Effects of dignity therapy on psychological distress and wellbeing of palliative care patients and family caregivers – a randomized controlled study

Background This study extended the original Dignity Therapy (DT) intervention by including partners and family caregivers (FCs) of terminally-ill cancer patients with the overall aim of evaluating whether DT can mitigate distress in both patients nearing the end of life and their FCs. Methods In this multicenter, randomized controlled trial (RCT), a total of 68 patients with life expectancy < 6 months and clinically-relevant stress levels (Hospital Anxiety Depression total score; HADS$_{tot}$ ≥ 8) including their FCs were randomly assigned to DT, DT + (including their FCs), or standard palliative care (SPC) in a 1:1:1 ratio. Study participants were asked to complete a set of questionnaires pre- and post-intervention. Results The coalesced group (DT and DT +) revealed a significant increase in patients’ perceived quality of life (FACIT-Pal-14) following the intervention (mean difference 6.15, SD = 1.86, p < 0.01). We found a statistically significant group-by-time interaction effect: while the HADS$_{tot}$ of patients in the intervention group remained stable over the pre-post period, the control group’s HADS$_{tot}$ increased (F = 4.33, df = 1, 82.9; p < 0.05), indicating a protective effect of DT. Most patients and their FCs found DT useful and would recommend it to other individuals in their situation. Conclusions The DT intervention has been well-received and shows the potential to increase HRQoL and prevent further mental health deterioration, illness burden and suffering in terminally-ill patients. The DT intervention holds the potential to serve as a valuable tool for facilitating end-of-life conversations among terminally-ill patients and their FCs. However, the implementation of DT within the framework of a RCT in a palliative care setting poses significant challenges. We suggest a slightly modified and less resource-intensive version of DT that is to provide the DT inventory to FCs of terminally-ill patients, empowering them to ask the questions that matter most to them over their loved one’s final days. Trial registration This study was registered with Clinical Trial Registry (ClinicalTrials.gov -Protocol Record NCT02646527; date of registration: 04/01/2016). The CONSORT 2010 guidelines were used for properly reporting how the randomized trial was conducted

Intragenic deletions and a deep intronic mutation affecting pre-mRNA splicing in the dihydropyrimidine dehydrogenase gene as novel mechanisms causing 5-fluorouracil toxicity

Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme acting in the catabolism of the widely used antineoplastic agent 5-fluorouracil (5FU). DPD deficiency is known to cause a potentially lethal toxicity following administration of 5FU. Here, we report novel genetic mechanisms underlying DPD deficiency in patients presenting with grade III/IV 5FU-associated toxicity. In one patient a genomic DPYD deletion of exons 21–23 was observed. In five patients a deep intronic mutation c.1129–5923C>G was identified creating a cryptic splice donor site. As a consequence, a 44 bp fragment corresponding to nucleotides c.1129–5967 to c.1129–5924 of intron 10 was inserted in the mature DPD mRNA. The deleterious c.1129–5923C>G mutation proved to be in cis with three intronic polymorphisms (c.483 + 18G>A, c.959–51T>G, c.680 + 139G>A) and the synonymous mutation c.1236G>A of a previously identified haplotype. Retrospective analysis of 203 cancer patients showed that the c.1129–5923C>G mutation was significantly enriched in patients with severe 5FU-associated toxicity (9.1%) compared to patients without toxicity (2.2%). In addition, a high prevalence was observed for the c.1129–5923C>G mutation in the normal Dutch (2.6%) and German (3.3%) population. Our study demonstrates that a genomic deletion affecting DPYD and a deep intronic mutation affecting pre-mRNA splicing can cause severe 5FU-associated toxicity. We conclude that screening for DPD deficiency should include a search for genomic rearrangements and aberrant splicing

Assessment of Affective-Behavioral States in Parkinson's Disease Patients: Toward a New Screening Tool.

