Nevin Manimala

Prehosp Disaster Med. 2023 Mar 21:1-6. doi: 10.1017/S1049023X23000341. Online ahead of print.

ABSTRACT

INTRODUCTION: Terrorist attacks against hospitals and health care providers have disproportionally increased during the last decades. A significant proportion of these attacks targeted abortion clinics and abortion providers. In the light of the overturning of Roe v. Wade in 2022, an increase of anti-abortion terrorist attacks is anticipated. Therefore, it becomes imperative to gain further insight into the risk and characteristics of past terrorist attacks. This study aimed to review terrorist attacks against health care targets providing abortion services from 1970 through 2020.

METHODS: Data collection was performed using a retrospective database search through the Global Terrorism Database (GTD). The GTD was searched using the internal database functions for all terrorist attacks against abortion health care providers from January 1, 1970 – December 31, 2020. Temporal factors, location, attack and weapon type, and number of casualties or hostages were analyzed using descriptive statistics.

RESULTS: In total, 262 terrorist attacks were identified in five different countries. The majority (96.6%) occurred in the United States, with the highest counts during the last 20 years of the 20th century. Facility and infrastructure attacks were the most common attack types, followed by bombings and explosions. The attacks resulted in 34 injuries and nine fatalities. Kidnapping took place in three incidents. Of all successful attacks, 96.9% resulted in property damage.

CONCLUSION: Abortion-related health care facilities and providers have repeatedly been the target of terrorists over the past decades. Nearly all of these attacks took place in the United States, with the highest counts during the last 20 years of the 20th century.

PMID:36942568 | DOI:10.1017/S1049023X23000341

J Neuroendocrinol. 2023 Mar 2:e13250. doi: 10.1111/jne.13250. Online ahead of print.

ABSTRACT

To assess the risk factors for polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) and develop a practical approach for PCOS screening based on clinical characteristic, blood indicator, and anti-seizure medication (ASM) profiles. This cross-sectional study was conducted with 248 WWE who were consecutively enrolled from the Epilepsy Center of West China Hospital between April 2021 and March 2022. The epilepsy characteristics, blood indicators, and use of ASMs were compared between WWE with and without PCOS. Multivariate logistic regression was used to identify the factors independently associated with PCOS. The differential analysis showed that younger age at onset of epilepsy (<13 years), a history of birth hypoxia, obesity (BMI ≥25 kg/m² ), use of levetiracetam (LEV) (≥1 year), higher levels of cholesterol, luteinizing hormone (LH) and anti-Müllerian hormone (AMH), and lower levels of sex hormone-binding globulin were associated with PCOS (p < .05). Multivariate logistic regression identified that obesity (BMI ≥25 kg/m² ), use of LEV (≥1 year), and higher levels of AMH and LH were independently associated with PCOS in WWE (p < .05). Obesity (BMI ≥25 kg/m² ), LEV use (≥1 year), and elevated AMH and LH levels suggest an increased in the probability of occurrence of PCOS in WWE. The combination of these profiles provides a practical approach for screening PCOS in WWE.

PMID:36942563 | DOI:10.1111/jne.13250

JAMA. 2023 Mar 21. doi: 10.1001/jama.2023.3576. Online ahead of print.

NO ABSTRACT

PMID:36942555 | DOI:10.1001/jama.2023.3576

JAMA. 2023 Mar 21. doi: 10.1001/jama.2023.3651. Online ahead of print.

ABSTRACT

IMPORTANCE: Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making.

OBJECTIVE: To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE.

DESIGN, SETTING, AND PARTICIPANTS: Exploratory analysis of a multiplatform adaptive RCT of therapeutic-dose heparin vs usual care pharmacologic thromboprophylaxis in 3320 patients hospitalized for COVID-19 enrolled in North America, South America, Europe, Asia, and Australia between April 2020 and January 2021. Heterogeneity of treatment effect was assessed 3 ways: using (1) conventional subgroup analyses of baseline characteristics, (2) a multivariable outcome prediction model (risk-based approach), and (3) a multivariable causal forest model (effect-based approach). Analyses primarily used bayesian statistics, consistent with the original trial.

EXPOSURES: Participants were randomized to therapeutic-dose heparin or usual care pharmacologic thromboprophylaxis.

MAIN OUTCOMES AND MEASURES: Organ support-free days, assigning a value of -1 to those who died in the hospital and the number of days free of cardiovascular or respiratory organ support up to day 21 for those who survived to hospital discharge; and hospital survival.

RESULTS: Baseline demographic characteristics were similar between patients randomized to therapeutic-dose heparin or usual care (median age, 60 years; 38% female; 32% known non-White race; 45% Hispanic). In the overall multiplatform RCT population, therapeutic-dose heparin was not associated with an increase in organ support-free days (median value for the posterior distribution of the OR, 1.05; 95% credible interval, 0.91-1.22). In conventional subgroup analyses, the effect of therapeutic-dose heparin on organ support-free days differed between patients requiring organ support at baseline or not (median OR, 0.85 vs 1.30; posterior probability of difference in OR, 99.8%), between females and males (median OR, 0.87 vs 1.16; posterior probability of difference in OR, 96.4%), and between patients with lower body mass index (BMI <30) vs higher BMI groups (BMI ≥30; posterior probability of difference in ORs >90% for all comparisons). In risk-based analysis, patients at lowest risk of poor outcome had the highest propensity for benefit from heparin (lowest risk decile: posterior probability of OR >1, 92%) while those at highest risk were most likely to be harmed (highest risk decile: posterior probability of OR <1, 87%). In effect-based analysis, a subset of patients identified at high risk of harm (P = .05 for difference in treatment effect) tended to have high BMI and were more likely to require organ support at baseline.

CONCLUSIONS AND RELEVANCE: Among patients hospitalized for COVID-19, the effect of therapeutic-dose heparin was heterogeneous. In all 3 approaches to assessing HTE, heparin was more likely to be beneficial in those who were less severely ill at presentation or had lower BMI and more likely to be harmful in sicker patients and those with higher BMI. The findings illustrate the importance of considering HTE in the design and analysis of RCTs.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02735707, NCT04505774, NCT04359277, NCT04372589.

PMID:36942550 | DOI:10.1001/jama.2023.3651

Neuroradiol J. 2023 Mar 21:19714009231166100. doi: 10.1177/19714009231166100. Online ahead of print.

ABSTRACT

OBJECTIVES: Histological studies have shown alterations of thalamic nuclei in patients with Down syndrome (DS). The correlation of these changes on MRI (magnetic resonance imaging) is unclear. Therefore, this study investigates volumetric differences of thalamic nuclei in children with DS compared to controls.

METHODS: Patients were retrospectively identified between 01/2000 and 10/2021. Patient inclusion criteria were: (1) 0-18 years of age, (2) diagnosis of DS, and (3) availability of a brain MRI without parenchymal injury and a non-motion-degraded volumetric T1-weighted sequence. Whole thalamus and thalamic nuclei (n = 25) volumes were analyzed bilaterally relative to the total brain volume (TBV). Two-sided t-tests were used to evaluate differences between groups. Differences were considered significant if the adjusted p-value was <0.05 after correction for multiple hypothesis testing using the Holm-Bonferroni method.

RESULTS: 21 children with DS (11 females, 52.4%, mean age: 8.6 ± 4.3 years) and 63 age- and sex-matched controls (32 females, 50.8%, 8.6 ± 4.3 years) were studied using automated volumetric segmentation. Significantly smaller ratios were found for nine thalamic nuclei and the whole thalamus on the right and five thalamic nuclei on the left. TBV was significantly smaller in patients with DS (p < 0.001). No significant differences were found between the groups for age and sex.

CONCLUSIONS: In this exploratory volumetric analysis of the thalamus and thalamic nuclei, we observed statistically significant volumetric changes in children with DS. Our findings confirm prior neuroimaging and histological studies and extend the range of involved thalamic nuclei in pediatric DS.

PMID:36942548 | DOI:10.1177/19714009231166100

JAMA. 2023 Mar 21. doi: 10.1001/jama.2023.4080. Online ahead of print.

ABSTRACT

IMPORTANCE: Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption.

OBJECTIVE: To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion.

DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021.

INTERVENTIONS: Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines.

MAIN OUTCOMES AND MEASURES: The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety).

RESULTS: Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P = .72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P = .03).

CONCLUSIONS AND RELEVANCE: Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03218722.

PMID:36942533 | DOI:10.1001/jama.2023.4080

CNS Neurosci Ther. 2023 Mar 21. doi: 10.1111/cns.14167. Online ahead of print.

ABSTRACT

BACKGROUND: In Parkinson’s disease (PD), inflammation may lead to the degeneration of dopaminergic (DAergic) neurons. Previous studies showed that inflammatory mediators mainly contributed to this phenomenon. On the other hand, invasive neuromodulation methods such as deep brain stimulation (DBS) have better therapeutic effects for PD. One possibility is that DBS improves PD by influencing inflammation. Therefore, we further explored the mechanisms underlying inflammatory mediators and DBS in the pathogenesis of PD.

