bluuebunny/crossref_metadata_2025 huggingface dataset:
Does regulatory chill still concern states?
Authors: Boru Zeleke Temesgen
Published: April 2021

Public health measures taken by States have been subject to mounting arbitration legal challenges. These challenges resulted in an argument that investment agreements in general and the prevalence of the Investor-State Dispute Settlement (ISDS) mechanism, in particular, may force governments to refrain from introducing new legislative or policy measures due to a fear that the measures could be contested by investors. This situation, a fear to adopt legislative and similar other measures, is often referred to as “regulatory chill.” Recent arbitration cases show, however, that some of the cases involving pharmaceutical and similar other companies have been decided in favor of State Parties to the ISDS. In this regard, the legal claims initiated by Eli Lilly against the Government of Canada or the arbitration claims brought by Philip Morris against the Government of Australia and Uruguay can be cases in point. Due to these recent cases, some scholars have argued that the ISDS decisions (such as Eli Lilly and Government of Canada) demonstrate that regulatory chill may not be States’ concern anymore.

This paper examines the obligations of State Parties to the International Covenant on Economic, Social and Cultural Rights (ICESCR or Covenant) to ensure access to affordable health technologies (medicines, vaccines, etc.) and the likelihood of investment agreements to result in a “regulatory chill” that hinders the realization of the obligations. In order to do so, the paper takes the TPP’s (now CPTPP) investment chapter as a case in point.
Academic writing for publication: Putting the ‘international’ into context
Authors: Getahun Dawit Asrat , Hammad Waheed , Robinson-Pant Anna
Published: April 2021

There is a growing body of research on the impact of English-medium publication and associated higher education regimes on knowledge construction. However, not much is known about how academics outside the Global North make decisions about how and where to publish. Through a comparative case study, this article sets out to explore how academics in Ethiopia and Oman engage in writing for publication. Taking an academic literacies lens, the analysis reveals that their decisions were shaped by institutional values at the local level, as well as global hierarchies around knowledge construction. However, issues around identity, languages and disciplinary cultures also influenced how academics chose to position themselves in relation to local and international journals. The findings point to the need for new partnerships between journals in the Global North and South to prevent ‘publication drain’, and for universities to explore ways to address inequalities perpetuated through journal ranking and language hierarchies.
The efficacy and tolerance of prone positioning in non-intubation patients with acute hypoxemic respiratory failure and ARDS: a meta-analysis
Authors: Tan Wei , Xu Dong-yang , Xu Meng-jiao , Wang Zan-feng , Dai Bing , Li Li-li , Zhao Hong-wen , Wang Wei , Kang Jian
Published: April 2021

Background and aims:

The application of prone positioning with acute hypoxemic respiratory failure (AHRF) or acute respiratory distress syndrome (ARDS) in non-intubation patients is increasing gradually, applying prone positioning for more high-flow nasal oxygen therapy (HFNC) and non-invasive ventilation (NIV) patients. This meta-analysis evaluates the efficacy and tolerance of prone positioning combined with non-invasive respiratory support in patients with AHRF or ARDS.

Methods:

We searched randomized controlled trials (RCTs) (prospective or retrospective cohort studies, RCTs and case series) published in PubMed, EMBASE and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 1 July 2020. We included studies that compared prone and supine positioning with non-invasive respiratory support in awake patients with AHRF or ARDS. The meta-analyses used random effects models. The methodological quality of the RCTs was evaluated using the Newcastle–Ottawa quality assessment scale.

Results:

A total of 16 studies fulfilled selection criteria and included 243 patients. The aggregated intubation rate and mortality rate were 33% [95% confidence interval (CI): 0.26–0.42, I2 = 25%], 4% (95% CI: 0.01–0.07, I2 = 0%), respectively, and the intolerance rate was 7% (95% CI: 0.01–0.12, I2 = 5%). Prone positioning increased PaO2/FiO2 [mean difference (MD) = 47.89, 95% CI: 28.12–67.66; p < 0.00001, I2 = 67%] and SpO2 (MD = 4.58, 95% CI: 1.35–7.80, p = 0.005, I2 = 97%), whereas it reduced respiratory rate (MD = −5.01, 95% CI: −8.49 to −1.52, p = 0.005, I2 = 85%). Subgroup analyses demonstrated that the intubation rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 34% and 21%, respectively; and the mortality rate of shorter duration prone (⩽5 h/day) and longer duration prone (>5 h/day) were 6% and 0%, respectively. PaO2/FiO2 and SpO2 were significantly improved in COVID-19 patients and non-COVID-19 patients.

Conclusion:

Prone positioning could improve the oxygenation and reduce respiratory rate in both COVID-19 patients and non-COVID-19 patients with non-intubated AHRF or ARDS. The reviews of this paper are available via the supplemental material section.
Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial
Authors: Coles Alasdair J. , Arnold Douglas L. , Bass Ann D. , Boster Aaron L. , Compston D. Alastair S. , Fernández Óscar , Havrdová Eva Kubala , Nakamura Kunio , Traboulsee Anthony , Ziemssen Tjalf , Jacobs Alan , Margolin David H. , Huang Xiaobi , Daizadeh Nadia , Chirieac Madalina C. , Selmaj Krzysztof W.
Published: April 2021

Background:

In the 2-year CARE-MS I and II trials, alemtuzumab 12 mg administered on 5 consecutive days at core study baseline and on 3 consecutive days 12 months later significantly improved outcomes versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing–remitting multiple sclerosis patients. Here, we present the final 6-year CARE-MS extension trial results (CAMMS03409), and compare outcomes over 6 years in patients randomized to both treatment groups at core study baseline.

