Renal injury at first presentation as a predictor for poor outcome in severe paracetamol poisoning referred to a liver transplant unit

Background  Paracetamol poisoning remains a leading cause of morbidity and mortality. Identifying indices of poor prognosis at first presentation is key to both improving clinical care and determining targets for intervention. Renal failure is a feature of severe paracetamol poisoning. The aim of this study was to investigate the relationship between renal function (serum creatinine, Cr) at first hospital presentation and time of tertiary referral to outcomes in severe paracetamol poisoning. Methods  This was a retrospective cohort analysis of patients referred to the Scottish Liver Transplant Unit due to paracetamol poisoning between 1992 and 2004. The relation between degree of renal injury and outcomes, including worst prothrombin time, Kings College Hospital Criteria (KCHC) and death were examined. The effects of age, nature (single or multiple) and stated size of overdose, hepatic enzyme induction (gamma-glutamyl transpeptidase, GGT), degree of liver injury (aspartate aminotransferase, prothrombin time), blood pressure and renal injury were assessed. Results  Data from 522 patients were included. Renal impairment (Cr >120 mmol/l) was present in 48.8% of patients with liver injury at time of first presentation. Creatinine at first admission predicted poorer outcome in terms of worse prothrombin time, KCHC and death (p < 0.001). Associated risk factors for renal dysfunction included later presentation, staggered ingestion, increased age, hypotension and elevated GGT at first admission. Conclusions  Creatinine at first admission appears to be a predictor of poor outcome in paracetamol overdose. A better understanding of mechanisms involved in causing renal dysfunction may offer potential therapeutic targets for improving outcome in this common poisoning.     

The extent of and factors associated with self-reported overdose and self-reported receipt of naloxone among people who inject drugs (PWID) in England,Wales and Northern Ireland

BackgroundOverdose is a major cause of death among PWID, and for opioid overdoses naloxone administration can reduce harm. However, globally there is limited national level data on the extent of non-fatal overdose and naloxone uptake. The first national level data on the extent of self-reported overdose and self-reported receipt of naloxone among UK PWID, providing a baseline to monitor the impact of the recent policy change regarding naloxone availability, is presented.MethodsData on self-reported overdose and receipt of naloxone during the preceding year for 2013–2014 from a national survey of PWID was analysed. Participants who reported injecting during the preceding year were included.ResultsParticipants (3850) were predominantly male (75%); mean age was 36 years. The most commonly injected drugs were: heroin (91%), crack (45%) and amphetamine (29%). 15% (591) reported overdosing during the preceding year. There were no differences in the proportion reporting overdose by age or gender, but overdose was more common among those who: injected multiple drugs; recently ceased addiction treatment; injected with used needles/syringes; ever had transactional sex; had used a sexual health clinic or emergency department and lived in Wales or Northern Ireland. Among those reporting an overdose during the preceding year, a third reported two to four overdoses and 7.5% five or more overdoses; half reported receiving naloxone. Those reporting naloxone receipt in the preceding year were more likely to: live in Wales or Northern Ireland; ever received used needles/syringes; ever been imprisoned; and less likely to have injected two drug types.ConclusionThese data provide a baseline for monitoring the impact of the 2015 UK policy change to improve take-home naloxone access. Interventions tackling overdose should promote naloxone awareness and access, and target those who; are poly-drug injectors, have ceased treatment, share needles/syringes and whose drug use links to sexual activity.     

Impaired heart rate variability and altered cardiac sympathovagal balance after antidepressant overdose

