Magdalena Koperny

Vortioxetine: A review of the pharmacology and clinical profile of the novel antidepressant

The aim of this paper was to review the up-to-date evidence base on pharmacology and clinical properties of vortioxetine. Vortioxetine is a novel antidepressant, approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). Because vortioxetine exhibits both an antidepressant and anxiolytic effect, it may be effective in treating both depressive and anxiety disorders, such as generalized anxiety disorder (GAD). Based on its pharmacodynamics profile and preclinical studies, it is believe that the drugs clinical action is mediated mainly by selective blockade of serotonin reuptake (by inhibiting the serotonin transporter [SERT]) and direct modulation of 5-HT receptors activity (such as 5-HT3, 5-HT7, 5-HT1D and 5-HT1B). In patients with MDD the recommended doses range is 5-20mg/day. Vortioxetine was shown to be more effective than placebo both in MDD and GAD. In terms of side effects, nausea, vomiting, diarrhea, and dry mouth were most commonly observed in individuals receiving vortioxetine. In direct comparison to duloxetine, vortioxetine is found to have a smaller efficacy but had a lower risk of developing the common antidepressant-induced adverse effects.

Limited responsiveness related to the minimal important difference of patient-reported outcomes in rare diseases

OBJECTIVES To explore the responsiveness of patient-reported outcomes (PROs) in interventional studies involving patients with rare lysosomal storage diseases (LSDs). STUDY DESIGN AND SETTING We searched eight databases for experimental and nonexperimental studies. Pairs of trained reviewers independently screened articles and subsequently extracted data from the eligible studies. Among studies with 10 or more patients using a valid PRO, we assessed the responsiveness of PROs based on a reanalysis of the data using minimal important difference estimates. Our analyses focused on statistically significant within-group differences in PROs for observational studies or the statistically significant between-group differences in PRO scores for controlled studies. RESULTS Of 2,679 unique records, 62 interventional studies addressing patients with Fabry (55%), Gaucher (19%), Pompe (16%), and mucopolysaccharidoses (11%) proved eligible. The most frequently used PROs were the Short-Form-36 (25 studies), Brief Pain Inventory (20 studies), EuroQoL-5D (9 studies), and the Fatigue Severity Scale (6 studies). Observational studies suggest that PROs sometimes detect significant within-group changes when present. Randomized trials raise questions regarding the responsiveness of PROs to small differences between groups. CONCLUSIONS Most studies have relied on generic PROs to evaluate quality of life and symptoms in patients with rare LSDs. PROs appear more responsive in observational studies than randomized trials.

Risk and surrogate benefit for pediatric Phase I trials in oncology: A systematic review with meta-analysis

Background Pediatric Phase I cancer trials are critical for establishing the safety and dosing of anti-cancer treatments in children. Their implementation, however, must contend with the rarity of many pediatric cancers and limits on allowable risk in minors. The aim of this study is to describe the risk and benefit for pediatric cancer Phase I trials. Methods and findings Our protocol was prospectively registered in PROSPERO (CRD42015015961). We systematically searched Embase and PubMed for solid and hematological malignancy Phase I pediatric trials published between 1 January 2004 and 1 March 2015. We included pediatric cancer Phase I studies, defined as “small sample size, non‑randomized, dose escalation studies that defined the recommended dose for subsequent study of a new drug in each schedule tested.” We measured risk using grade 3, 4, and 5 (fatal) drug-related adverse events (AEs) and benefit using objective response rates. When possible, data were meta-analyzed. We identified 170 studies meeting our eligibility criteria, accounting for 4,604 patients. The pooled overall objective response rate was 10.29% (95% CI 8.33% to 12.25%), and was lower in solid tumors, 3.17% (95% CI 2.62% to 3.72%), compared with hematological malignancies, 27.90% (95% CI 20.53% to 35.27%); p < 0.001. The overall fatal (grade 5) AE rate was 2.09% (95% CI 1.45% to 2.72%). Across the 4,604 evaluated patients, there were 4,675 grade 3 and 4 drug-related AEs, with an average grade 3/4 AE rate per person equal to 1.32. Our study had the following limitations: trials included in our review were heterogeneous (to minimize heterogeneity, we separated types of therapy and cancer types), and we relied on published data only and encountered challenges with the quality of reporting. Conclusions Our meta-analysis suggests that, on the whole, AE and response rates in pediatric Phase I trials are similar to those in adult Phase I trials. Our findings provide an empirical basis for the refinement and review of pediatric Phase I trials, and for communication about their risk and benefit.

Lurasidone versus typical antipsychotics for schizophrenia

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To review the efficacy and safety of lurasidone versus typical antipsychotics for adults with schizophrenia or related disorders.

Ogniska zakażeń szpitalnych w województwie małopolskim w latach 2011-2013

Despite the continuous advances of medicine and higher safety standards for patients, nosocomial infections are a major problem accompanying of treatment process. Infected patients are exposed to prolonged hospital stay, require additional medical procedures, theresofore their treatment and care are associated with additional costs for health facility. In the present study the number of outbreaks of nosocomial infections, which occurred in hospitals in the Malopolska province and in Poland, as well as etiological factors of the infections in the years 2011–2013 were analyzed. In the analyzed period we observed increase in the number of outbreaks of infections in Poland and in Malopolska (from 339 to 394 and from 19 to 26 in Poland and Malopolska respectively). The most frequently identified factor is C. difficile and Rotavirus, followed by K. pneumoniae ESBL, and Norovirus. There was a decrease in the number of outbreaks of unknown etiology, both in Poland and in Malopolska. The analysis identified an increase in the number of outbreaks caused by C. difficile, Noroviruses and Rotaviruses, as the main problem in the recent years. This trend occurs in the Malopolska region and in the country. However, the analysis of the reports shows improved reportability of outbreaks in Malopolska and in Poland which will allow for better control of nosocomial infections.

Finansowanie najdroższych terapii lekowych w Polsce a problemy w dostępie do nich. Analiza poziomu finansowania i opłacalności programów terapeutycznych

Financing of the most expensive drug therapies in Poland. Analysis of the funding level of the therapeutic health programs One of the most discussed topics about organization of the Polish health care system is providing full accessibility to the financing of the latest drug therapies. According to the institutions implementing the programs most serious causes of problems in access to innovative pharmacotherapy are too low level of funding programs and their low profitability, or even hospitals pay the extra to such benefits. Due to the increasingly high cost of treatment of severe illnesses and ongoing development of new medical technologies, in choosing the method of treatment are taken into account the results of economic analyzes. The authors, by analyzing the level of funding and implementation of treatment programs, have attempted to answer the question whether the claims are true, and health care providers and Polish patients have equal access to the most expensive drug therapies? To verify the above hypothesis also performed an cost analysis of selected therapeutic programs. Cost analysis conducted based on the identification and analysis of the costs of four therapeutic health programs indicated that the refund value of National Health Fund for providers implementing health programs may be substantially higher than the costs incurred by them. The current way of financing most expensive innovation therapy has many weaknesses, but most frequently mentioned causes of the problems with the availability of treatment programs are not supported by actual data.