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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
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Jessica Toro
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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
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Loreto Castro
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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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Frontotemporal Dementias in Latin America: History, Epidemiology, Genetics, and Clinical Research
(2021)
Jorge J. Llibre-Guerra
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BEHRENS PELLEGRINO, MARIA ISABEL
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Mirna Lie Hosogi
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Lucia Montero
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Teresa Torralva
<jats:p><jats:bold>Introduction:</jats:bold> The historical development, frequency, and impact of frontotemporal dementia (FTD) are less clear in Latin America than in high-income countries. Although there is a growing number of dementia studies in Latin America, little is known collectively about FTD prevalence studies by country, clinical heterogeneity, risk factors, and genetics in Latin American countries.</jats:p><jats:p><jats:bold>Methods:</jats:bold> A systematic review was completed, aimed at identifying the frequency, clinical heterogeneity, and genetics studies of FTD in Latin American populations. The search strategies used a combination of standardized terms for FTD and related disorders. In addition, at least one author per Latin American country summarized the available literature. Collaborative or regional studies were reviewed during consensus meetings.</jats:p><jats:p><jats:bold>Results:</jats:bold> The first FTD reports published in Latin America were mostly case reports. The last two decades marked a substantial increase in the number of FTD research in Latin American countries. Brazil (165), Argentina (84), Colombia (26), and Chile (23) are the countries with the larger numbers of FTD published studies. Most of the research has focused on clinical and neuropsychological features (<jats:italic>n</jats:italic> = 247), including the local adaptation of neuropsychological and behavioral assessment batteries. However, there are little to no large studies on prevalence (<jats:italic>n</jats:italic> = 4), biomarkers (<jats:italic>n</jats:italic> = 9), or neuropathology (<jats:italic>n</jats:italic> = 3) of FTD.</jats:p><jats:p><jats:bold>Conclusions:</jats:bold> Future FTD studies will be required in Latin America, albeit with a greater emphasis on clinical diagnosis, genetics, biomarkers, and neuropathological studies. Regional and country-level efforts should seek better estimations of the prevalence, incidence, and economic impact of FTD syndromes.</jats:p>
Scopus© Citations 10 1
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Isolation of Ciprofloxacin and Ceftazidime-Resistant Enterobacterales From Vegetables and River Water Is Strongly Associated With the Season and the Sample Type
(2021)
Constanza Díaz-Gavidia
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Carla Barría
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RIVAS JIMENEZ, LINA MARIA
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Patricia García
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Francisca P. Alvarez
<jats:p>The dissemination of antibiotic-resistant bacteria (ARB) from water used for crop irrigation to vegetables is poorly studied. During a year, five farmer markets in a city in Central Chile were visited, and 478 vegetable samples (parsleys, corianders, celeries, lettuces, chards, and beets) were collected. Simultaneously, 32 water samples were collected from two rivers which are used to irrigate the vegetables produced in the area. Resistant Enterobacterales were isolated and identified. Colistin resistance gene <jats:italic>mcr-1</jats:italic> and extended spectrum β-lactamases (ESBL) were molecularly detected. The association of environmental factors was evaluated, with the outcomes being the presence of Enterobacterales resistant to four antibiotic families and the presence of multidrug resistance (MDR) phenotypes. Parsley, coriander, and celery showed the highest prevalence of resistant Enterobacterales (41.9% for ciprofloxacin and 18.5% for ceftazidime). A total of 155 isolates were obtained, including <jats:italic>Escherichia coli</jats:italic> (<jats:italic>n</jats:italic>=109), <jats:italic>Citrobacter</jats:italic> sp. (<jats:italic>n</jats:italic>=20), <jats:italic>Enterobacter cloacae</jats:italic> complex (<jats:italic>n</jats:italic>=8), <jats:italic>Klebsiella pneumoniae</jats:italic> (<jats:italic>n</jats:italic>=8), and <jats:italic>Klebsiella aerogenes</jats:italic> (<jats:italic>n</jats:italic>=1). Resistance to ampicillin (63.2%) and ciprofloxacin (74.2%) was most frequently found; 34.5% of the isolates showed resistance to third-generation cephalosporins, and the MDR phenotype represented 51.6% of the isolates. In two <jats:italic>E. coli</jats:italic> isolates (1.29%), the gene <jats:italic>mcr-1</jats:italic> was found and ESBL genes were found in 23/62 isolates (37%), with <jats:italic>bla</jats:italic><jats:sub>CTX-M</jats:sub> being the most frequently found in 20 isolates (32%). Resistant Enterobacterales isolated during the rainy season were less likely to be MDR as compared to the dry season. Understanding environmental associations represent the first step toward an improved understanding of the public health impact of ARB in vegetables and water.</jats:p>
1Scopus© Citations 28
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Genomic analysis of the diversity, antimicrobial resistance and virulence potential of clinical Campylobacter jejuni and Campylobacter coli strains from Chile
