Browsing by Author "Mohamed, F."

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Acute human self-poisoning with bispyribac-containing herbicide Nominee: a prospective observational study
(Informa Healthcare, 2010) Gawarammana, I.B.; Roberts, D.M.; Mohamed, F.; Roberts, M.S.; Medley, G.; Jayamanne, S.; Dawson, A.
INTRODUCTION: Self-poisoning with herbicides is an important reason for hospital admission and death in Asia. Although some herbicides have a well-described toxicity profile in humans, many of the newer compounds rely on extrapolation from animal results as no published literature on clinical outcomes of human self-poisoning has been described. One example of these compounds is bispyribac, a selective herbicide used in rice and wheat cultivation that is marketed in two containers, one containing bispyribac 400 g/L with a solvent and the other the surfactant, polyethylene glycol. We present the first case series of acute human self-poisoning with an herbicide product containing bispyribac. METHODS: Clinical data for all patients who presented with acute poisoning from a bispyribac-containing herbicide (Nominee) to two general hospitals in Sri Lanka from June 2002 to January 2009 were collected prospectively. Admission and serial blood samples were collected from consenting patients to confirm exposure and to study the toxicokinetics of bispyribac, respectively. RESULTS: One hundred ten patients with a history of bispyribac ingestion presented after a median time of 4 h post-ingestion. There were three deaths at 15, 6, and 5 h post-ingestion because of asystolic cardiac arrest. All three patients had reduced Glasgow Coma Score (GCS) (3, 12, and 13, respectively) of whom the former two had co-ingested ethanol and developed tonic-clonic seizures. Admission blood sample was obtained from the former two of these patients but bispyribac was detected in only one of these patients. The other patient presented 2.5 h post-ingestion with a GCS of 12 but bispyribac was not detected. Excluding the patient with undetectable bispyribac, a conservative estimate of the case fatality ratio at 1.81% (95% confidence interval 0.32-5.8) can be made. The majority of the remaining patients had self-limiting upper gastrointestinal symptoms and eight patients had an abnormal GCS on presentation to hospital. The overall median hospital stay was 3 days. Bispyribac was not detectable on admission in 21 patients; in the remaining patients, the median plasma concentration was 50.55 microg/mL (interquartile range 1.28-116.5; n=32). The peak concentration was noted around 3 h post-ingestion and plasma bispyribac concentration did not predict the severity of poisoning. CONCLUSION: The majority of patients developed self-resolving symptoms and were successfully managed in rural general hospitals without transfer to larger tertiary hospitals. Patients who died developed significant poisoning within 6 h and plasma bispyribac concentrations did not appear to predict mortality. The lack of correlation between bispyribac outcomes and the available plasma concentrations may be because of exposure to nonbispyribac components or other undefined factors. Clinical outcomes from acute self-poisoning with bispyribac-containing herbicides appear to be relatively more favorable than other commonly used herbicides.
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.
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.
A case series of duplication errors due to brand name confusion - experience from a Sri Lankan teaching hospital
(Sri lanka Medical Association, 2015) Mamunuwa, A.M.V.G.N.; Jayamanne, S.F.; Coombes, J.; Lynch, C.B.; Perera, D.M.P.; Pathiraja, V.M.; Shanika, L.G.T.; Mohamed, F.; Dawson, A.H.
INTRODUCTION AND OBJECTIVES: Confusion with drug names has been identified as a leading cause of medication errors. The majority of these errors result from look-alike or sound-alike drugs. This case series aims to provide examples of duplication errors due to brand confusion where there are no similarities in the names. METHOD: Information for this case series was extracted from a database prospectively collected from Colombo North Teaching Hospital as part of a study conducted to evaluate the impact of the addition of a clinical pharmacist to the standard inpatient care. RESULTS: Of 800 patients reviewed during the study period of 7 months, clinical pharmacist identified 8 cases of duplication errors due to prescribing both generic and brand names of the same drug, but with no similarities in names. Cases identified include a duplication of frusemide caused by the lack of awareness that 'Amifru' {a combination of frusemide and amiloride) contains frusemide. Similarly, a patient was prescribed 'H. Pylori Kit' plus the three individual drugs included in the 'Kif prescribed using their generic names. A patient was found to be taking two different brands of carbidopa plus levodopa not knowing the two contained the same drugs. CONCLUSION: Brand confusion does not necessarily arise from look-alike or sound-alike drug names. It can be due to numerous brands of generic ingredients and lack of awareness of drug names among the patients. Employing trained clinical pharmacists in the wards, educating patients on discharge drugs and appropriate labeling of medicines may prevent these errors.
