Nevin Manimala

Clin Toxicol (Phila). 2022 May 12:1-7. doi: 10.1080/15563650.2022.2072315. Online ahead of print.

ABSTRACT

BACKGROUND: Historically, the first step in treating cyanide (CN^–) toxicity utilized antidotes to induce methemoglobinemia. This is concerning in patients who are already hypoxemic or have elevated carboxyhemoglobin. Hydroxocobalamin (OHCbl) is now the first-line antidote for CN^– toxicity and is not known to induce methemoglobinemia. We observed elevated methemoglobin (MetHb) levels in several patients treated with OHCbl and sought to investigate the incidence of MetHb formation following administration of OHCbl.

METHODS: Chart review: A single-center, retrospective case series of patients who received 5 or 10 g of hydroxocobalamin from 01/01/2011 through 04/30/2019. Data was analyzed using descriptive statistics. In-vitro study: Discarded blood was separated into whole blood and plasma samples. OHCbl and normal saline was added to reach 0×, 1×, 2×, and 4× peak therapeutic concentrations and analyzed at times 0, 2, and 4 h after administration.

RESULTS: Chart review: Twenty-seven cases of OHCbl administration were identified. The median age was 53 years (IQR 38 – 64) and 20 (74.1%) were male. Exposure to a house fire or smoke inhalation was the reason for OHCbl administration in 21 (77.8%) patients. Five (18.5%) patients received 10 g of OHCbl while the rest received 5 g. Six (22.2%) patients developed methemoglobinemia, all after 5 g OHCbl administration; four had been exposed to fire and smoke, two received the medication for severe acidosis of unknown etiology not related to fire or smoke. The median peak level was 7.1% (IQR 2.2 – 16.4%) at a median time of 11.4 h post-administration. Two patients received methylene blue (MB), neither responded. Death occurred in 17 (63%) cases. In-vitro study: We observed a dose dependent elevation in total hemoglobin but did not detect any increase in MetHb.

CONCLUSION: We observed a noteworthy temporal association between the formation of methemoglobinemia and the administration of hydroxocobalamin. This does not appear to be an artifact of the CO-oximeters. This could have profound implications for patients who are already hypoxemic or have impaired oxygen carrying capacity from carboxyhemoglobin.

PMID:35549585 | DOI:10.1080/15563650.2022.2072315

Stat Methods Med Res. 2022 May 12:9622802221097211. doi: 10.1177/09622802221097211. Online ahead of print.

ABSTRACT

In medical research, the receiver operating characteristic curve is widely used to evaluate accuracy of a continuous biomarker. The area under this curve is known as an index for overall performance of the biomarker. This article develops three new estimators of the area under the receiver operating characteristic curve in ranked set sampling. The first estimator is obtained under normality assumption. The two other estimators are constructed by applying a Box-Cox transformation on data, and then using either a parametric estimator or a kernel-density-based estimator. A simulation study is carried out to compare the proposed estimators with those available in the literature. It emerges that the new estimators offer some advantages in specific situations. Application of the methods is demonstrated using real data in the context of medicine.

PMID:35549545 | DOI:10.1177/09622802221097211

J Psychopharmacol. 2022 May 13:2698811221089035. doi: 10.1177/02698811221089035. Online ahead of print.

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) is a prevalent neuropsychiatric illness for which it is important to resolve underlying brain mechanisms. Current treatments are often unsuccessful, precipitating a need to identify predictive markers.

AIM: We evaluated (1) alterations in brain responses to an emotional faces functional magnetic resonance imaging (fMRI) paradigm in individuals with MDD, compared to controls, (2) whether pretreatment brain responses predicted antidepressant treatment response, and (3) pre-post change in brain responses following treatment.

METHODS: Eighty-nine medication-free, depressed individuals and 115 healthy controls completed the fMRI paradigm. Depressed individuals completed a nonrandomized, open-label, 8-week treatment with escitalopram, including the option to switch to duloxetine after 4 weeks. We examined patient-control group differences in regional fMRI responses at baseline, whether baseline fMRI responses predicted treatment response at 8 weeks, including early life stress moderating effects, and change in fMRI responses in 36 depressed individuals rescanned following 8 weeks of treatment.

RESULTS: Task reaction time was 5% slower in patients. Multiple brain regions showed significant task-related responses, but we observed no statistically significant patient-control group differences (Cohen’s d < 0.35). Patient pretreatment brain responses did not predict antidepressant treatment response (area under the curve of the receiver operator characteristic (AUC-ROC) < 0.6) and brain responses were not statistically significantly changed after treatment (Cohen’s d < 0.33).

CONCLUSION: This represents the largest prediction study to date examining emotional faces fMRI features as predictors of antidepressant treatment response. Brain response to this fMRI emotional faces paradigm did not distinguish depressed individuals from healthy controls, nor was it predictive of antidepressant treatment response.Clinical Trial Registration: Site: https://clinicaltrials.gov, Trial Number: NCT02869035, Trial Title: Treatment Outcome in Major Depressive Disorder.

PMID:35549538 | DOI:10.1177/02698811221089035

Acta Radiol. 2022 May 12:2841851221100317. doi: 10.1177/02841851221100317. Online ahead of print.

ABSTRACT

BACKGROUND: Pisotriquetral joint (PTJ) disorders are an important cause of ulnar-sided wrist pain but are often underrecognized. Ulnar variance (UV) has been associated with several wrist pathologies.

PURPOSE: To determine the effect of UV on PTJ in patients with trauma.

MATERIAL AND METHODS: A total of 143 patients (77 men, 66 women; mean age=41.64 ± 18.07 years) were included. Patients with fractures, severe and high-energy trauma, arthritic conditions, avascular necrosis, congenital deformity, bone and soft-tissue tumors, suboptimal image quality, and incorrect joint position were excluded. UV and the amount of PTJ subluxation were evaluated using coronal and sagittal computed tomography images.

RESULTS: PTJ subluxation was divided into five grades. A statistically significant difference was found between the presence of PTJ subluxation and sex (P = 0.045). PTJ subluxation was more common in men (46.8%) than in women (30.3%). There was no significant difference between the presence of PTJ subluxation and age (P = 0.758). The patients were also divided into three groups as positive, neutral, and negative UV. A statistically significant relationship was found between the UV and presence of PTJ subluxation (P = 0.01). PTJ subluxation was significantly less in the neutral (none=51.1%, present=48.9%; P < 0.05) and negative (none=77.8%, present=22.2%; P < 0.05) groups.

CONCLUSION: PTJ subluxation was found to be less among the groups with neutral and negative UV in our study population. PTJ subluxation is more common in men while there is no relationship with age. UV and gender may be risk factors for PTJ subluxation by affecting force dynamics at the wrist joint.

PMID:35549516 | DOI:10.1177/02841851221100317

Scand J Rheumatol. 2022 May 12:1-8. doi: 10.1080/03009742.2022.2058178. Online ahead of print.

ABSTRACT

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology that affects approximately 1% of the population. The disease presents a temporal variability in different geographic areas. We investigated RA incidence over a 40-year-period in a defined area of north-west Greece, with a total population of about 400 000 inhabitants.

METHOD: This incidence study was based on retrospective review of clinical records among adults with RA newly diagnosed from 1980 to 2019 at the referral university hospital of Ioannina. An incident case was defined as any patient diagnosed with RA based on the 1987 American College of Rheumatology criteria, over 16-years-old, and resident in the study area for at least 1 year before diagnosis.

RESULTS: Out of 1411 cases diagnosed, women constituted a 2.65-fold higher number than men, with a lower mean age at diagnosis. The overall age-adjusted annual incidence rate (95% confidence interval) was 9.5 (8.5-10.5) for the total observation period, 11.7 (10.7-13.0) in 1980-1989, 10.4 (9.4-10.8) in 1990-1999, 9.8 (8.9-10.8) in 2000-2009, and 6.1 (5.3-6.9) in 2010-2019, presenting a statistically significant decline over time, along with a constant decrease in rheumatoid factor (RF)-positive incidence for both sexes.

CONCLUSION: Our findings suggest a decrease in the incidence of RA over 40 years in a geographically defined Greek population. Also, the progressive decrease in the incidence of RF-positive disease may relate to less severe expression of RA in Greek patients. These trends could be explained by different clinical, serological, and genetic factors reported in Greece compared to northern European countries.

PMID:35545952 | DOI:10.1080/03009742.2022.2058178

East Mediterr Health J. 2022 Apr 28;28(4):272-280. doi: 10.26719/emhj.22.013.

ABSTRACT

BACKGROUND: Childhood road traffic injuries (RTIs) are a major public health problem worldwide. Reliable and valid information on childhood RTIs is essential to reduce the number of deaths.

AIMS: To determine the burden of deaths from RTIs in children aged 0-14 years from 2006 to 2019 in Turkey.

METHODS: This descriptive study examined the change in road traffic fatalities in children according to age, gender, road user type, and place. The necessary data for this study were obtained from the Turkish Statistical Institute. We used Microsoft Excel to analyse data from 4614 children who died from RTIs in 2006-2019 in Turkey.

