the associated gut microbiome are currently being discussed as crucial environmental risk factors that determine disease onset and subsequent progression. In people with multiple sclerosis, supplementation of the short-chain fatty acid propionic acid, as a microbial metabolite derived from the fermentation of a high-fiber diet, has previously been shown to regulate inflammation accompanied by neuroprotective properties. We set out to determine whether the neuroprotective impact of propionic acid is a direct mode of action of short-chain fatty acids on CNS neurons. We analysed neurite recovery in the presence of the short-chain fatty acid propionic acid and butyric acid in a reverse-translational disease-in-a-dish model of human-induced primary neurons differentiated from people with multiple sclerosis-derived induced pluripotent stem cells. We found that recovery of damaged neurites is induced by propionic acid and butyric acid. We could also show that administration of butyric acid is able to enhance propionic acid-associated neurite recovery. Whole-cell proteome analysis of induced primary neurons following recovery in the presence of propionic acid revealed abundant changes of protein groups that are associated with the chromatin assembly, translational, and metabolic processes. We further present evidence that these alterations in the chromatin assembly were associated with inhibition of histone deacetylase class I/II following both propionic acid and butyric acid treatment, mediated by free fatty acid receptor signalling. While neurite recovery in the presence of propionic acid is promoted by activation of the anti-oxidative response, administration of butyric acid increases neuronal ATP synthesis in people with multiple sclerosis-specific induced primary neurons.
Altered functional connectivity of the default mode network in non-arteritic anterior ischaemic optic neuropathy
Authors: Guo Pengde , Zhou Jian , Su Yan , Wang Weixin , Hua Haiqin , Zhao Pengbo , Wang Yan , Kang Shaohong , Liu Ming 
Published: June 2024

Abstract
The functional connectivity of the default mode network is important in understanding the neuro-pathophysiological abnormalities in patients with non-arteritic anterior ischaemic optic neuropathy. Independent component analysis can effectively determine within and between network connectivity of different brain components. Therefore, in order to explore the association between the default mode network and other brain regions, we utilized independent component analysis to investigate the alteration of functional connectivity of the default mode network. Thirty-one patients with non-arteritic anterior ischaemic optic neuropathy and 31 healthy controls, matched for age, sex and years of education, were recruited. For patients and healthy controls, functional connectivity within and between the default mode network and other brain regions were evaluated by independent component analysis. Compared with healthy controls, patients with non-arteritic anterior ischaemic optic neuropathy showed reduced functional connectivity within the default mode network in the right cerebellar tonsil and left cerebellum posterior lobe and increased functional connectivity in the left inferior temporal and right middle frontal gyri. Furthermore, patients with non-arteritic anterior ischaemic optic neuropathy showed reduced functional connectivity between the default mode network and other brain regions in the left cerebellar tonsil and increased functional connectivity in the right putamen, left thalamus, right middle temporal and left middle frontal gyri. In conclusion, negative correlations between several clinical parameters and functional connectivity of the default mode network were observed. The study contributes to understanding the mechanism of functional reorganization in non-arteritic anterior ischaemic optic neuropathy.
Virologic Failure and Drug Resistance After Programmatic Switching to Dolutegravir-based First-line Antiretroviral Therapy in Malawi and Zambia
Authors: Skrivankova Veronika Whitesell , Huwa Jacqueline , Muula Guy , Chiwaya Geldert D , Banda Esau , Buleya Shameem , Chihota Belinda , Chintedza Joseph , Bolton Carolyn , Tweya Hannock , Kalua Thokozani , Hossmann Stefanie , Kouyos Roger , Wandeler Gilles , Egger Matthias , Lessells Richard J 
Published: June 2024

Abstract

Background
People with human immunodeficiency virus (PWH) on first-line, nonnucleoside reverse-transcriptase inhibitor–based antiretroviral therapy (ART) were routinely switched to tenofovir-lamivudine-dolutegravir. We examined virologic outcomes and drug resistance in ART programs in Malawi, where switching was irrespective of viral load, and Zambia, where switching depended on a viral load &lt;1000 copies/mL in the past year.

Methods
We compared the risk of viremia (≥400 copies/mL) at 1 and 2 years by viral load at switch and between countries using exact methods and logistic regression adjusted for age and sex. We performed HIV-1 pol Sanger sequencing on plasma samples with viral load ≥1000 copies/mL.

