The effects of diuretic deprescribing in adult patients: A systematic review to inform an evidence-based diuretic deprescribing guideline.

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.

Allocation and value of curative oncological treatment in frail and fit older patients with esophageal cancer: An observational cohort study.

INTRODUCTION: The Value-Based Health Care (VBHC) model of care provides insights into patient characteristics, outcomes, and costs of care delivery that help clinicians counsel patients. This study compares the allocation and value of curative oncological treatment in frail and fit older patients with esophageal cancer in a dedicated VBHC pathway. MATERIALS AND METHODS: Data was collected from patients with primary esophageal cancer without distant metastases, aged 70 years or older, and treated at a Dutch tertiary care hospital between 2015 and 2019. Geriatric assessment (GA) was performed. Outcomes included treatment discontinuation, mortality, quality of life (QoL), and physical functioning over a one-year period. Direct hospital costs were estimated using activity-based costing. RESULTS: In this study, 89 patients were included with mean age 75 years. Of 56 patients completing GA, 19 were classified as frail and 37 as fit. For frail patients, the treatment plan was chemoradiotherapy and surgery (CRT&S) in 68% (13/19) and definitive chemoradiotherapy (dCRT) in 32% (6/19); for fit patients, CRT&S in 84% (31/37) and dCRT in 16% (6/37). Frail patients discontinued chemotherapy more often than fit patients (26% (5/19) vs 11% (4/37), p = 0.03) and reported lower QoL after six months (mean 0.58 [standard deviation (SD) 0.35] vs 0.88 [0.25], p < 0.05). After one year, 11% of frail and 30% of fit patients reported no decline in physical functioning and QoL and survived. Frail and fit patients had comparable mean direct hospital costs (€24 K [SD €13 K] vs €23 K [SD €8 K], p = 0.82). DISCUSSION: The value of curative oncological treatment was lower for frail than for fit patients because of slightly worse outcomes and comparable costs. The utility of the VBHC model of care depends on the availability of sufficient data. Real-world evidence in VBHC can be used to inform treatment decisions and optimization in future patients by sharing results and monitoring performance over time. TRIAL REGISTRATION: The study was retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107 (date of registration: 22-10-2019).

Impact of COVID-19 Treatment on Real-World Outcomes in Inflammatory Bowel Disease.

BACKGROUND: While there are multiple safe and effective agents for COVID-19 treatment, their impact in inflammatory bowel disease (IBD) remains uncertain. AIMS: Our objective was to assess the effects of these therapies on both IBD and COVID outcomes. METHODS: A single-center retrospective study of adult patients with IBD who contracted COVID-19 between 12/2020 and 11/2022 was performed. Patients were stratified by COVID-19 treatment (antivirals and/or intravenous antibodies) vs no therapy. The primary outcome was the development of severe COVID-19 infection, defined by need for supplemental oxygen, corticosteroids and/or antibiotics, or hospitalization. Secondary outcomes included rates of withholding advanced IBD therapy (defined as biologic agents or small molecules) and of post-COVID-19 IBD flare. RESULTS: Of 127 patients with COVID-19 infection, 70% were on advanced therapies, 35% received COVID-19 treatment, and 15% developed severe COVID-19. Those treated for COVID-19 were more likely to be on corticosteroids [odds ratio (OR) 4.61, 95% confidence interval (CI) 1.72-12.39, p = 0.002] or advanced IBD therapies (OR 2.78, 95% CI 1.04-7.43, p = 0.041). After adjusting for age, race, sex, corticosteroid use, obesity, COVID-19 vaccination status, and severe COVID-19 infection, those treated for COVID-19 were more likely to have IBD therapy held (OR 6.95, 95% CI 1.72-28.15, p = 0.007). There was no significant difference in rates of post-COVID-19 IBD flares or severe COVID-19 infection. There were no COVID-related deaths. CONCLUSIONS: Patients with IBD on advanced therapies were frequently treated for acute COVID-19. Although COVID-19 treatment was associated with temporary withholding of IBD therapy, it did not result in increased IBD flares.

