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1.
ESMO Open ; 9(7): 103626, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38968929

RESUMEN

BACKGROUND: Determining the maximum tolerated dose (MTD) remains the primary objective for the majority of dose-finding oncology trials. Whilst MTD determination often relies upon clinicians to identify dose-limiting toxicities (DLTs) experienced by patients during the trial, research suggests that clinicians may underreport patient's adverse events. Therefore, contemporary practice may be exposed to recommending intolerable doses to patients for further investigation in subsequent trials. There is increasing interest in patients self-assessing their own symptoms using patient-reported outcomes (PROs) in dose-finding trials. DESIGN: We present Utility-PRO-Continual Reassessment Method (U-PRO-CRM), a novel trial design which simultaneously uses clinician-rated and patient-rated DLTs (Clinician-DLTs and Patient-DLTs, respectively) to make dose (de-)escalation decisions and to recommend an MTD. U-PRO-CRM contains the published PRO-CRM as a special case and provides greater flexibility to trade-off the rate of Patient-DLTs and Clinician-DLTs to find an optimal dose. We present simulation results for U-PRO-CRM. RESULTS: For specified trade-offs between Clinician-DLT and Patient-DLT rate, U-PRO-CRM outperforms the PRO-CRM design by identifying the true MTD more often. In the special case where U-PRO-CRM generalises to PRO-CRM, U-PRO-CRM performs as well as its published counterpart. U-PRO-CRM minimises the number of patients overdosed whilst maintaining a similar proportion of patients allocated to the true MTD. CONCLUSIONS: By using a utility-based dose selection approach, U-PRO-CRM offers the flexibility to define a trade-off between the risk of patient-rated and clinician-rated DLTs for an optimal dose. Patient-centric dose-finding strategies, which integrate PROs, are poised to assume an ever more pivotal role in significantly advancing our understanding of treatment tolerability. This bears significant implications in shaping the future landscape of early-phase trials.

2.
ISA Trans ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38972823

RESUMEN

This work investigates the less conservative stability conditions for linear systems with a time-varying delay. At first, augmented Lyapunov-Krasovskii functionals(LKFs) are constructed with state vectors that have not been utilized in the existing works, and an augmented zero equality that can be derived according to the augmented vector is proposed. By utilizing them, a stability condition is proposed in the form of a linear matrix inequality. And, by using novel delay-dependent LKFs and the introduced ones, improved results are obtained than the previous result. The addition of the delay-dependent LKFs increases the number of decision variables in the results. Therefore, any vectors of integral inequalities utilized in the proposed criterion are appropriately adjusted to reduce computational complexity. To check the excellence and validity of the proposed results, several numerical examples are applied.

3.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39012178

RESUMEN

The x-ray imaging crystal spectrometer (XICS) for Korea Superconducting Tokamak Advanced Research is applied to measure multiple atomic states, such as Ar16+, Ar17+, W43+, and W44+, with keeping the same spectrometer configuration because all spectra are well separated within the detector boundary. The first experimental results from the recently installed full W tiles in the lower divertor utilizing the XICS are discussed.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39037008

RESUMEN

Background: Previous studies suggest an association between late pregnancy exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) and increased postpartum hemorrhage (PPH) risk. This is the first pregnancy registry study to compare PPH outcomes among women with psychiatric illness exposed or unexposed to SSRIs/SNRIs proximate to delivery. Methods: This study used data from the National Pregnancy Registry for Psychiatric Medications to evaluate the relationship between SSRI/SNRI exposure in late pregnancy and PPH risk. The sample included n = 953 participants with retrospectively collected medical record data on postpartum blood loss, n = 453 unexposed to SSRIs/SNRIs during pregnancy, and n = 500 exposed at least during the week of delivery. PPH was defined as an estimated blood loss ≥500 mL following vaginal delivery or ≥1,000 mL following cesarean section (C-section), with onset of excessive bleeding occurring within the first 24 hours postpartum. Univariate and multivariate logistic regression analyses were performed to determine odds ratios. Results: Overall PPH incidence was 13.1%. SSRI/SNRI exposure was associated with a PPH unadjusted odds ratio of 1.42 compared to no exposure (95% confidence interval [CI: 0.97, 2.08]) and an adjusted odds ratio of 1.33 (95% CI [0.90, 1.97]). When stratified by delivery type, the odds ratio following vaginal delivery among women exposed to SSRIs/SNRIs was 1.04 (95% CI [0.63, 1.70]) versus 2.31 (95% CI [1.25, 4.26]) for C-section delivery; the adjusted C-section odds ratio was 2.21 (95% CI [1.18, 4.13]). Conclusions: Although these findings align with accumulating evidence suggesting SSRI/SNRI exposure may confer a modestly increased risk of PPH, particularly after C-section, the study was underpowered to make definitive conclusions. These preliminary data highlight the need for further research with larger sample sizes. Nevertheless, the findings underscore the importance of greater clinical monitoring for PPH following C-section, especially in women who may have other known PPH risk factors and are exposed to SSRIs/SNRIs in late pregnancy.

