Functional Activity Status Research Articles

External treatment of traditional Chinese medicine for cancer pain: A systematic review and network meta-analysis.

Cancer pain is one of the most intolerable and frightening symptoms of cancer patients. However, the clinical effect of the three-step analgesic ladder method (TSAL) is not satisfactory. The combination of external treatment of traditional Chinese medicine (TCM) can improve the clinical effect. This study used network meta-analysis to compare the effects of different external treatment methods of TCM combined with TSAL on cancer pain. Databases searched by our team included Google Scholar, Web of Science, Scopus, Embase, PubMed, and Cochrane Library. Randomized controlled trials related to the external treatment of TCM combined with TSAL for cancer pain were screened from the establishment of the database till now. The above literature extracted clinical efficacy, NRS score, KPS score, analgesic onset time, and duration as the main results after the screening. The 95% confidence interval (95% CI) of OR value and SMD value was used as the effect index to compare the difference in efficacy of different interventions, and the ranking was conducted. STATA 17.0 software was used for the statistical analysis of the above data. A total of 78 studies were included, including 8 interventions and 5742 participants. Based on ranking probability, the clinical effective rate of manual acupuncture combined with TSAL was the best when the intervention time was set at 4 weeks [OR = 5.42, 95% CI (1.99,14.81)], and the improvement effect on KPS score was also the best [SMD = 0.97, 95% CI (0.61, 1.33)]. Acupoint external application was the best intervention in reducing NRS score [SMD = -1.14, 95% CI (-1.90, -0.93)]. Acupoint moxibustion combined with TSAL was considered to be the most effective intervention to prolong the duration of analgesia [SMD = 1.69, 95% CI (0.84, 2.54)] and shortening the onset time of analgesia [SMD = -3.00, 95% CI (-4.54, -1.47)]. TSAL combined with manual acupuncture is the best in terms of clinical efficacy and improvement of patients' functional activity status. With the extension of treatment time, the intervention of this kind of treatment on the clinical effect is more pronounced. Acupoint external application also has a unique advantage in reducing the pain level of patients. From the point of view of analgesic duration and duration of analgesia, combined acupoint moxibustion has the best effect.

Abstract A131: Fulvestrant resistance in an MCF-7 model for breast cancer is associated with complete loss of ER pathway activity and gain of MAPK-AP1 pathway activity

Abstract Background: 10-15 signal transduction pathways govern major cellular processes, e.g. cell division, differentiation and migration, both in physiology and pathophysiology. They are frequently abnormally active in cancer and can drive cancer growth and metastasis. Resistance to targeted drugs directed towards specific signaling pathways like the ER pathway, can be mediated by induction of activity of other signaling pathways. The past decade we developed a new method to quantitatively measure functional activity status of signal transduction pathways in individual cell and tissue samples, based on Bayesian computational model inference of pathway activity from measurements of mRNA levels of target genes of the pathway-associated transcription factor1,2,3. Assays have been developed for androgen (AR) and estrogen receptor (ER), Hedgehog (HH), Wnt, TGFb, Notch, NFkB, PI3K, JAK-STAT 1/2 and 3, and MAPK-AP1 pathways. They can be performed simultaneously on a single cell or tissue sample using Affymetrix HG-U133 Plus 2.0 microarray or qPCR, and provide quantitative pathway activity scores expressed on a log2odds scale. Method. Pathway analysis using these assays was performed on public Affymetrix expression microarray data (GSE74391,4) from ER-positive MCF-7 cells that were either sensitive or resistant to fulvestrant (n=26). Results. Resistance to fulvestrant was associated with complete loss of functional ER pathway activity (difference 16 log2odds score, p=0.00029) and gain of MAPK-AP1 pathway activity (difference 5.8 log2odds, p=0.00029) in ER positive MCF-7 cells. In the resistant MCF-7 cells, PI3K and MAPK-AP1 pathway activity were negatively correlated (Pearson 0.652, p=0.002), suggesting mutually exclusive pathway activation. Conclusion. Our pathway assays enabled identification of the previously unidentified mechanism of resistance to fulvestrant in a cell culture model system for breast cancer, demonstrating that: (1) ER positivity is a prerequisite, but not sufficient, for ER pathway activity, in agreement with our earlier clinical studies1,5,6;; (2) MAPK pathway activity may confer resistance to hormonal therapy; (3) in the absence of MAPK-AP1 pathway activity, the PI3K pathway may be an alternative resistance pathway; (3) signalling pathway assays are well suited to (quantitatively) investigate activity of signal transduction pathways which may confer resistance to a (targeted) drug treatment.

