Protocolized reduction of non-resuscitation fluids versus usual care in septic shock patients (REDUSE): a randomized multicentre feasibility trial.

BACKGROUND/PURPOSE: Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care. METHODS: Adults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion. RESULTS: Median (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960-8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804-12,401) in the control group (n = 48); corresponding to a Hodges-Lehmann median difference of 3560 ml [95% confidence interval 1614-5302]; p < 0.001). Outcome data on all-cause mortality, days alive and free of mechanical ventilation and acute kidney injury or ischemic events in the ICU within 90 days of inclusion were recorded in 98/98 (100%), 95/98 (98%) and 95/98 (98%) of participants respectively. Cognition and health-related quality of life at six months were recorded in 39/52 (75%) and 41/52 (79%) of surviving participants, respectively. Ninety out of 134 patients (67%) of eligible patients were randomized, and 15/98 (15%) of the participants experienced at least one protocol violation. CONCLUSION: Protocolized reduction of non-resuscitation fluids in patients with septic shock resulted in a large decrease in fluid administration compared with usual care. A trial using this design to test if reducing non-resuscitation fluids improves outcomes is feasible. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05249088, 18 February 2022. https://clinicaltrials.gov/ct2/show/NCT05249088.

Tramadol for chronic pain in adults: protocol for a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials.

BACKGROUND: Chronic pain in adults is a frequent clinical symptom with a significant impact on patient well-being. Therefore, sufficient pain management is of utmost importance. While tramadol is a commonly used pain medication, the quality of evidence supporting its use has been questioned considering the observed adverse events. Our objective will be to assess the benefits and harms of tramadol compared with placebo or no intervention for chronic pain. METHODS/DESIGN: We will conduct a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis to assess the beneficial and harmful effects of tramadol in any dose, formulation, or duration. We will accept placebo or no intervention as control interventions. We will include adult participants with any type of chronic pain, including cancer-related pain. We will systematically search the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, and BIOSIS for relevant literature. We will follow the recommendations by Cochrane and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The risk of systematic errors ('bias') and random errors ('play of chance') will be assessed. The certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. DISCUSSION: Although tramadol is often being used to manage chronic pain conditions, the beneficial and harmful effects of this intervention are unknown. The present review will systematically assess the current evidence on the benefits and harms of tramadol versus placebo or no intervention to inform clinical practice and future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019140334.

Dietary beauvericin and enniatin B exposure cause different adverse health effects in farmed Atlantic salmon.

The extensive use of plant ingredients in novel aquafeeds have introduced mycotoxins to the farming of seafood. The emerging enniatin B (ENNB) and beauvericin (BEA) mycotoxins have been found in the novel aquafeeds and farmed fish. Little is known about the potential toxicity of ENNs and BEA in farmed fish and their feed-to-organ transfer. Atlantic salmon (Salmo salar) pre-smolt (75.3 ± 8.10 g) were fed four graded levels of spiked chemical pure ENNB or BEA feeds for three months, in triplicate tanks. Organismal adverse health end-point assessment included intestinal function (protein digestibility), disturbed hematology (red blood cell formation), bone formation (spinal deformity), overall energy use (feed utilization), and lipid oxidative status (vitamin E). Both dietary BEA and ENNB had a low (<∼0.01%) transfer to organs (kidney > liver > brain > muscle), with a higher transfer for ENNB compared to BEA. BEA caused a growth reduction combined with a decreased protein digestion and feed conversion rate- ENNB caused a stunted growth, unrelated to feed utilization capacity. In addition, ENNB caused anemia while BEA gave an oxidative stress response. Lower bench-mark dose regression assessment showed that high background levels of ENNB in commercial salmon feed could pose a risk for animal health, but not in the case of BEA.

Electrical stimulation of the dorsal clitoral nerve in the treatment of idiopathic defecatory urgency. A pilot study.

