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1.
PLoS One ; 19(8): e0308129, 2024.
Article in English | MEDLINE | ID: mdl-39106264

ABSTRACT

In Lower-Middle-Income-Countries women are encouraged to present at a birthing facility for skilled care, but attending early can be associated with additional harm. Women admitted in latent labour are more likely to receive a cascade of unnecessary interventions compared with those attending a birthing facility during active labour. One reason that women present early is pain, with higher rates of admission among those who pain catastrophise. The aim of this study was to explore the prevalence of pain catastrophising in nulliparous women in Nepal and to identify predictors for pain catastrophising. A cross sectional study was conducted using a semi-structured survey. The survey was completed by 170 women (18-32 years) in one higher education institution in Kathmandu. The survey included the pain catastrophising scale (PCS), current and previous pain and information about period pain, sociodemographic variables of age, ethnicity, and religion. The prevalence of pain catastrophising reported at a cut off score of PCS≥20 was 55.9% and at a cut off score of PCS≥30 was 17.1%. All women with a PCS ≥30 reported having painful periods. Those with a PCS≥20 were four times [95%CI 1.93-8.42] more likely to report painful periods affecting their daily activities (p<0.001) and those with PCS≥30 three times [95%CI1.10-10.53] more likely (p<0.05). In both cases ethnicity and age were not associated. Women with higher PCS were less likely to take pain medication. A high prevalence of pain catastrophising was reported. It is important to understand how women's previous negative experiences of pain and pain catastrophising are perceived and if they are contributing to the rise in obstetric intervention, particularly caesarean births, in Nepal. We recommend repeating this study with a larger sample representing a more diverse population.


Subject(s)
Catastrophization , Parity , Parturition , Humans , Female , Adult , Nepal/epidemiology , Prevalence , Adolescent , Pregnancy , Young Adult , Cross-Sectional Studies , Catastrophization/psychology , Catastrophization/epidemiology , Parturition/psychology , Surveys and Questionnaires , Pain Measurement
2.
EMBO J ; 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39174852

ABSTRACT

Tumor cell heterogeneity defines therapy responsiveness in neuroblastoma (NB), a cancer derived from neural crest cells. NB consists of two primary subtypes: adrenergic and mesenchymal. Adrenergic traits predominate in NB tumors, while mesenchymal features becomes enriched post-chemotherapy or after relapse. The interconversion between these subtypes contributes to NB lineage plasticity, but the underlying mechanisms driving this phenotypic switching remain unclear. Here, we demonstrate that SWI/SNF chromatin remodeling complex ATPases are essential in establishing an mesenchymal gene-permissive chromatin state in adrenergic-type NB, facilitating lineage plasticity. Targeting SWI/SNF ATPases with SMARCA2/4 dual degraders effectively inhibits NB cell proliferation, invasion, and notably, cellular plasticity, thereby preventing chemotherapy resistance. Mechanistically, depletion of SWI/SNF ATPases compacts cis-regulatory elements, diminishes enhancer activity, and displaces core transcription factors (MYCN, HAND2, PHOX2B, and GATA3) from DNA, thereby suppressing transcriptional programs associated with plasticity. These findings underscore the pivotal role of SWI/SNF ATPases in driving intrinsic plasticity and therapy resistance in neuroblastoma, highlighting an epigenetic target for combinational treatments in this cancer.

