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BACKGROUND: Recent therapeutic advances and screening technologies have improved survival among patients with lung cancer, who are now at high risk of developing second primary lung cancer (SPLC). Recently, an SPLC risk-prediction model (called SPLC-RAT) was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. The predictive performance of SPLC-RAT was evaluated in a hospital-based cohort of lung cancer survivors. METHODS: The authors analyzed data from 8448 ever-smoking patients diagnosed with initial primary lung cancer (IPLC) in 1997-2006 at Mayo Clinic, with each patient followed for SPLC through 2018. The predictive performance of SPLC-RAT and further explored the potential of improving SPLC detection through risk model-based surveillance using SPLC-RAT versus existing clinical surveillance guidelines. RESULTS: Of 8448 IPLC patients, 483 (5.7%) developed SPLC over 26,470 person-years. The application of SPLC-RAT showed high discrimination area under the receiver operating characteristics curve: 0.81). When the cohort was stratified by a 10-year risk threshold of ≥5.6% (i.e., 80th percentile from the SPLC-RAT development cohort), the observed SPLC incidence was significantly elevated in the high-risk versus low-risk subgroup (13.1% vs. 1.1%, p < 1 × 10-6 ). The risk-based surveillance through SPLC-RAT (≥5.6% threshold) outperformed the National Comprehensive Cancer Network guidelines with higher sensitivity (86.4% vs. 79.4%) and specificity (38.9% vs. 30.4%) and required 20% fewer computed tomography follow-ups needed to detect one SPLC (162 vs. 202). CONCLUSION: In a large, hospital-based cohort, the authors validated the predictive performance of SPLC-RAT in identifying high-risk survivors of SPLC and showed its potential to improve SPLC detection through risk-based surveillance. PLAIN LANGUAGE SUMMARY: Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC). However, no evidence-based guidelines for SPLC surveillance are available for lung cancer survivors. Recently, an SPLC risk-prediction model was developed and validated using data from population-based epidemiological cohorts and clinical trials, but real-world validation has been lacking. Using a large, real-world cohort of lung cancer survivors, we showed the high predictive accuracy and risk-stratification ability of the SPLC risk-prediction model. Furthermore, we demonstrated the potential to enhance efficiency in detecting SPLC using risk model-based surveillance strategies compared to the existing consensus-based clinical guidelines, including the National Comprehensive Cancer Network.
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Supervivientes de Cáncer , Neoplasias Pulmonares , Neoplasias Primarias Secundarias , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/terapia , Riesgo , Fumar , PulmónRESUMEN
OBJECTIVE: We characterized the quality of statistical methods for studies of racial and ethnic disparities in the surgical-relevant literature during 2021-2022. BACKGROUND: Hundreds of scientific papers are published each year describing racial and ethnic disparities in surgical access, quality, and outcomes. The content and design quality of this literature has never been systematically reviewed. METHODS: We searched for 2021-2022 studies focused on describing racial and/or ethnic disparities in surgical or perioperative access, process quality, or outcomes. Identified studies were characterized in terms of three methodological criteria: 1) adjustment for variables related to both race/ethnicity and outcomes, including social determinants of health (SDOH); 2) accounting for clustering of patients within hospitals or other subunits ("providers") and; 3) distinguishing within- and between-provider effects. RESULTS: We identified 224 papers describing racial and/or ethnic differences. Of the 38 single institution studies, 24 (63.2%) adjusted for at least one SDOH variable. Of the 186 multisite studies, 113 (60.8%) adjusted for at least one SDOH variable, and 43 (23.1%) accounted for clustering of patients within providers using appropriate statistical methods. Only 10 (5.4%) of multi-institution studies made efforts to examine how much of overall disparities were driven by within versus between provider effects. CONCLUSIONS: Most recently published papers on racial and ethnic disparities in the surgical literature do not meet these important statistical design criteria and therefore may risk inaccuracy in the estimation of group differences in surgical access, quality, and outcomes. The most potent leverage points for these improvements are changes to journal publication guidelines and policies.
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PURPOSE: In advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI) monotherapy is often preferred over intensive ICI treatment for frail patients and those with poor performance status (PS). Among those with poor PS, the additional effect of frailty on treatment selection and mortality is unknown. METHODS: Patients in the veterans affairs national precision oncology program from 1/2019-12/2021 who received first-line ICI for advanced NSCLC were followed until death or study end 6/2022. Association of an electronic frailty index with treatment selection was examined using logistic regression stratified by PS. We also examined overall survival (OS) on intensive treatment using Cox regression stratified by PS. Intensive treatment was defined as concurrent use of platinum-doublet chemotherapy and/or dual checkpoint blockade and non-intensive as ICI monotherapy. RESULTS: Of 1547 patients receiving any ICI, 66.2% were frail, 33.8% had poor PS (≥ 2), and 25.8% were both. Frail patients received less intensive treatment than non-frail patients in both PS subgroups (Good PS: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.51 - 0.88; Poor PS: OR 0.69, 95% CI 0.44 - 1.10). Among 731 patients receiving intensive treatment, frailty was associated with lower OS for those with good PS (hazard ratio [HR] 1.53, 95% CI 1.2 - 1.96), but no association was observed with poor PS (HR 1.03, 95% CI 0.67 - 1.58). CONCLUSION: Frail patients with both good and poor PS received less intensive treatment. However, frailty has a limited effect on survival among those with poor PS. These findings suggest that PS, not frailty, drives survival on intensive treatment.
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Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Femenino , Anciano , Inmunoterapia/métodos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Persona de Mediana Edad , Fragilidad , Anciano de 80 o más AñosRESUMEN
We present a case of eosinophil-rich linear IgA bullous disease (LABD) following the administration of a messenger RNA COVID-19 booster vaccine. A 66-year-old man presented to the emergency department with a 3-week history of a pruritic blistering rash characterized by fluid-filled bullae and multiple annular and polycyclic plaques. He was initially diagnosed with bullous pemphigoid based on a biopsy showing a subepidermal blister with numerous eosinophils. However, direct immunofluorescence studies showed linear IgA and IgM deposition along the basement membrane zone with no immunoreactivity for C3 or IgG. Additionally, indirect immunofluorescence was positive for IgA basement membrane zone antibody. The patient was subsequently diagnosed with LABD and initiated on dapsone therapy with resolution of his lesions at 3-month follow-up. This case illustrates the growing number of autoimmune blistering adverse cutaneous reactions from vaccination. Dermatopathologists should be aware that features of autoimmune blistering diseases can overlap and may not be distinguishable based on these histopathological findings alone. Confirmation with direct immunofluorescence and/or serological studies may be necessary for accurate diagnosis.
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Enfermedades Autoinmunes , COVID-19 , Dermatosis Bullosa IgA Lineal , Prurigo , Vacunas , Masculino , Humanos , Anciano , Dermatosis Bullosa IgA Lineal/patología , Eosinófilos/patología , Inmunoglobulina A , VesículaRESUMEN
BACKGROUND: Approximately 25% of outpatient antibiotic prescriptions are unnecessary among family physicians in Canada. Minimizing unnecessary antibiotics is key for community antibiotic stewardship. However, unnecessary antibiotic prescribing is much harder to measure than total antibiotic prescribing. We investigated the association between total and unnecessary antibiotic use by family physicians and evaluated inter-physician variability in unnecessary antibiotic prescribing. METHODS: This was a cohort study based on electronic medical records of family physicians in Ontario, Canada, between April 2011 and March 2016. We used predefined expected antibiotic prescribing rates for 23 common primary care conditions to calculate unnecessary antibiotic prescribing rates. We used multilevel Poisson regression models to evaluate the association between total antibiotic volume (number of antibiotic prescriptions per patient visit), adjusted for multiple practice- and physician-level covariates, and unnecessary antibiotic prescribing. RESULTS: There were 499 570 physician-patient encounters resulting in 152 853 antibiotic prescriptions from 341 physicians. Substantial inter-physician variability was observed. In the fully adjusted model, we observed a significant association between total antibiotic volume and unnecessary prescribing rate (adjusted rate ratio 2.11 per 10% increase in total use; 95% CI 2.05-2.17), and none of the practice- and physician-level variables were associated with unnecessary prescribing rate. CONCLUSIONS: We demonstrated substantial inter-physician variability in unnecessary antibiotic prescribing in this cohort of family physicians. Total antibiotic use was strongly correlated with unnecessary antibiotic prescribing. Total antibiotic volume is a reasonable surrogate for unnecessary antibiotic use. These results can inform community antimicrobial stewardship efforts.
