Evaluation of antiretroviral-related errors and interventions by the clinical pharmacist in hospitalized HIV-infected patients.

OBJECTIVES: The aim of the study was to identify antiretroviral-related errors in the prescribing of medication to HIV-infected inpatients and to ascertain the degree of acceptance of the pharmacist's interventions. METHODS: An observational, prospective, 1-year study was conducted in a 750-bed tertiary-care teaching hospital by a pharmacist trained in HIV pharmacotherapy. Interactions with antiretrovirals were checked for contraindicated combinations. Inpatient antiretroviral prescriptions were compared with outpatient dispensing records for reconciliation. Renal and hepatic function was monitored to determine the need for dose adjustments. RESULTS: The prescriptions for 247 admissions (189 patients) were reviewed. Sixty antiretroviral-related problems were identified in 41 patients (21.7%). The most common problem was contraindicated combinations (n=20; 33.3%), followed by incorrect dose (n=10; 16.7%), dose omission (n=9; 15%), lack of dosage reduction in patients with renal or hepatic impairment (n=6; 10% and n=1; 1.7%, respectively), omission of an antiretroviral (n=6; 10%), addition of an alternative antiretroviral (n=5; 8.3%) and incorrect schedule according to outpatient treatment (n=3; 5%). Fifteen out of 20 errors were made during admission. A multivariate analysis showed that factors associated with an increased risk of antiretroviral-related problems included renal impairment [odds ratio (OR) 3.95; 95% confidence interval (CI) 1.39-11.23], treatment with atazanavir (OR 3.53; 95% CI 1.61-7.76) and admission to a unit other than an infectious diseases unit (OR 2.50; 95% CI 1.28-4.88). Use of a nonnucleoside reverse transcriptase inhibitor was a protective factor (OR 0.33; 95% CI 0.13-0.81). Ninety-two per cent of the pharmacist's interventions were accepted. CONCLUSION: Antiretroviral-related errors affected more than one-in-five patients. The most common causes of error were contraindicated or not recommended drug-drug combinations and dose-related errors. A clinical pharmacist trained in HIV pharmacotherapy could help to detect errors and reduce the duration of their effect.

Measurement of ductions and fields of binocular single vision (BSV): orthoptic practice in the UK and Ireland.

To evaluate the current clinical practice of quantifying ductions and fields of BSV in the UK and Ireland using an online questionnaire. An anonymous online questionnaire with twenty-one questions was distributed in February 2019 via the British and Irish Orthoptic Society (BIOS) members' newsletter. Objectives were to investigate: methods used, frequency of assessment, limiting factors and opinions of importance. Informed consent was gained to include the responses in the study. The data was analyzed using descriptive statistics and Wilcoxon Signed Ranks Testing. The questionnaire was completed by 105 orthoptists. The methods reported to quantify ductions and fields of BSV respectively were: Goldmann (33% and 34%), Aimark (22 and 23%), Lister (7%), Octopus (5 and 4%), Thomson ocular motility analyzer (2 and 3%), Binocular vision analyzer (2%) and no method reported (30% and 32%). The frequency of measuring ductions and fields of BSV per week (median 1-2) was significantly less than the number of patients seen with limited ocular motility per week (median 6-9). The main reasons for never or rarely measuring ductions or fields of BSV were not enough time, no method available and only on selected patients. Respondents indicated that they would measure ductions and fields of BSV more frequently if a quicker portable method was available (median 3-5 times per week). Most agreed that measurements of ductions and fields of BSV are important (89 and 95% respectively). There is no standardized method of quantitively measuring ductions or fields of BSV, with almost a third of respondents not measuring either. Although most orthoptists agreed these measurements are important, they are infrequently performed. The main factors limiting these assessments are insufficient time and lack of a testing method. If a faster portable device was available, orthoptists would measure ductions and fields of BSV more frequently.

[Analysis of the duration of and reasons for changing the first combination of antiretroviral therapy]. / Análisis de la duración y los motivos de cambio de la primera combinación de tratamiento antirretroviral.

