Category: Statistics

J Anal Toxicol. 2024 Apr 24:bkae033. doi: 10.1093/jat/bkae033. Online ahead of print.

ABSTRACT

Total Blood Carbon Monoxide (TBCO) showed promising results in improving accuracy of CO determinations in blood and presenting better stability to different storage conditions. Therefore, it was proposed as alternative biomarker to carboxyhemoglobin (COHb) for CO poisoning diagnosis. However, given that current interpretation reference values exist for COHb only, it is difficult to implement TBCO analysis in routine. Therefore, we aimed at determining TBCO reference values for postmortem CO poisoning cases. A previously validated method for TBCO analysis via gas chromatography-mass spectrometry was applied to cardiac, peripheral, cranial and spleen blood samples collected from 92 autopsies. Autopsy cases included 21 non-CO related and 71 CO-related cases with varying postmortem intervals (PMI). Statistical analyses were performed using statistical software R Studio. When comparing lower to higher PMI for non-CO related cases, no significant differences were found, which suggests that CO formation or degradation at low PMIs does not occur. Spleen blood showed potential as alternative matrix for CO determinations in cases with sample availability issues, but needs to be evaluated for CO positive cases. Results for cardiac blood in CO-related autopsies showed a positive correlation between COHb and TBCO values (R = 0.78). This value is lower than what is found in the literature, suggesting that even though COHb and TBCO are correlated, a potential underestimation of the true CO exposure might occur if only COHb values are taken into consideration. Samples were divided into CO exposure groups based on COHb concentrations and with the data obtained, classification into following TBCO concentration groups are proposed: no significant CO exposure case <6 µmol/mL, medium CO exposure case 6-20 µmol/mL, high CO exposure case >20µmol/mL. Even if a higher number of samples in each group would enable to increase the confidence, these results are very promising and highlight the importance of TBCO measurement.

PMID:38662395 | DOI:10.1093/jat/bkae033

Invest Ophthalmol Vis Sci. 2024 Apr 1;65(4):39. doi: 10.1167/iovs.65.4.39.

ABSTRACT

PURPOSE: Little is known regarding differences in childhood growth between somatic and heritable retinoblastoma (Rb) populations. We aimed to compare childhood growth parameters between somatic and heritable Rb cohorts at birth and at time of diagnosis with Rb.

METHODS: A multinational, longitudinal cohort study was conducted with patients from 11 centers in 10 countries who presented with treatment naïve Rb from January to December 2019. Variables of interest included age, sex, and size characteristics at birth and at time of presentation, as well as germline mutation status. After Bonferroni correction, results were statistically significant if the P value was less than 0.005.

RESULTS: We enrolled 696 patients, with 253 analyzed after exclusion criteria applied. Between somatic (n = 39) and heritable (n = 214) Rb cohorts, with males and females analyzed separately, there was no significant difference in birth weight percentile, weight percentile at time of diagnosis, length percentile at time of diagnosis, weight-for-length percentile at time of diagnosis, or change of weight percentile from birth to time of diagnosis. Patients with heritable Rb had a smaller mean weight percentile at birth and smaller mean weight and length percentiles at time of diagnosis with Rb, although this difference was not statistically significant. All cohorts experienced a slight negative change of weight percentile from birth to time of diagnosis. No cohort mean percentiles met criteria for failure to thrive, defined as less than the 5th percentile.

CONCLUSIONS: Children with Rb seem to have normal birth and childhood growth patterns. There is no definitive evidence that somatic or heritable Rb has a biological or environmental impact on childhood growth parameters.

PMID:38662390 | DOI:10.1167/iovs.65.4.39

JAMA Netw Open. 2024 Apr 1;7(4):e247581. doi: 10.1001/jamanetworkopen.2024.7581.

NO ABSTRACT

PMID:38662376 | DOI:10.1001/jamanetworkopen.2024.7581

JAMA Netw Open. 2024 Apr 1;7(4):e248487. doi: 10.1001/jamanetworkopen.2024.8487.

NO ABSTRACT

PMID:38662374 | DOI:10.1001/jamanetworkopen.2024.8487

JAMA Netw Open. 2024 Apr 1;7(4):e247604. doi: 10.1001/jamanetworkopen.2024.7604.