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Antibacterianos , Médicos de Familia , Antibacterianos/uso terapéutico , Estudios de Cohortes , Registros Electrónicos de Salud , Humanos , Prescripción Inadecuada , Ontario , Pautas de la Práctica en MedicinaRESUMEN
BACKGROUND: Pharmacist prescribing authority is expanding, while antimicrobial resistance is an increasing global concern. We sought to synthesize the evidence for antimicrobial prescribing by community pharmacists to identify opportunities to advance antimicrobial stewardship in this setting. METHODS: We conducted a systematic review to characterize the existing literature on community pharmacist prescribing of systemic antimicrobials. We searched MEDLINE, EMBASE and International Pharmaceutical Abstracts for English-language articles published between 1999 and June 20, 2019, as well as hand-searched reference lists of included articles and incorporated expert suggestions. RESULTS: Of 3793 articles identified, 14 met inclusion criteria. Pharmacists are most often prescribing for uncomplicated urinary tract infection (UTI), acute pharyngitis and cold sores using independent and supplementary prescribing models. This was associated with high rates of clinical improvement (4 studies), low rates of retreatment and adverse effects (3 studies) and decreased health care utilization (7 studies). Patients were highly satisfied (8 studies) and accessed care sooner or more easily (7 studies). Seven studies incorporated antimicrobial stewardship into study design, and there was overlap between study outcomes and those relevant to outpatient antimicrobial stewardship. Pharmacist intervention reduced unnecessary prescribing for acute pharyngitis (2 studies) and increased the appropriateness of prescribing for UTI (3 studies). CONCLUSION: There is growing evidence to support the role of community pharmacists in antimicrobial prescribing. Future research should explore additional opportunities for pharmacist antimicrobial prescribing and ways to further integrate advanced antimicrobial stewardship strategies in the community setting. Can Pharm J (Ott) 2021;154:xx-xx.
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Mycosis fungoides (MF) is the most common primary cutaneous lymphoma in pediatric patients. Given the indolent nature of MF, symptoms often present in childhood but may not be diagnosed as MF until adulthood. Delayed diagnosis is associated with poor long-term prognosis. Thus, increased clinician recognition and accurate diagnosis of early-stage MF in pediatric patients is critically important. In this review, we summarize the clinical features of the most common pediatric MF subtypes and highlight important differences between pediatric and adult MF. Moreover, we reviewed all pediatric MF case series published between 2008 and 2018 to analyze treatment modalities and identify emerging therapies. As treatment of pediatric MF is complex, selection of therapy varies significantly depending upon the specific clinical characteristics, disease severity, and patients' preferences.
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Micosis Fungoide/diagnóstico , Micosis Fungoide/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Biopsia , Niño , Diagnóstico Diferencial , Humanos , Micosis Fungoide/patología , Estadificación de Neoplasias , Pronóstico , Neoplasias Cutáneas/patologíaRESUMEN
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin with high rates of metastasis and mortality. Besides well-established factors including genetic mutations and UV-induced DNA damage in Merkel cell carcinogenesis, the recent discovery of the Merkel cell polyomavirus (MCPyV) has shed light on the viral etiology of MCC. In the current study, we provide novel evidence that MCPyV small T (sT) antigen induces the DNA damage response (DDR) pathway. Our data show that in human MCC cells, the presence of MCPyV is associated with hyperphosphorylation of histone H2AX, a marker for DNA damage. We observed that overexpression of MCPyV sT antigen induced the phosphorylation of histone H2AX as well as the activation of ataxia telangiectasia mutant (ATM), an upstream kinase important for H2AX phosphorylation. Moreover, we observed that MCPyV sT expression also induced the hyperphosphorylation of other ATM downstream molecules (including 53BP1 and CHK2) as well as the hypermethylation of histone 3 and histone 4. These findings disclose a novel link between MCPyV sT and the DDR pathway in MCC. Given that measurement of DDR is clinically useful for evaluating treatment response to radio- and chemotherapy, our findings warrant further investigation to evaluate the potential implications of this pathway for MCC management.
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Antígenos Virales de Tumores/genética , Carcinoma de Células de Merkel/virología , Daño del ADN , Expresión Génica , Poliomavirus de Células de Merkel , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Células HEK293 , Histonas/metabolismo , Humanos , Células de Merkel/virología , Fosforilación , Neoplasias Cutáneas/virologíaRESUMEN
PURPOSE OF REVIEW: The effects of skin disease on stigmatization are important but understudied in the pediatric population. Given the highly visible nature of dermatologic conditions, stigmatization is a common problem that requires significant attention in patients with skin diseases. In this review, we examine the recent literature addressing stigmatization of patients suffering from common dermatologic diseases with the goal to increase clinician awareness of these issues and identify new avenues for future research. RECENT FINDINGS: A number of studies have examined the impact of skin disease on psychosocial well being and quality of life. Although some skin diseases are often overlooked medically and considered to be primarily cosmetic issues, the long-term consequences of skin diseases on psychosocial health, especially in pediatric patients, can be profound. SUMMARY: The precipitating factors for stigma vary widely depending on age, sex, and culture. In order to effectively reduce the impact of pediatric skin diseases on psychosocial health, physicians should be able to identify specific characteristics that may increase risks for stigmatization in chidlren. Carefully monitoring psychosocial development in pediatric patients with dermatological conditions in addition to proactively guiding patients and families to appropriate resources can benefit the child's development and overall long-term well being.
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Calidad de Vida/psicología , Enfermedades de la Piel/psicología , Estigma Social , Acné Vulgar/psicología , Niño , Dermatitis Atópica/psicología , Hemangioma/psicología , Humanos , Psoriasis/psicología , Enfermedades de la Piel/diagnóstico , Vitíligo/psicologíaRESUMEN
Immunodeficiency is most commonly related to inherited syndromes, infections, chemotherapy, or aging. As the population of individuals with immunodeficiency continues to grow, physicians are confronted with the task of diagnosing dermatologic disease in this population. Cutaneous involvement in immunodeficiency disorders serves as a useful tool that aids diagnosis and provides prognostic value. Given that cutaneous manifestations often herald an underlying immunodeficiency disorder, understanding the complexities of these diseases is important for appropriate clinical management. Although certain diseases may present with stereotypical cutaneous lesions, others may involve more variable lesions that require specialized consultation for diagnosis and treatment recommendations. In this review, we discuss a number of cutaneous findings associated with primary immunodeficiencies. Awareness of these cutaneous associations may aid in the early detection and prompt treatment of these potentially serious immunologic disorders.
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Enfermedades de Inmunodeficiencia Primaria/patología , Enfermedades Cutáneas Genéticas/patología , Piel/patología , HumanosAsunto(s)
Teléfono Celular , Veteranos , Humanos , Citas y Horarios , Sistemas Recordatorios , Cooperación del PacienteRESUMEN
BRAF inhibitors are highly effective therapies in treating a subset of melanomas but are associated with induction of secondary cutaneous squamous cell carcinoma (cSCC). Recently, Human Polyomavirus 6 (HPyV6) was found to actively express viral proteins in BRAF inhibitor-induced cSCCs; however, the specific cellular mechanisms by which HPyV6 may facilitate neoplastic cell growth require further investigation. The current study describes a novel pathogenic mechanism of action for HPyV6 small tumor (sT) antigen which involves binding to protein phosphatase 2A (PP2A) via its WFG motif and zinc binding sites. Our findings demonstrate an important role of HPyV6 sT for activation of PP2A's downstream oncogenic pathways (MEK/ERK/c-Jun), which may underlie the pathogenesis of BRAF inhibitor-induced neoplasms. J. Med. Virol. 89:742-747, 2017. © 2016 Wiley Periodicals, Inc.
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Antígenos Virales de Tumores/metabolismo , Interacciones Huésped-Patógeno , Sistema de Señalización de MAP Quinasas , Poliomavirus/patogenicidad , Proteína Fosfatasa 2/metabolismo , Humanos , Unión Proteica , Mapeo de Interacción de ProteínasRESUMEN
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer associated with the Merkel cell polyomavirus (MCPyV). The MCPyV genome, which is clonally integrated in the majority of MCCs, encodes the regulatory small T (sT) antigen. Previously, reports have established MCPyV sT antigen as a potent oncogene capable of inducing cell transformation. In the current study, we demonstrate a distinct role for c-Jun hyperactivation in MCPyV sT antigen pathogenesis. As MCPyV sT antigen's association with aggressive cancer growth has been previously established, this finding may represent a potential therapeutic target for the treatment of MCCs.
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Antígenos Virales de Tumores/metabolismo , Carcinoma de Células de Merkel/virología , Transformación Celular Neoplásica/metabolismo , Poliomavirus de Células de Merkel/metabolismo , Infecciones por Polyomavirus/virología , Proteínas Proto-Oncogénicas c-jun/metabolismo , Neoplasias Cutáneas/virología , Antígenos Virales de Tumores/genética , Carcinoma de Células de Merkel/genética , Carcinoma de Células de Merkel/inmunología , Carcinoma de Células de Merkel/metabolismo , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/inmunología , Perfilación de la Expresión Génica , Regulación Viral de la Expresión Génica , Células HEK293 , Humanos , Poliomavirus de Células de Merkel/genética , Poliomavirus de Células de Merkel/inmunología , Fosforilación , Infecciones por Polyomavirus/genética , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/metabolismo , Proteínas Proto-Oncogénicas c-jun/biosíntesis , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/metabolismo , Infecciones Tumorales por Virus/virologíaRESUMEN
Merkel cell polyomavirus (MCPyV), trichodysplasia spinulosa-associated polyomavirus (TSPyV), human polyomavirus 6 (HPyV6), and human polyomavirus 7 (HPyV7) are implicated in the pathogeneses of distinct hyperproliferative cutaneous growths and encode small tumor (sT) antigens. The current study demonstrates that the four sT antigens differentially regulate 4E-binding protein 1 (4E-BP1) serine 65 hyperphosphorylation. MCPyV and HPyV7 sT antigens were found to promote the presence of the hyperphosphorylated 4E-BP1-δ isoform, while TSPyV and HPyV6 sT antigens had no significant effects. Given that hyperphosphorylated 4E-BP1 is associated with an aggressive cancer phenotype, our findings confirm the previously reported pathogenicity of MCPyV sT and highlight a novel mechanism by which HPyV7 sT may mediate oncogenesis.
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Proteínas Adaptadoras Transductoras de Señales/genética , Antígenos Transformadores de Poliomavirus/inmunología , Poliomavirus de Células de Merkel/inmunología , Fosfoproteínas/genética , Polyomaviridae/inmunología , Infecciones por Polyomavirus/inmunología , Poliomavirus/inmunología , Proteínas de Ciclo Celular , Humanos , Infecciones por Polyomavirus/virología , Neoplasias Cutáneas/virologíaRESUMEN
Pressor response after stroke commonly leads to early death or susceptibility to stroke recurrence, and detailed mechanisms are still lacking. We assessed the hypothesis that the renin-angiotensin system contributes to pressor response after stroke by differential modulation of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla (RVLM), a key brain stem site that maintains blood pressure. We also investigated the beneficial effects of a novel renin inhibitor, aliskiren, against stroke-elicited pressor response. Experiments were performed in male adult Sprague-Dawley rats. Stroke induced by middle cerebral artery occlusion elicited significant pressor response, accompanied by activation of angiotensin II (Ang II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2 (CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2 signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM. Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity and reduced neuroinflammation in the RVLM; these effects were potentiated by Ang-(1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R signaling in the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes pressor response after stroke by differential modulations of MCP-1 in the RVLM. Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into the brain stem provides more effective amelioration of stroked-induced pressor response.
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Angiotensinas/metabolismo , Presión Sanguínea/fisiología , Tronco Encefálico/metabolismo , Quimiocina CCL2/metabolismo , Regulación de la Expresión Génica/fisiología , Accidente Cerebrovascular/patología , Análisis de Varianza , Angiotensinas/genética , Animales , Isquemia Encefálica/complicaciones , Quimiocina CCL2/genética , Modelos Animales de Enfermedad , Frecuencia Cardíaca/fisiología , Masculino , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Examen Neurológico , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/metabolismoRESUMEN
OBJECTIVE: Although smoking cessation is recommended for all patients with peripheral artery disease, there are little data regarding the prevalence of smoking among patients at the time of angiography or the effect of smoking cessation on clinical outcomes. METHODS: Consecutive patients with claudication or critical limb ischemia who underwent peripheral angiography from 2006 to 2013 were included in an observational cohort analysis. Smoking status was assessed at the time of angiography and during follow-up clinic visits. Kaplan-Meier analysis was used to assess the relationship between smoking cessation, mortality, and amputation-free survival. RESULTS: Among 739 patients (423 men and 316 women; mean age, 60 ± 12 years), 204 (28%) remained active smokers at the time of lower extremity angiography. At the time of angiography, the mean number of cigarettes smoked per day was 16 ± 10, and the mean pack-years was 40 ± 25. During the course of the subsequent year, 61 patients (30%) successfully quit smoking and maintained continued abstinence. Baseline medication use between groups did not differ significantly. The mean ankle-brachial index was also similar for quitters vs nonquitters (0.53 ± 24 vs 0.49 ± 0.22; P = .3). During follow-up to 5 years, patients who quit smoking had significantly lower all-cause mortality (14% vs 31%; hazard ratio, 0.40; 95% confidence interval, 0.18-0.90) and improved amputation-free survival (81% vs 60%; hazard ratio, 0.43, 95% confidence interval, 0.22-0.86) compared with patients who continued smoking, with most of the difference driven by reduced mortality among patients who quit smoking. The findings remained significant on multivariable analysis. CONCLUSIONS: Approximately one-third of active smokers with peripheral artery disease successfully quit smoking ≤ 1 year after lower extremity angiography. Patients who quit smoking have lower mortality and improved amputation-free survival compared with patients who continue smoking.
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Amputación Quirúrgica , Enfermedad Arterial Periférica/terapia , Conducta de Reducción del Riesgo , Cese del Hábito de Fumar , Prevención del Hábito de Fumar , Anciano , Distribución de Chi-Cuadrado , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Recuperación del Miembro , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/mortalidad , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Fumar/efectos adversos , Fumar/mortalidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Decision aids are intended to help people participate in decisions that involve weighing the benefits and harms of treatment options often with scientific uncertainty. OBJECTIVES: To assess the effects of decision aids for people facing treatment or screening decisions. SEARCH METHODS: For this update, we searched from 2009 to June 2012 in MEDLINE; CENTRAL; EMBASE; PsycINFO; and grey literature. Cumulatively, we have searched each database since its start date including CINAHL (to September 2008). SELECTION CRITERIA: We included published randomized controlled trials of decision aids, which are interventions designed to support patients' decision making by making explicit the decision, providing information about treatment or screening options and their associated outcomes, compared to usual care and/or alternative interventions. We excluded studies of participants making hypothetical decisions. DATA COLLECTION AND ANALYSIS: Two review authors independently screened citations for inclusion, extracted data, and assessed risk of bias. The primary outcomes, based on the International Patient Decision Aid Standards (IPDAS), were:A) 'choice made' attributes;B) 'decision-making process' attributes.Secondary outcomes were behavioral, health, and health-system effects. We pooled results using mean differences (MD) and relative risks (RR), applying a random-effects model. MAIN RESULTS: This update includes 33 new studies for a total of 115 studies involving 34,444 participants. For risk of bias, selective outcome reporting and blinding of participants and personnel were mostly rated as unclear due to inadequate reporting. Based on 7 items, 8 of 115 studies had high risk of bias for 1 or 2 items each.Of 115 included studies, 88 (76.5%) used at least one of the IPDAS effectiveness criteria: A) 'choice made' attributes criteria: knowledge scores (76 studies); accurate risk perceptions (25 studies); and informed value-based choice (20 studies); and B) 'decision-making process' attributes criteria: feeling informed (34 studies) and feeling clear about values (29 studies).A) Criteria involving 'choice made' attributes:Compared to usual care, decision aids increased knowledge (MD 13.34 out of 100; 95% confidence interval (CI) 11.17 to 15.51; n = 42). When more detailed decision aids were compared to simple decision aids, the relative improvement in knowledge was significant (MD 5.52 out of 100; 95% CI 3.90 to 7.15; n = 19). Exposure to a decision aid with expressed probabilities resulted in a higher proportion of people with accurate risk perceptions (RR 1.82; 95% CI 1.52 to 2.16; n = 19). Exposure to a decision aid with explicit values clarification resulted in a higher proportion of patients choosing an option congruent with their values (RR 1.51; 95% CI 1.17 to 1.96; n = 13).B) Criteria involving 'decision-making process' attributes:Decision aids compared to usual care interventions resulted in:a) lower decisional conflict related to feeling uninformed (MD -7.26 of 100; 95% CI -9.73 to -4.78; n = 22) and feeling unclear about personal values (MD -6.09; 95% CI -8.50 to -3.67; n = 18);b) reduced proportions of people who were passive in decision making (RR 0.66; 95% CI 0.53 to 0.81; n = 14); andc) reduced proportions of people who remained undecided post-intervention (RR 0.59; 95% CI 0.47 to 0.72; n = 18).Decision aids appeared to have a positive effect on patient-practitioner communication in all nine studies that measured this outcome. For satisfaction with the decision (n = 20), decision-making process (n = 17), and/or preparation for decision making (n = 3), those exposed to a decision aid were either more satisfied, or there was no difference between the decision aid versus comparison interventions. No studies evaluated decision-making process attributes for helping patients to recognize that a decision needs to be made, or understanding that values affect the choice.C) Secondary outcomes Exposure to decision aids compared to usual care reduced the number of people of choosing major elective invasive surgery in favour of more conservative options (RR 0.79; 95% CI 0.68 to 0.93; n = 15). Exposure to decision aids compared to usual care reduced the number of people choosing to have prostate-specific antigen screening (RR 0.87; 95% CI 0.77 to 0.98; n = 9). When detailed compared to simple decision aids were used, fewer people chose menopausal hormone therapy (RR 0.73; 95% CI 0.55 to 0.98; n = 3). For other decisions, the effect on choices was variable.The effect of decision aids on length of consultation varied from 8 minutes shorter to 23 minutes longer (median 2.55 minutes longer) with 2 studies indicating statistically-significantly longer, 1 study shorter, and 6 studies reporting no difference in consultation length. Groups of patients receiving decision aids do not appear to differ from comparison groups in terms of anxiety (n = 30), general health outcomes (n = 11), and condition-specific health outcomes (n = 11). The effects of decision aids on other outcomes (adherence to the decision, costs/resource use) were inconclusive. AUTHORS' CONCLUSIONS: There is high-quality evidence that decision aids compared to usual care improve people's knowledge regarding options, and reduce their decisional conflict related to feeling uninformed and unclear about their personal values. There is moderate-quality evidence that decision aids compared to usual care stimulate people to take a more active role in decision making, and improve accurate risk perceptions when probabilities are included in decision aids, compared to not being included. There is low-quality evidence that decision aids improve congruence between the chosen option and the patient's values.New for this updated review is further evidence indicating more informed, values-based choices, and improved patient-practitioner communication. There is a variable effect of decision aids on length of consultation. Consistent with findings from the previous review, decision aids have a variable effect on choices. They reduce the number of people choosing discretionary surgery and have no apparent adverse effects on health outcomes or satisfaction. The effects on adherence with the chosen option, cost-effectiveness, use with lower literacy populations, and level of detail needed in decision aids need further evaluation. Little is known about the degree of detail that decision aids need in order to have a positive effect on attributes of the choice made, or the decision-making process.