Purpose  Antidepressant overdose may be associated with significant cardiotoxicity, and recent data have shown that acute toxic effects are associated with impaired heart rate variability. This study was designed to examine the feasibility of non-invasive heart rate variability recording in patients that present to hospital after deliberate antidepressant ingestion. Methods  This was a prospective study of 72 consecutive patients attending the Emergency Department after deliberate antidepressant overdose and 72 age-matched patients that ingested paracetamol, as a control group. Single time-point continuous electrocardiographic recordings were used to allow spectral analyses of heart rate variability determined in low-frequency (LF) and high-frequency (HF) domains. The LF:HF ratio was used to represent overall sympathovagal cardiac activity. Results  Antidepressant overdose was associated with reduced overall heart rate variability: 1329 vs. 2018 ms² (P = 0.0239 by Mann–Whitney test). Variability in the LF domain was higher (64.8 vs. 49.8, P = 0.0006), whereas that in the HF domain was lower (24.3 vs. 36.4, P = 0.0001), and the LF:HF ratio was higher in the antidepressant group (2.4 vs. 1.2, P = 0.0003). Conclusions  Antidepressant overdose is associated with impaired heart rate variability in a pattern consistent with excess cardiac sympathetic activity. Further work is required to establish the significance of these findings and to explore whether the impairment of heart rate variability may be used to predict the development of arrhythmia in this patient group.     

Changes in urinary PGE<Subscript>2</Subscript> after ibuprofen treatment in preterm infants with patent ductus arteriosus

Purpose  To investigate changes in urinary PGE₂ after ibuprofen treatment in preterm infants with patent ductus arteriosus (PDA). Methods  Twenty preterm infants with a hemodynamically significant PDA (gestational age, 28.6 ± 2.3 weeks) and 20 controls (gestational age, 30.4 ± 1.5 weeks) were prospectively enrolled at 48–72 h of life. After enrollment, the former underwent conventional ibuprofen-lysine treatment. At 48–72 h (T₀) and 108–144 h of life (T₁), urine samples were noninvasively collected in both groups to measure urinary PGE₂ concentrations (enzyme immunoassay method), and renal function was investigated. Results  Urinary PGE₂ decreased significantly both in ibuprofen-treated patients (66.95 ± 16.78 vs. 27.15 ± 17.92 pg/mL, P < 0.001) and in controls (71.7 ± 16.2 vs. 53.2 ± 18.4 pg/mL, P < 0.001) from T₀ to T₁. However, urinary PGE₂ at T₁ was significantly lower (P < 0.001) in the ibuprofen group compared to the control group. Acute renal failure occurred in three ibuprofen-treated patients (15%). Conclusions  Ibuprofen markedly reduces (59.4%) urinary PGE₂ and may alter renal function in the newborn.     

The association between use of cardiovascular drugs and antidepressants: a nationwide register-based study

Purpose  To investigate whether cardiovascular drug classes and specific beta-blockers are associated with antidepressant drug use in a large study population of older people. Methods  We analyzed data from the Swedish Prescribed Drug Register from October-December 2005 for people aged 75 years and older (n = 732,230). Logistic regression analysis was used to study the association between the cardiovascular drugs and antidepressants, after adjustment for age, sex, and number of other dispensed drugs. Results  All the cardiovascular drug classes were negatively or not associated with use of any antidepressant, non-selective monoamine reuptake inhibitors, and SSRIs, after adjustment for age, sex, and number of other dispensed drugs. However, propranolol was associated with an increased use of any antidepressant, non-selective monoamine reuptake inhibitors, and SSRIs, after adjustment for age, sex, and number of other dispensed drugs. Atenolol was positively associated with non-selective monoamine reuptake inhibitors, although to a lesser extent than propranolol. Conclusions  None of the cardiovascular drug classes were associated with increased antidepressant drug use, after adjustment for age, sex, and use of other drugs. However, when focusing specifically on beta-blockers, our results indicate that propranolol may be the beta-blocker most closely associated with use of antidepressants in the elderly.     

