Somatosensory Outcomes Following Re-Surgery in Persistent Severe Pain After Groin Hernia Repair: A Prospective Observational Study.

Purpose: After groin hernia repair (globally more than 20 million/year) 2-4% will develop persistent severe pain (PSPG). Pain management is challenging and may require multimodal interventions, including re-surgery. Quantitative somatosensory testing (QST) is an investigational psychophysiological tool with the potential to uncover the pathophysiological mechanisms behind the pain, ie, revealing neuropathic or inflammatory components. The primary objective was to examine and describe the underlying pathophysiological changes in the groin areas by QST before and after re-surgery with mesh removal and selective neurectomy. Patients and Methods: Sixty patients with PSPG scheduled for re-surgery and with an inflammatory "component" indicated by blunt pressure algometry were examined in median (95% CI) 7.9 (5.8-11.5) months before and 4.0 (3.5-4.6) months after re-surgery. The QST-analyses included standardized assessments of cutaneous mechanical/thermal detection and pain thresholds. Suprathreshold heat stimuli were applied. Deep tissue sensitivity was tested by pressure algometry. Testing sites were the groin areas and the lower arm. Before/after QST data were z-transformed. Results: Re-surgery resulted in median changes in rest, average, and maximal pain intensity scores of -2.0, -2.5, and -2.0 NRS (0/10) units, respectively (P = 0.0001), and proportional increases in various standardized functional scores (P = 0.0001). Compared with the control sites, the cutaneous somatosensory detection thresholds of the painful groin were increased before re-surgery and increased further after re-surgery (median difference: 1.28 z-values; P = 0.001), indicating a successive post-surgical loss of nerve fiber function ("deafferentation"). Pressure algometry thresholds increased after re-surgery (median difference: 0.30 z-values; P = 0.001). Conclusion: In this subset of patients with PSPG who underwent re-surgery, the procedure was associated with improved pain and functional outcomes. While the increase in somatosensory detection thresholds mirrors the surgery-induced cutaneous deafferentation, the increase in pressure algometry thresholds mirrors the removal of the deep "pain generator". The QST-analyses are useful adjuncts in mechanism-based somatosensory research.

Methylphenidate as Needed for Fatigue in Patients With Advanced Cancer. A Prospective, Double-Blind, and Placebo-Controlled Study.

CONTEXT: Cancer-related fatigue is a highly prevalent symptom with a strong negative impact on patients' daily life. OBJECTIVES: To evaluate the efficacy of methylphenidate as needed for the management of fatigue in patients with advanced cancer. METHODS: A prospective, controlled, double-blind, and paired design, where the patient was her and/or his own control. Patients with advanced cancer with a tiredness score of ≥50 on a 0-100 visual analogue scale (VAS) were included. Patients were given 10 placebo and 10 methylphenidate tablets numbered 1-20 packed in blocks of four with two active and two placebo tablets (randomly arranged). Patients taking minimum three tablets were regarded evaluable. Primary effect parameters were mean differences in VAS for tiredness after two and five hours. With 28 evaluable patients, the study had a power of 0.90 to detect a mean difference of 15 between active and placebo. RESULTS: Thirty-eight patients were enrolled to get 28 evaluable patients. Mean tiredness score before taking the tablets was 75 for placebo and 72 for methylphenidate on VAS (0-100). Mean changes (decrease) for methylphenidate after two and five hours were 20 and 17, respectively, and eight and five for placebo. Comparing mean differences, a significant decrease for methylphenidate compared with placebo was observed after two hours (P = 0.004) and five hours (P = 0.001), respectively. CONCLUSION: In this controlled and double-blind study in patients with advanced cancer, methylphenidate as needed was significantly more effective than placebo in relieving fatigue after two and five hours.

Patient-reported symptoms and problems at admission to specialized palliative care improved survival prediction in 30,969 cancer patients: A nationwide register-based study.

