A multicenter prospective observational study on the use of type and screen method versus conventional type and crossmatch policy for pre-transfusion testing in the Indian population.

Despite knowing the benefits of the type and screen (TS) method in pre-transfusion testing (PTT), most transfusion centers in developing countries continue to be reluctant to adopt a TS strategy over the conventional type and antihuman globulin (AHG) crossmatch (TX) policy in their routine laboratory practice because of the cost of obtaining antibody screening reagents. To generate strong evidence, this multicenter, observational study was conducted in which we collected data prospectively over a 1-year period from six major blood centers in India. The primary objective of this study was to identify the discordance between TS and TX results. A secondary objective was to identify the allo-antibody specificity in patients with positive antibody detection tests. All patients with orders for red blood cell transfusion who met patient selection criteria were subjected to parallel testing by column agglutination technology (CAT) for both the antibody detection test (screen) using a commercial three-cell panel and for the AHG crossmatch. A total of 21,842 patients were tested. In 148 patients with incompatible crossmatches, samples from six patients gave negative results with the antibody detection test, whereas the antibody detection test was positive in samples from 118 patients among the 21,694 crossmatch-compatible cases. The TS approach achieved a positive percent agreement of 95.95 and was found to be significantly effective in preventing the transfusion of serologically incompatible blood. The risk associated with abbreviating the AHG crossmatch was found to be 0.009 percent. Most of the identified clinically significant alloantibodies were directed to Rh antigens (D>E>c>C>e), followed by anti-K and anti-M. This study has generated sufficient robust data for the Indian population by including patients from all major geographical areas of the country and concluded a satisfactory agreement level as well as non-inferiority to the current PTT policy. Therefore, TS policy can be implemented in developing countries with no compromise on blood safety, provided sufficient technical and infrastructural support are available.

Drug update - Baloxavir marboxil: Latest entrant into the arena of pharmacotherapy of influenza.

Influenza is a frequent cause of clinically significant human disease, with seasonal epidemics and occasional pandemics. Uncomplicated influenza in healthy individuals is managed symptomatically. Vaccination against influenza plays a vital role in the control of infection in humans. The currently available antivirals include adamantanes, neuraminidase inhibitors, and ribavirin. Baloxavir marboxil, the prodrug of baloxavir, is the latest addition to the family of anti-influenza drugs, and it received US-FDA approval on October 24, 2018. Baloxavir acts through a novel mechanism of inhibiting Cap-dependent endonuclease (CEN), the vital step in the transcription of viral RNA, and prevents further spread of the virus.

Dermatological Disorders in the Intensive Care Unit: A Descriptive Study at a Tertiary Care Centre.

BACKGROUND: Dermatological disorders are common in patients being treated in intensive care units (ICU). However, they are often neglected in context of a critically ill patient. Very few studies focusing on these dermatoses have been undertaken. OBJECTIVES: To determine the prevalence and spectrum of dermatological disorders in patients being treated in medical ICU of a tertiary care centre. METHODS: This was a descriptive study conducted over a period of one year. All the patients admitted in the medical ICU were examined for the presence of any preexisting or newly developed dermatological disorder. Dermatological disorders were initially classified into infective and non-infective disorders. Patients with dermatological findings were classified into two groups: those who survived and those who died; which were compared with each other with respect to age and sex distribution, length of ICU stay and dermatological findings. RESULTS: Out of 776 cases admitted in ICU during the study period, dermatological disorders were observed in 164 (21.13%) cases. Life-threatening dermatological disorders were seen in 3.05% cases. Twenty nine (17.68%) patients with dermatological findings died. Amongst these cases, infectious dermatological disorders were significantly less common; while no significant difference was noticed in context of reactive dermatological disorders. CONCLUSION: Dermatological disorders in ICU are common and have a wide spectrum. They often need treatment and may be indicative of underlying potentially fatal systemic illness. Besides, a subset of cutaneous lesions may develop in response to various medical interventions, immunosuppression and immobility. Knowledge of such dermatoses is thus, essential, both for the intensivist and dermatologist.