Methods:

Over a 4-year extension, alemtuzumab patients (alemtuzumab-only) received as-needed additional alemtuzumab (⩾12 months apart) for disease activity after course 2. SC IFNB-1a patients who entered the extension discontinued SC IFNB-1a and received 2 alemtuzumab 12 mg courses (IFN–alemtuzumab), followed by additional, as-needed, alemtuzumab.

Results:

Through year 6, 63% of CARE-MS I and 50% of CARE-MS II alemtuzumab-only patients received neither additional alemtuzumab nor other disease-modifying therapy, with lasting suppression of disease activity, improved disability, and slowing of brain volume loss (BVL). In CARE-MS I patients (treatment-naive; less disability; shorter disease duration), disease activity and BVL were significantly reduced in IFN–alemtuzumab patients, similar to alemtuzumab-only patients at year 6. Among CARE-MS II patients (inadequate response to prior treatment; more disability; longer disease duration), alemtuzumab significantly improved clinical and magnetic resonance imaging outcomes, including BVL, in IFN–alemtuzumab patients; however, disability outcomes were less favorable versus alemtuzumab-only patients. Safety profiles, including infections and autoimmunities, following alemtuzumab were similar between treatment groups.

Conclusion:

This study demonstrates the high efficacy of alemtuzumab over 6 years, with a similar safety profile between treatment groups.

ClinicalTrials.gov identifiers:

NCT00530348; NCT00548405; NCT00930553
KRAS/LKB1 and KRAS/TP53 co-mutations create divergent immune signatures in lung adenocarcinomas
Authors: Gu Meichen , Xu Tiankai , Chang Pengyu
Published: April 2021

Lung adenocarcinomas exhibit various patterns of genomic alterations. During the development of this cancer, KRAS serves as a driver oncogene with a relatively high mutational frequency. Emerging data suggest that lung adenocarcinomas with KRAS mutations can show enhanced PD-L1 expression and additional somatic mutations, thus linking the prospect of applying immune checkpoint blockade therapy to this disease. However, the responses of KRAS-mutant lung adenocarcinomas to this therapy are distinct, which is largely attributed to the heterogeneity in the tumoral immune milieus. Recently, it was revealed that KRAS-mutant lung adenocarcinomas simultaneously expressing either a LKB1 or TP53 mutation typically have different immune profiles of their tumours: tumours with a KRAS/TP53 co-mutation generally present with a significant upregulation of PD-L1 expression and tumoricidal T-cell accumulation, and those with a KRAS/LKB1 co-mutation are frequently negative for PD-L1 expression and have few tumoricidal immune infiltrates. In this regard, interrogating TP53 or LKB1 mutation in addition to PD-L1 expression will be promising in guiding clinical use of immune checkpoint blockade therapy for KRAS-mutant lung adenocarcinomas.
Favourable outcome of patients with breast cancer brain metastases treated with dual HER2 blockade of trastuzumab and pertuzumab
Authors: Bergen Elisabeth Sophie , Binter Amelie , Starzer Angelika Martina , Heller Gerwin , Kiesel Barbara , Tendl-Schulz Kristina , Bago-Horvath Zsuzsanna , Furtner Julia , Leitner Johannes , Exner Ruth , Fitzal Florian , Dieckmann Karin , Widhalm Georg , Preusser Matthias , Berghoff Anna Sophie , Bartsch Rupert
Published: April 2021

Background:

Dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab (TP) is a standard therapy of metastatic and localized HER2-positive breast cancer (BC), but its activity in breast cancer brain metastases (BCBM) is unknown.

Methods:

Patients with HER2-positive BCBM were identified from the Vienna Brain Metastasis Registry and clinical data including patient characteristics, therapies and overall survival (OS) were obtained. Patients were grouped into ‘TP’, ‘other-HER2-targeted therapy’ and ‘no-HER2-targeted therapy’ according to received first-line systemic therapy after diagnosis of BCBM. Radiological re-assessment of intracranial lesions was performed in patients treated with TP as systemic first-line therapy according to RANO response criteria for brain metastases (BM).

Results:

A total of 252 HER2-positive BC patients with BM were available for this analysis. Patients treated with TP as systemic first-line therapy after diagnosis of BM had a significantly longer OS compared with treatment with other-HER2-targeted therapy and no-HER2-targeted therapy (44 versus 17 versus 3 months, p < 0.001; log-rank test). Among radiologically re-assessed patients treated with TP as systemic first-line therapy after diagnosis of BM, 5/14 patients (35.7%) had complete intracranial remission (CR), 8/14 patients (57.1%) partial intracranial remission (PR), 1/14 patients (7.1%) stable intracranial disease (SD) and 0/14 patients (0.0%) progressive intracranial disease (PD) as best response resulting in an intracranial objective response rate (iORR) of 92.9% and an intracranial clinical benefit rate (iCBR) of 100.0%.

