bluuebunny/crossref_metadata_2025 huggingface dataset:
LSS-VGG16
Authors: Altun Sinan , Alkan Ahmet , Altun İdiris
Published: February 2023

Study Design:

This was a retrospective study.

Objection:

Lumbar Spinal Stenosis (LSS) is a disease that causes chronic low back pain and can often be confused with herniated disk. In this study, a deep learning-based classification model is proposed to make LSS diagnosis quickly and automatically with an objective tool.

Summary of Background Data:

LSS is a disease that causes negative consequences such as low back pain, foot numbness, and pain. Diagnosis of this disease is difficult because it is confused with herniated disk and requires serious expertise. The shape and amount of this stenosis are very important in deciding the surgery and the surgical technique to be applied in these patients. When the spinal canal narrows, as a result of compression on these nerves and/or pressure on the vessels feeding the nerves, poor nutrition of the nerves causes loss of function and structure. Image processing techniques are applied in biomedical images such as MR and CT and high classification success is achieved. In this way, computer-aided diagnosis systems can be realized to help the specialist in the diagnosis of different diseases.

Methods:

To demonstrate the success of the proposed model, different deep learning methods and traditional machine learning techniques have been studied.

Results:

The highest classification success was obtained in the VGG16 method, with 87.70%.

Conclusions:

The proposed LSS-VGG16 model reveals that a computer-aided diagnosis system can be created for the diagnosis of spinal canal stenosis. In addition, it was observed that higher classification success was achieved compared with similar studies in the literature. This shows that the proposed LSS-VGG16 model will be an important resource for scientists who will work in this field.
Bilateral Lesser Tuberosity Fractures: Technique and a Case Report with Literature Review
Authors: Zuchelli Daniel M. , Penny Gregory S. , Aibinder William R.
Published: February 2023

Isolated lesser tuberosity fractures are a rare subset of proximal humerus fractures and are often associated with seizures. Displaced fractures can lead to chronic pain, reduced shoulder function, and posterior instability. Operative treatment is frequently recommended with the displacement of more than 5 mm or angulation of more than 45 degrees. We report on a 31-year-old man with bilateral lesser tuberosity fractures who underwent operative fixation for 1 fracture and nonoperative fixation for the other.
First-line crizotinib therapy is effective for a novel SEC31A-anaplastic lymphoma kinase fusion in a patient with stage IV lung adenocarcinoma: a case report and literature reviews
Authors: Wu Rongrong , Liu Shinan , Lv Guoli , Deng Chaowen , Wang Ruolan , Zhang Shenglin , Zhu Dongyi , Wang Le , Lei Youming , Luo Zhuang
Published: February 2023

Anaplastic lymphoma kinase (ALK) fusion was found in 3–7% of all patients with nonsmall cell lung cancer. The efficacy of ALK-tyrosine kinase inhibitor (ALK-TKI) in EML4-ALK has been extensively studied, whereas little evidence is available on its efficacy in rare ALK fusions. Here, we report the performance of crizotinib in a 50-year-old male lung adenocarcinoma patient with a novel rare SEC31A-ALK fusion. Computed tomography (CT) scan revealed multiple patchy high-density shadows in both lungs. The larger ones are located near the spine in the right lung lower lobe (55 × 34 mm) and the left hilar region (45 × 26 mm), with multiple enlarged mediastinal and axillary lymph nodes. Biopsy by bronchoscopy revealed invasive adenocarcinoma. The pathological stage of T4N3M1b (clinical stage: IVA) was confirmed. Next-generation sequencing revealed SEC31A: exon20~ALK: exon20 fusion, ABCB1 amplification, FGF19 amplification, DAXX p.S213L, MUTYH p.R19*(germline mutation and pathogenic) with tumor mutational burden at 3.2 mutations/Mb, microsatellite stable, proficient mismatch repair and PD-L1 positive [immunohistochemistry, tumor proportion score(TPS) 1–49% (TPS = 25%)]. Based on these findings, crizotinib was recommended for the first-line treatment at 250 mg twice daily. The first CT assessment after 2-month therapy showed partial response (PR) for the two larger lesions, multiple shadows and nodules in both lungs and the mediastinal and axillary lymph nodes. Crizotinib at 250 mg twice a day was applied in the following 9 months. Assessment at every 3 months (up to 1-year after diagnosis) showed further absorption for all lesions (continuous PR). We reported a novel rare ALK fusion SEC31A: EXON20~ALK: exon20 and showed the effectiveness of crizotinib against the fusion. This study provided strong evidence for the efficacy of ALK-TKI for rare ALK fusion.
Methyltransferase-like 3 enhances cell proliferation and cisplatin resistance in natural killer/T-cell lymphoma through promoting N6-methyladenosine modification and the stability of staphylococcal nuclease and Tudor domain-containing protein 1 mRNA
Authors: Li Na , Wei Jingli , Zhang Qian , Zhang Qi , Liu Bailing
Published: February 2023