METHODS: We measured serum levels of two inflammatory markers, namely RANTES (regulated on activation, normal T cell expressed and secreted) and tumor necrosis factor-alpha (TNF-α), using Luminex assays in 109 preoperative DBS PD patients, 49 postoperative DBS PD patients, and 113 age- and sex-matched controls. The plasma protein data of the different groups were then statistically analyzed.

RESULTS: RANTES (p < 0.001) and TNF-α (p = 0.005) levels differed significantly between the three groups. A strong and significant correlation between RANTES levels and Hoehn-Yahr (H-Y) stage was observed in preoperative PD patients (r_s = 0.567, p < 0.001). Significant correlations between RANTES levels and Unified Parkinson’s Disease Rating Scale III (UPDRS III) score (r_s1 = 0.644, p = 0.033 and r_s2 = 0.620, p = 0.042) were observed in matched patients. No correlation was observed for TNF-α levels.

CONCLUSION: The results of this study indicate that PD patients have a persistent inflammatory profile, possibly via recruitment of activated monocytes, macrophages, and T lymphocytes to the central nervous system (CNS). DBS was shown to have a significant therapeutic effect on PD, which may arise by improving the inflammatory environment of the central nervous system.

PMID:36942520 | DOI:10.1111/cns.14167

Cardiol Young. 2023 Mar 21:1-6. doi: 10.1017/S1047951123000513. Online ahead of print.

ABSTRACT

BACKGROUND: Total abnormal pulmonary venous return anomaly is a CHD characterised by abnormal pulmonary venous flow directed to the right atrium. In this study, we aimed to compare the effects of these techniques on early rhythm problems in total abnormal pulmonary venous return anomaly cases operated with conventional or primary sutureless techniques.

METHOD: Seventy consecutive cases (median age 1 month, median weight 4 kg) who underwent total abnormal pulmonary venous return anomaly repair with conventional or primary sutureless technique between May 1 2020 and May 1 2022 were evaluated. The rate, diagnosis, and possible risk factors of postoperative arrhythmias were investigated. The results were evaluated statistically.

RESULTS: When the total abnormal pulmonary venous return anomaly subgroup of 70 cases was evaluated, 40 cases were supracardiac, 18 cases were infracardiac, 7 cases were cardiac, and 5 cases were mixed type. Twenty-eight (40%) cases had a pulmonary venous obstruction. Primary sutureless technique (57%, supracardiac n = 24, mixed = 3, infracardiac = 13) was used in 40 patients. Median cardiopulmonary bypass time (110 versus 95 minutes) and median aortic clamp time (70 versus 60 minutes), median peak lactate (4.7 versus 4.8 mmol/l) in the first 72 hours, and median peak vasoactive inotropic score in the first 72 hours of the primary sutureless and conventional technique used cases value (8 versus 10) were similar. The total incidence of arrhythmias in the conventional group was significantly higher than in the primary sutureless group (46.7% versus 22.5%, p = 0.04). Supraventricular early beat was observed in 3 (7.5%), sinus tachycardia was seen in 6 (15%), junctional ectopic tachycardia was seen in 1 (2.5%), intra-atrial reentry tachycardia was seen in 1 (2.5%), usual supraventricular tachyarrhythmia was seen in 2 cases (5%) in the primary sutureless group. In the conventional group, supraventricular early beat was observed in six of the cases (20%), sinus tachycardia in five (16.7%), junctional ectopic tachycardia in four (13.3%), intra-atrial reentry tachycardia (10%) in three, and supraventricular tachyarrhythmia in seven cases (23.3%). In the first 30 days, there was a similar mortality rate (10% versus 10%), with four patients in the primary sutureless group and three in the conventional group. The median follow-up period of the cases was 8 months (interquartile range (IQR) 6-10 months). In the follow-up, arrhythmias were detected in two cases (one supraventricular tachyarrhythmia and one intra-atrial reentry tachycardia) in the primary sutureless group and three cases (two supraventricular tachyarrhythmia, one intra-atrial reentry tachycardia) in the conventional technique. All cases were converted to normal sinus rhythm with cardioversion and combined antiarrhythmic therapy.

CONCLUSION: Different arrhythmias can be observed in the early period in patients with operated total abnormal pulmonary venous return anomaly. Although a higher rate of rhythm problems was observed in the early period in the conventional method compared to the primary sutureless technique, no significant effect was found on mortality and morbidity between the groups.