(2021)
Veronica Bravo
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Assaf Katz
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PORTE TORRE, LORENA ISABEL
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WEITZEL, THOMAS
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Carmen Varela
<jats:p><jats:italic>Campylobacter jejuni</jats:italic> and <jats:italic>Campylobacter coli</jats:italic> are the leading cause of human gastroenteritis in the industrialized world and an emerging threat in developing countries. The incidence of campylobacteriosis in South America is greatly underestimated, mostly due to the lack of adequate diagnostic methods. Accordingly, there is limited genomic and epidemiological data from this region. In the present study, we performed a genome-wide analysis of the genetic diversity, virulence, and antimicrobial resistance of the largest collection of clinical <jats:italic>C</jats:italic>. <jats:italic>jejuni</jats:italic> and <jats:italic>C</jats:italic>. <jats:italic>coli</jats:italic> strains from Chile available to date (n = 81), collected in 2017–2019 in Santiago, Chile. This culture collection accounts for more than one third of the available genome sequences from South American clinical strains. cgMLST analysis identified high genetic diversity as well as 13 novel STs and alleles in both <jats:italic>C</jats:italic>. <jats:italic>jejuni</jats:italic> and <jats:italic>C</jats:italic>. <jats:italic>coli</jats:italic>. Pangenome and virulome analyses showed a differential distribution of virulence factors, including both plasmid and chromosomally encoded T6SSs and T4SSs. Resistome analysis predicted widespread resistance to fluoroquinolones, but low rates of erythromycin resistance. This study provides valuable genomic and epidemiological data and highlights the need for further genomic epidemiology studies in Chile and other South American countries to better understand molecular epidemiology and antimicrobial resistance of this emerging intestinal pathogen.</jats:p>
Scopus© Citations 23 4
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Pharmacogenetics in Psychiatry: Perceived Value and Opinions in a Chilean Sample of Practitioners
(2021)
UNDURRAGA FOURCADE, JUAN PABLO
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Ignacio Bórquez-Infante
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Nicolás A. Crossley
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Miguel L. Prieto
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REPETTO LISBOA, MARIA GABRIELA
<jats:p>Use of pharmacogenetics (PGx) testing to guide clinical decisions is growing in developed countries. Published guidelines for gene–drug pair analysis are available for prescriptions in psychiatry, but information on their utilization, barriers, and health outcomes in Latin America is limited. As a result, this work aimed at exploring current use, opinions, and perceived obstacles on PGx testing among psychiatrists in Chile, via an online, anonymous survey. Among 123 respondents (5.9% of registered psychiatrists in the country), 16.3% reported ever requesting a PGx test. The vast majority (95%) of tests were ordered by clinicians practicing in the Metropolitan Region of Santiago. Having more than 20 years in practice was positively associated with prior use of PGx (p 0.02, OR 3.74 (1.19–11.80)), while working in the public health system was negatively associated (OR 0.30 (0.10–0.83)). Perceived barriers to local implementation included insufficient evidence of clinical utility, limited clinicians’ knowledge on PGx and on test availability, and health systems’ issues, such as costs and reimbursement. Despite the recognition of these barriers, 80% of respondents asserted that it is likely that they will incorporate PGx tests in their practice in the next five years. Given these results, we propose next steps to facilitate implementation such as further research in health outcomes and clinical utility of known and novel clinically actionable variants, growth in local sequencing capabilities, education of clinicians, incorporation of clinical decision support tools, and economic evaluations, all in local context.</jats:p>
1Scopus© Citations 10
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Atovaquone/Proguanil Resistance in an Imported Malaria Case in Chile
(2021)
Stella M. Chenet
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Alan Oyarce
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Jorge Fernandez
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Rafael Tapia-Limonchi
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WEITZEL, THOMAS
<jats:title>ABSTRACT</jats:title><jats:p>In November 2018, we diagnosed a cluster of falciparum malaria cases in three Chilean travelers returning from Nigeria. Two patients were treated with sequential intravenous artesunate plus oral atovaquone/proguanil (AP) and one with oral AP. The third patient, a 23-year-old man, presented with fever on day 29 after oral AP treatment and was diagnosed with recrudescent falciparum malaria. The patient was then treated with oral mefloquine, followed by clinical recovery and resolution of parasitemia. Analysis of day 0 and follow-up blood samples, collected on days 9, 29, 34, 64, and 83, revealed that parasitemia had initially decreased but then increased on day 29. Sequencing confirmed Tyr268Cys mutation in the <jats:italic>cytochrome b</jats:italic> gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and <jats:italic>P. falciparum dihydrofolate reductase</jats:italic> mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples. Molecular characterization of imported malaria contributes to clinical management in non-endemic countries, helps ascertain the appropriateness of antimalarial treatment policies, and contributes to the reporting of drug resistance patterns from endemic regions.</jats:p>