OBJECTIVE: To determine the duration of and reasons behind changing the various combinations of drugs used for the initiation of antiretroviral treatment in naïve patients. METHODS: A retrospective observational study that included all patients with HIV infection who started antiretroviral therapy in a high-tech university reference hospital during the period from 1 January 2003 and 31 December 2005. Patients were followed until 31 December 2008. To estimate the cumulative probability of discontinuation the Kaplan-Meier method was used. RESULTS: A total of 441 patients were included. The average duration of the first treatment was 384 (interquartile interval 84-1290) days. The regimen based on non-nucleoside reverse transcriptase inhibitors and those that included as nucleosides abacavir or tenofovir in combination with lamivudine or emtricitabine showed a significantly longer duration than the rest. The main reasons for termination were the side effects, although in a lesser percentage than that obtained in previous studies. No associations were found between the rest of the characteristics of the patients or of the treatment and the risk of termination. DISCUSSION: Although the duration of the first antiretroviral treatment remains short, currently fewer changes are made due to side effects and due to loss to follow-up. The reasons may be better tolerance and less complexity. However, more studies are needed to determine the benefits of one regimen or another, and to be able to generalise the results.

[Fusarium keratitis]. / Fusarium-Keratitis.

The case of a previously healthy 48-year-old patient (not a contact lens wearer) with a Fusarium keratitis is reported. He had developed a deep corneal ulcer with total stromal infiltration (Fusarium ssp.). An intensive topical and systemic antiinfectious medication was initiated, along with some procedures (keratoplasty, rinsing of the anterior chamber). However, the infection progressed (endophthalmitis), and an enucleation was necessary. Despite modern drug therapy and surgical intervention, fungal keratitis can cause an enucleation.

Perioperative antibiotic prophylaxis in Spanish hospitals: results of a questionnaire survey. Hospital Pharmacy Antimicrobial Prophylaxis Study Group.

A questionnaire survey was sent to a random sample of the Spanish network of National Health System public acute-care hospitals. Of responding institutions (representing 25% of Spanish hospital beds), nearly 75% had active surveillance programs for the prevention and control of surgical-site infections (SSIs), but only 20% performed postdischarge surveillance. Overall, perioperative antibiotic prophylaxis (PAP) was used in 84% of all surgical procedures. For 77% of procedures, there were written guidelines for the choice and use of PAP. Cefazolin was the most commonly used antibiotic (38%). Duration of PAP was shorter than 24 hours in 75% of procedures, and only a single dose was given in 52% of procedures. PAP was commonly used in breast (52%) and inguinal hernia repair (69%) procedures, as well as in laparoscopic abdominal surgery (86%). In summary, the use of PAP in Spanish hospitals is adequate, but improvements can be made in the frequency of prolonged PAP and in the use of broad-spectrum antibiotics. Surveillance systems for SSI, including postdischarge follow-up, also should be improved.

A cluster of fever and hypotension on a surgical intensive care unit related to the contamination of plasma expanders by cell wall products of Bacillus stearothermophilus.

OBJECTIVE: To evaluate an outbreak of fever and hypotension after cardiac surgical procedures and the role of polygeline, a plasma expander. DESIGN: Unmatched case-control study. SETTING: A six-bed cardiac surgery intensive care unit (SICU) of the Hospital Clinic of Barcelona (Spain), a 940-bed public teaching hospital. PATIENTS: Eight cases and 25 control patients admitted to the SICU over a 4-week epidemic period. MAIN OUTCOME MEASURES: Development of hypotension (systolic blood pressure < or = 90 mm Hg or a drop of 40 mm Hg from baseline systolic blood pressure) and fever (axillary temperature > 38.5 degrees C) within 24 hours of a cardiac surgical procedure. RESULTS: The single risk factor significantly different between cases and controls was the total volume of polygeline used throughout the surgical procedure for extracorporeal circulation: a median of 1,250 mL (mean, 1,312.5 +/- 842.5 mL) in cases versus 500 mL (mean, 566.0 +/- 159.9 mL) in controls (P = .0029). By multiple logistic regression analysis, polygeline use was the single risk factor significantly related to the outcome (odds ratio, 8.75; CI95, 1.36 to 56.2; P = .01). Neither blood cultures from patients nor cultures of the polygeline used yielded growth of any microorganism. Stopping use of the implicated polygeline lot controlled the outbreak. CONCLUSIONS: Use of polygeline was associated with an outbreak of fever and hypotension in a SICU. Information from the manufacturer indicated the likelihood of contamination of the product with Bacillus stearothermophilus components. The manufacturer has since changed the production and control processes, and no further adverse events have been seen.