Conclusion:

First-line therapy with dual HER2-inhibition of TP after BM diagnosis was associated with the longest median OS times in patients with BCBM.
Synthesis and Cytotoxic Activity of Several Novel N-Alkyl-Plinabulin Derivatives With Aryl Group Moieties
Authors: Chinh Pham The , Tham Pham Thi , Quynh Duong Huong , Tuyen Nguyen Van , Van Dinh Thuy , Phuong Phan Thanh , Thu Hang Tran Thi , Van Kiem Phan
Published: April 2021

Seven novel N-alkyl-plinabulin derivatives with aryl groups moieties (nitroquinoline, 1,4-dihydroquinoline, 4-methoxybenzene, and 4-chlorobenzene) have been synthesized via aldol condensation and alkylation in one-pot, and tested for their cytotoxicity against 4 cancer cell lines (KB, HepG2, Lu, and MCF7). Compounds ( Z)−3-((6,8-dimethyl-4-oxo-1,4-dihydroquinolin-2-yl)methylene)−6-(( Z)−4-methoxybenzylidene)−1-(prop-2-yn-1-yl)piperazine-2,5-dione (5a), ( Z)−6-(( Z)−4-methoxybenzylidene)−1-(prop-2-yn-1-yl)−3-((1,6,8-trimethyl-4-oxo-1,4-dihydroquinolin-2-yl)methylene)piperazine-2,5-dione (5b), and ( Z)−3-(( Z)−4-chlorobenzylidene)−1,4-dimethyl-6-((8-methyl-4-nitroquinolin-2-yl)methylene)piperazine-2,5-dione (8) showed strong cytotoxicity against 3 of the cancer cells lines (KB, HepG2 and Lu) with IC50 values ranging from 3.04 to 10.62 µM. The quinoline-derived compounds had higher cytotoxic activity than the benzaldehyde derivatives. The successful synthesis of these derivatives offers useful information for the development of more potent vascular disrupting agents based on plinabulin.
Association of Serum Vitamin D with Serum Cytokine Profile in Patients with Knee Osteoarthritis
Authors: Amini Kadijani Azade , Bagherifard Abolfazl , Mohammadi Fatemeh , Akbari Abolfazl , Zandrahimi Farshad , Mirzaei Alireza
Published: April 2021

Objective

The role of vitamin D in the pathogenesis of osteoarthritis (OA) is not well understood. In this study, we aimed to investigate the association of serum vitamin D with the serum cytokine profile in patients with primary knee OA.

Design

In a cross-sectional study, 116 patients with radiologic diagnosis of grade I to III knee OA were included. The study population included 79 (75.9%) females and 25 (24.1%) males with a mean age of 55.1 ± 9.6 years. The serum concentration of IL-6, IL-8, TNF-α, IL-4, IL-10, IL-13, and vitamin D were assessed using an enzyme-linked immunosorbent assay. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used for the assessment of patient’s reported disability associated with knee OA.

Results

Serum vitamin D status was deficient, insufficient, and sufficient in 18 (15.5%), 63 (54.3%), 35 (30.2%) patients, respectively. Higher levels of serum IL-6 were observed in patients with vitamin D deficiency ( P = 0.022). The mean serum vitamin D level was not associated with OA grade ( P = 0.88) and WOMAC scores of the patients ( P = 0.67). Serum IL-6 level was significantly associated with both OA grade and WOMAC scores of the patients ( P < 0.001 and P = 0.001, respectively). The vitamin D status was not significantly associated with the serum levels of other evaluated cytokines.

Conclusion

Vitamin D deficiency in knee OA seems to be associated with a higher release of IL-6. Therefore, vitamin D supplementation could reduce the disease burden by controlling the IL-6 release.
Clinical pharmacist interventions in elderly patients with mental disorders in primary care focused on psychotropics: a retrospective pre–post observational study
Authors: Stuhec Matej , Lah Lea
Published: April 2021

Background:

Mental disorders pose a significant clinical burden and affect approximately one-third of older adults. Although studies have shown positive impacts of clinical pharmacist (CP) interventions within the general population, the long-term effects of such cooperation on geropsychiatric patients in primary care settings are not yet known. This study evaluated whether CP interventions have a long-term impact on the quality of medication prescribing in geropsychiatric patients.

Methods:

We conducted a retrospective non-interventional observational pre–post study for the 2015–2017 period, involving patients aged 65 or above for whom a medication review was provided by a CP. The study included participants with mental disorders treated with polypharmacy, including at least one psychotropic. Potentially inappropriate medications (PIMs) in elderly patients were determined with the Priscus list, and potential type X drug–drug interactions (pXDDIs) with Lexicomp®. Up-to-date treatment guidelines were used to evaluate patient pharmacotherapy, and patient medication was evaluated before the initial medication review and again 6 months later.

Results:

The study included 48 patients (79.4 years, SD = 8.13) receiving a total of 558 medications (155 for the treatment of mental disorders). The number of medications decreased by 9.5% after the medication review. The CP proposed 198 interventions related to psychotropics, of which 108 (55%) were accepted by the general practitioners. All accepted (99.1%) interventions except one were still maintained 6 months after the interventions had been proposed. They led to a significant decrease in the total number of medications, PIMs, and pXDDIs ( p < 0.05), and improved treatment guidelines adherence.

