The strategy for the development of new drugs for Alzheimer's disease (AD) recognizes that an effective therapy requires early therapeutic intervention and a multifactorial approach that considers the individual initiators of AD development. Current knowledge of AD includes the understanding of pathophysiology, risk factors, biomarkers, and the evolving patterns of biomarker abnormalities. This knowledge is essential in identifying potential molecular targets for new drug development. This review summarizes promising AD drug candidates, many of which are currently in phase 2 or 3 clinical trials. New agents are classified according to the Common Alzheimer's Disease Research Ontology (CADRO). The main targets of new drugs for AD are processes related to amyloid beta and tau neurotoxicity, neurotransmission, inflammation, metabolism and bioenergetics, synaptic plasticity, and oxidative stress. These interventions are aimed at preventing disease onset and slowing or eliminating disease progression. The efficacy of pharmacotherapy may be enhanced by combining these drugs with other treatments, antioxidants, and dietary supplements. Ongoing research into AD pathophysiology, risk factors, biomarkers, and the dynamics of biomarker abnormalities may contribute to the understanding of AD and offer hope for effective therapeutic strategies in the near future.
- MeSH
- Alzheimerova nemoc * metabolismus farmakoterapie MeSH
- biologické markery * metabolismus MeSH
- klinické zkoušky jako téma * metody MeSH
- lidé MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical for clinical evaluation of the benefits and limits of helminth therapy.
- MeSH
- cizopasní červi fyziologie MeSH
- helmintoterapie * MeSH
- klinické zkoušky jako téma metody MeSH
- lidé MeSH
- samoléčba MeSH
- výzkumný projekt * trendy MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Deep transcranial magnetic stimulation (dTMS) is a modern non-invasive brain stimulation method demonstrated as effective in the treatment of major depression and obsessive-compulsive disorder (OCD). This review aims to survey present knowledge concerning the cognitive function changes identified in dTMS research. A systematic literature search in PubMed and Google Scholar was performed and 23 out of 64 studies on dTMS and cognitive functioning were included in the review. Ten studies were conducted with patients with affective disorders, six with healthy participants, two with schizophrenia patients, two with OCD patients, and one study each with patients suffering from central neuropathic pain, autistic disorder, and attention deficit hyperactivity disorder. The best outcomes were obtained after 20 sessions of high-frequency dTMS with OCD patients, where, in addition to clinical improvement, patients showed amelioration of cognitive functions, specifically in cognitive control domains. The studies on patients with depression appear to show inconsistent results, from cognitive improvement in open-label studies to no improvement versus sham dTMS in controlled trials. Experimental research in healthy volunteers suggests an influence of dTMS on memory and self-agency, and also contain contradictory results. Most studies did not demonstrate a significant improvement in cognitive functioning. However, randomized sham-controlled trials with larger groups of medication-free patients and inclusion of functional imaging or electrophysiological recording connected with dTMS application are necessary for more detailed and confident conclusions concerning the effect of dTMS on cognitive functions.
- MeSH
- duševní poruchy psychologie terapie MeSH
- klinické zkoušky jako téma metody MeSH
- kognice fyziologie MeSH
- lidé MeSH
- transkraniální magnetická stimulace metody trendy MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- systematický přehled MeSH
- MeSH
- bcr-abl fúzové proteiny genetika MeSH
- časové faktory MeSH
- chronická myeloidní leukemie farmakoterapie genetika patologie MeSH
- indukce remise MeSH
- inhibitory proteinkinas škodlivé účinky MeSH
- klinické zkoušky jako téma metody MeSH
- lidé MeSH
- lokální recidiva nádoru chemicky indukované diagnóza epidemiologie MeSH
- nenasazení léčby statistika a číselné údaje MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
The number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients keeps rising in most of the European countries despite the pandemic precaution measures. The current antiviral and anti-inflammatory therapeutic approaches are only supportive, have limited efficacy, and the prevention in reducing the transmission of SARS-CoV-2 virus is the best hope for public health. It is presumed that an effective vaccination against SARS-CoV-2 infection could mobilize the innate and adaptive immune responses and provide a protection against severe forms of coronavirus disease 2019 (COVID-19) disease. As the race for the effective and safe vaccine has begun, different strategies were introduced. To date, viral vector-based vaccines, genetic vaccines, attenuated vaccines, and protein-based vaccines are the major vaccine types tested in the clinical trials. Over 80 clinical trials have been initiated; however, only 18 vaccines have reached the clinical phase II/III or III, and 4 vaccine candidates are under consideration or have been approved for the use so far. In addition, the protective effect of the off-target vaccines, such as Bacillus Calmette-Guérin and measles vaccine, is being explored in randomized prospective clinical trials with SARS-CoV-2-infected patients. In this review, we discuss the most promising anti-COVID-19 vaccine clinical trials and different vaccination strategies in order to provide more clarity into the ongoing clinical trials.
