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.
- 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
- přehledy MeSH
- systematický přehled MeSH
BACKGROUND: Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea. METHODS: Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea. We will exclude patients with ongoing sepsis, need of systemic antibiotics, or those after recent bowel surgery or any other reason that prevents the FMT. Randomisation will be in 1:1 ratio. Patients in the control group will receive standard treatment based on oral diosmectite. In the intervention group, patients will receive, in addition to the standard of care, faecal microbiota transplantation via rectal tube, in the form of a preparation mixed from 7 thawed aliquots (50 mL) made from fresh stool of 7 healthy unrelated donors and quarantined deep frozen for 3 to 12 months. Primary outcome is treatment failure defined as intervention not delivered or diarrhoea persisting at day 7 after randomisation. Secondary outcomes include safety measures such as systemic inflammatory response, adverse events, and also diarrhoea recurrence within 28 days. Exploratory outcomes focus on gut barrier function and composition of intestinal microbiota. DISCUSSION: Faecal microbiota transplantation has been effective for dysbiosis in non-critically ill patients with recurrent C. difficile infections and it is plausible to hypothesize that it will be equally effective for symptoms of dysbiosis in the critically ill patients. In addition, animal experiments and observational data suggest other benefits such as reduced colonization with multi-drug resistant bacteria and improved gut barrier and immune function. The frozen faeces from unrelated donors are immediately available when needed, unlike those from the relatives, who require lengthy investigation. Using multiple donors maximises graft microbiota diversity. Nonetheless, in vulnerable critically ill patients, Faecal microbiota transplantation might lead to bacterial translocation and unforeseen complications. From growing number of case series it is clear that its off label use in the critically ill patients is increasing and that there is a burning need to objectively assess its efficacy and safety, which this trial aims. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT05430269).
- MeSH
- antibakteriální látky * škodlivé účinky terapeutické užití MeSH
- dysbióza terapie mikrobiologie MeSH
- feces mikrobiologie MeSH
- fekální transplantace * metody škodlivé účinky MeSH
- klinické zkoušky, fáze II jako téma MeSH
- kritický stav * MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- prospektivní studie MeSH
- průjem * terapie mikrobiologie MeSH
- randomizované kontrolované studie jako téma MeSH
- střevní mikroflóra * účinky léků MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
PURPOSE: The AIEOP-BFM ALL 2009 protocol included, at the end of the induction phase, a randomized study of patients with high-risk (HR) ALL to investigate if an intensive exposure to pegylated L-asparaginase (PEG-ASNASE, 2,500 IU/sqm once a week × 4) on top of BFM consolidation phase IB allowed us to decrease minimal residual disease (MRD) and improve outcome. PATIENTS AND METHODS: A total of 1,097 patients presented, from June 2010 to February 2017, with one or more of the following HR criteria: KMT2A::AFF1 rearrangement, hypodiploidy, prednisone poor response, poor bone marrow response at day 15 (Flow MRD ≥10%), or no complete remission (CR) at the end of induction. Of them, 809 (85.1%) were randomly assigned to receive (404) or not receive (405) four weekly doses of PEG-ASNASE. RESULTS: By intention to treat (ITT) analysis, there was no significant difference in the proportion of patients with polimerase chain reaction MRD ≥5 × 10-4 at the end of phase IB in the experimental versus control arm (13.9% v 17.0%, P = .25). The 5-year event-free survival (median follow-up 6.3 years) by ITT in the experimental and control arms was 70.4% (2.3) versus 75.0% (2.2; P = .18), and the 5-year overall survival was 81.5% (2.0) versus 84.0% (1.9; P = .25), respectively. The corresponding 5-year cumulative incidence of death in CR was 9.5% (1.5) versus 5.7% (1.2; P = .08), and that of relapse was 17.7% (1.9) versus 17.2% (1.9), respectively (P = .94). Adverse reactions in phase IB occurred in 22.2% and 8.9% of patients in the experimental and control arm, respectively (P < .001). CONCLUSION: Additional PEG-ASNASE in phase IB did not translate into a benefit for decreasing relapse incidence but was associated with higher toxicity. Further improvements with conventional chemotherapy might be difficult in the context of intensive treatment protocols.
