Search

Joseph Tkacz,1 Kristin A Evans,1 Daniel R Touchette,2 Edward Portillo,3 Charlie Strange,4 Anthony Staresinic,5 Norbert Feigler,5 Sushma Patel,5 Michael Pollack5 1Life Sciences, IBM Watson Health, Cambridge, MA, USA; 2Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois College of Pharmacy, Chicago, IL, USA; 3Pharmacy Practice Division, University of Wisconsin-Madison School of Pharmacy, Madison, WI, USA; 4Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, SC, USA; 5BioPharmaceuticals, US Medical Affairs, AstraZeneca, Wilmington, DE, USACorrespondence: Michael Pollack, AstraZeneca, 1800 Concord Pike, Wilmington, DE, 19850, USA, Tel +1 302 377 4911, Email michael.pollack1@astrazeneca.comPurpose: Patients with chronic obstructive pulmonary disease (COPD) may experience moderate (requiring outpatient care) or severe (requiring hospitalization) disease exacerbations. Guidelines recommend escalation from dual to triple therapy (inhaled corticosteroid + long-acting beta agonist + long-acting muscarinic antagonist) after two moderate or one severe exacerbation in a year. This study examined whether prompt initiation of triple therapy lowers risk of future exacerbations and reduces healthcare costs, compared to delayed/very delayed triple therapy after an exacerbation.Patients and Methods: This retrospective observational study of US healthcare claims included patients ≥ 40 years old with COPD who initiated triple therapy (1/1/2011– 3/31/2020) after ≥ 2 moderate or ≥ 1 severe exacerbation in the prior year. The earliest of the second moderate or first severe exacerbation was the index date. Patients were stratified by triple therapy timing: prompt (≤ 30 days post-index), delayed (31– 180 days), very delayed (181– 365 days). COPD exacerbations, all-cause and COPD-related healthcare utilization and costs were assessed during 12 months post-index (follow-up). Multivariable regression estimated the effect of each 30-day delay in triple therapy on the odds of exacerbations, number of exacerbations, and costs during follow-up, controlling for patient characteristics.Results: A total of 24,770 patients were included: 7577 prompt, 9676 delayed, 7517 very delayed. Each 30-day delay of triple therapy was associated with 11% and 7% increases in the odds of any exacerbation and a severe exacerbation, respectively (odds ratio [95% CI]: 1.11 [1.10– 1.13] and 1.07 [1.05– 1.08]), a 4.3% (95% CI: 3.9– 4.6%) increase in the number of exacerbations, a 1.8% (95% CI: 1.3– 2.3%) increase in all-cause costs, and a 2.1% (95% CI: 1.6– 2.6%) increase in COPD-related costs during follow-up.Conclusion: Promptly initiating triple therapy after two moderate or one severe exacerbation is associated with decreased morbidity and economic burden in COPD. Proactive disease management may be warranted to prevent future exacerbations and lower costs among patients with COPD.Keywords: costs, discharge, hospitalization, utilization

Eric T Wittbrodt,1 Lauren A Millette,1 Kristin A Evans,2 Machaon Bonafede,2 Joseph Tkacz,2 Gary T Ferguson3 1Medical Affairs, AstraZeneca, Wilmington, DE, USA; 2Life Sciences, Value-Based Care, IBM Watson Health, Cambridge, MA, USA; 3Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA Purpose: The aim of this study was to examine real-world differences in health care resource use (HRU) and costs among COPD patients in the USA treated with a dry powder inhaler (DPI) or pressurized metered-dose inhaler (pMDI) following a COPD-related hospitalization. Methods: This retrospective analysis used the Truven MarketScan® databases. Eligibility criteria included 1) age ≥40 years, 2) COPD diagnosis, 3) inpatient admission with a diagnosis of COPD exacerbation, 4) inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) prescription within 10 days of hospital discharge (index date), and 5) continuous enrollment for 12 months preindex and 90 days postindex. Outcomes included pre- and postindex HRU and costs. DPI and pMDI groups were compared on postindex outcomes via multivariate models controlling for demographic and baseline characteristics. Results: The sample included 1,960 DPI and 1,086 pMDI ICS/LABA patients. During the preindex period, pMDI patients were significantly more likely to be prescribed a short-acting β-agonist, experienced more COPD exacerbation-related hospital days, and had a greater number of pulmonologist visits compared to DPI patients (P

This study compared the effects of three supplementary diets—egg yolk, Artemia, and commercial pellets with 48% crude protein—on the growth performance and survival rate of redbreast tilapia (Coptodon rendalli) under intensive culture conditions at the Kamutjonga Inland Fisheries Institute in the Kavango East region of Namibia. The study was conducted from December 2023 to January 2024 using a complete randomized design replicated thrice. Results showed that fish fed with commercial pellets exhibited the highest specific growth rate (1.39 ± 0.80%) compared to egg yolk (0.94 ± 0.54%) and Artemia (0.33 ± 0.19%). Commercial pellets also had the best survival rate (76.19 ± 43.099), compared to egg yolk and Artemia (70.47 ± 40.69; 33 ± 19.05), respectively. However, egg yolk had the best feed conversion ratio (0.20 ± 0.05) compared to the commercial pellets (0.22 ± 0.04) and Artemia (0.26 ± 0.07). Critical water quality parameters were maintained within acceptable survival ranges for C. rendalli across all treatments. These findings highlight the importance of dietary protein content in optimizing the growth and survival of C. rendalli under intensive culture conditions and provide insights for effective feeding strategies. However, commercial pellets are expensive and inaccessible to small-scale fish farmers. As an alternative, egg yolk emerged as a viable and affordable feed option, promoting fish growth and supporting the establishment of small-scale farming practices in the region.

