RESUMO
Medication nonadherence is a leading cause of graft loss. Adherence monitoring technologies-reminder texts, smart bottles, video-observed ingestion, and digestion-activated signaling pills-may support adherence. However, patient, care partner, and clinician perceptions of these tools are not well studied. We conducted qualitative individual semistructured interviews and focus groups among 97 participants at a single center: kidney and liver transplant recipients 2 weeks to 18 months posttransplant, their care partners, and transplant clinicians. We assessed adherence practices, reactions to monitoring technologies, and opportunities for care integration. One-size-fits-all approaches were deemed infeasible. Interviewees considered text messages the most acceptable approach; live video checks were the least acceptable and raised the most concerns for inconvenience and invasiveness. Digestion-activated signaling technology produced both excitement and apprehension. Patients and care partners generally aligned in perceptions of adherence monitoring integration into clinical care. Key themes were importance of routine, ease of use, leveraging technology for actionable medication changes, and aversion to surveillance. Transplant clinicians similarly considered text messages most acceptable and video checks least acceptable. Clinicians reported that early posttransplant use and real-time adherence tracking with patient feedback may facilitate successful implementation. The study provides initial insights that may inform future adherence technology implementation.
Assuntos
Cuidadores , Transplante de Rim , Humanos , Transplantados , Adesão à MedicaçãoRESUMO
Trypanosome Lytic Factor (TLF) is a primate-specific high-density lipoprotein (HDL) complex that, through the cation channel-forming protein apolipoprotein L-1 (APOL1), provides innate immunity to select kinetoplastid parasites. The immunoprotective effects of TLF have been extensively investigated in the context of its interaction with the extracellular protozoan Trypanosoma brucei brucei, to which it confers sterile immunity. We previously showed that TLF could act against an intracellular pathogen Leishmania, and here we dissected the role of TLF and its synergy with host-immune cells. Leishmania major is transmitted by Phlebotomine sand flies, which deposit the parasite intradermally into mammalian hosts, where neutrophils are the predominant phagocytes recruited to the site of infection. Once in the host, the parasites are phagocytosed and shed their surface glycoconjugates during differentiation to the mammalian-resident amastigote stage. Our data show that mice producing TLF have reduced parasite burdens when infected intradermally with metacyclic promastigotes of L. major, the infective, fly-transmitted stage. This TLF-mediated reduction in parasite burden was lost in neutrophil-depleted mice, suggesting that early recruitment of neutrophils is required for TLF-mediated killing of L. major. In vitro we find that only metacyclic promastigotes co-incubated with TLF in an acidic milieu were lysed. However, amastigotes were not killed by TLF at any pH. These findings correlated with binding experiments, revealing that labeled TLF binds specifically to the surface of metacyclic promastigotes, but not to amastigotes. Metacyclic promastigotes of L. major deficient in the synthesis of surface glycoconjugates LPG and/or PPG (lpg1- and lpg5A-/lpg5B- respectively) whose absence mimics the amastigote surface, were resistant to TLF-mediated lysis. We propose that TLF binds to the outer surface glycoconjugates of metacyclic promastigotes, whereupon it kills the parasite in the acidic phagosome of phagocytes. We hypothesize that resistance to TLF requires shedding of the surface glycoconjugates, which occurs several hours after phagocytosis by immune cells, creating a relatively short-lived but effective window for TLF to act against Leishmania.
