Point-of-care Hepatitis C virus testing and linkage to treatment in an Australian inner-city emergency department.

BACKGROUND: In Australia, Hepatitis C Virus (HCV) treatment is declining, despite broad access to direct-acting antiviral medication. People who inject drugs are proportionally over-represented in emergency department presentations. Emergency department assessment of people who have injected drugs for HCV presents an opportunity to engage this marginalised population with treatment. We describe the outcomes of risk-based screening and point-of-care anti-HCV testing for emergency department patients, and linkage to outpatient antiviral treatment. METHODS: During the three-month study period, consecutive adult patients who presented to the emergency department during the study times were screened for risk factors and offered the OraQuick oral HCV antibody test. Those with reactive results were offered venepuncture in the emergency department for confirmatory testing and direct-acting antiviral treatment in clinic. The main outcome measures were the number and proportion of viremic participants that were linked to the hepatitis clinic, commenced treatment and achieved a sustained viral response. Secondary outcome measures were the proportion (%) of presentations screened that were oral antibody reactive, and the prevalence and type of HCV risk factors. RESULTS: During the study period, 2408 of the 3931 (61%) presentations to the emergency department were eligible for screening. Of these 2408 patients, 1122 (47%) participated, 307 (13%) declined participation and 977 (41%) could not be approached during their time in the emergency department. Among the 1122 participants, 378 (34%) reported at least one risk factor. Subsequently, 368 (97%) of the 378 participants underwent OraQuick anti-HCV test, and 50 (14%) had a reactive result. A risk factor of ever having injected drugs was present in 44 (88%) of participants who were sero-positive. Of the 45 that had blood tested, 30 (67%) were HCV ribonucleic acid (RNA) positive. Three participants died. Of the 27 remaining participants, 10 (37%) commenced treatment and 7 of these 10 (70%) obtained a cure. There was a high rate of homelessness (24%) among anti-HCV positive participants. CONCLUSION: Among emergency department participants with a risk factor for HCV, positive serology was common using a rapid point-of-care test. A history of injecting drug use was identified as the risk factor with highest yield for positive HCV serology, and is suitable as a single screening question. However, linkage to care post ED presentation was low in this marginalised population. There is a need for new pathways to improve the care cascade for marginalised individuals living with HCV infection.

Prevalence and predictors of fatigue in haemo-oncological patients.

BACKGROUND: Fatigue is a common symptom in patients with advanced malignancy, and has been associated with both physiological and psychological factors in patients with solid tumours. AIM: This study sought to explore the predictors of fatigue in a population with haematological malignancy. METHODS: Consecutive outpatients and inpatients attending a haematology centre completed the Memorial Symptom Assessment Scale, and clinical, treatment and demographic information were noted. RESULTS: Of 180 patients, fatigue was present in 69%, and causing considerable distress in 26%. Univariate analysis revealed fatigue was associated with poor performance status, low haemoglobin, feeling sad, worried, irritable and nervous. Multivariate modeling revealed that those factors predictive of fatigue were poor performance status, having active disease, feeling sad and irritable, while haemoglobin level was not predictive of fatigue. CONCLUSIONS: Fatigue is a multidimensional symptom in patients with haematological malignancy whose presence must prompt a holistic assessment of potential contributors that goes beyond correction of haemoglobin levels.

Hospitalisation of high-care residents of aged care facilities: are goals of care discussed?

BACKGROUND: Residents of residential aged care facilities (RACF) are commonly hospitalised towards the end of life. Determining the hospitalisation experiences, including the discussion of goals of treatment, is essential to best plan care including planning for end-of-life care for this population. AIM: To document hospital presentation characteristics, course, outcomes and care planning for high-care residents of RACF. METHODS: A retrospective review of medical records was conducted for all high-care residents aged >64 years presenting to a metropolitan hospital over a 6-month period. RESULTS: One hundred and eighty-six high-care residents of RACF presented to hospital 228 times. Transfer paperwork documented resuscitation status for 49 (21%) presentations, and a medical enduring power of attorney or advanced care plan for 85 (37%). Patients had high rates of comorbidities (average Charlson comorbidity index score = 3), polypharmacy (93%), impaired mobility (89%), impaired cognition (81%) and incontinence (76%). Resuscitation status was documented in 50 (55%) and family discussion in 38 (42%) of 91 admissions exceeding 48 h. Documented family discussion was significantly associated with complications or new events occurring during admission (odds ratio 1.56, 95% confidence interval 1.07-2.26). CONCLUSION: There were low rates of documentation of resuscitation status or family discussion for this highly vulnerable population. Neither hospitals nor community providers appear to take responsibility for future care planning. Acute hospitals could play a greater role in care planning because discussion around course of illness and goals of treatment may enhance patient management, satisfaction and reduce hospitalisations.

