OBJECTIVE: To review the available scientific evidence of perinatal outcome of planned home births and their reflection in the Czech Republic. DESIGN: Review article. SETTING: Institute for the Care of Mother and Child, Prague - Podolí. METHOD: An overview of recently published data. RESULTS: Results of studies that evaluate the safety of planned home births are inconsistent and burdened by methodological limitations (selection bias, the absence of randomized trials, insufficient sample size and the lack of a control group). Evidence of argument that home birth is as safe as hospital birth, are insufficient. Consensual acceptance of home birth is conditioned by the exclusion of individual risk of complications, presence of qualified personnel and availability of emergency transfer to hospital. CONCLUSION: Study of the safety of planned home births are methodologically limited and their results are inconsistent. Currently, there is no professional, organizational and legal framework for the management of planned home births in the Czech Republic.

• MeSH
• bezpečnost MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• medicína založená na důkazech * MeSH
• porod doma * MeSH
• těhotenství MeSH
• výsledek těhotenství MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVES: Democracy-based medicine is a combination of evidence-based medicine (systematic review), expert assessment, and worldwide voting by physicians to express their opinions and self-reported practice via the Internet. The authors applied democracy-based medicine to key trials in critical care medicine. DESIGN AND SETTING: A systematic review of literature followed by web-based voting on findings of a consensus conference. PARTICIPANTS: A total of 555 clinicians from 61 countries. INTERVENTIONS: The authors performed a systematic literature review (via searching MEDLINE/PubMed, Scopus, and Embase) and selected all multicenter randomized clinical trials in critical care that reported a significant effect on survival and were endorsed by expert clinicians. Then they solicited voting and self-reported practice on such evidence via an interactive Internet questionnaire. Relationships among trial sample size, design, and respondents' agreement were investigated. The gap between agreement and use/avoidance and the influence of country origin on physicians' approach to interventions also were investigated. MEASUREMENTS AND MAIN RESULTS: According to 24 multicenter randomized controlled trials, 15 interventions affecting mortality were identified. Wide variabilities in both the level of agreement and reported practice among different interventions and countries were found. Moreover, agreement and reported practice often did not coincide. Finally, a positive correlation among agreement, trial sample size, and number of included centers was found. On the contrary, trial design did not influence clinicians' agreement. CONCLUSIONS: Physicians' clinical practice and agreement with the literature vary among different interventions and countries. The role of these interventions in affecting survival should be further investigated to reduce both the gap between evidence and clinical practice and transnational differences.

• Klíčová slova
• anesthesia, consensus conference, critically ill, intensive care, mortality, survival,
• MeSH
• internacionalita * MeSH
• kritický stav MeSH
• lékaři MeSH
• lidé MeSH
• medicína založená na důkazech metody   MeSH
• mortalita v nemocnicích * MeSH
• multicentrické studie jako téma statistika a číselné údaje   MeSH
• péče o pacienty v kritickém stavu metody   MeSH
• randomizované kontrolované studie jako téma statistika a číselné údaje   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• systematický přehled MeSH

OBJECTIVES: This Grading of Recommendations Assessment, Development and Evaluation (GRADE) concept article offers systematic reviewers, guideline authors, and other users of evidence assistance in addressing randomized trial situations in which interventions or comparators differ from those in the target people, interventions, comparators, and outcomes. To clarify what GRADE considers under indirectness of interventions and comparators, we focus on a particular example: when comparator arm participants receive some or all aspects of the intervention management strategy (treatment switching). STUDY DESIGN AND SETTING: An interdisciplinary panel of the GRADE working group members developed this concept article through an iterative review of examples in multiple teleconferences, small group sessions, and e-mail correspondence. After presentation at a GRADE working group meeting in November 2022, attendees approved the final concept paper, which we support with examples from systematic reviews and individual trials. RESULTS: In the presence of safeguards against risk of bias, trials provide unbiased estimates of the effect of an intervention on the people as enrolled, the interventions as implemented, the comparators as implemented, and the outcomes as measured. Within the GRADE framework, differences in the people, interventions, comparators, and outcomes elements between the review or guideline recommendation targets and the trials as implemented constitute issues of indirectness. The intervention or comparator group management strategy as implemented, when it differs from the target comparator, constitutes one potential source of indirectness: Indirectness of interventions and comparators-comparator group receipt of the intervention constitutes a specific subcategory of said indirectness. The proportion of comparator arm participants that received the intervention and the apparent magnitude of effect bear on whether one should rate down, and if one does, to what extent. CONCLUSION: Treatment switching and other differences between review or guideline recommendation target interventions and comparators vs. interventions and comparators as implemented in otherwise relevant trials are best considered issues of indirectness.

• Klíčová slova
• Applicability, Certainty of evidence, Cross-over, External validity, GRADE, Treatment switching,
• MeSH
• lidé MeSH
• medicína založená na důkazech * MeSH
• randomizované kontrolované studie jako téma * MeSH
• zkreslení výsledků (epidemiologie) * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Background Conducting randomized controlled trials to investigate survival in a rare disease like pulmonary arterial hypertension has considerable ethical and logistical constraints. In many studies, such as the Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN) randomized controlled trial, evaluating survival is further complicated by bias introduced by allowing active therapy among placebo-treated patients who clinically deteriorate. Methods and Results SERAPHIN enrolled and followed patients in the same time frame as the US Registry to Evaluate Early And Long-term PAH Disease Management, providing an opportunity to compare observed survival for SERAPHIN patients with predicted survival had they received real-world treatment as in the Registry to Evaluate Early And Long-term PAH Disease Management. From the Registry to Evaluate Early And Long-term PAH Disease Management (N=3515), 734 patients who met SERAPHIN eligibility criteria were selected and their data used to build a prediction model for time to death up to 3 years based on 10 baseline prognostic variables. The model was used to predict a survival curve for each of the 742 SERAPHIN patients via their baseline variables. The average of these predicted survival curves was compared with observed survival of the placebo (n=250) and macitentan 10 mg (n=242) groups using a log-rank test and Cox proportional hazard model. Observed mortality risk for patients randomized to placebo, 62% of whom were taking background pulmonary arterial hypertension therapy, tended to be lower than that predicted for all SERAPHIN patients (16% lower; P=0.259). The observed placebo survival curve closely approximated the predicted survival curve for the first 15 months. Beyond that time, observed risk of mortality decreased compared with predicted mortality, potentially reflecting the impact of crossover of patients in the placebo group to active therapy. Over 3 years, risk of mortality observed with macitentan 10 mg was 35% lower than predicted mortality ( P=0.010). Conclusions These analyses show that, in a rare disease, real-world observational data can complement randomized controlled trial data to overcome some challenges associated with assessing survival in the setting of a randomized controlled trial. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifiers: NCT00660179 and NCT00370214.

• Klíčová slova
• hypertension, pulmonary, macitentan, prognosis, rare diseases, survival,
• MeSH
• antagonisté endotelinového receptoru škodlivé účinky   terapeutické užití   MeSH
• antihypertenziva škodlivé účinky   terapeutické užití   MeSH
• časové faktory MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• klinické zkoušky, fáze III jako téma MeSH
• lidé středního věku MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• multicentrické studie jako téma MeSH
• plicní arteriální hypertenze diagnóza   farmakoterapie   mortalita   MeSH
• pozorovací studie jako téma MeSH
• příčina smrti MeSH
• progrese nemoci MeSH
• randomizované kontrolované studie jako téma MeSH
• rizikové faktory MeSH
• senioři MeSH
• výsledek terapie MeSH
• vzácné nemoci diagnóza   farmakoterapie   mortalita   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antagonisté endotelinového receptoru MeSH
• antihypertenziva MeSH

There is a large body of evidence documenting the effects of long-chain polyunsaturated fatty acids with the first double bond at the third position from methyl-terminal (so called omega-3 fatty acids (FAs)) on different components of cardiovascular disease (CVD) risk. However, it may seem the more answers on the topic we learn, the more questions remain to be elucidated. There are three levels of evidence documenting the impact of fish omega-3 FAs on CVD risk. Epidemiological data have shown unequivocally the increased intake of fish is associated with lower CVD morbidity and mortality. Numerous experimental studies have shown (almost always) positive effects of omega-3 FAs on lipoprotein metabolism, coagulation and platelet function, endothelial function, arterial stiffness etc. Most importantly, there are a few prospective clinical endpoint trials (DART, JELIS, GISSI Prevenzione and GISSI-HF) that have examined the impact of omega-3 FAs supplementation on cardiovascular outcomes in different patient populations. Recent meta-analyses of these and other clinical studies have yielded somewhat conflicting results. In this review we will summarize current evidence of omega-3 FAs effects on cardiovascular risk focusing on new data from recent clinical trials as well as possible practical implications for clinical practice.