An observational study to assess the possibility of patient participation in implementing pharmacovigilance in a busy tertiary care hospital.

BACKGROUND: Adverse drug reactions are an important cause of morbidity and mortality worldwide. Monitoring adverse drug reaction is the primary function of Pharmacovigilance Programme of India (PvPI). The national program at the inception allowed only physicians, nurses, and pharmacists to report adverse drug reactions but has recently permitted even the consumers or patients to report. The knowledge, attitude, and practice of patients toward such a program have not been studied, and hence, the present study was conducted to assess the same. METHODS: A questionnaire was prepared based on the review of literature and was filled up by the interviewer based on inputs from patients attending various outpatient departments and dispensary of a tertiary care center after obtaining informed consent. Descriptive statistical analysis was carried out, and the results are expressed in terms of means and proportions for continuous and categorical data, respectively. RESULTS: Majority of the patients were male (58.3%) and were using smart phones (63.9%). Most of the participants (91.6%) felt reporting adverse drug reaction is important, but only 37.7% thought of reporting the same. A very low percentage of participants (10%) were aware about the PvPI and the helpline number. CONCLUSION: The Indian health consumer is highly unaware about the existence of the PvPI and various tools available to report adverse drug reactions. It is the need of the hour to create awareness of the same by using the positive attitude toward the program.

Magnetically Coated Bioabsorbable Stents for Renormalization of Arterial Vessel Walls after Stent Implantation.

The insertion of a stent in diseased arteries is a common endovascular procedure that can be compromised by the development of short- and long-term inflammatory responses leading to restenosis and thrombosis, respectively. While treatment with drugs, either systemic or localized, has decreased the incidence of restenosis and thrombosis these complications persist and are associated with a high mortality in those that present with stent thrombosis. We reasoned that if stents could be made to undergo accelerated endothelialization in the deployed region, then such an approach would further decrease the occurrence of stent thrombosis and restenosis thereby improving clinical outcomes. Toward that objective, the first step necessitated efficient capture of progenitor stem cells, which eventually would become the new endothelium. To achieve this objective, we engineered intrinsic ferromagnetism within nonmagnetizable, biodegradable magnesium (Mg) bare metal stents. Mg stents were coated with biodegradable polylactide (PLA) polymer embedding magnetizable iron-platinum (FePt) alloy nanoparticles, nanomagnetic particles, nMags, which increased the surface area and hence magnetization of the stent. nMags uniformly distributed on stents enabled capture, under flow, up to 50 mL/min, of systemically injected iron-oxide-labeled (IO-labeled) progenitor stem cells. Critical parameters enhancing capture efficiency were optimized, and we demonstrated the generality of the approach by showing that nMag-coated stents can capture different cell types. Our work is a potential paradigm shift in engineering stents because implants are rendered as tissue in the body, and this "natural stealthiness" reduces or eliminates issues associated with pro-inflammatory immune responses postimplantation.

A literature update elucidating production of Panax ginsenosides with a special focus on strategies enriching the anti-neoplastic minor ginsenosides in ginseng preparations.

Ginseng, an oriental gift to the world of healthcare and preventive medicine, is among the top ten medicinal herbs globally. The constitutive triterpene saponins, ginsenosides, or panaxosides are attributed to ginseng's miraculous efficacy towards anti-aging, rejuvenating, and immune-potentiating benefits. The major ginsenosides such as Rb1, Rb2, Rc, Rd., Re, and Rg1, formed after extensive glycosylations of the aglycone "dammaranediol," dominate the chemical profile of this genus in vivo and in vitro. Elicitations have successfully led to appreciable enhancements in the production of these major ginsenosides. However, current research on ginseng biotechnology has been focusing on the enrichment or production of the minor ginsenosides (the less glycosylated precursors of the major ginsenosides) in ginseng preparations, which are either absent or are produced in very low amounts in nature or via cell cultures. The minor ginsenosides under current scientific scrutiny include diol ginsenosides such as Rg3, Rh2, compound K, and triol ginsenosides Rg2 and Rh1, which are being touted as the next "anti-neoplastic pharmacophores," with better bioavailability and potency as compared to the major ginsenosides. This review aims at describing the strategies for ginsenoside production with special attention towards production of the minor ginsenosides from the major ginsenosides via microbial biotransformation, elicitations, and from heterologous expression systems.