The effect of antibiotic therapy for Clostridioides difficile infection on mortality and other patient-relevant outcomes: a systematic review and meta-analysis.

BACKGROUND: Current practice guidelines favour fidaxomicin over vancomycin and exclude metronidazole from the recommended standard regimen for Clostridioides difficile infection (CDI), based on lower recurrence rates with fidaxomicin, giving little weight to mortality or the clinical implications of recurrences. OBJECTIVES: To compile the effects of metronidazole, glycopeptides (vancomycin or teicoplanin), and fidaxomicin for CDI on mortality and other patient-relevant outcomes. DATA SOURCES: PubMed, the Cochrane Library, ClinicalTrials.gov, conference proceedings, and Google Scholar, until August 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs). PARTICIPANTS: Adult patients experiencing primary or recurrent CDI. INTERVENTIONS: Glycopeptides versus fidaxomicin or metronidazole (comparators). ASSESSMENT OF RISK OF BIAS: We used the Risk of Bias 2 (RoB 2) tool for randomized trials, focusing on the outcome of all-cause mortality. METHODS OF DATA SYNTHESIS: Random effects meta-analyses were performed for dichotomous outcomes. Outcomes were summarized preferentially for all randomly assigned patients. RESULTS: Thirteen trials were included. There was no significant difference in all-cause mortality (risk ratio [RR] < 1 favouring the comparator) between vancomycin and fidaxomicin (RR 0.86, 95% CI 0.64-1.14, 8 RCTs, 1951 patients) or metronidazole (RR 0.78, 95% CI 0.46-1.32, 4 RCTs, 808 patients), with low and very low certainty of evidence, respectively. No significant difference in initial treatment failure between fidaxomicin and vancomycin was found, however, initial treatment failure was higher with metronidazole (RR 1.58, 95% CI 1.10-2.27, 5 RCTs, 843 patients). No study reported on symptomatic recurrence necessitating re-treatment among all randomly assigned patients. Among initially cured patients, symptomatic recurrence necessitating re-treatment was lower with fidaxomicin than with vancomycin (RR 0.54, 95% CI 0.42-0.71, 6 RCTs, 1617 patients). None of the studies reported on other CDI complications or the burden of infection on daily activities. CONCLUSIONS: Setting patient-relevant outcomes for CDI independently of the RCT definitions and results might lead to less confidence in the guidance for CDI management.

The effectiveness of clinical guideline implementation strategies in oncology-a systematic review.

IMPORTANCE: Guideline recommendations do not necessarily translate into changes in clinical practice behaviour or better patient outcomes. OBJECTIVE: This systematic review aims to identify recent clinical guideline implementation strategies in oncology and to determine their effect primarily on patient-relevant outcomes and secondarily on healthcare professionals' adherence. METHODS: A systematic search of five electronic databases (PubMed, Web of Science, GIN, CENTRAL, CINAHL) was conducted on 16 december 2022. Randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) assessing the effectiveness of guideline implementation strategies on patient-relevant outcomes (overall survival, quality of life, adverse events) and healthcare professionals' adherence outcomes (screening, referral, prescribing, attitudes, knowledge) in the oncological setting were targeted. The Cochrane risk-of-bias tool and the ROBINS-I tool were used for assessing the risk of bias. Certainty in the evidence was evaluated according to GRADE recommendations. This review was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42021268593. FINDINGS: Of 1326 records identified, nine studies, five cluster RCTs and four controlled before-and after studies, were included in the narrative synthesis. All nine studies assess the effect of multi-component interventions in 3577 cancer patients and more than 450 oncologists, nurses and medical staff. PATIENT-LEVEL: Educational meetings combined with materials, opinion leaders, audit and feedback, a tailored intervention or academic detailing may have little to no effect on overall survival, quality of life and adverse events of cancer patients compared to no intervention, however, the evidence is either uncertain or very uncertain. PROVIDER-LEVEL: Multi-component interventions may increase or slightly increase guideline adherence regarding screening, referral and prescribing behaviour of healthcare professionals according to guidelines, but the certainty in evidence is low. The interventions may have little to no effect on attitudes and knowledge of healthcare professionals, still, the evidence is very uncertain. CONCLUSIONS AND RELEVANCE: Knowledge and skill accumulation through team-oriented or online educational training and dissemination of materials embedded in multi-component interventions seem to be the most frequently researched guideline implementation strategies in oncology recently. This systematic review provides an overview of recent guideline implementation strategies in oncology, encourages future implementation research in this area and informs policymakers and professional organisations on the development and adoption of implementation strategies.