Voltage- and gamma-aminobutyric acid-activated membrane currents in the human medulloblastoma cell line MHH-MED-3.

The whole-cell patch clamp technique was used to characterize voltage- and neurotransmitter-activated currents in the medulloblastoma cell line MHH-MED-3 and cells from tissue slices and primary cultures of two medulloblastoma biopsies. These preparations revealed similar electrophysiological properties. All tested cells displayed 4-aminopyridine-sensitive delayed rectifying K(+) currents, gamma-aminobutyric acid(A) receptor-mediated Cl(-) currents and most of them inward rectifier K(+) currents. Transient inward currents were mainly carried by low-voltage activated T-type Ca(2+) channels in MHH-MED-3 cells, and tetrodotoxin-sensitive Na(+) channels in cells from the primary culture. From these characteristics we conclude that medulloblastoma cells share physiological features with developing cerebellar granule cells at an immature stage.

Alkaloids from Crinum macowanii.

Eleven alkaloids have been isolated from fresh bulbs of Crinum macowanii (Amaryllidaceae). Macowine is reported here for the first time. The structure and stereochemistry of this new alkaloid as well as of the known ones were determined by physical and spectroscopic methods.

Bioactive alkaloids from Brunsvigia radulosa.

A phytochemical investigation of the bulbs of Brunsvigia radulosa yielded the new alkaloid 1-O-acetylnorpluviine, together with the known structures 1-epideacetylbowdensine, crinamine, crinine, hamayne, lycorine, anhydrolycorin-6-one and sternbergine. All structures were established by spectroscopic evidence. Some of the 13C assignments which were reported for crinamine and hamayne were corrected by means of 2D NMR techniques. In order to provide a further structure for biological testing, crinamine was converted to apohaemanthamine. The alkaloids were tested for activity against two strains of cultured Plasmodium falciparum and for cytotoxicity with BL6 mouse melanoma cells.

Evaluation of scavenging activity assessed by Co(II)/EDTA-induced luminol chemiluminescence and DPPH* (2,2-diphenyl-1-picrylhydrazyl) free radical assay.

The scavenging activities of three standard antioxidants, quercetin, ascorbic acid, and trolox, were evaluated by Co(II)/ethylenediamine-tetraacetic acid (EDTA)-induced luminol chemiluminescence and the 2,2-diphenyl-1-picrylhydrazyl (DPPH*) free radical assay. Therefore, the aim of this study was to characterise an enzyme-free and time-independent chemiluminescence method for the assessment of the scavenging profile of compounds in a cell-free system using the Co(II)/EDTA-luminol-peroxide system. These results showed that the three standards were efficient and effective in inhibiting both Co(II)/EDTA-induced luminol chemiluminescence and the free radical DPPH*. For all the data obtained in this work, the scavenging activity for the standards tested decreased in the following order: quercetin > trolox > ascorbic acid. The present study has applied a simple and precise procedure for the study of hydroxyl radical scavenging activity by Co(II)/EDTA-induced luminol chemiluminescence, and this was assessed by DPPH* free radical scavenging.

Thermal consequences of photorefractive keratectomy.

