bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of the African Medicines Agency: progress, challenges and regulatory readiness
Authors: Ncube Bakani Mark , Dube Admire , Ward Kim 
Published: March 2021

AbstractInsufficient access to quality, safe, efficacious and affordable medical products in Africa has posed a significant challenge to public health for decades. In part, this is attributed to weak or absent policies and regulatory systems, a lack of competent regulatory professionals in National Medicines Regulatory Authorities (NMRAs) and ineffective regional collaborations among NMRAs. In response to national regulatory challenges in Africa, a number of regional harmonisation efforts were introduced through the African Medicines Regulatory Harmonisation (AMRH) initiative to, among others, expedite market authorisation of medical products and to facilitate the alignment of national legislative frameworks with the AU Model Law on Medical Products Regulation. The goals of the model law include to increase collaboration across countries and to facilitate the overall regional harmonisation process. The AMRH initiative is proposed to serve as the foundation for the establishment of the African Medicines Agency (AMA). The AMA will, as one of its mandates, coordinate the regional harmonisation systems that are enabled by AU Model Law domestication and implementation. In this paper, we review the key entities involved in regional and continental harmonisation of medicines regulation, the milestones achieved in establishing the AMA as well as the implementation targets and anticipated challenges related to the AU Model Law domestication and the AMA’s establishment. This review shows that implementation targets for the AU Model Law have not been fully met, and the AMA treaty has not been ratified by the minimum required number of countries for its establishment. In spite of the challenges, the AU Model Law and the AMA hold promise to address gaps and inconsistencies in national regulatory legislation as well as to ensure effective medicines regulation by galvanising technical support, regulatory expertise and resources at a continental level. Furthermore, this review provides recommendations for future research.
Posterior-Chain Resistance Training Compared to General Exercise and Walking Programmes for the Treatment of Chronic Low Back Pain in the General Population: A Systematic Review and Meta-Analysis
Authors: Tataryn Nicholas , Simas Vini , Catterall Tailah , Furness James , Keogh Justin W. L. 
Published: March 2021

Abstract
Background
While chronic exercise training has been demonstrated to be an effective non-pharmacological treatment for chronic low back pain (CLBP), there has been a relative lack of evidence or clinical guidelines for whether a posterior chain resistance training programme provides any benefits over general exercise (GE).

Objectives
To determine if chronic posterior chain resistance training (PCRT), defined as exercise programmes of ≥6 weeks duration focused on the thoracic, lumbar and hip extensor musculature, is more effective than GE in improving pain, level of disability, muscular strength and the number of adverse events in recreationally active and sedentary individuals with CLBP.

Methods
Four electronic databases were systematically searched from 25 September 2019 until 30 August 2020. Using the Joanna Briggs Institute (JBI) Critical Appraisal Tools checklist for randomized controlled trials (RCTs), articles were critically appraised and compared against the inclusion/exclusion criteria. Standardized mean difference (SMD), risk difference (RD) and confidence interval (CI) were calculated using Review Manager 5.3.

Results
Eight articles were included, with a total of 408 participants (203 PCRT, 205 GE). Both PCRT and GE were effective in improving a number of CLBP-related outcomes, but these effects were often significantly greater in PCRT than GE, especially with greater training durations (i.e. 12–16 weeks compared to 6–8 weeks). Specifically, when compared to GE, PCRT demonstrated a greater reduction in pain (SMD = − 0.61 (95% CI − 1.21 to 0.00), p = 0.05; I2 = 74%) and level of disability (SMD = − 0.53 (95% CI − 0.97 to − 0.09), p = 0.02; I2 = 52%), as well as a greater increase in muscle strength (SMD = 0.67 (95% CI 0.21 to 1.13), p = 0.004; I2 = 0%). No differences in the number of adverse events were reported between PCRT and GE (RD = − 0.02 (95% CI − 0.10 to 0.05), p = 0.57; I2 = 72%).

Conclusion
Results of the meta-analysis indicated that 12–16 weeks of PCRT had a statistically significantly greater effect than GE on pain, level of disability and muscular strength, with no significant difference in the number of adverse events for recreationally active and sedentary patients with CLBP. Clinicians should strongly consider utilizing PCRT interventions for 12–16 weeks with patients with CLBP to maximize their improvements in pain, disability and muscle strength. Future research should focus on comparing the efficacy and adverse events associated with specific PCRT exercise training and movement patterns (i.e. deadlift, hip lift) in treating this population.

