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Background Clinical research suggests that posttraumatic stress disorder (PTSD) patients exposed to multiple traumatic events (TEs) rather than a single TE have increased morbidity and dysfunction. Although epidemiological surveys in the United States and Europe also document high rates of multiple TE exposure, no population‐based cross‐national data have examined this issue. Methods Data were analyzed from 20 population surveys in the World Health Organization World Mental Health Survey Initiative (n = 51,295 aged 18+). The Composite International Diagnostic Interview (3.0) assessed 12‐month PTSD and other common DSM‐IV disorders. Respondents with 12‐month PTSD were assessed for single versus multiple TEs implicated in their symptoms. Associations were examined with age of onset (AOO), functional impairment, comorbidity, and PTSD symptom counts. Results 19.8% of respondents with 12‐month PTSD reported that their symptoms were associated with multiple TEs. Cases who associated their PTSD with four or more TEs had greater functional impairment, an earlier AOO, longer duration, higher comorbidity with mood and anxiety disorders, elevated hyperarousal symptoms, higher proportional exposures to partner physical abuse and other types of physical assault, and lower proportional exposure to unexpected death of a loved one than cases with fewer associated TEs. Conclusions A risk threshold was observed in this large‐scale cross‐national database wherein cases who associated their PTSD with four or more TEs presented a more “complex” clinical picture with substantially greater functional impairment and greater morbidity than other cases of PTSD. PTSD cases associated with four or more TEs may merit specific and targeted intervention strategies.

Objective Acupuncture has become a popular complementary treatment in oncology. This study is based on RNA-Seq transcriptome sequencing technology to investigate the molecular mechanisms underlying the effect of acupuncture-mediated regulation of the Leptin/AMPK signaling pathway on mitochondrial dysfunction-induced fatigue in breast cancer patients after chemotherapy. Methods Peripheral blood samples from 10 patients with post-operative chemotherapy for breast cancer were selected for transcriptome sequencing to screen the key molecular pathways involved in fatigue after chemotherapy in breast cancer patients. Besides, peripheral blood samples were collected from 138 post-operative chemotherapy patients with breast cancer to study the composite fatigue and quality of life scores. Flow cytometry was used to detect T lymphocyte subsets in peripheral blood-specific immune cells. In addition, a blood cell analyzer was used to measure peripheral blood leukocyte counts, and MSP-PCR was used to detect mitochondrial DNA mutations in peripheral blood leukocytes. Results Transcriptome bioinformatics analysis screened 147 up-regulated mRNAs and 160 down-regulated mRNAs. Leptin protein was confirmed as the key factor. Leptin was significantly higher in the peripheral blood of breast cancer patients who developed fatigue after chemotherapy. Acupuncture treatment effectively improved post-chemotherapy fatigue and immune status in breast cancer patients, suppressed the expression of Leptin/AMPK signaling pathway-related factor and leukocyte counts, and significantly reduced the rate of mitochondrial DNA mutations in peripheral blood leukocytes. Conclusion The Leptin/AMPK signaling pathway may be the key molecular pathway affecting the occurrence of fatigue after chemotherapy in breast cancer patients. Leptin may improve post-chemotherapy fatigue in breast cancer patients by activating AMPK phosphorylation and alleviating mitochondrial functional impairment.

Purpose Work participation after breast cancer treatment is generally negatively affected. Occupational health professionals might improve work-related outcomes by bridging the gap between sick-listed employees’ levels of functioning and work demands. To aid them in this task, this review explored the association between functional impairments and work-related outcomes in breast cancer survivors. Methods Publications from January 2000–March 2016 were identified through five online databases (i.e. Pubmed, EMBASE, PsycINFO, CINAHL and the Cochrane Library). Quantitative and qualitative studies were included if they focused on functional impairments and work-related outcomes in breast cancer survivors. Two reviewers independently selected studies, extracted data and performed quality assessment. Results The search identified 998 studies, of which 20 studies met eligibility criteria. Impairments in physical functioning negatively affected return to work (RTW) and work ability in quantitative and qualitative studies. Studies measuring cognitive functioning with tests found no association with work-related outcomes, whereas the results of studies using self-reported measures were ambiguous. Social functioning was less commonly investigated and findings differed across work-related outcomes. Emotional functioning was not associated with work-related outcomes in quantitative studies, while in qualitative studies feelings such as insecurity were described as influencing RTW. Conclusions Functional impairments can severely hamper work participation in breast cancer survivors. This provides important opportunities for occupational health professionals to enhance RTW in breast cancer survivors, such as adequately addressing illness perceptions and work expectations. Ongoing research is warranted to aid occupational health professionals in providing effective vocational guidance and improve work-related outcomes in breast cancer survivors.

