bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effectiveness of training strategies to improve healthcare provider practices in low-income and middle-income countries
Authors: Rowe Alexander K , Rowe Samantha Y , Peters David H , Holloway Kathleen A , Ross-Degnan Dennis 
Published: January 2021

IntroductionIn low/middle-income countries (LMICs), training is often used to improve healthcare provider (HCP) performance. However, important questions remain about how well training works and the best ways to design training strategies. The objective of this study is to characterise the effectiveness of training strategies to improve HCP practices in LMICs and identify attributes associated with training effectiveness.MethodsWe performed a secondary analysis of data from a systematic review on improving HCP performance. The review included controlled trials and interrupted time series, and outcomes measuring HCP practices (eg, percentage of patients correctly treated). Distributions of effect sizes (defined as percentage-point (%-point) changes) were described for each training strategy. To identify effective training attributes, we examined studies that directly compared training approaches and performed random-effects linear regression modelling.ResultsWe analysed data from 199 studies from 51 countries. For outcomes expressed as percentages, educational outreach visits (median effect size when compared with controls: 9.9 %-points; IQR: 4.3–20.6) tended to be somewhat more effective than in-service training (median: 7.3 %-points; IQR: 3.6–17.4), which seemed more effective than peer-to-peer training (4.0 %-points) and self-study (by 2.0–9.3 %-points). Mean effectiveness was greater (by 6.0–10.4 %-points) for training that incorporated clinical practice and training at HCPs’ work site. Attributes with little or no effect were: training with computers, interactive methods or over multiple sessions; training duration; number of educational methods; distance training; trainers with pedagogical training and topic complexity. For lay HCPs, in-service training had no measurable effect. Evidence quality for all findings was low.ConclusionsAlthough additional research is needed, by characterising the effectiveness of training strategies and identifying attributes of effective training, decision-makers in LMICs can improve how these strategies are selected and implemented.
Interests and needs of eye care providers in clinical decision support for glaucoma
Authors: Stagg Brian , Stein Joshua D , Medeiros Felipe A , Cummins Mollie , Kawamoto Kensaku , Hess Rachel 
Published: January 2021

ObjectiveTo study whether clinicians who treat glaucoma are interested in using clinical decision support (CDS) tools for glaucoma, what glaucoma clinical decisions they feel would benefit from CDS, and what characteristics of CDS design they feel would be important in glaucoma clinical practice.Methods and analysisWorking with the American Glaucoma Society, the Utah Ophthalmology Society and the Utah Optometric Association, we identified a group of clinicians who care for patients with glaucoma. We asked these clinicians about interest in CDS, what glaucoma clinical decisions would benefit from CDS, and what characteristics of CDS tool design would be important in glaucoma clinical practice.ResultsOf the 105 clinicians (31 optometrists, 10 general ophthalmologists and 64 glaucoma specialists), 93 (88.6%) were either ‘definitely’ or ‘probably’ interested in using CDS for glaucoma. There were no statistically significant differences in interest between clinical specialties (p=0.12), years in practice (p=0.85) or numbers of patients seen daily (p=0.99). Identifying progression of glaucoma was the clinical decision the largest number of clinicians felt would benefit from CDS (104/105, 99.1%). An easy to use interface was the CDS characteristic the largest number of clinicians felt would be ‘very important’ (93/105, 88.6%).ConclusionOf this group of clinicians who treat glaucoma, 88.6% were interested in using CDS for glaucoma and 99.1% felt that identification of glaucomatous progression could benefit from CDS. This level of interest supports future work to develop CDS for glaucoma.
Lumbosacral injuries in elite Paralympic athletes with limb deficiency: a retrospective analysis of patient records
Authors: Heneghan Nicola R , Collacott Esther , Martin Paul , Spencer Simon , Rushton Alison 
Published: January 2021

