Individual risk profiling for breast cancer recurrence: towards tailored follow-up schemes.

BACKGROUND: Breast cancer follow-up is not tailored to the risk of locoregional recurrences (LRRs) in individual patients or as a function of time. The objective of this study was to identify prognostic factors and to estimate individual and time-dependent LRR risk rates. METHODS: Prognostic factors for LRR were identified by a scoping literature review, expert consultation, and stepwise multivariate regression analysis based on 5 years of data from women diagnosed with breast cancer in the Netherlands in 2005 or 2006 (n=17,762). Inter-patient variability was elucidated by examples of 5-year risk profiles of average-, medium-, and high-risk patients, whereby 6-month interval risks were derived from regression estimates. RESULTS: Eight prognostic factors were identified: age, tumour size, multifocality, gradation, adjuvant chemo-, adjuvant radiation-, hormonal therapy, and triple-negative receptor status. Risk profiles of the low-, average-, and high-risk example patients showed non-uniform distribution of recurrence risks (2.9, 7.6, and 9.2%, respectively, over a 5-year period). CONCLUSION: Individual risk profiles differ substantially in subgroups of patients defined by prognostic factors for recurrence and over time as defined in 6-month time intervals. To tailor follow-up schedules and to optimise allocation of scarce resources, risk factors, frequency, and duration of follow-up should be taken into account.

Differential cortical activation during observation and observation-and-imagination.

The activity of the brain during observation or imagination of movements might facilitate the relearning of motor functions after stroke. The present study examines whether there is an additional effect of imagination over observation-only. Eight healthy subjects observed and observed-and-imagined a movement of a hand; 64-channel EEG was used to measure brain activity. The synchronization of the theta (4-8 Hz), alpha (8-13 Hz) and beta (13-25 Hz) frequency bands was calculated and plotted in topoplots. The temporal changes of the sensorimotor area (C3, C4) and the centro-parietal cortex (Pz) were analyzed in the two experimental conditions. During observation-and-imagination, a significant larger desynchronization (p = 0.004) in the sensorimotor area was found compared to observation-only in all electrodes and frequency bands. In addition, temporal differences were found between observation and observation-and-imagination in the alpha frequency bands. During observation-and-imagination, modulations of EEG rhythms were stronger than during observation-only in the theta, alpha and beta frequency bands and during almost the whole activity fragment. These findings suggest an additive effect of imagination to observation in the rehabilitation after stroke.

Patient preferences for next generation neural prostheses to restore bladder function.

STUDY DESIGN: A survey administered to 66 individuals with spinal cord injury (SCI) implementing a choice-based conjoint (CBC) analysis. Six attributes with three levels each were defined and used to generate choice sets with treatment scenarios. Patients were asked to choose the scenario that they preferred most. OBJECTIVES: To determine the utility weights for treatment characteristics as well as the overall preference for the three types of neural prostheses (NP), that is Brindley, rhizotomy-free Brindley, and pudendal nerve stimulation. Earlier studies have revealed the importance of restoration of bladder function, but no studies have been performed to determine the importance of NP features. SETTING: Two academic affiliated medical systems' SCI outpatient and inpatient rehabilitation programs, Cleveland, OH. METHODS: CBC analysis followed by multinomial logit modeling. Individual part-worth utilities were estimated using hierarchical Bayes. RESULTS: Side effects had the greatest significant impact on subject choices, followed by the effectiveness on continence and voiding. NPs with rhizotomy-free sacral root stimulation were preferred (45% first choice) over pudendal afferent nerve stimulation (39% second choice) and sacral root stimulation with rhizotomy (53% third choice). Almost 20% did not want to have an NP at all times. CONCLUSION: CBC has shown to be a valuable tool to support design choices. The data showed that persons would prefer a bladder NP with minimally invasive electrodes, which would give them complete bladder function, with no side effects and that can be operated by pushing a button and they do not have to recharge themselves.

Influence of gravity compensation on muscle activation patterns during different temporal phases of arm movements of stroke patients.

BACKGROUND: Arm support to help compensate for the effects of gravity may improve functional use of the shoulder and elbow during therapy after stroke, but gravity compensation may alter motor control. OBJECTIVE: To obtain quantitative information on how gravity compensation influences muscle activation patterns during functional, 3-dimensional reaching movements. METHODS: Eight patients with mild hemiparesis performed 2 sets of repeated reach and retrieval movements, with and without unloading the arm, using a device that acted at the elbow and forearm to compensate for gravity. Electromyographic (EMG) patterns of 6 upper extremity muscles were compared during elbow and shoulder joint excursions with and without gravity compensation. RESULTS: Movement performance was similar with and without gravity compensation. Smooth rectified EMG (SRE) values were decreased from 25% to 50% during movements with gravity compensation in 5 out of 6 muscles. The variation of SRE values across movement phases did not differ across conditions. CONCLUSIONS: Gravity compensation did not affect general patterns of muscle activation in this sample of stroke patients, probably since they had adequate function to complete the task without arm support. Gravity compensation did facilitate active arm movement excursions without impairing motor control. Gravity compensation may be a valuable modality in conventional or robot-aided therapy to increase the intensity of training for mildly impaired patients.