Abstract Background Improving maternal healthcare services is crucial to achieving the Sustainable Development Goal (SDG-3), which aims to reduce maternal mortality and morbidity. There is a consensus among different researchers that proper utilization of maternal healthcare services can improve the reproductive health of women, and this can be achieved by providing Antenatal Care (ANC) during pregnancy, Health Facility Delivery (HFD), and Postnatal Care (PNC) to all pregnant women. The main aim of this study was to investigate the utilization and factors associated with maternal and child healthcare services among women of reproductive age in the pastoralist communities in Kenya. Methods A cross-sectional survey was conducted among 180 pastoralist women who gave birth in the past two years across ten mobile villages in Marsabit County between 2nd January and 29th February 2019. Three key outcomes were analyzed, whether they attended ANC 4+ visits, delivered at HF, and received PNC. Pearson χ2 test and multivariate logistic regression analysis were conducted by IBM SPSS27.0 following Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. The significance level was set at p

Natural resource management (NRM) plays a pivotal role in ensuring the sustainability of ecosystems, which are essential for human health and well-being. This systematic review examines the impact of various NRM practices on water quality and their subsequent effects on public health. Specifically, it focuses on interventions such as watershed management, pollution control, land use management, water treatment, and ecosystem restoration. We conducted a comprehensive search across PubMed, Scopus, and Web of Science, supplemented by gray literature from Google Scholar, WHO reports, and government and NGO publications, covering studies published between 2014 and 2024. A total of 42 studies met the inclusion criteria, encompassing diverse geographical regions with significant representation from developing countries. The findings indicate that effective NRM practices, particularly those aimed at reducing pollutants, managing watersheds, and promoting sustainable land use, significantly improve water quality by lowering levels of chemical contaminants, microbial pathogens, and physical pollutants. Improved water quality directly correlates with reduced incidences of waterborne diseases, chronic health conditions from long-term chemical exposure, and acute health effects from immediate pollutant exposure. The review underscores the need for tailored NRM strategies that consider local environmental and socio-economic contexts. It also highlights the importance of community involvement, regulatory frameworks, and continuous monitoring to enhance the effectiveness of NRM interventions. Despite the positive impacts, barriers such as limited financial resources, technical expertise, and community engagement pose challenges to the implementation of these practices. In conclusion, the systematic review demonstrates that comprehensive and context-specific NRM practices are crucial for improving water quality and public health outcomes. Policymakers and practitioners are encouraged to adopt integrated water resource management approaches, prioritize sustainable practices, and engage local communities to achieve long-term health and environmental benefits.

The cultivation of Auricularia heimuer, a species of edible mushroom, heavily relies on the availability of wood resources serving as substrate for the growth of the species. To ensure the sustainable development of the A. heimuer industry and optimize the utilization of corncob as a substrate, this study sought to investigate the potential use of corncob as a substrate for the cultivation of A. heimuer. The purpose of this study was to explore the utilization of corncob lignocellulose by A. heimuer at the mycelium, primordium, and fruiting stages, by specifically examining the expression profiles of both carbohydrate-active enzymes (CAZymes) and the transcriptome of differentially expressed genes (DEGs) relevant to corncob biomass degradation. The results revealed 10,979, 10,630, and 11,061 DEGs at the mycelium, primordium, and fruiting stages, respectively, while 639 DGEs were identified as carbohydrate-active enzymes. Of particular interest were 46 differentially expressed CAZymes genes that were associated directly with lignocellulose degradation. Furthermore, the study found that A. heimuer exhibited adaptive changes that enabled it to effectively utilize the cellulose present in the corncob. These changes were observed primarily at the primordium and fruiting stages. Key genes involved in lignocellulose degradation were also identified, including g6952, g8349, g12487, and g2976 at the mycelium stage, g5775, g2857, g3018, and g11016 at the primordium stage, and g10290, g2857, g12385, g7656, and g8953 at the fruiting stage. This study found that lytic polysaccharide monooxygenase (LPMO) played a crucial role in the degradation of corncob cellulose, further highlighting the complexity of the molecular mechanisms involved in the degradation of lignocellulose biomass by A. heimuer. The study sheds light on the molecular mechanisms underlying the ability of A. heimuer to degrade corncob biomass, with implications for the efficient utilization of lignocellulose resources. The findings from this study may facilitate the development of innovative biotechnologies for the transformation of corncob biomass into useful products.

Background: The global shortage of nurses is posing a significant threat to the provision and sustainability of quality health care services worldwide. The importance of nursing organizational culture and validated tools to accurately measure it, is of paramount importance in mitigation of this shortage, especially in Low- and middle-income-countries like Kenya. Methodology: This was a cross-sectional online validation survey among 212 nursing personnel working in various healthcare facilities across Kenya. The aim of the study was to assess the validity and reliability of the psychometric properties of the Practice Environment Scale of Nursing Work Index within the framework of nursing organizational culture in Kenya and determine how Kenyan nurses rate their organizational culture. Data was analyzed using SPSS version 28. Cronbach’s alpha was used to determine reliability while Exploratory Factor Analysis and Confirmatory Factor Analysis were used to test validity. Results: The 5-structure of Lake’s PES-NWI was unsupported by confirmatory factor analysis and a new 7-Factor Kenyan PES-NWI version was created. The new tool was reliable and with acceptable fit. Participants showed a mixed rating of their organizational culture with overall organizational culture largely rated neutral (M = 2.51, SD = 1.01). Conclusion: The Kenyan PES-NWI is a valid and reliable tool that could be used to assess organizational culture. The study highlighted the critical need to further develop context-specific tools to accurately measure nursing organizational culture work environments particularly in Low and-Middle-Income countries like Kenya facing significant nursing shortages. As nursing becomes increasingly dynamic and complex, it is essential for nursing and healthcare researchers to re-validate research tools to continuously improve them.

