Family reported outcomes, an unmet need in the management of a patient's disease: appraisal of the literature

Abstract: Background: A person’s chronic health condition or disability can have a huge impact on the quality of life (QoL) of the whole family, but this important impact is often ignored. This literature review aims to understand the impact of patients' disease on family members across all medical specialities, and appraise existing generic and disease-specific family quality of life (QoL) measures. Methods: The databases Medline, EMBASE, CINHAL, ASSIA, PsycINFO and Scopus were searched for original articles in English measuring the impact of health conditions on patients' family members/partner using a valid instrument. Results: Of 114 articles screened, 86 met the inclusion criteria. They explored the impact of a relative's disease on 14,661 family members, mostly 'parents' or 'mothers', using 50 different instruments across 18 specialities including neurology, oncology and dermatology, in 33 countries including the USA, China and Australia. These studies revealed a huge impact of patients' illness on family members. An appraisal of family QoL instruments identified 48 instruments, 42 disease/speciality specific and six generic measures. Five of the six generics are aimed at carers of children, people with disability or restricted to chronic disease. The only generic instrument that measures the impact of any condition on family members across all specialities is the Family Reported Outcome Measure (FROM-16). Although most instruments demonstrated good reliability and validity, only 11 reported responsiveness and only one reported the minimal clinically important difference. Conclusions: Family members' QoL is greatly impacted by a relative's condition. To support family members, there is a need for a generic tool that offers flexibility and brevity for use in clinical settings across all areas of medicine. FROM-16 could be the tool of choice, provided its robustness is demonstrated with further validation of its psychometric properties.Peer reviewe

EEG correlated functional MRI and postoperative outcome in focal epilepsy

Background: The main challenge in assessing patients with epilepsy for resective surgery is localising seizure onset. Frequently, identification of the irritative and seizure onset zones requires invasive EEG. EEG correlated functional MRI (EEG-fMRI) is a novel imaging technique which may provide localising information with regard to these regions. In patients with focal epilepsy, interictal epileptiform discharge (IED) correlated blood oxygen dependent level (BOLD) signal changes were observed in approximately 50% of patients in whom IEDs are recorded. In 70%, these are concordant with expected seizure onset defined by non-invasive electroclinical information. Assessment of clinical validity requires post-surgical outcome studies which have, to date, been limited to case reports of correlation with intracranial EEG. The value of EEG-fMRI was assessed in patients with focal epilepsy who subsequently underwent epilepsy surgery, and IED correlated fMRI signal changes were related to the resection area and clinical outcome. Methods: Simultaneous EEG-fMRI was recorded in 76 patients undergoing presurgical evaluation and the locations of IED correlated preoperative BOLD signal change were compared with the resected area and postoperative outcome. Results: 21 patients had activations with epileptic activity on EEG-fMRI and 10 underwent surgical resection. Seven of 10 patients were seizure free following surgery and the area of maximal BOLD signal change was concordant with resection in six of seven patients. In the remaining three patients, with reduced seizure frequency post-surgically, areas of significant IED correlated BOLD signal change lay outside the resection. 42 of 55 patients who had no IED related activation underwent resection. Conclusion: These results show the potential value of EEG-fMRI in presurgical evaluation

Comparison of the paper-based and electronic versions of the Dermatology Life Quality Index (DLQI): evidence of equivalence

BACKGROUND: The use of patient-reported outcome measures in electronic format has been increasing. However, these formats are usually not validated or compared to the original paper-based formats, so there is no evidence that they are completed in the same way. OBJECTIVES: The aim of this study was to compare the conventional paper version and a web-based application version (iPad® ) of the DLQI to assess equivalence of scores. METHODS: The study employed a randomized cross-over design using a within-subjects comparison of the two formats of the questionnaire. International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines were followed. Subjects aged over 18 years with any confirmed skin condition were recruited from a teaching hospital dermatology outpatient clinic. Expected Intra-class correlation coefficient (ICC) was 0.9 (α = 0.05) RESULTS: A total of 104 patients were recruited, median age=53.5 years (IQR=37.3-67.8, 43% male). The Intraclass correlation coefficient (ICC) showed high concordance between the total DLQI scores from paper and iPad® versions (ICC = 0.98; 95% CI 0.97-0.99). Patients took a median of 78 seconds to complete the electronic version and 73 seconds for paper (p=0.008): 76% preferred the electronic version and perceived completion to take a shorter time. CONCLUSIONS: There is high concordance, and thus equivalence, between the iPad and paper versions of the DLQI, with an ICC of 0.98, and a clear patient preference for the iPad version

Appropriate and inappropriate influences on outpatient discharge decision making in dermatology : a prospective qualitative study