BackgroundCompared to injury data in able-bodied athletes, relatively little literature exists for Paralympic athletes. Injury data underpins the design and evaluation of injury prevention strategies in elite sport. The aim of this study was to investigate frequency, characteristics and management of lumbosacral injuries in elite athletes with limb deficiency.MethodsA retrospective analysis of injuries in elite athletes with limb deficiency (2008 to 2017) was conducted using available data extracted from The English Institute of Sport (EIS) clinical records. Eligibility criteria: funded athletes, eligible for EIS physiotherapy support with full or partial limb deficiency. Data were analysed descriptively using frequencies.ResultsA total of 107 injuries from 32 athletes were included. Participants comprised 18 men (59%), from 9 sports, with mean age for index injuries of 27 years (range 18 to 38 years) and 15 with congenital limb deficiency (47%). Average number of index injuries for congenital and traumatic limb deficient groups were 13 and 19, respectively. Where injury onset was recorded (n=79), half of injuries occurred during training (40%, n=43). Arthrogenic structures accounted for 32.7% of injuries, myogenic 26.2%, with neurogenic, discogenic and osteogenic each <5%. The number of treatments delivered in each injury episode ranged from 1 to 43, with symptom resolution taking 2 to 439 days.ConclusionElite athletes with limb deficiency experience lumbosacral injuries predominantly involving muscles and joints. While consistency and accuracy of data recording limits definitive conclusions, findings highlight the importance of precision in recording injury data as part of surveillance to enable implementation of effective injury prevention strategies.
NTPDase8 protects mice from intestinal inflammation by limiting P2Y6 receptor activation: identification of a new pathway of inflammation for the potential treatment of IBD
Authors: Salem Mabrouka , Lecka Joanna , Pelletier Julie , Gomes Marconato Danielle , Dumas Aline , Vallières Luc , Brochu Gaetan , Robaye Bernard , Jobin Christian , Sévigny Jean 
Published: January 2021

ObjectiveNucleotides are danger signals that activate inflammatory responses via binding P2 receptors. The nucleoside triphosphate diphosphohydrolase-8 (NTPDase8) is an ectonucleotidase that hydrolyses P2 receptor ligands. We investigated the role of NTPDase8 in intestinal inflammation.DesignWe generated NTPDase8-deficient (Entpd8–/–) mice to define the role of NTPDase8 in the dextran sodium sulfate (DSS) colitis model. To assess inflammation, colons were collected and analysed by histopathology, reverse transcriptase-quantitative real-time PCR (RT-qPCR) and immunohistochemistry. P2 receptor expression was analysed by RT-qPCR on primary intestinal epithelium and NTPDase8 activity by histochemistry. The role of intestinal P2Y6 receptors was assessed by bone marrow transplantation experiments and with a P2Y6 receptor antagonist.ResultsNTPDase8 is the dominant enzyme responsible for the hydrolysis of nucleotides in the lumen of the colon. Compared with wild-type (WT) control mice, the colon of Entpd8–/– mice treated with DSS displayed significantly more histological damage, immune cell infiltration, apoptosis and increased expression of several proinflammatory cytokines. P2Y6 was the dominant P2Y receptor expressed at the mRNA level by the colonic epithelia. Irradiated P2ry6–/– mice transplanted with WT bone marrow were fully protected from DSS-induced intestinal inflammation. In agreement, the daily intrarectal injection of a P2Y6 antagonist protected mice from DSS-induced intestinal inflammation in a dose-dependent manner. Finally, human intestinal epithelial cells express NTPDase8 and P2Y6 similarly as in mice.ConclusionNTPDase8 protects the intestine from inflammation most probably by limiting the activation of P2Y6 receptors in colonic epithelial cells. This may provide a novel therapeutic strategy for the treatment of inflammatory bowel disease.
Sacubitril/valsartan in the treatment of systemic right ventricular failure
Authors: Zandstra Tjitske E , Nederend Marieke , Jongbloed Monique R M , Kiès Philippine , Vliegen Hubert W , Bouma Berto J , Tops Laurens F , Schalij Martin J , Egorova Anastasia D 
Published: January 2021