The prognostic value of quality of life in atrial fibrillation on patient value.

BACKGROUND: In this study, the prognostic value of AF-related quality of life (AFEQT) at baseline on Major Adverse Cardiovascular Events (MACE) and improvement of perceived symptoms (EHRA) was assessed. Furthermore, the relationship between QoL and AF-related hospitalizations was assessed. METHODS: A cohort of AF-patients diagnosed between November 2014 and October 2019 in four hospitals embedded within the Netherlands Heart Network were prospectively followed for 12 months. MACE was defined as stroke, myocardial infarction, heart failure and/or mortality. Subsequently, MACE, EHRA score improvement and AF-related hospitalizations between baseline and 12 months of follow-up were recorded. RESULTS: In total, 970 AF-patients were available for analysis. In analyses with patients with complete information on the confounder subset 36/687 (5.2%) AF-patients developed MACE, 190/432 (44.0%) improved in EHRA score and 189/510(37.1%) were hospitalized during 12 months of follow-up. Patients with a low AFEQT score at baseline more often developed MACE (OR(95%CI): 2.42(1.16-5.06)), more often improved in EHRA score (OR(95%CI): 4.55(2.45-8.44) and were more often hospitalized (OR(95%CI): 4.04(2.22-7.01)) during 12 months post diagnosis, compared to patients with a high AFEQT score at baseline. CONCLUSIONS: AF-patients with a lower quality of life at diagnosis more often develop MACE, more often improve on their symptoms and also were more often hospitalized, compared to AF-patients with a higher quality of life. This study highlights that the integration of patient-reported outcomes, such as quality of life, has the potential to be used as a prognostic indicator of the expected disease course for AF.

Green tea and green tea extract in oncological treatment: A systematic review.

Purpose: Teas are an essential part of traditional phytotherapy. The aim of this systematic review is to assess the clinical evidence using green tea catechins in cancer care. Methods: A systematic search was conducted searching five electronic databases concerning the effectiveness and risks of epigallocatechin gallate (EGCG) on cancer patients. Results: Seven studies with 371 patients were included. Patients were mainly suffering from breast and prostate cancer. Dosing ranged from 28 mg to 1600 mg EGCG, intervention time from 7 days to 6 months with different applications (topical 2 studies; oral 5 studies). The studies showed heterogeneous methodological quality and results leading not to conduct a meta-analysis. There was a small decrease in prostate-specific-antigen levels in one study (N=60; T0:(mean±SD) 9.6±5.2 ng/ml, T1: 8.4±4.3 ng/ml vs. T0: 9.9±8.5 ng/ml, T1: 10.0±9.0 ng/ml; p=0.04), whereas in a second study only a trend was seen. Topical green tea was as effective as metronidazole powder in reducing the odor of fungating malignant wounds (1 study; N=30) with a consequent increase in quality of life (QoL) (p<0.001), improvement of appetite (p<0.001), malodorous control (p<0.001), social activities (p<0.001). Radiotherapy-induced diarrhea was lower in the green tea intervention group compared to placebo (1 study; N=42; week 4+5: without diarrhea p=0.002). Conclusions: The studies suggest that EGCG is as effective as a local antibiotic in malodorous control and improvement of QoL of fungating malignant wounds. Green tea could be a possible complementary method for treating acute radiation-induced diarrhea. Due to limitations, further studies with higher methodological quality and larger sample sizes are needed.

Beyond pain and disability: an explanatory mixed methods study exploring outcomes after physiotherapy intervention in patients with chronic low back pain.

