RESUMO
The Drug-Gene Interaction Database (DGIdb, https://dgidb.org) is a publicly accessible resource that aggregates genes or gene products, drugs and drug-gene interaction records to drive hypothesis generation and discovery for clinicians and researchers. DGIdb 5.0 is the latest release and includes substantial architectural and functional updates to support integration into clinical and drug discovery pipelines. The DGIdb service architecture has been split into separate client and server applications, enabling consistent data access for users of both the application programming interface (API) and web interface. The new interface was developed in ReactJS, and includes dynamic visualizations and consistency in the display of user interface elements. A GraphQL API has been added to support customizable queries for all drugs, genes, annotations and associated data. Updated documentation provides users with example queries and detailed usage instructions for these new features. In addition, six sources have been added and many existing sources have been updated. Newly added sources include ChemIDplus, HemOnc, NCIt (National Cancer Institute Thesaurus), Drugs@FDA, HGNC (HUGO Gene Nomenclature Committee) and RxNorm. These new sources have been incorporated into DGIdb to provide additional records and enhance annotations of regulatory approval status for therapeutics. Methods for grouping drugs and genes have been expanded upon and developed as independent modular normalizers during import. The updates to these sources and grouping methods have resulted in an improvement in FAIR (findability, accessibility, interoperability and reusability) data representation in DGIdb.
Assuntos
Medicina de Precisão , Humanos , Bases de Dados de Produtos Farmacêuticos , Descoberta de Drogas , Internet , Interface Usuário-Computador , Vocabulário ControladoRESUMO
Extensive scientific evidence consistently demonstrates the clinical validity and utility of HLA-B*15:02 pre-screening in averting severe cutaneous adverse reactions (SCARs), namely Stevens-Johnson syndrome and toxic epidermal necrolysis, associated with carbamazepine or oxcarbazepine usage. Current practice guidelines and drug labeling actively advocate for pharmacogenetic pre-screening before initiating these antiepileptic drugs (AED), with particular emphasis on patients of Asian descent. However, there is a potential need to strengthen compliance with these recommendations. This retrospective study aimed to describe the pharmacogenetic pre-screening, documentation, and SCARs incidence for patients of Asian ancestry initiated on carbamazepine or oxcarbazepine at a large Northeastern USA healthcare system. Between 1 July 2016 and August 1, 2021, 27 patients with documented Asian heritage in the electronic health record (EHR) were included. The overall rate of HLA-B*15:02 pre-screening before carbamazepine or oxcarbazepine initiation was 4%. None who underwent pharmacogenetic pre-screening carried the associated HLA-B risk allele, and no SCARs were reported. Notably, pharmacogenetic results were not discretely entered into the EHR, and the results were only found as attached documents in the miscellaneous section of the EHR. There remains a significant opportunity for improving HLA-B*15:02 pre-screening for patients starting carbamazepine and oxcarbazepine to prevent SCARs in the USA.
Assuntos
Anticonvulsivantes , Síndrome de Stevens-Johnson , Humanos , Anticonvulsivantes/efeitos adversos , Oxcarbazepina/efeitos adversos , Farmacogenética/métodos , Estudos Retrospectivos , Cicatriz/induzido quimicamente , Cicatriz/complicações , Carbamazepina/efeitos adversos , Antígenos HLA-B/genética , Síndrome de Stevens-Johnson/genética , Síndrome de Stevens-Johnson/prevenção & controle , BenzodiazepinasRESUMO
PURPOSE: Combinatorial pharmacogenetic (PGx) panels intended to aid psychiatric prescribing are available to clinicians. Here, we evaluated the documentation of PGx panel results and subsequent prescribing patterns within a tertiary health care system. METHODS: We performed a query of psychiatry service note text in our electronic health record using 71 predefined PGx terms. Patients who underwent combinatorial PGx testing were identified, and documentation of test results was analyzed. Prescription data following testing were examined for the frequency of prescriptions influenced by genes on the panel along with the medical specialties involved. RESULTS: A total of 341 patients received combinatorial PGx testing, and documentation of results was found to be absent or incomplete for 198 patients (58%). The predominant method of documentation was through portable document formats uploaded to the electronic health record's "Media" section. Among patients with at least 1 year of follow-up, a large majority (194/228, 85%) received orders for medications affected by the tested genes, including 132 of 228 (58%) patients receiving at least 1 non-psychiatric medication influenced by the test results. CONCLUSION: Results from combinatorial PGx testing were poorly documented. Medications affected by these results were often prescribed after testing, highlighting the need for discrete results and clinical decision support.
