Category: Nevin Manimala

JAMA Netw Open. 2022 Mar 1;5(3):e222101. doi: 10.1001/jamanetworkopen.2022.2101.

ABSTRACT

IMPORTANCE: Understanding mental health and substance use treatment seeking and suicidality among suicide decedents is important to determine prevention efforts.

OBJECTIVE: To evaluate differences in treatment seeking and suicidality between suicide decedents who died by firearms and those who died by other methods.

DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional data were collected on 234 652 suicide decedents from 2003 to 2018. Participant information was reported by their state of residence to the National Violent Death Reporting System. Statistical analysis was performed from July 1, 2021, to January 21, 2022.

MAIN OUTCOMES AND MEASURES: Main outcomes were treatment for mental health and substance use at time of death, previous treatment for mental health and substance use, history of suicidal ideation or plans, history of suicide attempts, and disclosure of suicidal ideation or plans.

RESULTS: A total of 234 652 participants (182 520 male [77.8%]; 205 966 White [87.8%]; mean [SD] age, 46.3 [18.2] years [range, 3-112 years]) were included in this study. Compared with suicide decedents who died by another method (n = 117 526 [50.1%]), those who died by firearm (n = 117 126 [49.9%]) were more likely to have disclosed thoughts or plans of suicide within the month prior to death (odds ratio [OR], 1.16 [95% CI, 1.13-1.18]) and were less likely to have previously attempted suicide (OR, 0.44 [95% CI, 0.43-0.46]). Compared with those who died by poisoning, those who used a firearm were more likely to have had a history of suicidal thoughts or plans (OR, 1.19 [95% CI, 1.15-1.23]) and to have disclosed their thoughts or plans of suicide within the month prior to death (OR, 1.06 [95% CI, 1.03-1.10]). Compared with those who died by hanging, those who used a firearm were more likely to have disclosed their thoughts or plans of suicide to another person within the month prior to their death (OR, 1.14 [95% CI, 1.11-1.17]).

CONCLUSIONS AND RELEVANCE: These findings provide information that suggests who is at risk to die by firearm suicide. Community-based interventions in suicide prevention could help reduce access to firearms during a time of crisis. The finding that firearm suicide decedents were more likely to disclose their suicidal thoughts or plans provides an important avenue for prevention.

PMID:35285919 | DOI:10.1001/jamanetworkopen.2022.2101

JAMA Netw Open. 2022 Mar 1;5(3):e222117. doi: 10.1001/jamanetworkopen.2022.2117.

ABSTRACT

IMPORTANCE: Penicillin allergy labels influence clinical decision-making, yet most children who are labeled do not have type 1 hypersensitivity allergic reactions and instead have a history of predictable adverse reactions or unspecified illness symptoms while receiving penicillin for viral infections. Studies describing penicillin allergy labeling in the pediatric outpatient setting are lacking.

OBJECTIVE: To describe the epidemiology and factors associated with penicillin allergy labels across 2 large US pediatric primary care networks.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal birth cohort study was conducted in 90 primary care pediatric practices serving a diverse population of children across Houston, Texas, Austin, Texas, Philadelphia, Pennsylvania, and parts of New Jersey. Participants were children born between January 2010 and June 2020 who had a health care visit in the first 14 days of life and at least 2 additional visits in the first year of life at one of 90 primary care pediatric practices. Censoring criteria were additionally applied to exclude data from children no longer seeking health care in the 90 clinics over time. Statistical analysis was performed from February to May 2021.

EXPOSURES: Basic patient demographics, health care utilization, penicillin exposure, and primary clinic location.

MAIN OUTCOMES AND MEASURES: Addition of penicillin allergy label in the electronic medical record.

RESULTS: Among 334 465 children in the birth cohort, 164 173 (49.1%) were female; 72 831 (21.8%) were Hispanic, 59 598 (17.8%) were non-Hispanic Black, and 148 534 (44.4%) were non-Hispanic White; the median (IQR) age at censoring was 3.8 (1.7-6.6) years; 18 015 (5.4%) were labeled as penicillin allergic, but the prevalence of penicillin allergy labeling ranged from 0.9% to 10.2% across practices. Children were labeled at a median (IQR) age of 1.3 (0.9-2.3) years. Non-Hispanic White children were more likely to be labeled compared with non-Hispanic Black children after controlling for potential confounders (adjusted odds ratio, 1.7 [95% CI, 1.6-1.8]). There were 6797 allergic children (37.7%) labeled after receiving 1 penicillin prescription and 1423 (7.9%) labeled after receiving 0 penicillin prescriptions.

CONCLUSIONS AND RELEVANCE: In this cohort study of more than 330 000 children, penicillin allergy labeling was common and varied widely across practices. Children were labeled early in life, and almost half were labeled after receiving 1 or 0 penicillin prescriptions. These findings raise questions regarding the validity of penicillin allergy labels. Future work exploring the fidelity of and outcomes associated with penicillin allergy-labeling in children is warranted.