Results
A total of 2832 PWH were eligible (Malawi 1422, Zambia 1410); the median age was 37 years, and 2578 (91.0%) were women. At switch, 77 (5.4%) were viremic in Malawi and 42 (3.0%) in Zambia (P = .001). Viremia at switch was associated with viremia at 1 year (adjusted odds ratio (OR), 6.15; 95% confidence interval [CI], 3.13–11.4) and 2 years (7.0; 95% CI, 3.73–12.6). Viremia was less likely in Zambia than in Malawi at 1 year (OR, 0.55; 0.32–0.94) and 2 years (OR, 0.33; 0.18–0.57). Integrase sequencing was successful for 79 of 113 eligible samples. Drug resistance mutations were found in 5 PWH (Malawi 4, Zambia 1); 2 had major mutations (G118R, E138K, T66A and G118R, E138K) leading to high-level dolutegravir resistance.

Conclusions
Restricting switching to dolutegravir-based ART to PWH with a viral load &lt;1000 copies/mL may reduce subsequent viremia and, consequently, the emergence of dolutegravir drug resistance mutations.

Clinical Trials Registration
Clinicaltrials.gov (NCT04612452).
Systematic Review and Meta-analysis of the Association BetweenMycoplasma Genitaliumand Pelvic Inflammatory Disease (PID)
Authors: Htaik Kay , Vodstrcil Lenka A , Plummer Erica L , Sfameni Amelia M , Machalek Dorothy A , Manhart Lisa E , Bradshaw Catriona S 
Published: June 2024

AbstractBackgroundDifferences in opinion concerning the contribution of Mycoplasma genitalium to pelvic inflammatory disease (PID) has resulted in inconsistencies across global testing and treatment guidelines. We conducted a systematic review and meta-analysis to determine the association between M. genitalium and PID and M. genitalium positivity within PID cases to provide a contemporary evidence base to inform clinical practice (PROSPERO registration: CRD42022382156).MethodsPubMed, Embase, Medline, and Web of Science were searched to 1 December 2023 for studies that assessed women for PID using established clinical criteria and used nucleic acid amplification tests to detect M. genitalium. We calculated summary estimates of the (1) association of M. genitalium with PID (pooled odds ratio [OR]) and 2) proportion of PID cases with M. genitalium detected (pooled M. genitalium positivity in PID), using random-effects meta-analyses, with 95% confidence intervals (CI).ResultsNineteen studies were included: 10 estimated M. genitalium association with PID, and 19 estimated M. genitalium positivity in PID. M. genitalium infection was significantly associated with PID (pooled OR = 1.67 [95% CI: 1.24–2.24]). The pooled positivity of M. genitalium in PID was 10.3% [95% CI: 5.63–15.99]. Subgroup and meta-regression analyses showed that M. genitalium positivity in PID was highest in the Americas, in studies conducted in both inpatient and outpatient clinic settings, and in populations at high risk of sexually transmitted infections.ConclusionsM. genitalium was associated with a 67% increase in odds of PID and was detected in about 1 of 10 clinical diagnoses of PID. These data support testing women for M. genitalium at initial PID diagnosis.
Riches and Poverty in English Protestant Culture, c.1550–1800: Vernacularising the Parable of Dives and Lazarus
Authors: Hitchcock David , Waddell Brodie 
Published: June 2024

Abstract
The story of the rich glutton Dives and the poor beggar Lazarus (Luke 16:19–31) was a popular subject in sermons, pamphlets, poems and ballads in early modern England. This article is the first substantial analysis of how the short but powerful biblical narrative was adapted and explained over the course of the sixteenth, seventeenth and eighteenth centuries. It shows that—despite the huge religious, social and economic changes of this period—the message remained remarkably consistent. The beggar Lazarus himself was always depicted as a straightforwardly positive figure, offering an unusually clear association of poverty with virtue. However, many authors also used him to present a model of acceptable behaviour that imposed severe limits on the agency of the poor, and some turned him into a foil to criticise sharply those who failed to conform to such a model. Meanwhile, most portrayals of the rich man Dives presented his sinful misuse of his wealth as a lesson about not only the dangers of luxury but also the virtue of charity. A few authors offered more extreme interpretations that fitted with their specific circumstances, including radical condemnations of the rich and powerful during the political unrest of the mid-seventeenth century. Even more noticeable, however, is the striking resilience of a very ‘traditional’ core message, which previous scholarship on early modern religious attitudes towards wealth and poverty has tended to neglect.
The Quebec Act (1774) and the Hanoverian Church–State Relationship
Authors: Walsh Ashley 
Published: June 2024