Assuntos
Interações Hospedeiro-Parasita/fisiologia , Imunidade Inata , Leishmaniose Cutânea , Lipoproteínas HDL/metabolismo , Animais , Humanos , Leishmania major , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/metabolismo , Leishmaniose Cutânea/patologia , Lipoproteínas HDL/imunologia , CamundongosRESUMO
BACKGROUND: The American Society of Breast Surgeons recommends genetic testing (GT) for all women with breast cancer (BC), but implementation and uptake of GT has not been well-described. METHODS: A retrospective chart review was performed for newly diagnosed BC patients or patients with a newly identified recurrence of BC seen in a multidisciplinary clinic (MDBC) who were offered genetic counseling (GC) and GT. RESULTS: The 138 women attending the MDBC had a median age of 54 years and comprised non-Hispanic whites (46%), Asians (28%), Hispanics (17%), blacks (4%), and other (5%). Of the 105 (76%) patients without prior GT, 100 (95%) accepted GC, with 93 (93%) of these 100 patients undergoing GT. The patients meeting the National Comprehensive Cancer Network (NCCN) guidelines for GT were more likely to undergo GT. Testing was performed with a 67- to 84-gene panel, together with an 8- to 9-gene STAT panel if needed. Among 120 patients with reports available, including 33 patients previously tested, 15 (12%) were positive (1 BLM, 1 BRCA1, 3 BRCA2, 1 BRIP1, 1 CFTR, 1 CHEK2, 1 MUTYH, 1 PALB2, 1 PRSS1, 1 RAD50, 1 RET, and 2 TP53), 44 (37%) were negative, and 61 (51%) had an uncertain variant. The median time to STAT results (n = 50) was 8 days. The STAT results were available before surgery for 47 (98%) of the 48 STAT patients undergoing surgery. CONCLUSIONS: New BC patients attending the MDBC demonstrated high rates of acceptance of GC and GT. The combination of GC and GT can offer timely information critical to patient risk assessment and treatment planning.
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Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico , Estudos Retrospectivos , Testes Genéticos/métodos , Genes BRCA2 , Aconselhamento Genético , Predisposição Genética para Doença , Mutação em Linhagem GerminativaRESUMO
BACKGROUND: Although sentinel lymph node dissection (SLND) after neoadjuvant chemotherapy (NAC) is feasible, axillary management for patients with pretreatment biopsy-proven axillary metastases and who are clinically node-negative after NAC (ycN0) remains unclear. This retrospective study was performed to determine the rate of axillary lymph node recurrence for such patients who had wire-directed (WD) SLND. METHODS: Patients treated with NAC from 2015 to 2020 had axillary nodes evaluated by pretreatment ultrasound. Core biopsies were done on abnormal nodes, and microclips were placed in nodes during biopsy. For patients with biopsy-proven node metastases who received NAC and were ycN0 by clinical exam, WD SLND was done. Patients with negative nodes on frozen section had WD SLND alone; those with positive nodes had WD SLND plus axillary lymph node dissection (ALND). RESULTS: Of 179 patients receiving NAC, 62 were biopsy-proven node-positive pre-NAC and ycN0 post-NAC. Thirty-five (56%) patients were node-negative on frozen section and had WD SLND alone. Twenty-seven (43%) patients had WD SLND + ALND. Forty-seven patients had postoperative regional node irradiation. With median follow-up of 40 months, there were recurrences in 4 (11%) of 35 patients having WD SLND and 5 (19%) of 27 having WD SLND + ALND, but there was only one axillary lymph node recurrence, identified by CT scan. CONCLUSIONS: Axillary node recurrence was very uncommon after WD SLND for patients who had pretreatment biopsy-proven node metastases and were ypN0 after NAC. These patients would be unlikely to derive clinical benefit from the addition of completion ALND to SLND.
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Neoplasias da Mama , Linfonodo Sentinela , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/etiologia , Terapia Neoadjuvante , Estudos Retrospectivos , Excisão de Linfonodo/efeitos adversos , Linfonodos/patologia , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela , Axila/patologia , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologiaRESUMO
COVID Watch is a remote patient monitoring program implemented during the pandemic to support home dwelling patients with COVID-19. The program conferred a large survival advantage. We conducted semi-structured interviews of 85 patients and clinicians using COVID Watch to understand how to design such programs even better. Patients and clinicians found COVID Watch to be comforting and beneficial, but both groups desired more clarity about the purpose and timing of enrollment and alternatives to text-messages to adapt to patients' preferences as these may have limited engagement and enrollment among marginalized patient populations. Because inclusiveness and equity are important elements of programmatic success, future programs will need flexible and multi-channel human-to-human communication pathways for complex clinical interactions or for patients who do not desire tech-first approaches.