Conclusions:

CP interventions decreased the number of medications, PIMs, and pXDDIs, and almost all interventions were maintained 6 months later. These results provide evidence for the positive effects of CP interventions in a primary care setting. Additional research with a larger sample size and a randomized study design is needed.
Improving communication between healthcare providers and pulmonary arterial hypertension patients: a survey of patient preferences
Authors: Brewer Jacqueline , Bartlett Mary , Harris David , Hui Christine
Published: April 2021

Effective communication within the patient–provider relationship is a key aspect of shared decision‐making and associated with several positive patient outcomes. Although previous studies suggest that patients’ and providers’ conceptualization of what constitutes effective communication differ, there is no available literature discussing patient preferences for communication. The objective of this study was to determine the words and phrases pulmonary arterial hypertension patients prefer to hear when discussing their disease with their physician. A total of 227 pulmonary arterial hypertension patients completed a survey that included a 20‐item questionnaire specifically designed to assess patient preference for words and phrases when discussing their disease and treatment; statistically significant differences were observed across all items of the questionnaire. Patients preferred their physician ask them how they have “been feeling” (63%) rather than how they have “been doing”. In addition, 96% of patients indicated that they wanted to hear that this is “… the best medicine for you” rather than this is “the best medicine”. Considerably more patients (60%) indicated they want their physician to say, “We want you to have fewer symptoms” rather than “We want you to feel more normal.” They also indicated they wanted the “most effective” medicine (82%) rather than the “most aggressive” medicine (7%). The results of this study suggest that pulmonary arterial hypertension patients have strong preferences for the language their providers use when discussing their disease and treatment options. Given the role that effective communication has on important health outcomes, pulmonary arterial hypertension providers need to consider these findings when communicating with patients.
Efficacy and safety of pulmonary vasodilators in the patients with Eisenmenger syndrome: a meta‐analysis of randomized controlled trials
Authors: Hou Yulin , Wen Li , Shu Tingting , Dai Rong , Huang Wei
Published: April 2021

Few meta‐analyses evaluated the efficacy and safety of pulmonary vasodilators in patients with Eisenmenger syndrome. Recently, some studies have reported conflicting results regarding improvements in exercise capacity. This study evaluated the efficacy and safety of pulmonary vasodilators in patients with Eisenmenger syndrome. Relevant studies were identified by searching major databases. Pooled outcomes were used to assess the efficacy and safety of pulmonary vasodilators. In total, five studies with 508 patients were included. Meta‐analysis indicated that the pulmonary vasodilators reduced the mortality (odd risk (OR) = 0.35; 95% CI, 0.13 to 0.95; P = 0.04), slashed the mean pulmonary artery pressure (mean difference (MD) = −4.35 mmHg; 95% CI, −7.19 to −1.50; P = 0.003), decreased pulmonary vascular resistance index (MD = −480.08 dyn · s · cm−5 · m2; 95% CI, −753.51 to −206.64; P = 0.0006), increased the 6‐min walk distance (MD = 28.38 m; 95% CI, 2.99 to 53.77; P = 0.03), and elevated the systemic oxygen saturation at rest (MD = 1.00%; 95% CI, 0.12 to 1.88; P = 0.03). Four studies reported side effects, but only two studies reported serious adverse effects which were mostly rare and curable. The present meta‐analysis indicated that pulmonary vasodilators decrease mortality and improve hemodynamics and exercise capacity in patients with Eisenmenger syndrome. Overall, pulmonary vasodilators are well tolerated.
Chinese Flower and Bird Painting: A New Form of Art Therapy for Depression
Authors: Zhang Biyun , Chen Jingyao , Huang Xiaoyan , Xu Wenhao
Published: April 2021

Depression is a complex psychological disorder. Although psychological counseling and traditional Western art therapy have obtained robust results in the diagnosis and treatment of depression, they are not well accepted in China due to cultural differences. Chinese flower and bird painting has been favored in China and beyond. It is of considerable significance to studying the auxiliary treatment of depression by using Chinese flower and bird painting. First of all, during observation of the painting style and works of patients with different severities of depression, such phenomena as broken strokes, roughness at the end of the painting brush, stroke discontinuity, and uneven breath are noted. These signs reflect impatience and lack of control in patients with depression. Subsequently, a three-stage Chinese flower and bird painting art therapy intervention focusing on breathing training to improve ink brush control is established, and this adjuvant art therapy was applied to 56 people with mild and moderate depression. Experimental results show that, via a 24-week Chinese flower and bird painting art therapy intervention, the observation group has a greater decline in Hamilton Rating Scale for Depression (HAMD) scores than the control group ( p < .05). The study on electroencephalogram (EEG) shows that The normal rate of brain waves of the observation group in the middle and late stages of treatment and after treatment is 73%, significantly higher than 32% in the control group. This research shows that Chinese flower and bird painting can be used as a new and effective adjuvant treatment for depression in line with Chinese characteristics and is worthy of in-depth research.
Competition in a Variety Seeking Market With Brand Name Awareness
Authors: Xiong Liyang , Yu Honglei , Wang Zhanqing
Published: April 2021

This article investigates service and price competition in a variety seeking market, with the consideration of brand name awareness on consumers. Variety seeking behavior is modeled as a decrease in the willingness to pay for product purchased on the previous occasion. Under a three-stage Hotelling-type model, we show that variety seeking intensifies the competition when both firms are equally known. However, when one firm is better known than the other, it softens the competition observing the differentiation of equilibrium policies. In addition, variety seeking increases both the price and service gaps to exaggerate market differentiation. Under both scenarios firms adjust the service level in the second period so as to prevent consumers from switching, if keeping prices committed across periods. Furthermore, if consumers on average have a higher propensity to one firm, the variety seeking behavior leads to a higher total profits and a higher consumer surplus.
Investigating the Institutional Determinants of Financial Development: Empirical Evidence From SAARC Countries
Authors: Ellahi Nazima , Kiani Adiqa Kausar , Awais Muhammad , Affandi Hina , Saghir Rabia , Qaim Sarah
Published: April 2021