Nasal-type natural killer/T-cell lymphoma (NKTCL) is a typical class of non-Hodgkin’s lymphoma, which is quite malignant because of its high resistance to chemotherapy. N6-methyladenosine (m6A) modification, a prevalent modification of eukaryotic RNA, was emerging as an important regulatory mechanism in progression of various tumors. Here, we demonstrated that methyltransferase-like 3 (METTL3), an RNA methyltransferase, was obviously upregulated in human NKTCL cell lines (NK-92, YTS, SNT-8, and SNK-6) compared with normal NK cells. Knockdown of METTL3 noticeably repressed proliferation and facilitated apoptosis in SNT-8 cells, whereas overexpression of METTL3 showed opposite results in SNK-6 cells. In the mechanism exploration, we found that METTL3 stimulated the m6A modification of staphylococcal nuclease and Tudor domain-containing protein 1 (SND1) mRNA, recruited YTH m6A RNA binding protein 1 to recognize the m6A site, thereby enhancing its mRNA stability. Rescue experiments demonstrated that METTL3 significantly prohibited NKTCL cell chemotherapy sensitivity to cisplatin (DDP) through regulating SND1 expression. Furthermore, knockdown of SND1 suppressed tumor growth and reduced DDP resistance in vivo. Taken together, our findings uncovered the role of METTL3 in the regulation of chemotherapy resistance in NKTCL oncogenesis.
Cardiovascular Subphenotypes in Acute Respiratory Distress Syndrome*
Authors: Chotalia Minesh , Ali Muzzammil , Alderman Joseph E. , Bansal Sukh , Patel Jaimin M. , Bangash Mansoor N. , Parekh Dhruv
Published: February 2023

OBJECTIVES:

To use clustering methods on transthoracic echocardiography (TTE) findings and hemodynamic parameters to characterize circulatory failure subphenotypes and potentially elucidate underlying mechanisms in patients with acute respiratory distress syndrome (ARDS) and to describe their association with mortality compared with current definitions of right ventricular dysfunction (RVD).

DESIGN:

Retrospective, single-center cohort study.

SETTING:

University Hospital ICU, Birmingham, United Kingdom.

PATIENTS:

ICU patients that received TTE within 7 days of ARDS onset between April 2016 and December 2021.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Latent class analysis (LCA) of TTE/hemodynamic parameters was performed in 801 patients, 62 years old (interquartile range, 50–72 yr old), 63% male, and 40% 90-day mortality rate. Four cardiovascular subphenotypes were identified: class 1 (43%; mostly normal left and right ventricular [LV/RV] function), class 2 (24%; mostly dilated RV with preserved systolic function), class 3 (13%, mostly dilated RV with impaired systolic function), and class 4 (21%; mostly high cardiac output, with hyperdynamic LV function). The four subphenotypes differed in their characteristics and outcomes, with 90-day mortality rates of 19%, 40%, 78%, and 59% in classes 1–4, respectively (p < 0.0001). Following multivariable logistic regression analysis, class 3 had the highest odds ratio (OR) for mortality (OR, 6.9; 95% CI, 4.0–11.8) compared with other RVD definitions. Different three-variable models had high diagnostic accuracy in identifying each of these latent subphenotypes.

CONCLUSIONS:

LCA of TTE parameters identified four cardiovascular subphenotypes in ARDS that more closely aligned with circulatory failure mechanisms and mortality than current RVD definitions.
Effect of Admission and Discharge Times on Hospital Mortality in Patients With Sepsis
Authors: Zhou Xiaoming , Weng Jie , Xu Zhe , Yang Jinweng , Lin Jiaying , Hou Ruonan , Zhou Zhiliang , Wang Liang , Wang Zhiyi , Chen Chan
Published: February 2023

Objectives:

To assess whether the time of admission/discharge time from the ICU and weekend admission are independently associated with hospital mortality in critically ill patients with sepsis.

Design:

Retrospective study. Each 24-hour period (08:00 to 07:59 hr) was split into three time periods, defined as “day” (08:00 to 16:59 hr), “evening” (17:00 to 23:59 hr), and “night” (00:00 to 07:59 hr). Weekends were defined as 17:00 hours on Friday to 07:59 hours on Monday. Multivariate logistic regression models were conducted to assess the association between the ICU admission/discharge time, weekend admission, and hospital mortality.

Setting:

Single-center ICUs in China.

Patients:

Characteristics and clinical outcomes of 1,341 consecutive septic patients admitted to the emergency ICU, general ICU, or cardiovascular ICU in a tertiary teaching hospital were collected.

Interventions:

None.

Measurements and Main Results:

ICU mortality rates were 5.8%, 11.9%, and 10.6%, and hospital mortality rates were 7.3%, 15.6%, and 17.1% during the day, evening, and night time, respectively. Hospital mortality was adjusted for patient to nurse (P/N) ratio, disease severity, Charlson index, age, gender, mechanical ventilation, and shock. Notably, ICU admission time and weekend admission were not predictors of mortality after adjustment. The P/N ratio at admission was significantly associated with mortality (p < 0.05). The P/N ratio and compliance with the Surviving Sepsis Campaign (SSC) were significantly correlated. After risk adjustment for illness severity at time of ICU discharge and Charlson index, the time of discharge was no longer a significant predictor of mortality.

Conclusions:

ICU admission/discharge time and weekend admission were not independent risk factors of hospital mortality in critically ill patients with sepsis. The P/N ratio at admission, which can affect the compliance rate with SSC, was a predictor of hospital survival. Unstable state on transfer from the ICU was the main risk factor for in-hospital death. These findings may have implications for the management of septic patients.
The Fate of Entrustable Professional Activities After Graduation: A Survey Study Among Graduated Physician Assistants
Authors: de Raad Timo , Wiersma Fraukje , Kuilman Luppo , ten Cate Olle
Published: February 2023

Introduction:

Entrustable professional activities (EPAs) are used during training but may also have significance after graduation. This domain has not yet been much explored. We investigated the use of EPAs among alumni of Master Physician Assistant programs in the Netherlands, where EPAs have been used since 2010. We aim to describe if and how EPAs have a role after graduation. Are EPAs used for continuous entrustment decisions or when shifting work settings?

