bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Current Status of Clinical Trials on Biologics for Cartilage Repair and Osteoarthritis Treatment: An Analysis of ClinicalTrials.gov Data
Authors: Zhang Zijun , Schon Lew 
Published: May 2022

Objective Biologics are increasingly used for cartilage repair and osteoarthritis (OA) treatment. This study aimed to provide an overview of the clinical trials conducted on this subject. Design Two-word combinations of two sets of key words “cartilage”; “joint”; “osteoarthritis” and “biologics”; “stem cells”; “cell implantation” were used to search the database of ClinicalTrials.gov and supplemented with searches of PubMed and EMbase. The registered trials were analyzed for clinical conditions, completion status, phases, and investigated biologics. Recently completed trials with posted/published results were summarized. Results From 2000 to 2022, a total of 365 clinical trials were registered at ClinicalTrials.gov to use biologics for cartilage repair and OA treatment. Since 2006, the number of registered trials accelerated at an annual rate of 16.4%. Of the 265 trials designated with a phase, 72% were early Phase 1, Phase 1, and Phase 2. Chondrocytes and platelet-rich plasma (PRP) were studied in nearly equal number of early- and late-stage trials. Mesenchymal stem/stromal cells (MSCs) were the most commonly investigated biologics (38%) and mostly derived from bone marrow and adipose tissue (70%). In last 5 years, 32 of the 72 completed trials posted/published results, among which seven Phase 3 trials investigated chondrocytes, PRP, bone marrow aspirate concentrate, hyaluronic acid, collagen membrane, and albumin. Conclusions There was a rapid increase in the number of registered clinical trials in recent years, using a variety of biologics for cartilage repair and OA treatment. Majority of the biologics still require late-stage trials to validate their clinical effectiveness.
The Role of Interleukin-4 and Interleukin-10 in Osteoarthritic Joint Disease: A Systematic Narrative Review
Authors: van Helvoort E.M. , van der Heijden E. , van Roon J.A.G. , Eijkelkamp N. , Mastbergen S.C. 
Published: May 2022

Objective A fusion protein of interleukin-4 and interleukin-10 (IL4-10 FP) was developed as a disease-modifying osteoarthritis drug (DMOAD), and chondroprotection, anti-inflammation, and analgesia have been suggested. To better understand the mechanisms behind its potential as DMOAD, this systematic narrative review aims to assess the potential of IL-4, IL-10 and the combination of IL-4 and IL-10 for the treatment of osteoarthritis. It describes the chondroprotective, anti-inflammatory, and analgesic effects of IL-4, IL-10, and IL4-10 FP. Design PubMed and Embase were searched for publications that were published from 1990 until May 21, 2021 (moment of search). Key search terms were: Osteoarthritis, Interleukin-4, and Interleukin-10. This yielded 2,479 hits, of which 43 were included in this review. Results IL-4 and IL-10 showed mainly protective effects on osteoarthritic cartilage in vitro and in vivo, as did IL4-10 FP. Both cytokines showed anti-inflammatory effects, but also proinflammatory effects. Only in vitro IL4-10 FP showed purely anti-inflammatory effects, indicating that proinflammatory effects of one cytokine can be counteracted by the other when given as a combination. Only a few studies investigated the analgesic effects of IL-4, IL-10 or IL4-10 FP. In vitro, IL-4 and IL4-10 FP were able to decrease pain mediators. In vivo, IL-4, IL-10, and IL4-10 FP were able to reduce pain. Conclusions In conclusion, this review describes overlapping, but also different modes of action for the DMOAD effects of IL-4 and IL-10, giving an explanation for the synergistic effects found when applied as combination, as is the case for IL4-10 FP.
Global Variation in Studies of Articular Cartilage Procedures of the Knee: A Systematic Review
Authors: Steinmetz R. Garrett , Guth J. Jared , Matava Matthew J. , Smith Matthew V. , Brophy Robert H. 
Published: May 2022