A more regulated and better working financial sector contributes toward achieving monetary growth based on proficient resource allocation and reducing information asymmetries. Current trends in research highlight the significance of factors determining the financial sector’s development; therefore, this study explores the institutional drivers, which are indispensable for developing the financial industry in the South Asian Association of Regional Cooperation (SAARC) region. Specifically, it examines the impact of institutional factors, trade openness, real output, legal origin, and inflation on the financial sector’s development. By employing the panel data method of generalized method of moments (GMM), the study concluded that trade openness, institutional factors, legal origin, and real gross domestic product (GDP) have a positive and significant impact on financial depth. However, the inflation rate has been found to affect it negatively. Finally, the study presents policy recommendations based on empirical findings.
The Effects of Mother-Child Mediated Learning Strategies on Cognitive Modifiability and Psychological Resilience of Children With Learning Disabilities: A Replication of Tzuriel and Shomron’s Study (2018) With Nigerian Children
Authors: Ugwuanyi Christian Sunday , Okeke Chinedu I. O. , Eseadi Chiedu , Adimora Ebere Dorothy , Agah John Joseph , Obikwelu Chizoba L. , Onyishi Charity N. , Ossai Osita Victor , Ngwoke Anthonia N. , Okenyi Emmanuel C. , Ezema Victor S. , Adene Friday M. , Anyaegbunam Emenike N. , Ejiofor Juliana N. , Amaeze Fidelis E. , Eskay Michael
Published: April 2021

This study determined the effects of mother-child mediated learning (MCML) strategies on the psychological resilience (PR) and cognitive modifiability (CM) of children with learning disabilities (LD) using a structural equation modeling (SEM) approach. The study utilized a sample of 60 mothers and 60 children with LD. These children were both male (63%) and female (37%) primary five level children diagnosed with LD and were sampled from inclusive primary schools in Enugu State, Nigeria. The mean age and standard deviation of the children was 10.5 ± 1.04 years. Data collected were analyzed using a SEM approach. The findings of the study showed that (a) the causal model for the explanation of the effects of MCML on the PR and CM of pupils with LD significantly fitted in the observed causal model and (b) MCML had a significant effect on the PR as well as CM of children with LD. One implication of this study is that the PR, as well as the CM of children with LD, can be enhanced through MCML.
A Systematic Review of the Cost-Utility of Spinal Cord Stimulation for Persistent Low Back Pain in Patients With Failed Back Surgery Syndrome
Authors: McClure Jesse J. , Desai Bhargav D. , Ampie Leonel , You Wen , Smith Justin S. , Buchholz Avery L.
Published: April 2021

Study Design:

Systematic Review.

Objectives:

To review the literature surrounding the cost-effectiveness of implanting spinal cord stimulators for failed back surgery syndrome.

Methods:

A systematic review was conducted inclusive of all publications in the Medline database and Cochrane CENTRAL trials register within the last 10 years (English language only) assessing the cost-effectiveness of Spinal Cord Stimulator device implantation (SCSdi) in patients with previous lumbar fusion surgery.

Results:

The majority of reviewed publications that analyzed cost-effectiveness of SCSdi compared to conventional medical management (CMM) or re-operation in patients with failed back surgery syndrome (FBSS) showed an overall increase in direct medical costs; these increased costs were found in nearly all cases to be offset by significant improvements in patient quality of life. The cost required to achieve these increases in quality adjusted life years (QALY) falls well below $25 000/QALY, a conservative estimate of willingness to pay.

Conclusions:

The data suggest that SCSdi provides both superior outcomes and a lower incremental cost: effectiveness ratio (ICER) compared to CMM and/or re-operation in patients with FBSS. These findings are in spite of the fact that the majority of studies reviewed were agnostic to the type of device or innervation utilized in SCSdi. Newer devices utilizing burst or higher frequency stimulation have demonstrated their superiority over traditional SCSdi via randomized clinical trials and may provide lower ICERs.
Achieving Value in Spine Surgery: 10 Major Cost Contributors
Authors: Philipp Lucas R. , Leibold Adam , Mahtabfar Aria , Montenegro Thiago S. , Gonzalez Glenn A. , Harrop James S.
Published: April 2021

Study Design:

Narrative Review.

Objectives:

The increasing cost of healthcare overall and for spine surgery, coupled with the growing burden of spine-related disease and rising demand have necessitated a shift in practice standards with a new emphasis on value-based care. Despite multiple attempts to reconcile the discrepancy between national recommendations for appropriate use and the patterns of use employed in clinical practice, resources continue to be overused—often in the absence of any demonstrable clinical benefit. The following discussion illustrates 10 areas for further research and quality improvement.

Methods:

We present a narrative review of the literature regarding 10 features in spine surgery which are characterized by substantial disproportionate costs and minimal—if any—clear benefit. Discussion items were generated from a service-wide poll; topics mentioned with great frequency or emphasis were considered. Items are not listed in hierarchical order, nor is the list comprehensive.