Assuntos
Sistemas de Apoio a Decisões Clínicas , Medicina , Humanos , Farmacogenética/métodos , Prescrições de Medicamentos , Registros Eletrônicos de SaúdeRESUMO
BACKGROUND: Lung cancer is the leading cause of cancer-related mortality in the United States and is projected to account for 127,070 deaths in 2023. Although the lung cancer mortality rate has been decreasing over the last decade, demographic disparities in mortality still exist. We sought to determine the impact of demographic factors on lung cancer mortality and trends in the United States. PATIENTS AND METHODS: We queried the Centers for Disease Control and Prevention (CDC) database for mortality statistics with an underlying cause of death of lung and bronchus cancer from 1999 through 2020. Age-adjusted mortality rates (AAMR) were calculated per 100,000 people. We assessed the AAMR by demographic variables, including race, geographic density, sex, age, and US census region. Temporal trends were evaluated using Joinpoint regression software, and average annual percent change (APC) was calculated. RESULTS: From 1999 through 2020, lung cancer led to 3,380,830 deaths. The AAMR decreased by 55.1 to 31.8, with an associated average APC of -2.6%. In 1999, men had an AAMR almost twice as high as women, but these differences became less pronounced over time. Rural populations experienced the highest AAMR and the slowest rate of decrease compared with urban populations, who experienced the lowest AAMR and fastest decrease. Non-Hispanic Black individuals experienced the highest AAMR, with an annual decrease of -3.0%. The West experienced the fastest decrease at -3.1% annually, whereas the Midwest experienced the slowest decrease at -2.0% annually. CONCLUSIONS: Although the mortality rate of lung cancer has been decreasing since 1999, not all demographic groups have experienced the same rates of decrease, and disparities in outcomes are still prevalent. Vulnerable subgroups need targeted interventions, such as the incorporation of patient navigators, improved screening chest CT scan access and follow-up, and telehealth expansion, which will improve the likelihood of earlier-stage diagnoses and the potential for curative treatments.
RESUMO
Mesothelioma is a rare cancer that originates from the mesothelial surfaces of the pleura and other sites, and is estimated to occur in approximately 3,500 people in the United States annually. Pleural mesothelioma is the most common type and represents approximately 85% of these cases. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pleural mesothelioma. These NCCN Guidelines Insights highlight significant updates to the NCCN Guidelines for Mesothelioma: Pleural, including revised guidance on disease classification and systemic therapy options.
Assuntos
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Humanos , Pleura , Mesotelioma/diagnóstico , Mesotelioma/terapia , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/terapiaRESUMO
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance for relapse, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable molecular biomarkers.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Terapia de Alvo Molecular/métodos , Estadiamento de NeoplasiasRESUMO
Mesothelioma is a rare cancer originating in mesothelial surfaces of the peritoneum, pleura, and other sites. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on peritoneal mesothelioma (PeM). The NCCN Guidelines for PeM provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated PeM. The diagnosis of PeM may be delayed because PeM mimics other diseases and conditions and because the disease is so rare. The pathology section was recently updated to include new information about markers used to identify mesothelioma, which is difficult to diagnose. The term "malignant" is no longer used to classify mesotheliomas, because all mesotheliomas are now defined as malignant.
Assuntos
Mesotelioma Maligno , Mesotelioma , Humanos , Oncologia , Mesotelioma/diagnóstico , Mesotelioma/terapia , PeritônioRESUMO
The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for management of disease in patients with NSCLC. These NCCN Guidelines Insights focus on neoadjuvant and adjuvant (also known as perioperative) systemic therapy options for eligible patients with resectable NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Terapia NeoadjuvanteRESUMO
PURPOSE OF REVIEW: Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality. The electronic health record (EHR) provides an opportunity to monitor ADRs, mainly through the utilization of drug allergy data and pharmacogenomics. This review article explores the current use of the EHR for ADR monitoring and highlights areas that require improvement. RECENT FINDINGS: Recent research has identified several issues with using EHR for ADR monitoring. These include the lack of standardization between EHR systems, specificity in data entry options, incomplete and inaccurate documentation, and alert fatigue. These issues can limit the effectiveness of ADR monitoring and compromise patient safety. The EHR has great potential for monitoring ADR but needs significant updates to improve patient safety and optimize care. Future research should concentrate on developing standardized documentation and clinical decision support systems within EHRs. Healthcare professionals should also be educated on the significance of accurate and complete ADR monitoring.