PurposeObjective functional tests like the five-repetition sit-to-stand test (5R-STS) can supplement an objective dimension to conventional patient-reported outcome measures. The reliability of unsupervised obtainment of 5R-STS performance is currently unknown.MethodsWe included patients with degenerative pathologies of the lumbar spine. Patients performed the 5R-STS during the initial clinical visit (supervised), as well as at home after instruction by a physiotherapist. At home, patients were first timed by a relative (unsupervised) and subsequently produced a video recording of themselves performing the 5R-STS for digital measurement (telesupervised). Two raters independently assessed the recordings.ResultsOne hundred and twenty-one patients were recruited, of which 100 were eligible. Eighty-eight reported unsupervised results. Sixty-four returned recordings, of which 61 were ratable. Both unsupervised (r: 0.94, 95% CI 0.91–0.96, p < 0.001) and telesupervised (r: 0.90, 95% CI 0.83–0.94, p < 0.001) measurements demonstrated excellent correlation with clinical test times. Patients did not perform more slowly at home (p > 0.05). The interrater agreement for digital judgement of the telesupervised recording was excellent (ICC: 0.996, 95% CI 0.993–0.998, p < 0.001). We confirmed convergent validity with self-reported disability, back pain, and quality of life (all p < 0.05), but not with leg pain (p = 0.189).ConclusionsUnsupervised at-home assessment using the 5R-STS is highly reliable. There does not appear to be a specific need for patients to return for a supervised 5R-STS follow-up. Rather, instructions can be provided, and the test performed and rated by a partner or family member at home. This is logistically and economically advantageous for patients, clinicians, and researchers.Trial registry numberClinicalTrials.gov Identifier: NCT03321357.Graphical abstractThese slides can be retrieved under Electronic Supplementary Material.

Objective: To evaluate the relationship between symptom and functional improvement and remission in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) enrolled in an 11-week open-label dose-optimization phase of an methylphenidate extended release (MPH-MLR) pivotal study. Methods: Assessments included the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P) and ADHD Rating Scale, Fourth Edition (ADHD-RS-IV). Definitions included the following: symptom improvement (≥30% decrease in ADHD-RS-IV total score); symptom remission (ADHD-RS-IV total score ≤18); functional improvement (decrease in WFIRS-P total score ≥0.25 [minimally important difference]); and functional remission (WFIRS-P total score ≤0.65). Results: Two hundred children completed the open-label phase. At initial assessment, functional impairment was evident across all WFIRS-P domains and similar between children and adolescents. Those who were treatment naive had more functional impairment (WFIRS-P total: 0.82 vs. 0.70, p = 0.02). Significant improvements in all WFIRS-P domains were noted at open-label end (p < 0.001), with the largest improvement in Learning. At open-label end, 94% of children and adolescents demonstrated symptom improvement, of which 57% also showed functional improvement, and 75% of children and adolescents showed symptom remission, of which 81% also showed functional remission. Conclusions: Children and adolescents treated with MPH-MLR showed moderate-to-large improvement in functioning during 3 months of treatment, both overall and in specific domains. However, a significant number of those who would be considered symptomatic responders failed to show improvement in functioning or continue to have significant functional impairment. Treatment with MPH-MLR showed that both symptomatic and functional remission are achievable goals. Identification of children and adolescents who have been successfully treated for their symptoms, but continue to suffer functional impairment, will allow us to offer additional targeted treatment interventions over and above medication to address residual difficulties.

Several recent phase 3 clinical trials of attention-deficit/hyperactivity disorder (ADHD) medications have used the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P). Here, we assess WFIRS-P response in individual patients in two pivotal trials of lisdexamfetamine dimesylate (LDX) and guanfacine extended release (GXR). We also analysed pooled WFIRS-P data from seven phase 3 studies of ADHD medications to shed light on factors associated with baseline functional impairment. The proportion of patients with a change in WFIRS-P score that exceeded the minimal important difference (MID) criteria for response was greater for LDX than placebo in the Family, Learning and School, and Risky Activities domains, and was greater for GXR than placebo in the Social Activities, Learning and School, and Family domains. Responders had significantly worse baseline scores in all WFIRS-P domains (all p < 0.001) than non-responders. In the pooled analyses, baseline WFIRS-P scores in all domains were significantly worse in participants with oppositional defiant disorder (ODD) than in those without ODD. Having combined type or hyperactive-impulsive type ADHD, being enrolled into a study in Europe, being male and being younger also had modest negative effects on baseline WFIRS-P scores. The present analysis of WFIRS-P response shows that previously reported group-level improvements in WFIRS-P functional impairment score translated into clinically relevant improvements in many individual participants. Functional impairment is a diverse and subjective construct that is influenced by multiple factors. Optimal management of individuals with ADHD should involve monitoring improvements in functioning and quality of life, as well as symptomatic improvement.

Most studies on health expectancies rely on self-reported health from surveys to measure the prevalence of disabilities or ill health in a population At best, such studies only correct for sample selection based on a limited number of characteristics observed on the invitees Using longitudinal data from the Trondelag Health Study (HUNT), I investigate the extent to which adjustments for a health-related sample selection affect the age profiles for the prevalence of functional impairment (FI) and the associated disability-free life expectancy (DFLE). I estimate a probit model with sample selection under the identifying restriction that the strength of the health-related selection is of similar order to the strength of the selection on observable characteristics. I then compute the selection-adjusted FI prevalence rates and trace out the implications for DFLE using the Sullivan method. The analysis confirms that poor health measured at younger ages correlates with non-response behaviour in later waves of the survey, and that even for a conservative lower bound for the assumed degree of health-related selection, the estimated age profiles for DFLE lie systematically below the corresponding profiles when controlling only for selection on observable characteristics. Health related non-response downwardly biases the raw sample prevalence rates for FI obtained from survey data and contributes to overestimating the expansion in DFLE.

