Continued Use Research Articles

Breast Cancer in Users of Levonorgestrel-Releasing Intrauterine Systems

This study uses data from nationwide Danish registries to assesses breast cancer risk with continuous use of levonorgestrel-releasing intrauterine systems, accounting for other hormonal exposures.

Technology and Continuous Glucose Monitoring Access, Literacy, and Use Among Patients at the Diabetes Center of an Inner-City Safety-Net Hospital: Mixed Methods Study.

Despite the existence of an increasing array of digital technologies and tools for diabetes management, there are disparities in access to and uptake and use of continuous glucose monitoring (CGM) devices, particularly for those most at risk of poor diabetes outcomes. This study aims to assess communication technology and CGM access, literacy, and use among patients receiving treatment for diabetes at an inner-city safety-net hospital. A survey on digital technology ownership and use was self-administered by 75 adults with type 1 and type 2 diabetes at the diabetes clinic of Grady Memorial Hospital in Atlanta, Georgia. In-depth interviews were conducted with 16% (12/75) of these patient participants and 6 health care providers (HCPs) to obtain additional insights into the use of communication technology and CGM to support diabetes self-management. Most participants were African American (66/75, 88%), over half (39/75, 52%) were unemployed or working part time, and 29% (22/75) had no health insurance coverage, while 61% (46/75) had federal coverage. Smartphone ownership and use were near universal; texting and email use were common (63/75, 84% in both cases). Ownership and use of tablets and computers and use and daily use of various forms of media were more prevalent among younger participants and those with type 1 diabetes, who also rated them as easier to use. Technology use specifically for diabetes and health management was low. Participants were supportive of a potential smartphone app for diabetes management, with a high interest in such an app helping them track blood sugar levels and communicate with their care teams. Younger participants showed higher levels of interest, perceived value, and self-efficacy for using an app with these capabilities. History of CGM use was reported by 56% (42/75) of the participants, although half (20/42, 48%) had discontinued use, above all due to the cost of the device and issues with its adhesive. Nonuse was primarily due to not being offered CGM by their HCP. Reasons given for continued use included convenience, improved blood glucose control, and better tracking of blood glucose. The in-depth interviews (n=18) revealed high levels of satisfaction with CGM by users and supported the survey findings regarding reasons for continued use. They also highlighted the value of CGM data to enhance communication between patients and HCPs. Smartphone ownership was near universal among patients receiving care at an inner-city hospital. Alongside the need to address barriers to CGM access and continued use, there is an opportunity to leverage increased access to communication technology in combination with CGM to improve diabetes outcomes among underresourced populations.

On-Farm Grain Yield Stability and Farmer Perceptions on Pre-release Pearl Millet Lines in Zimbabwe

Farmer participation in on-farm research does not only accelerate information gathering but also results in adoption of new research products. Here, we report on-farm trials conducted across five districts of Matabeleland province in Zimbabwe to explicate grain yield stability and farmer perceptions on eight pre-release pearl millet (Pennisetum glaucum L.) lines. The results indicated that genotypic effects on grain yield were significant in both individual and across-site analysis of variance and that farmers prioritize earliness and grain yield as must-have traits in millet varieties. The five districts were grouped into two distinct environments, with four districts (i.e., Bulilima, Gwanda, Matopos and Tsholotsho) in one group (i.e., DGrp1) and Mangwe district forming the second group (DGrp2). Pearl millet pre-release lines PM1 (1.425 kg ha-1), PM9 (1.043 kg ha-1) and PM6 (761.8 kg ha-1) showed high yield, stability and were the most preferred by farmers. In conclusion, on-farm trials may offer the quickest possible solution to boost low-pearl millet production resulting from the continuous use of unproductive landraces and old varieties by farmers.

