| 1. |
- Ariano, RE, et al.
(author)
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Pharmacokinetics and pharmacodynamics of meropenern in febrile neutropenic patients with bacteremia
- 2005
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In: Annals of Pharmacotherapy. - 1060-0280. ; 39:1, s. 32-38
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Journal article (peer-reviewed)abstract
- Background: Pharmacodynamic investigations with antimicrobials define the relationship between the infecting organism and achievable drug concentrations with clinical outcome. Objective: To examine this relationship for meropenem in a population of patients who are at high risk of infection-related morbidity and mortality. Methods: The study was a retrospective analysis of a multicenter, randomized, blinded clinical trial. A population-based predictive model was created using data from adults with febrile neutropenia and the nonparametric modeling program, NPEM. Patient age, body weight, and serum creatinine level were covariates in the model used to predict unbound concentrations for each patient. Pathogen susceptibility was estimated using product literature minimum inhibitory concentrations for effectiveness against 50% of microorganisms (MIC50) for specific organisms. The pharmacodynamic index of percent time above MIC (% T>MIC) was analyzed for its association with clinical outcome. Results: A 2-compartment pharmacokinetic model using patient covariates of body weight and renal function best described the pharmacokinetics of meropenem in febrile neutropenic patients. Sixty patients with confirmed gram-positive or -negative bacteremia were studied. An average of 83% T>MIC was identified for the 42 clinical responders compared with 59% T>MIC for the 18 nonresponders (p=0.04). An 80% clinical response rate was evident when the % T>MIC for meropenem exceeded 75% of the dosing interval (p=0.01). Conclusions: To our knowledge, this is the first published report of a relationship between a pharmacodynamic index and clinical outcome in a febrile neutropenic population. Based on this relationship, dosing with intravenous meropenem 500 mg every 6 hours is predicted to be comparable to the currently recommended 1 g every 8 hours for serious infections. Our model provides further justification for a prospective clinical trial to evaluate a pharmacodynamically targeted meropenem dosing schedule as to its ability to improve clinical outcome in these patients.
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| 2. |
- De Fazio, Salvatore, et al.
(author)
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Role of CYP3AS in abnormal clearance of methadone
- 2008
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In: The Annals of Pharmacotherapy. - 1060-0280 .- 1542-6270. ; 42:6, s. 893-897
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To report a case of unusually low concentrations of methadone in a polydrug abuser during maintenance treatment with methadone. CASE SUMMARY: A 25-year-old man (weight 55 kg, height 165 cm) with a 12-year history of polydrug abuse was admitted to an opiates withdrawal methadone program. At the time of our observation, he was using both cannabinoids and heroin; no other medical conditions were discovered. Within the opiates withdrawal methadone program, under medical supervision, the patient started methadone therapy (20 mg/day). Two weeks later, an Abuscreen assay for methadone screening in the urine was negative and, to prevent the development of withdrawal symptoms, the dose of methadone was increased to 60 mg/day. One day later, the patient was asked to collect another urine sample in the presence of a nurse. The Abuscreen for methadone in urine remained negative. Evaluation of urinary samples collected over 24 hours documented low concentrations of methadone and high levels of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (the primary metabolite of methadone). Evaluation for the presence of the most common polymorphisms in the cytochrome P450 and P-glycoprotein genes showed that the patient was heterozygous for the CYP3A5*1 allele and for 2 single nucleotide polymorphisms in the P-glyooprotein gene (1236C/T and 3435C/T). DISCUSSION: In this patient, poor methadone adherence was ruled out because of the presence of physicians and nurses during both methadone maintenance treatment and Abuscreen screening. Moreover, because the patient reported only heroin and cannabis at the time of evaluation, drug interactions were ruled out as possible causes for the rapid clearance of methadone. CONCLUSIONS: In this case, CYP3A5 polymorphism may have played a role in the rapid methadone metabolism.
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| 3. |
- Hedenrud, Tove, et al.