PURPOSE: To investigate the effect of dorsal clitoral nerve stimulation (DCNS) on bothersome urgency to defecate with or without fecal incontinence and the patient-reported discomfort or adverse effect with the method. METHODS: For dorsal clitoral nerve stimulation, a battery powered, handheld stimulator was used, set to a pulse width of 200 µs and a frequency of 20 Hz. One electrode was placed at the preputium of the clitoris and acted as cathode while an anode electrode was placed on the belly. Prior to stimulation the patients were asked to complete a bowel habit diary throughout 14 consecutive days before and during stimulation. RESULTS: Fourteen out of the 16 patients included completed the study. A decrease in the number of episodes (per day) with strong urgency declined in eight patients but increased in four cases during the stimulation period. An increase in episodes with moderate or mild urgency was observed in 11 and 6 cases, respectively, and a decrease in defecation without the feeling of urgency or passive incontinence decreased in two thirds of the patients. Two patients discontinued the study prematurely, on due to worsening in symptoms and one due to pelvic pain. CONCLUSION: Although the results may be promising, much still must be learned about the method including mode and duration of stimulation, better electrodes and more patient friendly equipment together with the development of better questionnaires to assess the patient burden of urgency.

Comparison of long-term outcome of sacral nerve stimulation for constipation and faecal incontinence with focus on explantation rate, additional visits, and patient satisfaction.

BACKGROUND: The aim of the present study was to compare sacral nerve stimulation (SNS) for constipation (SNS-C) with SNS for idiopathic faecal incontinence (SNS-IFI) regarding explantation rate, additional visits, and improvement of patient satisfaction 5 years after implantation. METHODS: From our prospective database (launched in 2009), we extracted all SNS-C patients 5 years post-implantation, and the SNS-IFI patients implanted just before and just after each SNS-C patient. We retrospectively evaluated the explantation rate, number of additional visits, and patient satisfaction using a visual analogue scale (VAS). We hypothesized that compared with those in the SNS-IFI group: (1) the explantation rate would be higher in SNS-C patients, (2) the number of additional visits would be higher in SNS-C patients, and (3) in patients with an active implant at 5 years, the improvement in VAS would be the same. RESULTS: We included 40 SNS-C patients and 80 SNS-IFI patients. In the SNS-C group 7/40 (17.5%), patients were explanted, compared to 10/80 (12.5%) patients in the SNS-IFI group (p = 0.56). The mean number of additional visits in the SNS-C group was 3.5 (95% CI 2.8-4.1)) and 3.0 (95% CI 2.6-3.6)) in the SNS-IFI group (p = 0.38). Additional visits due to loss of efficacy were significantly higher in the SNS-C patients (p = 0.03). The reduction in VAS score (delta VAS) at 5 years was 37.1 (95% CI 20.9-53.3) in the SNS-C group, and 46.0 (95% CI 37.9-54.0) in the SNS-IFI group (p = 0.27). CONCLUSIONS: No significant difference was found regarding explantation rate, number of additional visits, or improvement of VAS at 5 years after SNS implantation between SNS-C patients and SNS-IFI patients.

Uncarboxylated matrix Gla-protein: A biomarker of vitamin K status and cardiovascular risk.

BACKGROUND: Dephosphorylated uncarboxylated matrix Gla-protein (dp-ucMGP) is a biomarker of functional vitamin K status. High plasma dp-ucMGP concentrations reflect a low vitamin K status and have been related to vascular calcification. Our aims were to assess plasma levels of dp-ucMGP and their association with cardiovascular risk in a general population. METHODS: Plasma dp-ucMGP measurements were performed using the IDS-iSYS InaKtif MGP assay in 491 consecutive participants in a Danish general population study (229 males and 262 females, aged 19-71 years). Multivariable linear and logistic regressions were used to assess the association between dp-ucMGP levels and cardiovascular risk factors. RESULTS: Mean ± standard deviation (SD) for dp-ucMGP was 465 ± 181 pmol/L, and upper 95th percentile was 690 pmol/L. In logistic regression analyses, an increase in dp-ucMGP category (<300, 300-399, 400-499, ≥500 pmol/L) was positively associated with obesity, odds ratio (OR) 2.27 (95% confidence interval (CI) 1.54-3.33), history of cardiovascular disease, OR 1.77 (CI 1.02-3.05), and above-median estimated pulse wave velocity (ePWV), OR 1.54 (CI 1.21-1.96), when adjusted for age, sex, and lifestyle factors. 1 SD increase in diastolic and systolic blood pressure (BP) corresponded to a 5.5% (CI 2.9-8.0%) and 4.7% (CI 2.1-7.4%) increase in dp-ucMGP, respectively, when adjusted for age and sex. CONCLUSION: Plasma dp-ucMGP levels were positively associated with obesity, BP, ePWV, and history of cardiovascular disease. These findings support that dp-ucMGP is a biomarker of cardiovascular risk, and that vitamin K status could play a role in vascular calcification. The strong association with obesity deserves further attention.