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.
Community-based cluster randomised trial of safe storage to reduce pesticide self-poisoning in rural Sri Lanka: study protocol
(BioMed Central, 2011) Pearson, M.; Konradsen, F.; Gunnell, D.; Dawson, A.H.; Pieris, R.; Weerasinghe, M.; Knipe, D.W.; Jayamanne, S.; Metcalfe, C.; Hawton, K.; Wickremasinghe, A.R.; Atapattu, W.; Bandara, P.; de Silva, D.; Ranasinghe, A.; Mohamed, F.; Buckley, N.A.; Gawarammana, I.; Eddleston, M.A.
BACKGROUND: The WHO recognises pesticide poisoning to be the single most important means of suicide globally. Pesticide self-poisoning is a major public health and clinical problem in rural Asia, where it has led to case fatality ratios 20-30 times higher than self-poisoning in the developed world. One approach to reducing access to pesticides is for households to store pesticides in lockable "safe-storage" containers. However, before this approach can be promoted, evidence is required on its effectiveness and safety. METHODS/DESIGN: A community-based cluster randomised controlled trial has been set up in 44,000 households in the North Central Province, Sri Lanka. A census is being performed, collecting baseline demographic data, socio-economic status, pesticide usage, self-harm and alcohol. Participating villages are then randomised and eligible households in the intervention arm given a lockable safe storage container for agrochemicals. The primary outcome will be incidence of pesticide self-poisoning over three years amongst individuals aged 14 years and over. 217,944 person years of follow-up are required in each arm to detect a 33% reduction in pesticide self-poisoning with 80% power at the 5% significance level. Secondary outcomes will include the incidence of all pesticide poisoning and total self-harm. DISCUSSION: This paper describes a large effectiveness study of a community intervention to reduce the burden of intentional poisoning in rural Sri Lanka. The study builds on a strong partnership between provincial health services, local and international researchers, and local communities. We discuss issues in relation to randomisation and contamination, engaging control villages, the intervention, and strategies to improve adherence.
Duplication errors due to brand name confusion; It is not always the name-Short case series
(John Wiley & Sons, 2023) Mamunuwa, N.; Jayamanne, S.; Wijekoon, N.; Coombes, J.; Perera, D.; Shanika, T.; Mohamed, F.; Lynch, C.; de Silva, A.; Dawson, A.
Confusion of drug names has been identified as a leading cause of medication errors and potential iatrogenic harm. Most of these errors occur because of look-alike or sound-alike drugs. This case series gives examples of duplication errors due to brand confusion, where there are no similarities in the names.
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.
Effects of provincial ban of two toxic organophosphorus insecticides on pesticide poisoning hospitaladmissions
(Informa Healthcare, 2012) Eddleston, M.; Adhikari, S.; Egodage, S.; Ranganath, H.; Mohamed, F.; Manuweera, G.; Azher, S.; Jayamanne, S.; Juzczak, E.; Sheriff, M.R.; Dawson, A.H.; Buckley, N.A.