Abstract 2371: Breast cancer induces tolerogenic state of healthy activated CD4+ lymphocytes, characterized by reduced PI3K, NFκB, JAK-STAT, Notch, and increased TGFβpathway activity

Abstract Tumor cells can induce immunotolerance, which is reversed by checkpoint blockade immunotherapy in some patients, although response prediction remains a challenge. CD4+ T cells play an important role in activating adaptive immune responses with their conversion to a suppressed state impairing anti-tumor immune responses. CD4+ T cells function by activating and controlling various signal transduction pathways. Over the past decade we have developed tests that quantitatively measure functional activities of signal transduction pathways (e.g. Hedgehog, Wnt, TGFβ Notch, NFκB, PI3K, JAK-STAT 1/2 and 3, and MAPK). They are based on Bayesian computational model inference of pathway activities from measurements (expression microarray, qPCR) of mRNA levels of target genes of the transcription factor associated with the respective signalling pathways1,2. These tests were extensively biologically validated, including on immune cells, and can be used to characterize their functional activity status. In the present study, this approach was used to investigate cellular mechanisms underlying breast cancer-induced immunosuppression of CD4+ T cells. Method: Generation of Affymetrix gene expression data has been previously described (J Clin Invest 2013;123(7):2873-92) and data is publically available (GEO dataset GSE36766). Briefly, breast cancer tissue sections from fresh surgical specimens were mechanically dissociated in X-VIVO 20. Following activation with anti-CD3/CD28, CD4+ T cells from healthy donor blood were incubated with primary tumor supernatants (SN) and compared to controls. Signaling pathway activities were measured using Affymetrix expression data from the individual CD4+ T cell treatment groups. Results: CD4+ T cell activation resulted in induction of PI3K, NFkB, JAK-STAT1/2, JAK-STAT3, Notch, and parallel decrease in TGFβ pathway activities. Incubation with primary tumor SN did not affect pathway activity in non-activated CD4+ T cells, but reduced activity of PI3K, NFκB, JAK-STAT1/2, JAK-STAT3, Notch, while increasing TGFβ pathway activity in activated CD4+ T cells. Conclusion: A soluble factor(s) from breast tumor tissues increases TGFβ and reduces effector immune pathway activity in activated CD4+ T cells and thereby can induce an immunotolerant state. Investigation into the nature of this soluble factor(s) is in progress. These data demonstrate that signaling pathway assays can be used to quantitatively measure the functional state of immune responses in CD4+ lymphocytes. The ultimate goal is to apply this approach for predicting and monitoring immunotherapy responses and identifying novel drug targets that can reverse tumor-induced immunosuppression. Ref: 1. Verhaegh W, et al. Cancer Res 2014;74(11):2936-45; 2. Ooijen H. van, et al. Am J Pathol 2018;188(9):1956-1972. Citation Format: Anja Van De Stolpe, Wim Verhaegh, Arie van Doorn, Grégory Noël, Chunyan Gu-Trantien, Karen Willard-Gallo. Breast cancer induces tolerogenic state of healthy activated CD4+ lymphocytes, characterized by reduced PI3K, NFκB, JAK-STAT, Notch, and increased TGFβpathway activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2371.

Cognitive rehabilitation is advantageous in terms of fatigue and independence in pediatric cancer treatment: a randomized-controlled study.