Concomitant overdosing of other drugs in patients with paracetamol poisoning

AIMS: Paracetamol is frequently involved in intended self-poisoning, and concomitant overdosing of other drugs is commonly reported. The purpose of the study was to investigate further concomitant drug overdose in patients with paracetamol poisoning and to evaluate its effects on the outcome of the paracetamol intoxication. METHODS: Six hundred and seventy-one consecutive patients admitted with paracetamol poisoning were studied and concomitant drug intake was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, hepatic dysfunction, liver cell damage, and renal dysfunction associated with concomitant overdosing of other drugs was evaluated by multivariate analysis. RESULTS: Concomitant drug overdose was found in 207 patients (31%, 95% confidence interval [CI] 27, 34%). Concomitant overdosing of benzodiazepines (99 cases), opioid analgesics (38 cases), acetylsalicylic acid (33 cases), and NSAID (32 cases) predominated. Concomitant benzodiazepine overdose was an independent risk factor in the development of hepatic encephalopathy (odds ratio [OR] 1.91; CI 1.00, 3.65) and renal dysfunction (OR 1.81; CI 1.00, 3.22). Concomitant overdosing of opioid analgesics was a protective factor in the development of hepatic encephalopathy (OR 0.26; CI 0.07, 0.96). Concomitant acetylsalicylic acid overdose was a risk factor in the development of hepatic encephalopathy (OR 4.87; CI 1.52, 15.7) and death or liver transplantation (OR 6.04; CI 1.69, 21.6). A tendency towards a more favourable outcome was observed in patients with concomitant NSAID overdose. CONCLUSIONS: Concomitant overdosing of benzodiazepines or analgesics is frequent in patients admitted with paracetamol poisoning. Concomitant benzodiazepine or acetylsalicylic acid overdose was associated with more severe toxicity, whereas concomitant overdosing of opioid analgesics was associated with less toxicity.     

Drug-related overdoses within a medically supervised safer injection facility

BackgroundIn September 2003, North America's first supervised injection facility (SIF) opened in Vancouver, Canada. We sought to examine the incidence and characteristics of overdose events at the SIF.MethodsThe Vancouver SIF evaluation involves a comprehensive database within the SIF and the Scientific Evaluation of Supervised Injection (SEOSI) cohort consisting of 1046 SIF users. We examined the incidence and features of overdoses at the SIF and the responses made by SIF staff. Cox regression was used to examine factors associated with time to overdose among SEOSI participants.ResultsBetween 1 March 2004 and 30 August 2005, there were 336 overdose events at the SIF, yielding a rate of 1.33 (95% CI: 0.0–3.6) overdoses per 1000 injections. The most common indicator of overdose was depressed respiration (60%), and the most common intervention involved the administration of oxygen (87%). In total, 90 SEOSI participants had an overdose at the SIF during the study period. Factors independently associated with time to overdose included fewer years injecting (RH = 0.98, 95% CI: 0.96–1.00 per year), daily heroin use (RH = 1.82, 95% CI: 1.16–2.85), and having a history of overdose (RH = 1.92, 95% CI: 1.21–3.06).ConclusionsThere have been a large number of overdoses within the SIF, and it is noteworthy that none of these overdoses resulted in a fatality. These findings suggest that SIF can play a role in managing overdoses among IDU and indicate the need for further evaluation of the impact of SIF on morbidity and mortality associated with overdose.     

Influence of renal function on the pharmacokinetics of cerivastatin in normocholesterolemic adults

