Pharmacokinetics of tolfenamic acid in patients with cirrhosis of the liver

Summary Six patients with alcoholic cirrhosis of the liver received 100 mg tolfenamic acid p.o. and i.v. The disposition of tolfenamic acid could be described by a two-compartment open body model, with a mean central compartment volume of 8.71, and a -phase volume of 251. The elimination rate constant k_e averaged 1.13 h^–1 and the half-life of the -phase was 1.73 h; the mean total plasma clearance was 159 ml/min. These pharmacokinetic parameters differed only slightly from those in two groups of healthy volunteers studied previously; k_e was significantly reduced by about 30% in the patients but none of the other parameters differed significantly. There was good correlation between individual elimination rate constants or plasma clearances with the liver function tests, serum albumin and P-coagulation factors. Oral absorption was good and bioavailability of about 100% was shown by comparison of the areas under the plasma concentration — time curves after i.v. and p.o. administration. Metabolism was qualitatively and quantitatively very similar to previous observations in healthy volunteers. There seems no reason to reduce the dose of tolfenamic acid in patients with compensated alcoholic cirrhosis.     

Fine-needle biopsy of the pancreas: Results of 204 routinely performed biopsies in 190 patients

Two-hundred and four fine-needle aspiration biopsies of the pancreas have been performed in 190 patients during a 12-year period. Sixty-one of these were performed percutaneously guided by endoscopic retrograde cholangio-pancreatography, percutaneous transhepatic cholangiography, angiography, or ultrasonography; and 143 were taken intraoperatively. In 77 (67%) out of 115 patients with pancreatic cancer, a correct cytological diagnosis was obtained. Two biopsies were reported as malignant in 1 patient who ultimately was found to have chronic pancreatitis (false positives). The frequency of not representative biopsies varied from 20.8% in patients with suspected cancer biopsied intraoperatively to 48.4% in patients biopsied preoperatively. A correct cytological diagnosis of malignancy was obtained preoperatively in 54.6% of patients with cancer, in 60.0% of patients evaluated without later operation, and in 71.1% of patients biopsied during laparotomy for suspected pancreatic cancer. The overall false-negative rate was 9.8%. The predictive value of a positive test was almost 100%, whereas the predictive value of a negative test was only 69.6% (total material). Analyses may indicate that a more aggressive approach with multiple punctures may lower the not representative biopsy rate and increase the diagnostic accuracy in patients with pancreatic cancer.

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Resumen Doscientas y cuatro biopsias pancreáticas por aspiración con aguja fina han sido realizadas en 190 pacientes en un período de 12 años. Sesenta y una de éstas fueron realizadas por vía percutánea guiada por colangiopancreatografía endoscópica retrógrada, colangiografía percutánea transhepática, angiografía, o ultrasonografía, y 143 fueron intraoperatorias. En 77 (67%) de 115 pacientes con cáncer del páncreas se obtuvo un diagnóstico citológico correcto. Dos biopsias fueron informadas como malignas en un paciente en quien finalmente se demostró pancreatitis crónica (falsas positivas). La frecuencia de biopsias no representativas varió entre 20.8% en pacientes con sospecha de cáncer y biopsia realizada intraoperatoriamente, a 48.4% en pacientes con biopsias realizadas en la fase preoperatoria. El diagnóstico citológico correcto de malignidad fue logrado preoperatoriamente en 54.6% de los pacientes con cáncer, en el 60.0% de los pacientes evaluados y sin operación posterior y en el 71.1% de los pacientes en quienes se realizó biopsia durante la laparotomía por sospecha de cáncer pancreático. La tasa global de resultados falsos negativos fue de 9.8%. El valor de predicción de una prueba positiva fue de casi 100%, mientras el valor de predicción de una prueba negativa fue de sólo 69.6% (material total). La implicación práctica de esto es que cuando se obtenga un resultado negativo se debe proceder con la toma de nuevas biopsias. En conclusión, creemos que la biopsia del páncreas con aguja fina es un procedimiento seguro que puede ser recomendado en todas las fases del proceso diagnóstico o terapéutico de lesiones pancreáticas, y que es valioso en la planeación de la terapia en pacientes con cáncer. Sinembargo, las biopsias negativas en casos de sospecha clínica de cáncer no siempre excluyen su presencia. Mayor análisis puede indicar que una actitud más agresiva, con punciones mÚltiples, puede disminuir la tasa de biopsias no representativas y aumentar la precisión diagnóstica en pacientes con cáncer pancreático.

