Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group

OBJECTIVE: To provide a uniform platform from which to study acute liver failure, the U.S. Acute Liver Failure Study Group has sought to standardize the management of patients with acute liver failure within participating centers. METHODS: In areas where consensus could not be reached because of divergent practices and a paucity of studies in acute liver failure patients, additional information was gleaned from the intensive care literature and literature on the management of intracranial hypertension in non-acute liver failure patients. Experts in diverse fields were included in the development of a standard study-wide management protocol. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure monitoring is recommended in patients with advanced hepatic encephalopathy who are awaiting orthotopic liver transplantation. At an intracranial pressure of > or =25 mm Hg, osmotic therapy should be instituted with intravenous mannitol boluses. Patients with acute liver failure should be maintained in a mildly hyperosmotic state to minimize cerebral edema. Accordingly, serum sodium should be maintained at least within high normal limits, but hypertonic saline administered to 145-155 mmol/L may be considered in patients with intracranial hypertension refractory to mannitol. Data are insufficient to recommend further therapy in patients who fail osmotherapy, although the induction of moderate hypothermia appears to be promising as a bridge to orthotopic liver transplantation. Empirical broad-spectrum antibiotics should be administered to any patient with acute liver failure who develops signs of the systemic inflammatory response syndrome, or unexplained progression to higher grades of encephalopathy. Other recommendations encompassing specific hematologic, renal, pulmonary, and endocrine complications of acute liver failure patients are provided, including their management during and after orthotopic liver transplantation. CONCLUSIONS: The present consensus details the intensive care management of patients with acute liver failure. Such guidelines may be useful not only for the management of individual patients with acute liver failure, but also to improve the uniformity of practices across academic centers for the purpose of collaborative studies.     

The Relationship of Visiting Insect Diversity and Density of Valeriana jatamansi with Increasing Altitude in Western Himalaya

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - In light of the recent evidences that pollinators have a significant implication for maintenance of...     

Formulation and Evaluation of Sustained Release Extrudes Prepared via Novel Hot Melt Extrusion Technique

The purpose of the present investigation is to emphasize the application of hot-melt extrusion technique (HMET) for the preparation of sustained release matrix formulation of highly dosed, freely soluble drugs. In this study, sustained release multiple unit dosage of venlafaxine hydrochloride (VH) was prepared by HMET. Custom design was used to screen the effect of four factors-type of polymer (ethylcellulose and eudragit RSPO) (X ₁), amount of polymer (X ₂), type of plasticizer (DBS, ATBC, TEC, and PEG) (X ₃), and plasticizer concentration (X ₄), on the drug release at 8 h (Y1) and machine torque (Y2). The experiments were carried out according to a four-factor 16-run statistical model and subjected to 12-h dissolution study in purified water. The significance of the model was indicated by ANOVA. Results of in vitro release study indicate that formulations prepared with higher amount of ethylcellulose and DBC show significant retardation at 8 h. The result shows that increase in concentration of polymer with the combination of water insoluble plasticizer (DBS and ATBC) has better sustained release while increasing concentration of TEC and PEG results faster in vitro release. Besides that increase in plasticizer concentration helps in reducing the melt temperature and machine torque. The in vivo study was performed, and formulations were compared using area under the plasma concentration-time curve (AUC_0-∞), time to reach peak plasma concentration (T_max), and peak plasma concentration (C_max). The drug release profiles of extrudes were found to fit both diffusion and surface erosion models. Further to this, scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction analysis of the hot-melt extrudates demonstrated that VH remained crystalline and was homogeneously dispersed throughout the polymer matrix.     

The effect of chin cup therapy on the growth and development of the cranial base and midface

The purpose of this study was to determine how the growth rates of certain cranial base and midfacial points and dimensions were affected by force application to the mandible by the chin cup. Control and treated samples consisting of Japanese girls with skeletal Class III relationships were analyzed. Each sample consisted of lateral cephalometric radiographs taken annually (control group) or semiannually (treated group) from early childhood through adolescence. The control sample was composed of seven persons and the treated sample of ten persons. The subjects of the treated sample were required to wear a chin cup a minimum of 12 hours per day. The total force delivered was 500 g, 250 g per side, and the direction of force was, on average, through the condyle. No other appliances were used. The results of this study indicate that the chin cup causes a closing of the cranial flexure angle N-S-Ba, inhibits posterior growth of the point basion, and imposes a vertical growth tendency on the points nasion and sella. The chin cup significantly inhibits anterior and posterior vertical maxillary growth and growth of upper anterior facial height. Because development of vertical posterior facial height is inhibited more than anterior facial height, a clockwise rotation of the maxilla occurs. The chin cup also causes flaring and a decrease in eruption rate of the maxillary incisors. It has no effect on the eruption rate of the maxillary molars, but accelerates their rate of mesial movement as compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rationale and design of the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST)

Major Depressive Disorder (MDD) affects one in five patients with Chronic Kidney Disease (CKD) and is an independent risk factor for hospitalization and death before and after dialysis initiation. However, it remains an under-recognized and under-treated problem, in part due to the lack of well-controlled studies that support or refute the efficacy and safety of antidepressant medications in CKD patients. Major trials of antidepressant treatment excluded patients with stages 3–5 CKD, precisely those at higher risk for both depression and increased mortality. The Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) is a randomized, double-blinded, placebo-controlled trial of sertraline, a selective serotonin reuptake inhibitor (SSRI). It will enroll 200 adults with stages 3–5 CKD and MDD excluding kidney transplant and chronic dialysis patients. Sertraline will be administered at an initial dose of 50 mg once daily or matching placebo followed by a dose escalation strategy consisting of 50 mg increments at 2 week intervals (as tolerated) to a maximum dose of 200 mg. The primary outcome is improvement in depression symptom severity measured by the Quick Inventory of Depressive Symptomatology scale. Secondary outcomes include safety endpoints and improvement in quality of life. Changes in cognitive function, adherence to medications, nutritional status, inflammation, and platelet function will be explored as potential mechanisms by which depression may mediate poor outcomes. We discuss the rationale and design of the CAST study, the largest placebo-controlled trial aimed to establish safety and efficacy of a SSRI in the acute phase treatment of CKD patients with MDD.