PURPOSE: The primary aim of this study was to explore relevant outcome domains for patients with chronic low back pain (CLBP) undergoing physiotherapy. A secondary aim was to examine potential discrepancies between meaningful changes in pain and disability and the global perception of improvement. METHODS: An explanatory mixed methods design was employed. Twenty-two patients with CLBP completed self-reported measures before and after a physiotherapy programme. After the intervention, three focus groups were conducted with patients who perceived an overall improvement. Discussions were recorded, transcribed and analysed using thematic analysis. RESULTS: Quantitative analysis showed an inconsistent relationship between changes in pain and disability measures and global improvements as perceived by patients. Two main themes emerged from the thematic analysis: "pain relief" (subthemes: reducing pain intensity and other symptoms; reducing medication intake; improving sleep quality) and "gaining control over the LBP condition" (subthemes: ability to self-manage; return to function; and sense of well-being and normality). CONCLUSION: Patients with CLBP perceived multiple outcomes from physiotherapy treatment that cover the domains of global, physical, mental and social health. These study findings suggest that the targets of measurement for physiotherapy need to be expanded in order to reflect outcome domains valued by patients.Implications for rehabilitationMinimum important changes in pain intensity and disability were not valid indicators of global improvements as perceived by patients.Patients with chronic low back pain undergoing physiotherapy perceived gains in multiple health domains that ranged beyond pain and disability domains.Physiotherapy outcome assessment needs to integrate other patient-relevant outcomes such as medication intake, sleep quality, ability to self-manage and sense of well-being.

Impact of Sodium Levels on Functional Outcomes in Patients With Stroke - A Swiss Stroke Registry Analysis.

CONTEXT: Correction of hyponatremia might represent an additional treatment for improving stroke patients' clinical outcomes. OBJECTIVE: Admission hyponatremia is associated with worse clinical outcome in stroke patients, but whether normalization of hyponatremia improves outcome is unknown. We investigated whether normalization of hyponatremia affects patients' disability, mortality, and stroke recurrence within 3 months; length of hospitalization; and discharge destination. DESIGN: This was a registry-based analysis of data collected between January 2016 and December 2018. We linked data from Swiss Stroke Registry (SSR) with electronic patients' records for extracting sodium values. SETTING: We analyzed data of hospitalized patients treated at University Hospital of Basel. PATIENTS: Stroke patients whose data and informed consent were available. MAIN OUTCOME MEASURE: Modified Rankin Scale (mRS) score at 3 months. The tested hypothesis was formulated after SSR data collection but before linkage with electronic patients' records. RESULTS: Of 1995 patients, 144 (7.2%) had hyponatremia on admission; 102 (70.8%) reached normonatremia, and 42 (29.2%) remained hyponatremic at discharge. An increase of initial sodium was associated with better functional outcome at 3 months (odds ratio [OR] 0.94; 95% CI, 0.90-0.99, for a shift to higher mRS per 1 mmol/L sodium increase). Compared with normonatremic patients, patients who remained hyponatremic at discharge had a worse functional outcome at 3 months (odds ratio 2.46; 95% CI, 1.20-5.03, for a shift to higher mRS). No effect was found on mortality, recurrence, or length of hospitalization. CONCLUSIONS: In hospitalized acute stroke patients, persistent hyponatremia is associated with worse functional outcome. Whether active correction of hyponatremia improves outcome remains to be determined in prospective studies.

Translating Evidence to Advanced Parkinson's Disease Patients: A Systematic Review and Meta-Analysis.