Improved longevity and efficacy of sacral nerve stimulation by simple adjustments at follow-up.

AIM: Sacral nerve stimulation (SNS) for faecal incontinence (FI) at subsensory amplitudes as low as 50% of the sensory threshold has been found to be effective at 3 months' follow-up. Furthermore, alternative pacemaker settings may improve functional outcome in patients with suboptimal treatment efficacy. In this work we aim to explore if sub-sensory stimulation as low as 50% of sensory threshold is effective at 1-year follow-up. We also aimed to investigate if 31 Hz (frequency) or 90 µs (pulse width) stimulation improved treatment efficacy in dissatisfied patients. METHOD: All patients in whom the stimulation was effective in controlling FI (satisfied group) were encouraged to have the stimulation amplitude reduced. Those in whom the device was less effective (dissatisfied group) were offered alternative frequency settings or pulse width (31 Hz or 90 µs). Patients were follow-up after 12 months and evaluated by a visual analogue scale (VAS) for patient satisfaction, the Cleveland Clinic Continence Score (CCCS), Rockwood Faecal Incontinence Quality of Life Scale (QoL) and a bowel habit diary. RESULTS: Two hundred and nineteen patients were contacted, with a response rate of 71% (n = 155). Those who were successfully contacted comprised 110 (71%) patients classed as satisfied and 45 (29%) as dissatisfied. Seventy-five (68%) of the satisfied patients agreed to have their stimulation amplitude reduced. At 1-year follow-up the median amplitude had reduced from 1.5 V [interquartile range (IQR) 0.85-2.0 V] to 0.75 V (IQR 0.45-1.4 V) (P-value < 0.001) representing an overall reduction of 39% (6.6-62.5%). There were no significant differences in VAS, CCCS or QoL despite subsensory stimulation at 1-year follow-up. In 28% of the dissatisfied patients alternative pacemaker settings improved VAS to satisfactory levels. CONCLUSION: Subsensory stimulation is as effective as stimulation at or above the sensory threshold. High-frequency stimulation (31 Hz) can improve functional outcome in patients with loss of efficacy.

Randomized trial of facilitated subcutaneous immunoglobulin in multifocal motor neuropathy.

BACKGROUND AND PURPOSE: To optimize subcutaneous therapy with immunoglobulins, large volume infusion of immunoglobulin G facilitated by pretreatment with hyaluronidase (fSCIG) was compared to conventional infusion of multiple small dosages (cSCIG) in 20 patients with multifocal motor neuropathy. METHODS: A randomized, non-inferiority and observer-blinded cross-over design was applied with a treatment period of 24 weeks for each therapy. RESULTS: In 18 patients fSCIG was feasible, two patients leaving the study due to side-effects. The primary study variable, isometric strength, was unchanged, being 100.8% [95% confidence interval (CI) 94.8%-107.1%) in fSCIG and 105.9% (95% CI 99.8%-112.0%) in cSCIG. Secondary end-points of disability, functions, impairments and quality of life showed no differences between the two treatments. Mild and short-lasting generalized side-effects were similar in the two groups, whereas the relative frequency of localized side-effects at the injection site was increased after fSCIG [0.63 (95% CI 0.23-1.00) vs. 0.09 (95% CI 0.00-0.22), P = 0.005]. The preference of the patients favoured fSCIG for two out of five visual analogue scale scores as well as the total mean score of all preferences (P = 0.03). CONCLUSIONS: Facilitated SCIG seems effective, feasible and safe. In addition, it is preferred by patients but is accompanied by a higher frequency of short-lasting localized side-effects.

Ivabradine for coronary artery disease and/or heart failure-a protocol for a systematic review of randomised clinical trials with meta-analysis and Trial Sequential Analysis.

