Economic burden of adverse drug reactions and potential for pharmacogenomic testing in Singaporean adults.

Adverse drug reactions (ADRs) contribute to hospitalization but data on its economic burden is scant. Pre-emptive pharmacogenetic (PGx) testing can potentially reduce ADRs and its associated costs. The objectives of this study were to quantify the economic burden of ADRs and to estimate the breakeven cost of pre-emptive PGx testing in Singapore. We collected itemized costs for 1000 random non-elective hospitalizations of adults admitted to a tertiary-care general hospital in Singapore. The presence of ADRs at admission and their clinical characteristics were reported previously. The economic burden of ADRs was assessed from two perspectives: (1) Total cost and (2) incremental costs. The breakeven cost of PGx testing was estimated by dividing avoidable hospitalization costs for ADRs due to selected drugs by the number of patients taking those drugs. The total cost of 81 admissions caused by ADRs was US$570,404. Costs were significantly higher for bleeding/elevated international normalized ratio (US$9906 vs. US$2251, p = 6.58 × 10-3) compared to other ADRs, and for drugs acting on the blood coagulation system (US$9884 vs. US$2229, p = 4.41 × 10-3) compared to other drug classes. There were higher incremental laboratory costs due to ADRs causing or being present at admission. The estimated breakeven cost of a pre-emptive PGx test for patients taking warfarin, clopidogrel, chemotherapeutic and neuropsychiatric drugs was US$114 per patient. These results suggest that future studies designed to directly measure the clinical and cost impact of a pre-emptive genotyping program will help inform clinical practice and health policy decisions

A qualitative study of physician perspectives on adaptation to electronic health records

BACKGROUND: Electronic Health Records (EHRs) have the potential to improve many aspects of care and their use has increased in the last decade. Because of this, acceptance and adoption of EHRs is less of a concern than adaptation to use. To understand this issue more deeply, we conducted a qualitative study of physician perspectives on EHR use to identify factors that facilitate adaptation. METHODS: We conducted semi-structured interviews with 9 physicians across a range of inpatient disciplines at a large Academic Medical Center. Interviews were conducted by phone, lasting approximately 30 min, and were transcribed verbatim for analysis. We utilized inductive and deductive methods in our analysis. RESULTS: We identified 4 major themes related to EHR adaptation: impact of EHR changes on physicians, how physicians managed these changes, factors that facilitated adaptation to using the EHR and adapting to using the EHR in the patient encounter. Within these themes, physicians felt that a positive mindset toward change, providing upgrade training that was tailored to their role, and the opportunity to learn from colleagues were important facilitators of adaptation. CONCLUSIONS: As EHR use moves beyond implementation, physicians continue to be required to adapt to the technology and to its frequent changes. Our study provides actionable findings that allow healthcare systems to focus on factors that facilitate the adaptation process for physicians

Acute flaccid paralysis with anterior myelitis - California, June 2012-June 2014.

In August 2012, the California Department of Public Health (CDPH) was contacted by a San Francisco Bay area clinician who requested poliovirus testing for an unvaccinated man aged 29 years with acute flaccid paralysis (AFP) associated with anterior myelitis (i.e., evidence of inflammation of the spinal cord involving the grey matter including anterior horn cell bodies) and no history of international travel during the month before symptom onset. Within 2 weeks, CDPH had received reports of two additional cases of AFP with anterior myelitis of unknown etiology. Testing at CDPH's Viral and Rickettsial Disease Laboratory for stool, nasopharyngeal swab, and cerebrospinal fluid (CSF) did not detect the presence of an enterovirus (EV), the genus of the family Picornaviridae that includes poliovirus. Additional laboratory testing for infectious diseases conducted at the CDPH Viral and Rickettsial Disease Laboratory did not identify a causative agent to explain the observed clinical syndrome reported among the patients. To identify other cases of AFP with anterior myelitis and elucidate possible common etiologies, CDPH posted alerts in official communications for California local health departments during December 2012, July 2013, and February 2014. Reports of cases of neurologic illness received by CDPH were investigated throughout this period, and clinicians were encouraged to submit clinical samples for testing. A total of 23 cases of AFP with anterior myelitis of unknown etiology were identified. Epidemiologic and laboratory investigation did not identify poliovirus infection as a possible cause for the observed cases. No common etiology was identified to explain the reported cases, although EV-D68 was identified in upper respiratory tract specimens of two patients. EV infection, including poliovirus infection, should be considered in the differential diagnosis in cases of AFP with anterior myelitis and testing performed per CDC guidelines

[Smoking and alcohol use among Chilean teenagers aged 10 to 14 years].