BACKGROUND Assessment of affective-behavioral states in patients with Parkinson's disease (PD) undergoing deep brain stimulation (DBS) is essential. OBJECTIVE To analyze well-established questionnaires as a pilot-study with the long term aim to develop a screening tool evaluating affective-behavioral dysfunction, including depression, anxiety, apathy, mania, and impulse control disorders, in PD patients screened for DBS. METHODS Two hundred ninety-seven inpatients with PD underwent standardized neuropsychiatric testing including German versions of Beck Depression Inventory-II, Hospital Anxiety and Depression Scale, Apathy Evaluation Scale, Self-Report Manic Inventory, and Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale, to assess appropriateness for DBS. Statistical item reduction was based on exploratory factor analysis, Cronbach's alpha, item-total correlations, item difficulty, and inter-item correlations. Confirmatory factor analysis was conducted to assess factorial validity. An expert rating was performed to identify clinically relevant items in the context of PD and DBS, to maintain content validity. We compared the shortened subscales with the original questionnaires using correlations. To determine cutoff points, receiver operating characteristics analysis was performed. RESULTS The items of the initial questionnaires were reduced from 129 to 38 items. Results of confirmatory factor analyses supported the validity of the shortened pool. It demonstrated high internal consistency (Cronbach's alpha = 0.72-0.83 across subscales), and the individual subscales were correlated with the corresponding original scales (rs = 0.84-0.95). Sensitivities and specificities exceeded 0.7. CONCLUSION The shortened item pool, including 38 items, provides a good basis for the development of a screening tool, capturing affective-behavioral symptoms in PD patients before DBS implantation. Confirmation of the validity of such a screening tool in an independent sample of PD patients is warranted

Multicentre investigation on electrically evoked compound action potential and stapedius reflex: how do these objective measures relate to implant programming parameters?

Objectives: The aims of this study were to collect data on electrically evoked compound action potential (eCAP) and electrically evoked stapedius reflex thresholds (eSRT) in HiResolutionTM cochlear implant (CI) users, and to explore the relationships between these objective measures and behavioural measures of comfort levels (M-levels). Methods: A prospective study on newly implanted subjects was designed. The eCAP was measured intra-operatively and at first fitting through neural response imaging (NRI), using the SoundWaveTM fitting software. The eSRT was measured intra-operatively by visual monitoring of the stapes, using both single-electrode stimulation and speech bursts (four electrodes stimulated at the same time). Measures of M-levels were performed according to standard clinical practice and collected at first fitting, 3 and 6 months of CI use. Results: One hundred seventeen subjects from 14 centres, all implanted unilaterally with a HiResolution CII Bionic Ear® or HiRes 90K®, were included in the study. Speech burst stimulation elicited a significantly higher eSRT success rate than single-electrode stimulation, 84 vs. 64% respectively. The NRI success rate was 81% intra-operatively, significantly increasing to 96% after 6 months. Fitting guidelines were defined on the basis of a single NRI measurement. Correlations, analysis of variance, and multiple regression analysis were applied to generate a predictive model for the M-levels. Discussion: Useful insights were produced into the behaviour of objective measures according to time, electrode location, and fitting parameters. They may usefully assist in programming the CI when no reliable feedback is obtained through standard behavioural procedures

Search for pair-produced vector-like B quarks in proton-proton collisions at s\sqrt{s} = 8 TeV

A search for the production of a heavy B quark, having electric charge -1/3 and vector couplings to W, Z, and H bosons, is carried out using proton-proton collision data recorded at the CERN LHC by the CMS experiment, corresponding to an integrated luminosity of 19.7 inverse femtobarns. The B quark is assumed to be pair-produced and to decay in one of three ways: to tW, bZ, or bH. The search is carried out in final states with one, two, and more than two charged leptons, as well as in fully hadronic final states. Each of the channels in the exclusive final-state topologies is designed to be sensitive to specific combinations of the B quark-antiquark pair decays. The observed event yields are found to be consistent with the standard model expectations in all the final states studied. A statistical combination of these results is performed and upper limits are set on the cross section of the strongly produced B quark-antiquark pairs as a function of the B quark mass. Lower limits on the B quark mass between 740 and 900 GeV are set at a 95% confidence level, depending on the values of the branching fractions of the B quark to tW, bZ, and bH. Overall, these limits are the most stringent to date

Search for supersymmetry with photons in pp collisions at s\sqrt s = 8 TeV

Two searches for physics beyond the standard model in events containing photons are presented. The data sample used corresponds to an integrated luminosity of 19.7 inverse femtobarns of proton-proton collisions at $\sqrt{s}$ = 8 TeV, collected with the CMS experiment at the CERN LHC. The analyses pursue different inclusive search strategies. One analysis requires at least one photon, at least two jets, and a large amount of transverse momentum imbalance, while the other selects events with at least two photons and at least one jet, and uses the razor variables to search for signal events. The background expected from standard model processes is evaluated mainly from data. The results are interpreted in the context of general gauge-mediated supersymmetry, with the next-to-lightest supersymmetric particle either a bino- or wino-like neutralino, and within simplified model scenarios. Upper limits at 95% confidence level are obtained for cross sections as functions of the masses of the intermediate supersymmetric particles

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes