bluuebunny/crossref_metadata_2025 huggingface dataset:
The Logic and Value of the Presumption of Doli Incapax (Failing That, an Incapacity Defence)
Authors: Hamer David , Crofts Thomas
Published: June 2023

Children who do not understand the serious wrongness of their actions lack criminal capacity and cannot be convicted. At common law, children under seven are deemed to lack criminal capacity, children over 14 possess full capacity and children between seven and 14 are rebuttably presumed to lack capacity; the prosecution must prove capacity beyond reasonable doubt. Australia has increased the minimum age of criminal responsibility (MACR) to 10 and is considering a further increase. England & Wales and Northern Ireland have raised the MACR to 10 but have abolished the rebuttable presumption: at age 10, all children are assigned full criminal capacity. This article agrees with international calls for the MACR to be raised but argues that it is more important that the rebuttable presumption should be retained and extended. Children’s brains and decision-making capacities continue to develop throughout their teenage years at different rates. The rebuttable presumption provides individualised justice for children facing developmental difficulties. To wrongfully convict a child who lacks capacity will unjustly damage their life chances. Where a child does have capacity, a variety of evidence may be available to the prosecution to prove it. If the prosecution fails to discharge the burden, the child should be acquitted. The acquittal may be mistaken, but this error is far less harmful than a wrongful conviction.
La promotion de l’évolution optimale de la santé mentale chez les enfants et les adolescents
Authors: Arruda Wilma , Bélanger Stacey A , Cohen Janice S , Hrycko Sophia , Kawamura Anne , Lane Margo , Patriquin Maria J , Korczak Daphne J
Published: June 2023

Les dispensateurs de soins pédiatriques sont souvent le premier point de contact des enfants et des adolescents aux prises avec des problèmes de santé mentale, mais ils ne possèdent pas nécessairement les ressources (p. ex., l’accès à une équipe multidisciplinaire) ni la formation nécessaires pour procéder à leur dépistage ou à leur prise en charge. Le présent document de principes conjoint décrit les principaux rôles et les principales compétences à maîtriser pour évaluer et traiter les problèmes de santé mentale chez les enfants et les adolescents, de même que les facteurs qui optimisent le plus possible l’évolution de la santé mentale dans ces groupes d’âge. Il contient des conseils fondés sur des données probantes à propos du dépistage des préoccupations en matière de santé mentale chez les jeunes et leur famille ainsi qu’à propos des échanges sur le sujet. Les interventions préventives et thérapeutiques dont l’efficacité est démontrée en milieu communautaire sont abordées. Le présent document de principes, qui est fondamental, traite également des changements à l’enseignement de la médecine ainsi qu’aux systèmes et aux politiques de santé qui s’imposent pour améliorer la pratique clinique et les efforts de revendications au Canada, y compris les modèles de rémunération appropriés, les approches des soins abordées étape par étape, le financement gouvernemental ciblé, l’enseignement et la formation professionnelle.
Thermal niche of the dinoflagellate Karlodinium veneficum across different salinity and light levels
Authors: Vidyarathna Nayani K , Ahn So Hyun (Sophia) , Glibert Patricia M
Published: June 2023

The interactive effects of temperature (15–30°C), salinity (5–30) and light (low-100 and high-300 μmol photons m−2 s−1) on growth, thermal niche properties and cellular carbon (C) and nitrogen (N) of the toxic dinoflagellate, Karlodinium veneficum, were studied to understand its potential for change under future climate conditions in the eutrophic Chesapeake Bay. Cell growth was highest under conditions of 25–28°C, salinity 10–20 and high light, which represented the preferred physical niche for bloom formation in the present day. In the Chesapeake Bay, blooms generally occur at 25–29°C and salinity 10–14, while low-biomass occurrences have been found at salinities 15–29, consistent with the laboratory findings. High light increased the thermal sensitivity of K. veneficum and lowered the thermal optima for growth. Under conditions of low light, and salinity 10–20, cells exhibited the highest thermal optima for growth. The highest upper thermal maxima were observed at salinity 30, suggesting that cells in the lower estuary would be more thermally resistant than those in upper and mid-estuarine regions, and therefore these higher salinity regions may provide over-summering habitats for K. veneficum. Cellular C and N were highly varied at the preferred salinity and temperature niche and C:N ratios showed decreasing trends with temperature.
An Economic Framework for Vaccine Prioritization
Authors: Akbarpour Mohammad , Budish Eric , Dworczak Piotr , Kominers Scott Duke
Published: June 2023

We propose an economic framework for determining the optimal allocation of a scarce supply of vaccines that become gradually available during a public health crisis, such as the COVID-19 pandemic. Agents differ in observable and unobservable characteristics, and the designer maximizes a social welfare function over all feasible mechanisms—accounting for agents’ characteristics, as well as their endogenous behavior in the face of the pandemic. The framework emphasizes the role of externalities and incorporates equity as well as efficiency concerns. Our results provide an economic justification for providing vaccines immediately and for free to some groups of agents, while at the same time showing that a carefully constructed pricing mechanism can improve outcomes by screening for individuals with the highest private and social benefits of receiving the vaccine. The solution casts light on the classic question of whether prices or priorities should be used to allocate scarce public resources under externalities and equity concerns.
Anti-instantons on a class of quaternionic Kähler manifolds
Authors: Fowdar Udhav
Published: June 2023

We construct the first examples of (abelian) anti-instantons on certain non-compact quaternionic Kähler 8-manifolds and by contrast we show that no abelian anti-instantons exist on compact quaternionic Kähler 8-manifolds.
Chest CT utilization in COVID-19: a dosimetric and diagnostic-quality study
Authors: Saeed Mohammed K , Alshamrani Hassan A , Abdullah Youssef M , Ali Ali Sid Ahmed M , Almalki Y , Alqfail Khaled A
Published: June 2023

The purpose of this study is to look at the variations in chest computed tomography (CT) use, radiation dose and image quality in the 2019 novel coronavirus (COVID-19) pneumonia patients in Saudi Arabia. This is a retrospective study of 402 patients with COVID-19, who were treated between February and October 2021. Radiation dose was estimated using metrics of volume CT dose index (CTDIvol) and size-specific dose estimate (SSDE). The imaging performance of the CT scanners was evaluated by measuring different parameters, such as resolution and CT number uniformity, with an ACR-CT accreditation phantom. Expert radiologists assessed the diagnostic quality and occurrence of artefacts. For all of the image quality parameters tested, the majority of the scanner sites (80%) were found to be within the suggested acceptance limits. Ground-glass opacities were the most common finding in our patient sample (54%). On chest CT exams with typical appearance of COVID-19 pneumonia, the most respiratory motion artefacts (56.3%) were present, followed by those with indeterminate appearance (32.2%). There were significant differences in CT utilization, CTDIvol and SSDE across the collaborated sites. The use of CT scans and radiation doses varied in the COVID-19 patients, highlighting the optimizations of CT protocols at participating sites.
Social Motivation in Schizophrenia: What’s Effort Got to Do With It?
Authors: Catalano Lauren T , Green Michael F
Published: June 2023

Background and Hypothesis

Social motivation, defined as the fundamental human desire to seek out, engage in, and maintain interpersonal bonds, has become a growing area of research in schizophrenia. The major focus has been on understanding the impact of social reward-related processes. An obvious but rarely acknowledged fact is that social interactions, much like other goal-directed acts, require the exertion of effort. In this Review Article, we argue that social motivation in schizophrenia can be conceptualized through the lens of an established framework: effort-based decision-making (EBDM).

Study Design

We conducted a literature review on social reward processing in schizophrenia, then extended these findings by applying concepts and insights from the literature on EBDM to the study of social motivation.

Study Results

Within the EBDM framework, decisions about whether or not to pursue social interactions are bound by cost/benefit calculations. That is, people do not pursue social behaviors when the estimated “cost” of the required effort outweighs the anticipated “benefit” or reward. We propose that people with schizophrenia are less likely to engage in social interaction compared with healthy samples because they: (1) underestimate the benefits of relationships (based on expectations of reward/punishment), (2) overestimate the effort costs associated with social interaction, and/or (3) fail to integrate cost-benefit information in an optimal manner.

Conclusions

EBDM is an especially promising framework of social motivation that goes beyond the current focus on social reward processing to include a focus on effort.
Event-triggered adaptive finite time trajectory tracking control for an underactuated vessel considering unknown time-varying disturbances
Authors: Wang Qiwen , Zhang Qiang , Wang Yugang , Hu Yancai , Guo Shaoyi
Published: June 2023

This paper aims to solve the finite-time trajectory tracking problem of underactuated surface ships under the influence of dynamic uncertainty, unknown external time-varying interference and limited communication resources. An event-triggered robust adaptive finite-time trajectory tracking control method for underactuated ships is designed by combining the existing trajectory tracking control methods and engineering needs in actual navigation. It can obviously improve the tracking accuracy of the ship, and complete the tracking task safely and efficiently. This scheme transforms the composite uncertain vector synthesized by uncertain parameters and external disturbances into a linear parameterized form. Next, considering the limitation of communication resources, a relative threshold event triggering mechanism is introduced to further extend the triggering time interval on the basis of the fixed threshold triggering scheme. Then, an event-triggered robust adaptive finite-time trajectory tracking control scheme is designed for underactuated ships, and a rigorous stability proof is provided through Lyapunov stability theory. Simulation experiment is carried out in MATLAB and the results show that the finite-time trajectory tracking control scheme proposed in this paper can effectively solve the problems of dynamic uncertainty, unknown time-varying external interference and limitation of communication resources. This paper can provide theoretical support for the autonomous navigation of intelligent ships.
Quantitative measurement and application of droplets on physical surfaces based on LIF technology
Authors: Wu Fan , Zhou Shuaixiong , Cui Qingmin , Xu Renze , Li Hengkui , Yu Chao
Published: June 2023

Contaminated surfaces play a significant role in the transmission of respiratory infectious diseases. To address this issue, we presented a novel quantitative detection method for droplets on physical surfaces, based on the laser-induced fluorescence technique. The proposed detection method was demonstrated in a realistic high-speed train compartment scenario by simulating the process of droplet release during passengers' breathing and coughing. The experimental results showed that this method could offer high precision (10−1 mg/m2) for detecting minute substance concentrations, and its ease of operation makes it suitable for complex engineering environments. The results also revealed that under the combined effects of the indoor airflow and breathing airflow, the range of droplets released by breathing activity exceeded two rows in front of and behind the release position. Simultaneously, we observed that a large number of droplets settled on the seat surfaces on both sides of the same row as the releaser, with over 36% of these droplets concentrated on the backrest area of the seats. As the respiratory jet velocity increased, the location with the most sediment droplets (accounting for 8% of the total sedimentation) occurred on the seat directly in front of the releaser, and approximately 48% of the droplets were found on the back of this seat. Our proposed method overcomes the shortcomings of existing experimental methods in quantitatively capturing the motion characteristics of droplets in complex flow fields.
Multidisciplinary characterization of the new species Copemetopus mystakophoros and its symbionts with a proposal for the new class Copemetopea (Alveolata: Ciliophora)
Authors: Fokin Sergei I , Serra Valentina , Gammuto Leandro , Allievi Alessandro , Petroni Giulio , Modeo Letizia
Published: June 2023

The history of the genus Copemetopus is tortuous and studded with several misattributions. It was erected by Villeneuve-Brachon in 1940 after the discovery of Copemetopus subsalsus in saline ponds along the French coast of the Mediterranean Sea near Sète and associated with the class Heterotrichea in the family Metopidae, close to Bryometopus. After a long series of systematic revisions, it is now clear that Copemetopus is not a heterotrich and that it falls in the subphylum Intramacronucleata. Nevertheless, a lot more work is needed to fix the complex taxonomic status of the genus, which lacks a precise taxonomic collocation (it is presently referred to as incertae sedis). In the present study focused on a multidisciplinary and detailed description of a new species, of the genus, Copemetopus mystakophoros sp. nov., we also propose the erection of the new class, Copemetopea cl. nov. After careful literature and data revision, we believe that members of Copemetopus require a higher-ranked taxon in the phylum Ciliophora, given their molecular and morphological peculiarities.
Prophylactic Intrawound Antibiotics Significantly Reduce the Risk of Deep Infections in Fracture Fixation: Subgroup Meta-analyses of the Type of Fracture, Antibiotics, and Organism
Authors: Awad Mohamed E. , Chung Ji Young , Griffin Nicole , Stoneback Jason W. , Alfonso Nicholas A.
Published: June 2023

Objectives:

To analyze the efficacy of subgroups of various intrawound local antibiotics in reducing the rate of fracture-related infections.

Data Sources and Study Selection:

PubMed, MEDLINE via Ovid, Web of Science, Cochrane database, and Science Direct were searched for articles in English on July 5, 2022, and December 15, 2022.

Study Selection:

All clinical studies comparing the incidence of fracture-related infection between the administration of prophylactic systemic and topical antibiotics in fracture repair were analyzed.

Data Extraction:

Cochrane collaboration's assessment tool and the methodological bias and the methodological index for nonrandomized studies were used to detect bias and evaluate the quality of included studies, respectively.

Data Synthesis:

RevMan 5.3 software (Nordic Cochrane Centre, Denmark) was used to conduct the meta-analyses and generate forest plots.

Conclusions:

From 1990 to 2021, 13 studies included 5309 patients. Nonstratified meta-analysis showed that intrawound administration of antibiotics significantly decreased the overall incidence of infection in both open and closed fractures, regardless of the severity of open fracture and antibiotics class [OR = 0.58, (P = 0.007)] [OR = 0.33, (P < 0.00001)], respectively. The stratified analysis revealed that prophylactic intrawound antibiotics significantly lowered infection rate in open fracture patients with Gustilo–Anderson type I (OR = 0.13, P = 0.004), type II (OR = 0.29, P = 0.0002), type III (OR = 0.21, P < 0.00001), when either tobramycin PMMA beads (OR = 0.29, P < 0.00001) or vancomycin powder (OR = 0.51, P = 0.03) was applied. This study demonstrates prophylactic administration of intrawound antibiotics significantly decreases the overall incidence of infection in all subgroups of surgically fixated fractures but does not affect the patient's length of hospital stay.

Level of Evidence:

Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Single-Incision Fasciotomy Decreases Infection Risk Compared with Dual-Incision Fasciotomy in Treatment of Tibial Plateau Fractures With Acute Compartment Syndrome
Authors: DeKeyser Graham , Bunzel Eli , O'Neill Dillon , Nork Sean , Haller Justin , Barei David
Published: June 2023

Objectives:

Comparison of surgical site infection (SSI) rates in tibial plateau fractures with acute compartment syndrome treated with single-incision (SI) versus dual-incision (DI) fasciotomies.

Design:

Retrospective cohort study.

Setting:

Two, Level-1, academic, trauma centers.

Patients:

Between January 2001 and December 2021, one-hundred ninety patients with a diagnosis of tibial plateau fracture and acute compartment syndrome met inclusion criteria (SI: n = 127, DI: n = 63) with a minimum of 3-month follow-up after definitive fixation.

Intervention:

Emergent 4-compartment fasciotomy, using either SI or DI technique, and eventual plate and screw fixation of the tibial plateau.

Outcomes:

The primary outcome was SSI requiring surgical debridement. Secondary outcomes included nonunion, days to closure, method of skin closure, and time to SSI.

Results:

Both groups were similar in demographic variables and fracture characteristics (all P > 0.05). The overall infection rate was 25.8% (49 of 190), but the SI fasciotomy patients had significantly fewer SSIs compared with the DI fasciotomy patients [SI 18.1% vs. DI 41.3%; P < 0.001; OR 2.28, (confidence interval, 1.42–3.66)]. Patients with a dual (medial and lateral) surgical approach and DI fasciotomies developed an SSI in 60% (15 of 25) of cases compared with 21.3% (13 of 61) of cases in the SI group (P < 0.001). The nonunion rate was similar between the 2 groups (SI 8.3% vs. DI 10.3%; P = 0.78). The SI fasciotomy group required fewer debridement's (P = 0.04) until closure, but there was no difference in days until closure (SI 5.5 vs. DI 6.6; P = 0.09). There were zero cases of incomplete compartment release requiring return to the operating room.

