Understanding provision of chemotherapy to patients with end stage cancer: qualitative interview study

Objective To examine health professionals’ experiences of and attitudes towards the provision of chemotherapy to patients with end stage cancer

A Duality Based 2-Approximation Algorithm for Maximum Agreement Forest

We give a 2-approximation algorithm for the Maximum Agreement Forest problem on two rooted binary trees. This NP-hard problem has been studied extensively in the past two decades, since it can be used to compute the rooted Subtree Prune-and-Regraft (rSPR) distance between two phylogenetic trees. Our algorithm is combinatorial and its running time is quadratic in the input size. To prove the approximation guarantee, we construct a feasible dual solution for a novel linear programming formulation. In addition, we show this linear program is stronger than previously known formulations, and we give a compact formulation, showing that it can be solved in polynomial tim

Split scheduling with uniform setup times

We study a scheduling problem in which jobs may be split into parts, where the parts of a split job may be processed simultaneously on more than one machine. Each part of a job requires a setup time, however, on the machine where the job part is processed. During setup, a machine cannot process or set up any other job. We concentrate on the basic case in which setup times are job-, machine- and sequence-independent. Problems of this kind were encountered when modelling practical problems in planning dis- aster relief operations. Our main algorithmic result is a polynomial-time algorithm for minimising total completion time on two parallel identical machines. We argue, why the same problem with threemachines is not an easy extension of the two-machine case, leaving the complexity of this case as a tantalising open problem. We give a constant-factor approximation algorithm for the general case with any number of machines and a polynomial-time approximation scheme for a fixed number of machines. For the version with the objective to minimise total weighted completion time, we prove NP-hardness. Finally, we conclude with an overview of the state of the art for other split scheduling problems with job-, machine- and sequence-independent setup times

Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway

Aims/hypothesis: During hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF) of neurological patients with and without diabetes mellitus. However, polyol levels in patients without evident neurological abnormalities have not been investigated so far. The aim of this study was to determine CSF polyol concentrations in patients without major neurological disease with normal or elevated CSF glucose concentrations. Methods: This observational cohort study used CSF and plasma analyses, as well as clinical data, from 30 participants of the Anaesthetic Biobank of Cerebrospinal Fluid study. Biomaterial was collected from adult patients scheduled for elective surgery under spinal anaesthesia. CSF polyol concentrations were measured by GC/flame ionisation detector in ten patients with normal CSF glucose levels (group 1), ten patients with elevated CSF glucose levels (group 2) and ten patients with elevated CSF glucose levels and type 2 diabetes (group 3). We compared the concentrations of plasma glucose, CSF glucose, sorbitol and fructose, and CSF polyol/glucose ratios between the three groups, and determined the correlation between plasma glucose levels and CSF glucose, sorbitol and fructose levels. Results: Groups 2 and 3 had significantly higher CSF fructose levels compared with group 1 (p=0.036 and p<0.001, respectively). Group 3 showed significant differences compared with groups 1 and 2 for CSF sorbitol (p<0.001 and 0.036, respectively). Moreover, patients with diabetes had a significantly higher CSF sorbitol/glucose ratio compared with patients without diabetes. There was a strong positive correlation between plasma glucose and CSF glucose, sorbitol and fructose. Finally, age, sex, CSF/plasma albumin ratio and preoperative cognitive function scores were significantly correlated with plasma glucose and CSF glucose, sorbitol and fructose levels. Conclusions/interpretation: Hyperglycaemia causes a proportional increase in polyol concentrations in CSF of patients without major neurological disease. Furthermore, this study provides the first indication of upregulation of the cerebral polyol pathway in patients with diabetes without evident neurological abnormalities. Graphical abstract: [Figure not available: see fulltext.