RESULTS: The fatality rate from RTIs per 100 000 children aged 0-14 years increased from 1.41 in 2006 to 2.13 in 2019. The fatality rate for boys aged 0-9 and 10-14 years was higher than that for girls of the same age. The fatality rate for girls aged 0-9 years was higher than that for girls aged 10-14 years. The fatality rate for boys aged 10-14 years was higher than that for boys aged 0-9 years. Among the children who died from RTIs, 6.65% were drivers, 41.31% pedestrians and 52.04% passengers. Children lost their lives mostly as pedestrians on urban roads and as passengers on rural roads.

CONCLUSION: The death of children due to RTIs is a significant health burden in Turkey.

PMID:35545908 | DOI:10.26719/emhj.22.013

Am J Health Promot. 2022 May 11:8901171211041424. doi: 10.1177/08901171211041424. Online ahead of print.

ABSTRACT

PURPOSE: To assess whether trajectories of children’s physical health problems differ by parental college degree attainment in Louisiana areas highly impacted by the 2010 BP Deepwater Horizon oil spill (BP-DHOS).

DESIGN: Three waves of panel data (2014, 2016, and 2018) from the Gulf Coast Population Impact / Resilient Children, Youth, and Communities studies.

SETTING: BP-DHOS-impacted communities in coastal Louisiana.

PARTICIPANTS: Parents of children aged 4-18 in a longitudinal probability sample (n = 392).

MEASURES: Reported child physical health problems from the BP-DHOS, parental college degree attainment, and covariates.

ANALYSIS: Linear growth curve models are used to assess initial levels of and the rate of change in child physical unknown. The current study uses 3 waves physical health problems by parental college degree attainment. Explanatory variables are measured at baseline and the outcome variable is measured at all 3 waves.

RESULTS: Compared to children of parents without college degrees, children of college graduates had fewer initial health problems in 2014 (b = -.33; p = .02). Yet, this health advantage decreased over time, as indicated by their positive rate of change (b = .22; p = .01), such that the higher education health advantage was not statistically significant by 2018.

CONCLUSION: Children of college graduates experienced a physical health advantage following the BP-DHOS, but this gap closed over time. The closure of the gap was due to the children of college graduates experiencing significant increases in reported health problems over the study period.

PMID:35545862 | DOI:10.1177/08901171211041424

Brain Tumor Res Treat. 2022 Apr;10(2):108-112. doi: 10.14791/btrt.2021.0028.

ABSTRACT

BACKGROUND: Patients with large vestibular schwannomas have various surgical outcomes. The aim of this study is to evaluate facial nerve outcome and surgical complications in patients who underwent total and subtotal resection.

METHODS: Between October 2008 and September 2020, 72 patients underwent surgery in Rajavithi Hospital. Of these, 48 had total or subtotal resection. We classified these participants into two groups: VS ≥3 cm (Group A, n=30); and VS <3 cm (Group B, n=18). Both groups were compared in terms of clinical presentation, imaging data, facial nerve outcomes, and surgical complications. The retrosigmoid approach was used in each case, and all patients had follow-up for at least 1 year. Chi-square and Fisher’s exact test were used for statistical analysis.

RESULTS: The mean tumor size in Group A was 3.8 cm compared with 1.5 cm in Group B. In Group A, clinical signs of hearing dysfunction, gait ataxia, and facial paresthesia were present in 96.7%, 66.7%, 50% of patients respectively, compared with 100%, 5.6%, and 11.1% respectively in Group B. Radiographic signs of hydrocephalus were observed in 56.7% of Group A subjects, and 5.6% of those in Group B. At 1 year follow-up, 40% of patients with large VS and 94.4% of patients with small to medium size VS had good facial nerve outcomes (House-Brackmann [HB] facial grading scale grade I-III). Significant differences between the two groups were found only in gait ataxia (p<0.001), facial paresthesia (p=0.006), radiographic signs of hydrocephalus (p=0.002), facial nerve outcome 1 month (p<0.001) and facial nerve outcome 1 year (p<0.001).

CONCLUSION: In patients with large size VS, microsurgical resection had poor facial nerve outcomes compared with those of their counterparts with small to medium size VS. Planned subtotal resection with postoperative radiosurgery might attain superior facial nerve outcomes and result in better quality of life in subjects with large VS.

PMID:35545830 | DOI:10.14791/btrt.2021.0028

J Trauma Acute Care Surg. 2022 May 12. doi: 10.1097/TA.0000000000003666. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this study was to identify clinical and traffic factors that influence pediatric pedestrian versus automobile collisions (P-AC) with an emphasis on health care disparities.