© 2015 British Association of Dermatologists.BACKGROUND: Outpatient discharge decision making in dermatology is poorly understood. OBJECTIVE: To identify the influences on clinicians' thought processes when making discharge decisions in dermatology outpatient clinics. METHODS: Forty clinicians from 11 National Health Service Trusts in England were interviewed. The interviews were audiorecorded, transcribed, coded and thematically analysed. RESULTS: The mean age of the clinicians was 48.8 years (range 33.0-67.0), 17 (43%) were men and 19 (48%) had > 20 years of clinical experience. One hundred and forty-eight influences were reported, with five main themes: (i) disease-based influences included type of diagnosis (100% of clinicians), guidelines (100%) and treatment needed (100%); (ii) clinician-based influences included the clinician's level of experience (100%), seniority (37%), emotional attitude (95%), 'gut feeling' (25%), personal attitude towards discharge (45%) and level of perception (100%); (iii) patient-based influences included patients' ability to cope with their disease (100%), wishes (70%), quality of life (32%), command of English (40%) and cultural background (25%); (iv) practice-based influences included good primary care (100%), secondary support structure (100%) and clinic capacity pressure (67%); (v) policy-based influences included pressure from hospital managers (57%) and an active discharge policy (7%). Fourteen (9%) influences were potentially inappropriate. CONCLUSION: This study has identified multiple factors influencing outpatient discharge decision making. This provides the basis for developing evidence-based training to improve discharge decision appropriateness.Peer reviewe

Do Patient-Reported Outcomes Have a Role in the Management of Patients with Cystic Fibrosis?

Background: Health-related quality of life (HRQoL) is a rapidly growing area of expertise and the most commonly used patient-reported outcome (PRO). The impact of cystic fibrosis (CF) on HRQoL is liable to be great, making CF patients ideal candidates for the application of HRQoL instruments. The aims of this study were to assess the affect of CF on HRQoL, to ascertain the reliability and validity of the United Kingdom Sickness Impact Profile (UKSIP) and the Cystic Fibrosis Quality of Life Questionnaire (CFQoL) in the adult CF population, and to examine their role in the management of patients. Methods: Seventy participants were recruited from the All Wales Adult Cystic Fibrosis Centre at Llandough Hospital, UK. There were two stages to the study: self-report of the UKSIP and CFQoL; and completion of the same two questionnaires 7–10 days later. Results: The areas of HRQoL most impaired by CF were employment and concerns regarding the future. The UKSIP and CFQoL showed high internal consistency (rα = 0.89–0.93) and test–retest reliability (rs = 0.57–0.94, p < 0.005) in the CF population. Validity was variable with the UKSIP showing discrimination across socio-demographic factors, whilst the CFQoL showed increased sensitivity to clinical variables. Many parameters influenced patient-reported HRQoL, with the greatest correlations seen with the Borg score (p < 0.005). The use of a HRQoL instrument in CF annual reviews is recommended to provide holistic patient care. The results of this study underpin the value of HRQoL as a patient-reported outcome measure in the management of adult CF

Alpha/Beta Interferon Receptor Signaling Amplifies Early Proinflammatory Cytokine Production in the Lung during Respiratory Syncytial Virus Infection

Type I interferons (IFNs) are produced early upon virus infection and signal through the alpha/beta interferon (IFN-α/β) receptor (IFNAR) to induce genes that encode proteins important for limiting viral replication and directing immune responses. To investigate the extent to which type I IFNs play a role in the local regulation of inflammation in the airways, we examined their importance in early lung responses to infection with respiratory syncytial virus (RSV). IFNAR1-deficient (IFNAR1−/−) mice displayed increased lung viral load and weight loss during RSV infection. As expected, expression of IFN-inducible genes was markedly reduced in the lungs of IFNAR1−/− mice. Surprisingly, we found that the levels of proinflammatory cytokines and chemokines in the lungs of RSV-infected mice were also greatly reduced in the absence of IFNAR signaling. Furthermore, low levels of proinflammatory cytokines were also detected in the lungs of IFNAR1−/− mice challenged with noninfectious innate immune stimuli such as selected Toll-like receptor (TLR) agonists. Finally, recombinant IFN-α was sufficient to potentiate the production of inflammatory mediators in the lungs of wild-type mice challenged with innate immune stimuli. Thus, in addition to its well-known role in antiviral resistance, type I IFN receptor signaling acts as a central driver of early proinflammatory responses in the lung. Inhibiting the effects of type I IFNs may therefore be useful in dampening inflammation in lung diseases characterized by enhanced inflammatory cytokine production

Paper and electronic versions of HM-PRO, a novel patient-reported outcome measure for hematology: an equivalence study.

