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1.
Nature ; 612(7940): 495-502, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36450981

RESUMEN

Fanconi anaemia (FA), a model syndrome of genome instability, is caused by a deficiency in DNA interstrand crosslink repair resulting in chromosome breakage1-3. The FA repair pathway protects against endogenous and exogenous carcinogenic aldehydes4-7. Individuals with FA are hundreds to thousands fold more likely to develop head and neck (HNSCC), oesophageal and anogenital squamous cell carcinomas8 (SCCs). Molecular studies of SCCs from individuals with FA (FA SCCs) are limited, and it is unclear how FA SCCs relate to sporadic HNSCCs primarily driven by tobacco and alcohol exposure or infection with human papillomavirus9 (HPV). Here, by sequencing genomes and exomes of FA SCCs, we demonstrate that the primary genomic signature of FA repair deficiency is the presence of high numbers of structural variants. Structural variants are enriched for small deletions, unbalanced translocations and fold-back inversions, and are often connected, thereby forming complex rearrangements. They arise in the context of TP53 loss, but not in the context of HPV infection, and lead to somatic copy-number alterations of HNSCC driver genes. We further show that FA pathway deficiency may lead to epithelial-to-mesenchymal transition and enhanced keratinocyte-intrinsic inflammatory signalling, which would contribute to the aggressive nature of FA SCCs. We propose that the genomic instability in sporadic HPV-negative HNSCC may arise as a result of the FA repair pathway being overwhelmed by DNA interstrand crosslink damage caused by alcohol and tobacco-derived aldehydes, making FA SCC a powerful model to study tumorigenesis resulting from DNA-crosslinking damage.


Asunto(s)
Reparación del ADN , Anemia de Fanconi , Genómica , Neoplasias de Cabeza y Cuello , Humanos , Aldehídos/efectos adversos , Aldehídos/metabolismo , Reparación del ADN/genética , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Anemia de Fanconi/patología , Neoplasias de Cabeza y Cuello/inducido químicamente , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Infecciones por Papillomavirus , Carcinoma de Células Escamosas de Cabeza y Cuello/inducido químicamente , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Daño del ADN/efectos de los fármacos
2.
Inorg Chem ; 63(5): 2352-2362, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38267375

RESUMEN

The exploration of smart sensors is of great significance for the selectivity, sensitivity, and ability to show the low detection limit for the target analyte. Here, we have used the linker H2L (5-((anthracen-9-ylmethyl)amino)isophthalic acid) for the construction of {[Cd(L)(DMF)(H2O)2]·H2O}n (1) which is in order with the chromophore anthracene moiety and the free -NH functionality as a guest interaction site. This framework showed the luminescence recovery "turn-on" detection of the Al3+ ion in an aqueous solution. An exhaustive mechanism study disclosed that the Lewis acid-base-type interaction between the Al3+ ion and the -NH functionality of the linker in the framework revealed that the absorbance caused an enhancement for the "turn-on" sensing event. Besides the "turn-on" sensing event, the "turn-off" sensing phenomenon of 1 is also noticed when it detects the hazardous oxo-anions (MnO4- and CrO42-) with limit of detection values of 17.08 and 19.91 ppb, respectively. The detection of these diverse analytes are very fast (10 s) and they can also be recognized through a colorimetric response. The sensing mechanisms for these analytes are established by photoinduced electron transfer, Forster resonance energy transfer, and inert filter effect along with theoretical investigation. Furthermore, to show the sensing application of 1 in a versatile podium, a MOF gel composite, 1@AA (AA = Agar-Agar), was developed from 1 with AA. Interestingly, 1@AA showed the colorimetric detection of these analytes under UV light. Therefore, sensor 1 behaves as a smart sensory material for the recognition of the above analytes through a simultaneous "turn-on" and "turn-off" effect.