BACKGROUND: Smoking and alcohol use are risky behaviors that can start early in life. AIM: To determine the lifetime prevalence of tobacco and alcohol use in adolescents aged 10 to 14 years and related factors. SUBJECTS AND METHODS: A survey about smoking and alcohol use was answered by 1,392 teenagers aged 10 to 14 years (46% women) from seven schools in a small city near Santiago. Personal, family, and school factors were evaluated through self-report scales. Smoking and alcohol use, as dichotomous dependent variables, were defined as having consumed any of these substances throughout life. Prevalence was calculated as percentages with 95% confidence intervals. Association analyses were conducted using multivariable logistic regression models. RESULTS: Six and eleven percent of participants reported having smoked and used alcohol in their life, respectively. Smoking was associated with age, having behavioral problems, mothers� smoking, perceiving that parents had drug problems, and not living with both parents. Alcohol use was mainly associated with age, having behavioral problems, perceiving that other students consumed drugs, alcohol use by both parents, and perceiving a lack of family support. CONCLUSIONS: Tobacco and alcohol use is highly prevalent in adolescents aged 10-14 years. There were common risk factors for smoking and alcohol use such as age and having behavioral problems, while other factors were more specific such as mothers� smoking, or parental alcohol use

[Factors associated with health promoting behaviors among Chilean adolescents].

BACKGROUND: Health-promoting behaviors are important to prevent diseases and prolong life in the population. People develop these behaviors throughout life. However, better benefits for health are obtained with an early development. AIM: To determine the prevalence of health-promoting behaviors among early adolescents and its associated factors. MATERIAL AND METHODS: Cross-sectional survey performed in 1,465 students of high, medium and low socio-economic status, attending fifth to eighth grades of schools located in a small Chilean city. Participants answered a questionnaire that gathered information about frequency of health-promoting behaviors such as health responsibility and nutrition, physical exercise and stress management, life appreciation, social support and different personal, school and familial factors. RESULTS: A higher frequency of health-promoting behaviors was associated with better academic achievement, better school commitment, and higher perception of school membership. It also was associated with a better perception of health status and a higher conformity with physical appearance. CONCLUSIONS: Health promoting behaviors in these children are related to a better academic achievement and a higher integration with school environment

Nanoporous organosilica membrane for water desalination: theoretical study on the water transport

An unconventional nanoporous organosilica membrane has been tested in a vacuum membrane distillation (MD) process for water desalination. We propose a modified approach to understand the transport mechanism of water molecules through the nanopores of this membrane. The modified approach stems from the fact that the membrane has a hydrophilic surface (contact angle 80% increase in permeation flux if the pore size increased from 2 to 3 nm at 60 degrees C. However, pore wetting is expected if d(p) > 3,4 nm, particularly at low temperatures where the slower evaporation rate promoted greater pore intrusion. Concentration polarization was shown to be negligible which agreed well with experimentally observed water fluxes which remained relatively constant despite feed salinity increasing from 0 to 150 g L-1. Lastly, the membrane hydrophilicity was found to impact on water flux and pore intrusion in a complex relationship with pore size. Ultimately, hydrophilic pores less than 3 urn in diameter offer a good combination of good water flux and minimal water intrusion suggesting that ordered mesoporous organosilica membranes have potential in MD applications. (C) 2015 Elsevier B.V. All rights reserved

Alterations of immune response of non-small lung cancer with azacytidine

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

Plan estratégico 2022-2026 del Hotel Namáti Sauce

El Hotel Namáti Sauce se encuentra ubicado en el departamento San Martín, en el norte del Perú, a 45 minutos de la ciudad de Tarapoto. Se trata de una empresa del sector turismo y el objetivo de este trabajo de investigación es mejorar su utilidad y el posicionamiento de la marca. Asimismo, se espera se consolide como el mejor hotel de cuatro estrellas de la región San Martín, con altos niveles de satisfacción y compromiso con sus huéspedes, colaboradores, comunidad y demás stakeholders, por medio de una gestión responsable, sostenible y eficiente de los recursos que rodean el lugar, más conocido como Laguna Azul. En el trabajo de investigación se aplicó la metodología cuantitativa. Habiendo implementado las estrategias en el hotel, el análisis financiero muestra que los márgenes mejorarán en todos los periodos si se aplica un eficiente aprovechamiento de los recursos

Use of Intravenous Peramivir for Treatment of Severe Influenza A(H1N1)pdm09

Oral antiviral agents to treat influenza are challenging to administer in the intensive care unit (ICU). We describe 57 critically ill patients treated with the investigational intravenous neuraminidase inhibitor drug peramivir for influenza A (H1N1)pdm09 [pH1N1]. Most received late peramivir treatment following clinical deterioration in the ICU on enterically-administered oseltamivir therapy. The median age was 40 years (range 5 months-81 years). Common clinical complications included pneumonia or acute respiratory distress syndrome requiring mechanical ventilation (54; 95%), sepsis requiring vasopressor support (34/53; 64%), acute renal failure requiring hemodialysis (19/53; 36%) and secondary bacterial infection (14; 25%). Over half (29; 51%) died. When comparing the 57 peramivir-treated cases with 1627 critically ill cases who did not receive peramivir, peramivir recipients were more likely to be diagnosed with pneumonia/acute respiratory distress syndrome (p = 0.0002) or sepsis (p = <0.0001), require mechanical ventilation (p = <0.0001) or die (p = <0.0001). The high mortality could be due to the pre-existing clinical severity of cases prior to request for peramivir, but also raises questions about peramivir safety and effectiveness in hospitalized and critically ill patients. The use of peramivir merits further study in randomized controlled trials, or by use of methods such as propensity scoring and matching, to assess clinical effectiveness and safety

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM