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Polypharmacy and associated factors among community-dwelling older persons in a Swiss Canton
Clinical Therapeutics/Volume 37, Number 8S, 2015 Challenges of generic imatinib therapy for croatian patients with Gastrontestinal Stromal Tumors (GIST) I. Kraljickovic1; R. Likic1,2; I. Cegec1; M. Radacic Aumiler1; K. Makar Ausperger1; V. Erdeljic Turk1; and I. Francetic1,2 1 University hospital Zagreb, Zagreb, Croatia; and 2University of Zagreb, Zagreb, Croatia Despite proven effectiveness and safety during the last 30 years, unfounded skepticism about generic prescribing still persists. Recently, 2 patients on Imakrebin for metastatic GIST were admitted for ADR testing. The first reported stomach pain, cramps, skin rash, eye swelling, headache and chills while the second one complained of diarrhea, abdominal pain and hemorrhoids. They claimed symptoms were absent while on Glivec therapy. During hospitalization both were single-blindedly exposed to placebo, Glivec and Imakrebin. While the second patient was asymptomatic during testing, the first developed similar symptoms regardless of the administered substance, without signs or symptoms of acute allergy. All reported symptoms were listed as ADRs to Glivec, but could also be attributed to disease progression or considered psychosomatic and in our view therapy change in both patients was not required. In Croatia, all oncology treatments are financed by the National Health Insurance Fund. Due to budgetary constraints, original drugs are substituted with generics whenever possible. In case of objective intolerance original drug use is possible. Apart from Glivec, priced 1866€ for 30 pills of 400 mg, there are 4 generic parallels of imatinib available since 2013 in Croatia: Neopax (1615€ ), Astrea (1307€ ), Imakrebin (1307€ ) and Nibix (1177€ ), with actual prices significantly lower due to volume discounts.1 First generic imatinib in the USA will be launched, after substantial controversy, on February 1, 2016 by Sun Pharma.2 High prices of new tyrosine kinase inhibitors and Glivec, are significant cost burden for insurers and patients who require therapy for prolonged periods of time.3 Better communication among physicians themselves and with patients is crucial to avoid similar cases in the future. Generic prescribing promotion is still very much needed. 1. Croatian Healt Inshurance Fund, web page, January 26, 2015, http://www.hzzo.hr/zdravstveni-sustav-rh/trazilica-za-lijekove-svazecih-lista 2. Novartis, web page, January 26, 2015, http://www.novartis. com/newsroom/media-releases/en/2014/1785478.shtml 3. Experts in Chronic Myeloid Leukemia. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood. 2013 May 30;121(22):4439–4442.
Promoting public awareness of clinical trials in Montenegro B. Kucevic; M. Rolevski; M. Sahman-Zaimovic; Z. Besovic; and S. Mugosa Agency for Medicines and Medical Devices, Podgorica, Montenegro Introduction: In order to successfully build a clinical research infrastructure one of the key imperatives is that the public understand and strongly support clinical research. Literature data showed that the general public is not sufficiently informed about the purpose and importance of clinical trials. The aim of this study is to investigate awareness of general public in Montenegro regarding clinical trials.
August 2015
Material and Methods: The data from questionnaire completed by 400 randomly selected people aged 19 and over was collected. SPSS software was used for statistical analysis. Results: There were statistically significant gender differences with regards to clinical trials awareness. Only 44.2% of all male subjects versus 70.8% of all female ones were informed about the definition of clinical trials (P < 0.001). Both were mostly informed through the media. While 49.8% women thought that medicines on the market were clinically tested, 47.5% men were not sure about that (P = 0.037). The main motive for clinical trial enrolment for subjects under the age of 25 and over the age of 50 was curing the existing disease, while for subjects aged 26-50 was financial reimbursement (37.6% and 44.2% versus 34.9%; P < 0.001). Conclusions: These results indicate that additional educational efforts are needed in order to improve the knowledge of significance of clinical trials. Therefore, the Agency for Medicines and Medical Devices of Montenegro, in accordance with its competences - education about medicines, will be providing more information relevant to clinical trials to general public in the future.