3.
J Biol Chem ; 298(3): 101687, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35143842

RESUMEN

Pemphigus vulgaris (PV) is a potentially lethal autoimmune mucocutaneous blistering disease characterized by binding of IgG autoantibodies (AuAbs) to keratinocytes (KCs). In addition to AuAbs against adhesion molecules desmogleins 1 and 3, PV patients also produce an AuAb against the M3 muscarinic acetylcholine (ACh) receptor (M3AR) that plays an important role in regulation of vital functions of KCs upon binding endogenous ACh. This anti-M3AR AuAb is pathogenic because its adsorption eliminates the acantholytic activity of PV IgG; however, the molecular mechanism of its action is unclear. In the present study, we sought to elucidate the mode of immunopharmacologic action of the anti-M3AR AuAb in PV. Short-term exposures of cultured KCs to PV IgG or the muscarinic agonist muscarine both induced changes in the expression of keratins 5 and 10, consistent with the inhibition of proliferation and upregulated differentiation and in keeping with the biological function of M3AR. In contrast, long-term incubations induced a keratin expression pattern consistent with upregulated proliferation and decreased differentiation, in keeping with the hyperproliferative state of KCs in PV. This change could result from desensitization of the M3AR, representing the net antagonist-like effect of the AuAb. Therefore, chronic exposure of KCs to the anti-M3AR AuAb interrupts the physiological regulation of KCs by endogenous ACh, contributing to the onset of acantholysis. Since cholinergic agents have already demonstrated antiacantholytic activity in a mouse model of PV and in PV patients, our results have translational significance and can guide future development of therapies for PV patients employing cholinergic drugs.


Asunto(s)
Autoanticuerpos , Inmunoglobulina G , Pénfigo , Receptores Muscarínicos , Acantólisis/inmunología , Acantólisis/metabolismo , Acantólisis/patología , Animales , Autoanticuerpos/inmunología , Autoanticuerpos/farmacología , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina G/farmacología , Queratinocitos/metabolismo , Queratinocitos/patología , Ratones , Pénfigo/inmunología , Pénfigo/metabolismo , Pénfigo/patología , Pénfigo/terapia , Receptores Muscarínicos/inmunología , Receptores Muscarínicos/metabolismo
4.
Am J Physiol Gastrointest Liver Physiol ; 320(4): G609-G616, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33596155

RESUMEN

Exercises involving pelvic floor muscles including repetitive voluntary contractions of external anal sphincter (EAS) musculature have been used to improve fecal incontinence. Muscle fatigue is a prerequisite for successful strength training. However, muscle fatigue induced by these exercises has not been systematically studied. We aimed to assess the fatigability of EAS muscles during various exercise methods. Twelve nulliparous (21 ± 2.7 yr) women were studied. We evaluated fatigue during 40 repetitive 3-s contractions and 30-s long squeeze contractions both with and without an intra-anal compressible resistant load. The sequence of exercises was randomized. This load was provided by the continence muscles Resistance Exerciser Device. Anal canal pressures were recorded by high-resolution manometry. Exercise against a resistive load showed significant decrease in anal contractile integral (CI) and maximum squeeze pressure during repetitive short squeeze contractions compared with exercise without a load. Linear regression analysis showed a significant negative correlation between anal CI and successive contraction against load, suggesting "fatigue." Similar findings were observed for maximum squeeze pressure (slope with load = -4.2, P = 0.0003, vs. without load = -0.9, P = 0.3). Long squeeze contraction against a load was also more susceptible to fatigue than without a load (P < 0.0001). In conclusion, repetitive contractions against a compressible load induce fatigue and thus have the potential to strengthen the anal sphincter contractile function than contractions without a load. Fatigue rate in long squeeze contraction exercises with a load is significantly faster than that without a load, also indicating greater effectiveness in inducing muscle fatigue.NEW & NOTEWORTHY Fecal incontinence is a distressing disorder with a mainstay of treatment being pelvic floor muscle exercises. However, none of these exercises has proven occurrence of fatigability, which is an important prerequisite for successful muscle strengthening in rehabilitative exercises. In this study, we proved that we can fatigue the external anal sphincter muscles more efficiently by providing a resistive load during anal repetitive short squeeze contractions and long squeeze contraction exercise.