- MeSH
- akutní lymfatická leukemie * MeSH
- asparaginasa * MeSH
- kojenec MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- polyethylenglykoly MeSH
- prednison škodlivé účinky MeSH
- přežití po terapii bez příznaků nemoci MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- randomizované kontrolované studie jako téma MeSH
- recidiva MeSH
- výsledek terapie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
BACKGROUND: The fear of taking away hope hinders clinicians' willingness to share serious news with patients with advanced disease. Unrealistic illness expectations, on the other hand, can complicate decision making and end-of-life care outcomes. Exploration of the association between hope and illness expectations can support clinicians in better communication with their patients. AIM: The aim of this study was to explore whether realistic illness expectations are associated with reduced hope in people with advanced cancer. DESIGN: This is a cross-sectional secondary analysis of baseline data from a primary palliative care cluster-randomized trial CONNECT (data collected from July 2016 to October 2020). Hope was measured by Herth Hope Index. Illness expectations were measured by assessing patients' understanding of their treatment goals, life expectancy, and terminal illness acknowledgement. Multivariable regression was performed, adjusting for demographical and clinical confounders. SETTING/PARTICIPANTS: Adult patients with advanced solid cancers recruited across 17 oncology clinics. RESULTS: Data from 672 patients were included in the study, with mean age of 69.3 years (±10.2), 53.6% were female. Proportion of patients indicating realistic expectations varied based on which question was asked from 10% to 46%. Median level of hope was 39 (IQR = 36-43). Multivariate non-inferiority regression did not find any significant differences in hope between patients with more and less realistic illness expectations. CONCLUSIONS: Our results suggest that hope can be sustained while holding both realistic and unrealistic illness expectations. Communication about serious news should focus on clarifying the expectations as well as supporting people's hopes.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- motivace MeSH
- naděje MeSH
- nádory * terapie MeSH
- paliativní péče metody MeSH
- péče o umírající * MeSH
- průřezové studie MeSH
- randomizované kontrolované studie jako téma MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
CONTEXT: The optimal therapeutic agent with respect to metastatic sites is unclear in advanced urothelial carcinoma (UC). OBJECTIVE: To investigate the metastatic organotropism differential treatment response in patients with advanced or metastatic UC. EVIDENCE ACQUISITION: A systematic search and network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The primary endpoints of interest were the objective response rate, overall survival (OS), and progression-free survival with respect to different metastatic sites. EVIDENCE SYNTHESIS: Twenty-six trials comprising 9082 patients met our eligibility criteria, and a formal NMA was conducted. Durvalumab plus tremelimumab as first-line systemic therapy was significantly associated with better OS than chemotherapy in visceral metastasis (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.67-0.98). Pembrolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with visceral metastasis (HR 0.75, 95% CI 0.60-0.95). Atezolizumab as second-line systemic therapy was significantly associated with better OS than chemotherapy in patients with liver metastasis (in the population of >5% of tumor-infiltrating immune cells) and lymph node metastasis (HR 0.51, 95% CI 0.28-0.96, and HR 0.59, 95% CI 0.37-0.96, respectively). CONCLUSIONS: Administration of immune-oncology treatments with respect to metastatic sites in patients with advanced or metastatic UC might have a positive impact on survival outcomes in both the first- and the second-line setting. Nevertheless, further investigations focusing on metastatic organotropism differential response with reliable oncological outcomes are needed to identify the optimal management strategy for these patients. PATIENT SUMMARY: Although the supporting evidence for oncological benefits of therapeutic systemic agents with respect to metastatic sites is not yet strong enough to provide a recommendation in advanced or metastatic urothelial carcinoma, clinicians may take into account tumor organotropism only in discussion with the patient fully informed on the optimal treatment decision to be taken.