Conclusions:

Patients with DI fasciotomies were more than twice as likely to develop an SSI compared with SI patients despite similar fracture and demographic characteristics between the groups. Orthopaedic surgeons should consider prioritizing SI fasciotomies in this setting.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Backout of Distal Interlocking Screws after Retrograde Femoral Nailing with a Novel Device – A Case Series
Authors: Minhas Arjun , Berkay Fehmi , Hudson Tanner , Froehle Andrew W. , Horne Brandon , Orr Charlotte , Venkatarayappa Indresh , Jerele Jennifer
Published: June 2023

Objective:

To report upon a series of patients who have experienced the backout of distal interlocking screws after retrograde femoral nailing with the DePuy Synthes RFN-AdvancedTM Retrograde Femoral Nailing System (DePuy Synthes, Raynham, MA, USA).

Design:

Retrospective Case Series

Setting:

Level 1 Trauma Center

Patients:

Twenty-seven skeletally-mature patients with femoral shaft or distal femur fractures who underwent operative fixation with the DePuy Synthes RFN-AdvancedTM Retrograde Femoral Nailing System (RFNA) with 8 patients subsequently experiencing backout of distal interlocking screws.

Intervention:

The study intervention included retrospective review of patients’ charts and radiographs.

Main Outcome Measurement:

The incidence rate of distal interlocking screw backout.

Results:

Thirty percent of patients experienced the backout of at least one distal interlocking screw (mean: 1.625) after undergoing retrograde femoral nailing with the RFN-AdvancedTM system. Thirteen total screws backed out postoperatively. Screw backout was identified an average of 61 days postoperatively (range: 30 – 139). All patients complained of implant prominence and pain along the medial or lateral aspect of the knee. Five patients elected to return to the operating room to remove the symptomatic implant. The oblique distal interlocking screws comprised 62% of screw backouts.

Conclusions:

Given the high incidence rate of this complication, the associated costs of reoperation, and patient discomfort, we believe a further investigation into this implant complication is warranted.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Preoperative Opioid Prescribers and Lumbar Fusion
Authors: Lambrechts Mark J. , Toci Gregory R. , Fried Tristan B. , Issa Tariq Z. , Karamian Brian A. , Carter Michael V. , Breyer Garrett M. , Curran John G. , Hassan Waqas , Jeyamohan Hareindra , Minetos Paul D. , Stolzenberg David , Mehnert Michael , Canseco Jose A. , Woods Barrett I. , Kaye Ian David , Hilibrand Alan S. , Kepler Christopher K. , Vaccaro Alexander R. , Schroeder Gregory D.
Published: June 2023

Study Design:

Retrospective cohort study.

Objective:

To determine the impact of multiple preoperative opioid prescribers on postoperative patient opioid usage and patient-reported outcome measures after single-level lumbar fusion.

Summary of Background Data:

Prior literature has identified opioid prescriptions from multiple postoperative providers increase opioid usage rates. However, there is limited evidence on how multiple preoperative opioid prescribers affect postoperative opioid usage or clinical outcomes after a single-level lumbar fusion.

Patients and Methods:

A retrospective review of single-level transforaminal lumbar interbody fusion or posterolateral lumbar fusions between September 2017 and February 2020 at a single academic institution was performed. Patients were excluded if they were not identifiable in our state’s prescription drug-monitoring program. Univariate comparisons and regression analyses identified factors associated with postoperative clinical outcomes and opioid usage.

Results:

Of 239 patients, 160 (66.9%) had one or fewer preoperative prescribers and 79 (33.1%) had >1 prescribers. On regression analysis, the presence of multiple preoperative prescribers was an independent predictor of increased improvement in Visual Analog Scale (∆VAS) Back (β=−1.61, P=0.012) and the involvement of a nonoperative spine provider was an independent predictor of increased improvement in ∆VAS Leg (β = −1.53, P = 0.034). Multiple preoperative opioid prescribers correlated with an increase in opioid prescriptions postoperatively (β = 0.26, P = 0.014), but it did not significantly affect the amount of morphine milligram equivalents prescribed (β = −48.79, P = 0.146). A greater number of preoperative opioid prescriptions predicted worse improvements in VAS Back, VAS Leg, and Oswestry Disability Index and predicted increased postoperative opioid prescriptions, prescribers, and morphine milligram equivalents.

Conclusions:

Multiple preoperative opioid prescribers predicted increased improvement in postoperative back pain, whereas preoperative involvement of a nonoperative spine provider predicted improvements in leg pain after surgery. The number of preoperative opioid prescriptions was a better metric for predicting poor postoperative outcomes and increased opioid consumption compared with the number of preoperative opioid prescribers.
Analysis of Influencing Factors of Vertebral Height Loss After Pedicle Screw Fixation of Thoracolumbar Fracture
Authors: Shi Zongpo , Zhang Chen , Wang Boyao , Nicolas Yap San Min , Chen Ji , Yang Gaungxu
Published: June 2023

Study Design:

Retrospective case-control study.