BACKGROUND: Coronary artery disease and heart failure are both highly prevalent diseases with a global prevalence of 93 million and 40 million. These patients are at increased risk of morbidity and mortality. The management of these patients involves medical therapy, and both diseases can be treated using the heart rate-lowering drug ivabradine. However, the evidence regarding the use of ivabradine in the treatment of coronary artery disease and/or heart failure is unclear. Our objective is to assess the beneficial and harmful effects of ivabradine in the treatment of coronary artery disease and/or heart failure. METHODS: This protocol for a systematic review was undertaken using the recommendations of The Cochrane Collaboration, the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P), and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials assessing the use of ivabradine in the treatment of coronary artery disease and/or heart failure. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded on Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP), and BIOSIS in order to identify relevant trials. We will begin the searches in February 2019. All included trials will be assessed and classified at low risk of bias or at high risk of bias. Our primary conclusions will be based on the results from the primary outcomes at low risk of bias. Extracted data will be analysed using Review Manager 5.3 and Trial Sequential Analysis 0.9.5.10. We will create a 'Summary of Findings' table in which we will present our primary and secondary outcomes, and we will assess the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). DISCUSSION: The systematic review will have the potential to aid clinicians in decision-making regarding ivabradine and to benefit patients with coronary artery disease and/or heart failure. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018112082.

Oxygen supplementation for critically ill patients-A protocol for a systematic review.

BACKGROUND: In critically ill patients, hypoxaemia is a common clinical manifestation of inadequate gas exchange in the lungs. Supplemental oxygen is therefore given to all critically ill patients. This can result in hyperoxaemia, and some observational studies have identified harms with hyperoxia. The objective of this systematic review is to critically assess the evidence of randomised clinical trials on the effects of higher versus lower inspiratory oxygen fractions or targets of arterial oxygenation in critically ill adult patients. METHODS: We will search for randomised clinical trials in major international databases. Two authors will independently screen and select references for inclusion using Covidence, extract data and assess the methodological quality of the included randomised clinical trials using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will analyse the extracted data using Review Manager and Trial Sequential Analysis. To assess the quality of the evidence, we will create a 'Summary of Findings' table containing our primary and secondary outcomes using the GRADE assessment. DISCUSSION: Supplemental oxygen administration is widely recommended in international guidelines despite lack of robust evidence of its effectiveness. To our knowledge, no systematic review of randomised clinical trials has investigated the effects of oxygen supplementation in critically ill patients. This systematic review will provide reliable evidence to better inform future trialists and decision-makers on clinical practice on supplemental oxygen administration in critically ill patients.

The functional outcome of sacral nerve stimulation for faecal incontinence can be improved by using lead model 3889 and a standardized implantation technique.

AIM: Sacral nerve stimulation has been recognized as an effective treatment option for faecal incontinence when conservative therapy has failed. Refinement of the procedural technique and the use of a curved stylet may improve the functional outcome. Our aim was to explore the relationship between lead model, functional outcome, stimulation amplitude and the need for extra visits during the first year of follow-up. METHOD: Patient data from May 2009 to February 2017, which were prospectively collected in a local database, were extracted and analysed for differences between lead model and improvement in incontinence scores, stimulation amplitude and the need for additional visits during the first year of follow-up. RESULTS: A foramen lead model 3093(straight stylet) was used in 134 patients and lead model 3889(curved stylet) was used in 40 patients. There were no differences in baseline characteristics or incontinence scores. Comparing results between the two lead models we found that the improvement (delta value) in the Wexner score at 6 months' follow-up (P = 0.05) and the St Mark's score at 12 months' follow-up (P = 0.02) was greater in patients implanted with lead model 3889(curved stylet) compared with patients implanted with lead model 3093(straight stylet). Patients implanted with lead model 3889 (curved stylet) were less likely to have to alter the stimulation amplitude or pole configuration during the first year of follow-up (P = 0.04). No difference was found for stimulation amplitude (P = 0.170) or the need for additional visits (P = 0.663). CONCLUSION: Lead model 3889 (curved stylet) improves functional results compared with lead model 3093 (straight stylet) during the first year of follow-up. Lead model 3889 (curved stylet) reduces the need for reprogramming but has no influence on stimulation amplitude or the number of additional visits required.