BACKGROUND: Large, nationally representative studies of the association between quality of life and survival time in cancer patients in specialized palliative care are missing. AIM: The aim of this study was to investigate whether symptoms/problems at admission to specialized palliative care were associated with survival and if the symptoms/problems may improve prediction of death within 1 week and 1 month, respectively. SETTING/PARTICIPANTS: All cancer patients who had filled in the EORTC QLQ-C15-PAL at admission to specialized palliative care in Denmark in 2010-2017 were included through the Danish Palliative Care Database. Cox regression was used to identify clinical variables (gender, age, type of contact (inpatient vs outpatient), and cancer site) and symptoms/problems significantly associated with survival. To test whether symptoms/problems improved survival predictions, the overall accuracy (area under the receiver operating characteristic curve) for different prediction models was compared. The validity of the prediction models was tested with data on 5,508 patients admitted to palliative care in 2018. RESULTS: The study included 30,969 patients with an average age of 68.9 years; 50% were women. Gender, age, type of contact, cancer site, and most symptoms/problems were significantly associated with survival time. The predictive value of symptoms/problems was trivial except for physical function, which clearly improved the overall accuracy for 1-week and 1-month predictions of death when added to models including only clinical variables. CONCLUSION: Most symptoms/problems were significantly associated with survival and mainly physical function improved predictions of death. Interestingly, the predictive value of physical function was the same as all clinical variables combined (in hospice) or even higher (in palliative care teams).

A national center for persistent severe pain after groin hernia repair: Five-year prospective data.

Severe persistent pain after groin hernia repair impairs quality-of-life. Prospective, consecutive cohort study including patients with pain-related impairment of physical and social life. Relevant surgical records were obtained, and examinations were by standardized clinical and neurophysiological tests. Patients demonstrating pain sensitivity to pressure algometry in the operated groin underwent re-surgery, while patients with neuropathic pain received pharmacotherapy. Questionnaires at baseline (Q0) and at the 5-year time point (Q5Y) were used in outcome analyses of pain intensity (numeric rating scale [NRS] 0-10) and pain-related effect on the activity-of-daily-living (Activities Assessment Scale [AAS]). Data are mean (95% CI).Analyses were made in 172/204 (84%) eligible patients. In 54/172 (31%) patients re-surgery (meshectomy/selective neurectomy) was performed, while the remaining 118/172 (69%) patients received pharmacotherapy. In the re-surgery group, activity-related, and average NRS-scores at Q0 were 6.6 (5.6-7.9) and 5.9 (5.6-5.9), respectively. Correspondingly, NRS-scores at Q5Y was 4.1 (3.3-5.1) and 3.1 (2.3-4.0; Q0 vs. Q5Y: P < .0005), respectively. Although both groups experienced a significant improvement in AAS-scores comparing Q0 vs. Q5Y (re-surgery group: 28% (4-43%; P < .0001); pharmacotherapy group: 5% (0-11%; P = .005)) the improvement was significantly larger in the re-surgery group (P = .02).This 5-year cohort study in patients with severe persistent pain after groin hernia repair signals that selection to re-surgery or pharmacotherapy, based on examination of pain sensitivity, is associated with significant improvement in outcome. Analyzing composite endpoints, combining pain and physical function, are novel in exploring interventional effects.ClinicalTrials.gov Identifier NCT03713047.

How does pain experience relate to the need for pain relief? A secondary exploratory analysis in a large sample of cancer patients.

PURPOSE: To explore (1) the information obtained from related but conceptually different approaches to pain assessment and (2) the extent to which the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) can be used as a screening tool to predict patient-reported need for pain relief. METHODS: Cancer patients randomly sampled from 56 hospital departments were included. Questionnaire items assessed patients' (a) pain experience using the EORTC QLQ-C30 pain scale and its two pain items separately (pain intensity and pain interference) and (b) pain burden and (c) need for pain relief using the Three-Levels-of-Needs Questionnaire (3LNQ). RESULTS: Of the 2364 patients contacted by mail, 1447 (61 %) completed the questionnaires. Among these, 51 % reported at least "a little" pain on the pain intensity item. The number of patients reporting pain to be a burden was similar, and pain experience and pain burden were highly correlated (correlation coefficients ranged from 0.85 to 0.91). Pain experience and pain burden were moderately correlated with the need for pain relief. A receiver-operating characteristic (ROC) curve analysis showed that the EORTC QLQ-C30 discriminated between patients with and without a need for pain relief to an acceptable degree (area under the curve (AUC) 0.73-0.77). The cut-point a little gave a sensitivity of 84 % and specificity of 59 % for the item "Have you had pain?" and a sensitivity of 72 % and a specificity of 72 % for the pain scale. CONCLUSIONS: The majority of patients who experienced pain felt it to be a problem. Pain experience and pain burden were substantially related to need for pain relief, and the latter could be predicted from the EORTC QLQ-C30.

Demarcation of secondary hyperalgesia zones: Punctate stimulation pressure matters.

BACKGROUND: Secondary hyperalgesia is increased sensitivity in normal tissue near an injury, and it is a measure of central sensitization reflecting injury-related effects on the CNS. Secondary hyperalgesia areas (SHAs), usually assessed by polyamide monofilaments, are important outcomes in studies of analgesic drug effects in humans. However, since the methods applied in demarcating the secondary hyperalgesia zone seem inconsistent across studies, we examined the effect of a standardized approach upon the measurement of SHA following a first degree burn injury (BI). NEW METHOD: The study was a two-observer, test-retest study with the two sessions separated by 6wk. An observer-blinded design adjusted to examine day-to-day and observer-to-observer variability in SHA was used. In 23 healthy volunteers (12 females/11 males) a BI was induced by a contact thermode (47.0°C, 420s, 2.5×5.0cm(2)). The SHA, demarcated by polyamide monofilaments (bending force: 0.2, 69 and 2569mN) and a "weighted-pin" stimulator (512mN), were assessed 45 to 75min after each BI. RESULTS: A random effect, linear mixed model demonstrated a logarithmic correlation between elicited skin pressures (mN/mm(2)) and the SHAs (P<0.0001). No day-to-day or observer-to-observer differences in SHAs were observed. Intraclass correlation coefficients, in the range of 0.51 to 0.84, indicated a moderate to almost perfect reliability between observers. COMPARISON WITH EXISTING METHODS: No standardized approach in SHA-assessment has hitherto been presented. CONCLUSIONS: This is the first study to demonstrate that demarcation of secondary hyperalgesia zones depends on the developed pressure of the punctate stimulator used.

The validity and reliability of the 'Cancer Caregiving Tasks, Consequences and Needs Questionnaire' (CaTCoN).

BACKGROUND: Caregivers are often involved in and affected by the patient's disease. The questionnaire 'Cancer Caregiving Tasks, Consequences and Needs Questionnaire' (CaTCoN) was developed to measure caregivers' experiences. The aim of this study is to evaluate the construct validity and reliability of the multi-item scales in the CaTCoN using psychometric analyses as well as tests of convergent and discriminant validity with the existing instruments FAMCARE and Family Inventory of Needs (FIN). MATERIAL AND METHODS: Based on theoretical considerations, a subscale structure in the CaTCoN was hypothesized, and the subscales were tested by item-item correlations, followed by factor analysis, calculation of internal consistency by Cronbach's alpha, and multitrait-scaling analysis. Further, theoretically based hypotheses about convergence and divergence between CaTCoN and FAMCARE/FIN (sub)scales were formulated and tested. RESULTS: Analyses were based on 590 caregivers' responses. Initially, 11 CaTCoN subscales were hypothesized. The item-item correlations and factor analysis lead to some revisions, but the analyses confirmed the hypothesized subscales to a large extent, resulting in nine CaTCoN subscales (Cronbach's alpha range 0.65-0.95). The hypothesized convergent CaTCoN and FAMCARE/FIN subscales correlated 0.59-0.74, and hypothesized divergent CaTCoN and FAMCARE/FIN subscales correlated -0.11-0.25, thus confirming the hypotheses concerning convergent and discriminant validity between CaTCoN and the existing questionnaires FAMCARE and FIN. CONCLUSION: Taken together the psychometric analyses and tests of convergent and discriminant validity indicate that the validity and reliability of the CaTCoN are satisfactory.

An evaluation of the response category translations of the EORTC QLQ-C30 questionnaire.