Intraocular penetration of topical lidocaine 4%.

PURPOSE: To evaluate the intraocular penetration of lidocaine 4% topically applied before phacoemulsification. SETTINGS: Institute of Ophthalmology, University of Verona, and Department of Medical Pharmacology, University of Padua, Italy. METHODS: Thirty eyes having phacoemulsification for senile cataract were anesthetized by topical application of lidocaine 4%. The drug was applied 3 times in 30 minutes in 15 eyes and 6 times in 60 minutes in 15 eyes. At the beginning of surgery, aqueous humor samples were obtained to measure the lidocaine levels. Blood samples were obtained in 6 patients 30 and 60 minutes after aqueous humor collection. The aqueous humor levels were compared with the amount of pain perceived by patients during surgery. RESULTS: Mean aqueous humor lidocaine concentration was 8.68 micrograms/mL +/- 2.43 (SD) after 3 instillations and 23.21 +/- 8.87 micrograms/mL after 6 instillations. Blood levels of lidocaine were negligible. Patients whose intraocular level was below 12 micrograms/mL perceived more pain during surgery. Only 2 eyes had these low levels after 6 instillations. CONCLUSIONS: Topically applied lidocaine 4% effectively penetrates the eye, providing analgesia for phacoemulsification. We suggest at least 6 instillations in the hour preceding surgery. In this study, pain during surgery was primarily related to poor intraocular levels of the anesthetic agent.

Tolerance to the repolarization effects of rac-sotalol during long-term treatment.

AIMS: To establish whether tolerance to the QT effect could ensue during maintenance treatment with rac-sotalol. METHODS: The effect of rac-sotalol on QT interval duration was studied in 10 patients after single oral administration (160 mg) and after 6-day multiple oral dosing (80 mg two or three times daily). In order to separate the pure Class III effect from the bradycardia-related QT prolongation, heart rate/QT relationship was preliminarly assessed in each patient after the administration of a pure beta-adrenoceptor blocker (propranolol, 80 mg orally). Repolarization changes were quantified as percent difference between the measured QT and the expected QT on the basis of the individual heart rate/QT relationship. RESULTS: In all patients QT interval prolongation was linearly correlated with rac-sotalol log plasma concentration. The maximal QT prolongation and peak plasma concentration were not significantly different following acute and chronic administrations (QT effect: +18.1+/-6.3% vs +14.2+/-3.3%; peak concentration: 1.64+/-0.49 mg l(-1) vs 1.83+/-0.66 mg l(-1)). Line slopes were also unchanged following chronic treatment (21.8+/-8.9 vs 21.1+/-9.2). In four cases a significant rightward shift of the line occurred during repeated administrations, consistent with the appearance of pharmacodynamic tolerance. The inconstancy of this change in responsiveness may either be ascribed to a genetically determined individual susceptibility or to a variable interplay between Class III effect, gradual QT prolongation due to long-term beta-adrenoceptor blockade and tolerance development. CONCLUSIONS: During maintenance treatment with rac-solatol, partial loss of repolarization effects occurred in some patients suggesting pharmacological tolerance.

Effect of moderate or severe liver dysfunction on the pharmacokinetics of gamma-hydroxybutyric acid.

OBJECTIVES: To assess the effect of moderate or severe liver dysfunction on the pharmacokinetics of gamma-hydroxybutyric acid (GHB). METHODS: The absorption and disposition kinetics of GHB were studied in eight cirrhotic patients without ascites (Child's class A) and eight cirrhotic patients with ascites (Child's class C), after administration of a single oral dose of 25 mg.kg-1. The liver metabolic function of each patient was evaluated by measuring antipyrine clearance and the formation rate of the lidocaine metabolite monoethylglycinexylidide (MEGX). RESULTS: Compared to those previously determined in eight healthy control subjects given the same GHB dose, mean AUC values were double or greater in the cirrhotic patients. Accordingly, apparent oral clearance was markedly reduced (from 9.1 to 4.5 and 4.1 ml.min-1.kg-1 in nonascitic and ascitic patients, respectively). Terminal half-life (t1/2), was significantly longer in nonascitic patients than in control subjects (32 vs 22 min). A further significant prolongation of t1/2, most likely due to an increased distribution volume, was observed in patients with ascites (56 min). Nonetheless, GHB plasma concentrations fell to either undetectable or negligible levels by the end of the usual dosing intervals (6-8 h). More limited changes were noted in the absorption parameters. The peak level (Cmax) increased only in nonascitic patients, but not proportionally to the increase in AUC. The time to Cmax increased from 30 to 45 min in both cirrhotic groups. These findings are consistent with a slowed rate of GHB absorption in cirrhotic patients. Adverse effects were similar, for intensity and duration, to those recorded in healthy volunteers, i.e., mild and transient. CONCLUSIONS: Although liver cirrhosis causes significant modifications of GHB disposition kinetics, the increase in t1/2 is not such as to cause drug accumulation on repetitive dosing. However, in consideration of the higher mean plasma levels observed in cirrhotic patients, it appears wise to keep the initial GHB daily dose at the lower end of the therapeutic range and to carefully monitor the patients if upward dose adjustments are required.

