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JAMA Neurology Jul 2024Claims data with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes are routinely used in clinical research. However, the use of ICD-10...
IMPORTANCE
Claims data with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes are routinely used in clinical research. However, the use of ICD-10 codes to define incident stroke has not been validated against expert-adjudicated outcomes in the US population.
OBJECTIVE
To develop and validate the accuracy of an ICD-10 code list to detect incident stroke events using Medicare inpatient fee-for-service claims data.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used data from 2 prospective population-based cohort studies, the Atherosclerosis Risk in Communities (ARIC) study and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, and included participants aged 65 years or older without prior stroke who had linked Medicare claims data. Stroke events in the ARIC and REGARDS studies were identified via active surveillance and adjudicated by expert review. Medicare-linked ARIC data (2016-2018) were used to develop a list of ICD-10 codes for incident stroke detection. The list was validated using Medicare-linked REGARDS data (2016-2019). Data were analyzed from September 1, 2022, through September 30, 2023.
EXPOSURES
Stroke events detected in Medicare claims vs expert-adjudicated stroke events in the ARIC and REGARDS studies.
MAIN OUTCOMES AND MEASURES
The main outcomes were sensitivity and specificity of incident stroke detection using ICD-10 codes.
RESULTS
In the ARIC study, there were 110 adjudicated incident stroke events among 5194 participants (mean [SD] age, 80.1 [5.3] years) over a median follow-up of 3.0 (range, 0.003-3.0) years. Most ARIC participants were women (3160 [60.8%]); 993 (19.1%) were Black and 4180 (80.5%) were White. Using the primary diagnosis code on a Medicare billing claim, the ICD-10 code list had a sensitivity of 81.8% (95% CI, 73.3%-88.5%) and a specificity of 99.1% (95% CI, 98.8%-99.3%) to detect incident stroke. Using any diagnosis code on a Medicare billing claim, the sensitivity was 94.5% (95% CI, 88.5%-98.0%) and the specificity was 98.4% (95% CI, 98.0%-98.8%). In the REGARDS study, there were 140 adjudicated incident strokes among 6359 participants (mean [SD] age, 75.8 [7.0] years) over a median follow-up of 4.0 (range, 0-4.0) years. More than half of the REGARDS participants were women (3351 [52.7%]); 1774 (27.9%) were Black and 4585 (72.1%) were White. For the primary diagnosis code, the ICD-10 code list had a sensitivity of 70.7% (95% CI, 63.2%-78.3%) and a specificity of 99.1% (95% CI, 98.9%-99.4%). For any diagnosis code, the ICD-10 code list had a sensitivity of 77.9% (95% CI, 71.0%-84.7%) and a specificity of 98.9% (95% CI, 98.6%-99.2%).
CONCLUSIONS AND RELEVANCE
These findings suggest that ICD-10 codes could be used to identify incident stroke events in Medicare claims with moderate sensitivity and high specificity.
PubMed: 38949838
DOI: 10.1001/jamaneurol.2024.2044 -
JAMA Pediatrics Jul 2024Lesbian, gay, bisexual, transgender, queer, and/or questioning (LGBTQ+) youth face worse mental health outcomes than non-LGBTQ+ peers. Family support may mitigate this,...
IMPORTANCE
Lesbian, gay, bisexual, transgender, queer, and/or questioning (LGBTQ+) youth face worse mental health outcomes than non-LGBTQ+ peers. Family support may mitigate this, but sparse evidence demonstrates this in clinical settings.
OBJECTIVES
To compare depression and suicide risk between LGBTQ+ and non-LGBTQ+ youth in primary care settings and to investigate whether family support mitigates these negative mental health outcomes.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study uses data from well care visits completed by adolescents aged 13 to 19 years from February 2022 through May 2023, including the Patient Health Questionnaire-9 Modified for Teens (PHQ-9-M) and the Adolescent Health Questionnaire (AHQ; an electronic screener assessing identity, behaviors, and guardian support), at 32 urban or suburban care clinics in Pennsylvania and New Jersey.
EXPOSURES
The primary exposure was self-reported LGBTQ+ status. Family support moderators included parental discussion of adolescent strengths and listening to feelings. Race and ethnicity (determined via parent or guardian report at visit check-in), sex, payer, language, age, and geography were covariates.
