Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Changes in biochemical markers of outcomes in haemodialysis patients following a clinical pharmacy intervention.(Ceylon College of Physicians, 2021) Kalpani, A.G.S.; Mohamed, F.; Hough, J.E.; de Silva, D.N.N.; Chandrasena, W.M.H.N.M.; Jayamanne, S.F.Introduction and Objectives Common complications of End-Stage Renal Disease (ESRD) include cardiovascular disease, diabetes, anaemia and mineral and bone disease. Achieving an optimum level of biochemical markers of outcomes is crucial in managing ESRD. This study was conducted to assess the changes in selected biochemical parameters following a clinical pharmacy intervention (CPI) in this population. Method A randomized controlled trial was conducted at outpatient haemodialysis units in North Central Province, Sri Lanka. Serum phosphate, serum calcium, haemoglobin, lipid profile, eGFR and 'adequacy of dialysis* (AoD) (determined by urea reduction ratio (URR); calculated based on pre-post blood urea nitrogen measurements and Kt/V measurements) were measured in patients at baseline (BL) and after one year (PI). The Intervention Group (IG), n=143 patients received comprehensive pharmaceutical care by the clinical pharmacist on four consecutive occasions at recruitment, and 2, 6 and 10 months after recruitment. While the Control Group (CG), n=140, received standard care. Results At the baseline, there was no significant difference in the biochemical markers of outcomes between the two groups and AoD was within the acceptable range. However, there was a significant improvement in the mean serum phosphate levels (IG 4.04±1.19 vs CG 5.00±1.67, p<0.0001), mean serum calcium levels (IG 8.90±1.35 vs CG 7.11±2.07, p<0.0001), and mean haemoglobin levels (IG 10.5±1.25 vs CG 9.4±1.87, p<0.0001) in the IG compared to the CG at the end of one year. However, eGFR, lipid profiles did not change significantly (p>0.05). AoD was within the acceptable range in both groups at baseline and post intervention and did not change significantly (p>0.05) Conclusions Improvement in the selected biochemical markers of outcomes resulting from CPI suggests better patient management outcomes in the ESRD population.Item Opportunities for optimization of drug therapy and characterization of drug-related problems in ckd/ckdu patients undergoing hemodialysis in Sri Lanka(Ceylon College of Physicians, 2021) Kalpani, A.G.S.; Mohamed, F.; Hough, J.E.; de Silva, D.N.N.; Jayamanne, S.F.Introduction and objectives Drug-related problems (DRPs) in ESRD patients undergoing haemodialysis have not been investigated in Sri Lanka. The present study was conducted to identify and characterize the potential drug-related problems and identify opportunities to optimize drug therapy in ESRD patients undergoing haemodialysis. Method As part of RCT at ambulatory hemodialysis (HD) units of Teaching Hospital Anuradhapura (THA) and District General Hospital (DGH) Polonnaruwa, randomly selected ESRD patients undergoing hemodialysis were recruited for the study. DRPs were identified by reviewing the clinic drug charts, patient clinic records and structured interviews with patients or caregivers to identify the patients* actual drug-taking behaviour. Identified DRPs were categorized using a PCNE classification system V.08. Results A total of 1350 drug related problems were identified in 283 ambulatory HD patients during the study period. Patients were taking an average of 10.64 drugs and had 4.77 DRPs. Unnecessary drug treatment (30.3%), effect of the drug treatment not optimal (29.9%) followed by untreated symptom or indication (24.5%) were the most prevalent DRP categories according to the PCNE classification system. The major cause for the identified DRPs was a prescriber related (50.22%) followed by patient related (30.0%) and dispensing related (16.9%) causes in ESRD patients undergoing HD. Conclusions ESRD patients undergoing HD had a large number of medications which increases the risk of potential DRPs. Significant opportunities exist for pharmacists' input to improve the quality use of medicines by identifying and resolving the DRPs in ESRD patients undergoing haemodialysis in the current Sri Lankan government hospital setting as part of multidisciplinary teamItem Opportunities for pharmacists to optimise quality use of medicines in a Sri Lankan hospital: An observational, prospective, cohort study(Wiley-Blackwell, 2017) Perera, D.M.P.; Coombes, J.A.; Shanika, L.G.T.; Dawson, A.; Lynch, C.; Mohamed, F.; Kalupahana, N.; de Silva, H.A.; Jayamanne, S.F.; Peters, N.B.; Myers, B.; Coombes, I.D.BACKGROUND: Quality use of medicines (QUM) has been identified as a priority in Sri Lanka. Aim: To identify opportunities to optimise QUM, and evaluate medication appropriateness and medication information exchanged with patients