Objective:

To explore the related factors of vertebral height loss (VHL) after pedicle screw fixation of thoracolumbar fracture and to determine the optimum prediction point.

Summary of Background Data:

With the widespread application of thoracolumbar fracture internal fixation, VHL after the operation is increasingly presented. However, there is no unified conclusion on the specific cause of VHL and how to predict it.

Methods:

A total of 186 patients were selected and divided into the loss group (n = 72) and the not-loss group (n = 114) according to whether the fractured vertebral height was lost after the operation. The two groups were compared concerning sex, age, body mass index, osteoporosis self-assessment tool for Asians (OSTA), fracture types, number of fractured vertebrae, preoperative Cobb angle and compression degree, number of screws, and extent of vertebral restore. Univariate analysis and Multivariate logistic regression analysis were performed to identify the independent factors for the VHL with the receiver operating characteristic curve and the optimal prediction value was calculated according to area under the curve.

Results:

Multivariate logistic regression analysis showed that OSTA (P < 0.05) and preoperative vertebral compression (P < 0.05) were significantly correlated with postoperative VHL, which were independent risk factors for postoperative VHL. The OSTA of 2.32 and the preoperative vertebral compression degree of 38.5% were the best prediction points for postoperative VHL based on the Youden Index analysis.

Conclusions:

The OSTA and preoperative vertebral compression were independent risk factors for VHL. The risk of postoperative VHL was significantly higher when the OSTA was ≤2.32 or the preoperative vertebral compression was ≥38.5%.

Level of Evidence:

Level III.
3D-printed Titanium Prosthetic Reconstruction of Unilateral Bone Deficiency After Surgical Resection of Tumor Lesions in the Upper Cervical Spine
Authors: Shen Jun , Yang Minglei , Zhong Nanzhe , Jiao Jian , Xiao Jianru
Published: June 2023

Main points:

Operational excision of tumor lesions in the upper cervical spine remains a tremendous challenge to surgeons due to the local complex anatomic relationships. Meanwhile, no commercially available device has been specially designed to address bone deficiency after surgical resection. Here, we described the reconstruction of unilateral bone deficiency after surgical resection of a giant cell tumor of the tendon sheath originating from the lateral atlantoaxial joint with the employment of a 3D printing technique and reviewed the relevant literature. In our study, 3 patients with giant cell tumor of the tendon sheath in the upper cervical spine achieved complete tumor removal, and received unilateral bone reconstruction with one-armed 3D-printed titanium prosthesis. During the follow-up, these patients remained neurologically intact and got back to a normal life without wearing the braces. Images demonstrated the satisfactory placement of 3D-printed prosthesis with no failure of fixation and no subsidence. In addition, 6 articles describing the employment of 3D-printed prostheses or models for tumor surgery in the upper cervical spine were reviewed, and satisfactory clinical outcomes were reported in these studies. Hence, 3D-printed titanium prosthetic reconstruction of bone deficiency in the upper cervical spine was a safe and effective technique.

Level of Evidence:

Level IV.
Long-Term Intake of Linezolid Elevates Drug Exposure and Reduces Drug Clearance and Elimination in Adults With Drug-Resistant Pulmonary Tuberculosis
Authors: Jeyakumar Shanmugam Murugaiha , Bhui Namrata K. , Singla Neeta , Vilvamani Sudha , Mariappan Muthu Vijayalakshmi , Padmapriyadarsini Chandrasekaran , Bhatnagar Anuj K. , Solanki Rajesh , Sridhar Rathinam
Published: June 2023

Purpose:

Pharmacokinetic (PK) studies are critical for dose optimization, and there is a paucity of linezolid (LZD) PK data for prolonged use in drug-resistant tuberculosis (DR-TB). Therefore, the authors evaluated the pharmacokinetics of LZD at two-time intervals in DR-TB during long-term use.

Methods:

PK evaluation of LZD was performed at the end of the 8th and 16th weeks of treatment in a randomly selected subset of adult pre-extensively drug-resistant pulmonary tuberculosis patients (n = 18) from a multicentric interventional study (Building Evidence to Advance Treatment of TB/BEAT study; CTRI/2019/01/017310), wherein a daily dose of 600 mg LZD was used for 24 weeks. Plasma LZD levels were measured using a validated high-pressure liquid chromatography (HPLC) method.

Results:

The LZD median plasma Cmax was comparable between the 8th and 16th weeks [18.3 mg/L, interquartile range (IQR: 15.5–20.8 and 18.8 mg/L, IQR: 16.0–22.7, respectively)]. However, the trough concentration increased significantly in the 16th week (3.16 mg/L, IQR: 2.30–4.76), compared with the 8th week (1.98 mg/L, IQR: 0.93–2.75). Furthermore, compared with the 8th week, in the 16th week, there was a significant increase in drug exposure (AUC0-24 = 184.2 mg*h/L, IQR: 156.4–215.8 versus 233.2 mg*h/L, IQR: 187.9–277.2), which corroborated with a longer elimination half-life (6.94 hours, IQR: 5.55–7.99 versus 8.47 hours, IQR:7.36–11.35) and decreased clearance (2.91 L/h, IQR: 2.45–3.33 versus 2.19 L/h, IQR: 1.49–2.78).