Objective The objective of this study was to determine whether there are significant differences in terms of indications, techniques, patient variables, and objective and subjective outcome scores as a function of the geographic locale of published studies of knee articular cartilage surgery. Methods An electronic database search was performed of clinical studies evaluating knee articular cartilage procedures from 2000 to 2021. Studies were separated into global regions (Europe, Asia, North America, and South America) based on the study country. All cartilage-based treatments in each region were recorded. Patient age and sex, mechanism of injury, cartilage lesion size and location, follow-up time, failure rate, and knee outcome scores utilized were summarized and compared by region. Results A total of 2,923 studies were analyzed. Eighty level 1 and 2 studies met the inclusion criteria. The majority were from Europe ( n = 60), followed by Asia ( n = 11), North America ( n = 7), and South America ( n = 2). The majority of procedures in European and North American studies were cell-based and marrow-stimulation procedures. In Asian studies, the most common procedures were marrow-stimulation, experimental, and biologic procedures as defined by the authors. Asian countries had a higher proportion of females ( P < 0.001) and an overall older patient population ( P < 0.001). Regional variation was also seen in terms of lesion location, mechanism of injury, and failure rate. Conclusion Most high-level evidence for articular cartilage-based procedures of the knee comes from European countries. These studies vary by patient age and sex, anatomic location, and mechanism of injury. Global variation should be taken into consideration when interpreting and applying studies of knee articular cartilage surgery.
Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis complicated with macrophage activation syndrome
Authors: Ding Yukang , Ge Yongpeng 
Published: May 2022

Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) has low survival rate, whereas macrophage activation syndrome (MAS) is a severe and life-threatening syndrome associated with autoimmune diseases. Their coexistence is very rare. This study aimed to describe the prevalence, clinical characteristics, and outcomes of anti-MDA5 antibodies-positive DM patients complicated with MAS. Methods: In this retrospective study, we enrolled DM patients with anti-MDA5 antibodies, who were hospitalized between 2016 and 2020 and included patients diagnosed with MAS. Results: We identified four (2%) DM patients with anti-MDA5 antibodies. They were females with interstitial lung disease (ILD). The level of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and ferritin were significantly higher in the MAS group than those without MAS ( p < 0.05). Patients with MAS were significantly more likely to develop a dysphagia ( p = 0.012). Literature review revealed eight similar cases. Together with the present study, we identified 12 patients complicated with ILD. The median age of disease onset was 52 years with a male to female ratio of 1:6. The median duration between DM onset and MAS diagnosis was 3 months. The mortality of MAS in anti-MDA5 antibody-positive DM was 50%. Patients who died were older than those who survived (56.7 years versus 35.5 years; p = 0.015). Conclusions: MAS was rare in anti-MDA5 antibody-positive DM. The higher the level of AST, LDH, and ferritin, the greater the risk of MAS. They were associated with high mortality rates, particularly in older patients.
The effect of a quality improvement project on post-operative opioid use following outpatient spinal surgery
Authors: Magnan Marie-Claude , Wai Eugene , Kingwell Stephen , Phan Philippe , Tierney Sarah , Stratton Alexandra 
Published: May 2022