Remodeling of muscle fibers approaching the human myotendinous junction.

The myotendinous junction (MTJ) is at high risk of strain injuries, due to high amounts of energy that is transferred through this structure. The risk of strain injury is significantly reduced by heavy resistance training (HRT), indicating a remodeling capacity of MTJ. We investigated the degree of remodeling of muscle fibers near the human MTJ. In 8 individuals, samples were taken from the semitendinosus and gracilis MTJ and they were stained immunohistochemically for myonuclei (DAPI), fibroblasts (TCF7L2), and satellite cells (CD56). A high portion of the muscle fibers adjacent to the MTJ contained a centrally located myonucleus (47 ± 8%, mean ± SD) and half of the muscle fibers were CD56 positive. The number of satellite cells and fibroblasts were not higher than what has previously been reported from muscle bellies. The immunohistochemical findings suggest that the rate of remodeling of muscle fibers near the MTJ is very high. The finding that there was no increased number of satellite cells and fibroblasts could be explained as a dynamic phenomenon. The effect of HRT should be evaluated in a randomized setting.

Stress ulcer prophylaxis in adult intensive care unit patients - a protocol for a systematic review.

BACKGROUND: In the intensive care unit (ICU), stress ulcer prophylaxis with proton pump inhibitors or histamine-2-receptor antagonists is standard of care although gastrointestinal bleeding remains uncommon. It remains unknown whether its use is associated with benefits or harms and the quality of evidence supporting the use of stress ulcer prophylaxis has been questioned. Accordingly, the objective of this systematic review was to critically assess the evidence from randomized clinical trials on the benefits and harms of stress ulcer prophylaxis vs. placebo or no prophylaxis in adult ICU patients. METHODS: We will systematically search for randomized clinical trials in major international databases. Two authors will independently screen and select trials for inclusion, extract data and assess the methodological quality using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will perform conventional meta-analyses using Review Manager, and STATA 15, and we will assess the risk of random errors using Trial Sequential Analysis. Also, we will assess and report the overall quality of evidence for all outcomes according to GRADE. DISCUSSION: The evidence on the benefits and harms of stress ulcer prophylaxis in adult ICU patients is unclear and an updated systematic review is warranted as new trials have been published. To control risks of systematic and random errors, we will use Cochrane and GRADE methodology and Trial Sequential Analysis. Our ambition with this systematic review is to provide updated, reliable and precise data to better inform decision makers on the use of stress ulcer prophylaxis in adult ICU patients.

Detection of evaluation bias caused by genomic preselection.

The aim of this simulation study was to investigate whether it is possible to detect the effect of genomic preselection on Mendelian sampling (MS) means or variances obtained by the MS validation test. Genomic preselection of bull calves is 1 additional potential source of bias in international evaluations unless adequately accounted for in national evaluations. Selection creates no bias in traditional breeding value evaluation if the data of all animals are included. However, this is not the case with genomic preselection, as it excludes culled bulls. Genomic breeding values become biased if calculated using a multistep procedure instead of, for example, a single-step method. Currently, about 60% of the countries participating in international bull evaluations have already adopted genomic selection in their breeding schemes. The data sent for multiple across-country evaluation can, therefore, be very heterogeneous, and a proper validation method is needed to ensure a fair comparison of the bulls included in international genetic evaluations. To study the effect of genomic preselection, we generated a total of 50 replicates under control and genomic preselection schemes using the structures of the real data and pedigree from a medium-size cow population. A genetic trend of 15% of the genetic standard deviation was created for both schemes. In carrying out the analyses, we used 2 different heritabilities: 0.25 and 0.10. From the start of genomic preselection, all bulls were genomically preselected. Their MS deviations were inflated with a value corresponding to selection of the best 10% of genomically tested bull calves. For cows, the MS deviations were unaltered. The results revealed a clear underestimation of bulls' breeding values (BV) after genomic preselection started, as well as a notable deviation from zero both in true and estimated MS means. The software developed recently for the MS validation test already produces yearly MS means, and they can be used to devise an appropriate test. Mean squared true MS of genomically preselected bulls was clearly inflated. After correcting for the simulated preselection bias, the true genetic variance was smaller than the parametric value used to simulate BV, and also below the variance based on the estimated BV. Based on this study, the lower the trait's heritability, the stronger the bias in estimated BV and MS means and variances. Daughters of genomically preselected bulls had higher true and estimated BV compared with the control scheme and only slightly elevated MS means, but no effect on genetic variances was observed.