In the advanced stages of Parkinson's disease (PD), patients frequently experience disabling motor complications. Treatment options include deep brain stimulation (DBS), levodopa-carbidopa intestinal gel (LCIG), and continuous subcutaneous apomorphine infusion (CSAI). Choosing among these treatments is influenced by scientific evidence, clinical expertise, and patient preferences. To foster patient engagement in decision-making among the options, scientific evidence should be adjusted to their information needs. We conducted a systematic review from the patient perspective. First, patients selected outcomes for a treatment choice: quality of life, activities of daily living, ON and OFF time, and adverse events. Second, we conducted a systematic review and meta-analysis for each treatment versus best medical treatment using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Finally, the evidence was transformed into comprehensible and comparable information. We converted the meta-analysis results into the number of patients (per 100) who benefit clinically from an advanced treatment per outcome, based on the minimal clinically important difference and the cumulative distribution function. Although this approach allows for a comparison of outcomes across the three device-aided therapies, they have never been compared directly. The interpretation is hindered by the relatively short follow-up time in the included studies, usually less than 12 months. These limitations should be clarified to patients during the decision-making process. This review can help patients integrate the evidence with their own preferences, and with their clinician's expertise, to reach an informed decision. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Effect of ß-Blockers for Burn Patients on Clinical Outcomes: Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the effects and safety of ß-blockers in hospitalized patients with burns. METHODS: A systematic review and meta-analysis of the literature. A broad search was conducted to identify all randomized controlled trials (RCTs) comparing ß-blockers to control in hospitalized patients with burns. The primary outcome was 3-month all-cause mortality. Secondary outcomes were clinical patient-relevant end points. We subgrouped results by children/adults and burn severity. Risk of bias was assessed using the individual domain approach. RESULTS: Four RCTs reported in 11 publications were included. Primary outcome of mortality was assessed in children (2 trials, n = 424) and adults (2 trials, n = 148) with severe burns. No significant difference was found between propranolol and control for mortality (risk ratio [RR] = 0.82, 95% CI = 0.48-1.39, 4 trials with broad confidence intervals in adults and children), sepsis (RR = 0.81, 95% CI = 0.46-1.43, 2 trials), and survivors' length of stay (absolute mean difference = 2.53, 95% CI = -2.58-7.63, 3 trials). There was no significant difference in bradycardia (RR = 1.33, 95% CI = 0.77-2.3, 2 trials), hypotension (RR = 1.26, 95% CI = 0.73-2.17, 3 trials), or cardiac arrhythmia (RR: 2.97, 95% CI: 0.12-71.87, 1 trial). The evidence was graded as very low certainty, due to trial's internal risk of bias, imprecision, and possible selective reporting. CONCLUSIONS: No sufficient evidence was found to support or refute an advantage for ß-blocker use in children or adults after burns. Additional studies are needed to create a consensus and formulate practice guidelines on the optimal ß-blocker to use, indications for initiation, and duration of treatment.

Publicly accessible evidence of health-related quality of life benefits associated with cancer drugs approved by the European Medicines Agency between 2009 and 2015.

OBJECTIVE: Health-related quality of life (HRQoL) is one of the most important patient-relevant study end-points for the direct measurement of the benefit of cancer drugs. Therefore, our aim is to detect cancer indications with no published information on HRQoL at the time of European Medicines Agency (EMA) approval and monitor any reported HRQoL evidence updates after at least three years of follow-up. METHODS: We included all cancer indications that were approved by the EMA between January 2009 and October 2015. Our main sources of information were the EMA website, clinicaltrials.gov and a systematic literature search in PubMed. Information on HRQoL outcomes was extracted alongside evidence on median overall survival. RESULTS: In total, we identified 110 indications, of which more than half (n = 58, 53%) were lacking available information on HRQoL assessments at the time of EMA approval. After a monitoring period of at least three years, 24 updates were identified, resulting in 34 (31%) therapies where information on HRQoL was still not available. For the 76 therapies with reported information on HRQoL, cancer-specific instruments were mostly used (n = 49/76). Regarding cumulative evidence on median overall survival and HRQoL, 33 (n = 33/110, 30%) as well as 15 (n = 15/110, 14%) cancer drugs were lacking information on both study end-points at the time of approval and after monitoring, respectively. CONCLUSION: Our results demonstrate that there is an urgent need of routine re-evaluation of reimbursed cancer drugs with initially missing information on major outcomes. Standardisation of the typology and quality of HRQoL assessments need to be improved to allow better comparability of results.

Mild to moderate hyponatremia at discharge is associated with increased risk of recurrence in patients with community-acquired pneumonia.