Conclusions:

Long-term daily intake of 600 mg LZD resulted in a significant elevation in trough concentration (>2.0 mg/L) in 83% of the study participants. Furthermore, increased LZD drug exposure may be partly because of decreased clearance and elimination. Overall, the PK data underscore the need for dose adjustment when LZDs are intended for long-term treatment.
Changes in Psychotropic Drug Blood Levels After SARS-CoV-2 Vaccination: A Two-Center Cohort Study
Authors: Kuzin Maxim , Gardin Fabian , Götschi Markus , Xepapadakos Franziskos , Kawohl Wolfram , Seifritz Erich , Trauzeddel Antje , Paulzen Michael , Schoretsanitis Georgios
Published: June 2023

Background:

Limited evidence from case reports suggests that coronavirus disease 2019 (COVID-19) vaccination may interact with the treatment outcomes of psychiatric medications. Apart from clozapine, reports on the effect of COVID-19 vaccination on other psychotropic agents are scarce. This study aimed to investigate the impact of COVID-19 vaccination on the plasma levels of different psychotropic drugs using therapeutic drug monitoring.

Methods:

Plasma levels of psychotropic agents, including agomelatine, amisulpride, amitriptyline, escitalopram, fluoxetine, lamotrigine, mirtazapine, olanzapine, quetiapine, sertraline, trazodone, and venlafaxine, from inpatients with a broad spectrum of psychiatric diseases receiving COVID-19 vaccinations were collected at 2 medical centers between 08/2021 and 02/2022 under steady-state conditions before and after vaccination. Postvaccination changes were estimated as a percentage of baseline.

Results:

Data from 16 patients who received COVID-19 vaccination were included. The largest changes in plasma levels were reported for quetiapine (+101.2%) and trazodone (−38.5%) in 1 and 3 patients, respectively, 1 day postvaccination compared with baseline levels. One week postvaccination, the plasma levels of fluoxetine (active moiety) and escitalopram increased by 31% and 24.9%, respectively.

Conclusions:

This study provides the first evidence of major changes in the plasma levels of escitalopram, fluoxetine, trazodone, and quetiapine after COVID-19 vaccination. When planning COVID-19 vaccination for patients treated with these medications, clinicians should monitor rapid changes in bioavailability and consider short-term dose adjustments to ensure safety.
Molecular and immune landscape of hepatocellular carcinoma to guide therapeutic decision-making
Authors: Dhanasekaran Renumathy , Suzuki Hiroyuki , Lemaitre Lea , Kubota Naoto , Hoshida Yujin
Published: June 2023

Liver cancer, primarily HCC, exhibits highly heterogeneous histological and molecular aberrations across tumors and within individual tumor nodules. Such intertumor and intratumor heterogeneities may lead to diversity in the natural history of disease progression and various clinical disparities across the patients. Recently developed multimodality, single-cell, and spatial omics profiling technologies have enabled interrogation of the intertumor/intratumor heterogeneity in the cancer cells and the tumor immune microenvironment. These features may influence the natural history and efficacy of emerging therapies targeting novel molecular and immune pathways, some of which had been deemed undruggable. Thus, comprehensive characterization of the heterogeneities at various levels may facilitate the discovery of biomarkers that enable personalized and rational treatment decisions, and optimize treatment efficacy while minimizing the risk of adverse effects. Such companion biomarkers will also refine HCC treatment algorithms across disease stages for cost-effective patient management by optimizing the allocation of limited medical resources. Despite this promise, the complexity of the intertumor/intratumor heterogeneity and ever-expanding inventory of therapeutic agents and regimens have made clinical evaluation and translation of biomarkers increasingly challenging. To address this issue, novel clinical trial designs have been proposed and incorporated into recent studies. In this review, we discuss the latest findings in the molecular and immune landscape of HCC for their potential and utility as biomarkers, the framework of evaluation and clinical application of predictive/prognostic biomarkers, and ongoing biomarker-guided therapeutic clinical trials. These new developments may revolutionize patient care and substantially impact the still dismal HCC mortality.
The Patient Safety Adoption Framework: A Practical Framework to Bridge the Know-Do Gap
Authors: Moyal-Smith Rachel , Margo Judy , Maloney Francine L. , Boulanger Jason , Lautner Patti , Folcarelli Patricia , Benjamin Evan
Published: June 2023

Objectives

Many patient safety initiatives fail to be adopted and implemented, even when proven effective. This creates the well-recognized know-do gap, referring to the discrepancy between what healthcare workers know should be done based on evidence and what takes place in practice. We aimed to develop a framework to improve the adoption and implementation of patient safety initiatives.

Methods

We conducted a background literature review followed by qualitative interviews with patient safety leaders to identify barriers and facilitators to adoption and implementation. Inductive thematic analysis was used to generate themes that informed the development of the framework. We used a consensus-building approach to co-create the framework and guidance tool with an Ad Hoc Committee made up of subject-matter experts and patient family advisors. The framework was tested for utility, feasibility, and acceptability through qualitative interviews.

Results

The Patient Safety Adoption Framework contains 5 domains and 6 subdomains. The domains are leadership (subdomains: prioritization, accountability, governance), culture and context, process (subdomains: co-creation, high reliability, engagement), meaningful measurement, and person-centeredness. A guidance tool was developed to provide practical guidance for improvement teams using the framework. Testing affirmed the framework and guidance tool with a high degree of acceptability, feasibility, and utility among implementers and subject-matter experts.