6.
ESMO Open ; 9(7): 103633, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38970841

RESUMEN

BACKGROUND: Cancer care has evolved rapidly, increasing the demand on healthcare resources. While many non-oral cancer treatments are administered in the hospital, not all necessitate complex medical care. Treatments that can be administered subcutaneously, intramuscularly, or as short intravenous infusions with a low risk of extravasation can be safely administered in the community. PATIENTS AND METHODS: Since 2017, the National University Cancer Institute, Singapore (NCIS) has operated a program called NCIS on-the-go (NOTG) comprising a network of community cancer treatment clinics located within 20 km of the hospital. NOTG provides 17 low-risk treatments and nursing services run by oncology-trained nurses without on-site physicians. Patients who receive their first dose of cancer treatment uneventfully in the cancer centre can opt-in to receive subsequent doses at any NOTG clinic. RESULTS: Treatment at NOTG has become more mainstream over the years, with its workload increasing by over sevenfold since 2017, and is now responsible for ∼10% of the total main cancer centre workload. The program is sustainable and financially viable to operate. A survey of 155 patients revealed a 96.8% user satisfaction rate, with the majority reporting tangible savings in travelling time, waiting time, and travelling costs. The diversion of low-risk treatments to NOTG has indirectly increased capacity and reduced waiting times at the main cancer centre for patients requiring complex cancer treatments, resulting in a win-win situation. CONCLUSIONS: NOTG represents an innovative model of care to deliver low-risk cancer treatments safely in the community and can be easily replicated in other countries.

7.
PLOS Glob Public Health ; 4(7): e0003380, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39042628

RESUMEN

With chronic disease prevalence on the rise globally, surveillance and monitoring are critical to improving health outcomes. Point-of-care (POC) testing can facilitate epidemiological research and enhance surveillance systems in limited resource settings, but previous research has identified bias between POC devices and laboratory testing. We compared the performance of two POC blood analyzers, the iSTAT handheld (Abbott, Princeton, NJ, USA) and the StatSensor Creatinine (Nova Biomedical, Waltham, MA, USA) to concurrent blood samples analyzed at a local laboratory that were collected from 89 agricultural workers in Guatemala. We measured creatinine and other measures of underlying health status with the POC and the lab blood samples. Pearson correlation coefficients, Bland-Altman plots, no intercept linear regression models and two-sample t-tests were used to evaluate the agreement between the POC and lab values collected across three study days and to assess differences by study day in a field setting. On average there was no observed difference between the iSTAT and lab creatinine measurements (p = 0.91), regardless of study day. Using lab creatinine as the gold standard, iSTAT creatinine results were more accurate compared to the Statsensor, which showed some bias, especially at higher values. The iSTAT had good agreement with the lab for sodium and blood urea nitrogen (BUN), but showed differences for potassium, anion gap, bicarbonate (TCO2), glucose, and hematocrit. In this tropical field setting, the research team devised a protocol to prevent the devices from overheating. In limited resource settings, POC devices carry advantages compared to traditional lab analyses, providing timely results to patients, researchers, and healthcare systems to better evaluate chronic health conditions. Technical challenges due to use of POC devices in high heat and humidity environments can be addressed using a standard protocol for transporting and operating the devices.

