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Validation of an NGS Panel Designed for Detection of Actionable Mutations in Tumors Common in Latin America
(2021)
Mauricio Salvo
;
Evelin González-Feliú
;
Jessica Toro
;
Iván Gallegos
;
Ignacio Maureira
<jats:p>Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America. Library preparation was optimized to account for low DNA integrity observed in formalin-fixed paraffin-embedded tissue. The workflow includes an automated bioinformatic pipeline that accounts for the underrepresentation of Latin Americans in genome databases. The panel detected small insertions, deletions, and single nucleotide variants down to allelic frequencies of 0.05 with high sensitivity, specificity, and reproducibility. The workflow was validated in 272 clinical samples from several solid tumor types, including gallbladder (GBC). More than 50 biomarkers were detected in these samples, mainly in BRCA1/2, KRAS, and PIK3CA genes. In GBC, biomarkers for PARP, EGFR, PIK3CA, mTOR, and Hedgehog signaling inhibitors were found. Thus, this small NGS panel is an accurate and sensitive method that may constitute a more cost-efficient alternative to multiple non-NGS assays and costly, large NGS panels. This kind of streamlined assay with automated bioinformatics analysis may facilitate the implementation of precision medicine in Latin America.</jats:p>
2Scopus© Citations 13
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Evaluating a Memory Clinic Using the RE-AIM Model. The Experience of the “Memory and Neuropsychiatry Clinic” in Hospital Del Salvador, Chile
(2021)
Tomas Leon
;
Loreto Castro
;
Franco Mascayano
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Brian Lawlor
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SLACHEVSKY CHONCHOL, ANDREA MARÍA
<jats:p>The development of healthcare services for dementia is key to improving access to care and post-diagnostic support for people living with dementia. Memory Units have emerged as a new healthcare service composed of multidisciplinary teams with the goal of improving diagnosis and/or management of dementia patients. The main objective of this study was to describe and evaluate the Reach and Effectiveness of a Memory Unit in a public hospital in Chile, using the RE-AIM model, a multi-component model that allows for the evaluation of the implementation of ongoing healthcare programs. Regarding “R” (Reach): from March 2018 up to June 2019, a total of 510 patients were referred and assessed. Most patients came from primary care (51.9%) and from outpatient services at the Hospital Salvador (39.2%), particularly from the Neurology (63.3%) and Psychiatry (16.0%) departments. We estimated that our Memory Unit assessed 5.39% of all of the dementia patients living in the area of referral. With respect to “E” (Effectiveness): 419 patients are still being followed up at the Memory Unit. Ninety-one patients (18%) were discharged. Of these, 55 (66%) were referred to primary healthcare, 28 (31%) to other outpatient services, 9 (10%) to a specialized mental healthcare center, and 9 (10%) to a daycare center. Due to the short period of time that the Memory Unit has been operating, no other RE-AIM dimensions could be evaluated at this juncture. To our knowledge, this is the first implementation study of a Memory Unit in Latin America, and the first using the RE-AIM model. Although cultural differences worldwide might play a role in the lack of international guidelines, the publication of the experience of the first year of this unit in Chile could inform new countries about this process. Ongoing challenges include continuing to collect data to complement the RE-AIM evaluation and developing a protocol that can be adopted elsewhere in Chile and Latin America. Further studies are needed to assess the benefits of a Memory Unit in comparison to regular care and to develop a model that assures continuity and coordination of care for people with dementia.</jats:p>
Scopus© Citations 8 2
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Validation of the simplified modified Rankin scale for stroke trials: Experience from the ENCHANTED alteplase-dose arm
(2020)
Xiaoying Chen
;
Jingwei Li
;
Craig S Anderson
;
Richard I Lindley
;
Maree L Hackett