Purpose To evaluate the psychometric properties of a German modification of the Weiss Functional Impairment Rating Scale—Parent Report for children with aggressive and oppositional behavior problems (WFIRS-P for ODD/CD). Methods Data were collected from a clinical sample of children (6–12 years; 96% boys) with oppositional defiant disorder (ODD) and conduct disorder (CD) ( N  = 219). The WFIRS-P conceptual framework was evaluated using confirmatory factor analyses (CFA). Reliability was estimated using internal consistency (Cronbach’s alpha) and omega statistics. Validity was assessed through correlations between WFIRS-P for ODD/CD domain scores and parent-rated scales on symptoms of ODD, CD, attention-deficit/hyperactivity disorder (ADHD), a broad range of other behavioral and emotional problems, and scales on health-related quality of life and family burden. Results CFA of the WFIRS-P for ODD/CD revealed that a bifactor model, with a general factor accounting for common variance ( ω H  = 0.23–0.48) and independent specific group factors accounting for additional variance in item scores ( ω S  = 0.37–0.60), best fits the data. Thus, CFA confirmed the theoretical assumption of a general construct of impairment (total scale) and additional specific impairments (subscales, e.g., family, social activities). Cronbach’s alpha coefficient exceeded 0.70 for all subscales. Omega statistics showed that both the general construct and specific factors accounted for item variance. As expected, correlations with symptoms scales for ODD/CD and ADHD were low to moderate. Conclusions The use of the parent-rated WFIRS for ODD/CD in identifying ODD- and CD-related impairment in children is psychometrically supported. The scale can be employed to assess functional impairment in children with aggressive behavior problems.

Background This study evaluates the descriptive and psychometric properties of the Persian version of the Weiss Functional Impairment Rating Scale-Parent Report Form (WFIRS-P) in a normal sample of Iranian children. Method Parents of 282 students (grades 1–6) completed the WFIRS-P. Means and standard deviations were computed for the total scale, each domain, and each item of the WFIRS-P. Internal consistency, interdomain correlations, and test-retest reliability were used to assess the reliability of the scale. Results Among the WFIRS-P domains, life skills had the highest rated impairment ( M  = 0.50, SD  = 0.37) and risky activities had the lowest. Internal consistency (α = .88) and test-retest reliability ( r  = 0.77) were strong for the WFIRS-P total scale. The correlation between the WFIRS-P domains and the total scale ranged from 0.52 to 0.81. Conclusions Results suggest that the Persian version of the WFIRS-P is a useful and psychometrically reliable measure for assessing functional skills in children.

Background The specific non‐motor symptoms associated with α‐synucleinopathies, including orthostatic hypotension (OH), cognitive impairment, and emotional abnormalities, have been a subject of ongoing controversy over the mechanisms underlying the development of a vicious cycle among them. The distinct structural alterations in white matter (WM) in patients with α‐synucleinopathies experiencing OH, alongside their association with other non‐motor symptoms, remain unexplored. This study employs axial diffusivity and density imaging (NODDI) to investigate WM damage specific to α‐synucleinopathies with concurrent OH, delivering fresh evidence to supplement our understanding of the pathogenic mechanisms and pathological rationales behind the occurrence of a spectrum of non‐motor functional impairments in α‐synucleinopathies. Methods This study recruited 49 individuals diagnosed with α‐synucleinopathies, stratified into an α‐OH group (n = 24) and an α‐NOH group (without OH, n = 25). Additionally, 17 healthy controls were included for supine and standing blood pressure data collection, as well as neuropsychological assessments. Magnetic resonance imaging (MRI) was utilized for the calculation of NODDI parameters, and tract‐based spatial statistics (TBSS) were employed to explore differential clusters. The fibers covered by these clusters were defined as regions of interest (ROI) for the extraction of NODDI parameter values and the analysis of their correlation with neuropsychological scores. Results The TBSS analysis unveiled specific cerebral regions exhibiting disparities within the α‐OH group as compared to both the α‐NOH group and the healthy controls. These differences were evident in clusters that indicated a decrease in the acquisition of the neurite density index (NDI), a reduction in the orientation dispersion index (ODI), and an increase in the isotropic volume fraction (FISO) (p < 0.05). The extracted values from these ROIs demonstrated significant correlations with clinically assessed differences in supine and standing blood pressure, overall cognitive scores, and anxiety‐depression ratings (p < 0.05). Conclusion Patients with α‐synucleinopathies experiencing OH exhibit distinctive patterns of microstructural damage in the WM as revealed by the NODDI model, and there is a correlation with the onset and progression of non‐motor functional impairments. Patients with α‐synucleinopathies experiencing OH exhibit distinctive patterns of microstructural damage in the WM as revealed by the NODDI model.