A Comparative Study of CSF Viral RNA Loads between HIV Positive Patients with Neurological Manifestations and Neurologically Asymptomatic HIV Patients.

INTRODUCTION: There are conflicting reports in literature about correlation of CSF viral RNA levels with neurological manifestations in HIV positive patients. Many studies in animals and human subjects have shown that CSF HIV-1 RNA can be useful as a specific marker of HIV induced neuropathology. To the contrary there are studies which show that neurological disease states can occur in absence of significant increase of CSF HIV RNA. MATERIALS AND METHODS: This was a prospective study conducted at Base hospital Delhi Cantt, New Delhi, a tertiary care hospitals for HIV patients. The study period was from 16 May 2006 to16 Jun 2011. The current study included forty (40) patients (Twenty HIV positive patients with neurological manifestations and twenty HIV positive patients clinically without any neurological manifestation). All potential study subjects and controls were explained the nature of this study and enrolled thereafter with written consent. RESULTS: In our study all the cases (HIV/AIDS patients with Neuro AIDS) and controls (HIV/AIDS patients without Neuro manifestations) were males only. 45% of the cases and 60% of controls were in the age group of 25 to 35 yrs and 35 % of cases and 40% of controls were in age group of 36 to 45 yrs. Among cases (HIV patients with neurological manifestations), The neurological manifestations in our 20 patients included; dementia-5, cryptococcal meningitis-4, Tubercular meningitis-4, CVA-3, Headache-3, (without CSF abnormality), 1 case each of pyogenic meningitis, Candida meningitis, Tremors and Herpes Zoster. Among the 20 cases fourteen patients had abnormal CSF (70%) whereas only one patient among the controls showed CSF abnormality (5%). Out of 20 cases, radio-imaging (CT Scan/ MRI) of brain was done in 18 cases. Twelve cases (66.66) had some abnormality on CT/ MRI. Various abnormalities seen were as under Calcified granuloma-1, Infarcts-5, Hydrocephalus-2, TBM (meningeal enhancement)-2, Candidiasis (Focal hypodensities in subcortical white matter of cerebral hemispheres)-1, Cryptococcoma-1, Cerebral atrophy-1, Focal enhancing lesions-2. In our study, mean CSF viral load in cases was 5236.3 copies/ml and in controls 502.4 copies/ml. Viral load in CSF among cases was significantly higher than viral load in CSF among controls. CONCLUSIONS: CSF HIV-1 RNA viral load estimation can be a useful tool for clinicians in confirming neurological involvement in HIV infected patients. Hence, in HIV positive patients suspected to have neurological involvement, CSF viral load studies should be done. Serial estimations of CSF HIV-1 RNA levels can be of prognostic significance. Estimation of CSF HIV-1 RNA level before and serially during administration of HAART can be useful to judge the efficacy of HAART.

Increasing the Use of Kidneys From Unconventional and High-Risk Deceased Donors.

In this paper, we have reviewed the literature and report on kidney donors that are currently used at relatively low rates. Kidneys from donors with acute kidney injury (AKI) seem to have outcomes equivalent to those from donors without AKI, provided one can rule out significant cortical necrosis. Kidneys from donors with preexisting diabetes or hypertension may have marginally lower aggregate survival but still provide patients with a significant benefit over remaining on the wait list. The Kidney Donor Profile Index derives only an aggregate association with survival with a very modest C statistic; therefore, the data indicated that this index should not be the sole reason to discard a kidney, except perhaps in patients with extremely low estimated posttransplant survival scores. It is important to note that the Scientific Registry of Transplant Recipients models of risk adjustment should allay concerns regarding regulatory issues for observed outcomes falling below expectations. The successful utilization of kidneys from donation after cardiac death over the past decade shows how expanding our thinking can translate into more patients benefiting from transplantation. Given the growing number of patients on the wait list, broadening our approach to kidney acceptance could have an important impact on the population with end-stage renal disease. Many lives could be prolonged by carefully considering use of kidneys that are often discarded.