PMID:35285918 | DOI:10.1001/jamanetworkopen.2022.2117

Lab Med. 2022 Mar 14:lmac014. doi: 10.1093/labmed/lmac014. Online ahead of print.

ABSTRACT

OBJECTIVE: The T-cell receptor β constant region 1 (TRBC1) antibody can identify T-cell clonality and distinguish pathological from normal T cells. This study aims to establish optimal cutpoints for establishing monotypia and validate the diagnostic abilities of the TRBC1 antibody when used as a reflex test in conjunction with an existing T-cell antibody panel.

MATERIALS AND METHODS: We used 46 normal peripheral blood specimens and examined 8 patients with reactive lymphoproliferations to determine the normal biological range of TRBC1 on CD4+ and CD8+ T cells. We also evaluated 43 patient specimens that were submitted for investigation of a lymphoproliferative disorder for CD2/CD3/CD4/CD5/CD7/CD8/CD16/CD26/CD45/CD56/TCR αβ/TCR γδ, along with TRBC1 expression. The results were compared to TCR gene rearrangement patterns using polymerase chain reaction (PCR) analysis.

RESULTS: Statistical analysis established differing cutoff points for establishing monotypia dependent on restricted TRBC1 or TRBC2 usage. Direct comparison with molecular analysis indicated that no specimen identified with the restricted expression of TRBC1 was reported as polyclonal by PCR with a concordance rate of 97% between a clonal PCR result and monotypic TRBC1 expression.

CONCLUSION: Incorporation of the TRBC1 antibody using statistically derived cutoff points in a reflex setting for the evaluation of a suspected T-cell neoplasm improves the identification of clonal T-cell populations by flow cytometry and correlates well with molecular methods.

PMID:35285909 | DOI:10.1093/labmed/lmac014

Int J Qual Health Care. 2022 Mar 14:mzac012. doi: 10.1093/intqhc/mzac012. Online ahead of print.

ABSTRACT

BACKGROUND: Doctors and nurses are frequently exposed to needlestick and sharps injuries (NSIs) because of their work. It is estimated that NSIs are more common than the reported rates to Infection Control Committee. The purpose of this study was to determine the incidence and reporting rates of NSIs in our hospital.

METHODS: After their consent forms were obtained for the questionnaire, 670 doctors and nurses were interviewed face-to-face by the Infection Control Committee nurse. The questionnaire consisted of 22 questions, and the answers were recorded. The questions were on demographic data and injuries. The data of NSIs, whose active surveillance was made in our hospital since 2005 and in the last 1 year were also analyzed retrospectively.

RESULTS: A total of 119 (17%) out of 670 people who participated in the study had at least one NSIs; 43 (36%) of the 119 people were doctors, and 76 (63.9%) were nurses. The most common injuries among doctors were found in assistant doctors (60%). No statistically significant differences were detected between the doctors and nurses in terms of injury status (p=0.398). The most common injuries were found in surgical clinics, and a significant difference was detected here when compared to other clinics. The data that 20 (17%) of the 118 people who were injured by the NSIs reported the injury were obtained from the Infection Control Committee database.

CONCLUSION: It is seen that injuries are high in surgical clinics and assistant doctors who have high work stress and workload. There were more injuries with sharp objects than the expected rates in our hospital although the reports were made very rarely. First of all, we should determine strategies, especially education, to reduce injuries, and then remove the obstacles to unreported injuries. Activities of clinics with high reporting rates needs to be search and adapt them to our clinic.

PMID:35285914 | DOI:10.1093/intqhc/mzac012

Eur J Orthod. 2022 Mar 14:cjac006. doi: 10.1093/ejo/cjac006. Online ahead of print.

ABSTRACT

AIM: To assess whether the efficacy of external tooth bleaching differs between untreated and orthodontically treated teeth.

MATERIALS AND METHOD: Three groups of subjects were formed; group Debonded included 24 consecutive orthodontically treated patients evaluated immediately after removal of fixed appliances. The Retention group included 24 consecutive orthodontically treated patients in the phase of retention. The Untreated group consisted of 24 arbitrarily selected undergraduate dental students without history of fixed-appliances orthodontic therapy. Each of the above three groups was further randomized into two subgroups, Bleaching and Placebo. Each subgroup received either a 38% hydrogen peroxide bleaching treatment or a placebo agent, respectively. Tooth colour changes were assessed at seven timepoints: 1 day before intervention; on the day of intervention before and after treatment; and at 7, 14, 21, and 90 days for parameters L*, a*, b*, and ΔΕ in all upper incisors and canines with the use of a reflectance spectrophotometer. Intra-rater agreement was estimated with the Intra-class Correlation Coefficient and method’s error was calculated using the Repeatability Coefficient. Regarding tooth colour changes, an analysis of variance was used to assess differences between groups.

