Melatonin and its analogs in insomnia and depression

Benzodiazepine sedative-hypnotic drugs are widely used for the treatment of insomnia. Nevertheless, their adverse effects, such as next-day hangover, dependence and impairment of memory, make them unsuitable for long-term treatment. Melatonin has been used for improving sleep in patients with insomnia mainly because it does not cause hangover or show any addictive potential. However, there is a lack of consistency on its therapeutic value (partly because of its short half-life and the small quantities of melatonin employed). Thus, attention has been focused either on the development of more potent melatonin analogs with prolonged effects or on the design of slow release melatonin preparations. The MT(1) and MT(2) melatonergic receptor ramelteon was effective in increasing total sleep time and sleep efficiency, as well as in reducing sleep latency, in insomnia patients. The melatonergic antidepressant agomelatine, displaying potent MT(1) and MT(2) melatonergic agonism and relatively weak serotonin 5HT(2C) receptor antagonism, was found effective in the treatment of depressed patients. However, long-term safety studies are lacking for both melatonin agonists, particularly considering the pharmacological activity of their metabolites. In view of the higher binding affinities, longest half-life and relative higher potencies of the different melatonin agonists, studies using 2 or 3mg/day of melatonin are probably unsuitable to give appropriate comparison of the effects of the natural compound. Hence, clinical trials employing melatonin doses in the range of 50-100mg/day are warranted before the relative merits of the melatonin analogs versus melatonin can be settled.     

Non‐Hodgkin's lymphoma presenting as breast masses: A series of 10 cases diagnosed on FNAC

Primary breast lymphoma (PBL) is a rare disease, which comprises 0.04–0.53% of all primary malignant tumors of the breast. The most frequent histological subtype is diffuse large B‐cell type (DLBCL) (40–70%). Differentiation of PBLs from other breast tumors such as poorly differentiated carcinomas and lobular carcinoma may at times be difficult on cytomorphology alone. An audit of breast lymphomas diagnosed on fine needle aspiration cytology (FNAC) over a period of 9 years (2001–2009) was performed. Ten cases were retrieved and the cytomorphology was reviewed along with immunochemistry (IHC), flow cytometry as well as histopathology, wherever available. The age of patients ranged from 17 to 83 years. Eight cases were diagnosed as non‐Hodgkin's lymphoma, high‐grade on FNAC. Histopathology was available in four of these cases and cell block was available in one case. Lymphoid cells were positive for leukocyte‐common antigen (LCA) and CD20 and negative for CD3 in these cases. The same was confirmed by flow cytometry on aspirated material in one case. A diagnosis of DLBCL was offered in these five cases. One case was a low‐grade NHL and another case was a young male, a known case of acute leukemia and had leukemic infiltration in the breast lump. We wish to emphasize the potential importance of FNAC in breast lymphoma and the same can be helpful to avoid unnecessary surgery in these cases. The differential diagnostic entities have been discussed. IHC and flow cytometry can be performed on the aspirated material and provide valuable information. Diagn. Cytopathol. 2013. © 2011 Wiley Periodicals, Inc.     

Factors associated with external ventricular drain placement accuracy: data from an electronic health record repository

Background

We evaluated external ventricular drain placement for factors associated with placement accuracy. Data were acquired using an electronic health record data requisition tool.

Method

Medical records of all patients who underwent ventriculostomy from 2003 to 2010 were identified and evaluated. Patient demographics, diagnosis, type of guidance and number of catheter passes were searched for and recorded. Post-procedural hemorrhage and/or infection were identified. A grading scale was used to classify accuracy of catheter placements. A multiple logistic regression model was developed to assess features associated with accurate catheter placement.

Results

One hundred nine patients who underwent 111 ventriculostomies from 2003 to 2010 were identified. Patient diagnoses were classified into vascular (63 %), tumor (21 %), trauma (14 %), and cyst (2 %). Procedures were performed freehand in 90 (81 %), with the Ghajar guide in 17 (15 %), and with image guidance in 4 (4 %) patients. Eighty-eight (79 %) catheters were placed in the correct location. Trauma patients were more likely to have catheters misplaced (p?=?0.007) whereas patients in other diagnostic categories were not significantly associated with misplaced catheters. Post-procedural hemorrhage was noted in 2 (1.8 %) patients on post-procedural imaging studies. Five (4.5 %) definite and 6 (5.4 %) suspected infections were identified.