Ketone Management in Pediatric Diabetes Centers in the USA: Current Practices and a Call for Improved Standardization

Introduction: Diabetic ketoacidosis (DKA) is the leading cause of mortality among youth with type 1 diabetes (T1D). Guidelines for DKA prevention exist; however, specific guidance about when to check ketones and how to manage youth using insulin pumps and automated insulin delivery (AID) systems is lacking. Methods: A 35-item online survey exploring clinical ketone management practices for youth with T1D in the USA was distributed to diabetes healthcare professionals (HCPs). Survey responses, including multiple-choice and Likert scale questions, were summarized and rates of agreement and disagreement (Likert scale 4, 5 vs. 1, 2, 3) are reported. Results: In total, 123 HCPs (51% physicians, 26% diabetes educators, 19% nurse practitioners) from 47 institutions completed the survey. Seventy percent worked at academic specialty centers. Ninety-seven percent reported >50% continuous glucose monitoring use in their clinic and 72% reported >50% insulin pump use. Although 79% reported having ketone management protocols, the level and duration of hyperglycemia at which ketone monitoring was advised ranged from >200 to 350 mg/dL and from 0 min to >6 h of duration. While 72% had distinct ketone management protocols for pump users, only 29% had specific protocols for AID. Sixty-two percent agreed that DKA due to infusion site failure was a significant problem in their practice, and 70% agreed there was a need to standardize ketone management guidelines. Conclusions: The preventable nature and high incidence of DKA highlight the need to build consensus for clinical ketone management and to develop tools to facilitate management, especially as the use of diabetes technologies continues to increase.

Lethal disruption of the bacterial gut community in Eastern subterranean termite caused by boric acid.

The Eastern subterranean termite, Reticulitermes flavipes (Kollar) (Blattodea: Rhinotermitidae), is a significant pest, causing extensive damage to structures that amount to substantial economic losses. Boric acid is widely used for wood preservation due to its stability and broad-spectrum insecticidal properties, yet its impact on termite gut microbiomes and the implications of such effects remain understudied. Our study evaluates the dose-dependent mortality of R. flavipes upon being provided boric acid treated filter papers and investigates the resulting dysbiosis within the termite gut microbiome. Consistent with reports from other insects, mortality increased in a dose-dependent manner, with the highest boric acid concentration (203.7 µg/cm2 of filter paper) significantly reducing termite survival. 16S rRNA gene sequencing of the gut bacterial microbiome revealed notable shifts in composition, indicating boric acid-induced dysbiosis. Aside from an overall decrease in bacterial diversity, the relative abundance of some symbionts essential for termite nutrition decreased in response to higher boric acid concentrations, while several opportunistic pathogens increased. Our findings extend the understanding of boric acid's mode of action in termites, emphasizing its ability to significantly modulate the bacterial symbiont community, which can have dire effects on termite biology. Considering its ability to protect wood from further termite consumption, our study supports the continued use of boric acid and related compounds for termite-resistant treatments for wood.

Evolution of Information Technology: A Comprehensive Review

Pervasive computing, wireless sensor networks, and M2M communication have fuelled the Internet of Things. The IoT connects and interacts with many physical items using unique internet addresses. This article covers the structure and technologies of the Internet of Things (IoT). The Internet of Things (IoT) needs a standard structure. Thus, it begins with a complete explanation of architectural designs and then discusses communication protocols and standards. The article also includes a succinct review of common IoT protocols and standards, helping the reader comprehend the topic. It also provides concrete solutions and tactics for addressing Internet of Things issues. The essay culminates by demonstrating the practical applications of the Internet of Things (IoT). Nolan's Stages Theory offered a new perspective on commercial IT development in 1973. The rapid digital revolution has changed its underlying foundation, despite its continuous use. The initial idea focused on IT in production. Later, it expanded to include the complex relationship between IT and organisational strategy. Since its inception, the methodology has helped business and IT leaders navigate IT adoption without technical details. Nolan's Stages Theory still applies, but cloud computing, artificial intelligence, big data, and the Internet of Things require a more evolved approach. The rapid progress of technology has blurred the barriers between IT and other company functions, requiring a complete digital transformation strategy. Information systems and organisational structures have grown in importance and interconnection. As firms gained independence and flexibility, IT systems developed. IT integration into key company activities has transformed it into a strategic enabler. Nolan's strict methodology provides valuable insights into history, but it limits understanding of the dynamic and transformational forces altering the digital landscape. Contemporary studies emphasise the need for flexible and adaptive frameworks to accommodate the rapid pace of technological advances and their impact on organisational structures and business models. Nolan's Stages Theory is still significant in IT administration, although it has limitations in today's networked and data-driven business contexts. Future research should develop sophisticated and forward-thinking models to help organizations navigate the digital transition.