AbstractThe aim of the study was to examine the pollution status of environmentally concerned heavy metals: lead, cadmium, chromium, arsenic, cobalt, nickel, copper, zinc, vanadium, and manganese in surface soil dusts at the Katima Mulilo urban motor park (KMUMP), Namibia. Composite surface soil dusts samples were randomly collected from three points at 10 m apart within the motor park, and a control site on a weekly basis over 8 weeks. Pooled sampled were homogenized and 20 sub-samples (

Abstract Background Malaria in pregnancy doubles the risk of low birthweight; up to 11% of all neonatal deaths in sub-Saharan Africa are associated with malaria in pregnancy. To prevent these and other adverse health consequences, the World Health Organization recommends administering intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine–pyrimethamine for all pregnant women at each antenatal care (ANC) visit, starting as early as possible in the second trimester. The target is for countries to administer a minimum of three doses (IPTp3+) to at least 85% of pregnant women. Methods A cluster randomized, controlled trial was conducted to assess the effect of delivery of IPTp by community health workers on the coverage of IPTp3 + and ANC visits in Malawi. Community delivery of IPTp was implemented within two districts in Malawi over a 21-month period, from November 2018 to July 2020. In control sites, IPTp was delivered at health facilities. Representative samples of women who delivered in the prior 12 months were surveyed at baseline (n = 370, December 2017) and endline (n = 687, August 2020). A difference in differences analysis was conducted to assess the change in coverage of IPTp and ANC over time, accounting for clustering at the health facility level. Results Overall IPTp coverage increased over the study period. At baseline, women received a mean of 2.3 IPTp doses (range 0–5 doses) across both arms, and at endline, women received a mean of 2.8 doses (range 0–9 doses). Despite overall increases, the change in IPTp3 + coverage was not significantly different between intervention and control groups (6.9%, 95% CI: -5.9%, 19.6%). ANC4 + coverage increased significantly in the intervention group compared with the control group, with a difference-in-differences of 25.3% points (95% CI: 1.3%, 49.3%). Conclusions In order to reduce the burden of malaria in pregnancy, new strategies are needed to improve uptake of effective interventions such as IPTp. While community health workers’ delivery of IPTp did not increase uptake in this study, they may be effective in other settings or circumstances. Further research can help identify the health systems characteristics that are conducive to community delivery of IPTp and the operational requirements for effective implementation. Trial registration: ClinicalTrials.gov Identifier: NCT03376217. Registered December 6, 2017, https://clinicaltrials.gov/ct2/show/NCT03376217 .

In semiarid regions, soil salinity, like drought, restricts crop productivity, causing food shortages among most inhabitants—the smallholder subsistence farmers. Seasonal wetlands formed in these regions during the rainy seasons could be utilised for rice (Oryza spp.) cultivation to increase food security, but rice is sensitive to salinity. Field and greenhouse-pot experiments were performed at the University of Namibia-Ogongo Campus, North-Central Namibia, to evaluate rice genotypes’ responses to seasonal wetland salinity. The field experiments assessed 16 rice genotypes for growth during the dry season and grain production during the rainy season, in saline and non-saline (control) seasonal wetlands. The saline-wetland salinity was predominantly NaCl; electrical conductivity levels increased from 2.8 dS m−1 (rainy season) to 34.3 dS m−1 (dry season), resulting in a 0–14% dry-season plant survival rate. The rainy-season wetland salinity decreased paddy yields in all rice genotypes; however, Pokkali produced the highest paddy and relative yields. The pot experiment assessed CG14 (salt-sensitive) and Pokkali (salt-tolerant) genotypes for growth using soils collected bi-monthly from the saline wetland. The rainy-season soil salinity reduced shoot growth in CG14 but did not affect growth in Pokkali, while the dry-season salinity killed both genotypes. The results of this study suggest the possibility of cultivating the salt-tolerant rice genotype, Pokkali, in the saline wetland during the rainy season due to salt dilution; however, the dry-season salinity levels would be detrimental to rice. More salinity-tolerance screening studies are warranted, in order to increase rice production and food security in Namibia and other flood-prone semiarid regions worldwide.

Objectives To assess outcomes of patients admitted to hospital with COVID-19 and to determine the predictors of mortality.Setting This study was conducted in six facilities, which included both government and privately run secondary and tertiary level facilities in the central and coastal regions of Kenya.Participants We enrolled 787 reverse transcriptase-PCR-confirmed SARS-CoV2-infected persons. Patients whose records could not be accessed were excluded.Primary and secondary outcome measures The primary outcome was COVID-19-related death. We used Cox proportional hazards regressions to determine factors related to in-hospital mortality.Results Data from patients with 787 COVID-19 were available. The median age was 43 years (IQR 30–53), with 505 (64%) being men. At admission, 455 (58%) were symptomatic with an additional 63 (9%) developing clinical symptoms during hospitalisation. The most common symptoms were cough (337, 43%), loss of taste or smell (279, 35%) and fever (126, 16%). Comorbidities were reported in 340 (43%), with cardiovascular disease, diabetes and HIV documented in 130 (17%), 116 (15%), 53 (7%), respectively. 90 (11%) were admitted to the Intensive Care Unit (ICU) for a mean of 11 days, 52 (7%) were ventilated with a mean of 10 days, 107 (14%) died. The risk of death increased with age (HR 1.57 (95% CI 1.13 to 2.19)) for persons >60 years compared with those

Introduction The high proportion of SARS-CoV-2 infections that have remained undetected presents a challenge to tracking the progress of the pandemic and estimating the extent of population immunity. Methods We used residual blood samples from women attending antenatal care services at three hospitals in Kenya between August 2020 and October 2021and a validated IgG ELISA for SARS-Cov-2 spike protein and adjusted the results for assay sensitivity and specificity. We fitted a two-component mixture model as an alternative to the threshold analysis to estimate of the proportion of individuals with past SARS-CoV-2 infection. Results We estimated seroprevalence in 2,981 women; 706 in Nairobi, 567 in Busia and 1,708 in Kilifi. By October 2021, 13% of participants were vaccinated (at least one dose) in Nairobi, 2% in Busia. Adjusted seroprevalence rose in all sites; from 50% (95%CI 42–58) in August 2020, to 85% (95%CI 78–92) in October 2021 in Nairobi; from 31% (95%CI 25–37) in May 2021 to 71% (95%CI 64–77) in October 2021 in Busia; and from 1% (95% CI 0–3) in September 2020 to 63% (95% CI 56–69) in October 2021 in Kilifi. Mixture modelling, suggests adjusted cross-sectional prevalence estimates are underestimates; seroprevalence in October 2021 could be 74% in Busia and 72% in Kilifi. Conclusions There has been substantial, unobserved transmission of SARS-CoV-2 in Nairobi, Busia and Kilifi Counties. Due to the length of time since the beginning of the pandemic, repeated cross-sectional surveys are now difficult to interpret without the use of models to account for antibody waning.