RESULTS: Bleaching was associated with an increase of the L* value and decrease of b* and a* values in both orthodontically treated and untreated teeth. Parameters ΔE, L*, and b* exhibited statistically significant differences between the Bleaching-Untreated and Bleaching-Retention subgroups. In the Bleaching subgroups, statistically significant differences were found between different teeth for all parameters.

CONCLUSIONS: Previous exposure to fixed orthodontic appliance influenced the efficacy of external tooth bleaching. The effect of bleaching was higher after orthodontic treatment and with longer period in retention. Canines changed in colour more than incisors, and the effect was reduced over time.

PMID:35285904 | DOI:10.1093/ejo/cjac006

JAMA Neurol. 2022 Mar 14. doi: 10.1001/jamaneurol.2022.0048. Online ahead of print.

ABSTRACT

IMPORTANCE: Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain.

OBJECTIVE: To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients.

MAIN OUTCOMES AND MEASURES: Recurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO).

RESULTS: The mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI, 1.8-15), presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI, 4.8-22).

CONCLUSIONS AND RELEVANCE: In this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.

PMID:35285869 | DOI:10.1001/jamaneurol.2022.0048

Interact Cardiovasc Thorac Surg. 2022 Mar 14:ivac068. doi: 10.1093/icvts/ivac068. Online ahead of print.

ABSTRACT

OBJECTIVES: Presentation, management and outcomes in the aortic dissection (AD) of ascending thoracic aortic aneurysm (ATAA) differ in gender and age. The purpose of this study is to investigate the dissection properties of male and female ATAAs.

METHODS: Peeling tests were performed to quantitatively determine the delamination strength and dissection energy of 41 fresh ATAA samples (22 males and 19 females) in relatively young (≤65 years) and elderly (>65 years) patients. The delamination strength of the ATAAs was further correlated with patient ages for males and females. The histological investigation was employed to characterize the dissected morphology.

RESULTS: For elderly patients, circumferential and longitudinal delamination strengths of the female ATAAs were statistically significantly lower than those of the males (circumferential: 31 ± 6 vs 42 ± 6 mN/mm, P < 0.01; longitudinal: 35 ± 7 vs 49 ± 10 mN/mm, P = 0.02). No significant differences were found in the delamination strength between males and females for relatively young patients. The circumferential and longitudinal delamination strengths were significantly decreased and strongly correlated with patient ages for females. However, these correlations were not present in males. Dissection routes propagated in the aortic media to create ruptured surfaces for all specimens. Peeling tests of the male ATAAs generate rougher surfaces than females.

CONCLUSIONS: There is a higher propensity of AD occurrence for the elderly females as compared to males with matched ages. Surgeons should be cognizant of the risk of AD onset later in life, especially in females.

PMID:35285896 | DOI:10.1093/icvts/ivac068

JAMA. 2022 Mar 14. doi: 10.1001/jama.2022.2832. Online ahead of print.

ABSTRACT

IMPORTANCE: Older patients and those with comorbidities who are infected with SARS-CoV-2 may be at increased risk of hospitalization and death. Sotrovimab is a neutralizing antibody for the treatment of high-risk patients to prevent COVID-19 progression.

OBJECTIVE: To evaluate the efficacy and adverse events of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease.

DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial including 1057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for progression conducted at 57 sites in Brazil, Canada, Peru, Spain, and the US from August 27, 2020, through March 11, 2021; follow-up data were collected through April 8, 2021.

INTERVENTIONS: Patients were randomized (1:1) to an intravenous infusion with 500 mg of sotrovimab (n = 528) or placebo (n = 529).

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute illness management or death); 5 secondary outcomes were tested in hierarchal order, including a composite of all-cause emergency department (ED) visit, hospitalization of any duration for acute illness management, or death through day 29 and progression to severe or critical respiratory COVID-19 requiring supplemental oxygen or mechanical ventilation.

RESULTS: Enrollment was stopped early for efficacy at the prespecified interim analysis. Among 1057 patients randomized (median age, 53 years [IQR, 42-62], 20% were ≥65 years of age, and 65% Latinx), the median duration of follow-up was 103 days for sotrovimab and 102 days for placebo. All-cause hospitalization lasting longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) (adjusted relative risk [RR], 0.21 [95% CI, 0.09 to 0.50]; absolute difference, -4.53% [95% CI, -6.70% to -2.37%]; P < .001). Four of the 5 secondary outcomes were statistically significant in favor of sotrovimab, including reduced ED visit, hospitalization, or death (13/528 [2%] for sotrovimab vs 39/529 [7%] for placebo; adjusted RR, 0.34 [95% CI, 0.19 to 0.63]; absolute difference, -4.91% [95% CI, -7.50% to -2.32%]; P < .001) and progression to severe or critical respiratory COVID-19 (7/528 [1%] for sotrovimab vs 28/529 [5%] for placebo; adjusted RR, 0.26 [95% CI, 0.12 to 0.59]; absolute difference, -3.97% [95% CI, -6.11% to -1.82%]; P = .002). Adverse events were infrequent and similar between treatment groups (22% for sotrovimab vs 23% for placebo); the most common events were diarrhea with sotrovimab (n = 8; 2%) and COVID-19 pneumonia with placebo (n = 22; 4%).