Results:

We describe the cost and clinical data for the following 10 items: Over-referral, Over-imaging & Overdiagnosis; Advanced Imaging for Low Back Pain; Advanced imaging for C-Spine Clearance; Advanced Imaging for Other Spinal Trauma; Neuromonitoring for Cervical Spine; Neuromonitoring for Lumbar Spine/Single-Level Surgery; Bracing & Spinal Orthotics; Biologics; Robotic Assistance; Unnecessary perioperative testing.

Conclusions:

In the pursuit of value in spine surgery we must define what quality is, and what costs we are willing to pay for each theoretical unit of quality. We illustrate 10 areas for future research and quality improvement initiatives, which are at present overpriced and underbeneficial.
Epidemiology of Severe Foot Injuries in US Collegiate Athletes
Authors: Chan Jimmy J. , Geller Joseph S. , Chen Kevin K. , Huang Hsin-Hui , Huntley Samuel R. , Vulcano Ettore , Aiyer Amiethab
Published: April 2021

Background:

The effects of foot injuries on collegiate athletes in the United States are of interest because of the short 5-year eligibility period in the National Collegiate Athletic Association (NCAA).

Purpose:

To discuss the epidemiology of severe NCAA foot injuries sustained over 10 years in 25 sports.

Study Design:

Descriptive epidemiology study.

Methods:

We utilized the NCAA Injury Surveillance System, which prospectively collects deidentified injury data for collegiate athletes. Severe injuries were classified as season- or career-ending injuries, injuries with >30-day time loss, or injuries requiring operative treatment. Injury rates (IRs) were analyzed per 100,000 athlete-exposures.

Results:

Of 3607 total foot injuries, 18.71% (n = 675) were classified as severe, with an IR of 5.73 per 100,000 athletic-exposures. For all severe injuries, the operative rate was 24.3%, the season-ending rate 37.0%, and the career-ending rate 4.4%. The proportion of recurrent injuries was 13.9%. Men’s sports with the highest severe foot IRs were basketball (IR = 10.71), indoor track (IR = 7.16), and football (IR = 7.08). Women’s sports with the highest severe foot IRs were cross-country (IR = 17.15), gymnastics (IR = 14.76), and outdoor track (IR = 14.65). Among all severe foot injuries, the most common was a fifth metatarsal fracture. The highest contact/noncontact injury ratios were phalangeal fracture, turf toe, and Lisfranc injury. The severe injuries with the highest operative rates were Lisfranc injuries, fifth metatarsal fractures, and midfoot fractures. The severe injuries associated with the highest season-ending IRs were Lisfranc injury, midfoot fracture, and general metatarsal fractures. Severe flexor/extensor injuries had the highest career-ending IRs, followed by turf toe. Severe injuries with the highest median time loss were sesamoidal fractures, calcaneal fractures, and plantar fascial injuries.

Conclusion:

Of all collegiate foot injuries sustained over a 10-year period, 18.7% were characterized as severe, and 24.3% of severe injuries required surgery. Basketball was the men’s sport with the highest severe IR, and cross-country was the women’s sport with the highest severe IR. Overall, female athletes experienced slightly higher severe foot IRs as compared with male athletes.
Clinical Outcomes of Arthroscopic Tenodesis Versus Tenotomy for Long Head of the Biceps Tendon Lesions: A Systematic Review and Meta-analysis of Randomized Clinical Trials and Cohort Studies
Authors: Liu Hongzhi , Song Xinqiu , Liu Pei , Yu Huachen , Zhang Qidong , Guo Wanshou
Published: April 2021

Background:

Controversy exists concerning whether tenotomy or tenodesis is the optimal surgical treatment option for proximal biceps tendon lesions.

Purpose:

To evaluate the clinical outcomes after arthroscopic tenodesis and tenotomy in the treatment of long head of the biceps tendon (LHBT) lesions.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

A systematic review was performed by searching PubMed, the Cochrane Library, Web of Science, and Embase to identify randomized controlled trials (RCTs) and cohort studies that compared the clinical efficacy of tenotomy with that of tenodesis for LHBT lesions. A standardized data extraction form was predesigned to obtain bibliographic information of the study as well as patient, intervention, comparison, and outcome data. A random-effects model was used to pool quantitative data from the primary outcomes.

Results:

A total of 21 eligible studies were separated into 3 methodological groups: (1) 4 RCTs with level 1 evidence, (2) 3 RCTs and 4 prospective cohort studies with level 2 evidence, and (3) 10 retrospective cohort studies with level 3 to 4 evidence. Analysis of the 3 groups demonstrated a significantly higher risk of the Popeye sign after tenotomy versus tenodesis (group 1: risk ratio [RR], 3.29 [95% CI, 1.92-5.49]; group 2: RR, 2.35 [95% CI, 1.43-3.85]; and group 3: RR, 2.57 [95% CI, 1.33-4.98]). Arm cramping pain remained significantly higher after tenotomy only in the retrospective cohort group (RR, 2.17 [95% CI, 1.20-3.95]). The Constant score for tenotomy was significantly worse than that for tenodesis in the prospective cohort group (standardized mean difference [SMD], –0.47 [95% CI, –0.73 to –0.21]), as were the forearm supination strength index (SMD, –0.75 [95% CI, –1.28 to –0.21]) and the Simple Shoulder Test (SST) score (SMD, –0.60 [95% CI, –0.94 to –0.27]).