MAIN OUTCOMES AND MEASURES
PHQ-9-M-derived mental health outcomes, including total score, recent suicidal ideation, and past suicide attempt.
RESULTS
The sample included 60 626 adolescents; among them, 9936 (16.4%) were LGBTQ+, 15 387 (25.5%) were Black, and 30 296 (50.0%) were assigned female sex at birth. LGBTQ+ youth, compared with non-LGBTQ+ youth, had significantly higher median (IQR) PHQ-9-M scores (5 [2-9] vs 1 [0-3]; P < .001) and prevalence of suicidal ideation (1568 [15.8%] vs 1723 [3.4%]; P < .001). Fewer LGBTQ+ youth endorsed parental support than non-LGBTQ+ youth (discussion of strengths, 8535 [85.9%] vs 47 003 [92.7%]; P < .001; and listening to feelings, 7930 [79.8%] vs 47 177 [93.1%]; P < .001). In linear regression adjusted for demographic characteristics and parental discussion of strengths, LGBTQ+ status was associated with a higher PHQ-9-M score (mean difference, 3.3 points; 95% CI, 3.2-3.3 points). In logistic regression, LGBTQ+ youth had increased adjusted odds of suicidal ideation (adjusted odds ratio, 4.3; 95% CI, 4.0-4.7) and prior suicide attempt (adjusted odds ratio, 4.4; 95% CI, 4.0-4.7). Parental support significantly moderated the association of LGBTQ+ status with PHQ-9-M score and suicidal ideation, with greater protection against these outcomes for LGBTQ+ vs non-LGBTQ+ youth.
CONCLUSIONS AND RELEVANCE
Compared with non-LGBTQ+ youth, LGBTQ+ youth at primary care visits had more depressive symptoms and higher odds of suicidal ideation and prior suicide attempt. Youth-reported parental support was protective against these outcomes, suggesting potential benefits of family support-focused interventions to mitigate mental health inequities for LGBTQ+ youth.
PubMed: 38949835
DOI: 10.1001/jamapediatrics.2024.1956 -
JAMA Internal Medicine Jul 2024The resting electrocardiogram (ECG) is commonly performed for cardiovascular disease (CVD) screening purposes in Japan. However, evidence is limited regarding the...
IMPORTANCE
The resting electrocardiogram (ECG) is commonly performed for cardiovascular disease (CVD) screening purposes in Japan. However, evidence is limited regarding the prognostic significance of ECG in clinical practice settings.
OBJECTIVE
To investigate the association between ECG abnormalities and CVD outcomes in a working-age population.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide cohort study included individuals aged 35 to 65 years from the Japan Health Insurance Association database, which covers approximately 40% (30 million) of the working-age population in Japan. Data from April 1, 2015, to March 31, 2022, were included, and analysis was conducted from October 1, 2022, to April 11, 2024.
EXPOSURES
Baseline ECG status (normal, 1 minor abnormality, ≥2 minor abnormalities, or major abnormality).
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of overall death and CVD hospital admission due to myocardial infarction, stroke, or heart failure. The secondary outcome was developing a new major ECG abnormality over the years of screening.
RESULTS
Of 3 698 429 individuals enrolled in the nationwide annual health check program (mean [SD] age, 47.1 [8.5] years; 66.6% male), 623 073 (16.8%) had 1 minor ECG abnormality, 144 535 (3.9%) had 2 or more minor ECG abnormalities, and 56 921 (1.5%) had a major ECG abnormality. During a median follow-up of 5.5 (IQR, 3.4-5.7) years, baseline ECG abnormality was independently associated with an increased incidence of the composite end points of overall death and CVD admission compared with normal ECG (incidence rates per 10 000 person-years: 92.7 [95% CI, 92.2-93.2] for normal ECG, 128.5 [95% CI, 127.2-129.9] for 1 minor ECG abnormality, 159.7 [95% CI, 156.6-162.9] for ≥2 minor ECG abnormalities, and 266.3 [95% CI, 259.9-272.3] for a major ECG abnormality; adjusted hazard ratios: 1.19 [95% CI, 1.18-1.20] for 1 minor ECG abnormality, 1.37 [95% CI, 1.34-1.39] for ≥2 minor ECG abnormalities, and 1.96 [95% CI, 1.92-2.02] for a major ECG abnormality). Furthermore, the presence and number of minor ECG abnormalities were associated with an increased incidence of developing new major ECG abnormalities (incidence rates per 10 000 person-years: 85.1 [95% CI, 84.5-85.5] for normal ECG, 217.2 [95% CI, 215.5-219.0] for 1 minor ECG abnormality, and 306.4 [95% CI, 302.1-310.7] for ≥2 minor ECG abnormalities; and adjusted hazard ratios: 2.52 [95% CI, 2.49-2.55] for 1 minor ECG abnormality and 3.61 [95% CI, 3.55-3.67] for ≥2 minor ECG abnormalities). Associations were noted regardless of baseline CVD risk.