ObjectivePharmacological options for patients with a failing systemic right ventricle (RV) in the context of transposition of the great arteries (TGA) after atrial switch or congenitally corrected TGA (ccTGA) are not well defined. This study aims to investigate the feasibility and effects of sacubitril/valsartan treatment in a single-centre cohort of patients.MethodsData on all consecutive adult patients (n=20, mean age 46 years, 50% women) with a failing systemic RV in a biventricular circulation treated with sacubitril/valsartan in our centre are reported. Patients with a systemic RV ejection fraction of ≤35% who were symptomatic despite treatment with β-blocker and ACE-inhibitor/angiotensin II receptor-blockers were started on sacubitril/valsartan. This cohort underwent structural follow-up including echocardiography, exercise testing, laboratory investigations and quality of life (QOL) assessment.ResultsSix-month follow-up data were available in 18 out of 20 patients, including 12 (67%) patients with TGA after atrial switch and 6 (33%) patients with ccTGA. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) decreased significantly (950–358 ng/L, p<0.001). Echocardiographic systemic RV fractional area change and global longitudinal strain showed small improvements (19%–22%, p<0.001 and −11% to −13%, p=0.014, respectively). The 6 min walking distance improved significantly from an average of 564 to 600 m (p=0.011). The QOL domains of cognitive function, sleep and vitality improved (p=0.015, p=0.007 and p=0.037, respectively).ConclusionsWe describe the first patient cohort with systemic RV failure treated with sacubitril/valsartan. Treatment appears feasible with improvements in NT-pro-BNP and echocardiographic function. Our positive results show the potential of sacubitril/valsartan for this patient population.
Do healthcare providers assess for risk factors and talk to patients about return to driving after a mild traumatic brain injury (mTBI)? Findings from the 2020 DocStyles Survey
Authors: Sarmiento Kelly , Waltzman Dana , Wright David 
Published: January 2021

BackgroundThere is a dearth of information and guidance for healthcare providers on how to manage a patient’s return to driving following a mild traumatic brain injury (mTBI).MethodsUsing the 2020 DocStyles survey, 958 healthcare providers were surveyed about their diagnosis and management practices related to driving after an mTBI.ResultsApproximately half (52.0%) of respondents reported routinely (more than 75% of the time) talking with patients with mTBI about how to safely return to driving after their injury. When asked about how many days they recommend their patients with mTBI wait before returning to driving after their injury: 1.0% recommended 1 day or less; 11.7% recommended 2–3 days; 24.5% recommended 4–7 days and 45.9% recommended more than 7 days. Many respondents did not consistently screen patients with mTBI for risk factors that may affect their driving ability or provide them with written instructions on how to safely return to driving (59.7% and 62.6%, respectively). Approximately 16.8% of respondents reported they do not usually make a recommendation regarding how long patients should wait after their injury to return to driving.ConclusionsMany healthcare providers in this study reported that they do not consistently screen nor educate patients with mTBI about driving after their injury. In order to develop interventions, future studies are needed to assess factors that influence healthcare providers behaviours on this topic.
Identification of neuroblastoma cell lines with uncommon TAZ+/mesenchymal stromal cell phenotype with strong suppressive activity on natural killer cells
Authors: Canzonetta Claudia , Pelosi Andrea , Di Matteo Sabina , Veneziani Irene , Tumino Nicola , Vacca Paola , Munari Enrico , Pezzullo Marco , Theuer Charles , De Vito Rita , Pistoia Vito , Tomao Luigi , Locatelli Franco , Moretta Lorenzo , Caruana Ignazio , Azzarone Bruno 
Published: January 2021

BackgroundNeuroblastoma (NB) is the most common, extracranial childhood solid tumor arising from neural crest progenitor cells and is a primary cause of death in pediatric patients. In solid tumors, stromal elements recruited or generated by the cancer cells favor the development of an immune-suppressive microenvironment. Herein, we investigated in NB cell lines and in NB biopsies, the presence of cancer cells with mesenchymal phenotype and determined the immune-suppressive properties of these tumor cells on natural killer (NK) cells.MethodsWe assessed the mesenchymal stromal cell (MSC)-like phenotype and function of five human NB cell lines and the presence of this particular subset of neuroblasts in NB biopsies using flow-cytometry, immunohistochemistry, RT-qPCR, cytotoxicity assays, western blot and silencing strategy. We corroborated our data consulting a public gene-expression dataset.ResultsTwo NB cell lines, SK-N-AS and SK-N-BE(2)C, exhibited an unprecedented MSC phenotype (CD105+/CD90+/CD73+/CD29+/CD146+/GD2+/TAZ+). In these NB-MSCs, the ectoenzyme CD73 and the oncogenic/immune-regulatory transcriptional coactivator TAZ were peculiar markers. Their MSC-like nature was confirmed by their adipogenic and osteogenic differentiation potential. Immunohistochemical analysis confirmed the presence of neuroblasts with MSC phenotype (CD105+/CD73+/TAZ+). Moreover, a public gene-expression dataset revealed that, in stage IV NB, a higher expression of TAZ and CD105 strongly correlated with a poorer outcome.Among the NB-cell lines analyzed, only NB-MSCs exhibited multifactorial resistance to NK-mediated lysis, inhibition of activating NK receptors, signal adaptors and of NK-cell cytotoxicity through cell-cell contact mediated mechanisms. The latter property was controlled partially by TAZ, since its silencing in NB cells efficiently rescued NK-cell cytotoxic activity, while its overexpression induced opposite effects in non-NB-MSC cells.ConclusionsWe identified a novel NB immunoregulatory subset that: (i) displayed phenotypic and functional properties of MSC, (ii) mediated multifactorial resistance to NK-cell-induced killing and (iii) efficiently inhibited, in coculture, the cytotoxic activity of NK cells against target cells through a TAZ-dependent mechanism. These findings indicate that targeting novel cellular and molecular components may disrupt the immunomodulatory milieu of the NB microenvironment ameliorating the response to conventional treatments as well as to advanced immunotherapeutic approaches, including adoptive transfer of NK cells and chimeric antigen receptor T or NK cells.
Advances in genetic technologies result in improved diagnosis of mismatch repair deficiency in colorectal and endometrial cancers
Authors: Evans D Gareth , Lalloo Fiona , Ryan Neil AJ , Bowers Naomi , Green Kate , Woodward Emma R , Clancy Tara , Bolton James , McVey Rhona J , Wallace Andrew J , Newton Katy , Hill James , McMahon Raymond , Crosbie Emma J 
Published: January 2021