- MeSH
- karcinom z přechodných buněk * farmakoterapie sekundární mortalita patologie MeSH
- lidé MeSH
- metastázy nádorů MeSH
- randomizované kontrolované studie jako téma * MeSH
- síťová metaanalýza * MeSH
- urologické nádory farmakoterapie patologie mortalita MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
Very low carbohydrate high fat (VLCHF) diet and high-intensity interval training (HIIT) are widely utilized for weight reduction and cardiorespiratory fitness improvement, respectively. To assess the acceptability of these approaches, it is essential to examine mental health-related indicators. This secondary analysis of a randomized controlled trial investigated the isolated and synergistic effects of VLCHF and HIIT on mental health-related indicators in individuals with excessive weight or obesity. Sixty-eight participants (age = 42 ± 10.2; 20-60 years; BMI = 29.8 ± 3.7) were analysed across four groups: HIIT (n = 15, 4 males, 11 females), VLCHF (n = 19, 4 males, 15 females), VLCHF + HIIT (n = 19, 4 males, 15 females), and control (n = 15, 4 males, 11 females). The 12-week intervention, involved VLCHF diet or HIIT sessions, depending on group affiliation and completing online questionnaires via Qualtrics software before and after the intervention. The questionnaires included the 12-item Short Form Survey (SF-12) for mental (MHS) and physical health scores (PHS), the Satisfaction with Life Scale (SWLS), and the Perceived Stress Scale (PSS). Using the Kruskal-Wallis test, we found no significant differences in mental health-related indicators between groups after 12 weeks, except for SWLS (p = 0.031; ES = 0.133; medium), which improved significantly in the VLCHF + HIIT group compared to the HIIT group. Our findings indicate that HIIT and VLCHF, alone or combined, do not significantly affect mental health-related indicators.
- MeSH
- dieta s omezením sacharidů * metody MeSH
- dieta s vysokým obsahem tuků * škodlivé účinky MeSH
- dospělí MeSH
- duševní zdraví * MeSH
- hmotnostní úbytek MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- obezita * MeSH
- randomizované kontrolované studie jako téma MeSH
- vysoce intenzivní intervalový trénink * metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: An inverse relationship between vitamin D supplementation and C-reactive protein (CRP) and hypertension has been reported, mostly through observational data. This inverse relationship, however, has not been confirmed in randomized controlled trials (RCTs). A meta-analysis of RCTs is needed to provide more robust evidence. OBJECTIVE: This systematic review of RCTs was conducted to assess the effect of vitamin D supplementation on CRP, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in postmenopausal women. METHODS: Four databases (PubMed, Web of Science, Embase, and Scopus) were systemically searched to identify relevant RCTs published in international scientific journals up to January 2023. Changes from baseline and SDs of CRP, SBP, and DBP were compared between postmenopausal women who received vitamin D supplementation and those who did not (controls). These parameters were applied to compute the overall effect sizes using the random-effects model. Data were summarized as mean difference (MD) with 95% CI. Heterogeneity among arms was scrutinized using the Cochrane's Q test and I2 statistic. Publication bias was judged by means of funnel plots and Egger's test. RESULTS: Seven studies with 6 arms on CRP, 6 arms on SBP, and 6 arms on DBP were included in the meta-analysis. Combined effect sizes suggested a significant effect of vitamin D supplementation on CRP (MD = -0.65 mg/L; 95% CI -0.93 to -0.37 mg/L; P < .001). In addition, CRP concentrations were significantly reduced after vitamin D supplementation in studies with a duration of more than 3 months (MD = -0.91 mg/L; 95% CI -1.37 to -0.45 mg/L; P < .001) and studies involving doses of ≤1,000 IU/d (MD = -2.10 mg/L; 95% CI -2.51 to -1.68 mg/L; P < .001). Vitamin D supplementation did not reduce SBP significantly (MD = -1.06 mm Hg; 95% CI -2.43 to 0.30 mm Hg; P = .127) and DBP (MD = 0.003 mm Hg; 95% CI -0.86 to 0.86 mm Hg; P = .994) levels compared with control groups. CONCLUSIONS: This meta-analysis concluded that vitamin D supplementation is associated with reduced CRP concentrations among postmenopausal women.