8.
Mol Metab ; 87: 101986, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38992428

RESUMEN

OBJECTIVE: During infection, metabolism and immunity react dynamically to promote survival through mechanisms that remain unclear. Pro-opiomelanocortin (POMC) cleavage products are produced and released in the brain and in the pituitary gland. One POMC cleavage product, alpha-melanocyte-stimulating hormone (α-MSH), is known to regulate food intake and energy expenditure and has anti-inflammatory effects. However, it is not known whether α-MSH is required to regulate physiological anti-inflammatory responses. We recently developed a novel mouse model with a targeted mutation in Pomc (Pomctm1/tm1 mice) to block production of all α-MSH forms which are required to regulate metabolism. To test whether endogenous α-MSH is required to regulate immune responses, we compared acute bacterial lipopolysaccharide (LPS)-induced inflammation between Pomctm1/tm1 and wild-type Pomcwt/wt mice. METHODS: We challenged 10- to 14-week-old male Pomctm1/tm1 and Pomcwt/wt mice with single i.p. injections of either saline or low-dose LPS (100 µg/kg) and monitored immune and metabolic responses. We used telemetry to measure core body temperature (Tb), ELISA to measure circulating cytokines, corticosterone and α-MSH, and metabolic chambers to measure body weight, food intake, activity, and respiration. We also developed a mass spectrometry method to measure three forms of α-MSH produced in the mouse hypothalamus and pituitary gland. RESULTS: LPS induced an exaggerated immune response in Pomctm1/tm1 compared to Pomcwt/wt mice. Both groups of mice were hypoactive and hypothermic following LPS administration, but Pomctm1/tm1 mice were significantly more hypothermic compared to control mice injected with LPS. Pomctm1/tm1 mice also had reduced oxygen consumption and impaired metabolic responses to LPS compared to controls. Pomctm1/tm1 mice had increased levels of key proinflammatory cytokines at 2 h and 4 h post LPS injection compared to Pomcwt/wt mice. Lastly, Pomcwt/wt mice injected with LPS compared to saline had increased total α-MSH in circulation 2 h post injection. CONCLUSIONS: Our data indicate endogenous α-MSH contributes to the inflammatory immune responses triggered by low-dose LPS administration and suggest that targeting the melanocortin system could be a potential therapeutic for the treatment of sepsis or inflammatory disease.

9.
Heliyon ; 10(13): e33041, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39040372

RESUMEN

The decommissioning of nuclear power plants has led to a surge in the production of radioactive waste, necessitating the development of accurate and reliable measurement methods for safe waste disposal. This study presents the development of a new concrete reference material (RM) containing beta, and gamma nuclides for quality assurance and quality control (QA/QC) in concrete measurements. The newly developed RM manufacturing method was used to ensure sample homogeneity; rigorous processes were followed according to ISO guidelines. The RM, designed to mimic real waste matrices, targeted six radionuclides: 60Co, 134Cs, 137Cs, 152Eu, 154Eu, and 90Sr. Homogeneity and stability tests, conducted according to ISO guidelines, confirmed the suitability of the concrete RM for QA/QC purposes. Reference values for the six radionuclides in RM ranged from 66.0 to 172.6 Bq kg-1. The expanded uncertainties of the reference values, at a 95 % confidence level (k = 2), ranged from approximately 7.1 %-17.2 %. The developed RM holds potential as proficiency test material and for validating and verifying analytical methods in radioactive waste analysis. Additionally, the manufacturing method introduced here opens doors for diverse applications, enabling the production of accurate and reliable reference materials for various waste matrices.