This study aimed to investigate the effect of task-oriented inpatient cognitive rehabilitation on fatigue perception and independence in daily activities. Forty (22 males, 18 females) children with pediatric cancer were randomized to either study [n = 22; 10.81 (1.33) years] or control [n = 18; 10.16 (1.24) years] groups. The study group received a cognitive rehabilitation intervention in addition to a routine therapy program, and the control group received a routine therapy program for 15 sessions. Cognitive status, fatigue, and daily life activity outcomes were assessed by blinded assessors in before and after interventions in the hospital setting. The study group showed a significant decrease in fatigue (P values for fatigue before, during, and after activity: P < 0.001) and in the control group (P values for fatigue only in during and post activity: P < 0.05). A statistically significant improvement was found in functional independence for the study group in all activities of daily living areas areas (P < 0.001), whereas no differences were found in the control group. Cognitive rehabilitation appears to provide beneficial effects in decreasing fatigue, improving functional status in activities of daily living, and increasing cognitive skills at the early stages in inpatient rehabilitation of pediatric cancer.

Effectiveness of multisensory stimulation in managing neuropsychiatric symptoms in older adults with major neurocognitive disorder: a systematic review

The objective of the review was to synthesize the effectiveness of multisensory stimulation in managing neuropsychiatric symptoms (NPS) in older adults with major neurocognitive disorder (NCD). Major neurocognitive disorder is characterized by changes in specific cognitive domains with a progressive deterioration in cognitive ability and capacity for independent living. Most older adults with this condition have one or more concomitant symptoms known as NPS. Evidence shows that nonpharmacological therapies have been effective in controlling these symptoms, with multisensory stimulation attracting further investigation. The review considered studies on older adults aged 65 years or over with major NCD. The intervention of interest was multisensory stimulation, and the comparator was usual care (e.g. no occupational therapy, no cognitive training, and no art therapy, but with possible control of activities such as looking at photographs or doing quizzes), or another intervention (e.g. occupational therapy, cognitive training and art therapy). Primary outcomes were NPS (agitation, aggression, motor disturbances, mood liability, anxiety, apathy, night-time behaviour, eating disorders, delusion and hallucination). Secondary outcomes were quality of life, functional status in activities of daily living, cognitive status and caregiver burden. Experimental study designs were considered. A broad range of keywords and a three-step search strategy were used to identify potentially eligible published and unpublished studies from January 1990 to June 2016 in major healthcare-related online databases. Studies in English, Spanish and Portuguese were included. Two independent reviewers assessed the methodological quality of eight included studies using the Joanna Briggs Institute (JBI) Critical Appraisal Checklists for Randomized Controlled Trials and Quasi-Experimental Studies. Data were extracted using the standardized data extraction tool from the JBI System for the Unified Management, Assessment and Review of Information (JBI SUMARI) and included details about the interventions, populations, study methods and outcomes of interest. Significant differences were found between participants, interventions, outcome measures (clinical heterogeneity), and designs (methodological heterogeneity). For these reasons, a meta-analysis could not be performed. Therefore, the results have been described in a narrative format. Eight studies (seven randomized controlled trials and one quasi-experimental study) were included, with a total sample of 238 participants (pre-intervention). Four studies confirmed the effectiveness of multisensory stimulation in domains such as physically nonaggressive behavior, verbally agitated behavior and agitation. However, these effects did not always persist in the long-term. Six studies showed poorly consistent results on the effects of multisensory stimulation in improving mood, with only one displaying significant effects. Similarly, despite poor results, two studies showed benefits concerning anxiety. Participants reported significantly decreased levels of anxiety over the course of the intervention, and this improvement persisted in the long-term. In regard to functional status in activities of daily living, two studies reported an improvement in the short-term. Moreover, the effectiveness in cognitive domains such as memory and attention to surroundings also showed inconsistent results across the seven studies that analyzed this outcome. Two studies reflected an improvement during the intervention, but also reported a gradual decline in the long-term. Only one study observed significantly better results during the intervention that persisted until the follow-up assessment. Apathy, night-time behavior, eating disorders, delusion and hallucination were NPS that were not explored in the studies that met the criteria to be included in this review. These findings suggest that multisensory stimulation could be an effective intervention for managing NPS in older adults with major NCD in a mild to severe stage, particularly for managing behavioral symptoms such as agitation. This research provides an indication of the likely effect of the multisensory stimulation on NPS such as agitation and anxiety, as well on cognitive status.