The effect of information on preferences stated in a choice-based conjoint analysis.

OBJECTIVE: The objective of the study was to investigate the effect of a priori information on preferences for treatment elicited in a discrete choice experiment. METHODS: A convenience sample of 100 subjects was randomly split into two groups. The groups received minimal or extensive information on the treatment of ankle and foot impairment in stroke. Then, they participated in a discrete choice experiment. Possible treatment was described using eight decision criteria with two to four levels each. Part-worth utility coefficients for the criteria levels, criteria importance and overall treatment preference were estimated. It was tested whether the amount of information that was received influenced the outcome of the discrete choice experiment. RESULTS: In the extensively informed group fewer reversals in the expected order of part-worth utilities were found. Criteria importance for four of the eight criteria and criteria importance ranking between the minimally and extensively informed subject groups were significantly different. The difference in part-worth utility of the levels had a minor effect on the predicted utility of the available treatments. CONCLUSION: The lower number of level rank reversals in the extensively informed subjects indicates a better understanding of outcome desirability and thus a better understanding of the decision task. The effect of more extensive information on predicted treatment preference was minimal. PRACTICE IMPLICATIONS: While interpreting the results of a discrete choice experiment, the effect of prior knowledge on the decision problem has to be taken into account. Although information seems to increase the understanding of the decision task, outcomes valuation can also be directed by information and more extensive information increases the cognitive burden which is placed on the subjects. Future research should focus on the exact nature and size of the effects and the results of this study should be clinically validated.

A scoping review of metamodeling applications and opportunities for advanced health economic analyses.

INTRODUCTION: Metamodels, also known as meta-models, surrogate models, or emulators, are used in several fields of research to negate runtime issues with analyzing computational demanding simulation models. This study introduces metamodeling and presents results of a review on metamodeling applications in health economics. AREAS COVERED: A scoping review was performed to identify studies that applied metamodeling methods in a health economic context. After search and selection, 13 publications were found to employ metamodeling methods in health economics. Metamodels were used to perform value of information analysis (n = 5, 38%), deterministic sensitivity analysis (n = 4, 31%), model calibration (n = 1, 8%), probabilistic sensitivity analysis (n = 1), or optimization (n = 1, 8%). One study was found to extrapolate a simulation model to other countries (n = 1, 8%). Applied metamodeling techniques varied considerably between studies, with linear regression being most frequently applied (n = 7, 54%). EXPERT COMMENTARY: Although it has great potential to enable computational demanding analyses of health economic models, metamodeling in health economics is still in its infancy, as illustrated by the limited number of applications and the relatively simple metamodeling methods applied. Comprehensive guidance specific to health economics is needed to provide modelers with the information and tools needed to utilize the full potential of metamodels.

Variation in the time to treatment for stage III and IV non-small cell lung cancer patients for hospitals in the Netherlands.

OBJECTIVES: Increased emphasis on molecular diagnostics can lead to increased variation in time to treatment (TTT) for patients with stage III and IV non-small cell lung cancer. This article presents the variation in TTT for advanced NSCLC patients observed in Dutch hospitals before the widespread use of immunotherapy. The aim of this article was to explore the variation in TTT between patients, as well as between hospitals. MATERIAL AND METHODS: Based on the Netherlands Cancer Registry, we used patient-level data (n = 4096) from all 78 hospitals that diagnosed stage III or IV NSCLC in the Netherlands in 2016. To investigate how patient characteristics and hospital-level effects are associated with TTT (from diagnosis until start treatment), we interpreted regression model results for five common patient profiles to analyze the influence of age, gender, tumor stage, performance status, histology, and referral status as well as hospital-level characteristics on the TTT. RESULTS AND CONCLUSIONS: TTT varies substantially between and within hospitals. The median TTT was 28 days with an inter-quartile range of 22 days. The hospital-level median TTT ranges from 17 to 68 days. TTT correlates significantly with tumor stage, performance status, and histology. The hospital-level effect, unrelated to hospital volume and type, affected TTT by several weeks at most. For most patients, TTT is within range as recommended in current guidelines. Variation in TTT seems higher for patients receiving either radiotherapy or targeted therapy, or for patients referred to another hospital and we hypothesize this is related to the complexity of the diagnostic pathway. With further advances in molecular diagnostics and precision oncology we expect variation in TTT to increase and this needs to be considered in designing optimal cancer care delivery.

Incidence and prognostic factors of chronic pain after isolated musculoskeletal extremity injury.

