Mitja Kos

Cost-effectiveness of UGT1A1 genotyping in second-line, high-dose, once every 3 weeks irinotecan monotherapy treatment of colorectal cancer.

AIM The aim of the present study was to evaluate the cost-effectiveness of UGT1A1 genotyping in second-line, high-dose, once every 3 weeks irinotecan monotherapy treatment of colorectal cancer. METHODS Standard therapy was compared with alternative strategies based on UGT1A1 genotyping from the US healthcare payer perspective. Two alternative strategies (dose reduction and prophylactic use of G-CSF with prior genotyping) and standard therapy were evaluated in a decision analysis, whereas alternative regimens were considered in discussion. The effectiveness outcome was severe neutropenia occurrence and number of life-years gained. RESULTS & CONCLUSION Genotyping in combination with a subsequent reduction of initial irinotecan dose for UGT1A1 7/7 genotype patients was cost-saving for the population of African and Caucasian origin. By contrast, UGT1A1 genotyping was not cost effective for the population of Asian ancestry. Furthermore, the prophylactic use of G-CSFs in UGT1A1 7/7 genotype patients was not cost effective in any population group. Finally, the application of a 3-weekly high-dose treatment regimen with a 20% reduced dosage compared with the low-dose weekly irinotecan regimen in patients with UGT1A1 7/7 genotype was less expensive and is more convenient for the patient.

Cost-effectiveness of antipsychotics for outpatients with chronic schizophrenia.

Aims:  The aim of the present analysis was to evaluate the cost‐effectiveness of alternative treatments for outpatients with chronic schizophrenia from the healthcare payers perspective.

Using the Simulated Patient Methodology to Assess Paracetamol-Related Counselling for Headache

Objectives Firstly, to assess paracetamol-related counselling. Secondly, to evaluate the patient’s approach as a determinant of counselling and to test the acceptability of the simulated patient method in Slovenian pharmacies. Methods The simulated patient methodology was used in 17 community pharmacies. Three scenarios related to self-medication for headaches were developed and used in all participating pharmacies. Two scenarios were direct product requests: scenario 1: a patient with an uncomplicated short-term headache; scenario 2: a patient with a severe, long-duration headache who takes paracetamol for too long and concurrently drinks alcohol. Scenario 3 was a symptom-based request: a patient asking for medicine for a headache. Pharmacy visits were audio recorded and scored according to predetermined criteria arranged in two categories: counselling content and manner of counselling. The acceptability of the methodology used was evaluated by surveying the participating pharmacists. Results The symptom-based request was scored significantly better (a mean 2.17 out of a possible 4 points) than the direct product requests (means of 1.64 and 0.67 out of a possible 4 points for scenario 1 and 2, respectively). The most common information provided was dosage and adverse effects. Only the symptom-based request stimulated spontaneous counselling. No statistically significant differences in the duration of the consultation between the scenarios were found. There were also no significant differences in the quality of counselling between the Masters of Pharmacy and Pharmacy Technicians. The acceptability of the SP method was not as high as in other countries. Conclusion The assessment of paracetamol-related counselling demonstrates room for practice improvement.

Cost-effectiveness analysis of HPV vaccination alongside cervical cancer screening programme in Slovenia.

BACKGROUND The objective of the present study is to evaluate the cost-effectiveness of human papillomavirus (HPV) vaccination alongside cervical cancer screening programme in Slovenia. METHODS A previously published Markov model representing natural history of HPV infection was adapted to Slovenian context. The model followed a cohort of 12-year-old girls to 85-year-old women. Two strategies were compared: HPV vaccination alongside conventional cytological screening versus screening alone. Analysis was performed from the health care payer perspective. RESULTS Vaccination with screening compared with screening alone was associated with an incremental cost-effectiveness ratio (ICER) of 23,178 EUR per quality adjusted life-year (QALY) gained and 54,536 EUR per life-year gained (LYG) at the discounting rate of 5%. Sensitivity analyses demonstrated that the ICER was most sensitive to the need for booster dose and to different values of discount rates. In case the booster dose was assumed 10 years after initial vaccination, the ICER value was increased to 58,690 EUR per QALY. On the other hand, using lower values of discount rates than the base case 5% significantly reduced the ICER value. CONCLUSION According to the cost-effectiveness thresholds of 30,000 EUR per QALY which was adopted by the Health Council in Slovenia, HPV vaccination alongside screening programme can be regarded as cost-effective. However, cost-effectiveness of HPV vaccination would become questionable in case a booster dose was needed to provide lifetime protection.