METHODS: A retrospective review was performed of pediatric (≤18 years old) P-AC treated at a Level I pediatric trauma center from 2008 to 2018. Demographic, clinical, and traffic scene data were analyzed. Area Deprivation Index (ADI) was used to measure neighborhood socioeconomic disadvantage (NSD) based on home addresses. Traffic scene data from the California Statewide Integrated Traffic Records System (SWITRS) were matched to clinical records. Traffic safety was assessed by the streetlight coverage, the proximity of the collision to home addresses, and sidewalk coverage. Descriptive statistics and univariate analysis for key variables and outcomes were calculated using Kruskal-Wallis, Wilcoxon, Chi-square, or Fisher’s exact tests. Statistical significance was attributed to p-values <0.05.

RESULTS: Among 770 patients, the majority were male (65%) and Hispanic (54%), with a median age of 8 years (IQR 4-12). Hispanic patients were more likely to live in more disadvantaged neighborhoods than non-Hispanic patients (67% vs. 45%, p < 0.01). There were no differences in clinical characteristics or outcomes across ADI quintiles. Using the SWITRS (N = 272), patients with more NSD were more likely injured during dark streetlight conditions (15% vs. 4% least disadvantaged; p = 0.04) and within 0.5 miles from home (p < 0.01). Pedestrian violations were common (65%). During after-school hours, 25% were pedestrian violations, compared to 12% driver violations (p = 0.02).

CONCLUSION: A larger proportion of Hispanic children injured in pedestrian versus automobile collisions lived in neighborhoods with more socioeconomic disadvantage. Hispanic ethnicity and NSD are each independently associated with P-AC. Poor streetlight conditions and close proximity to home were associated with the most socioeconomically disadvantaged neighborhoods. This research may support targeted prevention programs to improve pedestrian safety in children.

LEVEL OF EVIDENCE: Level III, Prognostic and Epidemiological.

PMID:35545801 | DOI:10.1097/TA.0000000000003666

Alzheimers Res Ther. 2022 May 11;14(1):65. doi: 10.1186/s13195-022-01011-w.

ABSTRACT

BACKGROUND: Blood phosphorylated tau (p-tau) forms are promising Alzheimer’s disease (AD) biomarkers, but validation in matrices other than ethylenediaminetetraacetic acid (EDTA) plasma is limited. Firstly, we assessed the diagnostic potential of p-tau231 and p-tau181 in paired plasma and serum samples. Secondly, we compared serum and cerebrospinal fluid (CSF) samples from biomarker-positive AD and biomarker-negative control participants.

METHODS: We studied three independent cohorts (n=115 total): cohorts 1 and 2 included individuals with paired plasma and serum, while cohort 3 included paired serum and CSF. Blood-based p-tau231 and p-tau181 were measured using in-house or commercial single molecule array (Simoa) methods.

RESULTS: Serum and plasma p-tau231 and p-tau181 were two- to three-fold increased in biomarker-positive AD versus biomarker-negative controls (P≤0.0008). Serum p-tau231 separated diagnostic groups with area under the curve (AUC) of 82.2% (cohort 3) to 88.2% (cohort 1) compared with 90.2% (cohort 1) for plasma. Similarly, p-tau181 showed AUC of 89.6% (cohort 1) to 89.8% (cohort 3) in serum versus 85.4% in plasma (cohort 1). P-tau231 and p-tau181 correlated slightly better in serum (rho=0.92 for cohort 1, 0.93 for cohort 3) than in plasma (rho=0.88, cohort 1). Within-individual p-tau181 (Quanterix) and p-tau231 concentrations were twice higher in plasma versus serum, but p-tau181 (in-house, Gothenburg) levels were not statistically different. Bland-Altman plots revealed that the relative difference between serum/plasma was larger in the lower range. P-tau levels in paired plasma and serum correlated strongly with each other (rho=0.75-0.93) as well as with CSF Aβ₄₂ (rho= -0.56 to -0.59), p-tau and total-tau (rho=0.53-0.73). Based on the results, it seems possible that serum p-tau reflects the same pool of brain-secreted p-tau as in CSF; we estimated that less than 2% of CSF p-tau is found in serum, being same for both controls and AD.

CONCLUSIONS: Comparable diagnostic performances and strong correlations between serum versus plasma pairs suggest that p-tau analyses can be expanded to research cohorts and hospital systems that prefer serum to other blood matrices. However, absolute biomarker concentrations may not be interchangeable, indicating that plasma and serum samples should be used independently. These results should be validated in independent cohorts.

PMID:35545792 | DOI:10.1186/s13195-022-01011-w