Assuntos
Hipersensibilidade a Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Registros Eletrônicos de Saúde , Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Hipersensibilidade a Drogas/diagnóstico , Pessoal de SaúdeRESUMO
The reaction chemistry of 1,1,3,3-tetramethyldisilazane (TMDSZ) in catalytic chemical vapor deposition (Cat-CVD), including its primary decomposition on a heated W filament and secondary gas-phase reactions in a Cat-CVD reactor, was studied using 10.5 eV vacuum ultraviolet single-photon ionization and/or laser-induced electron ionization in tandem with time-of-flight mass spectrometry. It has been demonstrated that TMDSZ initially breaks down to form various species, including methyl radical (â¢CH3), ammonia (NH3), and 1,1-dimethylsilanimine (DMSA). The activation energies (Ea) for the formation of â¢CH3 and NH3 were determined to be 61.2 ± 1.0 and 42.1 ± 0.9 kJ mol-1, respectively, in the temperature range of 1400-2000 and 900-2400 °C. It was found that the formation of DMSA may have two different contributing routes, i.e., a concerted one (Ea = 33.6 ± 2.3 kJ mol-1) at lower temperatures of 900-1500 °C and a stepwise one (Ea = 155.0 ± 7.8 kJ mol-1) at higher temperatures of 2100-2400 °C. The secondary gas-phase reactions occurring in the Cat-CVD reactor environment were found to stem from two competing processes. The first one, free-radical short-chain reactions initiated by â¢CH3 formation and propagated by H abstraction reactions, is the dominating chemical process, producing many high-mass stable alkyl-substituted or silyl-substituted disilazane or trisilazane products via radical recombination reactions. Head-to-tail cycloaddition of unstable DMSA is the second contributing chemical process, which forms cyclodisilazane species. In addition, evidence was found for the conversion of NH3 into H2 and N2 in the Cat-CVD reactor.
RESUMO
BACKGROUND: Evidence suggests that public, and some professional, understandings of palliative care are limited to care provided immediately before death, which contrasts palliative care's scope as care provided across a range of illness stages. OBJECTIVE: To examine how clinicians manage patients' understandings of palliative care during initial consultations. DESIGN: Initial palliative care consultations were video-recorded and analysed using conversation analytic methods. SETTING/PARTICIPANTS: Consultations were recorded in a specialist palliative care outpatient unit within an Australian public hospital. Participants included 20 newly referred patients and their families, and three palliative care clinicians. RESULTS: During initial consultations, it was observed that specialist palliative care clinicians frequently managed the possibility that patients may understand palliative care as limited to care provided immediately before death. Clinicians used recurrent practices that seemed designed to pre-empt and contradict patients' possible narrow understandings. When discussing the palliative care inpatient unit, clinicians recurrently explained inpatient care could include active treatment and referred to the possibility of being discharged. These practices contradict possible understandings that future admission to the inpatient unit would be solely for care immediately before death. DISCUSSION: The findings demonstrate that palliative care clinicians are aware of possible narrow understandings of their discipline among members of the public. The practices identified show how clinicians pre-emptively manage these understandings to patients newly referred to palliative care. CONCLUSIONS: These findings highlight scope for greater partnership with teams referring patients to palliative care, to assist patients in understanding the range of reasons for their referral. PATIENT OR PUBLIC CONTRIBUTION: The observational method of conversation analysis provides direct insight into matters that are relevant for patients, as raised in their consultations with clinicians. This direct evidence enables analysis of their lived experience, as it occurs, and grounds analysis in observable details of participants' conduct, rather than interpretations of subjective experiences. The patients' contributions, therefore, were to allow observation into their initial palliative care consultations.