PURPOSE: The aim of this study was to evaluate the translated response categories used in eight translations of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, which is used in many international clinical trials. Twenty-eight of the 30 items in the questionnaire have the same four response categories: "Not at all", "A little", "Quite a bit" and "Very Much". METHODS: People with knowledge of both English and one of eight European languages were asked to complete an Internet survey. The strength (intensity) of the translated categories was assessed using two separate approaches: one using a verbal response scale and the other a visual analogue scale (VAS). RESULTS: Two hundred and seventy-nine people participated in the survey. Most translations were rated similarly to English. The largest differences were for the German translation of "Quite a bit", which was rated 16.3 points lower than the corresponding English category on a 0-100 VAS. CONCLUSIONS: Most of the translated categories were found to be similar to the English versions and should continue to be used. We recommend that three translated categories should be considered for revision. Similar surveys could be used to assess the categories used in other translated quality of life instruments.

The relatives' perspective on advanced cancer care in Denmark. A cross-sectional survey.

PURPOSE: In order to improve advanced cancer care, evaluations are necessary. An important element of such evaluations is the perspective of the patient's relatives who have the role of being caregivers as well as co-users of the health care system. The aims were to investigate the scale structure of the FAMCARE scale, to investigate satisfaction with advanced cancer care from the perspective of the relatives of a representative sample of advanced cancer patients, and to investigate whether some sub-groups of relatives were more dissatisfied than others. METHOD: From 977 patients treated at 54 different Danish hospital departments, 569 patients provided us with the name and address of their relative. Of these, 544 received the FAMCARE scale that measures the families' satisfaction with advanced cancer care. For the four FAMCARE sub-scales, internal consistency was analyzed using Cronbach's alpha; convergent and discriminant validity was analyzed using multitrait-scaling analysis. Associations between the relatives' dissatisfaction and clinical and sociodemographic variables were investigated in explorative analyses using multiple logistic regressions. RESULTS: Of the relatives receiving the questionnaire, 467 (86%) responded. The original scale structure of FAMCARE could not be supported in the present sample, and therefore, results are reported at singe-item level. The proportion of dissatisfied relatives ranged from 5% to 28% (median 13%). Highest levels of dissatisfaction were found for time taken to make a diagnosis (28%) and the speed with which symptoms were treated (25%). Younger relatives were more dissatisfied than older relatives. Other sociodemographic and clinical variables had little impact on the relatives' levels of satisfaction. CONCLUSION: The relatives' level of dissatisfaction with some of the areas included in this survey needs to be taken seriously. Younger relatives were most dissatisfied.

Development and initial validation of the Three-Levels-of-Needs Questionnaire for self-assessment of palliative needs in patients with cancer.

CONTEXT: To improve palliative care, it is important that questionnaires accurately assess the needs of the patients. No questionnaire existed that combined three different and important approaches to needs assessment. We developed such a questionnaire, called the Three-Levels-of-Needs Questionnaire (3LNQ), based on literature searches. The 3LNQ measures 12 important needs with three different approaches when used as a supplement to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30): problem intensity, problem burden, and felt need. OBJECTIVES: To investigate the initial validity of the 3LNQ. METHODS: We used a relatively new method that investigates whether the questionnaire has the same meaning for the patients as for the researchers. To do this, 74 patients with advanced cancer filled out the questionnaire and participated in an open-ended interview. The patients' responses to the questionnaire before the interview were compared against the researchers' responses based on the interviews. Items showing substantial agreement were accepted as valid without further analysis. For the remaining items, reasons for disagreements were analyzed qualitatively. RESULTS: All items on problem intensity, eight of 12 items on problem burden, and three of 12 items on felt need were accepted as valid because of high agreement. Analysis of the qualitative data concerning the remaining items showed that most disagreements did not indicate problems with the patients' self-assessment. Instead, different causes for disagreements were elucidated, but these did not interfere with validity. CONCLUSION: The 3LNQ appears to measure palliative needs comprehensively, and this initial validation showed satisfactory results. The analysis gave important insights into the patients' perceptions of their own situations, into their expectations of the health care system, and into the complexity of needs assessment.

Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression.

BACKGROUND: Differential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise when testing for DIF in HRQoL instruments. We focus on logistic regression methods, which are often used because of their efficiency, simplicity and ease of application. METHODS: A review of logistic regression DIF analyses in HRQoL was undertaken. Methodological articles from other fields and using other DIF methods were also included if considered relevant. RESULTS: There are many competing approaches for the conduct of DIF analyses and many criteria for determining what constitutes significant DIF. DIF in short scales, as commonly found in HRQL instruments, may be more difficult to interpret. Qualitative methods may aid interpretation of such DIF analyses. CONCLUSIONS: A number of methodological choices must be made when applying logistic regression for DIF analyses, and many of these affect the results. We provide recommendations based on reviewing the current evidence. Although the focus is on logistic regression, many of our results should be applicable to DIF analyses in general. There is a need for more empirical and theoretical work in this area.

Interpretation of differential item functioning analyses using external review.

Differential item functioning (DIF) analyses are used to determine whether certain groups respond differently to a particular item of a test or questionnaire; however, these do not explain the reasons for observed response differences. Many studies have used external reviews of items, sometimes using blinded reviewers, to help interpret these results. The authors conducted a literature review of this topic to describe the current usage of external reviews alongside DIF analyses. It concentrated on studies of health-related quality of life instruments, but studies in other fields were also considered. Relatively few examples of blinded item reviews were identified, and these were mostly from educational studies. A case study using blinded bilingual reviewers alongside translation DIF analyses of a health-related quality of life instrument is described. Future researchers should consider conducting external item reviews alongside DIF analyses.

Does nonparticipation in studies of advanced cancer lead to biased quality-of-life scores?

BACKGROUND AND OBJECTIVE: Missing data are a common problem in palliative care research. Often the most impaired patients are unable to participate in studies. This may result in biased findings. We investigated whether observed patient reported outcomes should be adjusted for bias resulting from nonparticipation. METHODS: Of 791 patients with cancer admitted to palliative care, 304 (38%) participated by answering the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire. For the 15 symptoms and problems measured by the EORTC QLQ-C30 mean scores based on observed responses only were compared to two methods including imputed (estimated) scores based on patient characteristics for the missing data. RESULTS: All mean differences between scores based on observed responses only and the two methods including imputed scores for the missing data were less than 5 on a 0-100 scale. For 4 of the 30 comparisons a significant underestimation of symptomatology was found when using observed responses only. CONCLUSIONS: We did not find indications that using observed responses only resulted in clinically important underestimation of palliative care patients' symptomatology. Either nonparticipants' scores did not differ significantly from participants' or the variables used to describe the non-participants were insufficient predictors of the patients' scores. In any case, the study indicated that imputation of scores of nonparticipants in palliative care may not be worthwhile unless very good predictors are available.

The practical impact of differential item functioning analyses in a health-related quality of life instrument.

INTRODUCTION: Differential item functioning (DIF) analyses are commonly used to evaluate health-related quality of life (HRQoL) instruments. There is, however, a lack of consensus as to how to assess the practical impact of statistically significant DIF results. METHODS: Using our previously published ordinal logistic regression DIF results for the Fatigue scale of a HRQoL instrument as an example, the practical impact on a particular Norwegian clinical trial was investigated. The results were used to determine the difference in mean Fatigue scores assuming that the same trial was conducted in the UK. The results were then compared with published information on what would be considered a clinically important change in scores. RESULTS: The item with the largest DIF effect resulted in differences between the mean English and Norwegian Fatigue scores that, although small, could be considered clinically important. Sensitivity analyses showed that larger differences were found for shorter scales, and when the proportions in each response category were equal. DISCUSSION: Our scenarios suggest that translation differences in an item can result in small, but clinically important, differences at the scale score level. This is more likely to be problematic for observational studies than for clinical trials, where randomised groups are stratified by centre.

Differential item functioning (DIF) in the EORTC QLQ-C30: a comparison of baseline, on-treatment and off-treatment data.