Haloperidol for delirium in critically ill patients - protocol for a systematic review.

BACKGROUND: In the intensive care unit, the prevalence of delirium is high. Delirium has been associated with morbidity and mortality including more ventilator days, longer intensive care unit stay, increased long-term mortality, and cognitive impairment. Thus, the burden of delirium for patients, relatives, and societies is considerable. The objective of this systematic review was to critically access the evidence of randomised clinical trials on the effects of haloperidol vs. placebo or any other agents for delirium in critically ill patients. METHODS: We will search for randomised clinical trials in the following databases: Cochrane Library, MEDLINE, EMBASE, Science Citation Index, BIOSIS, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Health Sciences Literature, and Allied and Complementary Medicine Database. Two authors will independently screen and select references for inclusion using Covidence, extract data and assess the methodological quality of the included randomised clinical trials using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will analyse the extracted data using Review Manager, STATA 15, and Trial Sequential. ANALYSIS: The aim of this study was to assess the quality of the evidence, we will create a 'Summary of Findings' table containing our primary and secondary outcomes using the GRADE assessment. DISCUSSION: Our ambition with this systematic review is to provide reliable and powered evidence to better inform decision makers on the use of or future trials with haloperidol for the management of delirium in critically ill patients.

Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma patients.

The combination of lomustine and bevacizumab is a commonly used salvage treatment for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made a comparison to another frequently used combination therapy consisting of irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were treated with lomustine 90 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Toxicity was registered and compared to the toxicity observed in 219 recurrent GBM patients who had previously been treated with irinotecan 125 mg/m2 and bevacizumab 10 mg/kg every 2 weeks. The response rate was 37.1% for lom-bev and 30.1% for iri-bev. Median progression-free survival (PFS) was 23 weeks for lom-bev and 21 weeks for iri-bev (p = 0.9). Overall survival (OS) was 37 weeks for lom-bev and 32 weeks for iri-bev (p = 0.5). Lom-bev caused a significantly higher frequency of thrombocytopenia (11.4% grade 3-4) compared to iri-bev (3.5% grade 3-4). Iri-bev patients had more gastrointestinal toxicity with regard to nausea, vomiting, diarrhea, constipation and stomatitis. Within the limitations of the study lom-bev is a well-tolerated treatment for recurrent GBM, although hematological toxicity may be a dose limiting factor. No significant differences between lom-bev and iri-bev were observed with regard to PFS or OS. The differences in toxicity profiles between lom-bev and iri-bev could guide treatment decision in recurrent GBM therapy as efficacy is equal and no predictive factors for efficacy exist.

Needs and preferences among patients with high-grade glioma and their caregivers - A longitudinal mixed methods study.

Previous reports on the patient perspective of daily life during a 1-year high-grade glioma (HGG) trajectory from the time of diagnosis are sparse. The aim of this longitudinal mixed methods study is to identify the specific needs and preferences for rehabilitation and supportive care and how it links with physical activity, psychological measures and health quality longitudinally over the first year after diagnosis among patients with HGG and their caregivers by integrating qualitative and quantitative findings. Using a longitudinal mixed methods design, patients with malignant glioma (n = 30) and their caregivers (n = 33) were interviewed and completed questionnaires (patients only) about physical activity level, anxiety/depression and quality of life five times during the 1-year period. Their needs and preferences included interventions designed to re-define hope after diagnosis, health promoting physical activities initiated early, psychological symptom management strategies, and life planning. Caregivers are committed to their caregiving role, but their engagement is nonetheless challenged over time by enormous caregiver burdens. The identified specific needs and preferences favour supportive care, education, information and rehabilitation. Guidelines attentive to these needs and implemented in clinical practice have the potential to improve patients' health-related quality of life and support caregivers by involving them more actively in care and management.