Digital Health Interventions Are Effective for Irritable Bowel Syndrome Self-Management: A Systematic Review.

Digital health interventions (DHIs) could be a valuable self-management tool for patients with irritable bowel syndrome (IBS), but little research exists on IBS-focused DHIs and their effectiveness. This review aimed to identify DHIs for IBS and evaluate their characteristics, effectiveness, and feasibility. Our study team, including patient partners, conducted a systematic review using Medline, PsycINFO, Embase, Web of Science, and CINAHL from database inception to May 2024. Experimental and observational studies evaluating DHIs designed for use by IBS patients were included. Data extraction and assessment included study and DHI characteristics, effectiveness outcomes (symptom severity, quality of life, psychological indices, patient empowerment), and feasibility measures (adherence, usability, user satisfaction). Study quality and bias were assessed using a modified checklist of Downs and Black. Of the 929 identified, 13 studies of DHIs were included and deemed good quality on average (21,510 total participants) with six primary areas of focus: education, diet, brain-gut behavior skills, physiological support, health monitoring, and community engagement. Most DHIs were self-directed and reported statistically significant improvements in most effectiveness outcomes. Evidence suggests that DHIs focusing on brain-gut behavior skills or health monitoring may be most effective compared to other types of DHIs. However, their feasibility remains unclear, and the generalization of their impacts is limited. This review underscores the potential of DHIs in supporting IBS patients and improving their outcomes. However, additional research is warranted for continued intervention use in this population, including assessments on feasibility, safety, cost-effectiveness, and patient empowerment and experiences.

Endometrial Proliferation and Heavy Menstrual Bleeding Associated With Continuous Oral Contraceptive Use

Endometrial Proliferation and Heavy Menstrual Bleeding Associated With Continuous Oral Contraceptive Use

Outcomes and Healthcare Resource Utilization in Patients with COVID-19 Treated with Nirmatrelvir-Ritonavir: Real-World Data Analysis.

Background: Nirmatrelvir-ritonavir was granted emergency use authorization in Israel in January 2022 to treat high-risk patients with mild-to-moderate COVID-19. The aim of the study was to assess the association between nirmatrelvir-ritonavir treatment and COVID-19-related hospitalization and healthcare resource utilization (HCRU) in a country with a high level of vaccinations compared to patients who were offered treatment and declined. Methods: The Maccabi Healthcare Services dataset was used to identify high-risk SARS-CoV-2-positive adults from January to February 2022 who received nirmatrelvir-ritonavir within 5 days of symptom onset (treatment group) or who were offered nirmatrelvir-ritonavir treatment and declined it (reference group). COVID-19-related hospitalizations and all-cause mortality and HCRU within 30 days were compared between treatment and reference groups using inverse probability of treatment weighting. Results: Treatment and reference groups included 3460 (median age, 68.4 years) and 1654 (70.2 years) patients, respectively. Patients with ≥1 dose of COVID-19 vaccine accounted for 89.5% (treatment group) and 72.1% (reference group) of the total. Treatment was associated with a lower risk of COVID-19-related hospitalization (adjusted OR, 0.59 [95% CI, 0.41,0.83]). Results were similar by age group (18-64/≥65 years) and among patients with/without vaccination in the prior 180 days. There were 11 (0.3%) versus 11 (0.7%) deaths in the treatment and reference groups, respectively. Treated patients had lower inpatient HCRU and greater less intensive outpatient HCRU (e.g., telemedicine and emergency room visits). Conclusions: Nirmatrelvir-ritonavir treatment was associated with a reduced risk of COVID-19-related hospitalization and a shift to less intensive outpatient HCRU. Comparison with a reference group of nirmatrelvir-ritonavir-eligible patients who declined treatment enabled an unbiased outcome assessment. Real-world data gathered during the Omicron BA.1 variant wave of COVID-19 in Israel support the continued use of nirmatrelvir-ritonavir for high-risk adults of all ages, regardless of previous vaccinations.