Objective: The influence of impaired renal function on the pharmacokinetics of single and multiple doses of cerivastatin was evaluated in this non-randomized, non-blinded, 7-day, multiple-dose study. Methods: Thirty-five adults between the ages of 21 years and 75 years with normal renal function (CL_CR >90 ml/min/1.73 m², n=9), or patients with either mild (CL_CR 61 ml/min/1.73 m² to ≤90 ml/min/1.73 m², n=9), moderate (CL_CR 30 ml/min/1.73 m² to ≤60 ml/min/1.73 m², n=8), or severe (CL_CR <30 ml/min/1.73 m², but not on dialysis, n=9) renal impairment were given cerivastatin 0.3 mg daily each evening for 7 days. The steady-state pharmacokinetics of cerivastatin, including the area under the concentration–time curve (AUC)_0–24, peak plasma concentration (C_max), time to reach C_max (t_max) and elimination half-life (t_1/2), were determined on day 1 and day 7. The logarithm of the pharmacokinetic variables was analyzed using analysis of variance (ANOVA). Safety assessments included physical examination, fundoscopy, vital signs, electrocardiogram (ECG), adverse events, and laboratory safety indices. Results: The day-1 AUC in patients with mild renal impairment was similar to that of patients with normal function (19.6 μg/h/l vs 19.2 μg/h/l, respectively). However, the AUC for cerivastatin patients with moderate or severe renal impairment was 40–60% higher (30.8 μg/h/l and 29.0 μg/h/l, respectively). C_max values for patients with normal, mild, moderate, and severe renal impairment were 3.3, 3.4, 4.6, and 5.2 μg/l, respectively. This modest increase in plasma cerivastatin levels is nearly equivalent to a 0.4-mg daily dose, which has been recently approved in the United States. The mean t_1/2 of cerivastatin was less than 4.5 h in all patients, indicating that renal dysfunction did not promote cerivastatin accumulation. This observation was confirmed by the finding that the cerivastatin plasma levels on day 1 and day 7 were similar in all patient groups. Furthermore, the mean AUC and C_max values for both demethylated and hydroxylated cerivastatin were similar in the patients with the most severe renal dysfunction to the corresponding values in healthy subjects. Cerivastatin was well tolerated in all patients irrespective of renal function. Adverse events were observed in 37% of the subjects; nearly all were mild and generally of short duration, and most resolved without intervention. Incidence of adverse events was similar across all three renal groups and the control group. There were no clinically significant laboratory changes other than those consistent with renal disease. Conclusion: This study demonstrates that dosage adjustment of the daily 0.3-mg cerivastatin dose in patients with significant renal impairment is likely unnecessary. Received: 2 August 1999 / Accepted in revised form: 12 January 2000     

Reappraisal of treatment-induced renal dysfunction in patients receiving antiangiogenic agents in phase I trials

Background Several phase I trials are currently evaluating new antiangiogenic compounds. While hypertension and proteinuria have been largely reported as a class side effect of these agents, data on renal function [i.e. the glomerular filtration rate (GFR)] in patients (pts) treated with new antiangiogenic compounds in phase I trials are much scarcer. Patients and methods Between November 2005 and March 2008, we identified 72 pts with solid tumors who had been included in four Phase I trials testing antiangiogenic or related compounds. Thirty-two pts had received a pan-HER/VEGFR inhibitor (A), 29 had received a vascular-disrupting agent (B) and 11 had received a pan-VEGFR inhibitor in combination with CPT11 (C). For each patient, we retrospectively analyzed the serum creatinine level (SCr), Cr clearance (CrCl) calculated by both the Cockcroft and Gault and aMDRD equations at baseline, during treatment and at the end of treatment. Acute renal failure (ARF) was defined as a decrease of >25% in CrCl, and severe renal failure (SRF) as a decrease of >50% in CrCl. Chronic renal failure (CRF) was defined according to the KDOQI-KDIGO classification. Renal dysfunction was defined as Cl <60 ml/min with a normal Cr level (<125 μmol/l). Results Each pt had received an average of 4 cycles of treatment (1 to 12). During treatment, the incidence of ARF ranged from 40.2% to 44.4% (A = 11/32, B = 19/29, C = 2/11). Seven to 9.7% of these cases were severe (A = 1/32, B = 6/29, C = 0/11). Moreover, 26.4 to 27.7% of the pts had exhibited persistent renal insufficiency at the end of the study (A = 5/32, B = 15/29, C = 0/11). From the start till the end of treatment, ARF had been documented in 20.8% to 22.2% of the pts. The average reduction in clearance was 9.8 to 11.6 ml/min/1.73 m2 between baseline and the end of treatment. Conclusion The incidence of renal toxicity in phase I pts treated with antiangiogenic compounds was much higher than expected. Simple screening of Cr levels appears to be insufficient and careful nephrologic monitoring at baseline and during treatment should be implemented in early clinical trials assessing the risk/benefit ratio of new antiangiogenic compounds.     