3.
Laryngoscope ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39166775

ABSTRACT

OBJECTIVES: Persistent obstructive sleep apnea (OSA) after adenotonsillectomy (AT) has been reported in 20%-30% of children. The aim of this study was to determine the predictive value of drug-induced sleep endoscopy (DISE) at the time of AT on subjective AT outcomes. METHODS: This was a prospective cohort study of children aged 2-18 years being treated with AT for sleep disordered breathing (SDB) with one or more risk factors for AT failure: age >7 years, obesity, severe baseline OSA, Black race. All underwent DISE at the time of AT. Potential predictors of subjective AT outcome included age, sex, obesity, and DISE patterns. Multivariable linear regression was used to model predictors of post-AT Pediatric Sleep Questionnaire (PSQ) and OSA-18 outcomes. RESULTS: Pre- and post-AT PSQ/OSA-18 responses were available from 194 children. Mean age was 9.3 ± 3.5 years, with 59% obese, 50% female, and 67% White. After AT, mean PSQ score decreased from 0.60 ± 0.19 to 0.28 ± 0.22, p < 0.001 and mean OSA-18 score decreased from 66 ± 21 to 37 ± 18, p < 0.001. The most frequent sites of obstruction were the tonsils (92%), nasal airway (77%), adenoids (64%), and velopharynx (65%). Multivariable regression modeling demonstrated worse outcomes with obesity, male gender, and multilevel obstruction that included the nasal airway and tongue base in addition to adenotonsillar obstruction. CONCLUSIONS: Persistent OSA and symptom burden after AT was common in this population. Obesity, male gender, and multilevel obstruction during DISE were all associated with worse subjective outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

4.
Am J Drug Alcohol Abuse ; 50(4): 481-491, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39158536

ABSTRACT

Background: Many national studies fail to account for discordance between sexual orientation dimensions (e.g. a mismatch between sexual identity and sexual attraction) or sexual identity fluidity (e.g. changes in sexual identity over time).Objective: To examine the longitudinal relationships among sexual identity fluidity/stability, sexual orientation discordance/concordance, and alcohol and other drug use disorder symptoms.Methods: The study used nationally representative longitudinal data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health (PATH) study of US adolescents and adults (N = 24,591).Results: Substance use disorder symptoms were most prevalent (45.8%) among bisexual-stable females relative to all other sexual identity subgroups. The adjusted odds ratios (AORs) of substance use disorder symptoms were significantly higher among bisexual-stable females vs. heterosexual-stable females in all models (AOR range: 1.94-2.32), while no such associations were found for males. Sexual identity-attraction discordant females had significantly greater AORs (17/20 instances) of substance use disorder symptoms compared to concordant females; this finding was not as consistent for males (6/20 instances).Conclusion: Sexual orientation discordance was significantly associated with substance use disorder symptoms, especially among females discordant in their sexual identity and attraction. Bisexual-stable and discordant females are at highest risk of developing symptomatic substance use; it is vital that they receive screening, no matter where they are in their coming out process. This study highlights pitfalls of relying solely on cross-sectional data using a single sexual orientation dimension to understand the relationship between sexual orientation and substance use disorder.


Subject(s)
Sexual Behavior , Substance-Related Disorders , Humans , Female , Longitudinal Studies , Male , Substance-Related Disorders/epidemiology , Adult , Adolescent , Young Adult , United States/epidemiology , Sexual and Gender Minorities/statistics & numerical data , Middle Aged , Bisexuality/statistics & numerical data , Prevalence
5.
Regul Toxicol Pharmacol ; 152: 105687, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39168368

ABSTRACT

We conducted a literature review of urinary 2,4-D in populations not associated with a herbicide application. Of the 33 studies identified, the median/mean concentrations were similar for children, adults, and pregnant women regardless of geography. Individuals with highest concentrations may have had opportunities to directly contact 2,4-D outside of an application. Most studies were conducted in populations in North America and did not examine potential sources of 2,4-D, or what factors might influence higher or lower urinary 2,4-D concentrations. In the future, prioritizing the examination of 2,4-D biomonitoring in other regions and collecting information on sources and factors influencing exposures would better our understanding of 2,4-D exposures globally. In all the studies reviewed the concentrations of urinary 2,4-D observed were orders of magnitude below the US regulatory endpoints, suggesting that people are not being exposed to 2,4-D at levels high enough to result in adverse health effects.