BACKGROUND: Hyponatremia is the most common electrolyte disorder in hospitalized patients with pneumonia. Different studies have shown an association of hyponatremia on admission and worse patient's outcome. Yet, the impact of hyponatremia at discharge or of hyponatremia correction on patient's prognosis is unknown. METHODS: This is a preplanned secondary data analysis from a double-blind, randomized, placebo-controlled trial of hospitalized patients with community-acquired pneumonia and prednisone treatment. The primary outcome was the impact of hyponatremia on admission and at discharge on patient relevant outcomes (i.e. mortality, rehospitalization and recurrence rate) within 180 days. RESULTS: Of the 708 included patients, 185 (26.1%) were hyponatremic on admission. Of these, 28 (15.1%) were still hyponatremic at discharge. 34 (4.8%) patients developed hyponatremia during hospitalization despite being normonatremic on admission. Patients with hyponatremia at discharge had a higher rate of pneumonia recurrence as compared to normonatremic patients (OR 2.68; 95%-CI 1.09-6.95; p = 0.037). Among patients with hyponatremia at discharge, patients who were already hyponatremic on admission showed the strongest association with increased recurrence rate (OR 4.01; 95%-CI 1.08-12.64; p = 0.022). In contrast, recurrence rate was not affected in patients who were hyponatremic on admission but had normalized serum sodium levels at discharge (p = 0.73). CONCLUSION: Mild to moderate hyponatremia at discharge is associated with an increased risk of recurrence in hospitalized patients with pneumonia. This association is particularly strong for patients who are hyponatremic both on admission and at discharge, emphasizing the importance of hyponatremia correction during hospitalization.

Regional collaboration to improve atrial fibrillation care: Preliminary data from the Netherlands heart network.

BACKGROUND: Guideline non-adherence and variations in therapeutic and diagnostic trajectories result in suboptimal atrial fibrillation (AF) treatments. Large academic and referral hospitals demonstrated positive effects of dedicated outpatient AF clinics. Although similar results have not been indicated in (small) non-academic hospitals yet, ample opportunities are present when collaboration is initiated on a regional level. Therefore, this study assesses the effectiveness of outpatient AF clinics in a collaborative region in the Netherlands. METHODS: For this study baseline and 6 months follow-up data of a prospective cohort including newly or recently diagnosed AF-patients of 4 hospitals involved in the Netherlands Heart Network are used. From January'15 to March'16 patient relevant outcome measures (ie EHRA score, stroke, major bleedings, hospitalizations, serious adverse effects of medication, and mortality) are gathered. Descriptive and regression analyses are performed to assess the effectiveness of outpatient AF clinics. RESULTS: In the analyses 448 AF-patients were included. After 6 months, significant improvements regarding EHRA score (P < 0.01), hypertension (P < 0.01), and type of AF (P < 0.01) were indicated. Results of the patient relevant outcomes showed that AF-patients were hospitalized 23 times, no major bleedings and 2 strokes occurred. Furthermore, 0 AF-patients reported serious adverse effects of medication and no AF-patients deceased. CONCLUSIONS: Collaboration between cardiologists in a regional setting permits further improvement of AF care. Therefore, such quality targets are not exclusively reserved to large academic or referral hospitals. Although promising, future research should put effort in measuring the effectiveness of the outpatient AF clinics also on the long run.

Mistletoe in oncological treatment: a systematic review : Part 2: quality of life and toxicity of cancer treatment.

PURPOSE: One important goal of any cancer therapy is to improve or maintain quality of life. In this context, mistletoe treatment is discussed to be highly controversial. The aim of this systematic review is to give an extensive overview about the current state of evidence concerning mistletoe therapy of oncologic patients regarding quality of life and side effects of cancer treatments. METHODS: In September and October 2017, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL and "Science Citation Index Expanded" (Web of Science) were systematically searched. RESULTS: The search strategy identified 3647 articles and 28 publications with 2639 patients were finally included in this review. Mistletoe was used in bladder cancer, breast cancer, other gynecological cancers (cervical cancer, corpus uteri cancer, and ovarian cancer), colorectal cancer, other gastrointestinal cancer (gastric cancer and pancreatic cancer), glioma, head and neck cancer, lung cancer, melanoma and osteosarcoma. In nearly all studies, mistletoe was added to a conventional therapy. Regarding quality of life, 17 publications reported results. Studies with better methodological quality show less or no effects on quality of life. CONCLUSIONS: With respect to quality of life or reduction of treatment-associated side effects, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.