CONCLUSIONS AND RELEVANCE
The findings of this study suggest that the potential role of routine ECG screening for early prevention of CVD events, along with the optimal follow-up strategy, should be examined in future studies.
PubMed: 38949831
DOI: 10.1001/jamainternmed.2024.2270 -
JAMA Internal Medicine Jul 2024Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and clinically relevant adverse effect of chemotherapy, negatively impacting patient quality of...
IMPORTANCE
Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and clinically relevant adverse effect of chemotherapy, negatively impacting patient quality of life. The lack of effective preventive or therapeutic options regarding CIPN often requires changes in cancer therapy, potentially resulting in reduced survival.
OBJECTIVE
To determine whether sensorimotor training (SMT) and whole-body vibration (WBV) training reduce symptoms and decrease the onset of CIPN.
DESIGN, SETTING, AND PARTICIPANTS
This prospective multicenter randomized clinical trial (STOP) followed up patients over 5 years at 4 centers in or near Cologne, Germany. Patients undergoing treatment with oxaliplatin or vinca alkaloids were recruited. Participants were recruited from May 2014 to November 2020. Data were last analyzed in June 2021.
INTERVENTIONS
Participants in the intervention groups performed supervised SMT or WBV training sessions twice a week, each lasting approximately 15 to 30 minutes, concomitant to medical therapy.
MAIN OUTCOMES AND MEASURES
The primary end point was the incidence of CIPN. Secondary end points included subjective neuropathy symptoms, balance control, physical activity levels, quality of life, and clinical outcome. For cross-stratum evaluations, the Mantel-Haenszel test (MH) was used, and within individual strata, Fisher exact test was used for analysis.
RESULTS
A total of 1605 patients were screened, and 1196 patients did not meet all inclusion criteria, with 251 further excluded or declining participation. A total of 158 patients (mean [SD] age, 49.1 [18.0-82.0] years; 93 [58.9%] male) were randomized into 1 of 3 groups: 55 (34.8%) in SMT, 53 (33.5%) in WBV, and 50 (31.6%) in treatment as usual (TAU). The incidence of CIPN in participants was significantly lower in both intervention groups compared to the control group (TAU): (SMT, 12 of 40 [30.0%; 95% CI, 17.9%-42.1%] and WBV, 14 of 34 [41.2%; 95% CI, 27.9%-54.5%] vs TAU, 24 of 34 [70.6%; 95% CI, 58.0%-83.2%]; P = .002 for intention to treat-MH). Patients receiving vinca alkaloids and performing SMT benefited the most. Results were more pronounced in a per-protocol analysis (>75% participation in the intervention) (SMT, 8 of 28 [28.6%; 95% CI, 16.6%-40.5%] and WBV, 9 of 24 [37.5%; 95% CI, 24.4%-50.5%] vs TAU, 22 of 30 [73.3%; 95% CI, 61.6%-85.6%]). Improvements in favor of SMT compared to TAU were found for balance control bipedal with eyes open; bipedal with eyes closed; monopedal, vibration sensitivity, sense of touch, lower leg strength, pain reduction, burning sensation, chemotherapy dose reductions, and mortality.
CONCLUSION AND RELEVANCE
This randomized clinical trial provides initial evidence that neuromuscular training decreases the onset of CIPN.
TRIAL REGISTRATION
German Clinical Trials Register: DRKS00006088.
PubMed: 38949824
DOI: 10.1001/jamainternmed.2024.2354 -
JAMA Pediatrics Jul 2024COVID-19 vaccination is recommended throughout pregnancy to prevent pregnancy complications and adverse birth outcomes associated with COVID-19 disease. To date, data on...