The root and leaf extracts of Launaea cornuta have been locally used in traditional medicine for decades to manage inflammatory conditions and other oxidative-stress-related syndromes; however, their pharmacologic efficacy has not been scientifically investigated and validated. Accordingly, we investigated the in vitro antioxidant activity, anti-inflammatory ( in vitro, ex vivo, and in vivo ) efficacy, acute oral toxicity, and qualitative phytochemical composition of the aqueous root extract of L. cornuta . The ferric-reducing antioxidant power (FRAP) and the 2,2-diphenyl-2-pycrylhydrazyl (DPPH) radical scavenging test methods were used to determine the studied plant extract’s antioxidant activity. Besides, the anti-inflammatory efficacy of the studied plant extract was investigated using in vitro (anti-proteinase and protein denaturation), ex vivo (membrane stabilization), and in vivo (carrageenan-induced paw oedema in Swiss albino mice) methods. The studied plant extract demonstrated significant in vitro antioxidant effects, which were evidenced by higher DPPH radical scavenging and FRAP activities, in a concentration-dependent manner ( p 2000 mg/Kg BW), and was thus considered safe. Additionally, qualitative phytochemistry revealed the presence of various antioxidant- and anti-inflammatory-associated phytochemicals, which were deemed responsible for the reported pharmacologic efficacy. Further studies to characterise bioactive molecules and their mode(s) of pharmacologic efficacy are encouraged.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Objective To compare the effectiveness and cost-effectiveness of eccentric loading exercises (ELE) with prolotherapy injections used singly and in combination for painful Achilles tendinosis. Design A single-blinded randomised clinical trial. The primary outcome measure was the VISA-A questionnaire with a minimum clinically important change (MCIC) of 20 points. Setting Five Australian primary care centres. Participants 43 patients with painful mid-portion Achilles tendinosis commenced and 40 completed treatment protocols. Interventions Participants were randomised to a 12-week program of ELE (n=15), or prolotherapy injections of hypertonic glucose with lignocaine alongside the affected tendon (n=14) or combined treatment (n=14). Main outcome measurements VISA-A, pain, stiffness and limitation of activity scores; treatment costs. Results At 12 months, proportions achieving the MCIC for VISA-A were 73% for ELE, 79% for prolotherapy and 86% for combined treatment. Mean (95% CI) increases in VISA-A scores at 12 months were 23.7 (15.6 to 31.9) for ELE, 27.5 (12.8 to 42.2) for prolotherapy and 41.1 (29.3 to 52.9) for combined treatment. At 6 weeks and 12 months, these increases were significantly less for ELE than for combined treatment. Compared with ELE, reductions in stiffness and limitation of activity occurred earlier with prolotherapy and reductions in pain, stiffness and limitation of activity occurred earlier with combined treatment. Combined treatment had the lowest incremental cost per additional responder ($A1539) compared with ELE. Conclusions For Achilles tendinosis, prolotherapy and particularly ELE combined with prolotherapy give more rapid improvements in symptoms than ELE alone but long-term VISA-A scores are similar. Trial registration number ACTRN: 12606000179538. [ABSTRACT FROM AUTHOR]

Purpose. Postural management is used to help address the musculoskeletal and participation issues associated with cerebral palsy (CP). This study aimed to identify the factors influencing postural management in special schools. Method. A purpose-designed, cross-sectional, descriptive survey was sent to teachers, physiotherapists, occupational therapists and speech pathologists working with children with moderate-to-severe CP, aged 5-12 years, in special schools within South Australia. The instrument included four main areas: demographics, perceived benefits of postural management, factors facilitating or hindering the implementation of postural management programmes and suggestions for improvement. Results were analysed descriptively. Results. Forty-three therapists and 18 teachers completed the survey (response rate 81%). The most common factors hindering postural management were positioning equipment being unavailable or difficult to use, lack of time and school staff's knowledge and skills to carry out postural management. Facilitating factors included therapy staff providing a written postural management programme, open and regular communication between therapy and school staff and timetabling of postural management into the daily routine. Conclusions. Numerous factors impact on postural management for students in special schools. Practical solutions highlighted were increased training for school staff, timetabling of postural management into students' routines and provision of written postural management programmes. [ABSTRACT FROM AUTHOR]

The unfinished agenda in the theory and practice of fiscal decentralization is how fiscal decentralization affects the universal plague of poverty reduction in developing economies. Focusing on developing economies especially Ghana, and also employing secondary sources of information, this paper made an attempt to provide a holistic review of the concept of fiscal decentralization and its effects on poverty reduction from the optimist and pessimist views. The paper affirmed that fiscal decentralization has the potential for poverty reduction when it is characterized by greater financial autonomy of the local units with proper budgetary allocation, prioritization, accountability and responsiveness. Accountability and proper regulation may reduce some institutional setbacks such as corruption from the system. We, therefore, recommended for a more effective, efficient, and transparent institutional and legal framework to ensure effective fiscal transfer between the central and local governments in order to eliminate various lapses associated with fiscal decentralization as highlighted by the pessimists.