(author)
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Beliefs about medicines and adherence among Swedish migraineurs
- 2008
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In: The Annals of Pharmacotherapy. - 1060-0280 .- 1542-6270. ; 42:1, s. 39-45
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Journal article (peer-reviewed)abstract
- BACKGROUND: The problem of low adherence to drug therapy is as prevalent in migraine as in any other disorder, with important consequences for the patient, such as impaired quality of life and absence from work. Beliefs about medicines have been identified as one of the most significant factors for adherence.OBJECTIVE: To analyze whether beliefs about medicines and medication-related factors are associated with adherence to prophylactic drug therapy among migraineurs at a Swedish tertiary care clinic.METHODS: A questionnaire was distributed to migraineurs visiting a tertiary care clinic in Sweden. All participants had recently been prescribed prophylactic medicine. The questionnaire was comprised of background questions, questions about disease characteristics, perceived effects, and adverse effects of migraine medications used, the Beliefs about Medicines questionnaire, and the Medication Adherence Report Scale. Medication-related variables, collected from patients' records with consent, were also included. Logistic regression analysis was performed to analyze the association between beliefs about medicines, medication-related variables, and adherence to prophylactic drugs.RESULTS: Of the 174 participants in the study, 64% were considered to be adherent to their prescribed prophylactic medicine. Users of beta-blockers were significantly more adherent compared with patients using other drugs (eg, tricyclic antidepressants [TCAs] or antiepileptics); the reverse was true for patients taking TCAs. Respondents with the lowest level of education (CONCLUSIONS: About one-third of the migraineurs did not adhere to their prophylactic drugs. Beliefs about medicines and medication-related factors could not predict nonadherence. We recommend further research on medication-related variables in relation to adherence among migraineurs.
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| 4. |
- Isacson, Dag, et al.
(author)
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Nationwide survey of subjectively reported adverse drug reactions in Sweden
- 2008
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In: The Annals of Pharmacotherapy. - 1060-0280 .- 1542-6270. ; 42:3, s. 347-353
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Journal article (peer-reviewed)abstract
- BACKGROUND: Adverse drug reactions (ADRs) and the safety of drugs continue to be widely discussed. However, information on the prevalence of subjectively experienced ADRs (SADRs) and their subsequent burden in the general population is largely lacking. OBJECTIVE: To analyze, from an epidemiologic perspective, SADRs with respect to occurrence and health status. METHODS: A cross-sectional mail survey to a random national sample in Sweden of inhabitants aged 18-84 years was conducted; 61% (N = 4875) of the sample answered the questionnaire. Self-reported SADRs occurring during a 2-week period of using prescription, over-the-counter (OTC), or herbal drugs were classified according to Meyler's classification of ADRs. Self-perceived health status was assessed with a visual analog scale graded from 0 (worst possible health/death) to 1 (perfect health). RESULTS: SADRs were reported by 6.4% of the total study sample, 10.2% of the 2851 users of prescription drugs, 1.0% of the 2862 users of OTC drugs, and 0.1% of the 1352 users of herbal drugs. Of the total sample, 3.3% reported SADRs of the nervous system, 2.6% of the gastrointestinal system, and 0.6% of the cardiovascular system. Users of prescription drugs with SADRs reported a mean health status score of 0.655, while those who did not report SADRs scored 0.744. Among users of OTC and herbal drugs, the corresponding scores were 0.720 and 0.818, respectively. Those in the population who did not use any drugs rated their health status as 0.846. CONCLUSIONS: Both the prevalence of SADRs and the magnitude of the decrease in subjective health status in respondents experiencing them reflect the importance of individual subjective perceptions for public health. However, in a cross-sectional study like this, causal relationships cannot be firmly established. Further, other factors, such as comorbidity or disappointment with treatment outcomes, could be associated with the decrease in health status.
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| 5. |
- Moen, Janne, et al.