Cardiogenic shock (CS) is a devastating and fatal complication of acute myocardial infarction (AMI). CS can affect the pharmacokinetics and pharmacodynamics of medications. The unique properties of cangrelor make it the optimal P2Y12 inhibitor for CS-AMI, in terms of both efficacy and safety. The DAPT-SHOCK-AMI trial (ClinicalTrials.gov: NCT03551964; EudraCT: 2018-002161-19) will assess the benefits of cangrelor in patients with an initial CS-AMI undergoing primary angioplasty. This randomised, multicentre, placebo-controlled trial of approximately 550 patients (with an allowed 10% increase) in 5 countries using a double-blind design will compare initial P2Y12 inhibitor treatment strategies in patients with CS-AMI of (A) intravenous cangrelor and (B) ticagrelor administered as crushed tablets at a loading dose of 180 mg. The primary clinical endpoint is a composite of all-cause death, myocardial infarction (MI), or stroke within 30 days. The main secondary endpoints are (1) the net clinical endpoint, defined as death, MI, urgent revascularisation of the infarct-related artery, stroke, or major bleeding as defined by the Bleeding Academic Research Consortium criteria; (2) cardiovascular-related death, MI, urgent revascularisation, or heart failure; (3) heart failure; and (4) cardiovascular-related death, all (1-4) within 1 year after study enrolment. A platelet reactivity study that tests the laboratory antiplatelet benefits of cangrelor, when given in addition to standard antiplatelet therapy, will be conducted using vasodilator-stimulated phosphoprotein phosphorylation. The primary laboratory endpoints are the periprocedural rate of onset and the proportion of patients who achieve effective P2Y12 inhibition. The DAPT-SHOCK-AMI study is the first randomised trial to evaluate the benefits of cangrelor in patients with CS-AMI.
- MeSH
- adenosinmonofosfát * analogy a deriváty terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- dvojitá slepá metoda MeSH
- fosfoproteiny MeSH
- infarkt myokardu * komplikace MeSH
- inhibitory agregace trombocytů * škodlivé účinky terapeutické užití aplikace a dávkování MeSH
- kardiogenní šok * mortalita MeSH
- koronární angioplastika škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- purinergní receptory P2Y - antagonisté aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- senioři MeSH
- ticagrelor * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
BACKGROUND: The CLASSIC trial assessed the effects of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock. This pre-planned study provides a probabilistic interpretation and evaluates heterogeneity in treatment effects (HTE). METHODS: We analysed mortality, serious adverse events (SAEs), serious adverse reactions (SARs) and days alive without life-support within 90 days using Bayesian models with weakly informative priors. HTE on mortality was assessed according to five baseline variables: disease severity, vasopressor dose, lactate levels, creatinine values and IV fluid volumes given before randomisation. RESULTS: The absolute difference in mortality was 0.2%-points (95% credible interval: -5.0 to 5.4; 47% posterior probability of benefit [risk difference <0.0%-points]) with restrictive IV fluid. The posterior probabilities of benefits with restrictive IV fluid were 72% for SAEs, 52% for SARs and 61% for days alive without life-support. The posterior probabilities of no clinically important differences (absolute risk difference ≤2%-points) between the groups were 56% for mortality, 49% for SAEs, 90% for SARs and 38% for days alive without life-support. There was 97% probability of HTE for previous IV fluid volumes analysed continuously, that is, potentially relatively lower mortality of restrictive IV fluids with higher previous IV fluids. No substantial evidence of HTE was found in the other analyses. CONCLUSION: We could not rule out clinically important effects of restrictive IV fluid therapy on mortality, SAEs or days alive without life-support, but substantial effects on SARs were unlikely. IV fluids given before randomisation might interact with IV fluid strategy.
- MeSH
- Bayesova věta MeSH
- dospělí MeSH
- jednotky intenzivní péče MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- septický šok * terapie MeSH
- tekutinová terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- cystektomie metody MeSH
- lidé MeSH
- nádory močového měchýře * chirurgie patologie MeSH
- prospektivní studie MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