ABSTRACT

IMPORTANCE: Antipsychotics, such as quetiapine, are frequently prescribed to people with dementia to address behavioral symptoms but can also cause harm in this population.

OBJECTIVE: To determine whether warning letters to high prescribers of quetiapine can successfully reduce its use among patients with dementia and to investigate the impacts on patients’ health outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of a randomized clinical trial of overprescribing letters that began in April 2015 and included the highest-volume primary care physician (PCP) prescribers of quetiapine in original Medicare. Outcomes of patients with dementia were analyzed in repeated 90-day cross-sections through December 2018. Analyses were conducted from September 2021 to February 2024.

INTERVENTIONS: PCPs were randomized to a placebo letter or 3 overprescribing warning letters stating that their prescribing of quetiapine was high and under review by Medicare.

MAIN OUTCOMES AND MEASURES: The primary outcome of this analysis was patients’ total quetiapine use in days per 90-day period (the original trial primary outcome was total quetiapine prescribing by study PCPs). Prespecified secondary outcomes included measures of cognitive function and behavioral symptoms from nursing home assessments, indicators of depression from screening questionnaires in assessments and diagnoses in claims, metabolic diagnoses derived from assessments and claims, indicators of use of the hospital and other health care services, and death. Outcomes were analyzed separately for patients living in nursing homes and in the community.

RESULTS: Of the 5055 study PCPs, 2528 were randomized to the placebo letter, and 2527 were randomized to the 3 warning letters. A total of 84 881 patients with dementia living in nursing homes and 261 288 community-dwelling patients with dementia were attributed to these PCPs. There were 92 874 baseline patients (mean [SD] age, 81.5 [10.5] years; 64 242 female [69.2%]). The intervention reduced quetiapine use among both nursing home patients (adjusted difference, -0.7 days; 95% CI, -1.3 to -0.1 days; P = .02) and community-dwelling patients (adjusted difference, -1.5 days; 95% CI, -1.8 to -1.1 days; P < .001). There were no detected adverse effects on cognitive function (cognitive function scale adjusted difference, 0.01; 95% CI, -0.01 to 0.03; P = .19), behavioral symptoms (agitated or reactive behavior adjusted difference, -0.2%; 95% CI -1.2% to 0.8% percentage points; P = .72), depression, metabolic diagnoses, or more severe outcomes, including hospitalization and death.

CONCLUSIONS AND RELEVANCE: This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia. This intervention and others like it may be useful for future efforts to promote guideline-concordant care.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05172687.

PMID:38662373 | DOI:10.1001/jamanetworkopen.2024.7604

JAMA Netw Open. 2024 Apr 1;7(4):e247615. doi: 10.1001/jamanetworkopen.2024.7615.

ABSTRACT

IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown.

OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and evaluate the need for dosage adjustments.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of data from the ACTIV-1 (Accelerating COVID-19 Therapeutic Interventions and Vaccines) Immune Modulator (IM) randomized clinical trial conducted between October 16, 2020, and December 31, 2021. The trial included hospitalized adults who received abatacept in addition to standard of care for treatment of COVID-19 pneumonia. Data analysis was performed between September 2022 and February 2024.

EXPOSURE: Single intravenous infusion of abatacept (10 mg/kg with a maximum dose of 1000 mg).

MAIN OUTCOMES AND MEASURES: Mortality at day 28 was the primary outcome of interest, and time to recovery at day 28 was the secondary outcome. Drug exposure was assessed using the projected area under the serum concentration time curve over 28 days (AUC0-28). Logistic regression modeling was used to analyze the association between drug exposure and 28-day mortality, adjusted for age, sex, and disease severity. The association between time to recovery and abatacept exposure was examined using Fine-Gray modeling with death as a competing risk, and was adjusted for age, sex, and disease severity.

RESULTS: Of the 509 patients who received abatacept, 395 patients with 848 serum samples were included in the population pharmacokinetic analysis. Their median age was 55 (range, 19-89) years and most (250 [63.3%]) were men. Abatacept clearance increased with body weight and more severe disease activity at baseline. Drug exposure was higher in patients who survived vs those who died, with a median AUC0-28 of 21 428 (range, 8462-43 378) mg × h/L vs 18 262 (range, 9628-27 507) mg × h/L (P < .001). Controlling for age, sex, and disease severity, an increase of 5000 units in AUC0-28 was associated with lower odds of mortality at day 28 (OR, 0.52 [95% CI, 0.35-0.79]; P = .002). For an AUC0-28 of 19 400 mg × h/L or less, there was a higher probability of recovery at day 28 (hazard ratio, 2.63 [95% CI, 1.70-4.08] for every 5000-unit increase; P < .001). Controlling for age, sex, and disease severity, every 5000-unit increase in AUC0-28 was also associated with lower odds of a composite safety event at 28 days (OR, 0.46 [95% CI, 0.33-0.63]; P < .001). Using the dosing regimen studied in the ACTIV-1 IM trial, 121 of the 395 patients (30.6%) would not achieve an abatacept exposure of at least 19 400 mg × h/L, particularly at the extremes of body weight. Using a modified, higher-dose regimen, only 12 patients (3.0%) would not achieve the hypothesized target abatacept exposure.

CONCLUSIONS AND RELEVANCE: In this study, patients who were hospitalized with severe COVID-19 and achieved higher projected abatacept exposure had reduced mortality and a higher probability of recovery with fewer safety events. However, abatacept clearance was high in this population, and the current abatacept dosing (10 mg/kg intravenously with a maximum of 1000 mg) may not achieve optimal exposure in all patients.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940.

PMID:38662372 | DOI:10.1001/jamanetworkopen.2024.7615

JAMA Netw Open. 2024 Apr 1;7(4):e247629. doi: 10.1001/jamanetworkopen.2024.7629.

ABSTRACT

IMPORTANCE: Many veterans who served in Afghanistan and Iraq during Operations Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) were deployed to military bases with open burn pits and exposed to their emissions, with limited understanding of the long-term health consequences.

OBJECTIVE: To determine the association between deployment to military bases where open burn pits were used for waste disposal and the subsequent risk of developing respiratory and cardiovascular diseases.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study used Veterans Health Administration medical records and declassified deployment records from the Department of Defense to assess Army and Air Force veterans who were deployed between 2001 and 2011 and subsequently received health care from the Veterans Health Administration, with follow-up through December 2020. Data were analyzed from January 2023 through February 2024.

EXPOSURE: Duration of deployment to military bases with open burn pits.

MAIN OUTCOMES AND MEASURES: Diagnosis of asthma, chronic obstructive pulmonary disease, interstitial lung disease, hypertension, myocardial infarction, congestive heart failure, ischemic stroke, and hemorrhagic stroke.

RESULTS: The study population included 459 381 OEF and OIF veterans (mean [SD] age, 31.6 [8.7] years; 399 754 [87.0%] male). Median (IQR) follow-up from end of deployment was 10.9 (9.4-12.7) years. For every 100 days of deployment to bases with burn pits, veterans experienced increased adjusted odds for asthma (adjusted odds ratio [aOR], 1.01; 95% CI, 1.01-1.02), chronic obstructive pulmonary disease (aOR, 1.04; 95% CI, 1.02-1.07), hypertension (aOR, 1.02; 95% CI, 1.02-1.03), and ischemic stroke (aOR, 1.06; 95% CI, 0.97-1.14). Odds of interstitial lung disease, myocardial infarction, congestive heart failure, or hemorrhagic stroke were not increased. Results based on tertiles of duration of burn pit exposures were consistent with those from the continuous exposure measures.

CONCLUSIONS AND RELEVANCE: In this cohort study, prolonged deployment to military bases with open burn pits was associated with increased risk of developing asthma, COPD, and hypertension. The results also point to a possible increased risk in ischemic stroke. The novel ability to use integrated data on deployment and health outcomes provides a model for additional studies of the health impact of environmental exposures during military service.

PMID:38662371 | DOI:10.1001/jamanetworkopen.2024.7629

JAMA Netw Open. 2024 Apr 1;7(4):e248481. doi: 10.1001/jamanetworkopen.2024.8481.

ABSTRACT

IMPORTANCE: Psychiatric symptoms are reportedly common among adults with post-COVID-19 condition (PCC). However, nationally representative data regarding symptom prevalence, treatment uptake, and barriers to care are needed to inform the development of care models.

OBJECTIVES: To evaluate the prevalence of psychiatric symptoms in US adults with PCC compared with those without PCC and assess treatment uptake and cost-related barriers to treatment.