Polypharmacy and associated factors among community-dwelling older persons in a Swiss Canton S. Fustinoni1; D. Renard2; B. Santos-Eggimann1; and L. Seematter-Bagnoud1 1 Center for Aging Studies, Lausanne University Hospital, CH-1010 Lausanne, Switzerland; and 2Division of Clinical Pharmacology, Lausanne University Hospital, CH-1011 Lausanne, Switzerland Background: Polypharmacy in older persons has been scarcely studied in Switzerland. Our aim was to investigate which socio-demographic factors are associated to polypharmacy in a sample of Swiss older persons. Material and Methods: The study population consisted of community-dwelling persons aged 69+ years living in the canton de Vaud (Switzerland). Information about current medication was self-reported by 3133 participants in a postal survey nested into a population-based cohort study (participation rate: 71% of eligible subjects). Data were weighted to reflect the age and sex distribution of the source population. Polypharmacy was defined as currently taking five or more different registered drugs on a regular basis (further referred to as “drugs”). Results: Median age was 77 years; 57% were female. Most (84%) were taking at least one drug; the maximum reported was 17. Polypharmacy was present in 27% of our population and increased from 18% among persons aged 69–74 to 29% in those aged 75–84 and 38% in those aged 85+ (P < 0.001). Polypharmacy was observed in 38% of the subgroup reporting two or more chronic diseases versus 9% of those without comorbidity (P < 0.001). In multivariate logistic regression analysis, polypharmacy remained significantly associated with the number of chronic diseases (adjusted OR(per unit increment) 2.14; 95% CI, 1.85-2.48) and with oldest age (adjusted OR(85+ versus 69-74) 2.64; 95% CI, 1.61–4.34). No association was observed between either education level or gender and polypharmacy. Conclusions: Polypharmacy was reported in 27% of communitydwelling persons aged 69+ years. Comorbidity and age 85+ were significantly and independently associated factors. While polypharmacy was particularly frequent in the older age group, it already concerned nearly one in five persons at the age of 69–74. These findings emphasize the need for scheduled medication reviews not only in oldest-old, but also in the polymorbid youngest-old patients.
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Clinical Therapeutics Drugs regularly taken by community-dwelling older persons in a Swiss Canton D. Renard1; S. Fustinoni2; L. Seematter-Bagnoud2; and B. Santos-Eggimann2 1 Division of Clinical Pharmacology, Lausanne University Hospital, 1011 Lausanne, Switzerland; and 2Center for Aging Studies, Lausanne University Hospital, 1010 Lausanne, Switzerland Background: Studies about polypharmacy may fail to present data in a clinically meaningful way. Our aim was to report the frequency of drugs taken by older people according to clinically relevant pharmacological classes. Material and Methods: The study population consisted of community-dwelling persons aged 69+ years living in the canton de Vaud (Switzerland). Information about current medication was self-reported by 3133 participants in a postal survey nested into a population-based cohort study (participation rate: 71% of eligible subjects). Data were weighted to reflect the age and sex distribution of the source population. Results: Median age was 77 years; 57% were female; a majority (84%) were currently taking at least one registered drug on a regular basis. The frequency of major pharmacological classes was as follows: Percentage of participants currently taking at least one such drug on a regular basis (%) ALL CARDIOVASCULAR DRUGS, among which: Statins Renin-angiotensin system inhibitors Beta blockers Calcium channel blockers Diuretics Aspirin Clopidogrel Vitamin K antagonists ANTIDIABETICS Oral antidiabetic agents Insulins ALL DIGESTIVE DRUGS, among which: Antacids Laxatives CALCIUM AND VITAMIN D ANALGESICS Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) Acetaminophen Opioids Topical NSAIDs PSYCHOTROPIC DRUGS Antidepressants Anxiolytics Sedative-hypnotics Anti-psychotics
69.3 29.4 40.7 21.3 12.6 11.0 25.9 2.5 7.7 9.3 8.9 0.9 15.7 12.7 3.4 14.2 13.3 5.9 5.7 3.0 1.7 17.7 8.5 7.3 6.1 0.8
Conclusions: The most frequent class was cardiovascular agents (almost 70% of participants report taking at least one cardiovascular drug, and 9% report taking at least one anti-diabetic) followed by psychotropic drugs (18%). By contrast, reports of calcium/vitamin D (14%) and analgesics (13%) were low, suggesting underuse. Optimizing prescribing in this population should include a) carefully weighing the risk-benefit balance of cardiovascular and psychotropic drugs, which may be double-edged swords in a potentially fragile population and b) considering the risk of under-prescribing.