<jats:sec><jats:title>Background and aims</jats:title><jats:p> The structured, simplified modified Rankin scale questionnaire (smRSq) may increase reliability over the interrogative approach to scoring the modified Rankin scale (mRS) in acute stroke research and practice. During the conduct of the alteplase-dose arm of the international ENhanced Control of Hypertension ANd Thrombolysis StrokE stuDy (ENCHANTED), we had an opportunity to compare each of these approaches to outcome measurement. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Baseline demographic data were recorded together with the National Institutes of Health Stroke Scale (NIHSS). Follow-up measures obtained at 90 days included mRS, smRSq, and the 5-Dimension European Quality of life scale (EQ-5D). Agreements between smRSq and mRS were assessed with the Kappa statistic. Multiple logistic regression was used to identify baseline predictors of Day 90 smRSq and mRS scores. Treatment effects, based on Day 90 smRSq/mRS scores, were tested in logistic and ordinal logistic regression models. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> SmRSq and mRS scores had good agreement (weighted Kappa 0.79, 95% confidence interval (CI) 0.78–0.81), while variables of age, atrial fibrillation, diabetes mellitus, pre-morbid mRS (1 vs. 0), baseline NIHSS scores, and imaging signs of cerebral ischemia, similarly predicted their scores. Odds ratios for death or disability, and ordinal shift, 90-day mRS scores using smRSq were 1.05 (95% CI 0.91–1.20; one-sided P = 0.23 for non-inferiority) and 0.98 (95% CI 0.87–1.11; P = 0.02 for non-inferiority), similar to those using mRS. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> This study demonstrates the utility of the smRSq in a large, ethnically diverse clinical trial population. Scoring of the smRSq shows adequate agreement with the standard mRS, thus confirming it is a reliable, valid, and useful alternative measure of functional status after acute ischemic stroke. </jats:p></jats:sec><jats:sec><jats:title>Clinical Trial registration</jats:title><jats:p> URL: http://www.clinicaltrials.gov . Unique identifier: NCT01422616. </jats:p></jats:sec>
Scopus© Citations 9 7
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Prognostic significance of early urinary catheterization after acute stroke: Secondary analyses of the international HeadPoST trial
(2020)
Menglu Ouyang
;
Laurent Billot
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Lili Song
;
Xia Wang
;
Christine Roffe
<jats:sec><jats:title>Background</jats:title><jats:p> An indwelling urinary catheter (IUC) is often inserted to manage bladder dysfunction, but its impact on prognosis is uncertain. We aimed to determine the association of IUC use on clinical outcomes after acute stroke in the international, multi-center, cluster crossover, Head Positioning in Acute Stroke Trial (HeadPoST). </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Data were analyzed on HeadPoST participants (n = 11,093) randomly allocated to the lying-flat or sitting-up head position. Binomial, logistic regression, hierarchical mixed models were used to determine associations of early insertion of IUC within seven days post-randomization and outcomes of death or disability (defined as “poor outcome,” scores 3–6 on the modified Rankin scale) and any urinary tract infection at 90 days with adjustment of baseline and post-randomization management covariates. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Overall, 1167 (12%) patients had an IUC, but the frequency and duration of use varied widely across patients in different regions. IUC use was more frequent in older patients, and those with vascular comorbidity, greater initial neurological impairment (on the National Institutes of Health Stroke Scale), and intracerebral hemorrhage as the underlying stroke type. IUC use was independently associated with poor outcome (adjusted odds ratio (aOR): 1.40, 95% confidence interval (CI): 1.13–1.74), but not with urinary tract infection after adjustment for antibiotic treatment and stroke severity at hospital separation (aOR: 1.13, 95% CI: 0.59–2.18). The number exposed to IUC for poor outcome was 13. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> IUC use is associated with a poor outcome after acute stroke. Further studies are required to inform appropriate use of IUC. </jats:p></jats:sec>
Scopus© Citations 4 3
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Breaking the breach in Latin America: A pilot study of mechanical thrombectomy in the public healthcare system in Chile
(2020)
Rodrigo Rivera
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Cristian Amudio
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Enzo Brunetti
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Pascual Catalan
;
Juan Gabriel Sordo