Background: Prescribing opioids upon discharge after surgery is common practice; however, there are many inherent risks including dependency, diversion, and medical complications. Our prospective pre- and post-intervention study investigates the effect of a standardized analgesic prescription on the quantity of opioids prescribed and patients' level of pain and satisfaction with pain control in the early post-operative period. Methods: With the implementation of an electronic medical record, a standardized prescription was built employing multimodal analgesia and a stepwise approach to analgesics based on level of pain. Patients received an education handout pre-operatively explaining the prescription. Consecutive patients over a three-month period undergoing elective spine surgery as day or overnight stay cases who received usual care were compared to a similar cohort who received the standardized prescription and education. Patient satisfaction with post-operative pain control, post-operative pain scores, number of refills required, and opioids prescribed in oral morphine equivalents (OMEs) were compared before and after implementation of the standardized analgesic prescription. Results: Twenty-six patients received usual care (Control group) and 26 patients received the standardized prescription and education handout (Intervention group). There were significantly fewer OMEs prescribed in the Intervention group compared to the Control group. There was no difference between groups in: patient post-operative pain intensity score, post-operative satisfaction score, or number of refills required. Conclusions: This study demonstrates that a standardized prescription consisting of an appropriate amount of opioid and non-opioid analgesics is effective in reducing the OMEs prescribed post-operatively in elective spine surgery procedures, without compromising patient pain control or satisfaction or increasing the number of refills required.
Off-label medication use in pediatrics and associated factors at public hospitals in east Gojjam zone, Ethiopia
Authors: Belayneh Anteneh , Abatneh Eyasu , Abebe Dehinnet , Getachew Melese , Kebede Bekalu , Dessie Bekalu 
Published: May 2022

Objective: Due to a lack of appropriate pediatric preparations, health providers frequently use adult formulations in an off-label manner. This study aimed to assess pediatric off-label medication use patterns and associated factors in East Gojjam, Ethiopia. Methods: Institutional-based cross-sectional study was conducted from December 2020 to June 2021 at three randomly selected hospitals. Data were collected by using self-structured questionnaires and a data abstraction checklist from health care workers and prescriptions, respectively. The collected data were analyzed using SPSS version 25. Logistic regression analysis was used to assess the association between independent and dependent variables. Results: A total of 285 eligible health professionals from the pediatric unit and pharmacies, and 1,800 eligible prescriptions were involved in the study. The response rate of healthcare workers was 94.37%. Around 74.4% of professionals had good knowledge about off-label medication. Only 8% of participants had taken training on pediatric off-label medications. Of all prescriptions, 27.6% of them have contained at least one off-label medication. Phenobarbitone (16.1%) and phenytoin (12.7%) were the most frequently prescribed off-label medication. In all, 496 (27.6%) prescriptions contained off-label drugs in the form of overdose, cutting adult tablets into small portions, and formulating tablets/capsules into solution. Lack of information on off-label prescribing, shortage of pediatric drugs, and suitable dosage forms showed significant association with off-label prescribing with p-value < 0.001. Conclusion: Almost one-third of pediatric prescriptions contained off-label medication. Only a small number of healthcare workers had taken training on pediatric off-label medications. Lack of sufficient information on risks of off-label medication, shortage of pediatric medication, and suitable pediatric dosage forms were associated with the use of off-label medication compared to non-use. Further research should be done on the long-term effects associated with off-label prescribing in pediatrics to assess whether the potential risks are balanced with the therapeutical benefit.
Determinants of successful trial of labor after a previous cesarean delivery in East Wollega, Western Ethiopia: A case–control study
Authors: Dereje Lemane , Tilahun Temesgen , Markos Jote 
Published: May 2022