Background: This study aimed to identify and select informative Simple Sequence Repeat (SSR) markers that may be linked to resistance to important groundnut diseases such as Early Leaf Spot, Groundnut Rosette Disease, rust and aflatoxin contamination. To this end, 799 markers were screened across 16 farmer preferred and other cultivated African groundnut varieties that are routinely used in groundnut improvement, some with known resistance traits. Results: The SSR markers amplified 817 loci and were graded on a scale of 1 to 4 according to successful amplification and ease of scoring of amplified alleles. Of these, 376 markers exhibited Polymorphic Information Content (PIC) values ranging from 0.06 to 0.86, with 1476 alleles detected at an average of 3.7 alleles per locus. The remaining 423 markers were either monomorphic or did not work well. The best performing polymorphic markers were subsequently used to construct a dissimilarity matrix that indicated the relatedness of the varieties in order to aid selection of appropriately diverse parents for groundnut improvement. The closest related varieties were MGV5 and ICGV-SM 90704 and most distant were Chalimbana and 47–10. The mean dissimilarity value was 0.51, ranging from 0.34 to 0.66. Discussion: Of the 376 informative markers identified in this study, 139 (37%) have previously been mapped to the Arachis genome and can now be employed in Quantitative Trait Loci (QTL) mapping and the additional 237 markers identified can be used to improve the efficiency of introgression of resistance to multiple important biotic constraints into farmer-preferred varieties of Sub-Saharan Africa.

Abstract Background MRSA prevalence in nursing homes often exceeds that in hospitals, but reasons for this are not well understood. We sought to measure MRSA burden in a large number of nursing homes and identify facility characteristics associated with high MRSA burden. Methods We performed nasal swabs of residents from 26 nursing homes to measure MRSA importation and point prevalence, and estimate transmission. Using nursing home administrative data, we identified facility characteristics associated with MRSA point prevalence and estimated transmission risk in multivariate models. Results We obtained 1,649 admission and 2,111 point prevalence swabs. Mean MRSA point prevalence was 24%, significantly higher than mean MRSA admission prevalence, 16%, (paired t-test, p In multivariate models, higher MRSA point prevalence was associated with higher admission prevalence (p=0.005) and higher proportions of residents with indwelling devices (p=0.01). Higher estimated MRSA transmission risk was associated with higher proportions of residents with diabetes (p=0.01) and lower levels of social engagement (p=0.03). Conclusions MRSA importation was a strong predictor of MRSA prevalence, but MRSA burden and transmission were also associated with nursing homes caring for more residents with chronic illnesses or indwelling devices. Frequent social interaction among residents appeared to be protective of MRSA transmission, suggesting that residents healthy enough to engage in group activities do not incur substantial risks of MRSA from social contact. Identifying characteristics of nursing homes at risk for high MRSA burden and transmission may allow facilities to tailor infection control policies and interventions to mitigate MRSA spread.

Abstract Background A whole-genome genotyping array has previously been developed for Malus using SNP data from 28 Malus genotypes. This array offers the prospect of high throughput genotyping and linkage map development for any given Malus progeny. To test the applicability of the array for mapping in diverse Malus genotypes, we applied the array to the construction of a SNP-based linkage map of an apple rootstock progeny. Results Of the 7,867 Malus SNP markers on the array, 1,823 (23.2%) were heterozygous in one of the two parents of the progeny, 1,007 (12.8%) were heterozygous in both parental genotypes, whilst just 2.8% of the 921 Pyrus SNPs were heterozygous. A linkage map spanning 1,282.2 cM was produced comprising 2,272 SNP markers, 306 SSR markers and the S-locus. The length of the M432 linkage map was increased by 52.7 cM with the addition of the SNP markers, whilst marker density increased from 3.8 cM/marker to 0.5 cM/marker. Just three regions in excess of 10 cM remain where no markers were mapped. We compared the positions of the mapped SNP markers on the M432 map with their predicted positions on the ‘Golden Delicious’ genome sequence. A total of 311 markers (13.7% of all mapped markers) mapped to positions that conflicted with their predicted positions on the ‘Golden Delicious’ pseudo-chromosomes, indicating the presence of paralogous genomic regions or mis-assignments of genome sequence contigs during the assembly and anchoring of the genome sequence. Conclusions We incorporated data for the 2,272 SNP markers onto the map of the M432 progeny and have presented the most complete and saturated map of the full 17 linkage groups of M. pumila to date. The data were generated rapidly in a high-throughput semi-automated pipeline, permitting significant savings in time and cost over linkage map construction using microsatellites. The application of the array will permit linkage maps to be developed for QTL analyses in a cost-effective manner, and the identification of SNPs that have been assigned erroneous positions on the ‘Golden Delicious’ reference sequence will assist in the continued improvement of the genome sequence assembly for that variety.

Abstract Background IL-10 has a potent inhibitory effect on osteoclastogenesis. In vitro and in vivo studies confirm the importance of this cytokine in bone metabolism, for instance IL-10-deficient mice develop the hallmarks of osteoporosis. Although it is known that IL-10 directly inhibits osteoclastogenesis at an early stage, preventing differentiation of osteoclast progenitors to preosteoclasts, the precise mechanism of its action is not yet clear. Several major pathways regulate osteoclastogenesis, with key signalling genes such as p38, TRAF6, NF-κB and NFATc1 well established as playing vital roles. We have looked at gene expression in eleven of these genes using real-time quantitative PCR on RNA extracted from RANKL-treated RAW264.7 monocytes. Results There was no downregulation by IL-10 of DAP12, FcγRIIB, c-jun, RANK, TRAF6, p38, NF-κB, Gab2, Pim-1, or c-Fos at the mRNA level. However, we found that IL-10 significantly reduces RANKL-induced NFATc1 expression. NFATc1 is transcribed from two alternative promoters in Mus musculus and, interestingly, only the variant transcribed from promoter P1 and beginning with exon 1 was downregulated by IL-10 (isoform 1). In addition, immunofluorescence studies showed that IL-10 reduces NFATc1 levels in RANKL-treated precursors and suppresses nuclear translocation. The inhibitory effect of IL-10 on tartrate-resistant acid phosphatase-positive cell number and NFATc1 mRNA expression was reversed by the protein kinase C agonist phorbol myristate acetate, providing evidence that interleukin-10 disrupts NFATc1 activity through its effect on Ca2+ mobilisation. Conclusion IL-10 acts directly on mononuclear precursors to inhibit NFATc1 expression and nuclear translocation, and we provide evidence that the mechanism may involve disruption of Ca2+ mobilisation. We detected downregulation only of the NFATc1 isoform 1 transcribed from promoter P1. This is the first report indicating that one of the ways in which IL-10 directly inhibits osteoclastogenesis is by suppressing NFATc1 activity.