<jats:sec><jats:title>Background</jats:title><jats:p> Mechanical Thrombectomy (MT) is the standard of care for treatment of large vessel occlusion stroke. Until the beginning of 2020 MT was not funded nor widely implemented at the public healthcare level in Chile. </jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p> To describe the results of a pilot program created to provide access to public MT in Santiago - Chile. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Analysis from a prospectively collected database of MT cases performed between September 2017 and September 2019 in one center. A stroke network was developed with a single MT capable stroke center and five primary stroke centers. The primary efficacy endpoint was the rate of functional independence (mRS 0-2) at 90 days. Successful reperfusion was defined as 2 b-3 according to the thrombolysis in cerebral infarction scale. Safety outcomes include the rates of symptomatic intracranial hemorrhage and 90-day mortality. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> A total of 100 patients were treated over the study period. Their mean age was 62.8 ± 11.8 years and median baseline National Institute of Health Stroke Scale (NIHSS) measurement was 17. Seventy-seven percent of the patients received intra venous thrombolysis. Successful reperfusion was achieved in 95% of the cases. NIHSS at 24 hours showed a median drop of 7 points from baseline (p < 0.00001) and 50% of the follow-up patients were functionally independent at 90 days. Symptomatic Intracerebral hemorrhage occurred in 5% of the patients and 90-day all case mortality was 11%. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> We demonstrated the feasibility of a publicly funded MT program in Chile, with similar results as other international randomized control trials. </jats:p></jats:sec>
Scopus© Citations 10 4
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Structural brain abnormalities in schizophrenia in adverse environments: examining the effect of poverty and violence in six Latin American cities
(2020)
Nicolas A. Crossley
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Andre Zugman
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Francisco Reyes-Madrigal
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Leticia S. Czepielewski
;
Mariana N. Castro
<jats:title>Summary</jats:title><jats:sec id="S0007125020001439_sec_a1"><jats:title>Background</jats:title><jats:p>Social and environmental factors such as poverty or violence modulate the risk and course of schizophrenia. However, how they affect the brain in patients with psychosis remains unclear.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a2"><jats:title>Aims</jats:title><jats:p>We studied how environmental factors are related to brain structure in patients with schizophrenia and controls in Latin America, where these factors are large and unequally distributed.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a3" sec-type="methods"><jats:title>Method</jats:title><jats:p>This is a multicentre study of magnetic resonance imaging in patients with schizophrenia and controls from six Latin American cities. Total and voxel-level grey matter volumes, and their relationship with neighbourhood characteristics such as average income and homicide rates, were analysed with a general linear model.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a4" sec-type="results"><jats:title>Results</jats:title><jats:p>A total of 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total grey matter volume in both groups (<jats:italic>P</jats:italic> = 0.006). Controls showed a positive correlation between total grey matter volume and income (<jats:italic>R</jats:italic> = 0.14, <jats:italic>P</jats:italic> = 0.02). Surprisingly, this relationship was not present in patients with schizophrenia (<jats:italic>R</jats:italic> = −0.076, <jats:italic>P</jats:italic> = 0.17). Voxel-level analysis confirmed that this interaction was widespread across the cortex. After adjusting for global brain changes, income was positively related to prefrontal cortex volumes only in controls. Conversely, the hippocampus in patients with schizophrenia, but not in controls, was relatively larger in affluent environments. There was no significant correlation between environmental violence and brain structure.</jats:p></jats:sec><jats:sec id="S0007125020001439_sec_a5" sec-type="conclusions"><jats:title>Conclusions</jats:title><jats:p>Our results highlight the interplay between environment, particularly poverty, and individual characteristics in psychosis. This is particularly important for harsh environments such as low- and middle-income countries, where potentially less brain vulnerability (less grey matter loss) is sufficient to become unwell in adverse (poor) environments.</jats:p></jats:sec>
Scopus© Citations 10 1
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Could Subtle Obstetrical Brachial Plexus Palsy Be Related to Unilateral B Glenoid Osteoarthritis?
