Post-transplant infections: single center experience from the developing world.

OBJECTIVE: To describe our experience of post-transplant infections in allogeneic stem cell transplants at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan. METHODS: From July 2001 to September 2006, patients with malignant and non-malignant hematological disorders having human leukocyte antigen (HLA)-matched sibling donors were selected for transplant. Pre-transplant infection surveillance was carried out, and strict prophylaxis against infection was observed. After admission to the hospital, patients were kept in protective isolation rooms, equipped with a HEPA filter positive-pressure laminar airflow ventilation system. Bone marrow and/or peripheral blood stem cells were used as the stem cell source. Cyclosporin and prednisolone were used as prophylaxis against graft-versus-host disease (GVHD). The engraftment was monitored with cytogenetic/molecular analysis and change of blood group. Survival was calculated from the date of transplant to death or last follow-up. RESULTS: One hundred and fifty-four patients received allogeneic stem cell transplants from HLA-matched siblings for various hematological disorders at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan between July 2001 and September 2006. Indications for transplant included aplastic anemia (n=66), beta-thalassemia major (n=40), chronic myeloid leukemia (n=33), acute leukemia (n=8), and miscellaneous disorders (n=7). One hundred and twenty patients were male and 34 were female. The median age of the patient cohort was 14 years (range 1 1/4-54 years). One hundred and thirty-six patients and 135 donors were cytomegalovirus (CMV) IgG-positive. One hundred and forty patients (90.9%) developed febrile episodes in different phases of post-transplant recovery. Infective organisms were isolated in 150 microbiological culture specimens out of 651 specimens from different sites of infections (23.0% culture positivity). Post-transplant infections were confirmed in 120 patients (77.9%) on the basis of clinical assessment and microbiological, virological, and histopathological examination. Mortality related to infections was 13.0%. Fatal infections included CMV disease (100% mortality, 6/6), disseminated aspergillosis (66.7% mortality, 4/6), pseudomonas septicemia (42.9% mortality, 9/21), and tuberculosis (25% mortality, 1/4). CONCLUSIONS: More than 90% of our patients developed febrile episodes with relatively low culture yield. The majority of infections were treated effectively, however CMV, aspergillosis, and pseudomonas infections remained problematic with high mortality.     

Systemic delivery of β-blockers via transdermal route for hypertension

Hypertension is the most common cardiovascular disease worldwide. Moreover, management of hypertension requires long-term treatment that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Although there is availability of a plethora of therapeutically effective antihypertensive molecules, inadequate patient welfare is observed; this arguably presents an opportunity to deliver antihypertensive agents through a different route. Ever since the transdermal drug delivery came into existence, it has offered great advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. Attempts were made to develop the transdermal therapeutic system for various antihypertensive agents, including β-blockers, an important antihypertensive class. β-blockers are potent, highly effective in the management of hypertension and other heart ailments by blocking the effects of normal amounts of adrenaline in the heart and blood vessels. The shortcomings associated with β-blockers such as more frequent dose administration, extensive first pass metabolism and variable bioavailability, make them an ideal candidate for transdermal therapeutic systems. The present article gives a brief view of different β-blockers formulated as transdermal therapeutic system in detail to enhance the bioavailability as well as to improve patient compliance. Constant improvement in this field holds promise for the long-term success in technologically advanced transdermal dosage forms being commercialized sooner rather than later.     

Effect of ethylene glycol dimethacrylate on swelling and on metformin hydrochloride release behavior of chemically crosslinked pH–sensitive acrylic acid–polyvinyl alcohol hydrogel

Background

The present work objective was to prepare and to observe the effect of ethylene glycol dimethacrylate on swelling and on drug release behavior of pH-sensitive acrylic acid–polyvinyl alcohol hydrogel.

Methods

In the present work, pH sensitive acrylic acid–polyvinyl alcohol hydrogels have been prepared by free radical polymerization technique in the presence of benzoyl peroxide as an initiator. Different crosslinker contents were used to observe its effect on swelling and on drug release. Dynamic and equilibrium swelling studies of prepared hydrogels were investigated in USP phosphate buffer solutions of pH 1.2, 5.5, 6.5 and 7.5 with constant ionic strengths. Hydrogels were evaluated for polymer volume fraction, solvent interaction parameter, molecular weight between crosslinks, number of links per polymer chain, diffusion coefficient, sol–gel fraction and porosity. To demonstrate the release pattern of the drug, zero-order, first-order, higuchi and korsmeyer-peppas models were applied. Quality and consistency of hydrogels was examined by FTIR and surface morphology of hydrogels was examined by SEM.