Landslide hazard mapping in Chefchaouen, Morocco: AHP-GIS integration

ABSTRACT Chefchaouen province, located in northern Morocco, is prone to landslides because of its geological features, climate change, and human activities. We investigated landslide dynamics in this mountainous province using a multi-criteria spatial approach and GIS, applying the Analytical Hierarchy Process (AHP). Our findings identified 1267.877 km2 as low-risk, 1695.334 km2 as moderate-risk, and 904.2071 km2 as high-risk, mainly in the northern and northwestern regions. Forests were the most susceptible at 13.83%, followed by agricultural and bare lands, with water bodies least affected. Contributing factors include deforestation, wildfires, and agricultural practices. Our results highlight the need for targeted risk mitigation and continuous land use monitoring. Strategies like slope stabilisation and reforestation can improve landslide prediction and prevention, enhancing community resilience in Chefchaouen. This study’s innovative approach and insights into landslide prediction and prevention provide valuable knowledge to the field.

Antecedents the adoption of tour itineraries from smart travel apps: an integration of experiential consumption theory and innovation resistance theory

Purpose The purpose of this study investigate the antecedents the adoption of tour itineraries from smart travel apps. Travelers are progressively expanding their smart travel planning applications to organize their trip-related activities. With the help of these apps, users achieve their favorite tour itineraries and choose their preferred destinations. Design/methodology/approach This study aimed to examine the results of smart tour itineraries on travelers and elucidate the motivations for their continual use and why travel experts are increasingly using smart tour itineraries. Innovation resistance and experiential consumption theories were used in this study. SmartPLS 3.2.8 was used to consider 682 valid samples using structural equation modeling (SEM). Findings This analysis identified the following crucial factors: usage, value, risk and traditional barriers. Moreover, utilitarian and hedonic values significantly affected barriers. Finally, theoretical and practical suggestions are presented along with future research directions. Originality/value This study encompasses the tender of innovation resistance theory to travel itineraries by integrating experiential consumption theory in the context of smart tourism apps.

Consensus Statement on the Outcome of the European Herbal Health Products Summit - Which Way Forward?

Herbal medicinal products are a vital part of the healthcare system in Europe and beyond. Being predominantly sold as non-prescription medicines in pharmacies, they are very popular with patients, physicians, and pharmacists and are therefore an important part of self-medication. Interest in this sector has recently gained momentum, reflecting the ongoing revision of the general pharmaceutical legislation and the recent discussion on nutrition and health claims on foods based on the implementation report of Regulation (EC) No 1924/2006 by the European Parliament 1. Therefore, on 20th February 2024, the Society for Medicinal Plant and Natural Product Research (GA), in collaboration with the German Pharmaceutical Industry Association (BPI) and the German Medicines Manufacturers' Association (BAH, now Pharma Deutschland), hosted an in-person summit in Brussels entitled 'European Herbal Health Products Summit - Which way forward?'. The summit featured a wide range of speakers, including policymakers, regulatory authorities, industry representatives, and academic experts. It was divided into several sessions covering topics such as the future and relevance of herbal medicinal products in the EU, the revision of the EU pharmaceutical legislation, and the resulting impact on herbal medicinal products. Furthermore, the discussions delved into the "Health Claims Regulation" - the European Parliament's implementation report and the related regulatory challenges of herbal medicinal products at an EU level. This consensus paper summarises the current status and provided recommendations to pave the way for future strategies to ascertain the continued use of herbal medicinal products as an important therapeutic option for patients.