and carers on discharge in a Sri Lankan tertiary care hospital. METHODS: An observational, prospective, cohort study of patients systematically sampled from two medical wards. A research pharmacist determined their pre-admission medication regimen via interview at time of discharge. Issues of poor adherence and discrepancies between the pre- and post-admission medication regimens were recorded. Drug-related problems were categorised into opportunities to optimise drug therapy. The appropriateness of discharge medications was evaluated using a validated tool. The patient or carer was interviewed after discharge regarding the quality of medicine information exchanged in hospital. RESULTS: The 578 recruited patients were taking 1756 medications prior to admission, and 657 (37.4%) of these medications were not continued during admission. Opportunities to optimise drug therapy were identified on 1496 occasions during admission (median, 2.0 opportunities/patient), 215 opportunities, (14.4%) were resolved spontaneously by the medical team prior to discharge. The median score for appropriateness of medications on discharge was 1.5 per patient (interquartile range, 0.0–3.5). Of 427 patients surveyed after discharge, 52% recalled being asked about their medications on admission to hospital, 75% about previous adverse medication reactions and 39% recalled being informed about changes to their medications on discharge. CONCLUSION: Significant opportunities exist for pharmacists to enhance quality use of medicines for patients in the current hospitalbased healthcare system in Sri Lanka. © 2017 The Society of Hospital Pharmacists of Australia.Item Early identification of acute kidney injury in Russell's viper (Daboia russelii) envenoming using renal biomarkers(Public Library of Science, 2019) Ratnayake, I.; Mohamed, F.; Buckley, N.A.; Gawarammana, I.B.; Dissanayake, D.M.; Chathuranga, U.; Munasinghe, M.; Maduwage, K.; Jayamanne, S.; Endre, Z.H.; Isbister, G.K.BACKGROUND: Acute kidney injury (AKI) is a major complication of snake envenoming, but early diagnosis remains problematic. We aimed to investigate the time course of novel renal biomarkers in AKI following Russell's viper (Daboia russelii) bites. METHODOLOGY/PRINCIPAL FINDINGS: We recruited a cohort of patients with definite Russell's viper envenoming and collected serial blood and urine samples on admission (<4h post-bite), 4-8h, 8-16h, 16-24h, 1 month and 3 months post-bite. AKI stage (1-3) was defined using the Acute Kidney Injury Network criteria. AKI stages (1-3) were defined by the Acute Kidney Injury Network (AKIN) criteria. There were 65 Russell's viper envenomings and 49 developed AKI: 24 AKIN stage 1, 13 stage 2 and 12 stage 3. There was a significant correlation between venom concentrations and AKI stage (p = 0.007), and between AKI stage and six peak biomarker concentrations. Although most biomarker concentrations were elevated within 8h, no biomarker performed well in diagnosing AKI <4h post-bite. Three biomarkers were superior to serum creatinine (sCr) in predicting AKI (stage 2/3) 4-8h post-bite: serum cystatin C (sCysC) with an area under the receiver operating curve (AUC-ROC), 0.78 (95%CI:0.64-0.93), urine neutrophil gelatinase-associated lipocalin (uNGAL), 0.74 (95%CI:0.59-0.87) and urine clusterin (uClu), 0.81 (95%CI:0.69-0.93). No biomarker was better than sCr after 8h. Six other urine biomarkers urine albumin, urine beta2-microglobulin, urine kidney injury molecule-1, urine cystatin C, urine trefoil factor-3 and urine osteopontin either had minimal elevation, and/or minimal prediction for AKI stage 2/3 (AUC-ROC<0.7). CONCLUSIONS/SIGNIFICANCE: AKI was common and sometimes severe following Russell's viper bites. Three biomarkers uClu, uNGAL and sCysC, appeared to become abnormal in AKI earlier than sCr, and may be useful in early identification of envenoming.Item Case report: Opportunities for Medication Review and Reconciliation by a Clinical Pharmacist to Prevent Drug-Related Hospital Re-Admissions: Evidence from a Case Series in Sri Lanka(Pharmaceutical Journal of Sri Lanka, 2018) Shanika, L.G.T.; Wijekoon, C.N.; Jayamanne, S.; Coombes, J.; Perera, D.; Pathiraja, V.M.; Mamunuwa, N.; Mohamed, F.; Coombes, I.; Lynch, C.; de Silva, H.A.; Dawson, A.H.ABSTRACT: Medication review by a clinical pharmacist improves quality use of medicines in patients by identifying, reducing and preventing drug related problems and hospital re-admissions. This service is new to Sri Lanka. We present two cases from a non-randomized controlled trial conducted in a tertiary care hospital in Sri Lanka. The first case is from the control group where no clinical pharmacist was engaged and the next case is from the intervention group. The first case was a drug related hospital re-admission because of missing medicines in