Asunto(s)
Canal Anal/fisiología , Contracción Muscular , Fatiga Muscular , Fuerza Muscular , Diafragma Pélvico/fisiología , Entrenamiento de Fuerza/instrumentación , Incontinencia Fecal/fisiopatología , Femenino , Humanos , Trastornos del Suelo Pélvico/fisiopatología , Trastornos del Suelo Pélvico/terapia , Distribución Aleatoria , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
5.
J Gen Intern Med ; 36(3): 600-605, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33420560

RESUMEN

BACKGROUND: Many national guidelines recommend the use of patient provider agreements (PPAs) when prescribing opioids for chronic pain. There are no standards for PPA content, readability, or administration processes. OBJECTIVE: Conduct a national survey of providers who use PPAs to describe the process of administering them, assess views on their utility, and obtain PPAs to evaluate thematic content and readability. DESIGN: Cross-sectional electronic survey and request for PPAs. PARTICIPANTS: Registrants for the Safer/Competent Opioid Prescribing Education (SCOPE of Pain) Program between March 2013 and June 2017. MAIN MEASURES: Respondents' reports on how PPAs are administered and views on their usefulness. A sample of PPAs assessed for themes and readability. KEY RESULTS: Using a convenience sample of 62,530 SCOPE of Pain registrants, we obtained a cohort of 430 individuals from 43 states who use PPAs. The majority of respondents worked in primary care (64%) and pain (18%) specialties. Reviewing PPAs with patients was primarily done by prescribers (80%), and the average perceived time to administer PPAs was 13 min. Although 66% of respondents thought PPAs were "often" or "always" worth the effort, only 28% considered them "often" or "always" effective in reducing opioid misuse. The PPA reading burden surpassed recommended patient education standards, with only 2.5% at or below fifth-grade reading level. PPAs focused more on rules and consequences of patients' non-compliance than on a shared treatment plan. CONCLUSIONS: Most respondents perceive patient provider agreements (PPAs) as time-consuming and minimally effective in reducing opioid misuse yet still view them as valuable. PPAs are written far above recommended reading levels and serve primarily to convey consequences of non-compliance. Because PPAs are recommended by national safer opioid prescribing guidelines as a risk mitigation strategy, it would be beneficial to develop a standard PPA and study its effectiveness.


Asunto(s)
Dolor Crónico , Trastornos Relacionados con Opioides , Analgésicos Opioides/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Estudios Transversales , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Pautas de la Práctica en Medicina
6.
Gastrointest Endosc ; 93(6): 1276-1282, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33309653

RESUMEN

BACKGROUND AND AIMS: EMR and endoscopic submucosal dissection (ESD) are treatment modalities for Barrett's esophagus involving high-grade dysplasia or early cancer. Injectional corticosteroid therapy decreases the risk of procedure-related esophageal stricture (ES) formation. Our aim was to assess the efficacy of topical budesonide on the rate of ES formation after EMR or ESD. METHODS: Patients included prospectively from 3 tertiary endoscopy centers received 3 mg budesonide orally twice a day for 8 weeks after esophageal EMR or ESD of 50% or more of the esophageal circumference between January 1, 2014 and June 30, 2018. These patients were matched (1:3 ratio) retrospectively with a consecutive patient cohort who underwent EMR or ESD of 50% or more of the esophageal circumference without concomitant corticosteroid therapy. The primary endpoint was the presence of ES at the 12-week follow-up. RESULTS: Twenty-five patients (budesonide) were matched with 75 patients (no budesonide). Most underwent EMR for Barrett's esophagus with biopsy-proven high-grade dysplasia or suspected T1a cancer. Although most baseline characteristics did not differ significantly, patients in the budesonide cohort tended to have a higher proportion of circumferential EMR. The proportion of patients with ES was not significantly lower in the budesonide cohort (16% vs 28%). On logistic regression analysis, budesonide remained associated with a lower incidence of ES (P = .023); however, when controlling for baseline characteristics with a propensity score weighted logistic regression model, there was no significant effect on ES formation (P = .176). CONCLUSIONS: Topical budesonide might be associated with a reduction of ES after EMR or ESD; however, further studies are needed to verify our results.