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Atitude do Pessoal de Saúde , Atitude Frente a Saúde , COVID-19 , Monitorização Ambulatorial , Pacientes , Telemedicina , Humanos , COVID-19/epidemiologia , COVID-19/terapia , Pandemias , Preferência do Paciente , Pacientes/psicologia , Pacientes/estatística & dados numéricos , Monitorização Ambulatorial/métodos , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa , Desenvolvimento de Programas , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , IdosoRESUMO
BACKGROUND: Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice. METHODS: We conducted a qualitative study of oncology clinicians to identify barriers to using preemptive PGx testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a semi-structured interview informed by the Consolidated Framework for Implementation Research (CFIR). Interviews were analyzed using an inductive content analysis approach. RESULTS: Participants included sixteen medical oncologists and nine oncology pharmacists from one academic medical center and two community hospitals in Pennsylvania. Barriers to the use of preemptive PGx testing to guide chemotherapy dosing mapped to four CFIR domains: intervention characteristics, outer setting, inner setting, and characteristics of individuals. The most prominent themes included 1) a limited evidence base, 2) a cumbersome and lengthy testing process, and 3) a lack of insurance coverage for preemptive PGx testing. Additional barriers included clinician lack of knowledge, difficulty remembering to order PGx testing for eligible patients, challenges with PGx test interpretation, a questionable impact of preemptive PGx testing on clinical care, and a lack of alternative therapeutic options for some patients found to have actionable PGx variants. CONCLUSIONS: Successful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multifaceted effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study.
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Antineoplásicos/administração & dosagem , Tomada de Decisão Clínica , Neoplasias Gastrointestinais/tratamento farmacológico , Testes Farmacogenômicos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Oncologistas/estatística & dados numéricos , Padrões de Prática Médica , Pesquisa QualitativaRESUMO
PURPOSE: Oncologists may overestimate prognosis for patients with cancer, leading to delayed or missed conversations about patients' goals and subsequent low-quality end-of-life care. Machine learning algorithms may accurately predict mortality risk in cancer, but it is unclear how oncology clinicians would use such algorithms in practice. METHODS: The purpose of this qualitative study was to assess oncology clinicians' perceptions on the utility and barriers of machine learning prognostic algorithms to prompt advance care planning. Participants included medical oncology physicians and advanced practice providers (APPs) practicing in tertiary and community practices within a large academic healthcare system. Transcripts were coded and analyzed inductively using NVivo software. RESULTS: The study included 29 oncology clinicians (19 physicians, 10 APPs) across 6 practice sites (1 tertiary, 5 community) in the USA. Fourteen participants had previously had exposure to an automated machine learning-based prognostic algorithm as part of a pragmatic randomized trial. Clinicians believed that there was utility for algorithms in validating their own intuition about prognosis and prompting conversations about patient goals and preferences. However, this enthusiasm was tempered by concerns about algorithm accuracy, over-reliance on algorithm predictions, and the ethical implications around disclosure of an algorithm prediction. There was significant variation in tolerance for false positive vs. false negative predictions. CONCLUSION: While oncologists believe there are applications for advanced prognostic algorithms in routine care of patients with cancer, they are concerned about algorithm accuracy, confirmation and automation biases, and ethical issues of prognostic disclosure.