Mechanism of the effect of visfatin on human internal thoracic arteries Z. Bayram; I. Golbasý; and S.S. Ozdem Akdeniz University, Antalya, Turkey
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Background or Introduction: Visfatin, also known as pre-B-cell colony-enhancing factor and nicotinamide phosphoriboslytransferase (Nampt) is a novel adipocytokine. The present study aimed to investigate the functional effects and the possible underlying mechanism(s) of visfatin on human left internal thoracic artery (ITA) preparations. Material and Methods: Samples of redundant ITA obtained from patients undergoing a coronary artery bypass surgery were cut into 3-4 mm wide rings and suspended in 20 mL organ baths. Isometric tension was continuously recorded with isometric force transducers connected to a computer-based data acquisition system. Results: Contraction responses of human ITA rings to angiotensin II, endothelin-1, noradrenaline and phenylephrine did not change significantly before and after incubation with different visfatin concentrations. Visfatin (10−12 – 10−7 M) produced concentration-dependent relaxation responses in human ITA rings precontracted with phenylephrine (10−6 M) that were significantly higher in endothelium-intact than endothelium-denuded preparations. Incubation of tissues with cyclooxygenase inhibitor indomethacin (10−5 M) did not cause a significant alteration, while incubations with nitric oxide (NO) synthase inhibitor L-NAME (10−4 M) and specific guanylyl cyclase inhibitor ODQ (5 × 10−5 M) caused statistically significant decreases in relaxant responses to visfatin. Visfatin-induced relaxation responses were almost completely blocked in the presence of Nampt enzyme inhibitor FK866 (10 µM). Incubation of the tissues with a combination of high-conductance Ca2+-activated potassium channel blocker charybdotoxin and small- conductance Ca2+-activated potassium channel blocker apamin (10−7 M, both) did not cause a statistically significant alteration in visfatin-induced relaxations. Acetylcholine-induced (10−10 - 10−5 M) endothelium-dependent relaxations significantly increased whereas sodium nitroprusside-induced (10−10 - 10−5 M) endothelium-independent relaxations did not change following incubation of human ITA rings with 10−9 and 10−8 M visfatin. Conclusions: The findings of the present study demonstrated that visfatin did not affect contraction responses to various contractile agents, but produced concentration-dependent relaxation responses in endothelium-intact human ITA rings through Nampt enzymatic activity and NO-cGMP pathway. This study was supported by ‘The Scientific Research Projects Coordination Unit of Akdeniz University, Project number: 2012.03.0122.002.
Intra-Arterial Microdosing (IAM), a novel Drug development approach, proof of concept in Rats T. Burt; H. Wu; A.T. Layton; D.C. Rouse; B.B. Chin; T.C. Hawk; D.H. Weitzel; M. Cohen-Wolkowiez; S. Chow; and R.J. Noveck Duke University, Durham, North Carolina, USA Background: Intra-Arterial Microdosing (IAM) is a novel drug development approach combing intra-arterial drug delivery with microdosing. We aimed to demonstrate that IAM leads to similar target exposure as systemic full-dose administration but with minimal systemic exposure. Methods: Insulin 0.34 IU/kg was administered intra-arterially (ipsilateral femoral artery) to 2 CD IGS rats just prior to 60-minute 18F-FDG uptake imaging of ipsilateral (leg), contralateral (leg), and systemic (spine) muscles. Area under the curve (AUC) was calculated by the linear trapezoidal method and together with maximum glucose uptake (Emax) were summarized by descriptive statistics. Results: Contralateral and systemic Emax (mean ± SD: 0.323 ± 0.129 and 0.297 ± 0.205, respectively) and AUC (mean ± SD: 13.08 ± 8.12 and 13.39 ± 10.78, respectively) post IAM were similar but lower than ipsilateral Emax and AUC (0.615 ± 0.367 and 22.13 ± 15.33, respectively; Figure).
Volume 37 Number 8S
Promoting public awareness of clinical trials in Montenegro B. Kucevic; M. Rolevski; M. Sahman-Zaimovic; Z. Besovic; and S. Mugosa Agency for Medicines and Medical Devices, Podgorica, Montenegro Introduction: In order to successfully build a clinical research infrastructure one of the key imperatives is that the public understand and strongly support clinical research. Literature data showed that the general public is not sufficiently informed about the purpose and importance of clinical trials. The aim of this study is to investigate awareness of general public in Montenegro regarding clinical trials.