Conclusion:

The results demonstrated that compared with tenodesis, tenotomy had a higher risk of a Popeye deformity in all 3 study groups; worse functional outcomes in terms of the Constant score, forearm supination strength index, and SST score according to prospective cohort studies; and a higher incidence of arm cramping pain according to retrospective cohort studies.
Impact of Pediatric COVID-19 on Family Health-Related Quality of Life: A Qualitative Study from Latvia
Authors: Stars Inese , Smane Liene , Pucuka Zanda , Roge Ieva , Pavare Jana
Published: April 2021

Information on family health-related quality of life (FHRQoL) among families of children with the coronavirus disease 2019 (COVID-19) is limited. This qualitative study explores the impact of pediatric COVID-19 on FHRQoL from the parents’ perspective. Semi-structured interviews were conducted with parents (n = 20) whose children had tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Inductive thematic analysis revealed the following 10 themes that represented parents’ perception of FHRQoL while taking care of a child with COVID-19: pediatric COVID-19 as a disease with many unknowns; emotional saturation; internal family relationships in the context of “a new experience”; routine household activities and daily regimen while family is in lockdown; plenty of free time; a wide social support network; social stigma associated with COVID-19; different options for work; savings and debts; challenges with family housing and transport availability. Our results show that parents experience multiple effects of pediatric COVID-19 with regard to FHRQoL.
Memories of the 1947 Bengal Partition and Its Aftermath: Tanvir Mokammel’s Seemantorekha
Authors: Mukhopadhyay Sumallya
Published: April 2021

This article examines Tanvir Mokammel’s documentary Seemantorekha as a historical text that opens a representational space to engage with the memories of the 1947 Bengal Partition. Seemantorekha documents the journey of four individuals to their erstwhile homes in Bangladesh and West Bengal. In the moment of seeing their ancestral homes, they share the ‘Third Space’ of being, the premise of which transcends the ideological normative of nations and borders.
Rheumatology Patient Satisfaction With Telemedicine During the COVID-19 Pandemic in the United States
Authors: Mortezavi Mahta , Lokineni Sravani , Garg Megha , Chen Ya Li , Ramsey Allison
Published: April 2021

The spread of COVID-19 in the United States has led to the use of virtual visits in lieu of in-person care for the high-risk population of patients in rheumatology. We asked patients to score their satisfaction with these visits and if they would have preferred in-person care instead. Of 679 patients seen in May 2020, 512 (75.4%) were virtual (267 [52.1%] by telephone and 245 [47.9%] by video), and 359 (70%) responded to the survey. The majority of patients (74%) were satisfied with their virtual visit, but they were more likely to be satisfied if their visit was over video rather than phone. They preferred an in-person visit if they were meeting a doctor for the first time, and patients who required a language interpreter were significantly less satisfied with virtual care. There was no correlation of age, sex, diagnosis, or testing ordered with satisfaction. The main concern against virtual care was the inability to have a physical exam, while the main reasons in favor of it were avoidance of potential infection and convenience.
Reperfusion failure despite recanalization in stroke: New translational evidence
Authors: Amki Mohamad El , Wegener Susanne
Published: April 2021

Current treatment for acute ischemic stroke aims at recanalizing the occluded blood vessel to reperfuse ischemic brain tissue. Clot removal can be achieved pharmacologically with a thrombolytic drug, such as recombinant tissue plasminogen activator, or with mechanical thrombectomy. However, reopening the occluded vessel does not guarantee full tissue reperfusion, which has been referred to as reperfusion failure. When it occurs, reperfusion failure significantly attenuates the beneficial effect of recanalization therapy and severely affects functional recovery of stroke patients. The mechanisms of reperfusion failure are somewhat complex and not fully understood. Briefly, after stroke, capillaries show stalls, constriction and luminal narrowing, being crowded with neutrophils, and fibrin–platelet deposits. Furthermore, after recanalization in stroke patients, a primary clot can break, dislodge, and occlude distal arterial branches further downstream. In this review, we highlight a rodent model that allows studying the pathophysiological mechanisms underlying reperfusion failure after stroke. We also describe the vascular and intravascular changes involved in reperfusion, which may provide relevant therapeutic targets for improving treatment of stroke patients.
Why and how the work of Motor Neurone Disease Associations matters before and during bereavement: a consumer perspective
Authors: Aoun Samar M. , Cafarella Paul A. , Hogden Anne , Thomas Geoff , Jiang Leanne , Edis Robert
Published: April 2021

Background:

Studies on the experiences of consumers with Motor Neurone Disease Associations at end of life and bereavement are lacking, and their role and capability within the broader sectors of health and disability are unknown.

Objectives:

To ascertain the experiences and views of bereaved motor neurone disease caregivers with Motor Neurone Disease Associations about service gaps and needed improvements before and during bereavement and to propose a model of care that fits with consumer preferences and where Motor Neurone Disease Associations are effective enablers of care.

Methods:

A national bereavement survey was facilitated in 2019 by all Motor Neurone Disease Associations in Australia. A total of 363 respondents completed the section on support provided by Motor Neurone Disease Associations. A mixed-method design was used.

Results:

Respondents were generally positive about support received before bereavement (73-76%), except for emotional support (55%). Positive experiences related to the following: information, equipment advice/provision, advocacy/linking to services, showing empathy/understanding, personal contact and peer social support. Negative experiences included lack of continuity in case management and contact, perceived lack of competence or training, lack of emotional support and a lack of access to motor neurone disease services in rural areas. Suggested improvements were as follows: more contact and compassion at end of life and postdeath; better preparation for end of life; option of discussing euthanasia; providing referrals and links for counseling; access to caregiver support groups and peer interaction; provision of a genuine continuum of care rather than postdeath abandonment; guidance regarding postdeath practicalities; and more access to bereavement support in rural areas.