PMID:36942512 | DOI:10.1017/S1047951123000513

CNS Neurosci Ther. 2023 Mar 21. doi: 10.1111/cns.14182. Online ahead of print.

ABSTRACT

INTRODUCTION: Untreated basilar artery occlusion (BAO) carries 70% mortality. Guidelines recommend thrombectomy with or without thrombolysis.

AIM: We compared Modified Rankin Scores (mRS) at 3 and 12 months post thrombectomy to determine benefit of long-term follow up.

METHODS: Retrospective, single centre analysis of BAO thrombectomies between 2015 and 2019. Inclusion criteria were symptomatic BAO on CT angiography, absent early ischemic changes, premorbid independence and intervention within 24 h. All received stroke ward care. Results were analysed with simple statistics and binary logistic regression as appropriate.

RESULTS: Of 82 patients: most were male (61%, 50/82) with median age 68 years (IQR 17 years) and median NIHSS 14 (IQR 15). Median door-to-puncture time was 42 min (IQR 72 min). Total deaths were 34.1% (28/82) at 3 months, and 37.8% (31/82) at 12 months. Of 51 patients alive at 12 months: 41% (21/51) had improved mRS, 16% (8/51) had worse mRS and 43% (22/51) had unchanged mRS, compared to 3 months. Improvements to mRS were: one point in 57.1% (14/21), two points in 28.9% (6/21) and three points in 4.8% (1/21). Nursing home admission was avoided in 11.8% (6/51) who improved from mRS4. Increased age was associated with decreased likelihood of reaching the primary outcome OR 0.87, 95% CI 0.76-0.99 (p value = 0.03).

CONCLUSION: Over a quarter of patients improved beyond 3 months. Future studies should adopt long-term follow up as primary outcome.

PMID:36942501 | DOI:10.1111/cns.14182

ESC Heart Fail. 2023 Mar 21. doi: 10.1002/ehf2.14352. Online ahead of print.

ABSTRACT

AIMS: Although the haemodynamic effects of angiotensin receptor-neprilysin inhibitor (ARNI) on patients with heart failure have been demonstrated, the effect on glucose metabolism has not been fully elucidated. We retrospectively investigated the effect of ARNI on abnormal glucose metabolism in patients with stable chronic heart failure using an additional structural equation model (SEM) analysis.

METHODS: We analysed 34 patients who regularly visited to the outpatient department of our institute with heart failure from October 2021 and July 2022 and who were taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Seventeen patients switched from ACE inhibitors or ARBs to an ARNI (ARNI group), and the other 17 patients continued treatment with ACE inhibitors or ARBs (control group).

RESULTS: At baseline, although the ARNI group included fewer patients with heart failure with preserved ejection fraction in comparison with the control group (P = 0.004), patients with heart failure with mildly reduced ejection fraction, and heart failure with reduced ejection fraction were mostly biased towards the ARNI group (although not statistically significant). The baseline insulin resistance in the ARNI group was already significantly higher in comparison with the control group [fasting blood insulin, 9.7 (7.4, 11.6) vs. 7.8 (5.2, 9.2) μU/mL, P = 0.033; homoeostasis model assessment of insulin resistance (HOMA-IR), 3.10 (1.95, 4.19) vs. 2.02 (1.56, 2.42), P = 0.014]. Three months later, the fasting blood insulin and the HOMA-IR levels were both found to have decreased in comparison with the baseline values [baseline to 3 months: insulin, 9.7 (7.4, 11.6) to 7.3 (4.6, 9.4) μU/mL, P < 0.001; HOMA-IR, 3.10 (1.95, 4.19) to 1.96 (1.23, 3.09), P < 0.001]. An additional SEM analysis demonstrated that the initiation of ARNI had caused a reduction in the fasting blood insulin and the HOMA-IR levels at 3 months independently of the baseline fasting blood insulin and HOMA-IR levels, respectively. Similarly, the initiation of ARNI resulted in a significant reduction in serum uric acid levels (6.28 ± 0.35 to 5.80 ± 0.30 mg/dL, P = 0.008).

CONCLUSIONS: In conclusion, even in a short period of only 3 months, the administration of ARNI improved insulin resistance and consequently reduced the serum uric acid levels in patients with stable chronic heart failure. Although the ARNI group already had high insulin resistance at baseline, an additional SEM analysis revealed that the decreased insulin resistance was truly due to the effect of ARNI.

PMID:36942494 | DOI:10.1002/ehf2.14352