10.
Ann Oncol ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38942080

RESUMEN

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

11.
JAMA Netw Open ; 7(6): e2417873, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38935379

RESUMEN

Importance: Adjuvant endocrine therapy (AET) use among women with early-stage, hormone receptor-positive breast cancer reduces the risk of cancer recurrence, but its adverse symptoms contribute to lower adherence. Objective: To test whether remote monitoring of symptoms and treatment adherence with or without tailored text messages improves outcomes among women with breast cancer who are prescribed AET. Design, Setting, and Participants: This nonblinded, randomized clinical trial (RCT) following intention-to-treat principles included English-speaking women with early-stage breast cancer prescribed AET at a large cancer center with 14 clinics across 3 states from November 15, 2018, to June 11, 2021. All participants had a mobile device with a data plan and an email address and were asked to use an electronic pillbox to monitor AET adherence and to complete surveys at enrollment and 1 year. Interventions: Participants were randomized into 3 groups: (1) an app group, in which participants received instructions for and access to the study adherence and symptom monitoring app for 6 months; (2) an app plus feedback group, in which participants received additional weekly text messages about managing symptoms, adherence, and communication; or (3) an enhanced usual care (EUC) group. App-reported missed doses, increases in symptoms, and occurrence of severe symptoms triggered follow-ups from the oncology team. Main Outcomes and Measures: The primary outcome was 1-year, electronic pillbox-captured AET adherence. Secondary outcomes included symptom management abstracted from the medical record, as well as patient-reported health care utilization, symptom burden, quality of life, physician communication, and self-efficacy for managing symptoms. Results: Among 304 female participants randomized (app group, 98; app plus feedback group, 102; EUC group, 104), the mean (SD) age was 58.6 (10.8) years (median, 60 years; range, 31-83 years), and 60 (19.7%) had an educational level of high school diploma or less. The study completion rate was 87.5% (266 participants). There were no statistically significant differences by treatment group in AET adherence (primary outcome): 76.6% for EUC, 73.4% for the app group (difference vs EUC, -3.3%; 95% CI, -11.4% to 4.9%; P = .43), and 70.9% for the app plus feedback group (difference vs EUC, -5.7%; 95% CI, -13.8% to 2.4%; P = .17). At the 1-year follow-up, app plus feedback participants had fewer total health care encounters (adjusted difference, -1.23; 95% CI, -2.03 to -0.43; P = .003), including high-cost encounters (adjusted difference, -0.40; 95% CI, -0.67 to -0.14; P = .003), and office visits (adjusted difference, -0.82; 95% CI, -1.54 to -0.09; P = .03) over the previous 6 months compared with EUC participants. Conclusions and Relevance: This RCT found that a remote monitoring app with alerts to the patient's care team and tailored text messages to patients did not improve AET adherence among women with early-stage breast cancer; however, it reduced overall and high-cost health care encounters and office visits without affecting quality of life. Trial Registration: ClinicalTrials.gov Identifier: NCT03592771.


Asunto(s)
Antineoplásicos Hormonales , Neoplasias de la Mama , Cumplimiento de la Medicación , Aplicaciones Móviles , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Persona de Mediana Edad , Cumplimiento de la Medicación/estadística & datos numéricos , Antineoplásicos Hormonales/uso terapéutico , Anciano , Envío de Mensajes de Texto , Adulto , Quimioterapia Adyuvante
13.
Anim Microbiome ; 6(1): 37, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38943213

RESUMEN

BACKGROUND: Pinus koraiensis cone essential oil (PEO) contains functional compounds such as monoterpene hydrocarbons, and the administration of PEO reduced methane (CH4) emissions during growing phase of goats. However, the mode of action of PEO driven CH4 reduction is not known, especially how the administration of PEO can affect rumen microbiota and host metabolism in goats during the fattening phase. This study aimed to elucidate the potential microbial and host responses PEO supplementation in goats using metataxonomics (prokaryotes and protozoa) and metabolomics (rumen fluid and serum). RESULTS: Ten fattening Korean native goats were divided into two dietary groups: control (CON; basal diet without additives) and PEO (basal diet + 1.5 g/d of PEO) with a 2 × 2 crossover design and the treatment lasted for 11 weeks. Administration of PEO reduced CH4 concentrations in the exhaled gas from eructation by 12.0-13.6% (P < 0.05). Although the microbial composition of prokaryotes (bacteria and archaea) and protozoa in the rumen was not altered after PEO administration. MaAsLin2 analysis revealed that the abundance of Selenomonas, Christensenellaceae R-7 group, and Anaerovibrio were enriched in the rumen of PEO supplemented goats (Q < 0.1). Co-occurrence network analysis revealed that Lachnospiraceae AC2044 group and Anaerovibrio were the keystone taxa in the CON and PEO groups, respectively. Methane metabolism (P < 0.05) was enriched in the CON group, whereas metabolism of sulfur (P < 0.001) and propionate (P < 0.1) were enriched in the PEO group based on microbial predicted functions. After PEO administration, the abundance of 11 rumen and 4 serum metabolites increased, whereas that of 25 rumen and 14 serum metabolites decreased (P < 0.1). Random forest analysis identified eight ruminal metabolites that were altered after PEO administration, among which four were associated with propionate production, with predictive accuracy ranging from 0.75 to 0.88. Additionally, we found that serum sarcosine (serum metabolite) was positively correlated with CH4 emission parameters and abundance of Methanobrevibacter in the rumen (|r|≥ 0.5, P < 0.05). CONCLUSIONS: This study revealed that PEO administration reduced CH4 emission from of fattening goats with altered microbial interactions and metabolites in the rumen and host. Importantly, PEO administration affected utilizes various mechanisms such as formate, sulfur, methylated amines metabolism, and propionate production, collectively leading to CH4 reduction. The knowledge is important for future management strategies to maintain animal production and health while mitigate CH4 emission.