(author)
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Factors associated with multiple medication use in different age groups
- 2009
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In: The Annals of Pharmacotherapy. - 1060-0280 .- 1542-6270. ; 43:12, s. 1978-1985
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Journal article (peer-reviewed)abstract
- BACKGROUND: Multiple medicine use among elderly persons is likely to be the result of treatment regimens developed over a long period of time. By learning more about how multiple medication use develops, the quality of prescribing may be improved across the adult lifespan. OBJECTIVE: To describe patterns of multiple medicine use in the general Swedish population and its association with sociodemographic, lifestyle, and health status factors. METHODS: Data from a cross-sectional population health survey collected during 2001-2005 from 2816 randomly selected Swedish residents (age 30-75 y; response rate 76%) were analyzed. Multiple medicine use was restricted to prescription drugs and defined as the 75th percentile; that is, the 25% of the study group using the highest number of drugs per individual. RESULTS: Seventy-one percent of the respondents used some kind of drug, 51.5% used one or more prescription drug, 38.4% used one or more over-the-counter (OTC) medication, and 8.3% used one or more herbal preparation. The cutoff amounts defining multiple medicine use were: 2 or more medications for 30- to 49-year-olds, 3 or more for 50- to 64-year-olds, and 5 or more for 65- to 75-year-olds. No association between use of multiple medicines and use of OTC drugs or herbal preparations was found. When drugs were classified into therapeutic subgroups, 76.3% of those aged 30-49 years, 97.9% of those aged 50-64 years, and 100% of those aged 65-75 years were taking a unique combination of drugs. Multivariate analyses showed that diabetes and poor self-rated health were associated with multiple medicine use in all age cohorts. Female sex and hypertension were associated with multiple medicine use among those aged 30-49 and 50-64 years, current smoking among those aged 50-64 years, and obesity among those aged 65-75 years. CONCLUSIONS: Multiple medicine use was associated with morbidity and poor self-rated health across all age groups. The vast majority of users of multiple drugs are taking a unique combination of medications.
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| 7. |
- Thomsen, Linda Aagaard, et al.
(author)
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Systematic review of the incidence and characteristics of preventable adverse drug events in ambulatory care
- 2007
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In: Annals of Pharmacotherapy. - 1060-0280. ; 41:9, s. 1411-1426
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To estimate the incidence and describe characteristics of preventable adverse drug events (pADEs) in ambulatory care. DATA SOURCES: Studies were searched in PubMed (1966-March 2007), International Pharmaceutical Abstracts (1970-December 2006), the Cochrane database of systematic reviews (1993-March 2007), EMBASE (1980-February 2007), and Web of Science (1945-March 2007). Key words included medication error, adverse drug reaction, iatrogenic disease, outpatient, ambulatory care, primary health care, general practice, patient admission, hospitalization, observational study, retrospective studies, health services research, and follow-up studies. Additional articles were found in the reference sections of retrieved articles. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed articles assessing pADEs in ambulatory care, with detailed descriptions/frequency distributions of (1) ADE/pADE incidence, (2) clinical outcomes, (3) associated drug groups, and/or (4) underlying medication errors were included. Study country, year and design, sample size, follow-up time, ADE/pADE identification method, proportion of ADEs/pADEs and ADEs/pADEs requiring hospital admission, and frequency distribution of adverse outcome, associated drug groups, or medication errors were extracted. DATA SYNTHESIS: Twenty-nine studies met inclusion criteria: 14 were ambulatory-based and 15 were hospital-based. Seven studies enrolled only eldery patients. The median ADE incidence was 14.9 (range 4.0-91.3) per 1000 person-months, and the pADE incidence was 5.6 per 1000 person-months (1.1-10.1). The median ADE preventability rate was 21% (11-38%). The median incidence of ADEs requiring hospital admission was 0.45 (0.10-13.1) per 1000 person-months, and the median incidence of pADEs requiring hospital admission was 4.5 per 1000 person months. Cardiovascular drugs, analgesics, and hypoglycemic agents together accounted for 86.5% of pADEs, and 77.2% of pADEs resulted in symptoms of the central nervous system, electrolyte/renal system, and gastrointestinal tract. Medication errors resulting in pADEs occurred in the prescribing and monitoring stages. The most frequent drug therapy problem and error of commission reported in ambulatory-based studies on pADEs was the use of inappropriate drugs (42.7%; 40.4-450%). For pADEs requiring hospital admission, the most frequent drug therapy problem and error of omission reported was inadequate monitoring (45.4%; range 22.2-69.8%). Failure to prescribe prophylaxis to patients taking nonsteroidal antiinflammatory drugs or antiplatelet drugs frequently caused gastrointestinal toxicirty whereas lack of monitoring of diuretic, hypoglycemic, and anticoagulant use caused over- or under-diuresis, hyper- or hypoglycemia, and bleeding. CONCLUSIONS: ADEs in ambulatory care are common, with many being pre-ventable and many resulting in hospitalization. Quality improvement programs should target errors in prescribing and monitoring, especially for patients using cardiovascular, analgesic, and, hypoglycemic agents.
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