Senaka Rajapakse

Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomised controlled trial

BACKGROUND Severe cardiac glycoside cardiotoxicity after ingestion of yellow oleander seeds is an important problem in rural areas of Sri Lanka. Currently, patients must be transferred to the capital for temporary cardiac pacing. We did a randomised controlled trial to investigate whether anti-digoxin Fab could reverse serious oleander-induced arrhythmias. METHODS After a preliminary dose-finding study, 66 patients who presented to hospital with a serious cardiac arrhythmia were randomised to receive either 1200 mg of anti-digoxin Fab or a saline placebo. A 12-lead electrocardiogram, 3 min rhythm strip, and blood sample for measurement of electrolytes and cardiac glycosides were taken before treatment and at 12 timepoints thereafter. FINDINGS 34 patients received anti-digoxin Fab and 32 received placebo. The presenting arrhythmia had resolved completely after 2 h in 15 antibody-treated patients and two controls (p<0.001); 24 and five patients, respectively, were in sinus rhythm at 8 h (p<0.001). Kaplan-Meier analysis of time to first reversal showed a significant response to anti-digoxin Fab. The heart rate increased in cases, from 49.1 per min at baseline to 66.8 at 2 h, but not in controls (50.6 per min at baseline to 51.5; p<0.001). Mean serum potassium concentrations decreased from 4.9 mmol/L to 4.1 mmol/L at 2 h in cases; no such decrease occurred in controls. INTERPRETATION Anti-digoxin Fab fragments are a safe and effective treatment for serious cardiac arrhythmias induced by yellow oleander. Their use in small rural hospitals in Sri Lanka should minimise costly transfer of patients and reduce the numbers of deaths; however, further study will be required to confirm this reduction.

Primaquine in vivax malaria: an update and review on management issues

Primaquine was officially licensed as an anti-malarial drug by the FDA in 1952. It has remained the only FDA licensed drug capable of clearing the intra-hepatic schizonts and hypnozoites of Plasmodium vivax. This update and review focuses on five major aspects of primaquine use in treatment of vivax malaria, namely: a) evidence of efficacy of primaquine for its current indications; b) potential hazards of its widespread use, c) critical analysis of reported resistance against primaquine containing regimens; d) evidence for combining primaquine with artemisinins in areas of chloroquine resistance; and e) the potential for replacement of primaquine with newer drugs.

Atypical manifestations of chikungunya infection

Chikungunya fever is a viral infection transmitted to humans by the bite of infected mosquitoes. Typical chikungunya virus (CHIKV) infection results in an acute febrile illness characterized by severe joint pain and rash. Although chikungunya is generally not considered life threatening, atypical clinical manifestations resulting in significant morbidity have been documented, especially during epidemics. This review describes atypical manifestations following CHIKV infection reported in the literature, categorized as neurological, cardiovascular, skin, ocular, renal and other manifestations. The importance of vertical transmission from an infected mother resulting in neonatal infection is also highlighted. CHIKV infection can result in severe illness needing intensive care, with significant mortality. While there are many deaths reported which are directly attributable to CHIKV infection, background mortality is also increased during epidemics. In this context, considering CHIKV infection a benign and non fatal illness has to be revisited.

Acute yellow oleander ( Thevetia peruviana ) poisoning: cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside concentrations on presentation to hospital

OBJECTIVE To describe the cardiac arrhythmias, electrolyte disturbances, and serum cardiac glycoside levels seen in patients presenting to hospital with acute yellow oleander (Thevetia peruviana) poisoning and to compare these with published reports of digitalis poisoning. DESIGN Case series. SETTING Medical wards of Anuradhapura District General Hospital, Sri Lanka, and coronary care unit of the Institute of Cardiology, National Hospital of Sri Lanka, Colombo, the national tertiary referral centre for cardiology. PATIENTS 351 patients with a history of oleander ingestion. MEASUREMENTS ECG and blood sample analysis on admission. RESULTS Most symptomatic patients had conduction defects affecting the sinus node, the atrioventricular (AV) node, or both. Patients showing cardiac arrhythmias that required transfer for specialised management had significantly higher mean serum cardiac glycoside and potassium but not magnesium concentrations. Although there was considerable overlap between groups, those with conduction defects affecting both sinus and AV nodes had significantly higher mean serum cardiac glycoside levels. CONCLUSIONS Most of these young previously healthy patients had conduction defects affecting the sinus or AV nodes. Relatively few had the atrial or ventricular tachyarrhythmias or ventricular ectopic beats that are typical of digoxin poisoning. Serious yellow oleander induced arrhythmias were associated with higher serum cardiac glycoside concentrations and hyperkalaemia but not with disturbances of magnesium.