BACKGROUND: Pesticide self-poisoning causes one third of global suicides. Sri Lanka halved its suicide rate by banning WHO Class Iorganophosphorus (OP) insecticides and then endosulfan. However, poisoning with Class II toxicity OPs, particularly dimethoate and fenthion, remains a problem. We aimed to determine the effect and feasibility of a ban of the two insecticides in one Sri Lankan district. METHODS: Sale was banned in June 2003 in most of Polonnaruwa District, but not Anuradhapura District. Admissions with pesticide poisoning to the district general hospitals was prospectively recorded from 2002. RESULTS: Hospital admissions for dimethoate and fenthion poisoning fell by 43% after the ban in Polonnaruwa, while increasing by 23% in Anuradhapura. The pesticide case fatality fell from 14.4% to 9.0% in Polonnaruwa (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.41-0.84) and 11.3% to 10.6% in Anuradhapura (OR 0.93, 95%CI 0.70-1.25; p = 0.051). This reduction was not sustained, with case fatality in Polonnaruwa rising to 12.1% in 2006-2007. Further data analysis indicated that the fall in case fatality had actually been due to a coincidental reduction in case fatality for pesticide poisoning overall, in particular for paraquat poisoning. CONCLUSIONS: We found that the insecticides could be effectively banned from agricultural practice, as shown by the fall in hospital admissions, with few negative consequences. However, the ban had only a minor effect on pesticide poisoning deaths because it was too narrow. A study assessing the agricultural and health effects of a more comprehensive ban of highly toxic pesticides is necessary to determine the balance between increased costs of agriculture and reduced health care costs and fewer deaths.
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.
Importance of communicating medication changes to patients at discharge -a prospective case study
(Sri lanka Medical Association, 2015) Pathiraja, V.M.; Jayamanne, S.F.; Lynch, C.B.; Coombes, J.; Perera, D.M.P.; Mamunuwa, A.M.V.G.N.; Shanika, L.G.T.; Mohamed, F.; Dawson, A.H.
INTRODUCTION AND OBJECTIVES: Patients may inadvertently continue their previous medication regimen without understanding changes made by prescribers as part of in-patient care. Inadequate patient education at discharge can lead in some instances to readmission and increased morbidity. The objective of this study is to identify the importance of patient education with regard to changes to their medications. METHOD: This study was part of a prospective study carried out in two medical wards of Ragama teaching hospital to evaluate the effect of a clinical pharmacist's interventions on quality use of medicines. We identified cases from the control group of this study to illustrate the importance of patient education at discharge. RESULTS: From telephone follow-up (six days post discharge), only 89 of 337 patients in the control group reported being informed of changes to their pre-admission medications by a doctor or nurse. There were!24 cases where we have identified patients continuing at least one pre-admission medication which was stopped or changed while they were in hospital. A particular instance is a patient who continued to take sodium valproate post-discharge as per previous drug regimen after being diagnosed with valproate induced hepatitis. He was discharged on phenytoin. CONCLUSION: This study highlights the importance of ensuring patient education about changes made to existing medications whilst in hospital to ensure improved outcomes and reduce the risk of adverse events. The clinical pharmacist is well placed to assist medical teams by providing patients with appropriate education about medication changes and to provide appropriate educational material.
Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion
(Amsterdam, Elsevier/North Holland, 2015) Mohamed, F.; Buckley, N.A.; Jayamanne, S.; Pickering, J.W.; Peake, P.; Palangasinghe, C.; Wijerathna, T.; Ratnayake, I.; Shihana, F.; Endre, Z.H.
Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine samples from patients from 5 Sri Lankan hospitals. Functional AKI was diagnosed using serum creatinine (sCr) or serum cystatin C (sCysC). The 95th centile in healthy subjects defined the urinary biomarker cutoffs for diagnosing structural AKI. 50 poisoned patients provided 2 or more specimens, 76% developed functional AKI [AKIN stage 1 (n=12), 2 (n=7) or 3 (n=19)]; 19/26 patients with AKIN stage 2/3 also had functional AKI by sCysC criteria (≥50% increase). Urinary cystatin C (uCysC), clusterin (uClu) and NGAL (uNGAL) increased within 24h of ingestion compared with NoAKI patients and healthy controls. Each biomarker demonstrated moderate diagnostic utility [AUC-ROC: uCysC 0.79, uNGAL 0.79, uClu 0.68] for diagnosis of functional AKI at 16h. Death occurred only in subjects with functional AKI. Structural biomarker-based definitions detected more AKI than did sCr or sCysC, but did not independently predict death. Renal injury biomarkers did not add clinical value to patients who died rapidly due to multi-organ failure. Use of injury biomarkers within 16-24h may guide early intervention for reno-protection in less severe paraquat poisoning.
Management of paracetamol overdose in primary care hospitals in Sri Lanka: Are all the transfers justifiable?
(Sri Lanka Medical Association, 2018) Pathiraja, V. M.; Gawarammana, I. B.; Buckley, N. A.; Mohamed, F.; Jayamanna, S. F.; Dawson, A. H.
INTRODUCTION AND OBJECTIVES: National guidelines on the management of self-poisoning allows treatment of paracetamol poisoning in rural hospitals. Non-adherence to these guidelines may lead to unnecessary and costly transfers to larger referral hospitals. The objective of this study was to investigate if non-adherence to guidelines is justifiable.METHODS: In a prospective study, data was linked between primary and tertiary hospitals in Kurunegala and Matara districts. We examined the transfer patterns to two tertiary hospitals (THK and THM) and attempted to justify if the transfers were necessary.RESULT: There were 3129 admissions to primary hospitals and 904 (29%) patients were transferred to THK (809)and THM (95). The reason for transfer was mentioned as antidote requirement in 297, and in 607, antidote treatment was not mentioned as the reason for transfer. There was a significant difference of the median number of tablets ingested between those who had a reason mentioned 23 (IQR=18-30) and otherwise 21.5 (IQR 13-28) (p<0.000).485 (54%) were given an antidote at the tertiary care hospitals. 398 (44%) patients were not given an antidote andshould not have been transferred. Of the 297, who were transferred for antidotes, 147 (60%) were given antidotes and 51 were lost to follow up. Of those 607 who were transferred for other reasons, 238(48%) received antidotes and 112 were lost to follow up.CONCLUSION: Large numbers of patients who do not require treatment are transferred. A significant number of patients who require antidotes are not treated in the primary hospitals. This reflects that understanding treatment guidelines is poor.
Mechanism-specific injury biomarkers predict nephrotoxicity early following glyphosate surfactant herbicide (GPSH) poisoning
(Elsevier, 2016) Mohamed, F.; Endre, Z.H.; Pickering, J.W.; Jayamanne, S.; Palangasinghe, C.; Shahmy, S.; Chathuranga, U.; Wijerathne, T.; Shihana, F.; Gawarammana, I.; Buckley, N.A.
Acute kidney injury (AKI) is common following glyphosate surfactant herbicide (GPSH) self-poisoning. Serum creatinine (sCr) is the most widely used renal biomarker for diagnosis of AKI although a recent study in rats suggested that urinary kidney injury molecule-1 predicted AKI earlier and better after GPSH-induced nephrotoxicity. We explored the utility of a panel of biomarkers to diagnose GPSH-induced nephrotoxicity in humans. In a prospective multi-centre observational study, serial urine and blood samples were collected until discharge and at follow-up. The diagnostic performance of each biomarker at various time points was assessed. AKI was diagnosed using the Acute Kidney Injury Network (AKIN) definitions. The added value of each biomarker to sCr to diagnose AKI was assessed by the integrated discrimination improvement (IDI) metric. Of 90 symptomatic patients, 51% developed AKI and 5 patients who developed AKIN ≥ 2 died. Increased sCr at 8 and 16 hours predicted moderate to severe AKI and death. None of the 10 urinary biomarkers tested increased above normal range in patients who did not develop AKI or had mild AKI (AKIN1); most of these patients also had only minor clinical toxicity. Absolute concentrations of serum and urinary cystatin C, urinary interleukin-18 (IL-18), Cytochrome C (CytoC) and NGAL increased many fold within 8 hours in patients who developed AKIN ≥ 2. Maximum 8 and 16 hour concentrations of these biomarkers showed an excellent diagnostic performance (AUC-ROC ≥0.8) to diagnose AKIN ≥ 2. However, of these biomarkers only uCytoC added value to sCr to diagnose AKI when assessed by IDI metrics. GPSH-induced nephrotoxicity can be diagnosed within 24 hours by sCr. Increases in uCytoC and uIL-18 confirm GPSH-induces apoptosis and causes mitochondrial toxicity. Use of these biomarkers may help to identify mechanism specific targeted therapies for GPSH nephrotoxicity in clinical trials.
Mechanisms underlying early rapid increases in creatinine in paraquat poisoning
(Public Library of Science, 2015) Mohamed, F.; Endre, Z.; Jayamanne, S.; Pianta, T.; Peake, P.; Palangasinghe, C.; Chathuranga, U.; Jayasekera, K.; Wunnapuk, K.; Shihana, F.; Shahmy, S.; Buckley, N.
BACKGROUND: Acute kidney injury (AKI) is common after severe paraquat poisoning and usually heralds a fatal outcome. The rapid large increases in serum creatinine (Cr) exceed that which can be explained by creatinine kinetics based on loss of glomerular filtration rate (GFR). METHODS AND FINDINGS: This prospective multi-centre study compared the kinetics of two surrogate markers of GFR, serum creatinine and serum cystatin C (CysC), following paraquat poisoning to understand and assess renal functional loss after paraquat poisoning. Sixty-six acute paraquat poisoning patients admitted to medical units of five hospitals were included. Relative changes in creatinine and CysC were monitored in serial blood and urine samples, and influences of non-renal factors were also studied. RESULTS: Forty-eight of 66 patients developed AKI (AKIN criteria), with 37 (56%) developing moderate to severe AKI (AKIN stage 2 or 3). The 37 patients showed rapid increases in creatinine of >100% within 24 hours, >200% within 48 hours and >300% by 72 hours and 17 of the 37 died. CysC concentration increased by 50% at 24 hours in the same 37 patients and then remained constant. The creatinine/CysC ratio increased 8 fold over 72 hours. There was a modest fall in urinary creatinine and serum/urine creatinine ratios and a moderate increase in urinary paraquat during first three days. CONCLUSION: Loss of renal function contributes modestly to the large increases in creatinine following paraquat poisoning. The rapid rise in serum creatinine most probably represents increased production of creatine and creatinine to meet the energy demand following severe oxidative stress. Minor contributions include increased cyclisation of creatine to creatinine because of acidosis and competitive or non-competitive inhibition ofcreatinine secretion. Creatinine is not a good marker of renal functional loss after paraquat poisoning and renal injury should be evaluated using more specific biomarkers of renal injury
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 collaborators
BACKGROUND: 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]
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 team
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.
Population pharmacokinetics of an Indian F(ab')2 snake antivenom in patients with Russell's Viper (Daboia russelii) bites
(Public Library of Science, 2015) Isbister, G.K.; Maduwage, K.; Saiao, A.; Buckley, N.A.; Jayamanne, S.F.; Seyed, S.; Mohamed, F.; Chathuranga, U.; Mendes, A.; Abeysinghe, C.; Karunathilake, H.; Gawarammana, I.; Lalloo, D.G.; de Silva, H.J.
BACKGROUND: There is limited information on antivenom pharmacokinetics. This study aimed to investigate the pharmacokinetics of an Indian snake antivenom in humans with Russell's viper bites. METHODS/PRINCIPAL FINDINGS: Patient data and serial blood samples were collected from patients with Russell's viper (Daboia russelii) envenoming in Sri Lanka. All patients received Indian F(ab')2 snake antivenom manufactured by VINS Bioproducts Ltd. Antivenom concentrations were measured with sandwich enzyme immunoassays. Timed antivenom concentrations were analysed using MONOLIXvs4.2. One, two and three compartment models with zero order input and first order elimination kinetics were assessed. Models were parameterized with clearance(CL), intercompartmental clearance(Q), central compartment volume(V) and peripheral compartment volume(VP). Between-subject-variability (BSV) on relative bioavailability (F) was included to account for dose variations. Covariates effects (age, sex, weight, antivenom batch, pre-antivenom concentrations) were explored by visual inspection and in model building. There were 75 patients, median age 57 years (40-70y) and 64 (85%) were male. 411 antivenom concentration data points were analysed. A two compartment model with zero order input, linear elimination kinetics and a combined error model best described the data. Inclusion of BSV on F and weight as a covariate on V improved the model. Inclusion of pre-antivenom concentrations or different batches on BSV of F did not. Final model parameter estimates were CL,0.078 Lh-1, V,2.2L, Q,0.178Lh-1 and VP,8.33L. The median half-life of distribution was 4.6h (10-90%iles:2.6-7.1h) and half-life of elimination, 140h (10th-90th percentilesx:95-223h). CONCLUSION: Indian F(ab')2 snake antivenom displayed biexponential disposition pharmacokinetics, with a rapid distribution half-life and more prolonged elimination half-life.
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.