One Size Does Not Fit All--Regional Variation in the Impact of the Share 35 Liver Allocation Policy.

Allocation policies for liver transplantation underwent significant changes in June 2013 with the introduction of Share 35. We aimed to examine the effect of Share 35 on regional variation in posttransplant outcomes. We examined two patient groups from the United Network for Organ Sharing dataset; a pre-Share 35 group composed of patients transplanted between June 17, 2012, and June 17, 2013 (n = 5523), and a post-Share group composed of patients transplanted between June 18, 2013, and June 18, 2014 (n = 5815). We used Kaplan-Meier and Cox multivariable analyses to compare survival. There were significant increases in allocation Model for End-stage Liver Disease (MELD) scores, laboratory MELD scores, and proportions of patients in the intensive care unit and on mechanical, ventilated, or organ-perfusion support at transplant post-Share 35. We also observed a significant increase in donor risk index in this group. We found no difference on a national level in survival between patients transplanted pre-Share 35 and post-Share 35 (p = 0.987). Regionally, however, posttransplantation survival was significantly worse in the post-Share 35 patients in regions 4 and 10 (p = 0.008 and p = 0.04), with no significant differences in the remaining regions. These results suggest that Share 35 has been associated with transplanting "sicker patients" with higher MELD scores, and although no difference in survival is observed on a national level, outcomes appear to be concerning in some regions.

Rapid Resolution of Donor-Derived Glomerular Fibrin Thrombi After Deceased Donor Kidney Transplantation.

The aim of this study was to determine the clinical and histologic outcomes related to transplanting kidneys from deceased donors with glomerular fibrin thrombi (GFT). We included all cases transplanted between October 2003 and October 2014 that had either a preimplantation biopsy or an immediate postreperfusion biopsy showing GFT. The study cohort included 61 recipients (9.9%) with GFT and 557 in the control group without GFT. Delayed graft function occurred in 49% of the GFT group and 39% in the control group (p = 0.14). Serum creatinine at 1, 4, and 12 months and estimated GFR at 12 months were similar in the two groups. Estimated 1-year graft survival was 93.2% in the GFT group and 95.1% in the control group (p = 0.22 by log-rank). Fifty-two of the 61 patients in the GFT group (85%) had a 1-month protocol biopsy, and only two biopsies (4%) showed residual focal glomerular thrombi. At the 1-year protocol biopsy, the prevalence of moderate to severe interstitial fibrosis and tubular atrophy was 24% in the GFT group and 30% in the control group (p = 0.42). We concluded that GFT resolves rapidly after transplantation and that transplanting selected kidneys from deceased donors with GFT is a safe practice.

Elicitors' influenced differential ginsenoside production and exudation into medium with concurrent Rg3/Rh2 panaxadiol induction in Panax quinquefolius cell suspensions.

Cobalt nitrate, nickel sulphate, hydrogen peroxide, sodium nitroprusside, and culture filtrates of Pseudomonas monteili, Bacillus circularans, Trichoderma atroviridae, and Trichoderma harzianum were tested to elicit ginsenoside production in a cell suspension line of Panax quinquefolius. Abiotic elicitors preferentially increased panaxadiols whereas biotic elicitors upregulated the panaxatriol synthesis. Cobalt nitrate (50 µM) increased total ginsenosides content by twofold (54.3 mg/L) within 5 days. It also induced the Rc synthesis that was absent in the control cultures. Elicitation with P. monteili (2.5 % v/v, 5 days) also supported 2.4-fold enhancement in saponin yield. Elicitation by T. atroviridae or hydrogen peroxide induced the synthesis of Rg3 and Rh2 that are absent in ginseng roots. The highest ginsenosides productivity (3.2-fold of control) was noticed in cells exposed to 1.25 % v/v dose of T. atroviridae for 5 days. Treating cells with T. harzianum for 15 days afforded maximum synthesis and leaching (8.1 mg/L) of ginsenoside Rh1.

Bacteremic pneumococcal pneumonia: clinical outcomes and preliminary results of inflammatory response.