14.
Occup Environ Med ; 81(6): 308-312, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38937079

RESUMEN

OBJECTIVES: Previous radiologic and histopathologic studies suggest respirable crystalline silica (RCS) overexposure has been driving the resurgence of pneumoconiosis among contemporary US coal miners, with a higher prevalence of severe disease in Central Appalachia. We sought to better understand RCS exposure among US underground coal miners. METHODS: We analysed RCS levels, as measured by respirable quartz, from coal mine dust compliance data from 1982 to 2021. RESULTS: We analysed 322 919 respirable quartz samples from 5064 US underground coal mines. Mean mine-level respirable quartz percentage and mass concentrations were consistently higher for Central Appalachian mines than the rest of the USA. Mean mine-level respirable quartz mass concentrations decreased significantly over time, from 0.116 mg/m3 in 1982 to as low as 0.017 mg/m3 for Central Appalachian mines, and from 0.089 mg/m3 in 1983 to 0.015 mg/m3 in 2020 for the rest of the USA. Smaller mine size, location in Central Appalachia, lack of mine safety committee and thinner coal seams were predictive of higher respirable quartz mass concentrations. CONCLUSIONS: These data substantially support the association between RCS overexposure and the resurgence of coal workers' pneumoconiosis in the USA, particularly in smaller mines in Central Appalachia.


Asunto(s)
Minas de Carbón , Polvo , Exposición Profesional , Cuarzo , Dióxido de Silicio , Humanos , Exposición Profesional/análisis , Exposición Profesional/efectos adversos , Dióxido de Silicio/análisis , Dióxido de Silicio/efectos adversos , Estados Unidos , Polvo/análisis , Cuarzo/análisis , Región de los Apalaches/epidemiología , Exposición por Inhalación/análisis , Exposición por Inhalación/efectos adversos , Contaminantes Ocupacionales del Aire/análisis
15.
Nat Commun ; 15(1): 5129, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879678

RESUMEN

Glucagon, a hormone released from pancreatic α-cells, is critical for maintaining euglycemia and plays a key role in the pathophysiology of diabetes. To stimulate the development of new classes of therapeutic agents targeting glucagon release, key α-cell signaling pathways that regulate glucagon secretion need to be identified. Here, we focused on the potential importance of α-cell Gs signaling on modulating α-cell function. Studies with α-cell-specific mouse models showed that activation of α-cell Gs signaling causes a marked increase in glucagon secretion. We also found that intra-islet adenosine plays an unexpected autocrine/paracrine role in promoting glucagon release via activation of α-cell Gs-coupled A2A adenosine receptors. Studies with α-cell-specific Gαs knockout mice showed that α-cell Gs also plays an essential role in stimulating the activity of the Gcg gene, thus ensuring proper islet glucagon content. Our data suggest that α-cell enriched Gs-coupled receptors represent potential targets for modulating α-cell function for therapeutic purposes.


Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP Gs , Células Secretoras de Glucagón , Glucagón , Ratones Noqueados , Transducción de Señal , Glucagón/metabolismo , Animales , Células Secretoras de Glucagón/metabolismo , Ratones , Subunidades alfa de la Proteína de Unión al GTP Gs/metabolismo , Adenosina/metabolismo , Receptor de Adenosina A2A/metabolismo , Receptor de Adenosina A2A/genética , Masculino , Ratones Endogámicos C57BL , Islotes Pancreáticos/metabolismo
16.
Occup Environ Med ; 81(6): 296-301, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38886046