BACKGROUND: Chronic pain in patients is usually related to an episode of pain following acute injury, emphasizing the need to prevent progression from acute to chronic pain. Multiple factors in the acute phase might be responsible for perpetuating the pain. The presentation of patients at the emergency department (ED) presents a prime opportunity to identify patients at high risk for chronic pain and to start appropriate treatment. METHODS: The PROTACT study is a prospective follow-up study aiming to estimate the incidence and prognostic factors responsible for the development of chronic pain after musculoskeletal injury. Data including sociodemographic, pain, clinical, injury- or treatment-related and psychological factors of 435 patients were collected from registries and questionnaires at ED visit, 6-week, 3- and 6-month follow-up. RESULTS: At 6 months post-injury, 43.9% of the patients had some degree of pain (Numeric Rating Scale (NRS) ≥1) and 10.1% had chronic pain (NRS ≥4). Patients aged over 40 years, in poor physical health, with pre-injury chronic pain, pain catastrophizing, high urgency level and severe pain at discharge were found to be at high risk for chronic pain. CONCLUSIONS: Two prognostic factors, severe pain at discharge and pain catastrophizing, are potentially modifiable. The implementation of a pain protocol in the ED and the use of cognitive-behavioural techniques involving reducing catastrophizing might be useful.

Preferences of general practitioners regarding an application running on a personal digital assistant in acute stroke care.

An application was developed to optimize information exchange in acute stroke care, with which general practitioners (GPs) could consult hospital emergency units. However, it was difficult to obtain clear preferences from GPs regarding the functional requirements of the information to be transferred or the architecture of the application. Thirteen GPs volunteered to take part in the study. The GPs used a personal digital assistant in their daily work for a period of six weeks when visiting stroke patients during their evening, night and weekend shifts. A conjoint analysis was conducted to obtain the least and most preferred characteristics of the application, to facilitate implementation on a larger scale. The main outcome was that GPs preferred the decision-support facilities and the presence of information about the patient's medical history.

Early treatment of trans-tibial amputees: retrospective analysis of early fitting and elastic bandaging.

This study investigates the effects of early fitting in trans-tibial amputees. The assumption is that compared to elastic bandaging, the use of a rigid dressing in early fitting will result in quicker wound healing and earlier ambulation. A retrospective file search was carried out in three different hospitals, analysing the time to first prosthesis, the incidence of local and general complications and the functional outcome after discharge from hospital. Each of the hospitals used a different method of postoperative care: elastic bandaging, immediate postoperative application of the plaster cast or delayed application of the plaster cast within one week post amputation. In comparison to the elastic bandaging method (N=52), the use of a rigid dressing in the early fitting method (immediate and delayed, N=97) resulted in a statistically significant shorter period from amputation to the delivery of a first regular prosthesis (110 days vs 50 days) and a decreased risk of knee flexion contracture. Although, differences in local complications were not observed, the risk of pressure sores in other places than the stump was increased in early fitting. Instead of further reducing the time to first prosthesis by immediate fitting, the use of delayed fitting resulted in a statistically significant shorter period from amputation to the delivery of a first regular prosthesis (56 vs 40 days). However, delayed fitting was associated with an increased risk for reamputation. In conclusion, this study indicates that early fitting by use of a rigid dressing after trans-tibial amputation is the treatment of choice. If it is possible to apply a plaster cast in the operating room, the authors would prefer the immediate fitting method.

Cervical muscle dysfunction in the chronic whiplash associated disorder grade II (WAD-II).

STUDY DESIGN: In a cross-sectional study, surface electromyography measurements of the upper trapezius muscles were obtained during different functional tasks in patients with a chronic whiplash associated disorder Grade II and healthy control subjects. OBJECTIVES: To investigate whether muscle dysfunction of the upper trapezius muscles, as assessed by surface electromyography, can be used to distinguish patients with whiplash associated disorder Grade II from healthy control subjects. SUMMARY OF BACKGROUND INFORMATION: In the whiplash associated disorder, there is need to improve the diagnostic tools. Whiplash associated disorder Grade II is characterized by the presence of "musculoskeletal signs." Surface electromyography to assess these musculoskeletal signs objectively may be a useful tool. METHODS: Normalized smoothed rectified electromyography levels of the upper trapezius muscles of patients with whiplash associated disorder Grade II (n = 18) and healthy control subjects (n = 19) were compared during three static postures, during a unilateral dynamic manual exercise, and during relaxation after the manual exercise. Coefficients of variation were computed to identify the measurement condition that discriminated best between the two groups. RESULTS: The most pronounced differences between patients with whiplash associated disorder Grade II and healthy control subjects were found particularly in situations in which the biomechanical load was low. Patients showed higher coactivation levels during physical exercise and a decreased ability to relax muscles after physical exercise. CONCLUSIONS: Patients with whiplash associated disorder Grade II can be distinguished from healthy control subjects according to the presence of cervical muscle dysfunction, as assessed by surface electromyography of the upper trapezius muscles. Particularly the decreased ability to relax the trapezius muscles seems to be a promising feature to identify patients with whiplash associated disorder Grade II. Assessment of the muscle (dys)function by surface electromyography offers a refinement of the whiplash associated disorder classification and provides an indication to a suitable therapeutic approach.