Verapamil and norverapamil plasma levels in infants and children during chronic oral treatment.

Verapamil and norverapamil trough plasma levels were measured in 22 children, aged from 15 days to 17 years, under chronic oral treatment with the drug (mean daily dose +/- SD: 4.9 +/- 1.4 mg/kg) for supraventricular tachyarrhythmias (n = 20) or hypertrophic cardiomyopathy (n = 2). Overall, 67 determinations were available (1 to 11 per patient) and the mean concentration values (+/- SD) were 43.3 +/- 36.4 ng/ml for verapamil and 41.7 +/- 28.9 ng/ml for norverapamil. Verapamil and norverapamil trough concentrations were correlated with the daily dose (p < 0.05) but a wide intersubject variability was present at any given dose and the regression line did not pass through the origin of axes (x-axis intercept: 1.2 mg/kg for verapamil, 0.9 mg/kg for norverapamil). To study the influence of age on drug kinetics, verapamil plasma concentrations corrected by daily dose/kg ([V]/D) and norverapamil to verapamil concentration ratios (N/V) (taken as an index of metabolic clearance) were divided according to age quartiles. The median [V]/D was higher in the first and in the fourth age quartile than in the other two age groups. On the contrary, median N/V ratio increased with age, suggesting that drug metabolism was improving during the first year of life. Four children developed typical adverse reactions to the drug (bradycardia, AV block, hypotension). In one case verapamil plasma levels were definitely high (294 ng/ml). In the other three cases, concomitant factors (such as very young age and heart disease) seem to have contributed to drug toxicity.

Influence of age and gender on the in vitro serum protein binding of flecainide.

The in vitro protein binding of flecainide was studied by equilibrium dialysis in relation to serum concentrations of albumin and alpha 1-acid glycoprotein (AAG) in 22 healthy subjects of both sexes aged between 23 and 89 years. In the range of flecainide concentrations tested, protein binding of flecainide was not saturable and the percent value of the unbound fraction ranged between 0.48 and 0.68, mean value (SD) = 0.59 (+/- 0.06), without any significant difference between males and females or between young and old subjects. The flecainide unbound fraction was significantly correlated with serum albumin concentrations but not with total serum proteins or AAG concentrations.

Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers.

Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg-1. The AUC increased disproportionately with the dose and so the apparent oral clearance decreased significantly as the dose was increased, whereas the terminal half-life and mean residence time increased. The peak plasma concentrations normalised to the lowest dose fell significantly with increasing doses, whilst the corresponding peak times increased. These findings suggest that both the oral absorption and the elimination of GHB are capacity-limited processes. GHB did not bind to significant extent to plasma proteins over the therapeutic concentration range. The pharmacokinetic parameters in healthy volunteers were not significantly different from those previously observed in alcohol-dependent patients with compensated alcoholic liver disease.

Determination of lorajmine and its metabolite ajmaline in plasma and urine by a new high-performance liquid chromatographic method.

Lorajmine is a monochloroacetyl derivative of ajmaline with electrophysiological properties somewhat different from those of the compound of origin. Since lorajmine is rapidly hydrolyzed to ajmaline by plasma and tissue esterases, it is crucial to measure plasma levels of both drugs separately. A major problem in assaying lorajmine is its chemical instability in plasma both after blood sampling and during the extraction procedure. Furthermore, lorajmine (unlike ajmaline) is not fluorescent and has a very low UV absorbance, so the standard detectors for high-performance liquid chromatography cannot be used. We describe a new method that solves the problems of instability and sensitivity. Plasma esterases are first blocked pharmacologically (neostigmine); ajmaline is then measured by direct on-column injection of samples. Last, lorajmine is completely converted to ajmaline, extracted, and measured with a fluorescence detector. The molar concentration of ajmaline obtained in the last step, minus that found by direct injection, gives the concentration of lorajmine. Some examples of pharmacokinetic applications are also given.