Objective: Vaginal birth after cesarean could be considered a reasonable and safe option for most women with a previous cesarean section. However, it is not easy to select pregnant mothers who are a candidate for a trial of labor after cesarean. Therefore, this study is aimed to identify determinants of successful vaginal birth after previous cesarean delivery in public hospitals in East Wollega, Western Ethiopia, 2020. Methods: A facility-based unmatched case–control study was conducted on 115 cases and 115 controls. Cases were those women who successfully delivered vaginally and controls were those women delivered by cesarean section after trial of labor. Data were collected using a pre-tested structured questionnaire and organized using Epidata version 3.1. Descriptive analysis and logistic regressions were performed. The adjusted odds ratio with a 95% confidence interval was used and statistical significance was declared at P-value < 0.05. Results: The study revealed that rural residence (adjusted odds ratio = 3, 95% confidence interval = 1.25–7.21), having no history of stillbirth (adjusted odds ratio = 4.2, 95% confidence interval = 1.20–14.62), prior vaginal birth after cesarean (adjusted odds ratio = 2.4, 95% confidence interval = 1.2–6.4), counseling about a trial of labor after cesarean during antenatal follow-up (adjusted odds ratio = 4.7, 95% confidence interval = 1.88–11.74), and birth interval of >2 years (adjusted odds ratio = 8.9, 95% confidence interval = 3.25–24.67) were found to be determinants of successful vaginal birth after cesarean. Conclusion: Place of residence, history of stillbirth, history of vaginal birth after cesarean, counseling about mode of delivery during antenatal care, and birth interval were determinants of successful trial of labor after cesarean. Given these factors, it is recommended that care providers should advocate delaying pregnancy for at least 2 years and counseling women about trial of labor after cesarean during antenatal care follow-up.
Comparison of long-term results following ureteroscopic stone fragmentation with removal versus stone dusting without removal
Authors: Golomb Dor , Shvero Asaf , Mahajna Hamad , Levi Oleg , Goldberg Hanan , Tapiero Shlomi , Stabholz Yariv , Lotan Paz , Darawsha Abd-Elhalim , Ehrlich Yaron , Kleinmann Nir , Khasminsky Vadim , Zilberman Dorit , Winkler Harry , Lifshitz David 
Published: May 2022

Purpose: To compare long-term results following ureteroscopic stone fragmentation and removal versus stone dusting. Methods: We conducted a retrospective analysis of patients who underwent ureteroscopy for renal calculi at two high-volume tertiary centres between 2012 and 2013, therefore allowing long-term follow-up. The surgeons differed in their technique, some performing dusting for the most part and the others fragmentation. Inclusion criteria were stone free at the first follow-up and the sole use of laser lithotripsy is either by dusting or by fragmentation. Operative and post-operative data as well as re-treatment rates were compared between the groups. Stone-free rates and long-term stone recurrence rates were analysed by a single radiologist blinded to the treatment technique. Results: Between 2012 and 2013, 669 ureteroscopies were performed at both centres. The study group included 100 patients, which met the inclusion criteria, equally distributed between dusting and fragmentation. The cumulative stone diameter in patients treated with dusting was significantly larger (12.7 mm versus 17 mm, p = 0.006). Operative time was shorter in patients treated with dusting (56 minutes versus 47.2 minutes, p = 0.6). The mean follow-up was 58.9 (standard deviation (SD) 17.2) and 69.4 (SD 13.8) months for the fragmentation and dusting-treated patients, respectively( p = 0.06). The long-term recurrence rate in the fragmentation group was 22% compared to 38% in the dusting group ( p = 0 .08). Most of the patients in the dusting group required a repeat ureteroscopy during their follow-up (28% versus 6%, p = 0.003). A multivariable logistic regression analysis revealed that the fragmentation was not associated with a lower stone recurrence rate when compared to dusting (OR 0.6, 95% CI 0.199-1.810, p = 0.3). Conclusions: The recurrence rate of renal stones was not significantly influenced by the choice of surgical techniques. However, dusting was associated with a greater need for repeat ureteroscopy than fragmentation with removal. Level of evidence: Not applicable
Twenty-four hour urine parameters in nephrolithiasis patients with obstructive sleep apnea syndrome
Authors: Shahait Mohammed , Nevo Amihay , El-Asmar Jose M , Siripong Nalyn , Khater Nazih , Denk Jordan , Jackman Stephen , Averch Timothy , Semins Michelle 
Published: May 2022