the discharge prescription and the second case was a re-admission which was prevented by the intervention of a ward pharmacist by performing a clinical medication review of the prescription.Item A Randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming(Wiley-Blackwell, 2017) Isbister, G.K.; Jayamanne, S.; Mohamed, F.; Dawson, A.H.; Maduwage, K.; Gawarammana, I.; Lalloo, D.G.; de Silva, H.J.; Scorgie, F.E.; Lincz, L.F.; Buckley, N.A.BACKGROUND: Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom induced consumption coagulopathy (VICC). OBJECTIVES: We investigated the effect of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. METHODS: We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1:1) high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4U FFP. The primary outcome was the proportion of patients with an international normalized ratio (INR)<2, 6h post-antivenom. Secondary outcomes included anaphylaxis, major haemorrhage, death and clotting factor recovery. RESULTS: From 214 eligible patients, 141 were randomized; 71 to high-dose antivenom, 70 to low-dose antivenom/FFP; five had no post-antivenom bloods. The groups were similar except for a delay of 1h in antivenom administration for FFP patients. 6h post-antivenom 23/69 (33%) patients allocated high-dose antivenom had an INR<2 compared with 28/67 (42%) allocated low-dose antivenom/FFP [absolute difference 8%;95%Confidence Interval:-8% to 25%]. 15 patients allocated FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion related acute lung injury. Three deaths occurred in low-dose/FFP patients including one intracranial haemorrhage. There was no difference in recovery rates of INR or fibrinogen, but more rapid initial recovery of factor V and X in FFP patients. CONCLUSION: FFP post-antivenom in Russell's viper bites didn't hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting low-dose antivenom is sufficient. This article is protected by copyright. All rights reserved.Item High lethality and minimal variation after acute self-poisoning with carbamate insecticides in Sri Lanka - implications for global suicide prevention(Informa Healthcare, 2016) Lamb, T.; Selvarajah, L.R.; Mohamed, F.; Jayamanne, S.; Gawarammana, I.; Mostafa, A.; Buckley, N.A.; Roberts, M.S.; Eddleston, M.BACKGROUND: Highly hazardous organophosphorus (OP) insecticides are responsible for most pesticide poisoning deaths. As they are removed from agricultural practice, they are often replaced by carbamate insecticides of perceived lower toxicity. However, relatively little is known about poisoning with these insecticides. METHODS: We prospectively studied 1288 patients self-poisoned with carbamate insecticides admitted to six Sri Lankan hospitals. Clinical outcomes were recorded for each patient and plasma carbamate concentration measured in a sample to confirm the carbamate ingested. FINDINGS: Patients had ingested 3% carbofuran powder (719), carbosulfan EC25 liquid (25% w/v, 389), or fenobucarb EC50 liquid (50% w/v, 127) formulations, carbamate insecticides of WHO Toxicity Classes Ib, II, and II, respectively. Intubation and ventilation was required for 183 (14.2%) patients while 71 (5.5%) died. Compared with carbofuran, poisoning with carbosulfan or fenobucarb was associated with significantly higher risk of death [carbofuran 2.2%; carbosulfan 11.1%, OR 5.5 (95% CI 3.0-9.8); fenobucarb 6.3%, OR 3.0 (1.2-7.1)] and intubation [carbofuran 6.1%; carbosulfan 27.0%, OR 5.7 (3.9-8.3); fenobucarb 18.9%, OR 3.6 (2.1-6.1)]. The clinical presentation and cause of death did not differ markedly between carbamates. Median time to death was similar: carbofuran 42.3 h (IQR 5.5-67.3), carbosulfan 21.3 h (11.5-71.3), and fenobucarb 25.3 h (17.3-72.1) (p = 0.99); no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after OP insecticide poisoning. For survivors, median duration of intubation was 67.8 h (IQR 27.5-118.8) with no difference in duration between carbamates. Reduced GCS at presentation was associated with worse outcome although some patients with carbosulfan died after presentation with normal GCS. CONCLUSIONS: We did not find carbamate insecticide self-poisoning to vary markedly according to the carbamate ingested although the case fatality varied according to the concentration and formulation of the insecticide. Carbamate poisoning did not appear to be much less toxic than poisoning with some liquid OP insecticide formulations, e.g., chlorpyrifos EC40, that we have previously noted in these same hospitals (Lancet 2005, 366:1452-1459; QJM 2006, 99:513-522). Replacement of WHO Class II Toxicity OP insecticides in agriculture with high-strength liquid carbamate formulations may not substantially reduce case fatality after pesticide poisoning and, therefore, global suicide rates.Item Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial(Lancet