Adverse events of blood-pressure-lowering drugs: evidence of high incidence in a clinical setting

Objectives  Our primary objective was to determine the incidence of AEs of antihypertensive drugs in a cohort of outpatients attending a specialized clinic. The secondary objectives were to determine the incidence of AEs by classes of blood-pressure-lowering drugs used in monotherapy and to identify risk factors for the occurrence of AEs. Methods  In a prospectively planned cohort study, patients attending a hypertension outpatient clinic were systematically interrogated about the occurrence of AEs of blood-pressure-lowering drugs. We compared the incidence of AEs by classes of drugs employed in monotherapy and identified risk factors for the occurrence of AEs in a logistic regression model. Results  Participants were followed for 12.3 ± 12.2 months. In total, 534 (35.4%) of 1,366 patients treated with blood pressure drugs complained of at least one AE during the follow-up, corresponding to an incidence of 31.3 AEs per 1,000 patients/month [95% confidence interval (CI) 28.6–33.9). The systolic blood pressure in the initial evaluation (P = 0.002) and use of two or more drugs (P < 0.001) were associated with higher incidence of AEs. The incidence of AEs was higher among patients treated with calcium channel blockers in monotherapy than in patients treated with diuretics (47.2 vs. 7.6%, P < 0.001). Conclusion  Adverse events of blood-pressure-lowering drugs are quite frequent in a clinical context, and may influence the adherence to treatment. Patients under treatment with diuretics in monotherapy have the lower incidence of AEs.     

Pharmacokinetics of sertindole and dehydrosertindole in volunteers with normal or impaired renal function

Objective: To study the effect of renal impairment on the pharmacokinetics of sertindole. Methods: A single 4 mg oral dose of sertindole was given to normal subjects ( n = 6) and subjects with various degrees of impaired renal function ( n = 18) classified into mild, moderate, and severe/hemodialysis based on their creatinine clearance). The relationships between the pharmacokinetic parameters and the degree of renal impairment were investigated using regression analysis with creatinine clearance as an explanatory variable along with body weight. Subjects were also genotyped for CYP2D6-A or 2D6-B mutations. Results: The mean CL/f and t_1/2 values of sertindole ranged from 14 to 31 l · h⁻¹ and from 73 to 93 h, respectively, and were not significantly related to creatinine clearances. There was no indication of any influence of creatinine clearance on the fraction of sertindole (0.994–0.995) binding to plasma proteins. The total fraction of the sertindole dose removed by dialysis was less than 0.1%. Subjects with B/B genotype ( n = 2) for CYP2D6 were associated with a distinctly lower clearance of sertindole (6.3 vs 25.3 l · h⁻¹) than subjects with wt/wt genotype for CYP2D6. Conclusions: Since the pharmacokinetics of sertindole are unchanged by renal impairment, dosage adjustment does not appear to be necessary for subjects with various degrees of renal insufficiency or subjects with renal failure requiring hemodialysis. Received: 19 August 1996 / Accepted in revised form: 9 January 1997     

Clinical pharmacists’ interventions in a German University Hospital

Objective To evaluate pharmaceutical interventions by ward-based clinical pharmacists in Germany. Setting Two ward-based clinical pharmacists working at the Departments of Stem Cell Transplantation and Intensive Care Medicine. Methods Pharmaceutical interventions during ward rounds from December 1st 2006 to November 30th 2008 were recorded and classified according to our own system that was adopted from established classification systems. Main outcome measure Classification of (1) cause of intervention, (2) intervention, (3) outcome of intervention and (4) initiator of intervention. Results Altogether 2,312 interventions were documented. Besides 520 cases of information about drugs (rational selection, occurrence of infrequent adverse events or interactions), the main interventions were recommendations for the addition, the withdrawal or the replacement of a drug (n = 907, 50.6%) and advices for the change of dosage, dosing intervals or dose adjustment according to impaired renal or liver function (n = 584, 32.6%). The vast majority of the suggested interventions (92.8%) have been accepted. Conclusion The participation of a clinical pharmacist during ward rounds contributes to the optimisation of pharmacotherapy, in terms of choosing the most appropriate drug and/or the suitable dosage and may improve patient care.     