Conclusions

The Patient Safety Adoption Framework provides the essential components necessary to facilitate the adoption and implementation of patient safety initiatives. The framework offers a roadmap for healthcare organizations striving to close the know-do gap.
Intersecting Vulnerabilities: Unraveling the Complex Relationship between Women, Climate Change, and Mental Health in Bangladeshi Communities
Authors: Goudet Jean-Marc , Arif Faria Binte , Owais Hasan , Ahmed Helal Uddin , Ridde Valéry
Published: June 2023

Climate change is one of the biggest challenges that humanity is facing in the 21st century, and its impact is being felt all over the world. It is well documented that the impacts of climate change have a significant effect on human health, including mental health. This paper focuses on the gender effect of climate impacts on mental health based on qualitative study conducted in two fragile communities in Bangladesh. This study was conducted using qualitative methods, including participant observation, in-depth interviews, and focus group discussions. The study was carried out in two fragile communities in Bangladesh, which were selected based on their vulnerability to climate change impacts. The participants were selected using snowball sampling. A total of 59 interviews and 3 Focus Group Discussions (FGDs) were conducted. Climate change impacts have a significant effect on mental health in both men and women. However, there are gender differences in the experience of climate change impacts on mental health. Women are more vulnerable to climate change impacts on mental health due to their gender roles and responsibilities. Responsible for taking care of their families, they have to face additional challenges due to climate change impacts, such as increased workload, water scarcity, and food insecurity, social insecurity as many of their husband migrates to the cities for jobs. Women also face social and cultural barriers, which exacerbates their vulnerability to climate change impacts on mental health. Men, on the other hand, face challenges related to their livelihoods and economic security due to climate change impacts. This study highlights the gender differences in the experience of climate change impacts on mental health in two fragile communities in Bangladesh. Socioeconomic and environmental determinants appear to be embedded and lead to psychological suffering in relation to social roles and gender norms. Interventions should be designed to address the specific needs and challenges faced by women in these communities. Policymakers should take a gender-sensitive approach to address the mental health impacts of climate change in these communities. This study contributes to the growing body of research on the gendered impacts of climate change with a trajectory approach and provides insights for future research in this area.
Immunogenicity of a Two Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial
Authors: Rouphael Nadine G. , Branche Angela R. , Diemert David J. , Falsey Ann R. , Losada Cecilia , Baden Lindsey R. , Frey Sharon E. , Whitaker Jennifer A. , Little Susan J. , Kamidani Satoshi , Walter Emmanuel B. , Novak Richard M. , Rupp Richard , Jackson Lisa A. , Babu Tara M. , Kottkamp Angelica C. , Luetkemeyer Anne F. , Immergluck Lilly C. , Presti Rachel M. , Bäcker Martín , Winokur Patricia L. , Mahgoub Siham M. , Goepfert Paul A. , Fusco Dahlene N. , Atmar Robert L. , Posavad Christine M. , Netzl Antonia , Smith Derek J. , Telu Kalyani , Mu Jinjian , Makowski Mat , Makhene Mamodikoe K. , Crandon Sonja , Montefiori David C. , Roberts Paul C. , Beigel John H.
Published: June 2023

In this brief report, we compare the magnitude and durability of the serologic response of one versus two doses (separated by 56 days) of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults.
MAGNITUDE AND DETERMINANTS OF DELAYED BREASTFEEDING INITIATION AMONG MOTHERS WHO DELIVER BY CESAREAN SECTION IN A RURAL GENERAL HOSPITAL IN EAST AFRICA
Authors: Ogah Adenike Oluwakemi , Kapasa Monica
Published: June 2023

Background

The BFHI program and timely breastfeeding initiation may be threatened by the worldwide rise in cesarean section deliveries, and this might promote prelacteal feeding. What is the current burden and determinants of delayed breastfeeding initiation among mothers, who gave birth via cesarean section?

Subject and methods

This was the baseline data of a prospective cohort study, where 529 healthy, singleton mother-newborn pairs were recruited consecutively at birth, from Gitwe district hospital in Rwanda.

Results

Overall, the burden of cesarean section delivery, delayed initiation of breastfeeding and prelacteal feeding were 38.8%, 17.0% and 6.0%, respectively. Rate of delayed breastfeeding initiation among mothers, who delivered by cesarean section was 37.6%, compared to 4.0% among those that delivered vaginally, p<0.001. Prelacteal feeds were given to 12.7% of the babies that were delivered by cesarean section, compared to 1.9% among those delivered vaginally, p<0.001. Use of probably ‘unsafe’ water sources located in the household yards was strongly linked to both cesarean section delivery (p<0.000; OR=5.71; 95%CI=2.43, 13.41) and delayed breastfeeding initiation (p<0.000; OR=44.40; 95% CI 7.97, 247.32). Mothers delivered by c-section, who were prenatally exposed to potentially harmful substances, were more likely to delay breastfeeding initiation compared to unexposed mothers (p=0.001; OR=3.14; 95% CI 1.56, 6.31). Cesarean section delivery was more likely with HIV positive mothers (p=0.010; OR=7.14; 95% CI:1.61, 33.33), teenage and entrepreneur mothers. Rate of cesarean section delivery amongst HIV positive mothers was 88.9%, compared to 36.1% among HIV negative mothers.