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Résumé Deux cent quatre biopsies-aspirations à l'aiguille fine du pancréas ont été pratiquées chez 190 sujets au cours d'une période de 12 ans. Soixante et une d'entre elles ont été pratiquées par voie souscutanée en étant guidées par cathétérisme rétrograde, cholangiographie transpariétale, angiographie ou ultrasonographie et 143 ont été effectuées au cours de l'intervention. Chez 77 (67%) sujets appartenant à une série de 115 malades atteints de cancer du pancréas le diagnostic cytologique exact a été porté. Deux biopsies en faveur du diagnostic de cancer répondaient en réalité à des lésions de pancréatite chronique (faux positifs). La fréquence des biopsies ininterprétables chez les sujets suspects de cancer a varié de 20.8% lorsque l'examen a été pratiqué au cours de l'intervention à 48.4% lorsque ce mÊme examen a été effectué avant l'opération. Le taux de diagnostic cytologique exact de cancer a été respectivement de 54.6%, de 60.0% et 71.1% selon que la biopsie cytologique a l'aiguille a été pratiquée avant l'intervention, après un certain délai et au cours de l'opération. Au total, le taux des faux positifs s'est élevé à 9.8%. La fiabilité de la biopsie à l'aiguille a été proche de 100% en cas de biopsie positive mais seulement de 69.6% en cas de biopsie négative. L'analyse de l'ensemble de ces faits incite à adopter une attitude plus agressive c'est-à-dire à pratiquer des biopsies multiples au lieu d'une ponction unique pour réduire le taux des prélèvements ininterprétables et accroÎtre celui des résultats exacts.

     

ECT and Anticoagulation

Electroconvulsive therapy (ECT) is an effective and safe treatment for depression. Anticoagulation therapy is used to reduce morbidity or mortality from stroke or recurrent pulmonary embolus in various cardiac and vascular conditions. We report in detail the successful ECT treatment of a patient suffering from major depression with psychotic features who continued warfarin (Coumadin) anticoagulant therapy.     

Behavioral Health Screening and Care Coordination for Rural Veterans in a Federally Qualified Health Center

Many rural veterans receive care in community settings but could benefit from VA services for certain needs, presenting an opportunity for coordination across systems. This article details the Collaborative Systems of Care (CSC) program, a novel, nurse-led care coordination program identifying and connecting veterans presenting for care in a Federally Qualified Health Center to VA behavioral health and other services based upon the veteran’s preferences and eligibility. The CSC program systematically identifies veteran patients, screens for common behavioral health issues, explores VA eligibility for interested veterans, and facilitates coordination with VA to improve healthcare access. While the present program focuses on behavioral health, there is a unique emphasis on assisting veterans with the eligibility and enrollment process and coordinating additional care tailored to the patient. As VA expands its presence in community care, opportunities for VA-community care coordination will increase, making the development and implementation of such interventions important.

     

Nurse Decision-making for Suspected Urinary Tract Infections in Nursing Homes: Potential Targets to Reduce Antibiotic Overuse

ObjectivesTo determine what information is most important to registered nurses' (RNs) decisions to call clinicians about suspected urinary tract infections (UTIs) in nursing home residents.DesignWeb-based discrete choice experiment with 19 clinical scenarios.Setting and ParticipantsOnline survey with a convenience sample of RNs (N = 881) recruited from a health care research panel.MethodsClinical scenarios used information from 10 categories of resident characteristics: UTI risk, resident type, functional status, mental status, lower urinary tract status, body temperature, physical examination, urinalysis, antibiotic request, and goals of care. Participants were randomized into 2 deliberation conditions (self-paced, n = 437 and forced deliberation, n = 444). The degree to which evidence- and non–evidence-based information was important to decision-making was estimated using unconditional multinomial logistic regression.ResultsFor all nurses (22.8%) and the self-paced group (24.1%), lower urinary tract status had the highest importance scores for the decision to call a clinician about a suspected UTI. For the forced-deliberation group, body temperature was most important (23.7%), and lower urinary tract status was less important (21%, P = .001). The information associated with the highest odds of an RN calling about a suspected UTI was painful or difficult urination [odds ratio (OR) 4.85, 95% confidence interval (CI) 4.16–5.65], obvious blood in urine (OR 4.66, 95% CI 3.99–5.44), and temperature at 101.5° (OR 3.80, 95% CI 3.28–4.42). For the self-paced group, painful or difficult urination (OR 5.65, 95% CI 4.53–7.04) had the highest odds, whereas obvious blood in urine (OR 4.39, 95% CI 3.53–5.47) had highest odds for the forced-deliberation group.Conclusions and ImplicationsThis study highlighted the importance of specific resident characteristics in nurse decision-making about suspected UTIs. Future antimicrobial stewardship efforts should aim to not only improve the previously studied overprescribing practices of clinicians, but to improve nurses' assessment of signs and symptoms of potential infections and how they weigh resident information.     