RESUMO
BACKGROUND: Biosimilars are of increasing significance to pharmacy practice, with the potential to improve patient access to biologic therapies and help reduce overall health care costs. OBJECTIVES: This web-based survey assessed pharmacists' understanding of biosimilars, including interchangeability. METHODS: WebMD LLC fielded a survey including true or false and Likert-type questions to the Medscape pharmacist and certified pharmacy technician (CPT) panel in March 2021. Those practicing in community, home care or infusion, hospital or health system, managed care, outpatient, or specialty pharmacy settings and currently providing prescription services, or formulary or benefit management related to biologic products were included, to a quota of 500 responses. Results were analyzed descriptively. RESULTS: Data are reported for 507 of 992 respondents (265 did not meet eligibility criteria, 220 responded after the survey closed), including 498 pharmacists and 9 CPTs. These respondents worked in a community setting (66%), outpatient or ambulatory or other setting (16%), hospital or health system setting (14%), or managed care (5%). Overall, 87% and 91% of respondents knew that the biosimilar had equivalent efficacy and safety, respectively, to its reference product. Only 20% understood that a pharmacist can substitute a Food and Drug Administration-approved interchangeable without approval of the prescriber. However, 53% responded that they felt it was appropriate for a pharmacist to dispense an interchangeable in place of its reference product without authorization from the prescriber if consistent with state law; a numerically smaller proportion of community pharmacists understood this concept than the other groups (50% vs. 54%-61%). Only 11% of respondents knew that no biosimilars were designated as interchangeable at the time of the survey, with a numerically greater proportion of managed care pharmacists showing awareness than other groups. Slightly more than 50% of respondents felt that they were moderately or very comfortable in responding to patients' biosimilar questions. CONCLUSION: Gaps remain in pharmacists' understanding and comfort with key concepts about biosimilar products, including interchangeability, suggesting the need for further education.
Assuntos
Medicamentos Biossimilares , Assistência Farmacêutica , Farmácia , Humanos , Medicamentos Biossimilares/uso terapêutico , Farmacêuticos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Extubation to non-invasive ventilation (NIV) has been investigated as a strategy to wean critically ill adults from invasive ventilation and reduce ventilator-related complications. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, proceedings of four conferences and bibliographies (to June 2020) for randomised and quasi-randomised trials that compared extubation with immediate application of NIV to continued invasive weaning in intubated adults and reported mortality (primary outcome) or other outcomes. Two reviewers independently screened citations, assessed trial quality and abstracted data. RESULTS: We identified 28 trials, of moderate-to-good quality, involving 2066 patients, 44.6% with chronic obstructive pulmonary disease (COPD). Non-invasive weaning significantly reduced mortality (risk ratio (RR) 0.57, 95% CI 0.44 to 0.74; high quality), weaning failures (RR 0.59, 95% CI 0.43 to 0.81; high quality), pneumonia (RR 0.30, 95% CI 0.22 to 0.41; high quality), intensive care unit (ICU) (mean difference (MD) -4.62 days, 95% CI -5.91 to -3.34) and hospital stay (MD -6.29 days, 95% CI -8.90 to -3.68). Non-invasive weaning also significantly reduced the total duration of ventilation, duration of invasive ventilation and duration of ventilation related to weaning (MD -0.57, 95% CI -1.08 to -0.07) and tracheostomy rate. Mortality, pneumonia, reintubation and ICU stay were significantly lower in trials enrolling COPD (vs mixed) populations. CONCLUSION: Non-invasive weaning significantly reduced mortality, pneumonia and the duration of ventilation related to weaning, particularly in patients with COPD. Beneficial effects are less clear (or more careful patient selection is required) in non-COPD patients. PROSPERO REGISTRATION NUMBER: CRD42020201402.
Assuntos
Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica , Adulto , Estado Terminal/terapia , Humanos , Unidades de Terapia Intensiva , Doença Pulmonar Obstrutiva Crônica/terapia , Respiração Artificial , Desmame do RespiradorRESUMO
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Oncologia , Recidiva Local de NeoplasiaRESUMO
The gas-phase decomposition kinetics and thermochemistry of 1,1,1,3,3,3-hexamethyldisilazane (HMDSZ) and 1,1,3,3-tetramethyldisilazane (TMDSZ), two potential single-source precursors for the chemical vapor deposition of silicon carbonitride thin films, were systematically investigated using ab initio calculations at the B3LYP/6-311++G(d,p)//CCSD(T)/6-311++G(d,p) level of theory. Both concerted and stepwise decomposition routes for each molecule were examined, allowing for a comparison of the reactions involving the cleavages of common bonds of Si-C, Si-N, and N-H for the two molecules. A new set of reaction pathways open to TMDSZ due to the presence of a Si-H bond was also explored. It was found that all three bonds of Si-N, Si-C, and N-H could be broken more easily in TMDSZ than HMDSZ. Both HMDSZ and TMDSZ are capable of producing silene and silanimine species upon decomposition. In fact, the most kinetically and thermodynamically favorable pathways fall in the formation of these species. The concerted formation of 1-dimethylsilylaminosilene via the elimination of methane from TMDSZ is the most kinetically and thermodynamically favorable route between the two molecules with an activation barrier (ΔH0⧧) of 48.5 kcal mol-1 and reaction enthalpy (ΔH0) of 11.6 kcal mol-1, respectively. These values are lower than the corresponding lowest values in HMDSZ of ΔH0⧧ = 66.4 kcal mol-1 for the concerted production of 1,1-dimethylsilene and trimethylsilylamine and ΔH0 = 41.7 kcal mol-1 for the formation of CH4 and N-trimethylsilyl-1,1-dimethylsilanimine. Overall, this work has provided insights into the reactivity of the two molecules. It has been shown that TMDSZ is more reactive than its analog HMDSZ due to the presence of the Si-H bonds and reduced steric hindrance.