Pharmacokinetics of mezlocillin and sulbactam under continuous veno-venous hemodialysis (CVVHD) in intensive care patients with acute renal failure

Objective: In intensive care medicine, continuous detoxication methods, such as continuous veno-venous hemodialysis (CVVHD), are used for treating acute renal failure. However, in contrast to conventional hemodialysis, little is known about the pharmacokinetics of many drugs administered in this setting and guidelines for dosages of drugs often do not exist. This holds particularly true for broad-spectrum antibiotics, which are often required during intensive care. Methods: In this study, we investigated the pharmacokinetics of the acylureidopenicillin mezlocillin and the β-lactamase inhibitor sulbactam during CVVHD and deduced dosage recommendations from the kinetic parameters with the goal of maintaining trough levels of above 10 mg · l⁻¹ for mezlocillin and 5 mg · l⁻¹ for sulbactam. Six intensive care patients with acute renal failure, receiving mezlocillin (n=5) and/or sulbactam (n=4), were examined during CVVHD and during intervals between CVVHD. The serum concentrations and the amounts of the drugs excreted into the dialyzate and into the urine within one dosage interval were measured using high performance liquid chromatography (HPLC). Three of the patients were jaundiced, indicating functional impairment of the liver. Results: The clearances by CVVHD (CL_CVVHD) for mezlocillin ranged between 11.0 and 44.9 ml · min⁻¹ and the half lives ranged between 1.12 and 8.84 h. Low CL and long half lives were observed in the patients with jaundice. For sulbactam, CL_CVVHD ranged between 10.1 and 22.8 ml · min⁻¹ and serum half lives were 4.25–6.11 h, independent of liver function. Conclusion: Due to high hepatobiliary clearance of mezlocillin, dosage adjustments in patients with acute renal failure, treated by CVVHD, are needed only with concurrent impaired liver function. For sulbactam, the optimal dose was found to be 0.5 g, administered every 12 h, regardless of liver function. Received: 25 February 1997 / Accepted in revised form: 21 May 1997     

Phase II trial of pyrazoloacridine (NSC#366140) in patients with metastatic breast cancer

Purpose: Pyrazoloacridine (PZA) is an investigational nucleic acid binding agent that inhibits the activity of topoisomerases 1 and 2. We conducted a phase II clinical study to determine the efficacy and toxicities of PZA in patients with metastatic breast cancer (MBC). Experimental Design: In this phase II multicenter study, patients who were treated with no more than one prior chemotherapy for MBC were treated with 750 mg/m2 of PZA given as a 3-hour intravenous infusion every 3 weeks. Treatment cycles were continued until disease progression or unacceptable toxicities. The study was designed to distinguish between a response rate of <15% vs >30% (alpha = 0.10, beta = 0.10) using Simons optimal 2-stage design. At least 2 responses were required in the first 12 patients in the 1st stage and 6 of 35 in the 2nd stage to recommend the agent for further study. Results: Two patients in the first stage had a response allowing accrual to second stage. A total of 15 patients (out of 35 planned) were treated on the study prior to premature closure. Three patients had a partial response (20%) lasting 4.5–6 months. Two patients had stable disease for 3 and 5 months. The dose limiting toxicity was granulocytopenia with ten patients requiring dose reduction or dose delay for grade 4 neutropenia. Other grade 3 and 4 toxicities include vomiting (n = 2), nausea (n = 2), neurotoxicity (n = 1), fatigue (n = 1), anemia (n = 1), dyspnea 9n = 1) and renal (n = 1). Conclusions: Pyrazoloacridine demonstrated modest activity in patients with metastatic breast cancer.     