Trial registration
PROSPERO CRD42020155700.
The neotypification of Frontonia vernalis (Ehrenberg, 1833) Ehrenberg, 1838 and the description of Frontonia paravernalis sp. nov. trigger a critical revision of frontoniid systematics
Authors: Serra Valentina , D’Alessandro Aldo , Nitla Venkatamahesh , Gammuto Leandro , Modeo Letizia , Petroni Giulio , Fokin Sergei I. 
Published: March 2021

Abstract
Background
Among Oligohymenophorea (Ciliophora, Alveolata) the subclass Peniculia stands as one of the most well-known groups. Frontonia is the largest genus of Peniculia, and its representatives are spread in any type of water bodies as well as in soil. At a first glance, Frontonia species exhibit an overall similar morphology, and form a well-recognizable taxon of ciliates. Despite the general morphological homogeneity, the phylogenetic analysis based on the 18S rDNA sequencing showed that Frontonia is a non-monophyletic group. The systematics of this genus should be deeply reviewed, although additional issues complicate the task solving. First, type species of the genus is not yet clearly established, and no type material is available. In this context, the situation of F. vernalis, one of the first Frontonia ever described, is somehow puzzled: the description of this ciliate made by Ehrenberg (in 1833 and 1838) contains several inaccuracies and subsequent misidentifications by other authors occurred. Moreover, the 18S rDNA sequence of a putative F. vernalis is available on GenBank, but no morphological description of the correspondent specimens is provided; thus, in our opinion, it should be only prudently associated with F. vernalis or at least indicated as “F. vernalis”.

Results
In the present work, we provide the neotypification of F. vernalis newly found in Italy, presenting its multidisciplinary description and its neotype material. Similarly, we describe a novel species bearing Chlorella-like endosymbionts, Frontonia paravernalis sp. nov., retrieved in two far distant locations (Italy, Russia). A critical discussion on the status of Frontonia taxonomy and phylogeny is also presented, based on the 18S rDNA sequencing of both these two newly collected species and other 14 frontoniids isolated in different parts of the world. Finally, in the present study F. leucas was neotypified and proposed as the type species of the genus.

Conclusions
Green frontoniids form a monophyletic clade of freshwater organisms characterized by having a single contractile vacuole and bearing intracytoplasmatic Chlorella-like symbionts. With the neotypification of F. vernalis and F. leucas a fundamental step in Frontonia systematics was taken, and the bases for further taxonomic studies were laid.
Training registered nurses to conduct pre-implementation assessment to inform program scale-up: an example from the rural Transitions Nurse Program
Authors: Leonard Chelsea , Gilmartin Heather , McCreight Marina , Kelley Lynette , Mayberry Ashlea , Burke Robert E. 
Published: March 2021

Abstract
Objectives
Adapting evidence-based practices to local settings is critical for successful implementation and dissemination. A pre-implementation assessment evaluates local context to inform implementation, but there is little published guidance for clinician-implementers. The rural Transitions Nurse Program (TNP) is a care coordination intervention that facilitates care transitions for rural veterans. In year 1 of TNP, pre-implementation assessments were conducted by a centralized project team through multi-day visits at five sites nationwide. In year 2, we tested if local site TNP nurses could conduct pre-implementation assessments using evidence-based tools and coaching from the TNP team. This required developing a multicomponent pre-implementation strategy bundle to guide data collection and synthesis. We hypothesized that (1) nurses would find the pre-implementation assessment useful for tailoring TNP to local contexts and (2) nurses would identify similar barriers and facilitators to those identified at first year sites.

Methods
The bundle included guides for conducting key informant interviews, brainwriting, process mapping, and reflective journaling. We evaluated TNP nurse satisfaction and perceived utility of the structure and process of the training and bundle through pre-post surveys. To assess the outcome of data collection efforts, we interviewed nurses 4 months after completion of the pre-implementation assessment to determine if and how they used pre-implementation findings to tailor implementation of TNP to local contexts. To further assess outcomes, all data that the nurses collected were analyzed thematically. Themes related to barriers and facilitators were compared across years.