Conclusion:

This study provides consumer perspectives on driving new or improved initiatives by Motor Neurone Disease Associations and the need for a national standardised approach to training and service delivery, based on research evidence. A public health approach to motor neurone disease end-of-life care, of international applicability, is proposed to address the needs and preferences of motor neurone disease consumers, while supporting the capability of Motor Neurone Disease Associations within a multidisciplinary workforce to deliver that care.
Lateral resistance of mass timber shear wall connected by withdrawal-type connectors
Authors: Pang Sung-Jun , Ahn Kyung-Sun , Kang Seog Goo , Oh Jung-Kwon
Published: April 2021

In this study, the lateral resistances of mass timber shear walls were investigated for seismic design. The lateral resistances were predicted by kinematic models with mechanical properties of connectors, and compared with experimental data. Four out of 7 shear wall specimens consisted of a single Ply-lam panel and withdrawal-type connectors. Three out of 7 shear wall specimens consisted of two panels made by dividing a single panel in half. The divided panels were connected by 2 or 4 connectors like a single panel before being divided. The applied vertical load was 0, 24, or 120 kN, and the number of connectors for connecting the Ply-lam wall-to-floor was 2 or 4. As a result, the tested data were 6.3 to 52.7% higher than the predicted value by kinematic models, and it means that the lateral resistance can be designed by the behavior of the connector, and the prediction will be safe. The effects of wall-to-wall connectors, wall-to-floor connectors and vertical loads on the shear wall were analyzed with the experimental data.
Identification of polycistronic transcriptional units and non-canonical introns in green algal chloroplasts based on long-read RNA sequencing data
Authors: Zou Xiaoxiao , Verbruggen Heroen , Li Tianjingwei , Zhu Jun , Chen Zou , He Henqi , Bao Shixiang , Sun Jinhua
Published: April 2021

Background

Chloroplasts are important semi-autonomous organelles in plants and algae. Unlike higher plants, the chloroplast genomes of green algal linage have distinct features both in organization and expression. Despite the architecture of chloroplast genome having been extensively studied in higher plants and several model species of algae, little is known about the transcriptional features of green algal chloroplast-encoded genes.

Results

Based on full-length cDNA (Iso-Seq) sequencing, we identified widely co-transcribed polycistronic transcriptional units (PTUs) in the green alga Caulerpa lentillifera. In addition to clusters of genes from the same pathway, we identified a series of PTUs of up to nine genes whose function in the plastid is not understood. The RNA data further allowed us to confirm widespread expression of fragmented genes and conserved open reading frames, which are both important features in green algal chloroplast genomes. In addition, a newly fragmented gene specific to C. lentillifera was discovered, which may represent a recent gene fragmentation event in the chloroplast genome.

With the newly annotated exon-intron boundary information, gene structural annotation was greatly improved across the siphonous green algae lineages. Our data also revealed a type of non-canonical Group II introns, with a deviant secondary structure and intronic ORFs lacking known splicing or mobility domains. These widespread introns have conserved positions in their genes and are excised precisely despite lacking clear consensus intron boundaries.

Conclusion

Our study fills important knowledge gaps in chloroplast genome organization and transcription in green algae, and provides new insights into expression of polycistronic transcripts, freestanding ORFs and fragmented genes in algal chloroplast genomes. Moreover, we revealed an unusual type of Group II intron with distinct features and conserved positions in Bryopsidales. Our data represents interesting additions to knowledge of chloroplast intron structure and highlights clusters of uncharacterized genes that probably play important roles in plastids.
Decreased abundance of Akkermansia after adrenocorticotropic hormone therapy in patients with West syndrome
Authors: Xu Lu , Chen Dandan , Zhao Congying , Jiang Lihua , Mao Shanshan , Song Chao , Gao Feng
Published: April 2021

Background

Infants suffer from a severe epileptic encephalopathy known as West syndrome (WS). Treatment with adrenocorticotropic hormone (ACTH) indicates the involvement of the gut-brain axis in WS. Several pieces of evidence show the communication of the gut microbiota (GM) with the brain via the hypothalamic–pituitary–adrenal axis (HPA axis) and blood cytokines. This study aimed at (1) determining the GM diversity in infants having WS and (2) comparing the results of infants having WS with those of the healthy infants and also in the patients with WS before and after the ACTH therapy.

Results

In this study, 29 infants with WS and 29 healthy infants aged 3–13 months were recruited. Fecal samples were collected, and DNA was extracted and sequenced on the Illumina MiSeq platform. Kruskal-Wallis rank-sum test was used to analyze the between-group differences in the Chao1 index, Shannon index, and the abundances of GM at different taxonomy levels. R software was used to plot the graphs. The top five dominant GM genera between patients with WS and healthy infants showed no significant differences. However, the relative abundance of genus Akkermansia was observed to be significantly (P = 0.011) higher in the BT group than in the HC group and AT group. After 2 weeks of ACTH therapy, the relative abundance of Akkermansia significantly (P = 0.003) decreased.

Conclusion

The relative abundance of Akkermansia was observed to be significantly higher in patients with WS than that in healthy infants. However, the relationship between Akkermansia and WS pathogenesis needs to be clarified in further studies.