Assuntos
Neoplasias , Oncologistas , Algoritmos , Humanos , Aprendizado de Máquina , Oncologia , Neoplasias/terapia , PrognósticoRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) has disproportionately affected communities of color, with black persons experiencing the highest rates of disease severity and mortality. A vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to reduce the race mortality gap from COVID-19; however, hesitancy toward the vaccine in the black community threatens vaccine uptake. METHODS: We conducted focus groups with black barbershop and salon owners living in zip codes of elevated COVID-19 prevalence to assess their attitudes, beliefs, and norms around a COVID-19 vaccine. We used a modified grounded theory approach to analyze the transcripts. RESULTS: We completed 4 focus groups (N = 24 participants) in July and August 2020. Participants were an average age of 46 years, and 89% were black non-Hispanic. Hesitancy against the COVID-19 vaccine was high due to mistrust in the medical establishment, concerns with the accelerated timeline for vaccine development, limited data on short- and long-term side effects, and the political environment promoting racial injustice. Some participants were willing to consider the vaccine once the safety profile is robust and reassuring. Receiving a recommendation to take the vaccine from a trusted healthcare provider served as a facilitator. Health beliefs identified were similar to concerns around other vaccines and included the fear of getting the infection with vaccination and preferring to improve one's baseline physical health through alternative therapies. CONCLUSIONS: We found that hesitancy of receiving the COVID-19 vaccine was high; however, provider recommendation and transparency around the safety profile might help reduce this hesitancy.
Assuntos
COVID-19 , Vacinas , Negro ou Afro-Americano , Vacinas contra COVID-19 , Humanos , Pessoa de Meia-Idade , SARS-CoV-2RESUMO
BACKGROUND: Assessing the postoperative recovery of pediatric patients is challenging as there is no validated comprehensive patient-centered recovery assessment tool for this population. A qualitative investigative approach with in-depth stakeholder interviews can provide insight into the recovery process and inform the development of a comprehensive patient-centered postoperative assessment tool for children. METHODS: We conducted open-ended, semistructured interviews with children 6-12 years old undergoing elective surgery (n = 35), their parents (n = 37), and clinicians (n = 23) who commonly care for this population (nurses, anesthesiologists, and surgeons). A codebook was developed and analyzed using NVivo 12 Plus. The codebook was iteratively developed using a qualitative content analysis approach with modifications made throughout to refine codes. We report the results of this thematic analysis of patient, parent, and clinician transcripts. RESULTS: Postoperative recovery priorities/concerns overlapped and also diverged across the 3 groups. Topics prioritized by children included mobility and self-care, as well as access to a strong social support network following surgery. The majority of children reported feeling anxious about the surgery and separating from their parents, as well as sadness about their inability to participate in activities while recovering. Although children highly valued familial support during recovery, there was variable awareness of the impact of surgery on family members and support network. In contrast, parents focused on the importance of clear and open communication among themselves and the health care team and being equipped with appropriate knowledge and resources on discharge. The immediate repercussions of the child's surgery, such as pain, confusion, and nausea, appeared to be a primary focus of both parents and clinicians when describing recovery. Clinicians had a comprehensive awareness of the possible psychological impacts of surgery in children, while parents reported varying degrees of awareness or concern regarding longer-term or more latent impacts of surgery and anesthesia (eg, anxiety and depression). Prior experience with pediatric surgery emerged as a distinguishing characteristic for parents and clinicians as parents without prior experience expressed less understanding of or comfort with managing a child's recovery following surgery. CONCLUSIONS: A patient-centered qualitative investigative approach yielded insights regarding the importance of various aspects of recovery in pediatric patients, their parents, and members of the health care team. Specifically, this investigation highlighted the importance of clear communication providing anticipatory guidance for families presenting for elective surgery in an effort to optimize patient recovery. This information will be used in the development of a patient-centered recovery assessment tool.