CONCLUSIONS AND RELEVANCE: Among nonhospitalized patients with mild to moderate COVID-19 and at risk of disease progression, a single intravenous dose of sotrovimab, compared with placebo, significantly reduced the risk of a composite end point of all-cause hospitalization or death through day 29. The findings support sotrovimab as a treatment option for nonhospitalized, high-risk patients with mild to moderate COVID-19, although efficacy against SARS-CoV-2 variants that have emerged since the study was completed is unknown.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04545060.

PMID:35285853 | DOI:10.1001/jama.2022.2832

J Vis Exp. 2022 Feb 22;(180). doi: 10.3791/62643.

ABSTRACT

Cardiac reprogramming has become a potentially promising therapy to repair a damaged heart. By introducing multiple transcription factors, including Mef2c, Gata4, Tbx5 (MGT), fibroblasts can be reprogrammed into induced cardiomyocytes (iCMs). These iCMs, when generated in situ in an infarcted heart, integrate electrically and mechanically with the surrounding myocardium, leading to a reduction in scar size and an improvement in heart function. Because of the relatively low reprogramming efficiency, purity, and quality of the iCMs, characterization of iCMs remains a challenge. The currently used methods in this field, including flow cytometry, immunocytochemistry, and qPCR, mainly focus on cardiac-specific gene and protein expression but not on the functional maturation of iCMs. Triggered by action potentials, the opening of voltage-gated calcium channels in cardiomyocytes leads to a rapid influx of calcium into the cell. Therefore, quantifying the rate of calcium influx is a promising method to evaluate cardiomyocyte function. Here, the protocol introduces a method to evaluate iCM function by calcium (Ca²⁺) flux. An αMHC-Cre/Rosa26A-Flox-Stop-Flox-GCaMP3 mouse strain was established by crossing Tg(Myh6-cre)1Jmk/J (referred to as Myh6-Cre below) with Gt(ROSA)26Sor^{tm38(CAG-GCaMP3)Hze}/J (referred to as Rosa26A-Flox-Stop-Flox-GCaMP3 below) mice. Neonatal cardiac fibroblasts (NCFs) from P0-P2 neonatal mice were isolated and cultured in vitro, and a polycistronic construction of MGT was introduced to NCFs, which led to their reprogramming to iCMs. Because only successfully reprogrammed iCMs will express GCaMP3 reporter, the functional maturation of iCMs can be visually assessed by Ca²⁺ flux with fluorescence microscopy. Compared with un-reprogrammed NCFs, NCF-iCMs showed significant calcium transient flux and spontaneous contraction, similar to CMs. This protocol describes in detail the mouse strain establishment, isolation and selection of neonatal mice hearts, NCF isolation, production of retrovirus for cardiac reprogramming, iCM induction, the evaluation of iCM Ca²⁺ flux using our reporter line, and related statistical analysis and data presentation. It is expected that the methods described here will provide a valuable platform to assess the functional maturation of iCMs for cardiac reprogramming studies.

PMID:35285824 | DOI:10.3791/62643

Aging Ment Health. 2022 Mar 14:1-9. doi: 10.1080/13607863.2022.2046692. Online ahead of print.

ABSTRACT

OBJECTIVES: In this article, we assess the feasibility and acceptability and the effect of the Plan Ahead for community dwelling older adults. In addition, we investigated the effects of the program. In addition, we aimed to examine whether the completion of the specific Future Care Planning depended on the participants’ competence level.

METHODS: In this single group feasibility study, trained facilitators delivered the program to a sample of 234 community-residing older adults. Participants completed both pre, post assessments about the acceptability of the program and their completion of the recommended future care planning activities.

RESULTS: Based on participant’s report on the usefulness and satisfaction of the program after the completion of the program, we found that participants reported high levels of acceptance of the program. Participation rates also confirmed the feasibility of the program. In terms of effects of program implementation, statistically significant changes were noted for several outcomes, such as resource building and FCP activities. In particular, we found that these gains were particularly robust for participants in the low competence group.

CONCLUSION: Pilot program results suggest the feasibility of a short community program enhancing proactive planning for future care needs among older adults residing in their community.

PMID:35285774 | DOI:10.1080/13607863.2022.2046692