IMPORTANCE
COVID-19 vaccination is recommended throughout pregnancy to prevent pregnancy complications and adverse birth outcomes associated with COVID-19 disease. To date, data on birth defects after first-trimester vaccination are limited.
OBJECTIVE
To evaluate the associated risks for selected major structural birth defects among live-born infants after first-trimester receipt of a messenger RNA (mRNA) COVID-19 vaccine.
DESIGN, SETTING, AND PARTICIPANTS
This was a retrospective cohort study of singleton pregnancies with estimated last menstrual period (LMP) between September 13, 2020, and April 3, 2021, and ending in live birth from March 5, 2021, to January 25, 2022. Included were data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink.
EXPOSURES
Receipt of 1 or 2 mRNA COVID-19 vaccine doses in the first trimester, as part of the primary series.
MAIN OUTCOMES AND MEASURES
Selected major structural birth defects among live-born infants, identified from electronic health data using validated algorithms, with neural tube defects confirmed via medical record review.
RESULTS
Among 42 156 eligible pregnancies (mean [SD] maternal age, 30.9 [5.0] years) 7632 (18.1%) received an mRNA COVID-19 vaccine in the first trimester. Of 34 524 pregnancies without a first-trimester COVID-19 vaccination, 2045 (5.9%) were vaccinated before pregnancy, 13 494 (39.1%) during the second or third trimester, and 18 985 (55.0%) were unvaccinated before or during pregnancy. Compared with pregnant people unvaccinated in the first trimester, those vaccinated in the first trimester were older (mean [SD] age, 32.3 [4.5] years vs 30.6 [5.1] years) and differed by LMP date. After applying stabilized inverse probability weighting, differences in baseline characteristics between vaccinated and unvaccinated pregnant persons in the first trimester were negligible (standardized mean difference <0.20). Selected major structural birth defects occurred in 113 infants (1.48%) after first-trimester mRNA COVID-19 vaccination and in 488 infants (1.41%) without first-trimester vaccine exposure; the adjusted prevalence ratio was 1.02 (95% CI, 0.78-1.33). In secondary analyses, with major structural birth defect outcomes grouped by organ system, no significant differences between infants vaccinated or unvaccinated in the first trimester were identified.
CONCLUSIONS AND RELEVANCE
In this multisite cohort study, among live-born infants, first-trimester mRNA COVID-19 vaccine exposure was not associated with an increased risk for selected major structural birth defects.
PubMed: 38949821
DOI: 10.1001/jamapediatrics.2024.1917 -
JAMA Neurology Jul 2024Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic...
IMPORTANCE
Understanding the association between clinically defined relapses and radiological activity in multiple sclerosis (MS) is essential for patient treatment and therapeutic development.
OBJECTIVE
To investigate clinical events identified as relapses but not associated with new T2 lesions or gadolinium-enhanced T1 lesions on brain and spinal cord magnetic resonance imaging (MRI).
DESIGN, SETTING, AND PARTICIPANTS
This multicenter observational cohort study was conducted between January 2015 and June 2023. Data were extracted on June 8, 2023, from the French MS registry. All clinical events reported as relapses in patients with relapsing-remitting MS were included if brain and spinal cord MRI was performed within 12 and 24 months before the event, respectively, and 50 days thereafter with gadolinium injection.
EXPOSURES
Events were classified as relapses with active MRI (RAM) if a new T2 lesion or gadolinium-enhanced T1 lesion appeared on brain or spinal cord MRI or as acute clinical events with stable MRI (ACES) otherwise.
MAIN OUTCOMES AND MEASURES
Factors associated with ACES were investigated; patients with ACES and RAM were compared regarding Expanded Disability Status Scale (EDSS) course, relapse rate, confirmed disability accrual (CDA), relapse-associated worsening (RAW), progression independent of relapse activity (PIRA), and transition to secondary progressive (SP) MS, and ACES and RAM rates under each disease-modifying therapy (DMT) were estimated.