Findings
Five nurses at different VA medical centers used the pre-implementation strategy bundle to collect site-level data and completed pre-post surveys. Findings indicated that the pre-implementation assessment was highly recommended, and the bundle provided adequate training. Nurses felt that pre-implementation work oriented them to the local context and illustrated how to integrate TNP into existing processes. Barriers and facilitators identified by nurses were similar to those collected in year 1 by the TNP research team, including communication challenges, need for buy-in, and logistical concerns.

Conclusions
This proof-of-concept study suggests that evidence-based tools can effectively guide clinician-implementers through the process of conducting a pre-implementation assessment. This approach positively informed TNP implementation and oriented nurses to their local context prior to implementation.
Antibiograms of intensive care units at an Egyptian tertiary care hospital
Authors: Negm Essamedin M. , Mowafy Sherif M. S. , Mohammed Ahmad A. , Amer Marwa G. , Tawfik Ahmed E. , Ibrahim Ashraf E. S. , Hassan Tarek H. 
Published: March 2021

Abstract
Background
Intensive care unit (ICU) infection management is a growing challenge, and physicians should have regularly updated antibiograms. The aim of this study was to find out the prevalence of pathogens and to determine their antibiotic susceptibility in different ICUs of an Egyptian tertiary care hospital. This retrospective record-based cross-sectional study was conducted from the first of January to the last of December 2019 with a total of 45,221 diagnostic first-isolate culture/patient obtained from different ICUs in Zagazig University Hospitals. The antibiogram construction was done according to Clinical and Laboratory Standards Institute instructions and a Web-based antibiogram at Stanford University.

Results
The positive blood isolate was the most prevalent infection site (32.37%) followed by sputum and urine isolates. Gram-negative microorganisms (74.41%) were the most common pathogens, with Klebsiella pneumoniae as the most frequently identified one with an incidence of 33.51% followed by Escherichia coli with 19.3% incidence. Antibiotic sensitivity showed that colistin is the most effective antibiotic with 96.2%, 94.7%, and 89.9% sensitivity for Klebsiella, E. coli, and Acinetobacter, respectively, while carbepenems sensitivity was extremely low, showing 19.5% and 19% imipenem and meropenem sensitivity for Klebsiella, 48% imipenem and 52.7% meropenem sensitivity for E. coli, 20.1% imipenem and 20.3% meropenem sensitivity for Acinetobacter, and 17.3% imipenem and 15.2% meropenem sensitivity for Pseudomonas aeruginosa. Fungal infection in our results represented less than 1%.

Conclusion
Our study provides a local baseline epidemiological data which describes the extent of the ICU infections problem in this tertiary care hospital.

Trial registration
ClinicalTrials.gov (NCT04318613)
Multicenter Prospective Cohort Study of the Patient-Reported Outcome Measures PRO-CTCAE and CAT EORTC QLQ-C30 in Major Abdominal Cancer Surgery (PATRONUS): A Student-Initiated German Medical Audit (SIGMA) Study
Authors:   CHIR-Net SIGMA Study Group*, Mihaljevic André L. 
Published: March 2021

Abstract
Background
The patient-reported outcomes (PRO) version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the computerized adaptive testing (CAT) version of the EORTC quality-of-life questionnaire QLQ-C30 have been proposed as new PRO measures in oncology; however, their implementation in patients undergoing cancer surgery has not yet been evaluated.

Methods
Patients undergoing elective abdominal cancer surgery were enrolled in a prospective multicenter study, and postoperative complications were recorded according to the Dindo–Clavien classification. Patients reported PRO data using the CAT EORTC QLQ-C30 and the PRO-CTCAE to measure 12 core cancer symptoms. Patients were followed-up for 6 months postoperatively. The study was carried out by medical students of the CHIR-Net SIGMA study network.