Abstract Background Regions of interest identified through genetic linkage studies regularly exceed 30 centimorgans in size and can contain hundreds of genes. Traditionally this number is reduced by matching functional annotation to knowledge of the disease or phenotype in question. However, here we show that disease genes share patterns of sequence-based features that can provide a good basis for automatic prioritization of candidates by machine learning. Results We examined a variety of sequence-based features and found that for many of them there are significant differences between the sets of genes known to be involved in human hereditary disease and those not known to be involved in disease. We have created an automatic classifier called PROSPECTR based on those features using the alternating decision tree algorithm which ranks genes in the order of likelihood of involvement in disease. On average, PROSPECTR enriches lists for disease genes two-fold 77% of the time, five-fold 37% of the time and twenty-fold 11% of the time. Conclusion PROSPECTR is a simple and effective way to identify genes involved in Mendelian and oligogenic disorders. It performs markedly better than the single existing sequence-based classifier on novel data. PROSPECTR could save investigators looking at large regions of interest time and effort by prioritizing positional candidate genes for mutation detection and case-control association studies.

Nitrification is an important control on the form and distribution of nitrogen in freshwater ecosystems. However, the seasonality of nitrogen pools and the diversity of organisms catalyzing this process have not been well documented in oligotrophic lakes. Here, we show that nitrogen pools and nitrifying organisms in Flathead Lake are temporally and vertically dynamic, with nitrifiers displaying specific preferences depending on the season. While the ammonia-oxidizing bacteria (AOB) Nitrosomonadaceae and nitrite-oxidizing bacteria (NOB) Nitrotoga dominate at depth in the summer, the ammonia-oxidizing archaea (AOA) Nitrososphaerota and NOB Nitrospirota become abundant in the winter. Given clear seasonality in ammonium, with higher concentrations during the summer, we hypothesize that the succession between these two nitrifying groups may be due to nitrogen affinity, with AOB more competitive when ammonia concentrations are higher and AOA when they are lower. Nitrifiers in Flathead Lake share more than 99% average nucleotide identity with those reported in other North American lakes but are distinct from those in Europe and Asia, indicating a role for geographic isolation as a factor controlling speciation among nitrifiers. Our study shows there are seasonal shifts in nitrogen pools and nitrifying populations, highlighting the dynamic spatial and temporal nature of nitrogen cycling in freshwater ecosystems., (© 2024 The Authors. Environmental Microbiology published by John Wiley & Sons Ltd.)

In the central nervous system, oligodendrocyte precursor cells (OPCs) proliferate and differentiate into myelinating oligodendrocytes throughout life, allowing for ongoing myelination and myelin repair. With age, differentiation efficacy decreases and myelin repair fails; therefore, recent therapeutic efforts have focused on enhancing differentiation. Many cues are thought to regulate OPC differentiation, including neuronal activity, which OPCs can sense and respond to via their voltage-gated ion channels and glutamate receptors. However, OPCs' density of voltage-gated ion channels and glutamate receptors differs with age and brain region, and correlates with their proliferation and differentiation potential, suggesting that OPCs exist in different functional cell states, and that age-associated states might underlie remyelination failure. Here, we use whole-cell patch-clamp to investigate whether clemastine and metformin, two pro-remyelination compounds, alter OPC membrane properties and promote a specific OPC state. We find that clemastine and metformin extend the window of NMDAR surface expression, promoting an NMDAR-rich OPC state. Our findings highlight a possible mechanism for the pro-remyelinating action of clemastine and metformin, and suggest that OPC states can be modulated as a strategy to promote myelin repair., (© 2024. The Author(s).)

Importance: Methane is an important greenhouse gas that is typically produced under anoxic conditions. We show that methane is supersaturated in a large oligotrophic lake despite the presence of oxygen. Metagenomic sequencing indicates that diverse, widespread microorganisms may contribute to the oxic production of methane through the cleavage of methylphosphonate. We experimentally demonstrate that these organisms, especially members of the genus Acidovorax , can produce methane through this process. However, appreciable rates of methane production only occurred when both methylphosphonate and labile sources of carbon were added, indicating that this process may be limited to specific niches and may not be completely responsible for methane concentrations in Flathead Lake. This work adds to our understanding of methane dynamics by describing the organisms and the rates at which they can produce methane through an oxic pathway in a representative oligotrophic lake., Competing Interests: The authors declare no conflict of interest.