Methods:

In September 2020, all registered Dutch physician assistants (PAs) (n = 1441) were invited to participate in a voluntary, anonymous survey focusing on the use of EPAs after graduation. Survey items included questions regarding the use and usefulness of EPAs, views on continuous entrustment decisions, and how PAs document their competence.

Results:

A total of 421 PAs (response rate 29%) yielded information about the significance of EPAs after training. Among the respondents, 60% (n = 252) reported adding new competencies and skills after graduation. One-third (n = 120) of the respondents were trained in EPA-based programs. Almost all EPA-trained PAs (96%; n = 103) considered the EPA structure suitable to maintain and renew entrustment. Furthermore, PAs reported continued use of the EPA framework to seek formal qualifications through entrustment decisions.

Discussion:

This study shows that EPAs can play an ongoing role for PAs after graduation. EPA-trained PAs overwhelmingly support the continuous use of the EPA framework for entrustment decisions from graduation until retirement.
Advancing Research in Health Professions Education Through an Innovative Accelerator Panel
Authors: Kawczak Steven , Stoller James K.
Published: February 2023

Introduction:

Research and scholarship are critical to advance the effective design, implementation, and evaluation of health professions education activities as well as to study outcomes and disseminate observations to the community. Yet, many educators are neither involved in nor equipped to conduct quality education research. This gap underscores the continuing education need to guide and train health professions educators to rigorously investigate, prepare, and report their educational research.

Methods:

A novel session called the Education Research Accelerator was designed to increase knowledge about education research methods and resources and to improve participants' competence and performance in implementing studies. A panel helped prospective researchers develop ideas or advance projects toward completion by offering real-time feedback to pitched ideas; a live audience of learners participated virtually, expanding the impact of the session, facilitating connections, and potentially inspiring other research ideas. The outcomes of the Education Research Accelerator were evaluated immediately after the session and 18 months later.

Results:

The Education Research Accelerator conferred favorable outcomes for participants' competence in designing education research studies and awareness of using available resources. Long-term follow-up confirmed actual benefits to use effective methodology to advance education research projects and to use resources and connections established in the Education Research Accelerator.

Conclusions:

Although further study is needed, the Education Research Accelerator model is a novel intervention to enhance learning, forge needed connections, and increase the sophistication of conducting education research. We propose that the model can be replicated and applied in other settings.
Exploring the Study of Simulation as a Continuing Professional Development Strategy for Physicians
Authors: Tavares Walter , Piquette Dominique , Luong Dorothy , Chiu Michelle , Dyte Christopher , Fraser Kristin , Clark Marcia
Published: February 2023

Introduction:

Practicing physicians have the responsibility to engage in lifelong learning. Although simulation is an effective experiential educational strategy, physicians seldom select it for continuing professional development (CPD) for reasons that are poorly understood. The objective of this study was to explore existing evidence on simulation-based CPD and the factors influencing physicians' engagement in simulation-based CPD.

Methods:

A scoping review of the literature on simulation-based CPD included MEDLINE, Embase, and CINAHL databases. Studies involving the use of simulation for practicing physicians' CPD were included. Information related to motivations for participating in simulation-based CPD, study objectives, research question(s), rationale(s), reasons for using simulation, and simulation features was abstracted.

Results:

The search yielded 8609 articles, with 6906 articles undergoing title and abstract screening after duplicate removal. Six hundred sixty-one articles underwent full-text screening. Two hundred twenty-five studies (1993–2021) were reviewed for data abstraction. Only four studies explored physicians' motivations directly, while 31 studies described incentives or strategies used to enroll physicians in studies on simulation-based CPD. Most studies focused on leveraging or demonstrating the utility of simulation for CPD. Limited evidence suggests that psychological safety, direct relevance to clinical practice, and familiarity with simulation may promote future engagement.

Discussion:

Although simulation is an effective experiential educational method, factors explaining its uptake by physicians as a CPD strategy are unclear. Additional evidence of simulation effectiveness may fail to convince physicians to participate in simulation-based CPD unless personal, social, educational, or contextual factors that shape physicians' motivations and choices to engage in simulation-based CPD are explored.
Evaluation of Two Educational Modalities for the Clinical Practice Guideline for Opioid Therapy for Chronic Pain for US Military Physicians
Authors: Hurtado Suzanne L. , Simon-Arndt Cynthia M. , Belding Jennifer N. , Sanchez Sandra S. , Spevak Christopher , Osik Amy
Published: February 2023

Introduction:

The Department of Veterans Affairs and Department of Defense Clinical Practice Guideline (CPG) for the Management of Opioid Therapy for Chronic Pain was updated in 2017 with targeted guidance to provide safe opioid use while mitigating the increasing levels of prescription opioid misuse among military personnel. The objective of this study was to determine the effectiveness of two educational training modalities for the CPG (an online training [OLT] module and a mobile app) on provider's knowledge, practices, and comfort with the CPG. The OLT was a self-paced interactive slide-based module that emphasized practical application, and the app provided information on the revised CPG and provider and patient resources.