August 2015
Material and Methods: The data from questionnaire completed by 400 randomly selected people aged 19 and over was collected. SPSS software was used for statistical analysis. Results: There were statistically significant gender differences with regards to clinical trials awareness. Only 44.2% of all male subjects versus 70.8% of all female ones were informed about the definition of clinical trials (P < 0.001). Both were mostly informed through the media. While 49.8% women thought that medicines on the market were clinically tested, 47.5% men were not sure about that (P = 0.037). The main motive for clinical trial enrolment for subjects under the age of 25 and over the age of 50 was curing the existing disease, while for subjects aged 26-50 was financial reimbursement (37.6% and 44.2% versus 34.9%; P < 0.001). Conclusions: These results indicate that additional educational efforts are needed in order to improve the knowledge of significance of clinical trials. Therefore, the Agency for Medicines and Medical Devices of Montenegro, in accordance with its competences - education about medicines, will be providing more information relevant to clinical trials to general public in the future.
Polypharmacy and associated factors among community-dwelling older persons in a Swiss Canton S. Fustinoni1; D. Renard2; B. Santos-Eggimann1; and L. Seematter-Bagnoud1 1 Center for Aging Studies, Lausanne University Hospital, CH-1010 Lausanne, Switzerland; and 2Division of Clinical Pharmacology, Lausanne University Hospital, CH-1011 Lausanne, Switzerland Background: Polypharmacy in older persons has been scarcely studied in Switzerland. Our aim was to investigate which socio-demographic factors are associated to polypharmacy in a sample of Swiss older persons. Material and Methods: The study population consisted of community-dwelling persons aged 69+ years living in the canton de Vaud (Switzerland). Information about current medication was self-reported by 3133 participants in a postal survey nested into a population-based cohort study (participation rate: 71% of eligible subjects). Data were weighted to reflect the age and sex distribution of the source population. Polypharmacy was defined as currently taking five or more different registered drugs on a regular basis (further referred to as “drugs”). Results: Median age was 77 years; 57% were female. Most (84%) were taking at least one drug; the maximum reported was 17. Polypharmacy was present in 27% of our population and increased from 18% among persons aged 69–74 to 29% in those aged 75–84 and 38% in those aged 85+ (P < 0.001). Polypharmacy was observed in 38% of the subgroup reporting two or more chronic diseases versus 9% of those without comorbidity (P < 0.001). In multivariate logistic regression analysis, polypharmacy remained significantly associated with the number of chronic diseases (adjusted OR(per unit increment) 2.14; 95% CI, 1.85-2.48) and with oldest age (adjusted OR(85+ versus 69-74) 2.64; 95% CI, 1.61–4.34). No association was observed between either education level or gender and polypharmacy. Conclusions: Polypharmacy was reported in 27% of communitydwelling persons aged 69+ years. Comorbidity and age 85+ were significantly and independently associated factors. While polypharmacy was particularly frequent in the older age group, it already concerned nearly one in five persons at the age of 69–74. These findings emphasize the need for scheduled medication reviews not only in oldest-old, but also in the polymorbid youngest-old patients.
e39
Clinical Therapeutics Drugs regularly taken by community-dwelling older persons in a Swiss Canton D. Renard1; S. Fustinoni2; L. Seematter-Bagnoud2; and B. Santos-Eggimann2 1 Division of Clinical Pharmacology, Lausanne University Hospital, 1011 Lausanne, Switzerland; and 2Center for Aging Studies, Lausanne University Hospital, 1010 Lausanne, Switzerland Background: Studies about polypharmacy may fail to present data in a clinically meaningful way. Our aim was to report the frequency of drugs taken by older people according to clinically relevant pharmacological classes. Material and Methods: The study population consisted of community-dwelling persons aged 69+ years living in the canton de Vaud (Switzerland). Information about current medication was self-reported by 3133 participants in a postal survey nested into a population-based cohort study (participation rate: 71% of eligible subjects). Data were weighted to reflect the age and sex distribution of the source population. Results: Median age was 77 years; 57% were female; a majority (84%) were currently taking at least one registered drug on a regular basis. The frequency of major pharmacological classes was as follows: Percentage of participants currently taking at least one such drug on a regular basis (%) ALL CARDIOVASCULAR DRUGS, among which: Statins Renin-angiotensin system inhibitors Beta blockers Calcium channel blockers Diuretics Aspirin Clopidogrel Vitamin K antagonists ANTIDIABETICS Oral antidiabetic agents Insulins ALL DIGESTIVE DRUGS, among which: Antacids Laxatives CALCIUM AND VITAMIN D ANALGESICS Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) Acetaminophen Opioids Topical NSAIDs PSYCHOTROPIC DRUGS Antidepressants Anxiolytics Sedative-hypnotics Anti-psychotics
69.3 29.4 40.7 21.3 12.6 11.0 25.9 2.5 7.7 9.3 8.9 0.9 15.7 12.7 3.4 14.2 13.3 5.9 5.7 3.0 1.7 17.7 8.5 7.3 6.1 0.8
Conclusions: The most frequent class was cardiovascular agents (almost 70% of participants report taking at least one cardiovascular drug, and 9% report taking at least one anti-diabetic) followed by psychotropic drugs (18%). By contrast, reports of calcium/vitamin D (14%) and analgesics (13%) were low, suggesting underuse. Optimizing prescribing in this population should include a) carefully weighing the risk-benefit balance of cardiovascular and psychotropic drugs, which may be double-edged swords in a potentially fragile population and b) considering the risk of under-prescribing.