Objectives: To identify risk factors for progression to severe COVID-19 and estimate the odds of severe COVID-19 associated with vaccination among patients with systemic lupus erythematosus (SLE)., Methods: This retrospective cohort study identified adults with SLE in the Merative™ MarketScan ® Databases. Patients were continuously enrolled the year before 1 April 2020 (baseline) and had a COVID-19 diagnosis between 1 April 2020 and the earliest of death, enrolment end or 31 December 2021. Severe COVID-19 was defined as hospitalisation with a COVID-19 diagnosis. Demographics on 1 April 2020, baseline comorbidities, corticosteroid use ≤30 days before COVID-19 diagnosis and other SLE medication use ≤6 months before COVID-19 diagnosis were assessed. Vaccination was identified by claims for a COVID-19 vaccine or vaccine administration. Backward stepwise logistic regression estimated odds of progression to severe COVID-19 associated with patient characteristics and vaccination., Results: Among 2890 patients with SLE with COVID-19, 500 (16.4%) had a COVID-19-related hospitalisation. Significant risk factors for progression to severe COVID-19 included rituximab (OR (95% CI) 2.92 (1.67 to 5.12)), renal failure (2.15 (95% CI 1.56 to 2.97)), Medicaid (vs Commercial; 2.01 (95% CI 1.58 to 2.57)), complicated hypertension (1.96 (95% CI 1.38 to 2.77)) and time of infection, among others. Vaccination had a significant protective effect (0.68(95% CI 0.54 to 0.87)) among all patients with SLE with COVID-19, but the effect was not significant among those with prior use of belimumab, rituximab or corticosteroids., Conclusions: Certain chronic comorbidities and SLE medications increase the odds of progression to severe COVID-19 among patients with SLE, but vaccination confers significant protection. Vaccine effectiveness may be attenuated by SLE treatments. Protective measures such as pre-exposure prophylaxis and booster vaccines should be encouraged among patients with SLE., Competing Interests: Competing interests: S-JW and GA are employed by AstraZeneca. KAE, MM and LP are employed by Merative which received funding from AstraZeneca to conduct this study. CC is a paid consultant of AstraZeneca, as well as Eli Lilly, Pfizer and Sanofi. Results of this research have been presented in part at the 2022 American College of Rheumatology annual meeting (ACR Convergence) in Philadelphia, Pennsylvania, USA., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The aim of this study was to describe the clinical complications, treatment use, healthcare resource utilization (HCRU), and costs among patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) in the US., Methods: Merative MarketScan Databases were used to identify patients with SCD with recurrent VOCs from March 1, 2010, to March 1, 2019. Inclusion criteria were ≥ 1 inpatient or  ≥ 2 outpatient claims for SCD and ≥ 2 VOCs per year in any 2 consecutive years after the first qualifying SCD diagnosis. Individuals without SCD in these databases were used as matched controls. Patients were followed for ≥ 12 months, from their second VOC in the 2nd year (index date) to the earliest of inpatient death, end of continuous enrollment in medical/pharmacy benefits, or March 1, 2020. Outcomes were assessed during follow-up., Results: In total, 3420 patients with SCD with recurrent VOCs and 16,722 matched controls were identified. Patients with SCD with recurrent VOCs had a mean of 5.0 VOCs (standard deviation [SD] = 6.0), 2.7 inpatient admissions (SD 2.9), and 5.0 emergency department visits (SD 8.0) per patient per year during follow-up. Compared to matched controls, patients with SCD with recurrent VOCs incurred higher annual ($67,282 vs. $4134) and lifetime ($3.8 million vs. $229,000 over 50 years) healthcare costs., Conclusion: Patients with SCD with recurrent VOCs experience substantial clinical and economic burden driven by inpatient costs and frequent VOCs. There is a major unmet need for treatments that alleviate or eliminate clinical complications, including VOCs, and reduce healthcare costs in this patient population., (© 2023. The Author(s).)

Aims: To describe clinical complications, treatment use, healthcare resource utilization (HCRU), and costs among patients with transfusion-dependent β-thalassemia (TDT) in the United States., Materials and Methods: Merative MarketScan Databases were used to identify patients with β-thalassemia between 1 March 2010, and 1 March 2019. Patients were eligible for inclusion with ≥1 inpatient claim or ≥2 outpatient claims for β-thalassemia and ≥8 red blood cell transfusions (RBCTs) during any 12-month period after and including the date of the first qualifying β-thalassemia diagnosis code. Matched controls consisted of individuals without β-thalassemia. Clinical and economic outcomes of patients were assessed during ≥12 months of follow-up, defined as the period from the index date (i.e. the first RBCT) to either the end of continuous enrollment in benefits, inpatient death, or 1 March 2020., Results: Overall, 207 patients with TDT and 1035 matched controls were identified. Most patients received iron chelation therapy (ICT) (91.3%), with a mean of 12.1 (standard deviation [SD] = 10.3) ICT claims per-patient-per-year (PPPY). Many also received RBCTs, with a mean of 14.2 (SD = 4.7) RBCTs PPPY. TDT was associated with higher annual ($137,125) and lifetime ($7.1 million) healthcare costs vs. matched controls ($4183 and $235,000, respectively). Annual costs were driven by ICT (52.1%) and RBCT use (23.6%). Patients with TDT had 7-times more total outpatient visits/encounters, 3-times more prescriptions, and 33-times higher total annual costs than matched controls., Limitations: This analysis may underestimate the burden of TDT, as indirect healthcare costs (e.g. absenteeism, presenteeism, etc.) were not included. Results may not be generalizable to patients excluded from this analysis, including those with other types of insurance or without insurance., Conclusions: Patients with TDT have high HCRU and direct healthcare costs. Treatments that eliminate the need for RBCTs could reduce the clinical and economic burden of managing TDT.

Aims: Investigate trends in paid lanadelumab costs over time in a population of patients persistent for 18 months, and to understand overall hereditary angioedema (HAE) treatment cost trends, including costs of acute medication/short-term prophylaxis and supportive care. Lastly, we sought to describe the proportion of lanadelumab patients with evidence of down titration via changes in total paid amounts for lanadelumab in a fixed time period., Methods: Patients were identified in the Merative MarketScan Databases who had ≥1 claim for lanadelumab during 1/1/2018-6/30/2022 (index), a  ≤ 60-d gap in days of supply over 18 months, and were enrolled for ≥6 months pre-index and 18 months post-index. Lanadelumab and HAE-specific costs were assessed during follow-up months 0-6, 7-12, and 13-18. Down titration was defined as a  ≥ 25% decrease in lanadelumab costs from months 0-6 to months 7-12 or 13-18. Outcomes were compared between time periods using paired t -tests and McNemar's test., Results: Fifty-four lanadelumab users were included; 25 (46%) had evidence of down titration. Lanadelumab costs decreased from $316,724 to $269,861 to $246,919 in months 0-6, 7-12, and 13-18, respectively ( p  < .01); total HAE treatment costs decreased from $377,076 to $329,855 to $286,074 in months 0-6, 7-12, and 13-18, respectively ( p  < .01)., Limitations: Persistence was determined via days of supply on medication claims; use of the medication was not confirmed. Down titration was based on costs; the lanadelumab regimen could not be assessed. Results may not be generalizable to uninsured patients or those without commercial or Medicare insurance., Conclusions: Patients on long-term prophylaxis with lanadelumab experienced a significant reduction (24%) in HAE treatment costs over 18 months, driven by lower costs of acute medications and lanadelumab down titration. Down titration among appropriate patients with controlled HAE may lead to substantial savings in healthcare costs.