Femoroacetabular Impingement Syndrome

Femoroacetabular impingement syndrome (FAI), which might lead to early osteoarthritis, serves as a reason of hip pain. The main problem is considered as the abnormal contact between the femoral head and the acetabulum. In general, it presents as slowly progressing hip pain in young adults. There are 3 types of FAI including the cam, pincer and mixt types. The diagnosis is based upon the clinical history, functional activity status, physical examination and radiologic evaluation. The treatment is comprised of conservative regimen (activity limitation/modification and pain control) and surgery.

The effect of isokinetic and aerobic exercises on serum interleukin-6 and tumor necrosis factor alpha levels, pain, and functional activity in patients with knee osteoarthritis

Objectives. The aim of this study is to investigate the effects of isokinetic and aerobic exercise training programs on serum pro-inflammatory cytokine levels, pain, and functional activity in patients with knee osteoarthritis (OA).Methods. Forty-two postmenopausal women and men with knee OA according to American College of Rheumatology diagnostic criteria were included. Patients were randomized into isokinetic and aerobic exercises and control groups. In intervention groups, patients were included in predetermined exercise programs 3 times per week for 6 weeks. Severity of pain, functional activity status, muscle strength, functional capacity, and serum cytokine levels were evaluated at baseline and at the 6th week.Results. At the end of 6th week, there was no statistically significant decrease in serum pro-inflammatory cytokine levels in both the exercise groups, although C-reactive protein levels exhibited a strong trend toward significance. We found a significant decrease in visual analog scale and Western Ontario McMaster Osteoarthritis Index scores, and significant increase in functional capacity and muscle strength in both the exercise groups compared with those in the control group.

FRI0591-HPR Trigger Point Dry Needling as an Adjunct Treatment for Adhesive Capsulitis of the Shoulder: A Pilot Randomized Controlled Trial

BackgroundAdhesive capsulitis is a common shoulder condition of unknown etiology that is commonly treated by conservative therapy. Trigger point dry needling has been supposed to be beneficial in the treatment...

A multidimensional assessment of physical performance for older Japanese people with community-based long-term care needs.

A multidimensional assessment representing overall lower- and upper-extremity performance is necessary to identify functional decline among older adults. The aim of this study was to develop and validate a physical performance scale (PPS) using both cross-sectional and observational approaches in older adults with and without community-based long-term care (LTC) needs in Japan. A total of 416 community-living adults aged 75 years and over. The 7 items of the PPS include a range of physiological challenges, such as assessment of upper-extremity strength, lower-extremity strength, balance, and walking ability. Concurrent validity [correlating the PPS with self-reported functional status in activities of daily living (ADLs), instrumental ADLs, and Physical Function subscale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36PF)] and discriminative validity were assessed. Sensitivity to changes was evaluated with a 12-week exercise program. Total PPS score was significantly correlated with self-reported functional status such as ADLs, instrumental ADLs (IADLs), and SF-36PF (r = 0.53-0.62) and demonstrated no floor effect and minimal ceiling effect (8.7 %). The total PPS score showed large areas under the curve (AUC = 0.89; 95 % confidence interval, 0.86-0.92) with regard to discrimination between individuals with and without LTC needs. In observational analysis, total PPS score demonstrated small meaningful change in high-risk individuals requiring care (effect size 0.34). The PPS may be a useful tool for identifying functional status decline and improvement in older adults requiring community-based LTC.

Chilean version of the INECO Frontal Screening (IFS-Ch): Psychometric properties and diagnostic accuracy