Conclusions

External ventricular drain placement can be performed accurately in most patients. Patients with trauma are more likely to have catheters misplaced. Further development is required to identify and evaluate procedure outcomes using an electronic health record repository.     

Late evening snack: exploiting a period of anabolic opportunity in cirrhosis

Background and Aim: Cirrhosis is a state of accelerated starvation with impaired protein synthesis. Increased rate of gluconeogenesis and alterations in skeletal muscle signaling pathways result in anabolic resistance and consequent loss of muscle mass or sarcopenia in cirrhosis. Late evening snack (LES) is an intervention to reduce the postabsorptive (fasting) phase with the potential to improve substrate utilization and reverse sarcopenia. Published reports were evaluated to examine the effect of LES on regulation of substrate utilization (short‐term studies) and nutritional outcomes (long‐term studies). Methods: PubMed, EMBASE, Google scholar and OVID databases were searched. All studies published on LES in cirrhosis were included. Studies that included few (n < 3) subjects and patients with hepatocellular carcinoma were excluded. Results: Late evening snack decreased lipid oxidation and improved nitrogen balance, irrespective of the composition or type of formulation used. Daytime isocaloric isonitrogenous snacks did not have the metabolic or clinical benefit of LES. LES decreased skeletal muscle proteolysis. No studies have examined its effect on muscle protein synthesis. There was inconsistent translation into an increase in lean body or skeletal muscle mass. Improved quality of life occurs but decreased mortality or need for transplantation has not been reported. The optimal composition of LES has not been defined, but based on mechanistic considerations, a branched chain supplemented LES holds most promise. Conclusions: Late evening snack holds the most promise as an intervention to reverse anabolic resistance and sarcopenia of cirrhosis with improved quality of life in patients with cirrhosis. Long term benefit and improved survival need critical evaluation.     

Association Between Gut Microbial Abundance and Sight-Threatening Diabetic Retinopathy

PurposeTo study the association between gut microbial abundance and sight-threatening diabetic retinopathy among patients with a history of type 2 diabetes mellitus.MethodsAn observational case-control study was performed using a sample population of diabetics referred to a tertiary eye institute. Sample subjects were identified as cases if they were diagnosed with sight-threatening diabetic retinopathy and controls if they were not but had at least a 10-year history of diabetes. Fecal swabs for all patients were collected for enumeration and identification of sequenced gut microbes. Statistical analyses were performed to associate the clinically relevant Bacteroidetes to Firmicutes relative abundance ratio (B/F ratio) with sight-threatening diabetic retinopathy and an optimal cutoff value for the ratio was identified using Youden''s J statistics.ResultsA sample size of 58 diabetic patients was selected (37 cases, 21 controls). No statistically significant difference in the relative abundance among the predominant phyla between the groups were found. In our univariate analysis, the B/F ratio was elevated in cases compared to controls (cases, 1.45; controls, 0.94; P = 0.049). However, this statistically significant difference was not seen in our multivariate regression model. Optimal cutoff value of 1.05 for the B/F ratio was identified, and significant clustering of cases above this value was noted in beta diversity plotting.ConclusionsNo difference in gut microbial abundance for any particular phylum was noted between the control and diseased population. Increased gut microbial B/F ratio can be a potential biomarker for the development of sight-threatening diabetic retinopathy among type 2 diabetic patients.     

The power of policy change, federal collaboration, and state coordination in healthcare-associated infection prevention

Policymakers have prioritized the prevention of healthcare-associated infections (HAIs) as a double-win that can both improve health outcomes and reduce healthcare costs. In the past few years, state and federal policymakers have developed policies to improve coordination and promote transparency and prevention. At the federal level, congressional oversight, policy directives, and targeted funding have helped focus national HAI prevention efforts through the Department of Health and Human Services Action Plan to Prevent Healthcare-Associated Infections. The development of this action plan and the collaboration of its implementing agencies-the Centers for Disease Control and Prevention, the Centers for Medicare and Medicaid Services, and the Agency for Healthcare Research and Quality-have heightened nationwide awareness of HAIs and their preventability, and provided an infrastructure and tools to reduce HAIs. State policymakers have also acted to promote local transparency and tailor prevention efforts to local needs. The collaboration and action generated by these state and federal efforts have helped accelerate HAI prevention across the United States.