Assuntos
Anestesia , Procedimentos Cirúrgicos Eletivos , Necessidades e Demandas de Serviços de Saúde , Avaliação das Necessidades , Pais/psicologia , Equipe de Assistência ao Paciente , Assistência Centrada no Paciente , Cuidados Pós-Operatórios , Anestesia/efeitos adversos , Anestesia/psicologia , Anestesiologistas/psicologia , Atitude do Pessoal de Saúde , Criança , Comportamento Infantil , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Entrevistas como Assunto , Masculino , Enfermeiras e Enfermeiros/psicologia , Educação de Pacientes como Assunto , Satisfação do Paciente , Pesquisa Qualitativa , Indicadores de Qualidade em Assistência à Saúde , Cirurgiões/psicologia , Resultado do TratamentoRESUMO
Aß(1-42) peptide is a neurotoxic agent strongly associated with the etiology of Alzheimer's disease (AD). Current treatments are still of very low effectiveness, and deaths from AD are increasing worldwide. Huprine-derived molecules have a high affinity towards the enzyme acetylcholinesterase (AChE), act as potent Aß(1-42) peptide aggregation inhibitors, and improve the behavior of experimental animals. AVCRI104P4 is a multitarget donepezil-huprine hybrid that improves short-term memory in a mouse model of AD and exerts protective effects in transgenic Caenorhabditis elegans that express Aß(1-42) peptide. At present, there is no information about the effects of this compound on human erythrocytes. Thus, we considered it important to study its effects on the cell membrane and erythrocyte models, and to examine its protective effect against the toxic insult induced by Aß(1-42) peptide in this cell and models. This research was developed using X-ray diffraction and differential scanning calorimetry (DSC) on molecular models of the human erythrocyte membrane constituted by lipid bilayers built of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). They correspond to phospholipids representative of those present in the external and internal monolayers, respectively, of most plasma and neuronal membranes. The effect of AVCRI104P4 on human erythrocyte morphology was studied by scanning electron microscopy (SEM). The experimental results showed a protective effect of AVCRI104P4 against the toxicity induced by Aß(1-42) peptide in human erythrocytes and molecular models.
Assuntos
Peptídeos beta-Amiloides , Membrana Eritrocítica , Compostos Heterocíclicos de 4 ou mais Anéis , Modelos Moleculares , Fragmentos de Peptídeos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/toxicidade , Membrana Eritrocítica/química , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/ultraestrutura , Compostos Heterocíclicos de 4 ou mais Anéis/química , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/toxicidadeRESUMO
RATIONALE: The most common antibiotic used to treat people with cystic fibrosis (PWCF) is inhaled tobramycin, administered as maintenance therapy for chronic Pseudomonas aeruginosa lung infections. While the effects of inhaled tobramycin on P. aeruginosa abundance and lung function diminish with continued therapy, this maintenance treatment is known to improve long-term outcomes, underscoring how little is known about why antibiotics work in CF infections, what their effects are on complex CF sputum microbiomes and how to improve these treatments. OBJECTIVES: To rigorously define the effect of maintenance tobramycin on CF sputum microbiome characteristics. METHODS AND MEASUREMENTS: We collected sputum from 30 PWCF at standardised times before, during and after a single month-long course of maintenance inhaled tobramycin. We used traditional culture, quantitative PCR and metagenomic sequencing to define the dynamic effects of this treatment on sputum microbiomes, including abundance changes in both clinically targeted and untargeted bacteria, as well as functional gene categories. MAIN RESULTS: CF sputum microbiota changed most markedly by 1 week of antibiotic therapy and plateaued thereafter, and this shift was largely driven by changes in non-dominant taxa. The genetically conferred functional capacities (ie, metagenomes) of subjects' sputum communities changed little with antibiotic perturbation, despite taxonomic shifts, suggesting functional redundancy within the CF sputum microbiome. CONCLUSIONS: Maintenance treatment with inhaled tobramycin, an antibiotic with demonstrated long-term mortality benefit, primarily impacted clinically untargeted bacteria in CF sputum, highlighting the importance of monitoring the non-canonical effects of antibiotics and other treatments to accurately define and improve their clinical impact.
