Development of a middle-range theory of caregiver stress from the Roy Adaptation Model

A theory of caregiver stress derived from Roy Adaptation Model was developed to examine the relationships among stimuli, coping mechanism and adaptive modes. The theory hypothesized that objective burden in caregiving would be the most important stimulus that leaded to perceived caregiver stress. Higher perceived caregiver stress would result in ineffective responses (poor health function, lower self-esteem/mastery, role enjoyment, and marital satisfaction, and less ability to reciprocate). These adaptive modes should be interrelated. In addition, this study also examined the role of depression and the function of contextual stimuli in the model. However, statistical analysis did not support the initial RAM-derived theory. The primary model was modified by reevaluating the relations among constructs in empirical data using structural equation modeling. The robustness of the final data-derived model was further partially cross-validated with another sample and was further simplify. The findings showed that (a) Objective burden in care giving and perceived caregiver stress were not the most important determinants of their outcomes in the context of chronic caregiving; (b) Perceived caregiver stress and depression were related yet distinct concepts in predicting caregivers\u27 outcomes; (c) Depression was the most easily aroused outcome of perceived caregiver stress; (d) Contextual stimuli did not have either the main effect on perceived caregiver stress or a moderated effect on the relation between objective burden in caregiving and perceived caregiver stress. Instead, they influenced caregivers\u27 outcomes directly; (e) Gender was the only residual stimulus that was found to predict perceived caregiver stress. Residual stimuli in this study played more important roles in predicting focal stimuli, contextual stimuli, depression, and adaptive modes; and (f) There were no causal relationships among adaptive modes; instead, adaptive modes were either predicted by depression, contextual stimuli, or residual stimuli. The results provide valuable insights to the RAM as well as caregiving knowledge. It also pointed out the importance of using secondary data analysis and structural equation model in nursing research

The relationships between depression and other outcomes of chronic illness caregiving

BACKGROUND: Many caregivers with chronically ill relatives suffer from depression. However, the relationship of depression to other outcomes of chronic caregiving remains unclear. This study tested a hypothesized model which proposed that hours of care, stressful life events, social support, age and gender would predict caregivers' outcomes through perceived caregiver stress. Depression was expected to mediate the relationship between perceived stress and outcomes of chronic caregiving (physical function, self-esteem, and marital satisfaction). METHODS: The sample for this secondary data analysis consisted of 236 and 271 subjects from the Americans' Changing Lives, Wave 1, 1986, and Wave 2, 1989, data sets. Measures were constructed from the original study. Structural equation modeling was used to test the hypothesized model, and an exploratory structural modeling method, specification search, was used to develop a data-derived model. Cross-validation was used to verify the paths among variables. RESULTS: Hours of care, age, and gender predicted caregivers' outcomes directly or through perceived caregiver stress (p < .01). Depression mediated the relationship between perceived stress and psychological outcomes and explained 40% and 11% of the variance in self-esteem and marital satisfaction, respectively. CONCLUSION: Depression predicted psychological outcomes. Whether depression predicts physical health outcomes needs to be further explored

Feasibility of using quadriceps-strengthening exercise to improve pain and sleep in a severely demented elder with osteoarthritis – a case report

BACKGROUND: Osteoarthritis (OA) of the knee, which is prevalent among older adults in nursing homes, causes significant pain and suffering, including disturbance of nocturnal sleep. One nonpharmacologic treatment option is quadriceps-strengthening exercise, however, the feasibility of such a treatment for reducing pain from OA in severely demented elders has not been studied. This report describes our test of the feasibility of such an exercise program, together with its effects on pain and sleep, in a severely demented nursing home resident. CASE PRESENTATION: The subject was an elderly man with severe cognitive impairment (Mini-Mental Status Exam score 4) and knee OA (Kellgren-Lawrence radiographic grade 4). He was enrolled in a 5-week, 10-session standardized progressive-resistance training program to strengthen the quadriceps, and completed all sessions. Pain was assessed with the Western Ontario and MacMaster OA Index (WOMAC) pain subscale, and sleep was assessed by actigraphy. The patient was able to perform the exercises, with a revision to the protocol. However, the WOMAC OA pain subscale proved inadequate for measuring pain in a patient with low cognitive functioning, and therefore the effects on pain were inconclusive. Although his sleep improved after the intervention, the influence of his medications and the amount of daytime sleep on his nighttime sleep need to be considered. CONCLUSIONS: A quadriceps-strengthening exercise program for treating OA of the knee is feasible in severely demented elders, although a better outcome measure is needed for pain

Including Total EGFR Staining in Scoring Improves EGFR Mutations Detection by Mutation-Specific Antibodies and EGFR TKIs Response Prediction