Overdose and adverse drug event experiences among adult patients in the emergency department

IntroductionOverdose is a leading cause of injury and death in the United States. Emergency Department (ED) patients have an elevated prevalence of substance use. This study describes overdose/adverse drug event experiences among adult ED patients to inform strategies to address overdose risk.MethodsPatients seeking care at a large ED in the city of Flint, Michigan participated in a computerized self-assessment during 2011–2013 (n = 4571). Overdose was assessed with a broad definition and included occurrences that could be considered adverse drug events. Among those with this type of experience, additional items assessed symptoms, outcomes, and intent.Results12% reported an overdose history. Of participants' most serious overdoses, 74% were without clear intent for self-harm, although this was true of only 61% of overdoses involving opiates or sedatives, and 52% had symptoms present that indicated that it was life-threatening. Binge drinking on a monthly basis (ORs = 1.4) was associated with a medically serious overdose compared to never having an overdose. Compared to no drug use in the last year, use of one drug was associated with an OR of 1.8, two drugs was associated with an OR of 5.8, three drugs was associated with an OR of 8.4, and four or more drugs was associated with an OR of 25.1 of having had a medically serious overdose (all p < 0.05).ConclusionsMost overdose experiences among ED patients were without clear intent of self-harm. The ED may be an appropriate setting for efforts to reduce overdose risk, especially among polysubstance users.     

Which drugs cause overdose among opiate misusers? Study of personal and witnessed overdoses

Concern has been expressed at the widespread prescribing of methadone in view of its inherent toxicity. Commentators have opined that methadone is more toxic than heroin and causes more overdose deaths. However, data deficiencies and flawed analyses leave continuing uncertainty about this crucial policy issue. The relative contributions of heroin, other opiates (e.g. methadone) and non-opiate drugs to overdose and overdose deaths among drug misusers were examined in a community-recruited sample of 312 injecting drug misusers in London. Data were collected on last personal overdose (n=117), last witnessed overdose (n=167) and last witnessed fatal overdose (n=55), and on the different drugs that had been involved with these overdoses. Heroin was involved in 83% of last personal overdoses, 90% of last witnessed overdoses and 80% of last witnessed fatal overdoses, while other opiates were involved in only 18%, 8% and 26%, respectively. Methadone accounted for about half of these "other opiate" overdoses. Overdoses involving a combination of heroin and a non-opiate were common - 29%, 21% and 39%, respectively. Heroin was the drug most frequently involved in overdose across all three areas of study. However, combinations of heroin and a non-opiate were surprisingly frequent, especially in witnessed fatal overdoses (as reported recently by other investigators using different methodologies). Considering the wide extent of methadone prescribing to this group, methadone was remarkably infrequently reported as responsible (solely or in combination) for either personal overdoses, witnessed overdoses or witnessed fatal overdoses.     

Factors predicting hospital readmissions related to adverse drug reactions

Objective  To analyse the contribution of adverse drug reactions (ADR) to hospital readmissions. Methods  This was a case–control study in which unscheduled admissions of patients who had been admitted to the hospital during the two previous months were assessed during a 21-month period. The patient was considered a case when the main diagnosis of readmission complied with the World Health Organisation’s definition of an ADR. For each case, two controls were selected from those patients that had been admitted for ADR without readmission (n = 177). Information on drugs and other risk factors was obtained from cases by interview and from controls by clinical record review. Results  There were 26,559 unscheduled admissions of which 81 were readmissions associated with ADR (4.5% of the unscheduled readmissions). There were no statistically significant correlations with sex, age or medical history, with the exception of arterial hypertension. The main drug products causing readmission were acenocoumarol (15, 18.5%), antihypertensive-diuretics (14, 17.3%), anticancer drugs (11, 13.6%) and digoxin (seven, 8.6%). In the multivariate logistic analysis, the variables predicting readmission were acenocoumarol [odds ratio (OR) 12.2, 95% confidence interval (CI) 3.8–38.3, P < 0.0001], a record of diabetes mellitus (OR 2.6, 95% CI 1.3–5.5, P < 0.01), the number of drugs taken at the moment of ADR (OR 1.2, 95% CI 1.1–1.4, P < 0.001) and high blood pressure (OR 0.3, 95% CI 0.2–0.6, P < 0.001) even though the latter was a negative predictor, preventing readmission. Of the 81 readmissions associated with ADR, 28 (34.6%) were preventable. Conclusion  A medical record of diabetes mellitus, polypharmacy and acenocoumarol treatment were risk factors predicting hospital readmission related to ADR.