Subject(s)
2,4-Dichlorophenoxyacetic Acid , Biological Monitoring , Herbicides , 2,4-Dichlorophenoxyacetic Acid/urine , 2,4-Dichlorophenoxyacetic Acid/analysis , 2,4-Dichlorophenoxyacetic Acid/toxicity , Herbicides/urine , Herbicides/analysis , Humans , Biological Monitoring/methods , Female , Environmental Exposure/analysis , Environmental Exposure/adverse effects , Pregnancy , Adult
6.
Environ Sci Technol ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39012316

ABSTRACT

Reduction of Se(IV) by sulfur reducing bacteria (SRB) can remove Se from groundwater either by direct respiration or the production of H2S(g) and subsequent abiotic reduction. This study examined abiotic Se(IV) reduction by H2S(g) to determine the associated Se isotope fractionation. The extent of fractionation was compared to the results with studies of Se(IV) reduction in systems containing microorganisms to assess whether these processes could be distinguished. A solution containing Na2S was added in increasing concentrations to solutions containing Se(IV) as SeO32- to reduce and precipitate Se. Precipitates with three distinct colors were observed. Powder X-ray diffraction (PXRD) results yielded three distinct spectra for each of the three colors of precipitate, which corresponded to SenS8-n (orange) or Se(0) (red) and S(0) (yellow). The δ82Se values of the residual dissolved Se increased as the aqueous Se concentration decreased. The S/Se in solution affected the isotopic fractionation, with an 82ε of 10.1 ± 0.6‰ observed for solutions with S/Se < 1.7, and of 7.9 ± 0.3‰ for solutions with S/Se > 1.7.

7.
Am J Epidemiol ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39030726

ABSTRACT

Investigators conducting human subject research have typically conveyed only clinically actionable results back to individual participants. Shifting scientific culture around viewing participants as partners in research, however, is prompting investigators to consider returning as much data or results as the participant would like, even if they are not clearly actionable. Expanding return of individual results may add value for individual participants and their communities, refine future research questions and methods, build trust, and enhance retention of participants. Yet, gaps remain in understanding the implications of these changes for groups of 'vulnerable' participants, including pregnant and pediatric participants. We present the findings of a National Institutes of Health workshop on returning individual research results, particularly as applicable to pregnant and pediatric participants. Research participants who were panelists at the workshop agreed that they desire to receive their results. Workshop findings and current literature indicate that participants have differing preferences for what results they receive. One way to address the limits of current practice is to develop flexible digital platforms that convey individual results along with researchers' availability to answer questions, and to provide as much information as possible about actionable steps to control environmental exposures associated with disease risk.

8.
Oncologist ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39046894

ABSTRACT

BACKGROUND: The incidence of esophageal and gastric carcinoma (GEC) in elderly patients is increasing, yet patients ≥75 years have historically been underrepresented in clinical trials. We sought to investigate palliative chemotherapy administration patterns and survival outcomes in older adults. MATERIALS AND METHODS: A retrospective analysis identified patients aged 65-74 (young-old) and ≥75 years (older-old) diagnosed with advanced GEC. Patient and tumor characteristics were recorded, with descriptive analysis, time-to-event data analysis using Kaplan-Meier curves and multivariate Cox proportional hazards regression analysis performed. RESULTS: One hundred and ninety-eight "young-old" and 109 'older-old' patients were identified. Patient characteristics were similar between groups except for Charlson Co-morbidity Index (CCI), with lower co-morbidities in the "young-old" compared to "older-old" cohort (P < .001; CCI = 0 in 103 (52%) "young-old" vs 31 (28%) "older-old"). The primary diagnosis in both groups was adenocarcinoma. 119 (60%) "young-old" and 25 (23%) "older-old" patients received chemotherapy (P < .001). Performance status was the primary explanation for chemotherapy non-receipt in both cohorts; age was the explanation in 21 (25%) "older-old" patients and none in the "young-old" patients. PFS for first-line systemic therapy in "young-old" patients was 6.4 (95% CI 5.9-7.6) versus 7.5 months (95% CI 5.1-11.3) in "older-old" patients (P = .69) whilst respective OS was 12.3 (95% CI 10.1-15.5) and 10.4 months (95% CI 9.0-14.6) (P = .0816). Toxicity prompted chemotherapy cessation in 17 (15%) "young-old" and 3 (13%) "older-old" patients (P = .97). Multivariate analysis identified CCI and ECOG performance status as predictive for PFS and OS, respectively. No causative relationship was identified with other variables. CONCLUSION: Our study of real-world older-adults show that significant number of "older-old" patients with GEC do not receive chemotherapy. Among "older-old" adults who do receive systemic therapy, outcomes are comparable; this underscores the importance of geriatric assessment-guided care and suggests that age alone should not be a barrier to receipt of chemotherapy in patients with advanced GEC.