PURPOSE: Photorefractive keratectomy (PRK) is still a widely used method for the correction of refractive error despite the advent of laser in situ keratomileusis (LASIK). However, both procedures are associated with significant side effects such as corneal haze and regression. Several factors have been implicated in the etiology of haze, one of which is thermal loading of the cornea. The purpose of this study was to investigate the temperature changes occurring during PRK when performed at different ablation depths. METHODS: Noncontact, color-coded ocular thermography was performed with an infrared detector apparatus during PRK ablation on 19 ovine corneas. Five different refractive corrections were carried out ranging from -2.00 diopters (D) (ablation depth, 31.2 microm) to -10.00 D (ablation depth, 137.9 microm). RESULTS: A temperature rise at the corneal surface was demonstrated in all 19 corneas. The mean rise in temperature was 7.35 +/- 1.13 degrees C with a maximum rise in temperature of 8.97 degrees C. A positive correlation was found between the refractive correction and the peak rise in temperature (r2 = 0.57, p< 0.0001). The rate of temperature change was greater for smaller treatments than for larger treatments (r2 = 0.79, p < 0.0001). Corneas undergoing larger treatments were subject to greater rises in temperature for longer periods of time. CONCLUSIONS: This study suggests that the cornea undergoes a significant rise in temperature as a result of the PRK process. Further investigation is required to determine what effect this thermal loading has on the corneal wound healing response after PRK.

Cryptofolione derivatives from Cryptocarya alba fruits.

Cryptofolione (1) and the new cryptofolione derivative 6-(4,6-dimethoxy-8-phenyl-octa-1,7-dienyl)-4-hydroxy-tetrahydro-pyran-2-one (2) were isolated from the fruits of Cryptocarya alba. The structures were elucidated by spectroscopic methods. Cryptofolione showed activity towards Trypanosoma cruzi trypomastigotes, reducing their number by 77% at 250 microg mL(-1). Cryptofolione showed moderate cytotoxicity in both macrophages and T. cruzi amastigotes. It also displayed a mild inhibitory effect on the promastigote form of Leishmania spp. As both cytotoxic and trypanocidal effects are similar, the compound presented little selectivity in our assay models.

Alkaloids from Cyrtanthus elatus.

The alcoholic extract of the fresh bulbs of Cyrtanthus elatus yielded zephyranthine (1) and 1,2-O-diacetylzephyranthine (2), together with three other known alkaloids. Complete assignment of 1H and 13C NMR spectra of compounds 1 and 2 was done by employment of two-dimensional NMR techniques.

[Adverse effects associated with antimalarial chemoprophylaxis]. / Reacciones adversas asociadas a la quimioprofilaxis antipalúdica.

BACKGROUND: To evaluate the frequency and type of adverse drug reactions associated to the antimalarial chemoprophylaxis advised to travellers visiting endemic areas. SUBJECTS AND METHODS: We included the travellers who from july 1992 to june 1994 came to the Travellers Advise Department and made short-term travels to areas with malarial infection risk. The adverse drug reactions were reported by the travellers through a questionnaire handed at the consulting room. The pharmacological regimens advised were: a) chloroquine base 5 mg/kg/week. b) chloroquine base 5 mg/kg/week + proguanil 100 mg/day if weight less than 55 kg and 200 mg/day if weight more than 55 kg. c) mefloquine 250 mg/week. RESULTS: We evaluated 1,054 questionnaires for the study. The 18.4% of the travellers reported adverse drug reactions. The 12.4% of the travellers who were on chloroquine, the 17.2% of those who were on chloroquine + proguanil and the 20.3% from mefloquine group presented adverse drug reactions (differences without significance). Comparing the regimens studied, we observed that neuropsychiatric reactions were more frequent in the mefloquine group (p < 0.01), the gastrointestinal reactions were less common in the chloroquine group (p = 0.04) and the transitory eye disorders were more frequent in the chloroquine + proguanil group (p = 0.01). In the mefloquine group the travellers with adverse drug reactions had a significantly lower weight than those who did not present them (p < 0.01). CONCLUSIONS: The adverse drug reactions reported agree with the toxicologic profile described in the literature about these drugs. Mefloquine presents an outstanding neuropsychiatric toxicity and is worse tolerated in low weight patients.