Methods:

Active duty providers (N = 56) were randomly assigned to one of four groups (OLT only, app only, OLT and app combined, or neither OLT nor the app), and they completed a pre-test and an 8-week post-test.

Results:

Compared with those who received neither intervention, providers who received OLT only or the app only showed significant increases in knowledge over time. The combination of both OLT and app did not seem to significantly increase knowledge above either the OLT or the app alone. Neither the OLT, the app, nor their combination significantly increased either practices or comfort over time.

Discussion:

These results show that use of these educational tools, individually, was associated with an increase in provider knowledge, suggesting that these tools constitute a valuable addition to the available resources to optimize CPG implementation.
Use of Smartphone-Based Electronic Medical Records by Nurses in Tertiary Teaching Hospitals
Authors: Kim Suhyun , Lee Seonah
Published: February 2023

The adoption of smartphone-based electronic medical records is increasing in the healthcare sector. Nurses are the largest group using mobile electronic medical records. This study examined the system quality, information quality, service quality, usefulness, and ease of using mobile electronic medical records, the effects of the three qualities of the mobile electronic medical records on the usefulness and ease of use, and nurses' preference for using mobile electronic medical records. The participants were 210 nurses using a mobile electronic medical record system for over a month. An instrument modified from existing instruments was used. The data were analyzed using descriptive statistics and multiple regression analysis. The participants perceived the system and information quality more positively than the service quality of the mobile electronic medical records. They perceived the mobile electronic medical records as being useful and easy to use. System quality and information quality significantly affected the perception of the usefulness and ease of using the mobile electronic medical record. They preferred to use it as a means to identify patients' conditions at any time. For user satisfaction and the implications for nursing practice, the usability and functionality of a mobile electronic medical record system should be continuously assessed.
A Descriptive Comparative Pilot Study: Association Between Use of a Self-monitoring Device and Sleep and Stress Outcomes in Pregnancy
Authors: Auxier Jennifer , Asgari Mehrabadi Milad , Rahmani Amir M. , Axelin Anna
Published: February 2023

Pregnancy is a challenging time for maintaining quality sleep and managing stress. Digital self-monitoring technologies are popular because of assumed increased patient engagement leading to an impact on health outcomes. However, the actual association between wear time of such devices and improved sleep/stress outcomes remains untested. Here, a descriptive comparative pilot study of 20 pregnant women was conducted to examine associations between wear time (behavioral engagement) of self-monitoring devices and sleep/stress pregnancy outcomes. Women used a ring fitted to their finger to monitor sleep/stress data, with access to a self-monitoring program for an average of 9½ weeks. Based on wear time, participants were split into two engagement groups. Using a linear mixed-effects model, the high engagement group showed higher levels of stress and a negative trend in sleep duration and quality. The low engagement group showed positive changes in sleep duration, and quality and experienced below-normal sleep onset latency at the start of the pilot but trended toward normal levels. Engagement according to device wear time was not associated with improved outcomes. Further research should aim to understand how engagement with self-monitoring technologies impacts sleep/stress outcomes in pregnancy.
The Role of Physical Activity and Community Engagement in Understanding Mental Health Among Community-Dwelling Seniors
Authors: Enamela Pranathy , Prybutok Gayle L. , Prybutok Victor R.
Published: February 2023

Caregivers and health practitioners are often looking for good intervention techniques to help community-living older adults to improve their mental health. This study examined the relationship between physical activity and community engagement and their effect on mental well-being among older men and women. Data from National Health and Aging Trends Study from the years 2018 to 2020 were used to explore and test the posited relationships. Partial least-squares structural equation modeling was used to test the developed model that focused on the relationships among physical activity and mental well-being when controlling for demographics in older adults. Social interactions added importance to well-being among older men and women. Physical activity factors and community engagement all together have a positive impact on an older adults' mental well-being. This study provides statistically significant empirical evidence that older adults who are physically active and involved in the community exhibit greater mental well-being than those who isolate themselves.
Survey of Home Cleaning Practices With Noninvasive Ventilation Equipment
Authors: Qu Yiwei , Milross Maree , McGuiness Olivia , Menadue Collette , Piper Amanda
Published: February 2023

Purpose:

Home noninvasive ventilation (NIV) equipment is often observed to be dirty, potentially increasing patients' risk of respiratory infection. This study aimed to describe the cleaning practices of home NIV patients.

Methods:

This single-site, cross-sectional, observational study surveyed 100 patients from the respiratory failure clinic regarding cleaning instructions, cleaning habits, barriers, and motivators to cleaning. Open-ended responses were analyzed with basic content analysis and closed categorical responses with frequencies and percentages.

Results:

Of 100 participants, 77% responded. Cleaning instructions most commonly recalled included cleaning with soapy water for masks (26/47, 55%), head straps (19/47, 40%), and tubing (21/47, 45%); vinegar solution for humidifiers (9/39, 23%); and replacing filters (14/39, 36%). Fourteen respondents reported barriers to cleaning, including forgetfulness (7/14, 50%) and physical difficulties (6/14, 43%). Commonly reported cleaning practices included soapy water to soak masks (28/77, 36%) and tubing (35/77, 46%), weekly masks (34/77, 44%) and tubing cleaning (29/77, 38%), vinegar solution to clean humidifiers for the 36 humidifier users (15/36, 44%), monthly humidifier cleaning (13/36, 36%), and monthly filter cleaning/replacement (36/77, 47%).