Publishing Group, 2008) Eddleston, M.; Juszczak, E.; Buckley, N.A.; Senarathna, L.; Mohamed, F.; Dissanayake, W.; Hittarage, A.; Azher, S.; Jeganathan, K.; Jayamanne, S.; Sheriff, M.R.; Warrell, D.A.; Ox-Col Poisoning Study collaboratorsBACKGROUND: The case-fatality for intentional self-poisoning in the rural developing world is 10-50-fold higher than that in industrialised countries, mostly because of the use of highly toxic pesticides and plants. We therefore aimed to assess whether routine treatment with multiple-dose activated charcoal, to interrupt enterovascular or enterohepatic circulations, offers benefit compared with no charcoal in such an environment. METHODS: We did an open-label, parallel group, randomised, controlled trial of six 50 g doses of activated charcoal at 4-h intervals versus no charcoal versus one 50 g dose of activated charcoal in three Sri Lankan hospitals. 4632 patients were randomised to receive no charcoal (n=1554), one dose of charcoal (n=1545), or six doses of charcoal (n=1533); outcomes were available for 4629 patients. 2338 (51%) individuals had ingested pesticides, whereas 1647 (36%) had ingested yellow oleander (Thevetia peruviana) seeds. Mortality was the primary outcome measure. Analysis was by intention to treat. The trial is registered with controlled-trials.com as ISRCTN02920054. FINDINGS: Mortality did not differ between the groups. 97 (6.3%) of 1531 participants in the multiple-dosegroup died, compared with 105 (6.8%) of 1554 in the no charcoal group (adjusted odds ratio 0.96, 95% CI 0.70-1.33). No differences were noted for patients who took particular poisons, were severely ill on admission, or who presented early. INTERPRETATION: We cannot recommend the routine use of multiple-dose activated charcoal in rural Asia Pacific; although further studies of early charcoal administration might be useful, effective affordable treatments are urgently needed. Comment in : Is this the epitaph for multiple-dose activated charcoal? [Lancet. 2008]Item Acute human self-poisoning with imidacloprid compound: a neonicotinoid insecticide(Public Library of Science, 2009) Mohamed, F.; Gawarammana, I.; Robertson, T.A.; Roberts, M.S.; Palangasinghe, C.; Zawahir, S.; Jayamanne, S.; Kandasamy, J.; Eddleston, M.; Buckley, N.A.; Dawson, A.H.; Roberts, D.M.BACKGROUND: Deliberate self-poisoning with older pesticides such as organophosphorus compounds are commonly fatal and a serious public health problem in the developing world. The clinical consequences of self-poisoning with newer pesticides are not well described. Such information may help to improve clinical management and inform pesticide regulators of their relative toxicity. This study reports the clinical outcomes and toxicokinetics of the neonicotinoid insecticide imidacloprid following acute self-poisoning in humans. METHODOLOGY/PRINCIPAL FINDINGS: Demographic and clinical data were prospectively recorded in patients with imidacloprid exposure in three hospitals in Sri Lanka. Blood samples were collected when possible for quantification of imidacloprid concentration. There were 68 patients (61 self-ingestions and 7 dermal exposures) with exposure to imidacloprid. Of the self-poisoning patients, the median time to presentation was 4 hours (IQR 2.3-6.0) and median amount ingested was 15 mL (IQR 10-50 mL). Most patients only developed mild symptoms such as nausea, vomiting, headache and diarrhoea. One patient developed respiratory failure needing mechanical ventilation while another was admitted to intensive care due to prolonged sedation. There were no deaths. Median admission imidacloprid concentration was 10.58 ng/L; IQR: 3.84-15.58 ng/L, Range: 0.02-51.25 ng/L. Changes in the concentration of imidacloprid in serial blood samples were consistent with prolonged absorption and/or saturable elimination. CONCLUSIONS: Imidacloprid generally demonstrates low human lethality even in large ingestions. Respiratory failure and reduced level of consciousness were the most serious complications, but these were uncommon. Substitution of imidacloprid for organophosphorus compounds in areas where the incidence of self-poisoning is high may help reduce deaths from self-poisoning.Item Pralidoxime in acute organophosphorus insecticide poisoning--a randomised controlled trial(Public Library of Science, 2009) Eddleston, M.; Eyer, P.; Worek, F.; Juszczak, E.; Alder, N.; Mohamed, F.; Senarathna, L.; Hittarage, A.; Azher, S.; Jeganathan, K.; Jayamanne, S.; von Meyer, L.; Dawson, A.H.; Sheriff, M.H.; Buckley, N.A.BACKGROUND: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. METHODS AND FINDINGS: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receivepralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. CONCLUSIONS: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.