4Scopus© Citations 5
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Lifestyle Habits and Health Indicators in Migrants and Native Schoolchildren in Chile
(2021)
Mónica Suárez-Reyes
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Daiana Quintiliano-Scarpelli
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PINHEIRO FERNANDES, ANNA CHRISTINA
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Cristian Cofré-Bolados
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Tito Pizarro
<jats:p>In Chile, the migrant population has increased in the last years. Migrants adopt behaviors of this new culture, which can have an effect on their health. Contradictory results regarding differences between migrant and native children have been reported. The aim of this study was to explore the associations between nationality with health indicator and lifestyle habits among schoolchildren in Chile. A cross-sectional and observational study with a non-probabilistic sample was conducted in 1033 children (86.4% Chilean and 13.6% migrant) from second to fourth grade of seven public schools from low-income municipalities from the Metropolitan Region, Chile. Anthropometric measurements (weight, height, waist circumference, triceps and subscapular folds), handgrip strength, and standing long jump measurements, physical activity, self-esteem and food guidelines accomplishments were determined. Migrant children presented lower body mass index (BMI), Z-BMI, body fat% and waist circumference values; and higher handgrip strength, standing long jump, and more satisfactory compliance with food guidelines than natives (p < 0.05). No significant difference for physical activity and self-esteem was observed. In the adjusted models, migrants presented lower odds for overweight/obesity, risk of abdominal obesity, low handgrip strength and unsatisfactory food guidelines accomplishment in all models (p < 0.05). The nutritional and muscular fitness of migrant children was better than that of the Chilean ones.</jats:p>
1Scopus© Citations 8 1
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Compliance with the smoking ban in enclosed, semiopen and open areas of workplaces and public places in Chile
(2020)
PERUGA URREA, ARMANDO
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Xaviera Molina
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DELGADO BECERRA, OROZIMBA IRIS
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MATUTE WILLEMSEM, MARIA ISABEL
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OLEA NORMANDIN, ANDREA MARIA
<jats:sec><jats:title>Objective</jats:title><jats:p>To assess the national level of compliance with the Chilean comprehensive smoke-free legislation by observing healthcare facilities, education centres, government offices, hospitality venues and private workplaces, by type of area within workplaces and public places: enclosed, semiopen and open.</jats:p></jats:sec><jats:sec><jats:title>Methodology</jats:title><jats:p>In this cross-sectional observational study, we studied a national representative sample of 3253 venues obtained through a two-stage cluster sampling design. First, 57 municipalities were randomly selected, proportionally to the total number of venues of interest. Second, within each selected municipality, a maximum of 12 venues of each sector was selected systematically from a list of existing sites. We determined the non-compliance level by estimating the percentage of the visited venues where smoking was observed or suspected in banned areas of the premises.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Smoking or suspicion thereof was not observed in any enclosed area of any establishment. However, smoking violations were observed in semiopen areas ranging from less than 0.5% of schools and healthcare centres to around 10% of hospitality venues or 23.0% of higher education centres. Smoking violations were also observed in outdoor areas of 6.7% and 1.6% of the health centres and schools, respectively.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>The stark contrast in compliance with the smoking ban between the enclosed areas and the semiopen areas may be a consequence of the complex definition of semiopen areas in the regulations. The study also reflects the need to improve the overall enforcement of the smoke-free law, particularly in universities and hospitality venues.</jats:p></jats:sec>
Scopus© Citations 6 1
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Epidemiology of Parkinson’s Disease in Chile
(2021)
VIAL UNDURRAGA, FELIPE AGUSTIN
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DELGADO BECERRA, OROZIMBA IRIS
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Francisca Canal
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IDIAQUEZ RIOS, JUAN FRANCISCO
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Pedro Chana-Cuevas
<jats:p>Introduction: Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. There is no epidemiological description of PD in Chile and not many descriptions in Latin America. This study aims to describe the incidence and prevalence of PD in Chile. Methods: The study group was the population on the public health system in Chile between 2010 and 2018 that were registered in the GES system as having PD. Crude and standardized prevalence and incidence were calculated with a 95% confidence interval. Results: 33,345 patients were found in the register as confirmed cases with PD. The crude incidence in 2018 was 23.7/100,000; the crude prevalence in 2018 was 160.7/100,000. The male-to-female ratio was 1.03. Conclusion: The prevalence and incidence observed in the Chilean population are consistent with studies from other countries. </jats:p>
Scopus© Citations 8 114

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