BACKGROUND: Severe exacerbations requiring hospitalization contribute a substantial portion of the morbidity and costs of chronic obstructive pulmonary disease (COPD). Triple therapy (inhaled corticosteroid + long-acting β-agonist + long-acting muscarinic antagonist) is a recommended option for patients who experience recurrent COPD exacerbations or persistent symptoms. Few real-world studies have specifically examined the effect of prompt initiation of triple therapy, specifically among patients hospitalized for a COPD exacerbation. OBJECTIVE: To assess whether prompt initiation of triple therapy following a severe COPD exacerbation was associated with lower risk of subsequent exacerbations and lower health care use and costs and the effects of each 30-day delay of initiation. METHODS: Adults aged 40 years or older with COPD were identified in the Merative MarketScan Databases between January 1, 2010, and December 31, 2019, and were required to meet the following criteria: open or closed triple therapy (date of first closed prescription or last component of open=index treatment date), more than 1 inpatient admission with a primary COPD diagnosis (ie, severe exacerbation) in the prior 12 months (index exacerbation), 12 months of continuous enrollment before (baseline) and after (follow-up) index exacerbation, and absence of select respiratory diseases and cancer. Patients were stratified based on timing of open or closed triple therapy after the index exacerbation: prompt (≤30 days), delayed (31-180 days), or very delayed (181-365 days). Multivariable regression controlled for baseline characteristics (age, sex, insurance type, index year, comorbidities, prior treatment, and prior exacerbations) and estimated the odds of subsequent exacerbations, change in the number of exacerbations, and change in health care costs during 12-month follow-up associated with each 30-day delay of triple therapy initiation. RESULTS: A total of 6,772 patients met inclusion criteria (2,968 [43.8%] prompt, 1,998 [29.5%] delayed, and 1,806 [26.7%] very delayed). The adjusted odds of any exacerbation and a severe exacerbation during 12-month follow-up increased by 13% (odds ratio [95% CI]: 1.13 [1.11-1.15]) and 10% (1.10 [1.08-1.12]), respectively, for each 30-day delay in triple therapy initiation, and the mean number of exacerbations increased by 5.4% (95% CI = 4.7%-6.1%). There was a 3.0% increase (95% CI = 2.2%-3.8%) in mean all-cause costs and a 3.7% increase (95% CI = 2.9%-4.6%) in total COPD-related costs for each 30-day delay of triple therapy initiation. CONCLUSIONS: Longer delays in triple therapy initiation after a COPD hospitalization result in greater risk of subsequent exacerbations and higher health care resource use and costs. Adequate post-discharge follow-up care and earlier consideration of triple therapy may improve clinical and economic outcomes among patients with COPD. DISCLOSURES: This study was funded by AstraZeneca. Dr Evans is employed by Merative, formerly IBM Watson Health, and Mr Tkacz was employed by IBM Watson Health at the time of this study; Merative/IBM Watson Health received funding from AstraZeneca to conduct this study. Mr Pollack, Dr Staresinic, Dr Feigler, and Dr Patel are employed by AstraZeneca. Dr Touchette, Dr Portillo, and Dr Strange are paid consultants to AstraZeneca. Dr Strange also participates in research grants paid to the Medical University of South Carolina by AstraZeneca, CSA Medical, and Nuvaira, and is a consultant to GlaxoSmithKline, Morair, and PulManage regarding COPD.

Purpose: Nasal polyps (NPs) develop in 20% to 30% of patients with chronic rhinosinusitis. Severe forms of chronic rhinosinusitis with nasal polyposis (CRSwNP) may be treated with systemic corticosteroids (SCSs), which increase the risk for adverse clinical outcomes. This study compared the incidence of SCS-related adverse outcomes and health care resource utilization and costs between patients with CRSwNP who had SCS exposure and those who did not have SCS exposure., Methods: This retrospective cohort study used health care claims data from adult patients with CRSwNP identified in the IBM Ⓡ MarketScan Ⓡ Databases between January 2003 and June 2019. The first SCS prescription date in SCS users or a matched date in SCS nonusers (controls) represented the index date. Enrollment for ≥1 year before and after the index date was required. SCS-related adverse outcomes and costs were compared between all SCS users and controls, and among subgroups of patients who had claims for 1-3 and ≥4 SCS prescriptions in the 12-month postindex period. Comparisons were also made among SCS users and controls who previously had and did not have NP surgery, and those with and without comorbid asthma. Inverse probability of treatment weights was applied to all comparisons, which were evaluated for a variable-length follow-up period., Findings: SCS users (n = 37,740) had a greater risk for any adverse outcome than controls (n = 7032) (incidence rate ratio [IRR] = 1.10; 95% CI, 1.05-1.16). The risk for adverse outcomes was highest in the subgroups that did not have NP surgery and that had ≥4 SCS claims (n = 2993) versus controls who did not have NP surgery (n = 5078) (IRR = 1.30; 95% CI, 1.18-1.44). Similarly, patients with asthma and ≥4 SCS claims (n = 4195) had a greater risk for SCS-related outcomes versus controls with asthma (n = 1226) (IRR = 1.36; 95% CI, 1.19-1.55). SCS users incurred 60% higher all-cause costs versus non-SCS users (P < 0.001)., Implications: In patients with CRSwNP, SCS use was associated with a higher risk for adverse outcomes and with increased health care costs compared with controls without SCS exposure. Alternative treatment strategies that avoid and/or reduce SCS use may decrease health care costs and the risk for adverse outcomes among patients with CRSwNP., (Copyright © 2022 AstraZeneca. Published by Elsevier Inc. All rights reserved.)