On the (non-)existence of polynomial kernels for Pl-free edge modification problems

Given a graph G = (V,E) and an integer k, an edge modification problem for a graph property P consists in deciding whether there exists a set of edges F of size at most k such that the graph H = (V,E \vartriangle F) satisfies the property P. In the P edge-completion problem, the set F of edges is constrained to be disjoint from E; in the P edge-deletion problem, F is a subset of E; no constraint is imposed on F in the P edge-edition problem. A number of optimization problems can be expressed in terms of graph modification problems which have been extensively studied in the context of parameterized complexity. When parameterized by the size k of the edge set F, it has been proved that if P is an hereditary property characterized by a finite set of forbidden induced subgraphs, then the three P edge-modification problems are FPT. It was then natural to ask whether these problems also admit a polynomial size kernel. Using recent lower bound techniques, Kratsch and Wahlstrom answered this question negatively. However, the problem remains open on many natural graph classes characterized by forbidden induced subgraphs. Kratsch and Wahlstrom asked whether the result holds when the forbidden subgraphs are paths or cycles and pointed out that the problem is already open in the case of P4-free graphs (i.e. cographs). This paper provides positive and negative results in that line of research. We prove that parameterized cograph edge modification problems have cubic vertex kernels whereas polynomial kernels are unlikely to exist for the Pl-free and Cl-free edge-deletion problems for large enough l

Experiences with and needs for aftercare following the death of a loved one in the ICU:a mixed-methods study among bereaved relatives

Background: Bereaved relatives of intensive care unit (ICU) patients are at increased risk of psychological complaints. Aftercare might help them cope with processing the ICU admission and their loved one’s death. There is little (qualitative) evidence on how bereaved relatives experience aftercare. Also, the COVID-19 pandemic likely impacted aftercare provision. We aim to examine how many relatives in Dutch ICUs received aftercare before and during the pandemic and to qualitatively describe their experiences and needs regarding aftercare. Methods: A mixed-methods study among relatives of patients who died in an ICU before or during the COVID-19 pandemic. Bereaved relatives in six ICUs completed a questionnaire (n = 90), including two items on aftercare. These were analyzed using descriptive statistics and Chi-squared tests. Subsequently, both relatives that received and relatives that did not receive aftercare were interviewed about their experiences and needs regarding aftercare. The interviews were thematically analyzed. Results: After the passing of a loved one, 44% of the relatives were asked by a healthcare professional from the hospital how they were doing, and 26% had had a follow-up conversation. Both happened more often during the first wave of the pandemic than during the second wave or before the pandemic. The most common reason for not having had a follow-up conversation was not knowing about this option (44%), followed by not feeling a need (26%). Regarding the latter, interviewed relatives explained that this would not revive their loved one or that they had already discussed everything they wanted. Relatives who wanted a follow-up conversation, wanted this because this would help them realize the severity of their loved one’s illness, to exchange personal experiences, and/or to thank the ICU team. Those with a follow-up conversation said that they had reviewed the medical course of the admission and/or discussed their (mental) well-being. Conclusions: ICU healthcare professionals may play a vital role in addressing aftercare needs by asking relatives how they are doing in the weeks following the death of their loved one and offering them a follow-up conversation with an ICU physician. We recommend to include aftercare for bereaved relatives in ICU guidelines.</p

Experiences with and needs for aftercare following the death of a loved one in the ICU:a mixed-methods study among bereaved relatives

Background: Bereaved relatives of intensive care unit (ICU) patients are at increased risk of psychological complaints. Aftercare might help them cope with processing the ICU admission and their loved one’s death. There is little (qualitative) evidence on how bereaved relatives experience aftercare. Also, the COVID-19 pandemic likely impacted aftercare provision. We aim to examine how many relatives in Dutch ICUs received aftercare before and during the pandemic and to qualitatively describe their experiences and needs regarding aftercare. Methods: A mixed-methods study among relatives of patients who died in an ICU before or during the COVID-19 pandemic. Bereaved relatives in six ICUs completed a questionnaire (n = 90), including two items on aftercare. These were analyzed using descriptive statistics and Chi-squared tests. Subsequently, both relatives that received and relatives that did not receive aftercare were interviewed about their experiences and needs regarding aftercare. The interviews were thematically analyzed. Results: After the passing of a loved one, 44% of the relatives were asked by a healthcare professional from the hospital how they were doing, and 26% had had a follow-up conversation. Both happened more often during the first wave of the pandemic than during the second wave or before the pandemic. The most common reason for not having had a follow-up conversation was not knowing about this option (44%), followed by not feeling a need (26%). Regarding the latter, interviewed relatives explained that this would not revive their loved one or that they had already discussed everything they wanted. Relatives who wanted a follow-up conversation, wanted this because this would help them realize the severity of their loved one’s illness, to exchange personal experiences, and/or to thank the ICU team. Those with a follow-up conversation said that they had reviewed the medical course of the admission and/or discussed their (mental) well-being. Conclusions: ICU healthcare professionals may play a vital role in addressing aftercare needs by asking relatives how they are doing in the weeks following the death of their loved one and offering them a follow-up conversation with an ICU physician. We recommend to include aftercare for bereaved relatives in ICU guidelines.</p