Asunto(s)
Adenocarcinoma , Esófago de Barrett , Resección Endoscópica de la Mucosa , Neoplasias Esofágicas , Estenosis Esofágica , Budesonida/uso terapéutico , Resección Endoscópica de la Mucosa/efectos adversos , Estenosis Esofágica/etiología , Estenosis Esofágica/prevención & control , Humanos , Estudios Retrospectivos
7.
Am J Emerg Med ; 39: 254.e1-254.e3, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32631770

RESUMEN

As the 2019 coronavirus pandemic has unfolded, an increasing number of atypical presentations of COVID-19 have been reported. As patients with COVID-19 often present to emergency departments for initial care, it is important that emergency clinicians are familiar with these atypical presentations in order to prevent disease transmission. We present a case of a 21-year-old woman diagnosed in our ED with COVID-19 associated parotitis and review the epidemiology and management of parotitis. We discuss the importance of considering COVID-19 in the differential of parotitis and other viral-associated syndromes and emphasize the importance of donning personal protective equipment during the initial evaluation.


Asunto(s)
COVID-19/complicaciones , Servicio de Urgencia en Hospital/organización & administración , Control de Infecciones/métodos , Parotiditis/diagnóstico , Femenino , Humanos , Parotiditis/prevención & control , Parotiditis/virología , Equipo de Protección Personal , Adulto Joven
8.
ORL J Otorhinolaryngol Relat Spec ; 83(3): 203-205, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33657548

RESUMEN

Although nasal polyposis is a common clinical entity, there is limited literature describing the rare presentation of sudden prolapse of a massive nasal polyp resulting in an airway emergency in an adult. We present the first case report to our knowledge of a patient without any preceding sinonasal symptoms or history of anticoagulation who experienced acute upper airway obstruction due to sudden hemorrhage and prolapse of a large nasal polyp. Based on our experience treating this patient, we discuss special considerations in all phases of care to ensure safe and effective management of such an exceptional clinical scenario.


Asunto(s)
Obstrucción de las Vías Aéreas , Obstrucción Nasal , Pólipos Nasales , Adulto , Obstrucción de las Vías Aéreas/diagnóstico por imagen , Obstrucción de las Vías Aéreas/etiología , Humanos , Obstrucción Nasal/etiología , Obstrucción Nasal/cirugía , Pólipos Nasales/complicaciones , Pólipos Nasales/diagnóstico por imagen , Pólipos Nasales/cirugía , Prolapso
9.
Oncologist ; 25(5): e789-e797, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31784491

RESUMEN

BACKGROUND: Patients with pituitary metastasis (PM) have a relatively poor prognosis. We describe the presentation, management, and outcomes of patients with PM. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective review of patients diagnosed with PM at a single institution from 1996 to 2015. Eighty-five patients diagnosed with metastasis to the pituitary or sella turcica by pathology or based on a combination of neuroimaging and clinical findings were included. Univariate and multivariable Cox regressions evaluated associations between clinical factors and overall survival. RESULTS: The most frequent sites of primary malignancies resulting in PM were lung (26%) and breast (26%). Median age at diagnosis was 60 years (range, 18-95). The most common complaints at diagnosis included visual deficits (62%), headache (47%), and cranial nerve palsy (31%). Seventy percent of patients had pituitary insufficiency-adrenal insufficiency (59%), hypothyroidism (59%), or diabetes insipidus (28%). Management of PM included radiation therapy (76%), chemotherapy (68%), surgical resection (21%), or combination therapy (71%). Fifty percent and 52% of patients who received surgical treatment and irradiation, respectively, reported symptomatic improvement. Median overall survival (OS) was 16.5 months (95% confidence interval: 10.7-25.4). On multivariable analysis, a primary cancer site other than lung or breast (p = .020), age <60 years (p = .030), and surgical resection (p = .016) were associated with longer OS. CONCLUSION: Patients <60 years of age, those with primary tumor sites other than lung or breast, and those who undergo surgical resection of the pituitary lesion may have prolonged survival. Surgical resection and radiation treatment resulted in symptomatic improvement in ~50% of patients. IMPLICATIONS FOR PRACTICE: This study is the largest original series of patients with metastatic disease to the sella. In patients with pituitary metastasis, younger age, primary site other than lung or breast, and metastatic resection may prolong survival. Resection and radiation led to symptomatic improvement in ∼50% of patients. Seventy percent of patients had hypopituitarism. These hormonal deficiencies can be life threatening and can result in substantial morbidity if left untreated. Patients should be treated using a multimodality approach-including a potential role for surgery, radiation, chemotherapy, and hormone replacement-with the goal of improving survival and quality of life.