Mistletoe in oncological treatment: a systematic review : Part 1: survival and safety.

PURPOSE: Mistletoe treatment of cancer patients is discussed highly controversial in the scientific literature. Aim of this systematic review is to give an extensive overview about current state of research concerning mistletoe therapy of oncologic patients regarding survival, quality of life and safety. METHODS: In September and October 2017 Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL and "Science Citation Index Expanded" (Web of Science) were systematically searched. RESULTS: The search strategy identified 3647 hits and 28 publications with 2639 patients were finally included in this review. Mistletoe was used in bladder cancer, breast cancer, other gynecological cancers (cervical cancer, corpus uteri cancer, and ovarian cancer), colorectal cancer, other gastrointestinal cancer (gastric cancer and pancreatic cancer), glioma, head and neck cancer, lung cancer, melanoma and osteosarcoma. In nearly all studies, mistletoe was added to a conventional therapy. Patient relevant endpoints were overall survival (14 studies, n = 1054), progression- or disease-free survival or tumor response (10 studies, n = 1091). Most studies did not show any effect of mistletoe on survival. Especially high quality studies do not show any benefit. CONCLUSIONS: With respect to survival, a thorough review of the literature does not provide any indication to prescribe mistletoe to patients with cancer.

Measuring what matters to rare disease patients - reflections on the work by the IRDiRC taskforce on patient-centered outcome measures.

Our ability to evaluate outcomes which genuinely reflect patients' unmet needs, hopes and concerns is of pivotal importance. However, much current clinical research and practice falls short of this objective by selecting outcome measures which do not capture patient value to the fullest. In this Opinion, we discuss Patient-Centered Outcomes Measures (PCOMs), which have the potential to systematically incorporate patient perspectives to measure those outcomes that matter most to patients. We argue for greater multi-stakeholder collaboration to develop PCOMs, with rare disease patients and families at the center. Beyond advancing the science of patient input, PCOMs are powerful tools to translate care or observed treatment benefit into an 'interpretable' measure of patient benefit, and thereby help demonstrate clinical effectiveness. We propose mixed methods psychometric research as the best route to deliver fit-for-purpose PCOMs in rare diseases, as this methodology brings together qualitative and quantitative research methods in tandem with the explicit aim to efficiently utilise data from small samples. And, whether one opts to develop a brand-new PCOM or to select or adapt an existing outcome measure for use in a rare disease, the anchors remain the same: patients, their daily experience of the rare disease, their preferences, core concepts and values. Ultimately, existing value frameworks, registries, and outcomes-based contracts largely fall short of consistently measuring the full range of outcomes that matter to patients. We argue that greater use of PCOMs in rare diseases would enable a fast track to Patient-Centered Care.

Identifying critical steps towards improved access to innovation in cancer care: a European CanCer Organisation position paper.

In recent decades cancer care has seen improvements in the speed and accuracy of diagnostic procedures; the effectiveness of surgery, radiation therapy and medical treatments; the power of information technology; and the development of multidisciplinary, specialist-led approaches to care. Such innovations are essential if we are to continue improving the lives of cancer patients across Europe despite financial pressures on our healthcare systems. Investment in innovation must be balanced with the need to ensure the sustainability of healthcare budgets, and all health professionals have a responsibility to help achieve this balance. It requires scrutiny of the way care is delivered; we must be ready to discontinue practices or interventions that are inefficient, and prioritise innovations that may deliver the best outcomes possible for patients within the limits of available resources. Decisions on innovations should take into account their long-term impact on patient outcomes and costs, not just their immediate costs. Adopting a culture of innovation requires a multidisciplinary team approach, with the patient at the centre and an integral part of the team. It must take a whole-system and whole-patient perspective on cancer care and be guided by high-quality real-world data, including outcomes relevant to the patient and actual costs of care; this accurately reflects the impact of any innovation in clinical practice. The European CanCer Organisation is committed to working with its member societies, patient organisations and the cancer community at large to find sustainable ways to identify and integrate the most meaningful innovations into all aspects of cancer care.