RESULTS
Among 31 885 clinical events, 637 in 608 patients (493 [77.4%] female; mean [SD] age, 35.8 [10.7] years) were included. ACES accounted for 166 (26.1%) events and were more likely in patients receiving highly effective DMTs, those with longer disease duration (odds ratio [OR], 1.04; 95% CI, 1.01-1.07), or those presenting with fatigue (OR, 2.14; 95% CI, 1.15-3.96). ACES were associated with significant EDSS score increases, lower than those found for RAM. Before the index event, patients with ACES experienced significantly higher rates of relapse (relative rate [RR], 1.21; 95% CI, 1.01-1.46), CDA (hazard ratio [HR], 1.54; 95% CI, 1.13-2.11), and RAW (HR, 1.72; 95% CI, 1.20-2.45). Patients with ACES were at significantly greater risk of SP transition (HR, 2.58; 95% CI, 1.02-6.51). Although RAM rate decreased with DMTs according to their expected efficacy, ACES rate was stable across DMTs.
CONCLUSIONS AND RELEVANCE
The findings in this study introduce the concept of ACES in MS, which accounted for one-fourth of clinical events identified as relapses.
PubMed: 38949816
DOI: 10.1001/jamaneurol.2024.1961 -
JAMA Network Open Jul 2024The long-term estimated risk of development of cataracts among pediatric patients with uveitis is not clear.
IMPORTANCE
The long-term estimated risk of development of cataracts among pediatric patients with uveitis is not clear.
OBJECTIVE
To describe factors associated with the development of cataracts among pediatric patients with uveitis.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used the international TriNetX database to enroll pediatric patients with and without uveitis from January 1, 2002, to December 31, 2022. The nonuveitis cohort consisted of randomly selected control patients matched by age, sex, race and ethnicity, and specific comorbidities.
EXPOSURE
Diagnosis of uveitis, identified using diagnostic codes.
MAIN OUTCOMES AND MEASURES
The primary outcome was the risk of developing cataracts among the uveitis group compared with the nonuveitis comparison group, with hazard ratios (HRs) and 95% CIs reported.
RESULTS
A total of 22 687 pediatric patients with uveitis (mean [SD] age, 10.3 [5.6] years; 54.2% male) and 22 687 comparators without uveitis (mean [SD] age, 10.3 [5.6] years; 54.5% male) were enrolled in the study. The risk of cataracts was increased among pediatric patients with uveitis up to a follow-up duration of 20 years (HR, 17.17; 95%CI, 12.90-22.80) from the index date. Subgroup analyses revealed an elevated cataract risk across age groups: 0 to 6 years (HR, 19.09; 95% CI, 10.10-36.00), 7 to 12 years (HR, 27.16; 95% CI, 15.59-47.20), and 13 to 18 years (HR, 13.39; 95% CI, 8.84-20.30); both female sex (HR, 13.76; 95% CI, 9.60-19.71) and male sex (HR, 11.97; 95% CI, 8.47-16.91); and Asian (HR, 13.80; 95% CI, 3.28-58.07), Black or African American (HR, 10.41; 95% CI, 5.60-19.36), and White (HR, 15.82; 95% CI, 11.05-22.60) race. Furthermore, increased cataract risks were also observed among those with and without a history of immunosuppressive agents (with: HR, 26.52 [95% CI, 16.75-41.90]; without: HR, 17.69 [95% CI: 11.39-27.40]), a history of steroid eye drop use (with: HR, 29.51 [95% CI, 14.56-59.70]; without: HR, 16.49 [95% CI, 11.92-22.70]), and a history of intraocular procedures (with: HR, 11.07 [95%CI, 4.42-27.71]; without: HR, 14.49 [95% CI, 10.11-20.70]).
CONCLUSIONS AND RELEVANCE
In this cohort study of pediatric patients with uveitis, an elevated risk of cataracts following a uveitis diagnosis was found compared with pediatric patients without uveitis. The findings suggest that pediatric patients with uveitis should be monitored for cataract development.
Topics: Humans; Uveitis; Cataract; Male; Female; Child; Adolescent; Child, Preschool; Risk Factors; Cohort Studies; Infant; Proportional Hazards Models
PubMed: 38949811
DOI: 10.1001/jamanetworkopen.2024.19366 -
JAMA Network Open Jul 2024Addressing poor uptake of low-dose computed tomography lung cancer screening (LCS) is critical, especially for those having the most to gain-high-benefit persons with...