9.
Endocrinol Metab Clin North Am ; 53(3): 321-333, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39084810

ABSTRACT

The care of pregnant individuals with type 1 diabetes mellitus has experienced significant advancements in recent years. Preconception counseling has re-emerged as a core dimension of management. Continuous glucose monitoring plays an increasingly useful and beneficial role in gestational glycemic monitoring, a practice informed by improved maternofetal outcomes. While studies have not shown that continuous subcutaneous insulin infusion is superior to multiple daily injections of insulin for glycemic control, recent work has signaled that hybrid closed-loop systems with pregnancy-specific targets could meaningfully improve glycemic control and potentially ameliorate maternofetal outcomes while reducing self-care burden.


Subject(s)
Diabetes Mellitus, Type 1 , Pregnancy in Diabetics , Humans , Pregnancy , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 1/drug therapy , Female , Pregnancy in Diabetics/therapy , Insulin Infusion Systems/trends , Blood Glucose Self-Monitoring/methods , Insulin/administration & dosage , Insulin/therapeutic use , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use
10.
Diabetes Care ; 47(9): 1682-1687, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39042575

ABSTRACT

OBJECTIVE: To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin. RESEARCH DESIGN AND METHODS: A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61). RESULTS: The primary outcome, the treatment group difference in area under the curve for glucose >180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference -12 mg/dL, 95% CI -22 to -2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose <70 mg/dL occurred in one participant in each group. CONCLUSIONS: Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users.


Subject(s)
Blood Glucose , Diabetes Mellitus, Type 1 , Hypoglycemic Agents , Insulin , Humans , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/blood , Blood Glucose/drug effects , Blood Glucose/analysis , Adult , Insulin/administration & dosage , Insulin/therapeutic use , Male , Female , Administration, Inhalation , Middle Aged , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Postprandial Period , Insulin Infusion Systems , Insulin, Short-Acting/administration & dosage , Insulin, Short-Acting/therapeutic use
11.
Cancers (Basel) ; 16(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-39001383

ABSTRACT

Activating mutations in the RAS/MAPK pathway are observed in relapsed neuroblastoma. Preclinical studies indicate that these tumors have an increased sensitivity to inhibitors of the RAS/MAPK pathway, such as MEK inhibitors. MEK inhibitors do not induce durable responses as single agents, indicating a need to identify synergistic combinations of targeted agents to provide therapeutic benefit. We previously showed preclinical therapeutic synergy between a MEK inhibitor, trametinib, and a monoclonal antibody specific for IGF1R, ganitumab in RAS-mutated rhabdomyosarcoma. Neuroblastoma cells, like rhabdomyosarcoma cells, are sensitive to the inhibition of the RAS/MAPK and IGF1R/AKT/mTOR pathways. We hypothesized that the combination of trametinib and ganitumab would be effective in RAS-mutated neuroblastoma. In this study, trametinib and ganitumab synergistically suppressed neuroblastoma cell proliferation and induced apoptosis in cell culture. We also observed a delay in tumor initiation and prolongation of survival in heterotopic and orthotopic xenograft models treated with trametinib and ganitumab. However, the growth of both primary and metastatic tumors was observed in animals receiving the combination of trametinib and ganitumab. Therefore, more preclinical work is necessary before testing this combination in patients with relapsed or refractory RAS-mutated neuroblastoma.

12.
Cancers (Basel) ; 16(13)2024 Jul 06.
Article in English | MEDLINE | ID: mdl-39001537

ABSTRACT

Phosphosidesterases (PDEs) are key regulators of cyclic nucleotide signaling, controlling many hallmarks of cancer and playing a role in resistance to chemotherapy in non-small-cell lung cancer (NSCLC). We evaluated the anti-tumor activity of the anti-folate agent pemetrexed (PMX), alone or combined with biochemical inhibitors of PDE5, 8, 9, or 10, against squamous and non-squamous NCSLC cells. Genomic alterations to PDE genes (PDEmut) or PDE biochemical inhibition (PDEi) can sensitize NSCLC to PMX in vitro (observed in 50% NSCLC evaluated). The synergistic activity of PDEi with PMX required microdosing of the anti-folate drug. As single agents, none of the PDEis evaluated have anti-tumor activity. PDE biochemical inhibitors, targeting either cAMP or cGMP signaling (or both), resulted in significant cross-modulation of downstream pathways. The use of PDEi may present a new strategy to overcome PMX resistance of PDEwt NSCLC tumors but comes with important caveats, including the use of subtherapeutic PMX doses.

13.
Spine J ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39032609

ABSTRACT

BACKGROUND CONTEXT: The effectiveness of bracing with a thoraco-lumbo-sacral orthosis (TLSO) for adolescent idiopathic scoliosis (AIS) has been studied extensively, with a growing body of evidence supporting TLSO use. In this study we examine the effect of wear time and other important causal factors affecting curve progression and develop a risk model that can be applied to individual patients and is based on important casual factors. PURPOSE: Understand the impact of TLSO wear time and other risk factors in order to guide optimal treatment. STUDY DESIGN/SETTING: Prospective, multi-center, cohort study PATIENT SAMPLE: Individuals with a diagnosis of AIS, age of 10 to 16 years, primary Cobb angle of 20 to 45 degrees, Risser 0 to 2, <1 year post menarche if female, who were to be treated with a TLSO OUTCOME MEASURES: (1) Rate of primary curve progression, (2) surgery recommendation during TLSO treatment METHODS: Wear time was monitored with thermochrons. Participants were followed until the end of growth. We examined the causal effects of wear time and baseline skeletal maturity as measured by triradiate cartilage (TRC) status, Cobb angle, and age. We then fit an outcome prediction model (logistic regression) based on important casual factors. RESULTS: Our final cohort consisted of 145 individuals (baseline age 12.1-13.4 years). Wear time was an important cause of response to treatment, including an interaction with TRC status. Baseline Cobb angle and age were also meaningful causes of response. The prediction model was accurate (79%) and had good specificity (81%) and moderate sensitivity (68%) and an area under the receiver operating characteristic curve (AUC) of 0.81. Additionally, we were able to independently confirm previous estimates of treatment efficacy, with an odds ratio around 2.0. CONCLUSIONS: Our study showed the explicit causal effects of wear time, and baseline skeletal maturity, Cobb angle and age. The risk model we developed can be used for counseling patients and their families regarding TLSO wear and expectations for outcome.