Assuntos
Antibacterianos/farmacologia , Bactérias , Fibrose Cística/microbiologia , Microbiota/efeitos dos fármacos , Escarro/microbiologia , Tobramicina/farmacologia , Administração por Inalação , Adolescente , Adulto , Idoso , Antibacterianos/uso terapêutico , Bactérias/genética , Bactérias/isolamento & purificação , Infecções Bacterianas/prevenção & controle , Criança , Fibrose Cística/fisiopatologia , Volume Expiratório Forçado , Humanos , Quimioterapia de Manutenção , Metagenoma/efeitos dos fármacos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Fatores de Tempo , Tobramicina/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: This study assessed whether magnetic resonance imaging (MRI) could accurately predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for patients receiving standardized treatment, pre- and post-NAC MRI on the same instrumentation using a consistent imaging protocol, interpreted by a single breast fellowship-trained radiologist. METHODS: A single-institution retrospective analysis was performed including clinical, radiographic, and pathologic parameters for all patients with breast cancer treated with NAC from 2015 to 2018. Radiographic complete response (rCR) was defined as absence of suspicious MRI findings in the ipsilateral breast or lymph nodes. pCR was defined as the absence of invasive cancer or ductal carcinoma in-situ in breast or lymph nodes after operation (ypT0N0M0). RESULTS: Data for 102 consecutive patients demonstrated that 44 (43.1%) had rCR and 41 (40.1%) had pCR. pCR occurred in 12 (25.0%) of 48 estrogen receptor positive (ER+) patients, 29 (53.7%) of 54 ER- patients, and 25 (52.1%) of 48 human epidermal growth factor receptor 2 positive patients. The positive predictive value for MRI after NAC was 84.5% and the negative predictive value was 72.7%. The accuracy rate for MRI was 78.6%. Of the 44 patients with rCR, 12 (27.3%) had residual cancer on the pathologic specimen after surgical excision. CONCLUSION: rCR is not accurate enough to serve as a surrogate marker for pCR on MRI after NAC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante , Neoplasias da Mama/tratamento farmacológico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: The management of intraductal papillomas (IDPs) diagnosed on core needle biopsy (CNB) remains controversial regarding whether excision is required. We evaluated whether excision of IDPs might be overtreatment based on a consecutive patient population where all IDPs were routinely excised. MATERIALS AND METHODS: We retrospectively reviewed the records of consecutive patients treated with excision of IDPs at our institution from 2009 to 2016. We evaluated the rate of upgrade of IDPs on CNB and factors predicting for malignant upgrade. RESULTS: Of 153 CNB specimens, 136 (88.9%) were IDPs without atypia and 14 (9.2%) showed atypia. The overall upgrade rate on final pathology was 7.3% with 1.3% for invasive cancer, 2.7% for ductal carcinoma in situ, and 3.3% for atypical ductal hyperplasia. Of the 14 patients with atypia on CNB, two of these patients (14.2%) were found to have ductal carcinoma in situ. In the absence of atypia on CNB, upgrade rates were 1.5% for invasive and 1.5% for in situ carcinoma. Personal history of breast cancer and magnetic resonance imaging-guided biopsy predicted for malignant upgrade. CONCLUSIONS: IDPs on CNB have a low chance of harboring an occult malignancy. Given the low probability of upgrade to invasive breast cancer, it is reasonable to consider watchful surveillance in the absence of a prior personal history of breast cancer or atypia on CNB.
Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Papiloma Intraductal/patologia , Papiloma Intraductal/cirurgia , Procedimentos Desnecessários , Adulto , Idoso , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/diagnóstico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Papiloma Intraductal/diagnóstico , Estudos Retrospectivos , Conduta ExpectanteRESUMO
OBJECTIVE: This study evaluates whether nodal status differs between breast cancer patients with BRCA mutations and those confirmed not to harbor mutations. METHODS: A prospective database identified patients with breast cancer who underwent genetic testing and axillary staging. Comparative variables included age, as well as tumor characteristics such as size, grade, lymphovascular invasion (LVI), estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2-neu), and nodal status. RESULTS: Overall, 235 patients with breast cancer underwent genetic testing for BRCA mutations from June 2000 to May 2012. Of these patients, 74 (31.4 %) were found to express BRCA 1 and/or 2 mutations, and 161 (68.5 %) patients were verified to have no detectable BRCA mutation. Among the entire 235 patients tested, 92 (39.1 %) were found to have nodal disease. In univariable analysis, only LVI and tumor size correlated with presence of nodal metastasis. Of the 74 BRCA mutation carriers, 34 (45.9 %) had nodal metastasis compared with 58 of the 161 (36 %; p = 0.15) patients without a BRCA mutation. BRCA mutation carriers with nodal disease were more likely to have poorly differentiated tumors than those without mutations who had nodal disease (24/33 [72.7 %] vs. 27/57 [47.4 %]; p = 0.027). CONCLUSION: BRCA mutations are not themselves predictive of nodal metastasis. Patients with BRCA mutations did not have a statistically significant higher prevalence of nodal metastasis than those without mutations.