Asunto(s)
Neoplasias Hipofisarias , Calidad de Vida , Terapia Combinada , Humanos , Persona de Mediana Edad , Neoplasias Hipofisarias/cirugía , Estudios Retrospectivos
10.
Dig Dis Sci ; 65(5): 1324-1333, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31642008

RESUMEN

BACKGROUND: Significant disparities in hepatitis C (HCV) treatment existed in the interferon treatment era, such that patients with mental health and substance use disorders were less likely to be treated. We aimed to evaluate whether these perceptions continue to influence HCV treatment decisions. METHODS: We e-mailed HCV providers a survey to assess their perceptions of barriers to HCV treatment adherence and initiation. We assessed the frequency of perceived barriers and willingness to initiate HCV treatment in patients with these barriers. We identified a group of providers more willing to treat patients with perceived barriers to adherence and determined the associated provider characteristics using Spearman's rho and Wilcoxon rank-sum tests. RESULTS: A total of 103 providers (29%) responded to the survey. The most commonly endorsed perceived barriers to adherence were homelessness (65%), ongoing drug (58%), and ongoing alcohol use (33%). However, 90%, 68%, and 90% of providers were still willing to treat patients with these comorbidities, respectively. Ongoing drug use was the most common reason providers were never or rarely willing to initiate HCV treatment. Providers who were less willing to initiate treatment more frequently endorsed patient-related determinants of adherence, while providers who were more willing to initiate treatment more frequently endorsed provider-based barriers to adherence (e.g., communication). CONCLUSIONS: Most responding providers were willing to initiate HCV treatment in all patients, despite the presence of perceived barriers to adherence or previous contraindications to interferon-based treatments. Ongoing substance use remains the most prominent influencer in the decision not to treat.


Asunto(s)
Antivirales/uso terapéutico , Actitud del Personal de Salud , Personal de Salud/psicología , Hepatitis C/tratamiento farmacológico , Cumplimiento de la Medicación/psicología , Adulto , Toma de Decisiones Clínicas , Femenino , Hepacivirus , Hepatitis C/psicología , Humanos , Masculino , Persona de Mediana Edad
11.
Ann Hematol ; 98(4): 851-860, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30488326

RESUMEN

Beta-thalassemia (ß-thalassemia) is a frequently inherited monogenic disorder worldwide with severe physical and mental health comorbidities. The aim of this study is to evaluate the burden of psychiatric disorders in adult patients hospitalized with ß-thalassemia in the United States (US). We utilized the discharge data from the National Inpatient Sample (NIS) from 2010 through 2014 to identify hospitalized ß-thalassemia patients who are 18 years and older. We assessed categorical and continuous variables using chi-square test and Student's t test respectively. The burden of psychiatric disorders was assessed using descriptive statistics and represented in terms of frequency (n) and percentage (%). A p value threshold of < 0.05 was considered clinically significant. All statistical analyses were performed using SPSS version 22.0 (IBM Corp., Armonk, NY, USA). Of the 10,046 ß-thalassemia patients studied, 24.4% (n = 2448) reported psychiatric disorders. Mood disorders (15.2%; inclusive of 10.3% depression), followed by anxiety (9.4%), and substance abuse disorder (6.5%; 4.3% drug abuse, 2.2% alcohol abuse) were most prevalent. Comorbid mental illnesses increased the length of stay by 44.6% and total costs by 23.4%. All-cause mortality rate was reported at 1.9% in overall ß-thalassemia patients. This study highlights higher rates of psychiatric disorders such as depression and anxiety and correlated increases in length of stay and cost in hospitalized ß-thalassemia patients. To improve medical outcomes and curtail unnecessary health-care costs, implementation of an integrated care model can be considered.