IMPORTANCE
Addressing poor uptake of low-dose computed tomography lung cancer screening (LCS) is critical, especially for those having the most to gain-high-benefit persons with high lung cancer risk and life expectancy more than 10 years.
OBJECTIVE
To assess the association between LCS uptake and implementing a prediction-augmented shared decision-making (SDM) tool, which enables clinicians to identify persons predicted to be at high benefit and encourage LCS more strongly for these persons.
DESIGN, SETTING, AND PARTICIPANTS
Quality improvement interrupted time series study at 6 Veterans Affairs sites that used a standard set of clinical reminders to prompt primary care clinicians and screening coordinators to engage in SDM for LCS-eligible persons. Participants were persons without a history of LCS who met LCS eligibility criteria at the time (aged 55-80 years, smoked ≥30 pack-years, and current smoking or quit <15 years ago) and were not documented to be an inappropriate candidate for LCS by a clinician during October 2017 through September 2019. Data were analyzed from September to November 2023.
EXPOSURE
Decision support tool augmented by a prediction model that helps clinicians personalize SDM for LCS, tailoring the strength of screening encouragement according to predicted benefit.
MAIN OUTCOME AND MEASURE
LCS uptake.
RESULTS
In a cohort of 9904 individuals, the median (IQR) age was 64 (57-69) years; 9277 (94%) were male, 1537 (16%) were Black, 8159 (82%) were White, 5153 (52%) were predicted to be at intermediate (preference-sensitive) benefit and 4751 (48%) at high benefit, and 1084 (11%) received screening during the study period. Following implementation of the tool, higher rates of LCS uptake were observed overall along with an increase in benefit-based LCS uptake (higher screening uptake among persons anticipated to be at high benefit compared with those at intermediate benefit; primary analysis). Mean (SD) predicted probability of getting screened for a high-benefit person was 24.8% (15.5%) vs 15.8% (11.8%) for a person at intermediate benefit (mean absolute difference 9.0 percentage points; 95% CI, 1.6%-16.5%).
CONCLUSIONS AND RELEVANCE
Implementing a robust approach to personalized LCS, which integrates SDM, and a decision support tool augmented by a prediction model, are associated with improved uptake of LCS and may be particularly important for those most likely to benefit. These findings are timely given the ongoing poor rates of LCS uptake.
Topics: Humans; Lung Neoplasms; Aged; Male; Early Detection of Cancer; Female; Middle Aged; Decision Making, Shared; Aged, 80 and over; Tomography, X-Ray Computed; United States; Interrupted Time Series Analysis; Quality Improvement
PubMed: 38949809
DOI: 10.1001/jamanetworkopen.2024.19624 -
JAMA Network Open Jul 2024Improving end-of-life care in the intensive care unit (ICU) is a priority, but clinically modifiable factors of quality of dying and death (QODD) are seldom identified. (Observational Study)
Observational Study
IMPORTANCE
Improving end-of-life care in the intensive care unit (ICU) is a priority, but clinically modifiable factors of quality of dying and death (QODD) are seldom identified.
OBJECTIVES
To comprehensively identify factors associated with QODD classes of dying ICU patients, emphasizing clinically modifiable factors based on the integrative framework of factors associated with for bereavement outcomes.
DESIGN, SETTING, AND PARTICIPANTS
This observational cohort study was conducted at medical ICUs of 2 Taiwanese medical centers from January 2018 to March 2020 with follow-up through December 2022. Eligible participants included primary family surrogates responsible for decision making for critically ill ICU patients at high risk of death (Acute Physiology and Chronic Health Evaluation II score >20) but who survived more than 3 days after ICU admission. Data analysis was conducted from July to September 2023.
MAIN OUTCOMES AND MEASURES
QODD was measured by the 23-item ICU-QODD questionnaire. Factors associated with patient membership in 4 previously determined QODD classes (high, moderate, poor to uncertain, and worst) were examined using a 3-step approach for latent class modeling with the high QODD class as the reference category.