Objective: To study 24-hour urine metabolic abnormalities in patients with obstructive sleep apnea syndrome (OSAS), diagnosed by polysomnography. The purpose was to identify whether OSAS is independently associated with a distinctive set of 24-hour urine studies in a cohort of stone formers. Patients and Methods: Using our institutional stone database (2013–2017), 1132 consecutive patients with 24-hour urine collections were identified. After applying our exclusion criteria, the final cohort consisted of 376 patients of which 45 patients had OSAS. Descriptive statistics were used to compare 24-hour urine parameters between patients with and without OSAS. Logistic regression models were used to assess the association between OSAS and 24-hour urine parameters. Results: On univariate analysis, patients with OSAS were older (57.7 versus 48.2, p < 0.001) with a higher body mass index (BMI) (35 versus 27.8, p < 0.001), and higher likelihood of diabetes mellitus (DM) (57.8 versus 10.6%, p < 0.001) and hypertension (HTN) (60% versus 23.9%, p < 0.001). Patients with OSAS had higher 24-hour total amount of urine volume (2018 versus 1818 ml, p = 0.03), calcium (279.7 versus 208 mg, p = 0.02), oxalate (41.6 versus 31.3 mg, p < 0.001), yet lower 24-hour urine pH (5.75 versus 6.03, p = 0.001). On multivariable linear regression analysis, OSAS did not affect any of the 24-hour urinary parameters. Conclusion: OSAS is a prevalent comorbidity among nephrolithiasis patients. We found no major differences in 24-hour urine parameters between nephrolithiasis patients with OSAS and those without OSAS. Further study is needed to determine whether the severity of OSAS and compliance with treatment play a role in the pathogenesis of stone formation. Level of evidence: 2b
Evaluating the incidence, management, and recurrence of inguinal hernia during robotic prostatectomy: A literature review
Authors: Ivos Mia , Wilhelm Christopher , Sharma Pranav 
Published: May 2022

Objectives: Robotic radical prostatectomy (RARP) is a well-established treatment for localised prostate adenocarcinoma. The benefits of this minimally invasive technique include shortened operative time and improved patient recovery. However, the development of inguinal hernia (IH) before, during, and following RARP has been reported. The aim of this study is to evaluate the incidence, management, and recurrence of IHs in patients undergoing RARP for prostate cancer. Methods: A literature search was conducted using the PubMed database from August 2007 to October 2020 using the keywords ‘robotic prostatectomy’ and ‘inguinal hernia’. Studies evaluating the incidence and recurrence of IH in patients undergoing RARP were identified and included. The initial search identified 77 articles. After excluding one duplicate, six case reports, three editorial comments, four articles not in English, eight review articles, and 14 studies that did not mention hernia incidence, 41 studies were included in our final literature review. Results: Concomitant IH repair (IHR) during RARP resulted in decreased symptomatic hernia recurrence during the follow-up period. When compared to patients who had not undergone hernia repair, the patients who underwent IHR during RARP did not experience greater complications in the postoperative period. Conclusions: Patients that undergo an intraoperative IHR during RARP did not experience significant adverse postoperative complications. Although operative time can slightly increase compared to RARP alone, we recommend a thorough preoperative physical examination in all patients scheduled to undergo RARP to evaluate for IH in addition to a thorough discussion with the patient of the risks and benefits of intraoperative repair. Level of evidence: Not applicable
The reputational cost of military aggression: Evidence from the 2022 Russian invasion of Ukraine
Authors: Asadzade Peyman , Izadi Roya 
Published: May 2022

Large-scale military aggression is argued to damage the international image of the aggressor and mobilize global public opinion against it. Previous cross-country research also finds that negative views of the aggressor are usually limited to the government and do not extend to the citizens of the invading country. Our article provides micro-level evidence on attitude change toward Russia as a country, the Russian people, and the Russian government after its invasion of Ukraine. We use data from a survey conducted between the morning of 21 February 2022 (3 days before the Russian invasion of Ukraine) and the night of 28 February 2022 (5 days after the invasion) in the United States to evaluate how the Russian invasion of Ukraine affected attitudes toward the country, its people, and the government. We also conduct a subgroup analysis to explore the magnitude of attitude change across sociodemographic and political subgroups after the invasion. Our findings show fairly significant damage to the image of Russia as a country as well as the Russian government. However, the reputational damage of the Russian people is minimal. The results also suggest that Republican and religious subgroups had the largest attitude change on Russia and the Russian government.