RESUMO
Background: Pharmacy standing order policies allow pharmacists to dispense naloxone, thereby increasing access to naloxone. Objectives: To describe pharmacy standing order participation and associations of pharmacy and community characteristics that predict naloxone availability and dispensing across eight counties in Michigan. Methods: We conducted a telephone survey of 662 standing order pharmacies with a response rate of 81% (n = 539). Pharmacies were linked with census tract-level demographics, overdose fatality rates, and dispensing data. County maps were created to visualize pharmacy locations relative to fatality rates. Regression models analyzed associations between pharmacy type, neighborhood characteristics, fatality rates, and these outcomes: naloxone availability, having ever dispensed naloxone, and counts of naloxone dispensed. Results: The prevalence of standing order pharmacies was 54% (n = 662/1231). Maps revealed areas with higher fatality rates had fewer pharmacies participating in the standing order or lacked any pharmacy access. Among standing order pharmacies surveyed, 85% (n = 458/539) had naloxone available and 82% had ever dispensed (n = 333/406). The mean out-of-pocket cost of Narcan® was $127.77 (SD: 23.93). National chains were more likely than regional chains to stock naloxone (AOR = 3.75, 95%CI = 1.77, 7.93) and to have ever dispensed naloxone (AOR 3.02, 95%CI = 1.21,7.57). Higher volume of naloxone dispensed was associated in neighborhoods with greater proportions of public health insurance (IRR = 1.38, 95%CI = 1.21, 1.58) and populations under 44 years old (IRR = 1.24, 95%CI = 1.04, 1.48). There was no association with neighborhood overdose fatality rates or race in regression models. Conclusion: As deaths from the opioid epidemic continue to escalate, efforts to expand naloxone access through greater standing order pharmacy participation are warranted.
Assuntos
Overdose de Drogas , Transtornos Relacionados ao Uso de Opioides , Farmácias , Farmácia , Prescrições Permanentes , Adulto , Overdose de Drogas/tratamento farmacológico , Humanos , Michigan , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/complicações , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológicoRESUMO
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Imunoterapia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapiaRESUMO
The gas-phase decomposition kinetics and thermochemistry of bis(dimethylamino)silane (BDMAS), a potential precursor in the chemical vapor deposition of silicon nitride and silicon carbonitride thin films, were systematically studied using ab initio calculations at the CCSD(T)/6-311 + G(2d,p)//B3LYP/6-311 + + G(d,p) level of theory. The reaction routes were mapped out, exploring both the concerted and stepwise reactions in three different zones with the initial cleavage of Si-N, N-Me (Me = CH3), and Si-H, respectively. It was found that the energy needed to break N-Me at 80.6 kcal·mol-1 is lower than the ones for Si-N and Si-H, both at 87.4 kcal·mol-1. When compared with tris(dimethylamino)silane (TrDMAS), it has been shown that the three bonds of N-Me, Si-N, and Si-H in BDMAS can be ruptured more easily, suggesting that BDMAS could be a more efficient precursor gas than TrDMAS. Upon decomposition, BDMAS tends to form methyleneimine and silanimine species, where four methyleneimine species and three silanimine species were produced. From the investigation of the effect of temperature on the kinetic and thermodynamic competition of different decomposition pathways, it has been demonstrated that the concerted formation of N-dimethylaminosilyl methyleneimine (H2CâN-SiH2NMe2) by the elimination of CH4 from BDMAS is the most kinetically and thermodynamically favored pathway in the whole temperature range from 0 K (ΔH0 = 62.7 kcal·mol-1 and ΔH0 = 7.7 kcal·mol-1) up to 2673 K. In addition, lower temperatures favor the production of N-methyl methyleneimime (H2CâNMe), whereas high temperatures promote the formation of N-methylsilanimine (H2Si = NMe) and 1-dimethylamino-N-methylsilanimine (Me2NSi = NMe).