14.
J Addict Nurs ; 35(2): 43-50, 2024.
Article in English | MEDLINE | ID: mdl-38829993

ABSTRACT

OBJECTIVE: The purpose of this proof-of-concept pilot study was to test the initial feasibility and limited efficacy of ArtSpective™ for perinatal substance use (PSU), a novel, arts-based intervention designed to decrease stigmatizing attitudes toward PSU. METHODS: Using a pre-post mixed methods quasi-experimental design, ArtSpective™ for PSU was pilot tested for proof of concept among a convenience sample of 11 undergraduate and graduate students with experience in maternal-infant nursing from a Midwestern U.S. nursing school. As a proof-of-concept pilot study, we evaluated feasibility (acceptability, demand, and implementation) and limited efficacy. Participants completed presurveys and postsurveys that included satisfaction items, demographic items, and an adapted version of the Attitudes About Drug Use in Pregnancy Scale and participated in a focus group. Focus group data were analyzed using constant comparative methods, and survey data were analyzed using descriptive statistics and Wilcoxon signed rank tests. RESULTS: Participants reported high demand and satisfaction with the intervention and provided recommendations to improve scalability. ArtSpective™ demonstrated significant improvement in stigma toward PSU (pre vs. post: p = .003; d = .633). CONCLUSION: ArtSpective™ for PSU demonstrated initial feasibility and limited efficacy for improving nurse attitudes toward PSU. Efforts are needed to further test this novel intervention, adapt it to augment existing educational interventions, and improve its scalability.


Subject(s)
Feasibility Studies , Social Stigma , Substance-Related Disorders , Humans , Female , Pilot Projects , Substance-Related Disorders/nursing , Pregnancy , Adult , Pregnancy Complications , Young Adult , Art Therapy , Surveys and Questionnaires , Focus Groups , Male
15.
J Natl Cancer Inst ; 116(8): 1198-1205, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38710483

ABSTRACT

BACKGROUND: Lack of diversity in the cancer research workforce persists, which the new requirement for all National Cancer Institute (NCI)-designated cancer centers to have a Plan to Enhance Diversity (PED) seeks to address. However, it is not well understood how different cancer centers are approaching the development and execution of these plans. Our objective was to assess how cancer centers are establishing and pursuing their PED. METHODS: We conducted a cross-sectional survey of members of the Cancer Center Diversity, Equity and Inclusion Network, which includes all NCI-designated cancer centers and several emerging centers. A total of 62 cancer centers (75% of those invited), including 58 NCI-designated cancer centers (81% of those with this designation), participated and completed a questionnaire that assessed PED leadership, major challenges, implementation strategies, and approach to evaluate PED progress. RESULTS: The most common PED challenge identified is recruiting diverse faculty (68% of centers), and the most common strategy currently used to address this is reviewing and revising faculty recruitment practices (67%). The most common approach centers are using to measure PED progress is shifts in demographics (68%), and data on the demographics of faculty, leadership, and trainees are available at 79%, 81%, and 75% of centers, respectively. CONCLUSIONS: Almost all centers have established a PED leadership structure, however, there is considerable variation in the approaches used to realize PED goals and in the resources provided to support PED work. Realizing opportunities to share and implement common best practices and exemplar programs has the potential to elevate the impact of PED efforts nationally.


Subject(s)
Cancer Care Facilities , Cultural Diversity , National Cancer Institute (U.S.) , Humans , United States , Cross-Sectional Studies , Cancer Care Facilities/organization & administration , Cancer Care Facilities/statistics & numerical data , Surveys and Questionnaires , Leadership , Neoplasms/epidemiology , Male , Female , Biomedical Research/organization & administration
16.
Clin Auton Res ; 34(3): 341-352, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38769233

ABSTRACT

BACKGROUND: The cardiomyopathic and neuropathic phenotype of hereditary transthyretin amyloidosis are well recognized. Cardiovascular autonomic dysfunction is less systematically and objectively assessed. METHODS: Autonomic and clinical features, quantitative cardiovascular autonomic function, and potential autonomic prognostic markers of disease progression were recorded in a cohort of individuals with hereditary transthyretin amyloidosis and in asymptomatic carriers of TTR variants at disease onset (T0) and at the time of the first quantitative autonomic assessment (T1). The severity of peripheral neuropathy and its progression was stratified with the polyneuropathy disability score. RESULTS: A total of 124 individuals were included (111 with a confirmed diagnosis of hereditary transthyretin amyloidosis, and 13 asymptomatic carriers of TTR variants). Symptoms of autonomic dysfunction were reported by 27% individuals at T0. Disease duration was 4.5 ± 4.0 years [mean ± standard deviation (SD)] at autonomic testing (T1). Symptoms of autonomic dysfunction were reported by 78% individuals at T1. Cardiovascular autonomic failure was detected by functional testing in 75% individuals and in 64% of TTR carriers. Progression rate from polyneuropathy disability stages I/II to III/IV seemed to be shorter for individuals with autonomic symptoms at onset [2.33 ± 0.56 versus 4.00 ± 0.69 years (mean ± SD)]. CONCLUSIONS: Cardiovascular autonomic dysfunction occurs early and frequently in individuals with hereditary transthyretin amyloidosis within 4.5 years from disease onset. Cardiovascular autonomic failure can be subclinical in individuals and asymptomatic carriers, and only detected with autonomic function testing, which should be considered a potential biomarker for early diagnosis and disease progression.


Subject(s)
Amyloid Neuropathies, Familial , Disease Progression , Prealbumin , Humans , Amyloid Neuropathies, Familial/genetics , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/physiopathology , Male , Female , Middle Aged , Adult , Prealbumin/genetics , Aged , Heterozygote , Cohort Studies , Biomarkers/blood
17.
Cardiol Young ; : 1-5, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38783397

ABSTRACT

OBJECTIVE: Children with prolonged hospital admissions for CHD often develop delirium. Antipsychotic medications (APMs) have been used to treat delirium but are known to prolong the QTc duration. There is concern for prolongation of the QTc interval in cardiac patients who may be more vulnerable to electrocardiogram (ECG) changes and may have postoperative QTc prolongation already. The goal of this study was to determine the effect of APM on QTc duration in postoperative paediatric cardiac patients and determine the effect of quetiapine and risperidone in treating delirium and QTc prolongation. DESIGN: Retrospective study, July 1, 2017-May 31, 2022. SETTING: Tertiary children's hospital. PATIENTS: Included were patients admitted to the paediatric cardiac ICU at Children's Healthcare of Atlanta. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ECGs, delirium scores, and drug information were collected. Delirium was defined as Cornell Assessment of Pediatric Delirium (CAPD) score >9. Mixed effect models were performed to evaluate the effect of surgery on QTc change and the effect of antipsychotics on QTc and CAPD changes. There were 139 children, 55% male and 67% surgical admissions. Median age was 5.9 months. Mean QTc increased after cardiac surgery by 18 ms (p = 0.014, 95% CI 3.65-32.4). There was no significant change in QTc after antipsychotic administration (p = 0.064). The mean CAPD score decreased (12.5-7.2; p < 0.001). Quetiapine had the most improvement in delirium, and risperidone had the least improvement (77.8%, n = 14; 37.8%, n = 34, respectively; p = 0.002). CONCLUSIONS: The QTc interval did not have a statistically significant change after the administration of antipsychotics, while there was improvement in the CAPD score. APMs may be administered safely without significant prolongation of the QTc and are an effective treatment for delirium.

18.
NPJ Nat Hazards ; 1(1): 6, 2024.
Article in English | MEDLINE | ID: mdl-38720873

ABSTRACT

The flood depth in a structure is a key factor in flood loss models, influencing the estimation of building and contents losses, as well as overall flood risk. Recent studies have emphasized the importance of determining the damage initiation point (DIP) of depth-damage functions, where the flood damage is assumed to initiate with respect to the first-floor height of the building. Here we investigate the effects of DIP selection on the flood risk assessment of buildings located in Special Flood Hazard Areas. We characterize flood using the Gumbel extreme value distribution's location (µ) and scale (α) parameters. Results reveal that average annual flood loss (AAL) values do not depend on µ, but instead follow an exponential decay pattern with α when damage initiates below the first-floor height of a building (i.e., negative DIP). A linear increasing pattern of the AAL with α is achieved by changing the DIP to the first-floor height (i.e., DIP = 0). The study also demonstrates that negative DIPs have larger associated AAL, thus contributing substantially to the overall AAL, compared to positive DIPs. The study underscores the significance of proper DIP selection in flood risk assessment.