Varying (preferred) levels of involvement in treatment decision-making in the intensive care unit before and during the COVID-19 pandemic:a mixed-methods study among relatives

BackgroundIn the intensive care unit (ICU) relatives play a crucial role as surrogate decision-makers, since most patients cannot communicate due to their illness and treatment. Their level of involvement in decision-making can affect their psychological well-being. During the COVID-19 pandemic, relatives' involvement probably changed. We aim to investigate relatives' involvement in decision-making in the ICU before and during the pandemic and their experiences and preferences in this regard.MethodsA mixed-methods study among relatives of ICU patients admitted to an ICU before or during the COVID-19 pandemic. Relatives in six ICUs completed a questionnaire (n = 329), including two items on decision-making. These were analysed using descriptive statistics and logistic regression analyses. Subsequently, relatives (n = 24) were interviewed about their experiences and preferences regarding decision-making. Thematic analysis was used for analysing the qualitative data.ResultsNearly 55% of the relatives indicated they were at least occasionally asked to be involved in important treatment decisions and of these relatives 97.1% reported to have had enough time to discuss questions and concerns when important decisions were to be made. During the first COVID-19 wave relatives were significantly less likely to be involved in decision-making compared to relatives from pre-COVID-19. The interviews showed that involvement varied from being informed about an already made decision to deliberation about the best treatment option. Preferences for involvement also varied, with some relatives preferring no involvement due to a perceived lack of expertise and others preferring an active role as the patient's advocate. Discussing a patient's quality of life was appreciated by relatives, and according to relatives healthcare professionals also found this valuable. In some cases the preferred and actual involvement was in discordance, preferring either a larger or a smaller role.ConclusionsAs treatment alignment with a patient's values and preferences and accordance between preferred and actual involvement in decision-making is very important, we suggest that the treatment decision-making process should start with discussions about a patient's quality of life, followed by tailoring the process to relatives' preferences as much as possible. Healthcare professionals should be aware of relatives' heterogeneous and possibly changing preferences regarding the decision-making process

Phase I and pharmacokinetic study of the polyamine synthesis inhibitor SAM486A in combination with 5-fluorouracil/leucovorin in metastatic colorectal cancer

PURPOSE: The purpose of our study was to determine the maximum-tolerated\n dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the\n polyamine synthesis inhibitor SAM486A given in combination with\n 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients. EXPERIMENTAL\n DESIGN: Patients with advanced colorectal cancer were treated with 5-FU\n [bolus (400 mg/m(2)) followed by a 22-h infusion (600 mg/m(2))] and LV\n (200 mg/m(2)) and escalating doses of SAM486A, 1-3-h infusion daily for 3\n days. Plasma sampling was performed to characterize the pharmacokinetics\n and pharmacodynamics of the combination RESULTS: Twenty-seven patients\n with metastatic colorectal cancer and 1 with pseudomyxoma peritonei were\n treated. Twenty-six patients received SAM486A in the combination at doses\n ranging from 25 to 150 mg/m(2)/day. Dose-limiting toxicity consisting of\n fatigue grade 3 was seen at 150 mg/m(2)/day. Other adverse events included\n neutropenia, hand and foot syndrome, nausea, vomiting, diarrhea, and\n constipation. Fifteen of 26 patients evaluable for best response according\n to the Southwest Oncology Group criteria achieved a partial response [8\n (30%) of 26] or stable disease [9 (35%) of 26]. SAM486A did not influence\n the pharmacokinetics of 5-FU, and SAM486A clearance was similar to that\n when used as a single agent. CONCLUSIONS: The novel molecular agent\n SAM486A is tolerable and safe in combination with a standard 5-FU regimen\n in patients with advanced colorectal cancer. The dose of SAM486A\n recommended for additional studies with this combination is 125\n mg/m(2)/day. A disease-directed evaluation of SAM486A using this regimen\n is warranted