RESUMEN

OBJECTIVES: Spirometry is the primary lung function test utilised for medical surveillance and disability examination for coal mine dust lung disease. However, spirometry likely underestimates physiologic impairment. We sought to characterise abnormalities of single-breath diffusing capacity for carbon monoxide (DLCO) among a population of former coal miners. METHODS: Data from 3115 former coal miners evaluated at a West Virginia black lung clinic between 2006 and 2015 were retrospectively analysed to study the association between diffusion impairment (abnormally low DLCO), resting spirometry and the presence and severity of coal workers' pneumoconiosis on chest radiography. We developed ordinary least squares linear regression models to evaluate factors associated with per cent predicted DLCO (DLCOpp). RESULTS: Diffusion impairment was identified in 20.2% of subjects. Ten per cent of all miners with normal spirometry had diffusion impairment including 7.4% of never smokers. The prevalence of diffusion impairment increased with worsening radiographic category of pneumoconiosis. Mean DLCOpp decreased with increasing small opacity profusion subcategory in miners without progressive massive fibrosis. Linear regression analysis also showed significant decreases in DLCOpp with increasing small opacity profusion and presence of large opacities. CONCLUSIONS: Diffusion impairment is common among former coal miners, including among never smokers, miners without radiographic pneumoconiosis and miners with normal spirometry. These findings demonstrate the value of including DLCO testing in disability examinations of former coal miners and an important role for its use in medical surveillance of working miners to detect early chronic lung disease.


Asunto(s)
Antracosis , Minas de Carbón , Capacidad de Difusión Pulmonar , Espirometría , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Antracosis/fisiopatología , Antracosis/epidemiología , Anciano , Evaluación de la Discapacidad , West Virginia/epidemiología , Femenino , Adulto , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Exposición Profesional/efectos adversos , Modelos Lineales
17.
J Safety Res ; 89: 13-18, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38858035

RESUMEN

INTRODUCTION: Motor vehicle crashes (MVCs) are the leading cause of work-related deaths in the United States. The increasing popularity of the competitive rideshare market and the lack of oversight over workforce health and safety limits understanding of the current occupational hazards and associated risk factors faced by this precarious workforce. The objective of this analysis was to determine what the personal, social and occupational risk factors for work-related crashes in rideshare drivers are in the United States and suggest further research required to understand occupational health risks and opportunities for interventions. MATERIAL AND METHODS: We conducted a survey of a convenience sample of rideshare and taxi drivers using an online questionnaire. Rideshare respondents (n = 277) were recruited through an email that was distributed to people who subscribe to TheRideshareGuy.com. We examined the general characteristics of rideshare drivers by history of work-related MVCs and logistic regression models were used to determine major predictors of MVCs. RESULTS: Of 276 rideshare drivers that reported their crash history, one-third (n = 91, 33%) reported being involved in a work-related crash. Results from a multivariable logistic regression model showed rideshare MVCs were more likely in older drivers (aOR for 10 year increases in age, 1.55, p = 0.001), if drivers undertook 10 or more rideshare trips per day (aOR 1.84, p = 0.041), frequently or very frequently were driving on unfamiliar roads (aOR 1.72, p = 0.048) and driving whilst tired (aOR 3.03, p = 0.003). CONCLUSION: Precarious workers and health and safety is emerging as a major area of research focus. There is a unique opportunity to explore the occupational health risks in rideshare drivers to provide interventions that encourage growth of a healthy and fit rideshare workforce and promote work practices and future regulations aimed at improving safe work practices. PRACTICAL APPLICATIONS: This analysis paints a complex picture of personal and occupational factors that are associated with MVCs in rideshare drivers suggesting that additional policy development related to occupational health and safety of rideshare drivers could be constructive.


Asunto(s)
Accidentes de Tránsito , Humanos , Masculino , Estados Unidos/epidemiología , Femenino , Accidentes de Tránsito/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Factores de Riesgo , Encuestas y Cuestionarios , Conducción de Automóvil/estadística & datos numéricos , Adulto Joven , Accidentes de Trabajo/estadística & datos numéricos , Accidentes de Trabajo/prevención & control , Anciano , Modelos Logísticos
18.
Eur Rev Med Pharmacol Sci ; 28(10): 3669-3682, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38856143