Results
Data of 303 patients were obtained and analyzed across 15 sites. PRO-CTCAE symptoms ‘poor appetite’, ‘fatigue’, ‘exhaustion’ and ‘sleeping problems’ increased after surgery and climaxed 10–30 days postoperatively. At 3–6 months postoperatively, no PRO-CTCAE symptom differed significantly to baseline. Patients reported higher ‘social functioning’ (p = 0.021) and overall quality-of-life scores (p < 0.05) 6 months after cancer surgery compared with the baseline level. There was a lack of correlation between postoperative complications or death and any of the PRO items evaluated. Feasibility endpoints for student-led research were met.

Conclusion
The two novel PRO questionnaires were successfully applied in surgical oncology. Postoperative complications do not affect health-reported quality-of-life or common cancer symptoms following major cancer surgery. The feasibility of student-led multicenter clinical research was demonstrated, but might be enhanced by improved student training.
Management of acute paediatric fractures treated surgically in the UK: a cross-sectional study
Authors: Rashid MS , Dorman S , Humphry S ,   POTS study collaborators
Published: March 2021

Introduction The epidemiology of acute paediatric orthopaedic trauma managed surgically across the NHS is poorly described. Compliance against national standards for the management of supracondylar humeral fractures is also unknown at a national level. Methods Collaborators in 129 NHS hospitals prospectively collected data on surgically managed acute paediatric orthopaedic trauma cases. Data were collected over a seven-day period and included demographics, injury characteristics, operative details and timing of surgery. A national audit was also undertaken to evaluate compliance with the British Orthopaedic Association Standards for Trauma Guideline 11: Supracondylar Fractures of the Humerus in Children. Results Data were captured on 770 surgically treated cases. The three most common injuries were forearm fractures of both bones (n = 235), distal radius fractures (n = 194) and supracondylar elbow fractures (n = 89). The mode day of injury was Friday (n = 136) and the mode day of surgery was Saturday (n = 138). 88% of supracondylar fractures received surgery on the day of presentation or the following day. Only 14% of supracondylar fractures were treated surgically after 8pm; 33/89 used 2.0mm Kirschner wires, 38/89 used 1.6mm wires and 2/89 used 1.2mm wires. Conclusion Forearm fractures of both bones, distal radius fractures and supracondylar humeral fractures were the three most common injuries treated surgically. There is wide variation in compliance against national standards in the management of supracondylar humeral fractures with 88% undertaking surgery on the day of or the day following presentation but only 37% using the recommended 2.0mm Kirschner wires.
Microvascular reconstruction for head and neck cancers in high risk population: clinical outcomes and complications
Authors: Katna R , Singh S , Bhosale B , Deshpande A , Kalyani N ,   On behalf of Mumbai Oncology Group – Head and Neck
Published: March 2021

Introduction Microvascular reconstruction is the gold standard for reconstruction in oral cavity cancers. Age and comorbidities determine the type of reconstruction. We aimed to analyse the impact of high-risk comorbidities on perioperative morbidity. Methods This is a retrospective study of 317 patients undergoing microvascular reconstruction from January 2014 to December 2017. High risk patients were based on age, American Society of Anaesthesiologists (ASA) grade (III/IV) and Charlson comorbidity index (CCI) score >4; overall, 73 out of 317 patients were evaluated. Results Median age was 59 years. Five patients (6.8%) had complete flap failures and seven (9.5%) had minor complications (wound breakdown, bleeding, wound dehiscence, partial flap loss). ASA score of IV was significantly associated with morbidity while age >65 years and CCI >4 was not associated. The overall flap success rate was 93.2%. Conclusions A high-risk population has nearly similar outcomes for microvascular reconstruction as a younger age group. High ASA score adversely affects surgery-related outcomes.
Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review
Authors: Burnett Heather , Emich Helena , Carroll Chris , Stapleton Naomi , Mahadevia Parthiv , Li Tracy 
Published: March 2021