DESIGN, SETTING, AND PARTICIPANTS: Data from the 2022 National Health Interview Survey (NHIS), a nationally representative US cross-sectional survey, were analyzed between October 2023 and February 2024.

EXPOSURE: Current PCC, defined as new symptoms following SARS-CoV-2 infection lasting more than 3 months and ongoing at the time of interview.

MAIN OUTCOMES AND MEASURES: Depression symptoms were evaluated by the Patient Health Questionnaire-8 and anxiety symptoms were assessed using the General Anxiety Disorder-7 instrument. Participants were classified as having received treatment if they received mental health counseling or therapy or medications for mental health. Sleep difficulties, cognitive difficulties, disabling fatigue, and cost-related barriers were assessed from additional NHIS questions.

RESULTS: Of the 25 122 participants representing approximately 231 million US adults (median [IQR] age, 46 [32-61] years; 49.8% male and 50.2% female participants), a weighted prevalence (wPr) of 3.4% (95% CI, 3.1%-3.6%) had current PCC. Compared with other US adults, participants with current PCC were more likely to have depression symptoms (wPr, 16.8% vs 7.1%; adjusted odds ratio [AOR], 1.96; 95% CI, 1.51-2.55), anxiety symptoms (wPr, 16.7% vs 6.3%; AOR, 2.21; 95% CI, 1.53-3.19), sleep difficulties (wPr, 41.5% vs 22.7%; AOR 1.95; 95% CI, 1.65-2.29), cognitive difficulties (wPr, 35.0% vs 19.5%; AOR, 2.04; 95% CI, 1.66-2.50), and disabling fatigue (wPr, 4.0% vs 1.6%; AOR, 1.85; 95% CI, 1.20-2.86). Among participants who had depression or anxiety symptoms, those with PCC had a similar likelihood of not having received treatment (wPr, 28.2% vs 34.9%; AOR, 1.02; 95% CI, 0.66-1.57). However, participants with current PCC were more likely to report a cost-related barrier to accessing mental health counseling or therapy (wPr, 37.2% vs 23.3%; AOR, 2.05; 95% CI, 1.40-2.98).

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that people with PCC have a higher prevalence of psychiatric symptoms than other adults but are more likely to experience cost-related barriers to accessing therapy. Care pathways for PCC should consider prioritizing mental health screening and affordable treatment.

PMID:38662370 | DOI:10.1001/jamanetworkopen.2024.8481

JAMA Netw Open. 2024 Apr 1;7(4):e248496. doi: 10.1001/jamanetworkopen.2024.8496.

ABSTRACT

IMPORTANCE: A publicly funded fertility program was introduced in Ontario, Canada, in 2015 to increase access to fertility treatment. For in vitro fertilization (IVF), the program mandated an elective single-embryo transfer (eSET) policy. However, ovulation induction and intrauterine insemination (OI/IUI)-2 other common forms of fertility treatment-were more difficult to regulate in this manner. Furthermore, prior epidemiologic studies only assessed fetuses at birth and did not account for potential fetal reductions that may have been performed earlier in pregnancy.

OBJECTIVE: To examine the association between fertility treatment and the risk of multifetal pregnancy in a publicly funded fertility program, accounting for both fetal reductions and all live births and stillbirths.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, retrospective cohort study used linked administrative health databases at ICES to examine all births and fetal reductions in Ontario, Canada, from April 1, 2006, to March 31, 2021.

EXPOSURE: Mode of conception: (1) unassisted conception, (2) OI/IUI, or (3) IVF.

MAIN OUTCOMES AND MEASURES: The main outcome was multifetal pregnancy (ie, a twin or higher-order pregnancy). Modified Poisson regression generated adjusted relative risks (ARRs) and derived population attributable fractions (PAFs) for multifetal pregnancies attributable to fertility treatment. Absolute rate differences (ARDs) were used to compare the era before eSET was promoted (2006-2011) with the era after the introduction of the eSET mandate (2016-2021).