Bipolar disorder (BD) is a major healthcare and socio-economic challenge. Despite its substantial burden on society, the research activity in BD is much smaller than its economic impact appears to demand. There is a consensus that the accurate identification of the underlying pathophysiology for BD is fundamental to realize major health benefits through better treatment and preventive regimens. However, to achieve these goals requires coordinated action and innovative approaches to boost the discovery of the neurobiological underpinnings of BD, and rapid translation of research findings into development and testing of better and more specific treatments. To this end, we here propose that only a large-scale coordinated action can be successful in integrating international big-data approaches with real-world clinical interventions. This could be achieved through the creation of a Global Bipolar Disorder Foundation, which could bring government, industry and philanthropy together in common cause. A global initiative for BD research would come at a highly opportune time given the seminal advances promised for our understanding of the genetic and brain basis of the disease and the obvious areas of unmet clinical need. Such an endeavour would embrace the principles of open science and see the strong involvement of user groups and integration of dissemination and public involvement with the research programs. We believe the time is right for a step change in our approach to understanding, treating and even preventing BD effectively.
- MeSH
- big data * MeSH
- bipolární porucha diagnóza epidemiologie terapie MeSH
- celosvětové zdraví * MeSH
- klinické zkoušky jako téma metody MeSH
- lidé MeSH
- strojové učení trendy MeSH
- translační biomedicínský výzkum metody trendy MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
EMPA-REG OUTCOME is recognised by international guidelines as a landmark study that showed a significant cardioprotective benefit with empagliflozin in patients with type 2 diabetes (T2D) and cardiovascular disease. To assess the impact of empagliflozin in routine clinical practice, the ongoing EMPRISE study is collecting real-world evidence to compare effectiveness, safety and health economic outcomes between empagliflozin and DPP-4 inhibitors. A planned interim analysis of EMPRISE was recently published, confirming a substantial reduction in hospitalisation for heart failure with empagliflozin across a diverse patient population. In this commentary article, we discuss the new data in the context of current evidence and clinical guidelines, as clinicians experienced in managing cardiovascular risk in patients with T2D. We also look forward to what future insights EMPRISE may offer, as evidence is accumulated over the next years to complement the important findings of EMPA-REG OUTCOME.
- MeSH
- benzhydrylové sloučeniny škodlivé účinky terapeutické užití MeSH
- diabetes mellitus 2. typu diagnóza farmakoterapie mortalita MeSH
- glifloziny škodlivé účinky terapeutické užití MeSH
- glukosidy škodlivé účinky terapeutické užití MeSH
- hodnocení rizik MeSH
- hospitalizace MeSH
- kardiovaskulární nemoci diagnóza mortalita terapie MeSH
- klinické rozhodování MeSH
- klinické zkoušky jako téma metody MeSH
- lékařská praxe - způsoby provádění MeSH
- lidé MeSH
- medicína založená na důkazech * MeSH
- ochranné faktory MeSH
- rizikové faktory MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- výsledek terapie MeSH
- výzkumný projekt * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The last decade has witnessed developments in the CF drug pipeline which are both exciting and unprecedented, bringing with them previously unconsidered challenges. The Task Force group was brought together to consider these challenges and possible strategies to address them. Over the last 18 months, we have discussed internally and gathered views from a broad range of individuals representing patient organisations, clinical and research teams, the pharmaceutical industry and regulatory agencies. In this and the accompanying article, we discuss two main areas of focus: i) optimising trial design and delivery for speed and efficiency; ii) drug development for patients with rare CFTR mutations. We propose some strategies to tackle the challenges ahead and highlight areas where further thought is needed. We see this as the start of a process rather than the end and hope herewith to engage the wider community in seeking solutions to improved treatments for all patients with CF.
- MeSH
- cystická fibróza farmakoterapie genetika MeSH
- klinické zkoušky jako téma * metody normy MeSH
- lidé MeSH
- modulátory membránového transportu farmakologie MeSH
- mutace MeSH
- objevování léků * metody trendy MeSH
- protein CFTR genetika MeSH
- vyvíjení léků * organizace a řízení normy MeSH
- výzkumný projekt normy MeSH
- zlepšení kvality MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The 4th Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group was held in Munich on 25-26 October 2018. As in previous years, this summit served as a reference meeting for in-depth discussions on the topic of recently completed and presented CVOTs. This year, focus was placed on the CVOTs CARMELINA, DECLARE-TIMI 58 and Harmony Outcomes. Trial implications for diabetes management and the impact of the new ADA/EASD consensus statement treatment algorithm were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists and general practitioners. Discussions evolved from CVOTs to additional therapy options for heart failure (ARNI), knowledge gained for adjunct therapy of type 1 diabetes and, on the occasion of the 10 year anniversary of the FDA's "Guidance for Industry: "should CVOTs be continued and/or modified?" The 5th Cardiovascular Outcome Trial Summit will be held in Munich on 24-25 October 2019 ( http://www.cvot.org ).
- MeSH
- biomedicínský výzkum metody normy MeSH
- diabetes mellitus diagnóza farmakoterapie epidemiologie MeSH
- endokrinologie metody normy MeSH
- hypoglykemika škodlivé účinky terapeutické užití MeSH
- kardiologie metody normy MeSH
- kardiovaskulární nemoci diagnóza epidemiologie terapie MeSH
- klinické zkoušky jako téma metody normy MeSH
- kooperační chování MeSH
- lidé MeSH
- mezioborová komunikace MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kongresy MeSH