Asunto(s)
Costo de Enfermedad , Trastornos Mentales , Talasemia beta , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Trastornos Mentales/mortalidad , Trastornos Mentales/psicología , Persona de Mediana Edad , Prevalencia , Tasa de Supervivencia , Estados Unidos/epidemiología , Talasemia beta/mortalidad , Talasemia beta/psicología
12.
Dig Dis Sci ; 64(10): 3001-3012, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30903364

RESUMEN

BACKGROUND: Despite the availability of direct acting antiviral medications (DAAs), there are ongoing concerns about adherence to hepatitis C virus (HCV) treatment. We sought to understand the barriers to and facilitators of DAA adherence in the Veteran population. METHODS: Patients completed semi-structured interviews focused on barriers to and facilitators of HCV treatment adherence both pre- and post-DAA treatment. Adherence was assessed via provider pill count and self-report. Thematic analyses were conducted in the qualitative software program Atlas.ti in order to understand anticipated barriers to and facilitators of treatment adherence and completion. Charts were reviewed for clinical data and sustained virologic response (SVR12). RESULTS: Of 40 patients, 15 had cirrhosis and 10 had prior interferon-based treatment. Pre-treatment interviews revealed anticipated barriers to adherence such as side effects (n = 21) and forgetting pills (n = 11). Most patients (n = 27) reported following provider advice, and others had unique reasons not to (e.g., feeling like a "guinea pig"). Post-treatment interviews uncovered facilitators of treatment including wanting to cure HCV (n = 17), positive results (n = 18), and minimal side effects (n = 15). Three patients (8%) did not complete therapy (whom we further elaborate on) and 6 (15%) missed doses but completed treatment. SVR12 was achieved by all participants who completed therapy (93%). Patients who did not complete therapy or missed doses were all treatment naïve, mostly non-cirrhotic (8 of 9), and often anticipated concerns with forgetting their medications. CONCLUSIONS: This qualitative study uncovered several unanticipated determinants of HCV treatment completion and provides rationale for several targeted interventions such as incorporating structured positive reinforcement.


Asunto(s)
Antivirales , Barreras de Comunicación , Hepatitis C Crónica , Cumplimiento y Adherencia al Tratamiento , Veteranos , Anticipación Psicológica , Antivirales/efectos adversos , Antivirales/uso terapéutico , Femenino , Necesidades y Demandas de Servicios de Salud , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/psicología , Humanos , Masculino , Relaciones Profesional-Paciente , Prevención Secundaria/métodos , Respuesta Virológica Sostenida , Cumplimiento y Adherencia al Tratamiento/psicología , Cumplimiento y Adherencia al Tratamiento/estadística & datos numéricos , Estados Unidos/epidemiología , Veteranos/psicología , Veteranos/estadística & datos numéricos
13.
J Surg Oncol ; 117(4): 756-764, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29193098

RESUMEN

BACKGROUND AND OBJECTIVES: Primary surgery is the preferred treatment of T1-T4a sinonasal squamous cell carcinoma (SNSCC). METHODS: Patients with SNSCC in the National Cancer Data Base (NCDB) were analyzed. Factors that contributed to selecting primary surgical treatment were examined. Overall survival (OS) in surgical patients was analyzed. RESULTS: Four-thousand seven hundred and seventy patients with SNSCC were included. In T1-T4a tumors, lymph node metastases, maxillary sinus location, and treatment at high-volume centers were associated with selecting primary surgery. When primary surgery was utilized, tumor factors and positive margin guided worse OS. Adjuvant therapy improved OS in positive margin resection and advanced T stage cases. CONCLUSIONS: Tumor and non-tumor factors are associated with selecting surgery for the treatment of SNSCC. When surgery is selected, tumor factors drive OS. Negative margin resection should be the goal of a primary surgical approach. When a positive margin resection ensues, adjuvant therapy may improve OS.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias de los Senos Paranasales/cirugía , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Quimioradioterapia Adyuvante , Estudios de Cohortes , Femenino , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de los Senos Paranasales/tratamiento farmacológico , Neoplasias de los Senos Paranasales/patología , Neoplasias de los Senos Paranasales/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello , Tasa de Supervivencia
14.
Pharmacoepidemiol Drug Saf ; 27(12): 1295-1301, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30379371