Learning styles and approaches to learning among medical undergraduates and postgraduates

BackgroundThe challenge of imparting a large amount of knowledge within a limited time period in a way it is retained, remembered and effectively interpreted by a student is considerable. This has resulted in crucial changes in the field of medical education, with a shift from didactic teacher centered and subject based teaching to the use of interactive, problem based, student centered learning. This study tested the hypothesis that learning styles (visual, auditory, read/write and kinesthetic) and approaches to learning (deep, strategic and superficial) differ among first and final year undergraduate medical students, and postgraduates medical trainees.MethodsWe used self administered VARK and ASSIST questionnaires to assess the differences in learning styles and approaches to learning among medical undergraduates of the University of Colombo and postgraduate trainees of the Postgraduate Institute of Medicine, Colombo.ResultsA total of 147 participated: 73 (49.7%) first year students, 40 (27.2%) final year students and 34(23.1%) postgraduate students. The majority (69.9%) of first year students had multimodal learning styles. Among final year students, the majority (67.5%) had multimodal learning styles, and among postgraduates, the majority were unimodal (52.9%) learners.Among all three groups, the predominant approach to learning was strategic. Postgraduates had significant higher mean scores for deep and strategic approaches than first years or final years (p < 0.05). Mean scores for the superficial approach did not differ significantly between groups.ConclusionsThe learning approaches suggest a positive shift towards deep and strategic learning in postgraduate students. However a similar difference was not observed in undergraduate students from first year to final year, suggesting that their curriculum may not have influenced learning methodology over a five year period.

Scrub typhus: pathophysiology, clinical manifestations and prognosis

Scrub typhus is a zoonosis caused by the pathogen Orientia tsutsugamushi (O. tsutsugamushi). The disease has significant prevalence in eastern and Southeast Asia. Usually presenting as an acute febrile illness, the diagnosis is often missed because of similarities with other tropical febrile infections. Many unusual manifestations are present, and these are described in this review, together with an outline of current knowledge of pathophysiology. Awareness of these unusual clinical manifestations will help the clinician to arrive at an early diagnosis, resulting in early administration of appropriate antibiotics. Prognostic indicators for severe disease have not yet been clearly established.

Deaths due to absence of an affordable antitoxin for plant poisoning

There is a severe shortage of affordable antivenoms and antitoxins in the developing world. An anti-digoxin antitoxin for oleander poisoning was introduced in Sri Lanka in July, 2001, but because of its cost, stocks ran out in July, 2002. We looked at the effect of its introduction and withdrawal on case fatality, and determined its cost-effectiveness. The antitoxin strikingly reduced the case fatality; its absence resulted in a three-fold rise in deaths. At the present price of US2650 dollars per course, every life saved cost 10209 dollars and every life year cost 248 dollars. Reduction of the antitoxins price to 400 dollars would reduce costs to 1137 dollars per life gained; a further reduction to 103 dollars would save money for every life gained. Treatments for poisoning and envenoming should be included in the present campaign to increase availability of affordable treatments in the developing world.

Management of yellow oleander poisoning.