"Explosive" CaCO3 microcapsules driven by EDTA combined with a "signal booster" semiconductor Zn0.995Ce0.005O SERS substrate for ultra-sensitive SERS detection of chloramphenicol

BackgroundChloramphenicol (CAP) is a broad-spectrum antibiotic, and its continuous use in human medicine, livestock has resulted disturbances in ecosystem stability. The complex background and low concentration of CAP in aquatic environments present significant scientific challenges for its sensitive detection. Currently detection techniques such as high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) are hindered by their complex procedures and high costs. Surface-enhanced Raman spectroscopy (SERS), due to its unique ability for fingerprint recognition, has emerged as a powerful tool for analysis and detection. However, it is often limited by the low kurtosis expression of the target. ResultThe water-soluble explosive polyethylenimide grafted calcium carbonate (PEI@CaCO3) microcapsule was utilized to encapsulate the signal probe Ag@4-NTP and combine it with a semiconductor SERS substrate Zn0.995Ce0.005O, enabling ultra-sensitive detection of CAP through a signal attenuation strategy. Moreover, magnetic molecularly imprinted polymers (MMIP) and nucleic acid aptamers were employed as capture probes for achieving rapid and direct magnetic separation, followed by layer-by-layer assembly to construct the sensor probe. In the presence of CAP, the aptamers and rMMIPs selectively recognized the target, forming a PEI@CaCO3@Ag@4-NTP@Apt@CAP@rMMIPs "sandwich" structure (Microcapsule@Apt@rMMIPs). After multiple magnetic separations, the "igniter" EDTA solution was added, causing the CaCO3 capsules to rapidly "explode" and release a significant amount of Ag@4-NTP. This was then applied to the "signal booster" semiconductor SERS substrate. Under optimal conditions, this method exhibited a detection range of 1.0 × 10−5 M to 1.0 × 10−15 M, with a detection limit of 6.84 × 10−16 M. SignificantThe unite of magnetic MIP and nucleic acid aptamer to form a “sandwich” structure, in combination with a semiconductor SERS substrate, not only enhances the sensor's sensitivity but also offers significant economic advantages. Moreover, this innovative technology holds great promise for accurate and highly sensitive detection of pollutants in complex environments.

Bleeding vs Thrombosis: Treatment Strategy for Women Having Large Uterine Fibroids and DVT

Large uterine fibroids (UFs) are clonal neoplasms of the uterus that form during the mid and late-aged women. Such women generally consume oral contraceptive pills, tranexamic acid, or NSAIDS to manage heavy menstrual bleeding (HMB) and associated complications while waiting for a conclusive procedure or avoiding hysterectomy. The procoagulant effect of these medicinal agents can result in venous stasis of the lower limbs, leading to deep vein thrombosis (DVT), a challenging complication with HMB. We examine the complicated state of heavy bleeding with thrombosis and explore better management options. It has been seen that women with hypothyroidism have an increased risk of getting DVT due to an alteration in the coagulation system. These incidences are mostly associated with higher uterine weight, which is related to the extrinsic compression of the inferior vena cava. In such cases, the occurrence of postoperative thrombosis is riskier if hysterectomy/myomectomy is the only option. Utilization of appropriate anticoagulants with modification of the steroid-hormone system using hormone agonists or antagonists (e.g., levonorgestrel intrauterine system, high-dose progestin-only therapy, danazol, aromatase inhibitors, Vitamin-D supplements or selective estrogen receptor modulators) could be an effective technique, but adverse consequences of continued use should be monitored. More research is needed into the basic biology associated with the role of growth factors and genetic alterations in these malignancies. The development of new leiomyomas following conservative therapy is also a significant issue.