RESUMEN

PURPOSE: The purpose of the study is to assess the current state of the art in pediatric comparative effectiveness research, potential gaps, and areas for improvement. METHODS: Relevant articles from inception to February 2015 were retrieved from Embase and Medline. We sequentially screened titles, abstracts, and full texts, with independent validation. Data regarding general information and study methods including statistical analysis were extracted. Study quality was assessed using Newcastle-Ottawa Scale (NOS). Investigated drugs were ranked and compared with data on the prevalence of pediatric drug use. RESULTS: Three thousand nine hundred twenty-six abstracts were screened for eligibility and inclusion, and 164 articles were included in the review. Most studies were from North America (46.7%). Only 78 studies (47.6%) reported the design: 90.8% were cohort studies. Neonates were least frequently investigated. The drugs that were most often studied included systemic antibacterials (11.4%), psycholeptics (7.9%), and antiepileptics (7.6%). Adjustment for confounding was made using propensity scores in 8.5% of the studies. Studies that did not report the design were of lower quality. Many effectiveness studies were done on antineoplastic agents, which are not frequently used and few studies on analgesics and drugs for obstructive airway diseases which are frequently prescribed. CONCLUSIONS: There is ample opportunity to improve comparative effectiveness research for drugs used in pediatrics. Routinely prescribed drugs were seldom investigated. Modern methods for confounding adjustment, such as propensity scores, were rarely used.


Asunto(s)
Investigación sobre la Eficacia Comparativa/métodos , Estudios Observacionales como Asunto , Proyectos de Investigación , Antibacterianos/uso terapéutico , Anticonvulsivantes/uso terapéutico , Antipsicóticos/uso terapéutico , Niño , Investigación sobre la Eficacia Comparativa/estadística & datos numéricos , Humanos , Recién Nacido , Puntaje de Propensión , Resultado del Tratamiento
15.
Dig Dis Sci ; 62(8): 1933-1943, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28523579

RESUMEN

BACKGROUND: Provider perceptions regarding barriers to and facilitators of hepatitis C (HCV) treatment initiation and adherence have not been fully evaluated in the interferon-free treatment era. New treatments have provided opportunities for non-specialists to treat HCV, underscoring the importance of understanding primary care provider (PCP) and specialist perspectives. METHODS: Based on qualitative sampling principles, 12 PCPs and 12 hepatology providers (HPs) from the VA Pittsburgh Healthcare System completed audio-recorded semi-structured interviews. Qualitative analysts coded perceived barriers and facilitators from the interviews with 100% double coding. Codes were thematized and analyzed using Atlas.ti. RESULTS: Key barriers to treatment described by HPs and PCPs included patients' substance use disorders, mental health, transportation availability, history of non-adherence, and concern about side effects. PCPs also focused on medication cost as a system-based barrier. The main facilitators of treatment initiation and adherence described by both HPs and PCPs were provider education and encouragement. HPs focused almost exclusively on provider-based facilitators, while PCPs noted patient-based facilitators including past adherence, media exposure to information about HCV medications, a desire to clear the virus, and positive feedback regarding treatment response. CONCLUSIONS: Providers generally focused on perceived patient-level barriers to HCV treatment initiation and adherence, as well as provider-level facilitators; PCPs additionally noted patient preferences and system-level issues that guide decision making regarding treatment initiation. While HPs focused almost exclusively on provider-level facilitators, PCPs additionally focused on patient-level facilitators of treatment. These data provide novel insights and suggest focusing on patient, provider, and system-level strategies to further improve HCV treatment initiation and adherence.