Results

Decrease in swelling and in drug release was seen by increasing content of ethylene glycol dimethacrylate. A remarkable high swelling was observed at high pH indicating the potential of this hydrogel for delivery of drugs to intestine. By increasing the concentration of ethylene glycol dimethacrylate, porosity decreased. Order of release was observed first order in all cases and the mechanism was non–fickian diffusion. FTIR confirmed the formation of network. SEM results showed the incorporation of drug.

Conclusion

The prepared hydrogels can be suitably used for targeted drug delivery to the intestine.     

Electrophysiological determinants of antidromic reentry induced during atrial extrastimulation. Insights from a pacing model of Wolff-Parkinson-White syndrome

The electrophysiology of antidromic reentry, a less common phenomenon than orthodromic reentry, remains a poorly understood aspect of the Wolff-Parkinson-White (WPW) syndrome. We used a pacing model of ventricular preexcitation in patients without WPW, so that electrophysiological events in the normal pathway during atrial extrastimulation (A1-A2 technique) could be precisely delineated without the obscuring effect of an actual accessory pathway. Ventricular preexcitation was simulated by an A1-V1 sequential basic drive with A2-V2 extrastimulation at progressively shorter A1-A2 (equal to V1-V2) coupling intervals. At each coupling interval tested within the zone of atrioventricular (A-V) nodal effective refractory period (since anterograde block of A2 was considered mandatory for manifestation of antidromic reentry), responses were assessed after A2 alone (method I), V2 alone (method II), and A2 plus V2 (method III, the complete preexcitation model). The entire pacing protocol was performed at two A-V intervals, short (50 msec) and long (150-180 msec), thereby simulating different proximities between the A pacing site and "accessory pathway" location. Of 47 consecutive unmedicated patients screened for the study protocol, 38 failed to meet minimal prerequisites for possible initiation of antidromic reentry because of failure in 18 (38% of total) to achieve anterograde A-V nodal block of A2, even though 1:1 ventriculoatrial conduction to cycle lengths less than or equal to 500 msec (less than or equal to 400 msec in 12) was present; and poor or absent ventriculoatrial conduction in the others. The nine remaining candidates underwent the full pacing protocol. Antidromic reentry (retrograde atrial response following V2 in method III) was observed in only two cases (4% of total), and both were associated with retrograde His-Purkinje system delays (documented by method II) occurring in tandem with a long A-V interval, thereby allowing for completion of retrograde A-V nodal recovery after penetration by A2. Indeed, such a prolonged recovery time prevented initiation of antidromic reentry in six of the nine patients (proven by intact ventriculoatrial conduction in method II). Retrograde A-V nodal block of V2, independent of A2, prevented an antidromic echo in one case. Findings in our model help to clarify the various factors, including specific anterograde and retrograde A-V nodal properties; anatomic relation between the accessory and normal pathways; and the retrograde His-Purkinje system delays, that must prevail in a concerted fashion to permit the initiation of antidromic reentry during the A1-A2 technique in patients with the WPW syndrome.     

The use of psychiatry‐focused simulation in undergraduate nursing education: A systematic search and review

Evidence on the use of simulation to teach psychiatry and mental health (including addiction) content is emerging, yet no summary of the implementation processes or associated outcomes exists. The aim of this study was to systematically search and review empirical literature on the use of psychiatry‐focused simulation in undergraduate nursing education. Objectives were to (i) assess the methodological quality of existing evidence on the use of simulation to teach mental health content to undergraduate nursing students, (ii) describe the operationalization of the simulations, and (iii) summarize the associated quantitative and qualitative outcomes. We conducted online database (MEDLINE, Embase, ERIC, CINAHL, PsycINFO from January 2004 to October 2015) and grey literature searches. Thirty‐two simulation studies were identified describing and evaluating six types of simulations (standardized patients, audio simulations, high‐fidelity simulators, virtual world, multimodal, and tabletop). Overall, 2724 participants were included in the studies. Studies reflected a limited number of intervention designs, and outcomes were evaluated with qualitative and quantitative methods incorporating a variety of tools. Results indicated that simulation was effective in reducing student anxiety and improving their knowledge, empathy, communication, and confidence. The summarized qualitative findings all supported the benefit of simulation; however, more research is needed to assess the comparative effectiveness of the types of simulations. Recommendations from the findings include the development of guidelines for educators to deliver each simulation component (briefing, active simulation, debriefing). Finally, consensus around appropriate training of facilitators is needed, as is consistent and agreed upon simulation terminology.