Conclusion:

Few respondents could recall specific instructions about when and how to clean their equipment. Many reported routine cleaning, with varied methods and frequencies. Our results will inform future NIV equipment cleaning educational package design.
Stress and Rest Pulmonary Transit Times Assessed by Cardiovascular Magnetic Resonance
Authors: Opatřil Lukáš , Panovský Roman , Mojica-Pisciotti Mary , Krejčí Jan , Masárová Lucia , Kincl Vladimir , Řehořková Magdalena , Špinarová Lenka
Published: February 2023

Acquiring pulmonary circulation parameters as a potential marker of cardiopulmonary function is not new. Methods to obtain these parameters have been developed over time, with the latest being first-pass perfusion sequences in cardiovascular magnetic resonance (CMR). Even though more data on these parameters has been recently published, different nomenclature and acquisition methods are used across studies; some works even reported conflicting data. The most commonly used circulation parameters obtained using CMR include pulmonary transit time (PTT) and pulmonary transit beats (PTB). PTT is the time needed for a contrast agent (typically gadolinium-based) to circulate from the right ventricle (RV) to the left ventricle (LV). PTB is the number of cardiac cycles the process takes. Some authors also include corrected heart rate (HR) versions along with standard PTT. Besides other methods, CMR offers an option to assess stress circulation parameters, but data are minimal. This review aims to summarize the up-to-date findings and provide an overview of the latest progress on this promising, dynamically evolving topic.
The Coronary Sinus Reducer Stent for the Treatment of Refractory Angina Pectoris: From the Conception of Innovation to Clinical Application
Authors: Paz Yoav , Grosman-Rimon Liza , Levy Yair , Shinfeld Amihay
Published: February 2023

The Neovasc Coronary Sinus Reducer Stent (CSRS) was developed for the treatment of patients who continue to suffer from disabling symptoms despite optimal medical therapy. This patient population with refractory angina symptoms is expected to grow, since life expectancy of individuals with atherosclerotic coronary artery disease is increasing. In this paper, we discussed the development of a novel device the CSRS and the upside-down strategy to rebuild a retrograde coronary pressure that was attenuated by the atherosclerotic disease.
Access to Care After Autism Diagnosis During the COVID-19 Pandemic: A Quality Improvement Project
Authors: Landau-Taylor Jessica , McGivney Christine , Christiansen Audrey
Published: February 2023

Objective:

The aim of this study was to identify barriers and improve access to services for children diagnosed with autism spectrum disorder (ASD) during the COVID-19 pandemic.

Methods:

Sixty-two patients diagnosed with ASD between March 23 and June 30, 2020, at a large urban safety net hospital were identified by chart review. Patients were called from January to March 2021 and queried regarding access to services. Brief interventions were provided as part of a modified Plan-Do-Study-Act approach. A second chart review was conducted between April and May 2021 to determine whether families accessed any additional services.

Results:

At the time of initial evaluation, 12 patients (19%) had been able to access all recommended services, 32 (52%) had been able to access some recommended services, and 9 (15%) were not able to access any services. Service levels for 9 families (15%) were undetermined. Sixteen patients (26%) lacked any follow-up with their developmental behavioral pediatrician since their initial evaluation. Thirty patients (48%) reported changes to their individualized educational program or early intervention services, and 17 patients (27%) were receiving in-home applied behavior analysis. After the brief intervention, 13 patients had accessed new services, and 9 patients previously lost to follow-up had completed an appointment.

Conclusion:

Patients diagnosed with ASD in the spring of 2020 had significant difficulty accessing community services. The transition to telemedicine exacerbated this hospital's difficulty contacting patients for follow-up. Additional research is needed to fully characterize the disruptions to services experienced by patients diagnosed with ASD during the pandemic and to increase accessibility and equity of care.
Decisional Regret Among Caregivers of Infants with Differences of Sex Development Reared as Male
Authors: Fisher Rachel S. , Datillo Taylor M. , Baskin Laurence S. , Cheng Earl Y. , Kolon Thomas , Nokoff Natalie J. , Poppas Dix P. , Reyes Kristy J. , Mullins Larry L. , Wisniewski Amy B.
Published: February 2023

Objective:

Differences of sex development (DSD) are congenital conditions in which individuals are discordant in their chromosomal, phenotypic, and/or gonadal sex. Treatment of DSD can involve surgical intervention to external genitalia to make anatomy seem male-typical (i.e., male genitoplasty). Caregiver-perceived decisional regret regarding young boys with DSD was explored quantitatively and qualitatively.

Method:

Participants (N = 39) were caregivers of infants (N = 23) diagnosed with DSD (mean age = 8.9 months, standard deviation = 5.9 months) reared male participating in a longitudinal investigation of psychosocial outcomes. Qualitative data were collected at 6 to 12 months after baseline enrollment to evaluate caregiver decision-making corresponding to levels of regret concerning their child's treatment. All but one infant received genital surgery before caregiver reporting on their decisional regret. Quantitative exploratory analyses evaluated longitudinal predictors of decisional regret at 6 to 12 months.

Results:

When completing a write-in item inquiring about decision-making and potential regret, most caregivers (n = 16, 76%) reported that their child's genital surgery was their first medical decision. Two caregivers referenced gender assignment as a decision point. One-third of caregivers reported some level of decisional regret (33%), with 67% reporting no regret. No hypothesized predictors of decisional regret were statistically significant.