OBJECTIVEThis study sought to analyze the psychometric properties and diagnostic accuracy of the Chilean version of the INECO Frontal Screening (IFS-Ch) in a sample of dementia patients and control subjects.METHODSAfter adapting the instrument to the Chilean context and obtaining content validity evidence through expert consultation, the IFS-Ch was administered to 31 dementia patients and 30 control subjects together with other executive assessments (Frontal Assessment Battery [FAB], Modified version of the Wisconsin Card Sorting Test [MCST], phonemic verbal fluencies [letters A and P] and semantic verbal fluency [animals]) and global cognitive efficiency tests (Mini mental State Examination [MMSE] and Addenbrooke's Cognitive Examination-Revised [ACE-R]). Caregivers of dementia patients and proxies of control subjects were interviewed with instruments measuring dysexecutive symptoms (Dysexecutive Questionnaire [DEX]), dementia severity (Clinical Dementia Rating Scale [CDR]) and functional status in activities of daily living (Activities of Daily Living Scale [IADL] and Technology-Activities of Daily Living Questionnaire [T-ADLQ]). Convergent and discriminant validity, internal consistency reliability, cut-off points, sensitivity and specificity for the IFS-Ch were estimated.RESULTSEvidence of content validity was obtained. Evidence of convergent validity was also found showing significant correlations (p<0.05) between the IFS-Ch and the other instruments measuring: executive functions (FAB, r=0.935; categories achieved in the MCST, r=0.791; perseverative errors in the MCST, r= -0.617; animal verbal fluency, r=0.728; "A" verbal fluency, r=0.681; and "P" verbal fluency, r=0.783), dysexecutive symptoms in daily living (DEX, r= -0.494), dementia severity (CDR, r= -0.75) and functional status in activities of daily living (T-ADLQ, r= -0.745; IADL, r=0.717). Regarding reliability, a Cronbach's alpha coefficient of 0.905 was obtained. For diagnostic accuracy, a cut-off point of 18 points (sensitivity=0.903; specificity=0.867) and an area under curve of 0.951 were estimated to distinguish between patients with dementia and control subjects.DISCUSSIONThe IFS-Ch showed acceptable psychometric properties, supported by evidence of validity and reliability for its use in the measurement of executive functions in patients with dementia. The diagnostic accuracy of the IFS-Ch for detecting dementia patients was also considered acceptable.

Propiedades psicométricas y utilidad diagnóstica del Addenbrooke's Cognitive Examination-Revised (ACE-R) en una muestra de ancianos chilenos

The Addenbrooke's Cognitive Examination - Revised (ACE-R) is a good alternative to the Mini Mental State Examination (MMSE) for assessing cognitive capacities in dementia. To estimate the psychometric properties and diagnostic utility of the Addenbrooke's Cognitive Examination-Revised (ACE-R) in a Chilean elderly sample. ACE-R was adapted for the Chilean population (ACE-R-Ch) and then administered to 60 dementia patients, 22 mild cognitive impairment (MCI) patients and 45 control subjects in addition to the MMSE for assessing global cognitive efficiency. Caregivers of dementia patients and collateral sources of MCI patients and elderly subjects without dementia were interviewed with measures of dementia severity, functional status in activities of daily living and cognitive changes. Convergent validity, internal consistency reliability, cutoff points, sensitivity and specificity for ACE-R-Ch were estimated. Regarding convergent validity, the ACE-R-Ch showed significant correlations (p < 0,001) with another cognitive measure (r = 0,952 with MMSE), a rating for dementia severity (Spearman rho=-0,822 with CDR), functional capacity assessments (r = -0,70 with ADLQ-Ch; r = -0,725 with PFAQ-Ch; and r = 0,650 with IADL Scale) and a measure of cognitive changes (r = -0,633 with AD8-Ch). In terms of reliability, the test had a Cronbach alpha coefficient of 0.918. The best cut-off point to distinguish cases of dementia from control subjects was a score of 76, which reached a sensitivity of 0.92 and a specificity of 0.93. The ACE-R-Ch showed acceptable psychometric properties, becoming a valid and reliable instrument to assess global cognitive efficiency or cognitive impairment. Its diagnostic utility to detect dementia patients also worked very well in a Chilean elderly sample.

Geriatric syndromes as predictors of adverse outcomes of hospitalization

The aim of this study was to determine the association between the common geriatric syndromes and predefined adverse outcomes of hospitalization and to identify the most important independent predictors of adverse outcomes using information gained within 24 h of admission in older general medical patients. A prospective longitudinal cohort study of patients aged > or =75 years admitted to the rapid assessment medical unit in a teaching hospital was carried out. The role of geriatric syndromes in predicting outcomes was examined in univariate and multivariate models. The outcome measures were (i) length of hospital stay (LOS) of 28 days or more, (ii) institutionalization or change in residential care status to a more dependent category at discharge or during 3 months post-discharge, (iii) unplanned readmissions during 3 months and (iv) mortality in hospital or 3 months post-discharge. The presence of geriatric syndromes was significantly associated with increased LOS and institutionalization or change in residential care status to a more dependent category. The factors most predictive of these outcomes were impaired pre-admission functional status in activities of daily living, recurrent falls, urinary incontinence and supported living arrangements. The geriatric syndromes appeared less important in predicting unplanned readmission and death. The presence of geriatric syndromes in older general medical patients is an important determinant of adverse outcomes of hospitalization, particularly of LOS and admission to residential care. The predictors most useful for screening patients for these outcomes, within 24 h of admission, appear to be the presence of certain pre-existing geriatric syndromes before admission.