PURPOSE: Further examination of clinical outcomes and inflammatory response of bacteremic pneumococcal community-acquired pneumonia (CAP) is of great interest to enhance the care of patients with pneumococcal CAP. METHODS: This is a secondary analysis of the Community Acquired Pneumonia Organization (CAPO) to compare the time to clinical stability (TCS), length of hospital stay (LOS), and in-hospital mortality of hospitalized pneumococcal CAP patients with and without bacteremia. To measure the effect of bacteremia in pneumococcal CAP patients on outcomes, we modeled all-cause in-hospital mortality using a Poisson regression model, and TCS and LOS using Cox proportional hazards models. Adjusted multivariate regression models were also used to predict the probability of occurrence of each of the study outcomes. To investigate the inflammatory response, we measured the plasma levels of pro- and anti-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1rα, IL-6, IL-8, IL-10], inflammatory biomarkers [C-reactive protein (CRP), pro-calcitonin (PCT), and B-type natriuretic peptide (BNP)], and peripheral blood neutrophil responses in 10 patients, 4 bacteremic and 6 non-bacteremic pneumococcal CAP, upon admission and every other day during the first 6 days of hospitalization. Functional data were presented as median and standard error of the median (SEM); due to small number of samples no statistical comparisons were performed between groups. RESULTS: From 833 pneumococcal CAP patients, 394 patients (47 %) were bacteremic. Bacteremic pneumococcal CAP were less likely to reach TCS with an adjusted hazard ratio (AHR) of 0.82 (95 % CI 0.69-0.97; p = 0.02) and had higher in-hospital mortality with an AHR of 1.63 (95 % CI 1.06-2.50, p = 0.026). Bacteremic pneumococcal CAP patients had a longer LOS than non-bacteremic pneumococcal CAP (p < 0.003). Higher plasma levels of CRP, PCT, and BNP were found in bacteremic than in non-bacteremic patients. The bacteremic group had consistently higher plasma levels of both pro- and anti-inflammatory cytokines. The blood neutrophil functional responses were similar in both groups of patients. CONCLUSIONS: Bacteremic pneumococcal CAP patients were significantly associated with higher in-hospital mortality, lower TCS, and longer LOS. HIV-infected patients showed a greater mortality which was not statistically significant. Bacteremic pneumococcal CAP patients had higher levels of biomarkers and systemic cytokines.

Maternal death review in selected countries of South East Asia Region.

Understanding the underlying factors that led to maternal deaths through a maternal death review (MDR) throws light on the causes, characteristics and circumstances of the death. We reviewed and report on the implementation of MDR in India, Indonesia, Myanmar, Nepal and Sri Lanka, capturing the experiences of MDR initiatives, follow-up actions and lessons learnet. Overall, while the findings from MDRs have been used to design or change policies and strategies for improvement of services provided, there are still challenges in scaling up these initiatives, particularly in the larger countries.

[Should hospitalization be required after the emergency discharge of patients with borderline personality disorder who have attempted suicide (FRENCH CRISIS cohort)?]. / Faut-il hospitaliser les patients suicidants avec trouble de personnalité borderline après leur prise en charge aux urgences (étude prospective FRENCH CRISIS) ?

BACKGROUND: Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability and impulsivity. There is a high prevalence of BPD patients among those admitted to the emergency department for suicide attempts. However, little empirical research exists to assist clinicians in deciding whether to hospitalize a suicidal patient. Some authors have argued that hospitalization does not prevent suicide and could actually harm these patients, thereby leading to psychosocial regression. Parasuicidal behaviors could be reinforced by the attention given during hospitalization. OBJECTIVE: Our purpose was to determine whether the hospitalization of suicidal patients who have a high risk of BPD after discharge from the emergency department is associated with a recurrence of suicidal behavior at 6months. METHOD: We designed a prospective study, acquiring patients from three emergency hospitals. The participants were suicidal subjects admitted for voluntary drug intoxication and were 18years of age or older. The participants completed the Personality Disorder Questionnaire (PDQ-4+) to assess BPD symptomatology. Information on the recurrence of suicidal behavior at 6months was obtained by interview of patients and the review of the charts from the 3 hospitals involved in the study. Other assessments included the BDI-13 (severity of depression), the Hopelessness Scale (hopelessness), the TAS-20 (alexythymia), the AUDIT (alcohol disorder) and the MINI (axis I disorders). RESULTS: A total of 606 subjects admitted for a suicide attempt participated in this study. A total of 320 (52.8 %) of the subjects completed the PDQ-4+. The sample was divided into three groups: participants at high risk of having at least one BPD (n=197), a group at high risk of having at least one non-BPD PD (n=84) and a group with low risk of having a PD (n=39). Hospitalization following an emergency was not associated with a recurrence of suicide attempts at 6months among patients at high risk of BPD. A logistical regression analysis showed pre-hospitalization antidepressant prescription to be associated with recidivism (OR=2.1, P=.037). CONCLUSION: Our exploratory study suggests that hospitalization may not increase suicide attempts among patients with BPD when the health organization does not include a specific device such as DBT.

Fractional flow reserve at 2013: an update.

Fractional flow reserve (FFR) has become an extremely valuable tool for assessing the hemodynamic significance of intermediate coronary lesions in patients with stable coronary syndromes. This manuscript delineates the current data supporting FFR use to guide cardiovascular interventions in comparison to other invasive and non-invasive modalities. The correlation between FFR, symptom severity and likelihood of future major cardiovascular events are critically examined in view of the FAME-2 study results. The authors delineate the scientific gaps, potential pitfalls and misconceptions related to FFR with regards to current and emerging indications. Described are the most important developments related to FFR in 2012: instantaneous wave free ratio and non-invasive CT angiography based FFR. The manuscript proposes areas of future research to enhance the scientific data supporting current FFR clinical algorithms and strategies.

Dual antiplatelet therapy for primary and secondary prevention.

The concomitant use of aspirin and an ADP receptor (P2Y12) blocker, also known as dual antiplatelet therapy (DAPT), has been extensively investigated as a primary and secondary prevention strategy in an effort to reduce the risk of cardiovascular events. In this manuscript the authors review the current guideline recommendations for DAPT and discuss the scientific data that supports these recommendations. Reported are also the scientific knowledge gaps and how future studies are likely to delineate these issues. Incremental knowledge is not likely to be an alternative to individualized care provided by the astute clinician to his patient. In consideration for prescribing DAPT (drug, dosage and duration) the clinician will have to weigh the potential benefits (reduction in death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke) and risks (severe or life-threatening bleeding) for each and every patient.

A study on clinical diagnosis of tuberculosis in free ranging and captive wild animals of India.

Background: Tuberculosis (TB) is a disease of paramount importance at the wildlife-livestock-human interface. Aims: To study the occurrence and Mycobacterium (M) species involved in the TB of free-ranging and captive wild animals in various Indian states. Methods: A total of 396 clinical samples from 207 different wild animal species from various Indian national parks, zoological gardens, etc., were analyzed by lateral flow assay (LFA), Ziehl-Neelsen (ZN) staining, and PCR. Clinical samples include blood (n=156), faecal swabs (n=103), serum (n=73), and nasal swabs or trunk wash fluids (n=64). Results: Clinical signs of TB were absent in 202 animals, although 21 wild animals were seropositive for pathogenic Mycobacterium antigens by LFA. Clinical signs like progressive weight loss, and respiratory distress were exhibited by 4 sloth bears (Melursus ursinus) and an elephant (Elephas maximus), which were also found positive for LFA, PCR, and ZN staining. ZN staining showed positivity for acid-fast bacilli (AFB) in 9 (8.74%) faecal and 9 (14.06%) nasal swabs or trunk wash fluids of sloth bears (7 samples) and elephants (2 samples). M. tuberculosis was detected in 7 sloth bears and 2 elephants, whereas M. bovis was found in a spotted deer (Axis axis) by species-specific PCR. Conclusion: The circulation of TB organisms in wild animals warrants a strict surveillance programme to identify the carrier status of these animals so that effective TB control strategies can be formulated.