Background. Poisoning due to deliberate self-harm with the seeds of yellow oleander (Thevetia peruviana) results in significant morbidity and mortality each year in South Asia. Yellow oleander seeds contain highly toxic cardiac glycosides including thevetins A and B and neriifolin. A wide variety of bradyarrhythmias and tachyarrhythmias occur following ingestion. Important epidemiological and clinical differences exist between poisoning due to yellow oleander and digoxin; yellow oleander poisoning is commonly seen in younger patients without preexisting illness or comorbidity. Assessment and initial management. Initial assessment and management is similar to other poisonings. No definite criteria are available for risk stratification. Continuous ECG monitoring for at least 24 h is necessary to detect arrhythmias; longer monitoring is appropriate in patients with severe poisoning. Supportive care. Correction of dehydration with normal saline is necessary, and antiemetics are used to control severe vomiting. Electrolytes. Hypokalemia worsens toxicity due to digitalis glycosides, and hyperkalemia is life-threatening. Both must be corrected. Hyperkalemia is due to extracellular shift of potassium rather than an increase in total body potassium and is best treated with insulin-dextrose infusion. Intravenous calcium increases the risk of cardiac arrhythmias and is not recommended in treating hyperkalemia. Oral or rectal administration of sodium polystyrene sulfonate resin may result in hypokalemia when used together with digoxin-specific antibody fragments. Unlike digoxin toxicity, serum magnesium concentrations are less likely to be affected in yellow oleander poisoning. The effect of magnesium concentrations on toxicity and outcome is not known. Hypomagnesaemia should be corrected as it can worsen cardiac glycoside toxicity. Gastric decontamination. The place of emesis induction and gastric lavage has not been investigated, although they are used in practice. Gastric decontamination by the use of single dose and multiple doses of activated charcoal has been evaluated in two randomized controlled trials, with contradictory results. Methodological differences (severity of poisoning in recruited patients, duration of treatment, compliance) between the two trials, together with differences in mortality rates in control groups, have led to much controversy. No firm recommendation for or against the use of multiple doses of activated charcoal can be made at present, and further studies are needed. Single-dose activated charcoal is probably beneficial. Activated charcoal is clearly safe. Arrhythmia management. Bradyarrhythmias are commonly managed with atropine, isoprenaline, and temporary cardiac pacing in severe cases, although without trial evidence of survival benefit, or adequate evaluation of possible risks. Accelerating the heart rate with atropine or β-adrenergic agents theoretically increases the risk of tachyarrhythmias, and it has been claimed that atropine increases tachyarrhythmic deaths. Further studies are required. Tachyarrhythmias have a poor prognosis and are more difficult to treat. Lidocaine is the preferred antiarrhythmic; the role of intravenous magnesium is uncertain. Digoxin-specific antibody fragments. Digoxin-specific antibody fragments are effective in reverting life-threatening cardiac arrhythmias; prospective observational studies show a beneficial effect on mortality. High cost and lack of availability limit the widespread use of digoxin-specific antibody fragments in developing countries. Conclusions. Digoxin-specific antibody fragments remain the only proven therapy for yellow oleander poisoning. Further studies are needed to determine the place of activated charcoal, the benefits or risks of atropine and isoprenaline, the place and choice of antiarrhythmics, and the effect of intravenous magnesium in yellow oleander poisoning.

Leukotriene receptor antagonists for chronic urticaria: a systematic review

A significant proportion of patients with chronic urticaria respond inadequately to first line treatment with antihistamines. Leukotreine receptor antagonists (LTRA) are also used for chronic urticaria, although firm recommendations on their use are lacking. We performed a systematic review of randomised trials to determine the role of LTRA in treatment of chronic urticaria. A search of PUBMED, EMBASE, SCOPUS, LILACS, the Cochrane Central Register of Controlled Trials, and the Web of Science for relevant randomized control trials or cross over studies yielded 10 eligible studies. The heterogeneity of trials were high, preventing valid meta-analysis of data. Most trials indicated that LTRA are not superior to placebo or antihistamine therapy, while combination therapy of LTRA and antihistamines appear to be more efficacious compared to antihistamine alone. The side effect profile and tolerability of this group of drugs is acceptable. The use of LTRA as monotherapy cannot be recommended. LTRA are effective add-on therapy to anti-histamines, and their use in patients responding poorly to antihistamines is justifiable. Further well designed randomized controlled trials with clear and standardized outcome measures are needed to determine the role of LTRA in chronic urticaria.

Current status of HIV/AIDS in South Asia

Background: According to the United Nations Joint Program on HIV/AIDS, 33.2 million adults and children are living with the infection worldwide. Of these, two to three million are estimated to be in South Asia. All countries of the region have a low prevalence of human immunodeficiency virus (HIV). However, it is important to review the current epidemiological data to identify the trends of infection as it would have implications on prevention. Materials and Methods: We performed a MEDLINE search using phrases ‘South Asia’ plus ‘HIV’, ‘AIDS’, and names of individual countries in South Asia (limits: articles published in last 10 years, in English language). Clinical trials, reviews, meta-analyses, letters, editorials, and practice guidelines were all considered. The following countries were included as belonging to South Asia; Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan and Sri Lanka. Recent estimates and data on country status, and details of national control programs were obtained from websites of international agencies such as the World Bank and United Nations Joint Program on HIV/AIDS (UNAIDS). Results and Discussion: This review looks into many aspects of HIV infection in South Asia including country profiles with regard to infection, economic and psychological burden of illness and treatment issues in the South Asian context.