• MeSH
• hodnocení rizik MeSH
• kardiovaskulární nemoci etiologie   metabolismus   prevence a kontrola   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• omega-3 mastné kyseliny aplikace a dávkování   metabolismus   MeSH
• potravní doplňky * MeSH
• rizikové faktory MeSH
• výživová politika MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• omega-3 mastné kyseliny MeSH

CONTEXT: The European Association of Urology (EAU) Guidelines Panel on Upper Urinary Tract Urothelial Carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice. OBJECTIVE: To provide an overview of the EAU guidelines on UTUC as an aid to clinicians. EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using the following keywords: urinary tract cancer; urothelial carcinomas; upper urinary tract, carcinoma; renal pelvis; ureter; bladder cancer; chemotherapy; ureteroscopy; nephroureterectomy; adjuvant treatment; instillation; recurrence; risk factors; and survival. References were weighted by a panel of experts. EVIDENCE SYNTHESIS: Owing to the rarity of UTUC, there are insufficient data to provide strong recommendations (ie, grade A). However, the results of recent multicentre studies are now available, and there is a growing number of retrospective articles in UTUC. The 2017 tumour, node, metastasis (TNM) classification is recommended. Recommendations are given for diagnosis and risk stratification, as well as for radical and conservative treatment; prognostic factors are also discussed. A single postoperative dose of intravesical mitomycin after radical nephroureterectomy reduces the risk of bladder tumour recurrence. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk tumours and two functional kidneys. CONCLUSIONS: These guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours. PATIENT SUMMARY: Urothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis; appropriate diagnosis and management is most important. We present recommendations based on current evidence for optimal management.

• Klíčová slova
• Cytology, Guidelines, Nephroureterectomy, Renal pelvis, Risk factors, Survival, Ureter, Ureteroscopy, Urinary tract cancer, Urothelial carcinoma,
• MeSH
• karcinom diagnóza   mortalita   terapie   MeSH
• klinické rozhodování MeSH
• konsensus MeSH
• lidé MeSH
• medicína založená na důkazech normy   MeSH
• rizikové faktory MeSH
• staging nádorů MeSH
• urologické nádory diagnóza   mortalita   terapie   MeSH
• urologie normy   MeSH
• urotel patologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• směrnice pro lékařskou praxi MeSH

The 2nd Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes and Cardiovascular Disease (D&CVD) EASD Study Group was held on the 20th-21st October 2016 in Munich. This second Summit was organized in light of recently published CVOTs on diabetes, with the aim of serving as a reference meeting for discussion on this topic. Along with presentations on the results of the most recently published CVOTs, panel discussions on trial implications for reimbursement and the perspective of cardiologists and/or nephrologists, as well as on CVOTs weaknesses and potentials constituted the heart of the program. Future activities of the D&CVD EASD Study Group in 2017 include an annual meeting in Milano and the 3rd CVOT Summit on Diabetes of the D&CVD EASD Study Group, in Munich ( http://www.dcvd.org ).

• MeSH
• diabetes mellitus 2. typu komplikace   farmakoterapie   ekonomika   mortalita   MeSH
• hodnocení rizik MeSH
• hypoglykemika škodlivé účinky   ekonomika   terapeutické užití   MeSH
• kardiovaskulární nemoci ekonomika   etiologie   mortalita   prevence a kontrola   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• náklady na léky MeSH
• ochranné faktory MeSH
• rizikové faktory MeSH
• úhrada zdravotního pojištění MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• kongresy MeSH
• úvodníky MeSH
• Názvy látek
• hypoglykemika MeSH