RESUMO
BACKGROUND: Nearly 300 medications contain pharmacogenomic information in their labeling approved by the U.S. Food and Drug Administration. As this number continues to grow, community pharmacists will be called on to use available pharmacogenomic data at the point of dispensing. OBJECTIVE: This qualitative study aimed to describe how pharmacists envision the integration of pharmacogenomic data into the current workflows of community pharmacy practice. METHODS: Community pharmacists from a regional supermarket chain pharmacy in the greater Pittsburgh area were interviewed using a semistructured interview guide. Participating pharmacists were presented with 3 clinical scenarios, followed by questions, to gain insight into how they envisioned the integration of pharmacogenomic data into community pharmacy workflow. The interview transcriptions were transcribed and coded. The content was analyzed to deduce the final themes. Supporting quotes were selected to illustrate each theme. RESULTS: Ten community pharmacists from 3 different pharmacy locations participated in the study. A thematic analysis produced 6 themes: (1) integrating pharmacogenomic data into the dispensing software, (2) receiving an alert for pharmacogenomic information within the dispensing software, (3) accessing pharmacogenomic clinical guidelines to guide drug-decision-making, (4) contacting the prescriber by adding a task to the call queue, (5) placing a mandatory counseling alert on medications that were adjusted using pharmacogenomic data, and (6) counseling the patient on the first refill of a medication that was adjusted using pharmacogenomic data. CONCLUSION: This study describes how pharmacists envisioned the integration of pharmacogenomic data into community pharmacy workflow. The participants sought the integration of pharmacogenomic data into existing dispensing software, alerts for actionable prescribing changes using patient-specific pharmacogenomic data when available, and access to clinical decision support. In addition, the participants preferred to engage prescribers and receive alerts to counsel patients at prescription pick-up. These findings are key to integrating pharmacogenomic data into community pharmacy practice.
Assuntos
Serviços Comunitários de Farmácia , Farmácias , Aconselhamento , Humanos , Farmacêuticos , FarmacogenéticaRESUMO
BACKGROUND: The selection of later-line treatment for older patients with AJCC (version 7) stage IV non-small cell lung cancer (NSCLC) remains controversial. Nanoparticle albumin-bound (nab)-paclitaxel is approved with carboplatin for the first-line treatment of patients with NSCLC and subgroup analysis of phase 3 data has suggested superior survival in older patients. METHODS: The authors conducted a phase 2 study of nab-paclitaxel in 42 patients aged ≥70 years who had been treated previously with a platinum doublet regimen; patients also could have received a PD-1 inhibitor. The primary endpoint of the current study was grade 3 to 5 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). In addition to response rate, progression-free survival (PFS), and overall survival (OS), geriatric assessments also were performed before and during treatment, associations between baseline sarcopenia and outcomes were explored, and changes in T lymphocyte p16 before and during treatment were measured. The authors also performed a retrospective subgroup analysis of 19 older patients who were treated with nab-paclitaxel as part of a larger, randomized, phase 2 study; data were not combined. RESULTS: The rate of grade 3 to 5 toxicities was 33.7%. The most common grade 3 to 5 toxicities were decreased white blood cell count (11.9%), neutropenia (9.5%), and fatigue (11.9%). The response rate was 34.2% (2.6% complete response rate and 31.6% partial response rate). The median PFS was 5.2 months and the median OS was 9.3 months. Adverse prognostic factors were common: 42% of patients were frail and 39% of patients were prefrail, whereas 21% had an Eastern Cooperative Oncology Group performance status of 2 and 27% were sarcopenic. Only frailty was found to be predictive of inferior survival. A subgroup analysis of 19 older patients treated with nab-paclitaxel alone in a prior trial demonstrated a response rate of 15.8%, a PFS of 4.2 months, and an OS of 13.6 months. CONCLUSIONS: Fit and prefrail older patients with stage IV NSCLC should be considered for treatment with nab-paclitaxel after disease progression with doublet chemotherapy.