RESULTS
A total of 309 family surrogates (mean [SD] age, 49.83 [12.55] years; 184 women [59.5%] and 125 men [40.5%]) were included in the study. Of all surrogates, 91 (29.4%) were the patients' spouse and 66 (53.7%) were the patients' adult child. Patient demographics were not associated with QODD class. Two family demographics (age and gender), relationship with the patient (spousal or adult-child), and length of ICU stay were associated with QODD classes. Patients of surrogates perceiving greater social support were less likely to be in the poor to uncertain (adjusted odds ratio [aOR], 0.89; 95% CI, 0.83-0.94) and worst (aOR, 0.92; 95% CI, 0.87-0.96) QODD classes. Family meetings were associated with the poor to uncertain QODD class (aOR, 8.61; 95% CI, 2.49-29.74) and worst QODD class (aOR, 7.28; 95% CI, 1.37-38.71). Death with cardiopulmonary resuscitation was associated with the worst QODD class (aOR, 7.51; 95% CI, 1.12-50.25). Family presence at patient death was uniformly negatively associated with the moderate QODD class (aOR, 0.16; 95% CI, 0.05-0.54), poor to uncertain QODD class (aOR, 0.21; 95% CI, 0.05-0.82), and worst QODD class (aOR, 0.08; 95% CI, 0.02-0.38). Higher family satisfaction with ICU care was negatively associated with the poor to uncertain QODD class (aOR, 0.93; 95% CI, 0.87-0.98) and worst QODD class (aOR, 0.86; 95% CI, 0.81-0.92).
CONCLUSIONS AND RELEVANCE
In this cohort study of critically ill patients and their family surrogates, modifiable end-of-life ICU-care characteristics played a more significant role in associations with patient QODD class than did immutable family demographics, preexisting family health conditions, patient demographics, and patient clinical characteristics, thereby illuminating actionable opportunities to improve end-of-life ICU care.
Topics: Humans; Male; Female; Critical Illness; Middle Aged; Intensive Care Units; Aged; Terminal Care; Family; Taiwan; Cohort Studies; Surveys and Questionnaires; Adult; Bereavement
PubMed: 38949808
DOI: 10.1001/jamanetworkopen.2024.20388 -
Drugs in R&D Jul 2024Vupanorsen is a GalNAc-conjugated antisense oligonucleotide targeting angiopoietin-like 3 (ANGPTL3) mRNA shown to reduce atherogenic lipoproteins in individuals with...
BACKGROUND
Vupanorsen is a GalNAc-conjugated antisense oligonucleotide targeting angiopoietin-like 3 (ANGPTL3) mRNA shown to reduce atherogenic lipoproteins in individuals with dyslipidemia.
OBJECTIVES
The aim of this study was to satisfy Chinese regulatory requirements and support ethnic sensitivity assessment by evaluating pharmacokinetics (PK), pharmacodynamics (PD), and safety of vupanorsen in healthy Chinese adults with elevated triglycerides (TG).
METHODS
In this phase I, parallel-cohort, open-label study, 18 Chinese adults with elevated fasting TG (≥ 90 mg/dL) were randomized 1:1 to receive a single subcutaneous dose of vupanorsen 80 mg or 160 mg. PK parameters, PD markers (including ANGPTL3, TG, non-high-density lipoprotein cholesterol [non-HDL-C]), and safety were assessed.
RESULTS
Absorption of vupanorsen was rapid (median time to maximum concentration [T]: 2.0 h for both doses), followed by a multiphasic decline (mean terminal half-life 475.9 [80 mg] and 465.2 h [160 mg]). Exposure (area under curve [AUC] and maximum plasma concentration [C]) generally increased in a greater than dose-proportional manner from 80 mg to 160 mg. Time-dependent reductions in ANGPTL3 and lipid parameters were observed. Mean percentage change from baseline for the 80-mg and 160-mg doses, respectively, were - 59.7% and - 69.5% for ANGPTL3, - 41.9% and - 52.5% for TG, and - 23.2% and - 25.4% for non-HDL-C. No serious or severe adverse events (AEs), deaths, or discontinuations due to AEs were reported. Three participants experienced treatment-related AEs; all were mild and resolved by end of study.
CONCLUSIONS
This study provided the first clinical vupanorsen data in China. In Chinese participants with elevated TG, PK and PD parameters were consistent with those reported previously in non-Chinese participants, including in Japanese individuals. No safety concerns were noted.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT04916795.
PubMed: 38949758
DOI: 10.1007/s40268-024-00467-5