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Lobular/genética , Testes Genéticos , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/secundário , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Estudos RetrospectivosRESUMO
A single-laboratory validation (SLV) study was conducted on an LC/MS/MS method for the determination and confirmation of nicarbazin, expressed as 4,4-dinitrocarbanilide (DNC), in chicken tissues, including liver, kidney, muscle, skin with adhering fat, and eggs. Linearity was demonstrated with DNC standard curve solutions using a weighted (1/x) regression and confirmed with matrix-matched standards. Intertrial repeatability precision (relative standard deviation of repeatability; RSD(r) was from 2.5 to 11.3%, as determined in fortified tissues. The precision was verified with incurred tissue, and varied from 0.53 to 2.5%. Average recoveries ranged from 82% in egg to 98% in kidney. Although the average recoveries across all concentrations were within the acceptable range, the method was improved with the inclusion of an internal standard and the use of matrix-matched standards. Accuracy for the improved method in chicken liver varied from 93 to 99% across all concentrations (100-8000 ng/g) compared to recoveries below 80% at concentrations, between 100-400 ng/g in chicken liver for the original method. The limit of detection was estimated to be less than 3.0 ng/g in all tissue types, and the limit of quantitation was validated at 20 ng/g. Based on confirmatory ion ratios and peak retention times, the false-negative rate was estimated as 0.00% (95% confidence limits 0.00, 0.74%) from 484 fortified samples and 12 incurred residue samples analyzed using the U.S. and EU confirmation criteria. Small variations to the method parameters, with the exception of injection volume, did not have a significant effect on recoveries. Stability was determined for fortified tissues, extracts, and standard curve solutions. The data collected in this study satisfy the requirements of SLV studies established by the AOAC Stakeholder Panel for Veterinary Drug Residue and the method was awarded First Action Official Method status by the Expert Review Panel for Veterinary Drug Residues on May 7, 2013.
Assuntos
Carbanilidas/química , Galinhas/metabolismo , Cromatografia Líquida/métodos , Rim/química , Fígado/química , Nicarbazina/química , Espectrometria de Massas em Tandem/métodos , Tecido Adiposo/química , Animais , Carbanilidas/metabolismo , Cromatografia Líquida/normas , Coccidiostáticos/química , Coccidiostáticos/metabolismo , Ovos/análise , Músculo Esquelético/química , Nicarbazina/metabolismo , Pele/química , Espectrometria de Massas em Tandem/normasRESUMO
Objective: to evaluate the immune response to the SARS-CoV-2 vaccines in adults with immune-mediated rheumatic diseases (IMRDs) in comparison to healthy individuals, observed 1-20 weeks following the fourth vaccine dose. Additionally, to evaluate the impact of immunosuppressive therapies, vaccination schedules, the time interval between vaccination and sample collection on the vaccine's immune response. Methods: We designed a longitudinal observational study conducted at the rheumatology department of Hospital de Copiapó. Neutralizing antibodies (Nabs) titers against the Wuhan and Omicron variant were analyzed between 1-20 weeks after administration of the fourth dose of the SARS-CoV-2 vaccine to 341 participants (218 IMRD patients and 123 healthy controls). 218 IMRD patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic vasculitis (VS) and systemic scleroderma (SS) were analyzed. Results: Performing a comparison between the variants, Wuhan vs Omicron, we noticed that there were significant differences (p<0.05) in the level of the ID50, both for healthy controls and for patients with IMRDs. The humoral response of patients with IMRDs is significantly lower compared to healthy controls for the Omicron variant of SARS-CoV-2 (p = 0.0015). The humoral response of patients with IMRDs decreases significantly when the time interval between vaccination and sample collection is greater than 35 days. This difference was observed in the response, both for the Wuhan variant and for the Omicron variant. Conclusion: The IMRDs patients, the humoral response variation in the SARS-CoV-2 vaccine depends on doses and type of vaccine administered, the humoral response times and the treatment that these patients are receiving.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Doenças Reumáticas , SARS-CoV-2 , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Doenças Reumáticas/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Adulto , Idoso , Estudos Longitudinais , VacinaçãoRESUMO