© 2019 Goswami, Oliva, Ionova et al.Aim:To determine measurement equivalence of paper and electronic application of the hematologi-cal malignancy-patient-reported outcome (HM-PRO), a specific measure for the evaluation of patient-reported outcomes in HMs.Patients & methods:Following International Society of Pharmacoeconomicsand Outcomes Research ePRO Good Research Practice Task Force guidelines, a total of 193 adult patientswith different HMs were recruited into a multicenter prospective study. The paper and the electronic ver-sion of the instrument were completed in the outpatient clinics in a randomized crossover design with a30-min time interval to minimize the learning effect. Those who completed the paper version first, com-pleted the electronic version after 30 min and vice versa. Instrument version and order effects were testedon total score of the two parts of the HM-PRO (Part A: quality of life and Part B: signs & symptoms) in atwo-way ANOVA with patients as random effects. Intraclass correlation coefficients (95% CI) and Spear-man’s rank correlation coefficients were used to evaluate test–retest reliability and reproducibility. Theeffects of instrument version and order were tested on total score of the two parts of HM-PRO.Results:The questionnaire version and administration order effects were not significant at the 5% level. Therewere no interactions found between these two factors for HM-PRO (Part A [quality of life]; p=0.95); and(part B [signs and symptoms]; p=0.72]. Spearman’s rank correlation coefficients were greater than 0.9, andintraclass correlation coefficients ranged from 0.94 to 0.98; furthermore, the scores were not statisticallydifferent between the two versions, showing acceptable reliability indexes. Noteworthy, the differencebetween the completion time for both paper (mean=6:38 min) and electronic version (mean=7:29 min)was not statistically significant (n=100; p=0.11). Patients did not report any difficulty in completing theelectronic version during cognitive interviews and were able to understand and respond spontaneously.Conclusion:Measurement equivalence has been demonstrated for the paper and electronic applicationof the HM-PRO.Peer reviewe

NCESPARC+: an implementation of a SPARC architecture with hardware support to multithreading for the multiplus multiprocessor

NCESP ARC + is an implementation of the SP ARC v: 8 architecture with hardware support to a variable number of thread contexts, which is under development for use within the framework of the Multiplus distributed shared-memory multiprocessor. It is expected to provide an efficient and automatic mechanism to hide the latency of busy-waiting synchronization loops, cachecoherence protocol and remote memory access operations within the Multiplus multiprocessor. NCESPARC + performs context-switching in at most four processor cycles whenever there is an instruction cache miss, a data dependency in relation to the destination operand of a pending load instruction or a busy-waiting synchronization loop. It has a decoupled architecture which allows the main pipeline to process instructions from a given context while the Memory Interface Unit performs memory access operations related to that same context or to any other context. Results of simulation experiments show the impact of some architectural parameters on the NCESPARC + processor performance and demonstrate that the use of multiple thread contexts can e.ffectively produce a much better utilization of the processor when long latency operations are performed In addition, NCESPARC + processor performance with a single context is superior to that of a standard implementation of the SPARC architecture due to its decoupled architecture

Rapid identification of BCR/ABL1-like acute lymphoblastic leukaemia patients using a predictive statistical model based on quantitative real time-polymerase chain reaction: clinical, prognostic and therapeutic implications.

BCR/ABL1-like acute lymphoblastic leukaemia (ALL) is a subgroup of B-lineage acute lymphoblastic leukaemia that occurs within cases without recurrent molecular rearrangements. Gene expression profiling (GEP) can identify these cases but it is expensive and not widely available. Using GEP, we identified 10 genes specifically overexpressed by BCR/ABL1-like ALL cases and used their expression values - assessed by quantitative real time-polymerase chain reaction (Q-RT-PCR) in 26 BCR/ABL1-like and 26 non-BCR/ABL1-like cases to build a statistical "BCR/ABL1-like predictor", for the identification of BCR/ABL1-like cases. By screening 142 B-lineage ALL patients with the "BCR/ABL1-like predictor", we identified 28/142 BCR/ABL1-like patients (19·7%). Overall, BCR/ABL1-like cases were enriched in JAK/STAT mutations (P < 0·001), IKZF1 deletions (P < 0·001) and rearrangements involving cytokine receptors and tyrosine kinases (P = 0·001), thus corroborating the validity of the prediction. Clinically, the BCR/ABL1-like cases identified by the BCR/ABL1-like predictor achieved a lower rate of complete remission (P = 0·014) and a worse event-free survival (P = 0·0009) compared to non-BCR/ABL1-like ALL. Consistently, primary cells from BCR/ABL1-like cases responded in vitro to ponatinib. We propose a simple tool based on Q-RT-PCR and a statistical model that is capable of easily, quickly and reliably identifying BCR/ABL1-like ALL cases at diagnosis