Development and Initial Validation of a Patient Satisfaction With Pharmacy Performance Questionnaire (PSPP-Q)

The objective of this study was to develop a psychometrically valid, multidimensional, self-administered, general questionnaire measuring patient satisfaction with pharmacy performance for outpatients. A multiphase development process was employed to attain this goal. In Phase I, questionnaire’s content was generated using interviews with pharmacy users regarding their experiences and expectations relating to pharmacies. In Phase II, the content and format of the questionnaire was defined in a two-round modified Delphi study, where an expert panel estimated importance of generated items for patient satisfaction. In Phase III, the initial validation of the questionnaire, which included a random sample of 5,400 patients coming out of the selected pharmacies, took place. The outcome of the development process is a questionnaire that focuses on issues expressed as important by patients, takes into account services as well as the supporting structure, and includes items relevant to an individual pharmacy and demonstrates satisfactory psychometric properties.

Use of simulated patients to evaluate combined oral contraceptive dispensing practices of community pharmacists.

Background Combined oral contraceptive (COC) use is the most commonly used reversible method of birth control. The incorrect use of COCs is frequent and one of the most common causes of unintended pregnancies. Community pharmacists (CPs) are in a strategic position to improve COC use because they are the last health professional to interact with patients before drug use. Objective To evaluate the COC dispensing practices of CPs in a developing country. Method A cross-sectional study was conducted in community pharmacies of Assis and Ourinhos microregions, Brazil, between June 1, 2012, and October 30, 2012. Four simulated patients (SPs) (with counseled audio recording) visited community pharmacies with a prescription for Ciclo 21® (a COC containing ethinyl estradiol 30 mcg + levonorgestrel 15 mcg). The audio recording of every SP visit was listened to independently by 3 researchers to evaluate the COC dispensing practice. The percentage of CPs who performed a screening for safe use of COCs (i.e., taking of patients’ medical and family history, and measuring of blood pressure) and provided counseling, as well as the quality of the screening and counseling, were evaluated. Results Of the 185 CPs contacted, 41 (22.2%) agreed to participate in the study and finished the study protocol. Only 3 CPs asked the SP a question (1 question asked by each professional), and all of the questions were closed-ended, viz., “do you smoke?” (n = 2) and “what is your age?” (n = 1). None of the CPs measured the patient’s blood pressure. Six CPs provided counseling when dispensing COCs (drug dosing, 5 CPs; possible adverse effects, 2 CPs), and one CP provided counseling regarding both aspects. Conclusion The CPs evaluated did not dispense COC appropriately and could influence in the occurrence of negatives therapeutic outcomes such as adverse effects and treatment failure.

Satisfaction with Pharmacotherapy for Approved and Off-Label Indications—A Delphi Study

BACKGROUND: Prescribing for non-approved uses is widespread in the treatment of AIDS, cancer, and pediatric illnesses, but it is by no means limited to these areas. Few studies have been performed evaluating reasons for off-label prescribing. OBJECTIVE: To explore the satisfaction with drug therapy as one of the potential reasons for off-label uses by testing a hypothesis that the satisfaction with drug therapy for off-label indications is lower than for approved indications. METHODS: The study compared the satisfaction with drug therapy for known off-label indications with a control group of approved indications. Twenty-four of the first 50 single-ingredient drugs, according to their share in the drug cost budget of the Slovenian Compulsory Health Insurance, had 86 different off-label indications eligible for inclusion. A control group of 86 approved indications was randomly selected from the list of all possible approved indications for the same 24 drugs. A 2–round Delphi technique, involving an expert panel of physicians who are members of the drug regulatory agency, was used to evaluate the satisfaction with drug therapy for selected indications. RESULTS: After the second round of the Delphi study, the median scores of satisfaction with drug therapy for approved and off-label indications were 7.00 and 6.50, respectively (p = 0.001). CONCLUSIONS: The study shows that the satisfaction with available drug therapy for off-label indications is lower than for approved indications. The statistical association, biologic plausibility, and coherence with existing information, as well as the temporality of the association, provide supporting evidence that low satisfaction with drug therapy is one of the incentives for off-label use.