Conclusion:

Many caregivers of infants with DSD reared male view genital surgery as a first health care decision. Approximately one-third of caregivers reported some level of decisional regret. Further research is warranted to explore long-term decisional regret; it will be particularly important to investigate the decisional regret of patients with DSD.
Postoperative Complications After Interpolated Flap Repair for Mohs Defects of the Nose: A Multicenter Prospective Cohort Study
Authors: Perz Allison M. , Lukowiak Tess M. , Lee Michael P. , Neal Donald , Aizman Leora , Miller Christopher J. , Golda Nicholas , Albertini John G. , Holmes Todd , Bar Anna , Leitenberger Justin , Maher Ian , Sobanko Joseph F. , Chen David , Hollmig Tyler , Aasi Sumaira , Sutton Adam , Higgins H. William , Shin Thuzar M. , Weinberger Christine , Mattox Adam , Wysong Ashley , Etzkorn Jeremy R.
Published: February 2023

BACKGROUND

Dermatologists perform most interpolated flaps after skin cancer resection. Prospective, multicenter data on complications after interpolated flap repair in this setting are limited.

OBJECTIVE

To determine the rate of physician-reported complications after interpolated flap repair of the nose.

METHODS

Multicenter, prospective cohort study of 169 patients undergoing 2-stage interpolated flap repair of post-Mohs nasal defects. Frequency of bleeding, infection, dehiscence, necrosis, hospitalization, and death in the 30 days after flap placement and flap takedown are reported.

RESULTS

Patients experienced 23 complications after flap placement (13.61%) and 6 complications after flap takedown (3.55%) that were related to the surgical procedure. The most frequent complication after flap placement was bleeding (9, 5.33%, 95% confidence interval [CI]: 2.83%–9.82%). The most frequent complication after flap takedown was infection (5, 2.96%, 95% CI: 1.27%–6.74%). There was one hospitalization related to an adverse reaction to antibiotics. There were no deaths.

CONCLUSION

Most complications after interpolated flap repair for post-Mohs defects of the nose are minor and are associated with flap placement. Interpolated flap repair for post-Mohs defects can be performed safely in the outpatient setting under local anesthesia.
Therapeutic Drug Monitoring of Ganciclovir in Cytomegalovirus-Infected Patients With Solid Organ Transplants and Its Correlation to Efficacy and Toxicity
Authors: van der Wekken-Pas Lena C. , Totté Joan , Lunel Frans V. , van Zuilen Arjan , van Luin Matthijs
Published: February 2023

Background:

Cytomegalovirus causes morbidity and mortality, especially in immunocompromised patients, and is treated with (val)ganciclovir. Therapeutic drug monitoring of ganciclovir is often performed; however, clinically established target trough levels corresponding to efficacy are lacking. In 2021, our clinic increased the target trough level for ganciclovir from 1 to 2 mg/L to 2–4 mg/L. This study aims to compare both target trough levels in efficacy, toxicity, and occurrence of resistance.

Methods:

A retrospective cohort study was performed in adult solid organ recipients treated for cytomegalovirus infection with (val)ganciclovir. Clinical efficacy was defined as the absence of treatment failure, defined as > 1 log10 increase in viral load within 2 weeks of treatment initiation, therapy switch to foscarnet, and/or request for resistance analysis.

Results:

A total of 46 patients were involved in the study, with 200 ganciclovir trough levels obtained. The composite endpoint was recorded in 23 (69.7%) and 10 (76.9%) patients in the 1–2 mg/L and the 2–4 mg/L group, respectively (P = 0.18). No association was found between ganciclovir trough levels and the composite endpoint (P = 1.0). However, a correlation was found between ganciclovir trough levels and the occurrence of lymphopenia (P = 0.02).

Conclusions:

Our study could not establish a difference in clinical efficacy or toxicity between target trough levels of 1–2 mg/L or 2–4 mg/L because of the lack of clinical differences between the compared groups. However, a correlation was found between ganciclovir trough levels and lymphopenia, which warrants further investigation.
Doravirine Exposure Decreased by Dialysis in a HIV Patient: A Grand Round
Authors: Fromage Yeleen , Codde Cyrielle , Monchaud Caroline , Labriffe Marc , Lê Minh P. , Faucher Jean-François , Woillard Jean-Baptiste
Published: February 2023

Background:

The authors report the case of a 66-year-old male patient who was hemodialyzed 3 times per week for chronic renal failure and treated with 100 mg of doravirine once daily in combination with dolutegravir for HIV-1. No dose adjustment is required for doravirine in cases of severe renal injury, but the effect of dialysis on its exposure is poorly understood.

Methods & Results:

Two series of 2 samples were drawn before and after 4-hour hemodialysis and showed an average doravirine concentration decrease of 48.1 ± 6.7%. The effects of hemodialysis were important, contrary to what was expected and has been previously reported. In addition, intraindividual variability was low. Nevertheless, because the concentrations reported were largely above the inhibitory concentration 50 (IC50), no dose adjustment was required.

Conclusions:

The decrease in doravirine concentration due to hemodialysis observed in this case report was quite significant. Therefore, therapeutic drug monitoring might be recommended in certain patients undergoing doravirine treatment also on hemodialysis.
Successful and Safe Real-Time TDM-Guided Treatment of Invasive Pulmonary and Cerebral Aspergillosis Using Low-Dose Isavuconazole in a Patient with Primary Biliary Cirrhosis: Grand Round/A Case Study
Authors: Cojutti Pier Giorgio , Rinaldi Matteo , Giannella Maddalena , Viale Pierluigi , Pea Federico
Published: February 2023

Background:

The authors present a case of a 67-year-old woman with primary biliary cirrhosis (Child-Pugh class B) who was treated with isavuconazole for invasive pulmonary and cerebral aspergillosis. Isavuconazole treatment was initiated with the standard maintenance dose of 200 mg daily. Therapeutic drug monitoring (TDM) was performed to target trough concentrations within the desired range of 1.0–5.13 mg/L.

Methods:

Real-time TDM and pharmacokinetic analyses were used to determine the dose adjustments. Liver transaminases (alanine aminotransferase and gamma-glutamyl transferase) were assessed to monitor hepatotoxicity.

Results:

The trough plasma levels gradually increased over time up to 17.8 mg/L. TDM-guided clinical pharmacological advice was helpful to initially reduce the dose, then to temporarily suspend drug administration, and finally to calculate the correct dose that allowed for long-term treatment up to day 258. No major signs and/or symptoms of drug-related toxicity occurred, apart from a transient increase in gamma-glutamyl transferases that normalized after the drop in isavuconazole trough levels within the desired range.

Conclusions:

TDM-guided clinical pharmacological advice was essential for the successful and safe management of isavuconazole treatment in this patient with moderate liver dysfunction.
Bioanalytical Methods for Poly(ADP-Ribose) Polymerase Inhibitor Quantification: A Review for Therapeutic Drug Monitoring
Authors: Orleni Marco , Canil Giovanni , Posocco Bianca , Gagno Sara , Toffoli Giuseppe
Published: February 2023

Background:

Therapeutic drug monitoring (TDM) of poly(ADP-ribose) polymerase inhibitors (PARPis) is an exploratory practice aimed at improving the quality of treatment through personalized therapy. Currently, there are 4 European Medicines Agency-approved and US Food and Drug Administration–approved PARPis available clinically whose quantification requires validated analytical methods: olaparib, niraparib, rucaparib, and talazoparib. The purpose of this literature review was to highlight the pharmacological features of PARPis that could support their TDM practice and provide a detailed discussion of the available liquid chromatography coupled with tandem mass spectrometry methods for their quantification.

Methods:

Using several Medical Subject Heading terms, the literature was searched using several research engines, including SciFinder, Web of Science, Google Scholar, and PubMed, to find articles published before August 2022.

Results:

Exposure-efficacy and exposure-safety profiles, drug–drug interactions, and hepatic/renal impairment of PARPis provide the potential rationale to monitor their concentrations through TDM. Several bioanalytical methods for their quantification have been reported and compared, and a great deal of heterogeneity has been found among methods, regarding both their analytical and regulatory aspects.

Conclusions:

In addition to reducing toxicity and increasing the efficacy of PARPis therapy, TDM could be beneficial to thoroughly investigate the exposure–response relationships of PARPis and to establish pharmacokinetic thresholds for clinical decisions. Based on the comparison of published bioanalytical methods, their transferability and validation both play a key role in method selection. For future use in clinical TDM, we anticipate that bioanalytical methods should address every analytical need more thoroughly and should be validated with standardized guidelines.
Developmental Outcomes Following Abusive Head Trauma in Infancy: A Systematic Review
Authors: Sarmiento Cristina A. , Wyrwa Jordan M. , Chambliss Amy V. , Stearns-Yoder Kelly A. , Hoffberg Adam S. , Appel Amanda , Brenner Benjamin O. , Brenner Lisa A.
Published: February 2023

Objective:

A systematic review of the literature was conducted to identify measures used to evaluate developmental outcomes after abusive head trauma (AHT), as well as describe outcomes among those with AHT, and explore factors and interventions influencing such outcomes.

Design:

This systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The protocol is in PROSPERO, registration number CRD42020179592. On April 17, 2020, OVID Medline, Embase, OVID PsycINFO, Web of Science, CINAHL, Cochrane Library, and Google Scholar were searched (since inception). Inclusion criteria included original, peer-reviewed study data; AHT exposure; infants younger than 24 months at time of AHT; and evaluation of developmental outcomes. Reviewers independently evaluated studies for inclusion and assessed risk of bias using the Effective Public Health Practice Project quality assessment tool for quantitative studies. A descriptive synthesis approach was utilized as variability of study designs, follow-up periods, and outcome assessment tools precluded a meta-analytic approach.

Results:

Fifty-nine studies were included; 115 assessment tools were used to evaluate developmental outcomes; and 42 studies examined factors influencing outcomes. Two studies evaluated interventions. Five percent of studies (n = 3) were rated low risk of bias.

Conclusions:

Notable variation was observed in terms of case ascertainment criteria. Developmental outcomes after AHT have been assessed in a manner that limits understanding of how AHT impacts development, as well as the efficacy of interventions intended to improve outcomes. Researchers and clinicians are encouraged to adopt consistent diagnostic and assessment approaches.
Relationship Between Neighborhood Disadvantage and Mild Traumatic Brain Injury Symptoms
Authors: Miller Tessa , Kallenbach Madeline D. , Huber Daniel L. , Brett Benjamin L. , Nelson Lindsay D.
Published: February 2023

Objective:

To test the hypotheses that (1) higher neighborhood disadvantage is associated with greater injury-related symptom severity in civilians with mild traumatic brain injury (mTBI) and (2) neighborhood disadvantage remains predictive after controlling for other established predictors.