In this systematic review, we report on the effects of diuretic deprescribing compared to continued diuretic use. We included clinical studies reporting on outcomes such as mortality, heart failure recurrence, tolerability and feasibility. We assessed risk of bias and certainty of the evidence using the GRADE framework. We included 25 publications from 22 primary studies (15 randomized controlled trials; 7 nonrandomized studies). The mean number of participants in the deprescribing groups was 35, and median/mean age 64 years. In patients with heart failure, there was no clear evidence that diuretic deprescribing was associated with increased mortality compared to diuretic continuation (low certainty evidence). The risk of cardiovascular composite outcomes associated with diuretic deprescribing was inconsistent (studies showing lower risk for diuretic deprescribing, or comparable risk with diuretic continuation; very low certainty evidence). The effect on heart failure recurrence after diuretic deprescribing in patients with diuretics for heart failure, and of hypertension in patients with diuretics for hypertension was inconsistent across the included studies (low certainty evidence). In patients with diuretics for hypertension, diuretic deprescribing was well tolerated (moderate certainty evidence), while in patients with diuretics for heart failure, deprescribing diuretics can result in complaints of peripheral oedema (very low certainty evidence). The overall risk of bias was generally high. In summary, this systematic review suggests that diuretic discontinuation could be a safe and feasible treatment option for carefully selected patients. However, there isa lack of high-quality evidence on its feasibility, safety and tolerability of diuretic deprescribing, warranting further research.

[Image: see text]

• Klíčová slova
• deprescribing, diuretics, heart failure, hypertension, patient‐relevant outcomes, systematic review,
• MeSH
• depreskripce * MeSH
• diuretika * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• hypertenze farmakoterapie   MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• randomizované kontrolované studie jako téma MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• srdeční selhání * farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH
• Názvy látek
• diuretika * MeSH

The authors trace the history of metformin and its clinical use to the present day. Recent insights into its mode of action and latest data from experimental and clinical medicine have unraveled novel properties of metformin, which may be particularly useful in the treatment of conditions other than diabetes. Results of ongoing clinical trials will show whether or not the hypoglycemic effect of metformin will become only one of the many to be employed in clinical practice.

• MeSH
• aplikace orální MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• hmotnostní úbytek účinky léků   MeSH
• hodnocení rizik MeSH
• hypoglykemika aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• metformin aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• rizikové faktory MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• hypoglykemika MeSH
• metformin MeSH

The introduction of PD-1/PD-L1 pathway inhibitors is an important landmark in solid oncology with unprecedented practice-changing activity in various types of solid tumours. Among haematological malignancies, PD-1/PD-L1 inhibitors have been successful, so far, only in the treatment of classical Hodgkin lymphoma, which typically exhibits an over-expression of PD-1 ligands (PD-L1, PD-L2) due to alterations in chromosome 9p24.1. Such positive outcomes led to the US Food and Drug Administration approval of nivolumab use in relapsed Hodgkin lymphoma in 2016 as the first haematological indication. Although the results in other lymphoid malignancies have not been so striking, blockade of the PD-1/PD-L1 axis has led to meaningful responses in other lymphoma types such as diffuse large B-cell lymphoma, follicular lymphoma or several T-cell lymphomas. Monotherapy with PD-1/PD-L1 inhibitors in chronic lymphocytic leukaemia and multiple myeloma has been unsatisfactory, suggesting that a combinational approach with other synergistic drugs is needed. In the case of multiple myeloma, immunomodulatory agents together with corticosteroids represent the most promising combinations. Among myeloid malignancies, the anti-PD-1 monoclonal antibodies are examined dominantly in acute myeloid leukaemia and myelodysplastic syndromes in combination with potentially synergistic hypomethylating drugs such as 5-azacitidine, resulting in promising outcomes that warrant further investigation. We have described all available clinical results of PD-1/PD-L1 inhibitors in haematological malignancies and discussed related toxicities, as well as highlighted crucial preclinical studies in this review.

• Klíčová slova
• haematological malignancy, myeloma, nivolumab, pembrolizumab, programmed death 1 receptor,
• MeSH
• antigeny CD274 antagonisté a inhibitory   imunologie   metabolismus   MeSH
• antigeny CD279 antagonisté a inhibitory   imunologie   metabolismus   MeSH
• cílená molekulární terapie MeSH
• hematologické nádory farmakoterapie   imunologie   metabolismus   patologie   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• protinádorové látky škodlivé účinky   terapeutické užití   MeSH
• signální transdukce účinky léků   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigeny CD274 MeSH
• antigeny CD279 MeSH
• CD274 protein, human MeSH Prohlížeč
• PDCD1 protein, human MeSH Prohlížeč
• protinádorové látky MeSH