Postpartum Psychiatric Outcomes and Sick Leave After Discontinuing SSRI or SNRI in Pregnancy

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are consistently reported to be discontinued by approximately half of pregnant women. Little is known about how this may be associated with postpartum psychiatric health. To investigate associations of SSRI or SNRI discontinuation in pregnant women with depression or anxiety and psychiatric health and sick leave absence after childbirth. This population-based cohort study was conducted between 2006 and 2019 using data from Swedish population-based registers. Pregnant women with a filled prescription of an SSRI or SNRI in the 90 days before pregnancy without recorded comorbid or severe psychiatric conditions were included. Analyses were performed in November 2023. K-means for longitudinal data was used to cluster trajectories of SSRI and SNRI use during pregnancy, resulting in 2 trajectory groups based on the number of days covered, defined as continued and discontinued use groups. The primary outcome was psychiatric-related hospitalizations by 90 days after childbirth. Secondary outcomes included psychiatric-related outpatient visits, self-harm and suicide, and any-cause mortality by 90 days after childbirth and all outcomes plus sick leave absence by 1.5 years after childbirth. Among 27 773 pregnant women (17 241 aged ≥30 years [62.1%] at childbirth), 13 184 women (47.5%) had discontinued SSRI or SNRI use and 14 589 individuals (52.5%) had continued use. Individuals in the discontinued compared with continued use group were younger (5588 women [42.4%] vs 4944 women [33.9%] aged <30 years), less educated (4281 women [32.5%] vs 5821 women [39.9%] who completed postsecondary education or above), and more likely to have smoked in early pregnancy (1445 individuals [11.0%] vs 1180 individuals [8.1%]), been born in a non-Nordic country (1641 individuals [12.4%] vs 975 individuals [6.7%]), and used anxiolytics (1301 individuals [9.9%] vs 1119 individuals [7.7%]) and hypnotics and sedatives (1609 individuals [12.2%] vs 1510 individuals [10.4%]). Psychiatric-related hospitalizations occurred in 49 individuals (0.4%) in the discontinued vs 59 individuals (0.5%) in the continued use group in the 90 days after childbirth, with an adjusted hazard ratio (aHR) of 1.28 (95% CI, 0.85-1.91), while at 1.5 years after childbirth, the aHR was 0.81 (95% CI, 0.66-1.00). Lower hazard rates for psychiatric-related outpatient visits in the discontinued vs continued use group at 90 days (aHR, 0.59; 95% CI, 0.53-0.66) and 1.5 years (aHR, 0.60; 95% CI, 0.57-0.64) after childbirth were found. No difference in sick leave absence was found; however, individuals who discontinued had fewer days of sick leave by 1.5 years after childbirth than those who continued (mean [SD], 44.6 [70.6] days vs 53.1 [82.3] days). In this study, approximately half of pregnant women discontinued SSRIs or SNRIs, and discontinuation during pregnancy was not associated with adverse psychiatric-related outcomes, including hospitalizations, outpatient visits, suicidal behavior, or sick leave absence in the 90 days or 1.5 years after childbirth.

QT Prolongation Associated with Administration of Bedaquiline, a Novel Anti-Tuberculosis Drug.

Bedaquiline is a diarylquinoline compound that has recently been introduced and approved for use in the treatment of multidrug-resistant tuberculosis (MDR-TB). Its mechanism of action is inhibition of adenosine triphosphate-synthase. In combination with other antibiotics, bedaquiline-containing regimens administered for 6 months achieve cure rates of roughly 90%, in contrast to the previously used, 24-month-long WHO-recommended regimens for the treatment of MDR-TB. However, since its introduction, concerns have been raised about its effects on QT prolongation and its safety in routine clinical use. We reviewed the published experience regarding bedaquiline use, QT prolongation, and adverse cardiac events when the drug was used alone or in combination. Overall, data are reassuring that bedaquiline use in clinical practice is not associated with an excess of cardiac deaths or other clinically meaningful cardiac events. This review provides reassurance and support for the continued use of bedaquiline in the treatment of MDR-TB.