(2021)
Alexandre Lädermann
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Hugo Bothorel
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Philippe Collin
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Bassem Elhassan
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Luc Favard
<jats:p>Background: Several factors associated with B glenoid are also linked with obstetrical brachial plexus palsy (OBPP). The purpose of this observational study was to determine the incidence of OBPP risk factors in type B patients. Methods: A cohort of 154 patients (68% men, 187 shoulders) aged 63 ± 17 years with type B glenoids completed a questionnaire comprising history of perinatal characteristics related to OBPP. A literature review was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to estimate the incidence of OBPP risk factors in the general population. Results: Twenty-seven patients (18%) reported one or more perinatal OBPP risk factors, including shoulder dystocia (n = 4, 2.6%), macrosomia >4 kg (n = 5, 3.2%), breech delivery (n = 6, 3.9%), fetal distress (n = 8, 5.2%), maternal diabetes (n = 2, 1.3%), clavicular fracture (n = 2, 1.3%), and forceps delivery (n = 4, 2.6%). The comparison with the recent literature suggested that most perinatal OBPP risk factors were within the normal range, although the incidence of shoulder dystocia, forceps and vaginal breech deliveries exceeded the average rates. Conclusion: Perinatal factors related to OBPP did not occur in a higher frequency in patients with Walch type B OA compared to the general population, although some of them were in the high normal range.</jats:p>
Scopus© Citations 3 20
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Outcomes of Sepsis and Septic Shock in Cancer Patients: Focus on Lactate
(2021)
LOPEZ HERNANDEZ, RENE RAMON
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Rodrigo Pérez-Araos
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Fernanda Baus
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Camila Moscoso
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Álvaro Salazar
<jats:p>The number of oncological patients (OP) admitted to intensive care units (ICU) for sepsis/septic shock has dramatically increased in recent years. The definition of septic shock has been modified, adding hyperlactatemia as a severity biomarker for mortality. However, it remains poorly reported in septic OP. We performed a retrospective analysis from a prospective database of sepsis/septic shock patients admitted to our ICU between September 2017 and September 2019 and followed until day 90. We identified 251 patients and 31.9% had active oncological comorbidity, mainly solid tumor (81.3%). Septic shock criteria were met for 112 (44.6%). Hyperlactatemia was observed in 136 (54.2%) patients and this was associated with a lower survival rate. Overall 90-day mortality was 15.1%. In OP vs. non-OP, hyperlactatemia was more frequent (65% vs. 49.1%, <jats:italic>p</jats:italic> = 0.013) and associated with lower survival (65.4% vs. 85.7%, <jats:italic>p</jats:italic> = 0.046). In OP, poor performance status was also associated with lower survival (HR 7.029 [1.998–24.731], <jats:italic>p</jats:italic> = 0.002) In an adjusted analysis, cancer was associated with lower 90-day survival (HR 2.690 [1.402–5.160], <jats:italic>p</jats:italic> = 0.003). In conclusion, septic OP remains a high mortality risk group in whom lactate levels and performance status could help with better risk stratification.</jats:p>
Scopus© Citations 18 1
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Infant Feeding and Information Sources in Chilean Families Who Reported Baby-Led Weaning as a Complementary Feeding Method
(2021)
Daiana Quintiliano-Scarpelli
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Nicole Lehmann
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Bárbara Castillo
;
Estela Blanco
<jats:p>Baby-Led Weaning (BLW) is a new and emerging method of introducing complementary feeding in solid consistency, without the use of a spoon and entirely guided by the baby. This study aims to analyze the implementation of the BLW approach in relation to compliance with basic components and sources of information in Chilean families. Using a cross-sectional design, we assessed early nutrition, including breastfeeding and foods offered, maternal/child characteristics and sources of information on BLW among a non-probabilistic sample of mothers of children <24 months who reported practicing BLW (n = 261, median age = 28 years) in Chile. We found that 57.5% of mothers reported their child ate the same food as the family, 44.1% shared ≥3 meals with the family, 84.7% offered ≥3 foods at each meal and 75.6% reported only occasionally offering food with a spoon. The majority reported obtaining information on BLW from social media (82%). Moreover, 56% had offered cookies, 32% added salt and 9% sugar in the first 2 years. Exclusive breastfeeding for 6 months related to higher odds of consuming family foods (OR = 2.45, 95% CI 1.24–4.84), while having received information from professional sources and social media related to lower odds (OR = 0.45, 95% CI 0.22–0.88 and OR = 0.31, 95% CI 0.15–0.66, respectively). Those who had appropriate weight gain had lower odds of consuming ≥3 foods in meals (OR = 0.35, 95% CI 0.13–0.96). Among mothers who reported practicing BLW with their children, we observed a wide variety of feeding habits, sources of information and low compliance with the studied components. Eating the same food as the family was the most prevalent component and social media was the main source of information on BLW.</jats:p>
6Scopus© Citations 13
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Tool for Estimating the Probability of Having COVID-19 With 1 or More Negative RT-PCR Results
(2021)
Alejandro Jara
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Eduardo A Undurraga
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ARAOS BRALIC, RAFAEL IGNACIO
<jats:title>Abstract</jats:title> <jats:p>Early case detection and isolation of infected individuals are critical to controlling coronavirus disease 2019 (COVID-19). Reverse transcription polymerase chain reaction (RT-PCR) is considered the gold standard for the diagnosis of severe acute respiratory syndrome coronavirus 2 infection, but false negatives do occur. We built a user-friendly online tool to estimate the probability of having COVID-19 with negative RT-PCR results and thus avoid preventable transmission.</jats:p>
3Scopus© Citations 1

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