A multilaboratory study was conducted to determine the equivalence of the 3M Petrifilm Aerobic Count Plate and standard plating methodology for measuring viable bacteria and spores recovered from hard-surface carriers (stainless steel and porcelain), also known as "control carrier counts," used in AOAC antimicrobial efficacy test methods. Six laboratories participated in the study in which carriers inoculated with Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella enterica, and spores of Bacillus subtilis were evaluated using 3M Petrifilm Aerobic Count (AC) plates and standard plating side-by-side. The data were analyzed using a matched-pair t-test to determine the between-method effect with confidence intervals. For all test organisms pooled across all laboratories, the mean difference in log10 concentration between the standard plate count method and 3M Petrifilm AC Plates was -0.012, with a 95% confidence interval of (-0.090, +0.066), which was well within the -0.5, +0.5 interval established as the acceptance criterion. The between-carrier SD averaged 0.139; the between-replicate SD was 0.050. The carrier reproducibility, given that a single replicate per carrier is done, was estimated to be 0.148. Although differences were seen in the final concentrations of the test organisms among laboratories, there were no statistical differences between the enumeration methods. Based on the results from this study, 3M Petrifilm AC Plates are equivalent to standard plating methodology and can be used as an alternative procedure for the enumeration of test organisms used in AOAC Methods 955.14, 955.15, 964.02, and 966.04.
Assuntos
Bactérias Aeróbias/isolamento & purificação , Carga Bacteriana/métodos , Bactérias Aeróbias/efeitos dos fármacos , Comportamento CooperativoRESUMO
The burnout literature is replete with burnout score results from quantitative surveys. There is a paucity of qualitative research that seeks to understand the impact of physician stressors on work-life balance and burnout. This study aimed to identify factors that support and disrupt work-life balance, drivers of burnout, and potential solutions among academic dermatologists. The objective was to better understand factors that promote wellness and ameliorate burnout. Concurrent explanatory mixed methods consisted of scores on the Abbreviated Maslach Burnout Inventory and open-ended semi-structured telephone interviews. The results were that positive factors, such as supportive home life and satisfaction derived from academic endeavors, compete with ongoing feelings of exhaustion, frustration, and apathy. Negative stressors include the electronic medical record, insufficient staffing, administrative and clinical task burden, and perceived lack of interest from mid-level and senior health system leadership in addressing clinicians' needs. This was a single-center academic study. As with all qualitative studies, these results may not be generalizable to all dermatologists. In addition, some participants were concerned about their anonymity. Modifiable root causes of burnout require institutional commitment to sustain the pace required by academic dermatologists.
Assuntos
Esgotamento Profissional , Médicos , Humanos , Dermatologistas , Esgotamento Profissional/prevenção & controle , Inquéritos e Questionários , Satisfação no EmpregoRESUMO
Opioid misuse represents a major public health issue in the United States. One driver is overprescription for acute pain, with the size of initial prescription associated with subsequent long-term use. However, little work has been done to elicit clinician feedback about interventions to reduce opioid prescribing. To address this knowledge gap, qualitative analyses were conducted with clinicians who participated in a randomized controlled trial in which clinicians received monthly emailed feedback notifications about their opioid prescribing behaviors. Semistructured telephone interviews were conducted (N = 12) with urgent care (N = 7) and emergency department (N = 5) clinicians who participated in the trial between November 2020 and April 2021. Clinicians appreciated feedback about their prescribing behavior and found comparative data with peer clinicians to be most useful. Sharing opioid prescribing feedback data with clinicians can be an acceptable way to address opioid prescribing among emergency and urgent care clinicians.