Breast cancer in young women: Imaging and clinical course

The purpose of this study was to characterize presenting imaging findings in women younger than 40 diagnosed with invasive breast cancer in the context of pathology and clinical course. Retrospective chart and imaging reviews were performed in patients under 40 diagnosed with breast cancer between July 1, 2004, and December 31, 2013. Patient demographic, imaging, pathology, and clinical data were collected. Overall and recurrence-free survival were estimated using the Kaplan-Meier method. Univariate Cox proportional hazards models were performed to identify factors associated with recurrence-free survival. Our study cohort consisted of 110 patients with invasive mammary carcinoma. One hundred one (91.8%) presented with a palpable mass. The mean size of all lesions on imaging was 3.5 cm ± 2.9 cm. Malignant calcifications were present in 54 (49.1%) cases. Imaging demonstrated multifocal or multicentric disease in 45 (40.9%) cases. Seventy four (67.3%) cancers were high grade. Luminal genomic subtypes were the most common (n = 61, 55.5%). At presentation, 4 (3.6%) patients had bilateral malignancy and 8 (7.3%) patients had distant metastatic disease. Ninety seven (88.2%) underwent neoadjuvant chemotherapy and 67 (60.9%) underwent radiation therapy. Seventy five (68.2%) of the patients underwent mastectomy. The restricted mean time to recurrence was 9.01 years (standard error 3.162 months). ER positivity was associated with compromised recurrence-free survival. The overall survival rate was 0.962 at 10 years. Young patients diagnosed with breast cancer typically present with advanced breast imaging findings and undergo aggressive treatment. Recurrence often occurs >5 years from diagnosis, and ER positive subtypes are at increased risk for recurrence.     

Increased frequency of HLA-DPw2 in pauciarticular onset juvenile chronic arthritis

Thirty-six unrelated Danish patients with pauciarticular Juvenile Chronic Arthritis (PJCA) and 120 controls were typed for HLA-DPw1-w6 and the local specificity CDPHEI with bulk-expanded Primed Lymphocyte Typing (PLT) cells. The frequency of HLA-DPw2 was 52.8% in PJCA patients and 16.7% in controls (relative risk, RR = 4.5; P less than 0.001). The antigens HLA-Dw5 and/or Dw8 were present in 50% of the patients and in 21.3% of the controls (RR = 4.2; p less than 10(-3)). DPw2 was not associated (in linkage disequilibrium) with Dw5/w8 in patients or in controls, and the DP and D associations with PJCA were independent of each other. However, the combined presence of DPw2 and Dw5 and/or Dw8 gave a significantly higher risk of PJCA than each antigen alone indicating interaction of DP and DR gene products. PJCA is the first disease definitely found to be associated with a DP antigen.     

Persistent Subcutaneous Nodules in Children Hyposensitized with Aluminium-Containing Allergen Extracts

A follow-up study of 202 children who had received hyposensitization with aluminium-containing allergens showed that 1-3 years after cessation of hyposensitization 13 children still had severely pruiginous treatment-resistant subcutaneous nodules in their forearms. Because of their long persistence the nodules of six children were studied in detail. Histologically, the nodules showed infiltration with lymphocytes (forming germinal centres), macrophages, plasma cells, mast cells and a few eosinophils. In five patients aluminium crystals were found scattered between the cells and, in addition, the phagosomes of the macrophages contained aluminium. Patch tests for aluminium were positive in four of the six patients. It is concluded that persisting nodules during hyposensitization with aluminium-containing allergens may indicate development of aluminium hypersensitivity, and if this is confirmed hyposensitization should be discontinued.     

Impaired effortful cognition in depression

Depressed patients have been reported to have deficits in "effortful," but not effortless, cognitive functions compared to healthy volunteers. To test the hypothesis that the effortful cognitive deficits in major depression are not simply a function of psychiatric illness or hospitalization, we administered both effort-demanding and effortless cognitive tasks to 17 inpatients with major affective disorder and 17 hospitalized psychiatric controls. The depressed patients performed significantly more poorly than the controls on the effort-demanding task. The groups did not differ on the effortless task. These findings suggest that depressed patients are impaired in performing effort-demanding cognitive tasks compared to nondepressed psychiatric patients.