Mechanism of the effect of visfatin on human internal thoracic arteries Z. Bayram; I. Golbasý; and S.S. Ozdem Akdeniz University, Antalya, Turkey
e40
Background or Introduction: Visfatin, also known as pre-B-cell colony-enhancing factor and nicotinamide phosphoriboslytransferase (Nampt) is a novel adipocytokine. The present study aimed to investigate the functional effects and the possible underlying mechanism(s) of visfatin on human left internal thoracic artery (ITA) preparations. Material and Methods: Samples of redundant ITA obtained from patients undergoing a coronary artery bypass surgery were cut into 3-4 mm wide rings and suspended in 20 mL organ baths. Isometric tension was continuously recorded with isometric force transducers connected to a computer-based data acquisition system. Results: Contraction responses of human ITA rings to angiotensin II, endothelin-1, noradrenaline and phenylephrine did not change significantly before and after incubation with different visfatin concentrations. Visfatin (10−12 – 10−7 M) produced concentration-dependent relaxation responses in human ITA rings precontracted with phenylephrine (10−6 M) that were significantly higher in endothelium-intact than endothelium-denuded preparations. Incubation of tissues with cyclooxygenase inhibitor indomethacin (10−5 M) did not cause a significant alteration, while incubations with nitric oxide (NO) synthase inhibitor L-NAME (10−4 M) and specific guanylyl cyclase inhibitor ODQ (5 × 10−5 M) caused statistically significant decreases in relaxant responses to visfatin. Visfatin-induced relaxation responses were almost completely blocked in the presence of Nampt enzyme inhibitor FK866 (10 µM). Incubation of the tissues with a combination of high-conductance Ca2+-activated potassium channel blocker charybdotoxin and small- conductance Ca2+-activated potassium channel blocker apamin (10−7 M, both) did not cause a statistically significant alteration in visfatin-induced relaxations. Acetylcholine-induced (10−10 - 10−5 M) endothelium-dependent relaxations significantly increased whereas sodium nitroprusside-induced (10−10 - 10−5 M) endothelium-independent relaxations did not change following incubation of human ITA rings with 10−9 and 10−8 M visfatin. Conclusions: The findings of the present study demonstrated that visfatin did not affect contraction responses to various contractile agents, but produced concentration-dependent relaxation responses in endothelium-intact human ITA rings through Nampt enzymatic activity and NO-cGMP pathway. This study was supported by ‘The Scientific Research Projects Coordination Unit of Akdeniz University, Project number: 2012.03.0122.002.
Intra-Arterial Microdosing (IAM), a novel Drug development approach, proof of concept in Rats T. Burt; H. Wu; A.T. Layton; D.C. Rouse; B.B. Chin; T.C. Hawk; D.H. Weitzel; M. Cohen-Wolkowiez; S. Chow; and R.J. Noveck Duke University, Durham, North Carolina, USA Background: Intra-Arterial Microdosing (IAM) is a novel drug development approach combing intra-arterial drug delivery with microdosing. We aimed to demonstrate that IAM leads to similar target exposure as systemic full-dose administration but with minimal systemic exposure. Methods: Insulin 0.34 IU/kg was administered intra-arterially (ipsilateral femoral artery) to 2 CD IGS rats just prior to 60-minute 18F-FDG uptake imaging of ipsilateral (leg), contralateral (leg), and systemic (spine) muscles. Area under the curve (AUC) was calculated by the linear trapezoidal method and together with maximum glucose uptake (Emax) were summarized by descriptive statistics. Results: Contralateral and systemic Emax (mean ± SD: 0.323 ± 0.129 and 0.297 ± 0.205, respectively) and AUC (mean ± SD: 13.08 ± 8.12 and 13.39 ± 10.78, respectively) post IAM were similar but lower than ipsilateral Emax and AUC (0.615 ± 0.367 and 22.13 ± 15.33, respectively; Figure).
Volume 37 Number 8S