Asunto(s)
Actitud del Personal de Salud , Gastroenterología/métodos , Personal de Salud/psicología , Hepatitis C/psicología , Atención Primaria de Salud/métodos , Especialización , Adulto , Femenino , Gastroenterología/normas , Adhesión a Directriz , Conocimientos, Actitudes y Práctica en Salud , Personas con Mala Vivienda/psicología , Humanos , Masculino , Trastornos Mentales/psicología , Persona de Mediana Edad , Cooperación del Paciente/psicología , Prioridad del Paciente , Selección de Paciente , Percepción , Atención Primaria de Salud/normas , Investigación Cualitativa , Trastornos Relacionados con Sustancias/psicología
18.
Artículo en Inglés | MEDLINE | ID: mdl-26159894

RESUMEN

BACKGROUND/AIMS: Preoperative identification of malignant parotid lesions remains challenging, and thus, some surgeons use frozen section (FS) to assist them in their decision making. We evaluated the pathologic and cost benefit of FS after fine-needle aspiration (FNA) at our institution. METHODS: We assessed medical data for 260 patients undergoing parotidectomy with FS. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for radiology, FNA, and FS. RESULTS: The sensitivities, specificities, and accuracies of FNA and FS were 75.0, 96.4, and 93.2%, and 75.0, 100, and 96.8%, respectively. FS detected 0% of FNA false negatives and 80% of false positives. The additional pathology charge for FS alone per correctly identified benign lesion after a positive FNA was USD 1,443. CONCLUSION: FNA and FS are more reliable in the prognostication of the final pathology than radiology. At our center, FS appears to be of limited clinical use after benign FNAs, but may be more useful after positive, indeterminate, and nondiagnostic FNAs.


Asunto(s)
Adenoma/diagnóstico , Biopsia con Aguja Fina , Carcinoma/diagnóstico , Secciones por Congelación , Neoplasias de la Parótida/diagnóstico , Adenoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/cirugía , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias de la Parótida/cirugía , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Adulto Joven
19.
Br J Community Nurs ; 20(7): 322, 324-6, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26140316

RESUMEN

In addition to movement disorders, Parkinson's disease (PD) is associated with several nonmotor symptoms, including dysphagia (swallowing difficulties). Dysphagia can make the consumption of solid medicines difficult, which potentially contributes to the poor adherence that is common among people with PD. However, patients may be reluctant to admit that they experience dysphagia. Community nurses should actively enquire into swallowing difficulties among all patients, not only those with PD, and should work with pharmacists and other members of the multidisciplinary team to help optimise medication management to help improve adherence.


Asunto(s)
Antiparkinsonianos/administración & dosificación , Trastornos de Deglución/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/etiología , Enfermería en Salud Comunitaria , Trastornos de Deglución/enfermería , Humanos , Cumplimiento de la Medicación , Rol de la Enfermera , Enfermedad de Parkinson/enfermería , Reino Unido
20.
J Foot Ankle Surg ; 53(2): 137-40, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24345706

RESUMEN

The Infectious Disease Society of America has defined gas gangrene as an infection caused by Clostridium species. However, in many clinical settings, soft tissue infections that produce subcutaneous gas have been diagnosed as gas gangrene without identification of the presence of Clostridium species. Instead, the diagnosis was based on clinical and radiographic findings. A chart review was performed of 25 consecutive patients treated at the Atlantic Health System for infections of the lower extremity that were diagnosed as gas gangrene. Wound cultures from the 25 patients grew 31 different species of bacteria. The most prevalent organism was Staphylococcus aureus, which accounted for 17 of 31 (54.84%) different organisms identified and 19.77% of 86 separate aerobic or anaerobic cultures. The most prevalent genus was Streptococcus, which accounted for 20 (64.52%) of the organisms identified and 23.26% of the cultures. The most prevalent anaerobic genus was Peptostreptococcus, which accounted for 8 (25.81%) of the organisms identified and 9.3% of the cultures. None of the cultures grew Clostridium species. These findings showed that gas-forming soft tissue infections of the lower extremity, commonly diagnosed as gas gangrene, are rarely caused by Clostridium species.


Asunto(s)
Pie Diabético/microbiología , Gangrena Gaseosa/microbiología , Infecciones de los Tejidos Blandos/microbiología , Complicaciones de la Diabetes , Pie Diabético/diagnóstico , Gangrena Gaseosa/diagnóstico , Humanos , Infecciones de los Tejidos Blandos/diagnóstico
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