INTRODUCTION: Differential item functioning (DIF) analyses can be used to explore translation, cultural, gender or other differences in the performance of quality of life (QoL) instruments. These analyses are commonly performed using "baseline" or pretreatment data. We previously reported DIF analyses to examine the pattern of item responses for translations of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 QoL instrument, using only data collected prior to cancer treatment. We now compare the consistency of these results with similar analyses of on-treatment and off-treatment assessments and explore whether item relationships differ from those at baseline. METHODS: Logistic regression DIF analyses were used to examine the translation of each item in each multi-item scale at the three time points, after controlling for the overall scale score and other covariates. The consistency of results at the three time points was explored. RESULTS: For most EORTC QLQ-C30 subscales, the DIF results were very consistent across the three time points. Results for the Nausea and Vomiting scale varied the most across assessments. DISCUSSION: The results indicated that DIF analyses were stable across each time point and that the same DIF effects were usually found regardless of the treatment status of the respondent.

A simulation study provided sample size guidance for differential item functioning (DIF) studies using short scales.

OBJECTIVE: Differential item functioning (DIF) analyses are increasingly used to evaluate health-related quality of life (HRQoL) instruments, which often include relatively short subscales. Computer simulations were used to explore how various factors including scale length affect analysis of DIF by ordinal logistic regression. STUDY DESIGN AND SETTING: Simulated data, representative of HRQoL scales with four-category items, were generated. The power and type I error rates of the DIF method were then investigated when, respectively, DIF was deliberately introduced and when no DIF was added. The sample size, scale length, floor effects (FEs) and significance level were varied. RESULTS: When there was no DIF, type I error rates were close to 5%. Detecting moderate uniform DIF in a two-item scale required a sample size of 300 per group for adequate (>80%) power. For longer scales, a sample size of 200 was adequate. Considerably larger sample sizes were required to detect nonuniform DIF, when there were extreme FEs or when a reduced type I error rate was required. CONCLUSION: The impact of the number of items in the scale was relatively small. Ordinal logistic regression successfully detects DIF for HRQoL instruments with short scales. Sample size guidelines are provided.

The relationship between overall quality of life and its subdimensions was influenced by culture: analysis of an international database.

OBJECTIVE: To investigate whether geographic and cultural factors influence the relationship between the global health status quality of life (QL) scale score of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire and seven other subscales representing fatigue, pain, physical, role, emotional, cognitive, and social functioning. STUDY DESIGN AND SETTING: A large international database of QLQ-C30 responses was assembled. A linear regression model was developed predicting the QL scale score and including interactions between geographical/cultural groupings and the seven other scale scores. RESULTS: The pain subscale appeared to have relatively greater influence and fatigue relatively lower influence for those from other European regions compared with respondents from the UK when predicting overall quality of life (QoL). For Scandinavia physical functioning appeared to contribute relatively less. There was evidence of greater emphasis on cognitive functioning for those from South Asia and Latin America compared with the UK, whereas for those from Islamic countries, the role functioning scale appeared to have less influence and physical and social functioning more influence. CONCLUSION: These results provide evidence that different cultural groups may emphasize different aspects of their QoL. This has implications for studies using QoL questionnaires in international comparisons.

Multidimensional measurement of fatigue in advanced cancer patients in palliative care: an application of the multidimensional fatigue inventory.

To investigate the level, dimensionality, and correlates associated with fatigue in patients receiving specialist palliative care, 278 advanced cancer patients referred to a department of palliative medicine during a 2-year period were asked to complete the Multidimensional Fatigue Inventory (MFI-20), a self-assessment questionnaire measuring five dimensions of fatigue, and the Hospital Anxiety and Depression Scale. Of 267 eligible patients, 130 (49%) participated. Mean fatigue scores (0-100 scale) were very high, especially for general fatigue (81), physical fatigue (87), and reduced activity (85). Only some of the MFI-20 subscales were significantly correlated. Fatigue was not correlated with sociodemographic factors. Depressed patients had higher scores on all five subscales except physical fatigue. Anxious patients had higher levels on the mental fatigue subscale only. The variation in fatigue explained by depression varied markedly (4%-31%) among subscales. Fatigue levels were very high in this population. The lack of significant correlation between some subscales indicates that they measure different aspects of fatigue. This is also supported by the differences in associations between fatigue subscales and depression and anxiety.