19.
J Endocr Soc ; 8(6): bvae071, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38721109

ABSTRACT

Background: Customized and standard automated insulin delivery (AID) systems for use in pregnancies of women with preexisting type 1 diabetes (T1D) are being developed and tested to achieve pregnancy appropriate continuous glucose monitoring (CGM) targets. Guidance on the use of CGM for treatment decisions during pregnancy in the United States is limited. Methods: Ten pregnant women with preexisting T1D participated in a trial evaluating at-home use of a pregnancy-specific AID system. Seven-point self-monitoring of blood glucose (SMBG) was compared to the closest sensor glucose (Dexcom G6 CGM) value biweekly to assess safety and reliability based on the 20%/20 mg/dL criteria. Results: All participants completed the study with 7 participants satisfying the safety and reliability criteria with a mean absolute relative difference of 10.3%. Three participants did not fulfill the criteria, mainly because the frequency of SMBG did not meet the requirements. Conclusion: Dexcom G6 CGM is safe and accurate in the real-world setting for use in pregnant women with preexisting T1D with reduced SMBG testing as part of a pregnancy-specific AID system.

20.
Am J Clin Nutr ; 120(1): 196-210, 2024 07.
Article in English | MEDLINE | ID: mdl-38710447

ABSTRACT

BACKGROUND: Technology-assisted 24-h dietary recalls (24HRs) have been widely adopted in population nutrition surveillance. Evaluations of 24HRs inform improvements, but direct comparisons of 24HR methods for accuracy in reference to a measure of true intake are rarely undertaken in a single study population. OBJECTIVES: To compare the accuracy of energy and nutrient intake estimation of 4 technology-assisted dietary assessment methods relative to true intake across breakfast, lunch, and dinner. METHODS: In a controlled feeding study with a crossover design, 152 participants [55% women; mean age 32 y, standard deviation (SD) 11; mean body mass index 26 kg/m2, SD 5] were randomized to 1 of 3 separate feeding days to consume breakfast, lunch, and dinner, with unobtrusive weighing of foods and beverages consumed. Participants undertook a 24HR the following day [Automated Self-Administered Dietary Assessment Tool-Australia (ASA24); Intake24-Australia; mobile Food Record-Trained Analyst (mFR-TA); or Image-Assisted Interviewer-Administered 24-hour recall (IA-24HR)]. When assigned to IA-24HR, participants referred to images captured of their meals using the mobile Food Record (mFR) app. True and estimated energy and nutrient intakes were compared, and differences among methods were assessed using linear mixed models. RESULTS: The mean difference between true and estimated energy intake as a percentage of true intake was 5.4% (95% CI: 0.6, 10.2%) using ASA24, 1.7% (95% CI: -2.9, 6.3%) using Intake24, 1.3% (95% CI: -1.1, 3.8%) using mFR-TA, and 15.0% (95% CI: 11.6, 18.3%) using IA-24HR. The variances of estimated and true energy intakes were statistically significantly different for all methods (P < 0.01) except Intake24 (P = 0.1). Differential accuracy in nutrient estimation was present among the methods. CONCLUSIONS: Under controlled conditions, Intake24, ASA24, and mFR-TA estimated average energy and nutrient intakes with reasonable validity, but intake distributions were estimated accurately by Intake24 only (energy and protein). This study may inform considerations regarding instruments of choice in future population surveillance. This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12621000209897.


Subject(s)
Cross-Over Studies , Diet Records , Energy Intake , Nutrition Assessment , Humans , Female , Adult , Male , Mental Recall , Diet , Young Adult , Nutrients/administration & dosage , Middle Aged
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