ObjectivesThe burden of epidermal growth factor receptor (EGFR) exon 20 insertion mutation (Exon 20ins) in non-small cell lung cancer is not well understood. A systematic review was conducted to identify evidence on mutation frequency, prognostic impact, clinical, patient-reported, and economic outcomes associated with Exon 20ins.Materials and methodsSearches were conducted in Embase and Medline and supplemented with recent conference proceedings. Included studies were not limited by intervention, geography, or publication year.ResultsSeventy-eight unique studies were included; 53 reporting mutation frequency, 13 prognostic impact, 36 clinical outcomes, and one humanistic burden. No economic burden data were identified. The frequency of Exon 20ins mutation ranged from 0.1% to 4% of all NSCLC cases and 1% to 12% of allEGFRmutations. Data on the prognostic impact of Exon 20ins were heterogeneous but highlighted poorer outcomes in patients with Exon 20ins mutation compared with patients with otherEGFRmutations andEGFRwildtype across a wide range of therapies and treatment lines. Comparative evidence on the clinical efficacy and safety of currently available therapies were limited, as were sample sizes of studies reporting on real-world effectiveness. Nine single-arm trials and 27 observational studies reported clinical outcomes for patients with Exon 20ins. Trends towards better survival and response were observed for chemotherapy compared with TKIs as first-line treatments. For subsequent treatment lines, novel targeted therapies provided encouraging preliminary responses while results for chemotherapy were less favorable. Limited safety data were reported. One conference abstract described the symptom burden for Exon 20ins patients with fatigue and pain being most common.ConclusionFindings of the systematic review show a high unmet need for safe and efficacious treatments for patients with Exon 20ins as well and need for further evidence generation to better understand the patient-level and economic impact for these patients.
Incidence and surgical care of retinal detachment during the first SARS-CoV-2 lockdown period at a tertiary referral center in Austria
Authors: Schranz Markus , Georgopoulos Michael , Sacu Stefan , Reumueller Adrian , Reiter Gregor S. , Mylonas Georgios , Schmidt-Erfurth Ursula , Pollreisz Andreas 
Published: March 2021

Purpose
To assess the influence of the SARS-CoV-2 lockdown in spring on frequency, severity and quality of care of rhegmatogeneous retinal detachments (RRD) in a tertiary referral center in Vienna, Austria.

Methods
Single center, consecutive case series with historical controls. Patients presenting with primary RRD during the first Austrian SARS-CoV-2 lockdown (March 16th–May 3rd 2020) and a corresponding control group consisting of the same time period of the preceding 3 years.

Results
The mean number of patients with RD in the reference group (RG) was 22 (± 1) and in the lockdown group (LG) 15. Median total delay, defined as onset of symptoms until surgery, in the RG was 5 (lower quartile: 3.0; upper quartile: 8.0) compared to 7 (3.0; 12.0) days in the LG, (p = 0.740). During the lockdown 67% of patients were referred from an external ophthalmologist compared to 52% in the RG, (p = 0.395). 34% of patients in the RG presented with an attached macula compared to 33% in the LG (p = 0.597). PVR was present in 49% of cases in the RG compared to 73% in the LG. Single surgery success (SSS) rates were lower in the LG (73.3%) compared to the RG (85.3%), (p = 0.275).

Conclusion
Patients with RRD during the SARS-CoV-2 lockdown presented and were treated within acceptable time limits, showed the same macula-on ratios but a higher PVR rate and a tendency towards worse SSS rates compared to the time period of the preceding 3 years.
Bonnie and Clyde Revisited: A Conceptual Model of the Behavior of the Instigators of the GameStop Short Squeeze of 2021
Authors: Samsa Greg 
Published: March 2021

The efficient market hypothesis assumes that investors act independently, but social-media-enabled behavior among amateur investors demonstrably violates this assumption. This was dramatically illustrated by a recent short squeeze in the shares of GameStop. By analogy with conceptual models in the behavioral sciences, we outline a conceptual model attempting to explain the behavior of the participants, and explore some of the implications of this conceptual model for investors. This case study illustrates a systematic inefficiency in option pricing which only become apparent when extreme market conditions are encountered. Although the cognitive biases of amateur investors are of little importance for understanding stock prices, this is a special case where their cognitive biases do matter.
Singularity analysis and analytic solutions for the Benney–Gjevik equations
Authors: Paliathanasis Andronikos , Leon Genly , Leach P. G. L. 
Published: March 2021

Abstract
We apply the Painlevé test for the Benney and the Benney–Gjevik equations, which describe waves in falling liquids. We prove that these two nonlinear 1 + 1 evolution equations pass the singularity test for the travelling-wave solutions. The algebraic solutions in terms of Laurent expansions are presented.