RESULTS: Of all 1 724 899 pregnancies, 1 670 825 (96.9%) were by unassisted conception (mean [SD] maternal age, 30.6 [5.2] years), 24 395 (1.4%) by OI/IUI (mean [SD] maternal age, 33.1 [4.4] years), and 29 679 (1.7%) by IVF (mean [SD] maternal age, 35.8 [4.7] years). In contrast to unassisted conception, individuals who received OI/IUI or IVF tended to be older, reside in a high-income quintile neighborhood, or have preexisting health conditions. Multifetal pregnancy rates were 1.4% (95% CI, 1.4%-1.4%) for unassisted conception, 10.5% (95% CI, 10.2%-10.9%) after OI/IUI, and 15.5% (95% CI, 15.1%-15.9%) after IVF. Compared with unassisted conception, the ARR of any multifetal pregnancy was 7.0 (95% CI, 6.7-7.3) after OI/IUI and 9.9 (95% CI, 9.6-10.3) after IVF, with corresponding PAFs of 7.1% (95% CI, 7.1%-7.2%) and 13.4% (95% CI, 13.3%-13.4%). Between the eras of 2006 to 2011 and 2016 to 2021, multifetal pregnancy rates decreased from 12.9% to 9.1% with OI/IUI (ARD, -3.8%; 95% CI, -4.2% to -3.4%) and from 29.4% to 7.1% with IVF (ARD, -22.3%; 95% CI, -23.2% to -21.6%).

CONCLUSIONS AND RELEVANCE: In this cohort study of more than 1.7 million pregnancies in Ontario, Canada, a publicly funded IVF program mandating an eSET policy was associated with a reduction in multifetal pregnancy rates. Nevertheless, ongoing strategies are needed to decrease multifetal pregnancy, especially in those undergoing OI/IUI.

PMID:38662369 | DOI:10.1001/jamanetworkopen.2024.8496

JAMA Netw Open. 2024 Apr 1;7(4):e248889. doi: 10.1001/jamanetworkopen.2024.8889.

ABSTRACT

IMPORTANCE: With older drivers representing the fastest growing segment of the driver population and dementia prevalence increasing with age, policymakers face the challenge of balancing road safety and mobility of older adults. In states that require reporting a dementia diagnosis to the Department of Motor Vehicles (DMV), individuals with dementia may be reluctant to disclose symptoms of cognitive decline, and clinicians may be reluctant to probe for those symptoms, which may be associated with missed or delayed diagnoses.

OBJECTIVE: To assess whether DMV reporting policies for drivers with dementia are associated with primary care clinicians’ underdiagnosing dementia.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the 100% Medicare fee-for-service program and the Medicare Advantage plans from 2017 to 2019 on 223 036 primary care clinicians with at least 25 Medicare patients. Statistical analysis was performed from July to October 2023.

EXPOSURES: State DMV reporting policies for drivers with dementia.

MAIN OUTCOMES AND MEASURES: The main outcome was a binary variable indicating whether the clinician underdiagnosed dementia or not. Each clinician’s expected number of dementia cases was estimated using a predictive model based on patient characteristics. Comparing the estimation with observed dementia diagnoses identified clinicians who underdiagnosed dementia vs those who did not, after accounting for sampling errors.

RESULTS: Four states have clinician reporting mandates, 14 have mandates requiring drivers to self-report dementia diagnoses, and 32 states and the District of Columbia do not have explicit requirements. Among primary care clinicians in states with clinician reporting mandates (n = 35 620), 51.4% were female, 91.9% worked in a metropolitan area, and 19.9% of the patient panel were beneficiaries dually eligible for Medicare and Medicaid. Among primary care clinicians in states with patient self-reporting mandates (n = 57 548), 55.7% were female, 83.1% worked in a metropolitan area, and 15.4% of the patient panel were dually eligible for Medicare and Medicaid. Among clinicians in states without mandates, 55.7% were female, 83.0% worked in a metropolitan area, and 14.6% of the patient panel were dually eligible for Medicare and Medicaid. Clinicians in states with clinician reporting mandates had an adjusted 12.4% (95% CI, 10.5%-14.2%) probability of underdiagnosing dementia compared with 7.8% (95% CI, 6.9%-8.7%) in states with self-reporting and 7.7% (95% CI, 6.9%-8.4%) in states with no mandates, an approximately 4-percentage point difference (P < .001).

CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study of primary care clinicians suggest that mandatory DMV policies for clinicians to report patients with dementia may be associated with a higher risk of missed or delayed dementia diagnoses. Future research is needed to better understand the unintended consequences and the risk-benefit tradeoffs of these policies.

PMID:38662368 | DOI:10.1001/jamanetworkopen.2024.8889