BackgroundTesting cancers for mismatch repair deficiency (dMMR) by immunohistochemistry (IHC) is a quick and inexpensive means of triaging individuals for germline Lynch syndrome testing. The aim of this study was to evaluate tumour dMMR and the prevalence of Lynch syndrome in patients referred to the Manchester Centre for Genomic Medicine, which serves a population of 5.6 million.MethodsTumour testing used IHC for MMR proteins with targeted BRAF and MLH1 promotor methylation testing followed by germline mutation and somatic testing as appropriate.ResultsIn total, 3694 index tumours were tested by IHC (2204 colorectal cancers (CRCs), 739 endometrial cancers (ECs) and 761 other), of which 672/3694 (18.2%) had protein loss, including 348 (9.4%) with MLH1 loss. MLH1 loss was significantly higher for 739 ECs (15%) vs 2204 CRCs (10%) (p=0.0003) and was explained entirely by higher rates of somatic MLH1 promoter hypermethylation (87% vs 41%, p<0.0001). Overall, 65/134 (48.5%) patients with MLH1 loss and no MLH1 hypermethylation or BRAF c.1799T>A had constitutional MLH1 pathogenic variants. Of 456 patients with tumours showing loss of MSH2/MSH6, 216 (47.3%) had germline pathogenic variants in either gene. Isolated PMS2 loss was most suggestive of a germline MMR variant in 19/26 (73%). Of those with no germline pathogenic variant, somatic testing identified likely causal variants in 34/48 (71%) with MLH1 loss and in MSH2/MSH6 in 40/47 (85%) with MSH2/MSH6 loss.ConclusionsReflex testing of EC/CRC leads to uncertain diagnoses in many individuals with dMMR following IHC but without germline pathogenic variants or MLH1 hypermethylation. Tumour mutation testing is effective at decreasing this by identifying somatic dMMR in >75% of cases.
Diagnosis of cystic fibrosis in adulthood and eligibility for novel CFTR modulator therapy
Authors: Farley Hannah , Poole Sarah , Chapman Stephen , Flight William 
Published: January 2021

