Cross-sectional study of medical advertisements in a national general medical journal: evidence, cost, and safe use of advertised versus comparative drugs

Background Healthcare professionals are exposed to advertisements for prescription drugs in medical journals. Such advertisements may increase prescriptions of new drugs at the expense of older treatments even when they have no added benefits, are more harmful, and are more expensive. The publication of medical advertisements therefore raises ethical questions related to editorial integrity. Methods We conducted a descriptive cross-sectional study of all medical advertisements published in the Journal of the Danish Medical Association in 2015. Drugs advertised 6 times or more were compared with older comparators: (1) comparative evidence of added benefit; (2) Defined Daily Dose cost; (3) regulatory safety announcements; and (4) completed and ongoing post-marketing studies 3 years after advertising. Results We found 158 medical advertisements for 35 prescription drugs published in 24 issues during 2015, with a median of 7 advertisements per issue (range 0 to 11). Four drug groups and 5 single drugs were advertised 6 times or more, for a total of 10 indications, and we made 14 comparisons with older treatments. We found: (1) ‘no added benefit’ in 4 (29%) of 14 comparisons, ‘uncertain benefits’ in 7 (50%), and ‘no evidence’ in 3 (21%) comparisons. In no comparison did we find evidence of ‘substantial added benefit’ for the new drug; (2) advertised drugs were 2 to 196 times (median 6) more expensive per Defined Daily Dose; (3) 11 safety announcements for five advertised drugs were issued compared to one announcement for one comparator drug; (4) 20 post-marketing studies (7 completed, 13 ongoing) were requested for the advertised drugs versus 10 studies (4 completed, 6 ongoing) for the comparator drugs, and 7 studies (2 completed, 5 ongoing) assessed both an advertised and a comparator drug at 3 year follow-up. Conclusions and relevance In this cross-sectional study of medical advertisements published in the Journal of the Danish Medical Association during 2015, the most advertised drugs did not have documented substantial added benefits over older treatments, whereas they were substantially more expensive. From January 2021, the Journal of the Danish Medical Association no longer publishes medical advertisements.

Studying the anticonvulsive activity of new ligands of NDMA-receptor complex – imidazole-4,5-dicarbonic acid derivatives

NMDA receptors were proven to play a significant role in the processes of epileptogenesis. Experimental data indicate a significant anticonvulsant effect of NMDA receptor antagonists, but the use of the studied NMDA ligands remains limited due to their low efficiency and toxic effects. The aim of the study was to investigate the anticonvulsant effect of new ligands of the glutamate NMDA receptor complex imidazole-4,5-dicarboxylic acid (IDA) derivatives on a model of NMDA-induced convulsions in mice. The tested agents (IEM2258 and IEM2248) were injected into the lateral ventricles of a waking mouse brain at doses of 0.10.5 mmol in 5 l 15 minutes before the convulsant (NMDA). Valproic acid was used as a comparator drug. The results of the study showed that IDA derivatives exhibit anticonvulsant activity of various degrees of severity. A pronounced anticonvulsant effect was established for IEM2258 at a dose of 0.4 mmol: a significant reduction in the duration of convulsions (compared to the previous dose of the tested substance) and a total absence of NMDA-induced deaths. IEM2248 showed anticonvulsant activity at a dose of 0.2 mmol, in 100% of cases preventing fatal outcomes and completely protecting animals from the convulsions. Thus, the data obtained in this study showed dose-dependent anticonvulsant effect of new IDA derivatives (IEM2258 and IEM2248) due to the blockade of the NMDA receptor complex, that indicates the promising aspect for the development of these agents and further searching for effective and safe anticonvulsants among this pharmacological class.

Assessment of MT-279 compound effect on physical endurance of rats under conditions of chronic hypokinesia

The objective of the study was to assess the effect of a sodium salt 3-(2-oxo-3-phenyl- 2H-[1,2,4]triazine[2,3-c]quinazolin-6-yl) of propanoic acid (MT-279 compound) on physical endurance of rats under conditions of chronic hypokinesia (15 days) in comparison with 2-ethylthiobenzimidazole hydrobromide (2-ETBI). The results of the conducted experiment showed that chronic hypokinesia (15 days) caused a progressive decrease in the physical endurance of animals. The signs of this phenomenon occurred already on the Day 7 of the experiment. It manifested by a significant decrease in the duration of rats swimming, treadmill runtime and holding on rotating rods (rotarod test). The course of MT-279 compound (2.5 mg/kg, ip) administered to animals in the specified experimental conditions contributed to restoration of physical performance of the study subjects. Upon introduction of the compound, the duration of rats` swimming on Day 7 of the experiment increased by 108.2%, and on Day 15 - by 64.2%. Administration of 2-ETBI caused the growth of this indicator by 70.5% and 24.2%, respectively. Along with this, we revealed an increase of rats` treadmill running time. On Day 7 and Day 15 of the experiment, we recorded 55.2% and 68.4% growth of the indicator, respectively. Daily administration of 2-ETBI contributed to 41.7% and 59.7% increase of running time, respectively. On Day 7 of MT-279 compound administration under the conditions of chronic hypokinesia, the duration of rats` rod retention time increased by 58.7% compared to 6.2% for 2-ETBI. On Day 15 of the experiment, the physical endurance of animals assessed under this test compared to the control group was 89.0% and 72.3%, respectively. On Day 7, MT-279 compound was significantly superior to the comparator drug in all tests performed for assessment of the ability to improve physical endurance under conditions of chronic hypokinesia. On Day 15 of study, the statistically significant superiority of MT-279 compound over 2-ETBI was identified in all forced swimming and rotarod tests.

Change of indicators of a hemostasis at females with experimental gestosis under the influence of gaba derivatives

It is shown that in the conditions of experimental gestosis, induced by replacing drinking water of 1.8% sodium chloride at rats from the first day of gestation until birth, observes disturbances of coagulative properties and augmentation of thrombogenic potential of a blood to what shorting APTT, prothrombin and thrombin time, rising of level of a fibrinogen, hyperaggregation of thrombocytes testifies. GABA-derivative compounds WPC-147, WPC-189 and comparator drug sulodexide show anticoagulant and antiplatelet activity in the conditions of experimental gestosis, extending APTT, thrombin and a prothrombin time, reducing fibrinogen level, reducing platelet aggregation