Conclusion and Recommendations

HIV positivity and non-medical causes still drive the over-use of cesarean section for delivery in this rural community, and this impacted negatively on breastfeeding initiation, thereby promoting prelacteal feeding. The uncertain safety of the water sources and prenatal exposures to harmful social habits also need to be addressed.
SHaploseek: A sequencing-only high-resolution implementation of comprehensive preimplantation genetic testing
Authors: Backenroth Daniel , Altarescu Gheona , Zahdeh Fouad , Mann Tzvia , Murik Omer , Renbaum Paul , Segel Reeval , Zeligson Sharon , Hakam-Spector Elinor , Carmi Shai , Zeevi David A.
Published: June 2023

Purpose

We previously developed Haploseek, a clinically-validated, variant-agnostic comprehensive preimplantation genetic testing (PGT) solution. Haploseek is based on microarray genotyping of the embryo’s parents and relatives, combined with low-pass sequencing of the embryos. Here, to increase throughput and versatility, we aimed to develop a sequencing-only implementation of Haploseek.

Methods

We developed SHaploseek, a universal PGT method to determine genome-wide haplotypes of each embryo based on low-pass (≤5x) sequencing of the parents and relative(s) along with ultra-low pass (0.2-0.4x) sequencing of the embryos. We used SHaploseek to analyze five single lymphoblast cells and 31 embryos from 14 families. We validated the genome-wide haplotype predictions against either bulk DNA, Haploseek, or, at focal genomic sites, PCR-based PGT results.

Results

SHaploseek achieved >99% concordance with bulk DNA in two families from which single cells were derived from grown-up children. In embryos from 12 PGT families, all of SHaploseek’s focal site haplotype predictions were concordant with clinical PCR-based PGT results. Genome-wide, there was >99% median concordance between Haploseek and SHaploseek’s haplotype predictions. Concordance remained high at all assayed sequencing depths ≥2x, as well as with only 1ng of parental DNA input. In subtelomeric regions, significantly more haplotype predictions were high-confidence in SHaploseek compared to Haploseek.

Conclusion

As a single-platform comprehensive PGT solution with higher sensitivity in subtelomeric regions, SHaploseek constitutes a significantly improved, accurate, and cost-effective re-embodiment of Haploseek.
A Deep Learning Approach for Transgender and Gender Diverse Patient Identification in Electronic Health Records
Authors: Hua Yining , Wang Liqin , Nguyen Vi , Rieu-Werden Meghan , McDowell Alex , Bates David W. , Foer Dinah , Zhou Li
Published: June 2023

Background

Although accurate identification of gender identity in the electronic health record (EHR) is crucial for providing equitable health care, particularly for transgender and gender diverse (TGD) populations, it remains a challenging task due to incomplete gender information in structured EHR fields.

Objective

To develop a deep learning classifier to accurately identify patient gender identity using patient-level EHR data, including free-text notes.

Methods

This study included adult patients in a large healthcare system in Boston, MA, between 4/1/2017 to 4/1/2022. To identify relevant information from massive clinical notes and to denoise, we compiled a list of gender-related keywords through expert curation, literature review, and expansion via a fine-tuned BioWordVec model. This keyword list was used to pre-screen potential TGD individuals and create two datasets for model training, testing, and validation. Dataset I was a balanced dataset that contained clinician-confirmed TGD patients and cases without keywords. Dataset II contained cases with keywords. The performance of the deep learning model was compared to traditional machine learning and rule-based algorithms.

Results

The final keyword list consists of 109 keywords, of which 58 (53.2%) were expanded by the BioWordVec model. Dataset I contained 3,150 patients (50% TGD) while Dataset II contained 200 patients (90% TGD). On Dataset I the deep learning model achieved a F1 score of 0.917, sensitivity of 0.854, and a precision of 0.980; and on Dataset II a F1 score of 0.969, sensitivity of 0.967, and precision of 0.972. The deep learning model significantly outperformed rule-based algorithms.

Conclusion

This is the first study to show that deep learning algorithms can accurately identify gender identity using EHR data. Future work should leverage and evaluate additional diverse data sources to generate more generalizable algorithms.

Graphical abstract
Brain morphometry is not associated with non-motor outcomes after deep brain stimulation in Parkinson’s disease
Authors: Loehrer Philipp Alexander , Schumacher Wibke , Jost Stefanie T. , Silverdale Monty , Petry-Schmelzer Jan Niklas , Sauerbier Anna , Gronostay Alexandra , Visser-Vandewalle Veerle , Fink Gereon R. , Evans Julian , Krause Max , Rizos Alexandra , Antonini Angelo , Ashkan Keyoumars , Martinez-Martin Pablo , Gaser Christian , Chaudhuri K. Ray , Timmermann Lars , Baldermann Carlos , Dafsari Haidar S.
Published: June 2023

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy in advanced Parkinson’s disease (PD). Motor and non-motor outcomes, however, show considerable inter-individual variability. Morphometry-based metrics have recently received increasing attention to predict treatment effects. As evidence for the prediction of non-motor outcomes is limited, we sought to investigate the association between metrics of voxel-based morphometry and short-term non-motor outcomes following STN-DBS in this prospective open-label study. 49 PD patients underwent structural MRI and a comprehensive clinical assessment at preoperative baseline and 6-month follow-up. Voxel-based morphometry was used to assess associations between cerebral volume and non-motor outcomes corrected for multiple comparisons using a permutation-based approach. We replicated existing results associating atrophy of the superior frontal cortex with subpar motor outcomes. Non-motor outcomes, however, were not associated with morphometric features, limiting its use as a marker to inform patient selection and holistic preoperative counselling.