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Técnicas de Apoyo para la Decisión , Educación del Paciente como Asunto/métodos , Participación del Paciente , Procedimientos Quirúrgicos Electivos , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Metabolic byproducts serve as indicators of the chemical processes and can provide valuable information on pathogenesis by measuring the amplified output. Standardized techniques for metabolome extraction of skin samples serve as a critical foundation to this field but have not been developed. OBJECTIVES: We sought to determine the optimal cell lysage techniques for skin sample preparation and to compare GC-TOF-MS and UHPLC-QTOF-MS for metabolomic analysis. METHODS: Using porcine skin samples, we pulverized the skin via various combinations of mechanical techniques for cell lysage. After extraction, the samples were subjected to GC-TOF-MS and/or UHPLC-QTOF-MS. RESULTS: Signal intensities from GC-TOF-MS analysis showed that ultrasonication (2.7x107) was most effective for cell lysage when compared to mortar-and-pestle (2.6x107), ball mill followed by ultrasonication (1.6x107), mortar-and-pestle followed by ultrasonication (1.4x107), and homogenization (trial 1: 8.4x106; trial 2: 1.6x107). Due to the similar signal intensities, ultrasonication and mortar-and-pestle were applied to additional samples and subjected to GC-TOF-MS and UHPLC-QTOF-MS. Ultrasonication yielded greater signal intensities than mortar-and-pestle for 92% of detected metabolites following GC-TOF-MS and for 68% of detected metabolites following UHPLC-QTOF-MS. CONCLUSION: Overall, ultrasonication is the preferred method for efficient cell lysage of skin tissue for both metabolomic platforms. With standardized sample preparation, metabolomic analysis of skin can serve as a powerful tool in elucidating underlying biological processes in dermatological conditions.
Asunto(s)
Extractos Celulares/química , Espectrometría de Masas/métodos , Metabolómica/métodos , Piel/química , Animales , Metaboloma , Metabolómica/instrumentación , Proyectos Piloto , PorcinosRESUMEN
BACKGROUND: Recent therapeutic advances have improved survival among lung cancer (LC) patients, who are now at high risk of second primary lung cancer (SPLC). Hispanics comprise the largest minority in the U.S., who have shown a lower LC incidence and mortality than other races, yet their SPLC risk is poorly understood.We quantified the SPLC incidence patterns among Hispanics vs other races. METHODS: We used data from the Multiethnic Cohort, a population-based cohort of five races (African American, Japanese American, Hispanic, Native Hawaiian, and White), recruited between 1993-1996 and followed through 2017. We identified patients diagnosed with initial primary lung cancer (IPLC) and SPLC via linkage to SEER registries. We estimated the 10-year cumulative incidence of IPLC (in the entire cohort) and SPLC (among IPLC patients). A standardized incidence ratio (SIR) was calculated as the ratio of SPLC-to-IPLC incidence by race/ethnicity. RESULTS: Among 202,692 participants, 6,788 (3.3%) developed IPLC over 3,871,417 person-years. The 10-year cumulative IPLC incidence was lower among Hispanics (0.80%, [0.72-0.88]) vs Whites (1.67%, [1.56-1.78]) or Blacks (2.44%, [2.28-2.60]). However, the 10-year SPLC incidence following IPLC was higher among Hispanics (3.11%, [1.62-4.61]) vs Whites (2.80%, [1.94-3.66]) or Blacks (2.29%, [1.48-3.10]), resulting in a significantly higher SIR for Hispanics (SIR = 8.27, [5.05-12.78]) vs Whites (SIR = 5.60, [4.11-7.45]) or Blacks (SIR = 3.48, [2.42-4.84])(p < .001). CONCLUSION: Hispanics have a higher SPLC incidence following IPLC than other races, which may be potentially due to better survival after IPLC and extended duration for SPLC development. Continuing surveillance is warranted to reduce racial disparities among LC survivors.