Abstract
By providing for freedom of worship among Catholics in the conquered Province of Quebec, the Quebec Act (1774) later proved to be one element in the long and complicated process of Catholic emancipation in Britain, Ireland and the empire. Historians have examined the press campaign against the Quebec Act, contrasting the culture of Enlightenment toleration among its drafters and defenders with the Protestant zealotry of its opponents and, latterly, the Gordon rioters in 1780. But this characterisation neglects the ecclesiological debate about the connection between the legislation and the Hanoverian church–state relationship. Drawing on Enlightenment critiques of priestcraft and superstition, opponents of the Quebec Act claimed that it established, rather than tolerated, Catholicism. By contrast, defenders of the Quebec Act argued that priestcraft and superstition were declining among Canadian Catholics and that enshrining the right of Catholic priests to collect tithes did not represent a church establishment. The debate turned on the problem of Catholic loyalty in a Protestant state. Opponents of the Quebec Act held that Protestants alone could reconcile secular and spiritual loyalties through the royal supremacy. Supporters of the Quebec Act not only claimed that conquered Catholics could be loyal to the imperial state, but also that they merited a bishop and endowed priests to perform the public offices of their faith, holding out the possibility that Catholicism could be a civil religion.
Industrial, regional, and gender divides in British unemployment between the wars
Authors: Paker Meredith M 
Published: June 2024

Abstract
Despite a substantial body of literature on the severe unemployment crisis in interwar Britain, our understanding of its distributional impacts remains limited. Using newly digitized government data, this paper analyzes the gender, industrial, and regional composition of unemployment 1923–1936. I find that the unemployment rate was higher for men owing in part to a strongly gender-segmented labor market, that unemployment was widespread across industries and not just a product of the declining staple industries, that unemployment exhibited strong seasonality, and that regional unemployment differentials cannot be primarily attributed to regions’ varying industrial compositions. These results offer a more granular view of this mass unemployment episode.
Loop diuretic therapy with or without heart failure: impact on prognosis
Authors: Friday Jocelyn M , Cleland John G F , Pellicori Pierpaolo , Wolters Maria K , McMurray John J V , Jhund Pardeep S , Forsyth Paul , McAllister David A , Graham Fraser J , Jones Yola , Lewsey Jim 
Published: June 2024

Abstract

Background and Aims
Many patients are prescribed loop diuretics without a diagnostic record of heart failure. Little is known about their characteristics and prognosis.

Methods
Glasgow regional health records (2009–16) were obtained for adults with cardiovascular disease or taking loop diuretics. Outcomes were investigated using Cox models with hazard ratios adjusted for age, sex, socioeconomic deprivation, and comorbid disease (adjHR).

Results
Of 198 898 patients (median age 65 years; 55% women), 161 935 (81%) neither took loop diuretics nor had a diagnostic record of heart failure (reference group), 23 963 (12%) were taking loop diuretics but had no heart failure recorded, 7844 (4%) had heart failure recorded and took loop diuretics, and 5156 (3%) had heart failure recorded but were not receiving loop diuretics. Compared to the reference group, five-year mortality was only slightly higher for heart failure in the absence of loop diuretics [22%; adjHR 1.2 (95% CI 1.1–1.3)], substantially higher for those taking loop diuretics with no record of heart failure [40%; adjHR 1.8 (95% CI 1.7–1.8)], and highest for heart failure treated with loop diuretics [52%; adjHR 2.2 (95% CI 2.0–2.2)].

Conclusions
For patients with cardiovascular disease, many are prescribed loop diuretics without a recorded diagnosis of heart failure. Mortality is more strongly associated with loop diuretic use than with a record of heart failure. The diagnosis of heart failure may be often missed, or loop diuretic use is associated with other conditions with a prognosis similar to heart failure, or inappropriate loop diuretic use increases mortality; all might be true.
Trends in socioeconomic inequalities in self-rated health and mental distress during four decades in a Norwegian population: a HUNT Study
Authors: Vonen Hanne Dahl , Sund Erik R , Ariansen Inger , Krokstad Steinar 
Published: June 2024

Abstract

Background
Socioeconomic inequalities constitute an important focus area for public health, and it has long been established that higher educational level and longer lifespan are correlated. Little is known about decennial time trends in poor self-rated health and mental distress.

Methods
This study linked decennial cross-sectional survey data on self-rated health and mental distress from the Trøndelag Health Study (HUNT) from 1984 to 2019 with educational registry data using personal identification numbers. Survey participation ranged from 50 807 to 77 212. Slope index of inequality (SII) and relative index of inequality (RII) were calculated using generalized linear models in Stata. Analyses were stratified by sex and age, using the age categories of 30–59 years and 60–80 years.

Results
Absolute inequalities in self-rated health and mental distress between educational groups have stayed relatively stable throughout all rounds of HUNT. Relative inequalities in self-rated health and mental distress have generally increased, and both men and women with the lowest education level were more likely to experience poor self-rated health and mental distress relative to those with the highest education level. RII in self-rated health increased over time for both sexes and both age groups. RII for mental distress increased in both sexes and both age groups, except for men and women aged 60–80.

Discussion
This study shows that relative inequalities in self-rated and mental health in the Norwegian population are still persistent and have increased. Further knowledge about groups with a disadvantageous health situation should have implications for health care resource allocation.