Setting:

Level 1 trauma center and affiliated academic medical center.

Participants:

N = 171 individuals with mTBI.

Design:

Prospective cohort study.

Main Measures:

Rivermead Post Concussion Symptoms Questionnaire (RPQ) total score assessed less than 24 hours and at 2 weeks, 3 months, and 6 months postinjury. Linear mixed-effects models were used to assess the relationship between predictor variables and mTBI-related symptom burden (RPQ score). Neighborhood disadvantage was quantified by the Area Deprivation Index (ADI), a composite of 17 markers of socioeconomic position (SEP) scored at the census block group level.

Results:

Individuals in the upper ADI quartile of the national distribution displayed higher RPQ symptoms than those in the lower 3 quartiles (P < .001), with a nonsignificant ADI × visit interaction (P = .903). In a multivariable model, the effect of ADI remained significant (P = .034) after adjusting for demographics, individual SEP, and injury factors. Other unique predictors in the multivariable model were gender (gender × visit P = .035), health insurance type (P = .017), and injury-related litigation (P = .012).

Conclusion:

Neighborhood disadvantage as quantified by the ADI is robustly associated with greater mTBI-related symptom burden throughout the first 6 months postinjury. That the effect of ADI remained after controlling for demographics, individual SEP, and injury characteristics implies that neighborhood disadvantage is an important, understudied factor contributing to clinical recovery from mTBI.
Longitudinal Trends in Severe Traumatic Brain Injury Inpatient Rehabilitation
Authors: Totman Alissa A. , Lamm Adam G. , Goldstein Richard , Giacino Joseph T. , Bodien Yelena G. , Ryan Colleen M. , Schneider Jeffrey C. , Zafonte Ross
Published: February 2023

Objective:

The goal of this study is to describe national trends in inpatient rehabilitation facility (IRF) discharges for the most severely disabled cohort of patients with traumatic brain injury (TBI).

Methods:

Data from the Uniform Data System for Medical Rehabilitation for patients discharged from an IRF between January 1, 2002, and December 31, 2017, with a diagnosis of TBI and an admission Functional Independence Measure of 18, the lowest possible score, were obtained and analyzed.

Results:

Of the 252 112 patients with TBI discharged during the study period, 10 098 met the study criteria. From 2002 to 2017, the number of patients with an IRF admission Functional Independence Measure of 18 following TBI discharged from IRFs annually decreased from 649 to 488, modeled by a negative regression (coefficient = −2.97; P = .001), and the mean age (SD) increased from 43.0 (21.0) to 53.7 (21.3) years (coefficient = 0.70; P < .001). During the study period, the number of patients with the most severe disability on admission to IRF who were discharged annually as a proportion of total patients with TBI decreased from 5.5% to 2.5% (odds ratio = 0.95; P < .001) and their mean length of stay decreased from 41.5 (36.2) to 29.3 (24.9) days (coefficient = −0.83; P < .001].

Conclusion:

The number and proportion of patients with the most severe disability on IRF admission following TBI who are discharged from IRFs is decreasing over time. This may represent a combination of primary prevention, early mortality due to withdrawal of life-sustaining treatment, alternative discharge dispositions, or changes in admitting and reimbursement practices. Furthermore, there has been a decrease in the duration of IRF level care for these individuals, which could ultimately lead to poorer functional outcomes, particularly given the importance of specialized rehabilitative care in this population.
Are Social Determinants of Health Associated With Onset of Rehabilitation Services in Patients Hospitalized for Traumatic Brain Injury?
Authors: Bukhari Rayyan A. , Graham James E. , Kinney Adam R. , Hoffman Amanda , Malcolm Matt P.
Published: February 2023

Objective:

To examine the impact of community-level social determinants of health (SDoH) on the onset of occupational therapy (OT) and physical therapy (PT) services among individuals hospitalized for traumatic brain injury (TBI).

Setting:

14 acute care hospitals in the state of Colorado.

Participants:

We studied 5825 adults with TBI.

Design:

In a secondary analysis of de-identified electronic health record data, we performed multivariable logistic and linear regressions to calculate odds ratios (ORs) and 95% CIs for the likelihood of receiving services and duration to initiation of services among those who received them.

Main Measures:

Community-level SDoH, receipt of rehabilitation services, and onset of rehabilitation services.

Results:

Multivariable logistic and linear regressions revealed that those in top quartiles for community income were associated with duration to OT services, ranging from OR = 0.33 [05% CI, 0.07, 0.60] for quartile 2 to 0.76 [0.44, 1.08] for quartile 4 compared with those with the lowest quartile. Only the top quartile differed significantly for duration to PT services (0.63 [0.28, 0.98]). Relative to those with below the median community percentage of high school degree, those with above the median were associated with duration to PT services only (−0.32 [−0.60, −0.04]). Neither community percentage with bachelor's degree nor rural-urban designation was associated with duration to either therapy service.

Conclusion:

Further research is needed to determine whether our SDoH variables were too diffuse to capture individual experiences and impacts on care or whether community-level education and income, and rurality, truly do not influence time to therapy for patients hospitalized with TBI. Other, individual-level variables, such as age, comorbidity burden, and TBI severity, demonstrated clear relationships with therapy onset. These findings may help therapists evaluate and standardize equitable access to timely rehabilitation services.