Low Serum Carnitine Levels in Hemodialysis Patients; Relationship to Intra-Dialyt1C Hypotension and Functional Activity Status

Low Serum Carnitine Levels in Hemodialysis Patients; Relationship to Intra-Dialyt1C Hypotension and Functional Activity Status

Physician resource utilization after geriatric trauma.

As health care resources become increasingly strained, the value of physician consultation has come under heightened scrutiny. This report reviews the value of early consultation by the physical medicine and rehabilitation (PMR) service to an integrated trauma service for geriatric patients with multiple trauma. We retrospectively reviewed the records of 110 geriatric trauma patients (age > 60 years) with an Injury Severity Score > or = 15 to evaluate the effects of PMR consultation. Patients in group 1 were admitted to a general surgical service, and those in group 2 were admitted to a multidisciplinary trauma service. Demographic and physiologic factors, as well as short-term and long-term outcomes, were evaluated, and a subgroup analysis was performed to compare early (< or =3 days) versus late (>3 days) consultation by PMR. Although there were significant differences in Glasgow Coma Scale score and length of stay, no differences were found within groups in other demographic, physiologic, or outcome data. Focused review of PMR intervention based on early versus late consultation revealed no significant difference between the two groups. Furthermore, an after-discharge phone survey revealed no significant group differences in dependence on a care provider or nursing home placement, readmission to hospital, employment status, or current functional activity status. Long-term patient functional outcome and the in-house rehabilitation process are not affected by integration of PMR into a multidisciplinary trauma team or early PMR consultation.

Cognitive Status as a Predictor of Right Hemisphere Stroke Outcomes

The care of stroke patients continues to present a challenge to health care professionals. There is evidence that the quality of life following a stroke is related to functional status and also emotional, behavioral and cognitive abilities. The purpose of this study was to examine the relationship between emotional, behavioral and cognitive status and functional activity status of stroke survivors. The sample of 15 right hemisphere stroke patients was seen at four time periods after the stroke and they were assessed using the Neurobehavioral Rating Scale (NRS) and the Barthel Functional Index (BFI). The most frequently occurring mental status changes at six months were somatic concern, memory deficit, depressive mood and mental fatigue. There was a correlation between cognitive ability and functional ability. Although there was improvement over time in the scores of the NRS and BFI, there remained sufficient cognitive impairment to affect functional ability. Findings indicated the need for nurses to assess mental status when planning rehabilitation to establish realistic goals. Further research is needed with larger samples to examine the effects of stroke outcomes on functional ability.

Multidisciplinary studies of illness in aged persons: II. A new classification of functional status in activities of daily living

At The Benjamin Rose Hospital, a hospital for prolonged illness in Cleveland, Ohio, methods were established for obtaining quantitative information about the progressive loss of abilities and progressive increase in death rate of aged patients. The methods were initially designed in relation to fractures of the hip. In the present report, an Index of Independence in Activities of Daily Living was defined, newly evolved and more specific than previously available. The index was a composite evaluation of the functional independence or dependence of patients in bathing, dressing, going to toilet, transferring, continence, and feeding. Use of the Index of ADL in evaluating deterioration and progression of deterioration was demonstrated, and the significance of these applications was discussed. Evaluation 6 months after the occurrence of fracture revealed deterioration in activities of daily living in 38 per cent of patients classified as A (according to the Index of ADL) prior to fracture, in 56 per cent of those classified as B and C, and 100 per cent of those in the more dependent classes. Mortality in the 3 groups was 7, 18, and 20 per cent, respectively. Progression of deterioration during the second 6-month interval was more frequent in patients who had shown deterioration in the first 6-month interval than in patients who had not shown such previous deterioration. Mortality, too, was greater in patients showing previous deterioration.