Beyond the pandemic: evaluating the health care workforce’s readiness for sustained use of virtual care after COVID-19

Background and aims: This study aimed to investigate healthcare professionals (HCPs) preparedness to continue using telehealth beyond the COVID-19 pandemic, to examine the perceived ability of HCPs to appraise the reliability of online information sources (digital literacy) and, to examine whether a relationship exists between this and preparedness to continue using telehealth. Methods: Single-site cross-sectional survey of HCPs in an outpatient and community therapy setting. The survey was based on a rapid literature review guided by the Theory of Planned Behaviour and Technology Acceptance Model. Descriptive statistics were used to summarise participant demographics, preparedness for telehealth, and digital literacy (based on confidence in appraising online information). Multivariable logistic regression assessed the associations between preparedness to continue using telehealth, the ability to evaluate online information sources, and demographic variables. Results: A total of 783 HCPs were invited, 310 responded, with 287 participants included in the final analysis (37% response rate excluding incomplete surveys). The analysis shows that 54.8% of participants preferred to return to in-person care. Preparedness to continue telehealth varied by profession and clinical activity, with medical professionals and script provision showing the highest readiness for continued telehealth use and allied health professionals the least likely to continue using telehealth (36%). Most (89%) of HCPs felt confident identifying reliable online information sources and there was no relationship between perceived ability to evaluate online information and preparedness to use telehealth. Conclusion: Results suggest hesitancy amongst allied staff toward continued telehealth use post the pandemic, which may be due to the type of care they provide. Future studies on technologies that support HCPs in providing more intensive virtual care would be of benefit.

Occurrence of a population of the root-knot nematode, Meloidogyne incognita, with low sensitivity to two major nematicides, fosthiazate and fluopyram, in Japan.

The root-knot nematode (RKN), Meloidogyne incognita, affects food production globally and nematicides, such as fosthiazate and fluopyram, are frequently used in Japan to control damage caused by RKN. In aboveground pests, the emergence of a population with developed resistance is frequently found after the continuous use of the same pesticides; however, there are few studies on changes in the sensitivity of plant-parasitic nematodes, including RKN, to nematicides. We compared the sensitivity of two populations of M. incognita to fosthiazate and fluopyram, one population with a history of exposure to fosthiazate and 1,3-dichloropropene (Ibaraki population) and the other without nematicide use for decades (Aichi population). A concentration of fosthiazate and fluopyram causing 50% mortality at 24 h post-treatment (LC50) was markedly higher in the Ibaraki population (5.4 and 2.3 mg L-1) than in the Aichi population (0.024 and 0.011 mg L-1 in fosthiazate and fluopyram, respectively), indicating the low sensitivity of the Ibaraki population to fosthiazate and fluopyram. Experiments using different enzyme inhibitors indicated the involvement of acetylcholinesterase (AChE), which is the target of fosthiazate, and glutathione S-transferase (GST), a typical enzyme related to detoxification, in the low sensitivity mechanism. The activity of AChE was 33-fold higher in the Ibaraki population than in the Aichi population and there were many differences in their nucleotide sequences. In addition, the gene expression level of GST was 239-fold higher in the Ibaraki population than in the Aichi population. These results revealed differences in the sensitivity to nematicides among RKN populations. Two factors were identified as related to the mechanism of low sensitivity in the Ibaraki population. This is the first report showing the difference in the sensitivity to fluopyram between populations of M. incognita. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Alkylsulfones: novel chemical scaffolds targeting the vesicular acetylcholine transporter usher in a new generation of insecticides.

Insecticides targeting the nervous system have been the most widely used to control arthropod pests due to their fast onset of action leading to efficient crop protection. With their continued use, resistance has and will become an inevitable challenge that demands continued efforts in identifying and developing new insecticidal chemistries acting on novel targets. In a recent publication, the results of a comprehensive study investigating the mode of action of novel chemical scaffolds based on the 2-(3-ethylsulfonyl-2-pyridyl)-heterocycles, alkylsulfones, was presented, concluding that their primary target is the vesicular acetylcholine transporter. © 2024 Society of Chemical Industry.

6903 The Treatment May Be Worse Than The Disease: The Real-World Clinical Burden Of Disease And Treatment In Congenital Adrenal Hyperplasia

Abstract Disclosure: W. Huang: Consulting Fee; Self; Spruce Biosciences. Research Investigator; Self; Spruce Biosciences. R. Charlton: Employee; Self; Spruce Biosciences. S. Sile: Employee; Self; Spruce Biosciences. C. Dieyi: Employee; Self; STATinMED. S. Adams: Employee; Self; STATinMED. J. Maynard: Employee; Self; STATinMED. C.N. Barnes: Employee; Self; Spruce Biosciences. A.H. Hamrahian: Consulting Fee; Self; Spruce Biosciences. Research Investigator; Self; Spruce Biosciences. Background and Aims: Classic congenital adrenal hyperplasia (CAH) is a group of autosomal recessive conditions that affects the production of adrenal hormones, leading to deficiencies in cortisol and aldosterone, and excess in adrenal androgens. Current treatment includes mineralocorticoids and oral glucocorticoids (GCs) for physiologic cortisol replacement and hypothalamic-pituitary-adrenal (HPA) axis suppression to control androgen levels. The health impacts of hyperandrogenemia include accelerated skeletal maturation leading to adult short stature, precocious puberty, acne, hirsutism, male pattern baldness, adrenal rest tumors, and infertility. There are also serious adverse events due to the long-term use of supraphysiologic doses of GCs. The aim of this study was to explore the risks associated with CAH diagnosis and treatment. Methods: This cross-sectional study used medical administrative claims data within 2014-2021 from RWD Insights®, an all-payer claims database in the US. Adult patients were required to have a diagnosis of CAH (ICD-9/10-CM: 255.9, E25.0, E25.9) and continuous use of oral GCs (defined as a proportion of days covered of 75% or more in any given calendar year). Patients were further required to receive an average daily GC dose of ≥10mg/day hydrocortisone equivalent and be free of pituitary disorders. Non-CAH controls were also selected if they did not have a CAH diagnosis or any GC use. Demographic characteristics and comorbidity rates were compared between patients with and without CAH during the study period. For comorbidity rate comparisons, rate ratios (RR) and 95% confidence intervals (CI) were computed. Results: A total of 1,532,141 (CAH: 2,033; Non-CAH: 1,530,108) were eligible for the study. A lower proportion of the CAH cohort was elderly (i.e., 65+ years; 11% vs. 26%), and there were more females (67% vs. 57%), as compared to the non-CAH cohort. After propensity score matching (PSM) on demographic characteristics, there were 2,019 and 8,076 patients in the CAH and non-CAH cohort, respectively, and patient characteristics were balanced. There were higher rates of comorbidities in the CAH cohort. Some notable differences, RR (95%CI), include GC related comorbidities such as osteoporosis/necrosis, 3.48 (3.36, 3.60) and fractures, 2.14 (1.90, 2.39); metabolic disorders, 2.20 (2.08, 2.33), obesity, 1.35 (1.26-1.44), type 2 diabetes, 1.27 (1.18,1.36), and cardiovascular disorders, 1.24 (1.16, 1.33); and CAH related comorbidities, hirsutism, 11.70 (11.34, 12.06) and testicular hypofunction, 5.48 (5.24, 5.71). Conclusions: This study suggests the association of several comorbidities with CAH, highlighting the burden of both the disease and treatment. Novel, non-steroidal treatments that improve hormonal balance in CAH could ameliorate the systemic risks associated with hyperandrogenemia and chronic overexposure to GCs. Presentation: 6/1/2024