AbstractBackgroundCystic fibrosis (CF) is an autosomal recessive condition that primarily manifests as a chronic respiratory disease. CF is usually diagnosed in early childhood or through newborn screening although in a small but important group, diagnosis is not made until adulthood. Highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies are now available for most genetic causes of CF highlighting the importance of identifying people with late presentations of CF.AimWe aimed to identify the clinical characteristics of people diagnosed with CF in adulthood and their resulting eligibility for novel CFTR modulator therapies.DesignRetrospective single-centre cohort study.MethodsPatients diagnosed with CF at age 18 years or older were identified from a patient database. Paper and electronic medical records were reviewed and clinical, microbiological and radiological data at diagnosis were recorded.ResultsNineteen patients were identified. Median age at diagnosis was 38 years (range: 19–71) and 9 (47%) were female. All patients had a history of chronic respiratory symptoms and 18/19 (94%) had radiological evidence of bronchiectasis. All patients had two pathogenic CFTR mutations identified with 16/19 (84%) compound heterozygotes for the F508del mutation. The majority of patients had a CFTR genotype considered eligible for CFTR modulator therapy (84% and 89% according to European and US licences, respectively).ConclusionsAdult patients with unexplained chronic bronchiectasis should be thoroughly investigated for CF. A low index of suspicion will help to identify adults with undiagnosed CF who are likely to benefit from CFTR modulator therapy.
Effect of peripheral nerve blocks on postanesthesia care unit length of stay in patients undergoing ambulatory surgery: a retrospective cohort study
Authors: Polshin Victor , Petro Julie , Wachtendorf Luca J , Hammer Maximilian , Simopoulos Thomas , Eikermann Matthias , Santer Peter 
Published: January 2021

Background
Peripheral regional anesthesia and analgesia may increase the efficiency of ambulatory surgical centers by reducing pain and preventing nausea and vomiting, which are important modifiable causes of prolonged postanesthesia care unit (PACU) length of stay. We hypothesized that the use of peripheral nerve blocks (PNB) was associated with shorter PACU length of stay in ambulatory surgery.

Methods
In this retrospective cohort study, we analyzed data from adult ambulatory surgical cases, in which PNB was a viable anesthetic option (ie, was routinely performed for these procedures), at an academic medical center between 2008 and 2018. We assessed the association between the use of PNB and the primary endpoint of PACU length of stay. As key secondary endpoint, we compared intraoperative opioid doses. Analyses were adjusted for patient demographics, comorbidities and intraoperative factors.

Results
A total of 57 040 cases were analyzed, of whom 13 648 (23.9%) received a PNB. The use of PNB was associated with shorter PACU length of stay (a decrease of 7.3 min, 95% CI 6.1 to 8.6, p<0.001). This association was most pronounced in surgeries of long duration (decrease of 11.2 min, 95% CI 9.0 to 13.4) and in patients undergoing leg and ankle procedures (decrease of 15.1 min, 95% CI 5.5 to 24.6). Intraoperative opioid doses were significantly lower in patients receiving a nerve block (decrease of 9.40 mg oral morphine equivalents, 95% CI 8.34 to 10.46, p<0.001).

Conclusion
The use of PNB significantly reduced PACU length of stay in ambulatory surgical patients, which may in part be attributed to lower intraoperative opioid requirements.
Hydrostatic reduction of intussusception with intermittent radiography: an alternative to fluoroscopy or ultrasound-guided reduction in low-income and middle-income countries
Authors: Chowdhury Tanvir Kabir , Ahsan Md. Qumrul , Chowdhury Mohammad Zonaid , Chowdhury Md. Tameem Shafayat , Imam Md. Sharif , Alam Md. Afruzul , Farooq Md. Abdullah Al 
Published: January 2021

BackgroundAlthough hydrostatic reduction of intussusception with ultrasound (US) or fluoroscopy guidance is well known, it is not yet well established in many low-income and middle-income countries. The aim of the study is to report our results of hydrostatic reduction with intermittent radiography, which has the potential to be practiced in resource-limited settings.MethodsWe retrospectively analyzed our patients with intussusception from 2009 to 2019 (11 years). Hydrostatic reduction was performed using water-soluble contrast medium (iopamidol), and reduction was followed with intermittent X-rays taken after every 50 mL of diluted contrast injection. The procedure was not continuously monitored by US or fluoroscopy. Differences in outcome based on age and gender, and yearly trends of admission for intussusception, types of treatment and mortality were analyzed.ResultsAmong 672 patients, the ratio of boys to girls was 2.46:1.0, and their ages ranged from 1 month to 15 years (median 8 months). Hydrostatic reduction was performed successfully in 351 (52.23%) patients; 308 (45.83%) patients underwent surgery; and 13 (1.93%) patients died before any intervention. There were significant differences in age between patients with successful hydrostatic reduction (median 7 months) and patients needing surgery (median 9 months) (p<0.001). The number of successful hydrostatic reductions increased during the 11 years of the study (R2=0.88). One patient (0.15%) died after hydrostatic reduction, and 10 (1.49%) died after surgery.ConclusionHydrostatic reduction with intermittent radiography was performed successfully in more than half of the patients with acceptable complication rates.