Sedative load and frailty among community-dwelling population aged ≥65 years

OBJECTIVE To explore the association between use of sedative drugs and frailty. DESIGN Cross-sectional study. SETTING First wave of The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort of the community-dwelling population aged 50 years or older in Ireland. PARTICIPANTS Participants were 1642 men and 1804 women aged 65 years or older. MEASUREMENTS Regular use of sedative drugs determined according to the sedative load (SL) model, frailty phenotype status, and frailty deficit index (FI) score assessed using validated, established protocols. RESULTS Overall, 19% of the participants took sedative drugs, most frequently hypnotics and antidepressants. Sedative drug use was at 46% for frail, 23% for prefrail, and 9% for nonfrail participants. After adjustment for covariates, SL was positively associated with being prefrail (odds ratio [OR] 1.27; 95% confidence interval [CI] 1.11-1.46) and frail (OR 1.30; 95% CI 1.02-1.64). Advancing age but not sex remained significant (P < .001). After adjustment for covariates, the association between SL and the FI was also significant at P ≤ .001 (β = 1.77; 95% CI 1.13-2.42). CONCLUSION Higher SL was positively associated with phenotype frailty and the FI. This suggests that careful consideration must be given when prescribing sedatives to frail older adults, who are most vulnerable to adverse drug reactions and adverse health outcomes.

Body shape, body size and cigarette smoking relationships

Objectives:The aim of the present study was to explore whether smoking is positively related with the abdominal obesity.Methods:Cross-sectional data was analyzed from a random sample of 1,342 subjects, stratified by their age and gender. Cigarette smoking habits were assessed and anthropometric measures obtained during the health examination.Results:Statistically significant differences in waist circumference and waist-hip ratio were found among males in some of the age groups, body mass index however, was lower in older smokers. There were no differences between female smokers and non-smokers in all parameters.Conclusion:The results of the study do not support the hypothesis that smoking affects an abnormal fat distribution profile predominantly in the form of central adiposity as reported earlier.

Effects of synbiotic fermented milk containing Lactobacillus acidophilus La-5 and Bifidobacterium animalis ssp. lactis BB-12 on the fecal microbiota of adults with irritable bowel syndrome: A randomized double-blind, placebo-controlled trial

We conducted a randomized double-blind, placebo-controlled multicentric study to investigate the influence of a synbiotic fermented milk on the fecal microbiota composition of 30 adults with irritable bowel syndrome (IBS). The synbiotic product contained Lactobacillus acidophilus La-5, Bifidobacterium animalis ssp. lactis BB-12, Streptococcus thermophilus, and dietary fiber (90% inulin, 10% oligofructose), and a heat-treated fermented milk without probiotic bacteria or dietary fiber served as placebo. Stool samples were collected after a run-in period, a 4-wk consumption period, and a 1-wk follow-up period, and were subjected to real-time PCR and 16S rDNA profiling by next-generation sequencing. After 4wk of synbiotic (11 subjects) or placebo (19 subjects) consumption, a greater increase in DNA specific for L. acidophilus La-5 and Bifidobacterium animalis ssp. lactis was detected in the feces of the synbiotic group compared with the placebo group by quantitative real-time PCR. After 1wk of follow-up, the content of L. acidophilus La-5 and B. animalis ssp. lactis decreased to levels close to initial levels. No significant changes with time or differences between the groups were observed for Lactobacillus, Enterobacteriaceae, Bifidobacterium, or all bacteria. The presence of viable BB-12- and La-5-like bacteria in the feces resulting from the intake of synbiotic product was confirmed by random amplification of polymorphic DNA (RAPD)-PCR. At the end of consumption period, the feces of all subjects assigned to the synbiotic group contained viable bacteria with a BB-12-like RAPD profile, and after 1wk of follow-up, BB-12-like bacteria remained in the feces of 87.5% of these subjects. The presence of La-5-like colonies was observed less frequently (37.5 and 25% of subjects, respectively). Next-generation sequencing of 16S rDNA amplicons revealed that only the percentage of sequences assigned to Strep. thermophilus was temporarily increased in both groups, whereas the global profile of the fecal microbiota of patients was not altered by consumption of the synbiotic or placebo. In conclusion, daily consumption of a synbiotic fermented milk had a short-term effect on the amount and proportion of La-5-like strains and B. animalis ssp. lactis in the fecal microbiome of IBS patients. Furthermore, both synbiotic and placebo products caused a temporary increase in fecal Strep. thermophilus.