RESUMEN

OBJECTIVE: Currently, human immunodeficiency virus (HIV) and multi-drug resistant tuberculosis (MDR-TB) without extensive drug resistance (XDR) are significant challenges in terms of the global burden of disease. This study aimed to evaluate the trends of the global burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR, focusing on differences in socioeconomic status and sex for 204 countries and territories across periods from 1990 to 2019. MATERIALS AND METHODS: Data from the Global Burden of Disease (GBD) 2019 study were obtained to construct a separate index measuring the burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR. Incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated for each case and group. A population-attributable fraction approach was used to assess mortality and incidence of HIV/AIDS and MDR-TB coinfection. 95% uncertainty intervals (UIs) were presented for all measures. RESULTS: Our global estimates suggest that there were approximately 450,000 (95% UI 247,000-785,000) incident cases of MDR-TB without XDR and 109,000 (43,000-210,000) deaths caused by MDR-TB without XDR among individuals who were HIV-negative in 2019. For HIV-positive individuals, the corresponding figures were approximately 47,000 (33,000-67,000) incident cases of MDR-TB and 19,000 (8,000-36,000) deaths due to MDR-TB in the same year. In 2019, higher numbers of incident cases and deaths were observed in males compared to females among individuals who were HIV-negative. Conversely, for HIV-positive individuals, females had higher numbers of incident cases and deaths compared to males. Specifically, the estimated numbers for incident cases were 23,000 (15,000-33,000) for females and 24,000 (17,000-35,000) for males, while the estimated numbers for deaths were 9,600 (4,000-17,900) for females and 9,800 (4,100-18,500) for males. Male-to-female ratios have remained above 1.0 from 1990 to 2019 in both incident cases and number of deaths for HIV-negative individuals. However, for HIV and MDR-TB coinfection, both ratios were below 1.0 in most of the time series. CONCLUSIONS: Males had more cases and deaths due to MDR-TB without XDR than females in HIV-negative patients, while females faced a higher incidence and mortality in HIV/AIDS-MDR-TB without XDR. Interventions are needed to deal with such factors, which increase the burden of coinfection among females across the world.


Asunto(s)
Infecciones por VIH , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Femenino , Masculino , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/tratamiento farmacológico , Incidencia , Salud Global , Carga Global de Enfermedades , Factores Sexuales , Coinfección/epidemiología , Prevalencia , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Caracteres Sexuales
19.
ESMO Open ; 9(6): 103482, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38833967

RESUMEN

BACKGROUND: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications. MATERIALS AND METHODS: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility. RESULTS: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71). CONCLUSIONS: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics.


Asunto(s)
Predisposición Genética a la Enfermedad , Pruebas Genéticas , Mutación de Línea Germinal , Neoplasias , Humanos , Femenino , Estudios Retrospectivos , Masculino , Pruebas Genéticas/métodos , Adulto , Persona de Mediana Edad , Neoplasias/genética , Anciano , Adulto Joven , Asia/epidemiología , Adolescente , Anciano de 80 o más Años
20.
Hum Genet ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38902498

RESUMEN

Polygenic risk scores (PRSs) enable early prediction of disease risk. Evaluating PRS performance for binary traits commonly relies on the area under the receiver operating characteristic curve (AUC). However, the widely used DeLong's method for comparative significance tests suffer from limitations, including computational time and the lack of a one-to-one mapping between test statistics based on AUC and R 2 . To overcome these limitations, we propose a novel approach that leverages the Delta method to derive the variance and covariance of AUC values, enabling a comprehensive and efficient comparative significance test. Our approach offers notable advantages over DeLong's method, including reduced computation time (up to 150-fold), making it suitable for large-scale analyses and ideal for integration into machine learning frameworks. Furthermore, our method allows for a direct one-to-one mapping between AUC and R 2 values for comparative significance tests, providing enhanced insights into the relationship between these measures and facilitating their interpretation. We validated our proposed approach through simulations and applied it to real data comparing PRSs for diabetes and coronary artery disease (CAD) prediction in a cohort of 28,880 European individuals. The PRSs were derived using genome-wide association study summary statistics from two distinct sources. Our approach enabled a comprehensive and informative comparison of the PRSs, shedding light on their respective predictive abilities for diabetes and CAD. This advancement contributes to the assessment of genetic risk factors and personalized disease prediction, supporting better healthcare decision-making.

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