[Comparative study of an expert system application in the prescription of medications]. / Estudio comparativo de la aplicación de un sistema experto en la prescripción de medicamentos.

BACKGROUND: The aim of this study was to evaluate the impact of a expert drug system implementation on the drug prescription habits and on drug cost in an university hospital. MATERIAL AND METHODS: During a 3 months period, the drug prescriptions to patients admitted to the Internal medicine, lung, gastroenterology and hepatology units, have been evaluated through the expert drug system (Medisource). This expert drug system functions in according to patients characteristics such as age, weight, height, sex, renal function and liver function. It recommends the correct dose, detects interactions and adverse effects and makes suggestions in pregnancy and lactation. It also offers alternative drugs with their cost. During the study period physicians were unaware of the investigation being performed. RESULTS: 836 patients (63.9 +/- 16.5 years) with an average hospital stay length of 11.6 +/- 6.7 days were studied. The most common diagnoses were: lung obstructive chronic disease, cirrhosis, gastrointestinal hemorrhage and cancer. The total amount of drug prescribed was 6,308. The expert system detected 458 overdosages and 33 underdosages, mainly in antibiotics and antiulcer drugs, and 1,722 interactions. The drug costs reduction that could be obtained following the expert system recommendations was 4.5% in antibiotic drugs and 23% in antiulcer drugs. CONCLUSION: The frequency of drug overdosage and underdosage in patients admitted in an university hospital is relatively high. The expert systems available for drug decisions could solve this problem.

[Vancomycin and teicoplanin use as antibiotic prophylaxis in cardiac surgery: pharmacoeconomic study]. / Vancomicina y teicoplanina como profilaxis antibiótica en cirugía cardíaca: estudio farmacoeconómico.

BACKGROUND: To assess the economical impact of vancomycin use versus teicoplanin use as antibiotic prophylaxis for patients undergoing cardiac surgery for valve replacement (VR) and coronary artery by-pass (CABS) procedures. PATIENTS AND METHODS: This is an ancillary cost minimization analysis of a double blinded, parallel groups, randomised clinical trial (RCT), with the main objective of comparing the safety and efficacy of these antibiotics. 500 patients were included in the study; 267 in the CABS group and 233 in the VR group. The CABS patients received 1 g vancomicin or 400 mg teicoplanin, plus 150 mg netilmicin. The VR group received a second dose of each drug after extracorporeal circulation. In order to calculate the costs we considered the direct cost of the drug, the i.v. mix and the administration costs, together with personnel and structure costs. We considered two different situations: the administration of drugs within the surgical room theatre and in the medical ward. RESULTS: The demographic data of both groups were comparable. The frequency of severe adverse drug reactions (ADR) were similar (0.4%) in both groups, as well as the post-operative infection rates (8.6%). Differences were seen in the frequencies of low severity ADRs: 20.4% in the vancomycin group and 1.6% in the teicoplanin group. When the antibiotics were administered in the surgical room, among CABS patients the costs were 8,265 pts. for the teicoplanin group and 12,005 pts. for the vancomycin group; while among VR patients, costs were respectively 11,661 pts. and 14,528 pts. Administration costs of teicoplanin and vancomycin within a medical ward setting, however, the costs were 6,740 pts. and 2,809 pts. for CABS patients, and 5,308 pts. and 10,140 pts. for VR patients, respectively. CONCLUSIONS: The costs of antibiotic prophylaxis among cardiac surgery patients heavily depends on the setting and circumstances of drug administration. The minimization cost analysis indicates that teicoplanin is the most cost-effective option if the drug is administered within the surgical area, while vancomycin is the less costly option when administered within the medical ward. However, if the second option is to be chosen, it is necessary to assure the right plasmatic drug levels of the antibiotic at the beginning of the surgical procedure.