Epidermal growth factor receptor (EGFR) is a novel target for therapy in subsets of non-small cell lung cancer, especially adenocarcinoma. Tumors with EGFR mutations showed good response to EGFR tyrosine kinase inhibitors (TKIs). We aimed to identify the discriminating capacity of immunohistochemical (IHC) scoring to detect L858R and E746-A750 deletion mutation in lung adenocarcinoma patients and predict EGFR TKIs response. Patients with surgically resected lung adenocarcinoma were enrolled. EGFR mutation status was genotyped by PCR and direct sequencing. Mutation-specific antibodies for L858R and E746-A750 deletion were used for IHC staining. Receiver operating characteristic (ROC) curves were used to determine the capacity of IHC, including intensity and/or quickscore (Q score), in differentiating L858R and E746-A750 deletion. We enrolled 143 patients during September 2000 to May 2009. Logistic-regression-model-based scoring containing both L858R Q score and total EGFR expression Q score was able to obtain a maximal area under the curve (AUC: 0.891) to differentiate the patients with L858R. Predictive model based on IHC Q score of E746-A750 deletion and IHC intensity of total EGFR expression reached an AUC of 0.969. The predictive model of L858R had a significantly higher AUC than L858R intensity only (p = 0.036). Of the six patients harboring complex EGFR mutations with classical mutation patterns, five had positive IHC staining. For EGFR TKI treated cancer recurrence patients, those with positive mutation-specific antibody IHC staining had better EGFR TKI response (p = 0.008) and longer progression-free survival (p = 0.012) than those without. In conclusion, total EGFR expression should be included in the IHC interpretation of L858R. After adjusting for total EGFR expression, the scoring method decreased the false positive rate and increased diagnostic power. According to the scoring method, the IHC method is useful to predict the clinical outcome and refine personalized therapy

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Moderators of the effect of therapeutic exercise for knee and hip osteoarthritis: a systematic review and individual participant data meta-analysis

Background Many international clinical guidelines recommend therapeutic exercise as a core treatment for knee and hip osteoarthritis. We aimed to identify individual patient-level moderators of the effect of therapeutic exercise for reducing pain and improving physical function in people with knee osteoarthritis, hip osteoarthritis, or both. Methods We did a systematic review and individual participant data (IPD) meta-analysis of randomised controlled trials comparing therapeutic exercise with non-exercise controls in people with knee osteoathritis, hip osteoarthritis, or both. We searched ten databases from March 1, 2012, to Feb 25, 2019, for randomised controlled trials comparing the effects of exercise with non-exercise or other exercise controls on pain and physical function outcomes among people with knee osteoarthritis, hip osteoarthritis, or both. IPD were requested from leads of all eligible randomised controlled trials. 12 potential moderators of interest were explored to ascertain whether they were associated with short-term (12 weeks), medium-term (6 months), and long-term (12 months) effects of exercise on self-reported pain and physical function, in comparison with non-exercise controls. Overall intervention effects were also summarised. This study is prospectively registered on PROSPERO (CRD42017054049). Findings Of 91 eligible randomised controlled trials that compared exercise with non-exercise controls, IPD from 31 randomised controlled trials (n=4241 participants) were included in the meta-analysis. Randomised controlled trials included participants with knee osteoarthritis (18 [58%] of 31 trials), hip osteoarthritis (six [19%]), or both (seven [23%]) and tested heterogeneous exercise interventions versus heterogeneous non-exercise controls, with variable risk of bias. Summary meta-analysis results showed that, on average, compared with non-exercise controls, therapeutic exercise reduced pain on a standardised 0–100 scale (with 100 corresponding to worst pain), with a difference of –6·36 points (95% CI –8·45 to –4·27, borrowing of strength [BoS] 10·3%, between-study variance [τ2] 21·6) in the short term, –3·77 points (–5·97 to –1·57, BoS 30·0%, τ2 14·4) in the medium term, and –3·43 points (–5·18 to –1·69, BoS 31·7%, τ2 4·5) in the long term. Therapeutic exercise also improved physical function on a standardised 0–100 scale (with 100 corresponding to worst physical function), with a difference of –4·46 points in the short term (95% CI –5·95 to –2·98, BoS 10·5%, τ2 10·1), –2·71 points in the medium term (–4·63 to –0·78, BoS 33·6%, τ2 11·9), and –3·39 points in the long term (–4·97 to –1·81, BoS 34·1%, τ2 6·4). Baseline pain and physical function moderated the effect of exercise on pain and physical function outcomes. Those with higher self-reported pain and physical function scores at baseline (ie, poorer physical function) generally benefited more than those with lower self-reported pain and physical function scores at baseline, with the evidence most certain in the short term (12 weeks). Interpretation There was evidence of a small, positive overall effect of therapeutic exercise on pain and physical function compared with non-exercise controls. However, this effect is of questionable clinical importance, particularly in the medium and long term. As individuals with higher pain severity and poorer physical function at baseline benefited more than those with lower pain severity and better physical function at baseline, targeting individuals with higher levels of osteoarthritis-related pain and disability for therapeutic exercise might be of merit

Proteolytic control of the mitochondrial calcium uniporter complex

The mitochondrial calcium uniporter is a Ca²⁺-activated Ca²⁺ channel complex mediating mitochondrial Ca²⁺ uptake, a process crucial for Ca²⁺ signaling, bioenergetics, and cell death. The uniporter is composed of the pore-forming MCU protein, the gatekeeping MICU1 and MICU2 subunits, and EMRE, a single-passmembrane protein that links MCU and MICU1 together. As a bridging subunit required for channel function, EMRE could paradoxically inhibit uniporter complex formation if expressed in excess. Here, we show that mitochondrial mAAA proteases AFG3L2 and SPG7 rapidly degrade unassembled EMRE using the energy of ATP hydrolysis. Once EMRE is incorporated into the complex, its turnover is inhibited > 15-fold. Protease-resistant EMRE mutants produce uniporter subcomplexes that induce constitutive Ca²⁺ leakage into mitochondria, a condition linked to debilitating neuromuscular disorders in humans. The results highlight the dynamic nature of uniporter subunit assembly, which must be tightly regulated to ensure proper mitochondrial responses to intracellular Ca²⁺ signals