Whole Day Workload: Evaluation of a New Outcome Measure in Occupational Therapy for Adults With Type 1 Diabetes.

IMPORTANCE: Typical whole day workload is a metric with potential relevance to the occupational balance and well-being of individuals with chronic conditions. OBJECTIVE: To examine the reliability and validity of using multiple daily NASA Task Load Index measures (whole day TLX) as an indicator of typical whole day workload experienced by adults with Type 1 diabetes (T1D). DESIGN: Participants with T1D completed cross-sectional measures and 2 wk of ecological momentary assessments (EMA) and daily diaries. Reliability was assessed across subgroups (e.g., workers vs. nonworkers); validity was evaluated with multilevel confirmatory factor analysis and with tests of convergent and divergent validity with patient-reported outcomes and blood glucose measures. SETTING: Three outpatient endocrinology clinics in the United States. PARTICIPANTS: Data from 164 U.S. adults with T1D (42% Latino, 30% White). OUTCOMES AND MEASURES: Measures used included the whole day TLX (assessed via 2 wk of daily diaries), time in target blood glucose range (assessed with a continuous glucose monitor), illness intrusiveness (measured cross-sectionally), and stress (measured cross-sectionally and with EMA). RESULTS: Number of days required for at least 0.70 reliability of the average whole day TLX ranged between 2 and 6 days depending on the subgroup. Results supported convergent and divergent validity of the average of the whole day TLX, including associations with average stress (r = .63, p < .001) and time in target blood glucose range (r = -.25, p = .002). CONCLUSIONS AND RELEVANCE: The whole day TLX was a reliable and valid indicator of typical whole day workload. Plain-Language Summary: The health management responsibilities for Type 1 diabetes can be extremely burdensome. When these responsibilities are experienced, in addition to duties such as work and caregiving, the totality of demands experienced (i.e., whole day workload) can create further issues, such as unhealthy physiological changes and interference with self-care. We tested the psychometric properties of a measurement tool that assesses the typical level of workload people experience. This measure, referred to as the NASA Task Load Index (whole day TLX), was found to be a reliable and valid indicator of typical whole day workload. Occupational therapists may use the whole day TLX to track progress in interventions focused on reducing clients' whole day workload exposure to promote their health and well-being. Occupational therapists' expertise in areas such as activity analysis, task adaptation, and energy conservation makes them especially well-suited to intervene on whole day workload.

Reliability and Validity of Ecological Momentary Assessment Response Time-Based Measures of Emotional Clarity: Secondary Data Analysis.

BACKGROUND: Emotional clarity has often been assessed with self-report measures, but efforts have also been made to measure it passively, which has advantages such as avoiding potential inaccuracy in responses stemming from social desirability bias or poor insight into emotional clarity. Response times (RTs) to emotion items administered in ecological momentary assessments (EMAs) may be an indirect indicator of emotional clarity. Another proposed indicator is the drift rate parameter, which assumes that, aside from how fast a person responds to emotion items, the measurement of emotional clarity also requires the consideration of how careful participants were in providing responses. OBJECTIVE: This paper aims to examine the reliability and validity of RTs and drift rate parameters from EMA emotion items as indicators of individual differences in emotional clarity. METHODS: Secondary data analysis was conducted on data from 196 adults with type 1 diabetes who completed a 2-week EMA study involving the completion of 5 to 6 surveys daily. If lower RTs and higher drift rates (from EMA emotion items) were indicators of emotional clarity, we hypothesized that greater levels (ie, higher clarity) should be associated with greater life satisfaction; lower levels of neuroticism, depression, anxiety, and diabetes distress; and fewer difficulties with emotion regulation. Because prior literature suggested emotional clarity could be valence specific, EMA items for negative affect (NA) and positive affect were examined separately. RESULTS: Reliability of the proposed indicators of emotional clarity was acceptable with a small number of EMA prompts (ie, 4 to 7 prompts in total or 1 to 2 days of EMA surveys). Consistent with expectations, the average drift rate of NA items across multiple EMAs had expected associations with other measures, such as correlations of r=-0.27 (P<.001) with depression symptoms, r=-0.27 (P=.001) with anxiety symptoms, r=-0.15 (P=.03) with emotion regulation difficulties, and r=0.63 (P<.001) with RTs to NA items. People with a higher NA drift rate responded faster to NA emotion items, had greater subjective well-being (eg, fewer depression symptoms), and had fewer difficulties with overall emotion regulation, which are all aligned with the expectation for an emotional clarity measure. Contrary to expectations, the validities of average RTs to NA items, the drift rate of positive affect items, and RTs to positive affect items were not strongly supported by our results. CONCLUSIONS: Study findings provided initial support for the validity of NA drift rate as an indicator of emotional clarity but not for that of other RT-based clarity measures. Evidence was preliminary because the sample size was not sufficient to detect small but potentially meaningful correlations, as the sample size of the diabetes EMA study was chosen for other more primary research questions. Further research on passive emotional clarity measures is needed.

Visual-Motor Integration (VMI) Is Also Relevant for Computer, Smartphone, and Tablet Use by Adults: Introducing the Brief Box Clicking Test.

IMPORTANCE: Visual-motor integration (VMI) is typically examined in children to promote handwriting, but it may also be relevant for adults' capacity for technology use. OBJECTIVE: To examine the reliability and validity of speed of completion of the box clicking test, a web-based test of VMI. DESIGN: Participants in the Understanding America Study completed online surveys on a regular basis, including a very brief (less than 30 s) self-administered box clicking test. For validity testing, we examined whether box clicking speed was associated with constructs relevant to visual-perceptual skills and motor coordination, the skills underlying VMI. Test-retest reliability was examined by computation of intraclass correlation coefficients. PARTICIPANTS: A total of 11,114 adults. MEASURES: Measures included the completion time for the box clicking task and measures relevant to visual perception (e.g., perceptual speed) and motor coordination (e.g., self-reported functional limitation). RESULTS: Results suggested that the box clicking test was a VMI task. Slower test performance was associated with lower visual-perceptual speed and a greater likelihood of reporting difficulties with dressing, a motor coordination relevant task. Box clicking tests taken within at least 2 yr of one another had moderate test-retest stability, but future studies are needed to examine test-retest reliabilities over brief (e.g., 2-wk) time intervals. CONCLUSIONS AND RELEVANCE: The box clicking test may serve both as a tool for research and to clinically observe whether clients have VMI difficulties that interfere with computer, smartphone, or tablet use. Plain-Language Summary: Use of devices such as smartphones and computers is increasingly becoming integral for daily functioning. Visual-motor integration (VMI) has often been addressed by occupational therapists to support handwriting of children, but it may also be important for technology use by adults. Prior literature supports the relevance of VMI to technology use, and adults with various chronic conditions have been found to have decrements in VMI. We tested the psychometric properties of a brief box clicking test of VMI that could be used to examine VMI underlying technology use among adults. Overall, results suggested that the box clicking test was a VMI task. Just as speed of gait has been used as an index of functional mobility, speed on the box clicking task seemed serviceable as an index of VMI ability. The box clicking test may also be used for clinical observation of whether VMI interferes with technology use.

Differential predictive value of tissue-specific PD-L1 expression scores in adjuvant immunotherapy of melanoma.

BACKGROUND: Adjuvant treatment of stage II-IV melanoma with PD-1-based immune checkpoint inhibitors (ICI) has improved relapse-free survival (RFS) and has therefore become a standard-of-care treatment option. Approximately 25%-30% of patients still recur within 1 year. Predictive biomarkers reflecting real-world data are desired. The predictive relevance of tumour tissue PD-L1 expression in the adjuvant setting remains inconclusive. OBJECTIVES: This retrospective, observational study was conducted to evaluate the value of PD-L1 expression scores in different tumour tissue locations in predicting response towards adjuvant immunotherapeutic treatment. METHODS: Tumour tissue taken prior to anti-PD-1 adjuvant ICI in 243 stage II-IV melanoma patients was collected at University Skin Cancer Center Hamburg. PD-L1 expression was evaluated on immune cells (ICS), tumour cells (TPS) and combined (CPS). Scores were determined by independent pathological physician quantification and correlated with therapy outcome at different cut-off (CO) levels (relapse-free survival, RFS) for different tumour tissue locations (primary tumour, metastases). RESULTS: A total of 104 patients were eligible for analysis. Positivity of ICS, TPS and CPS showed no predictive RFS outcome association at different CO levels when analysed irrespective of tissue origin. In primary tumours, ICS at CO 1% showed a significantly improved RFS upon positivity (HR 0.22). In contrast, positivity to TPS (CO 1%) correlated significantly and independently with improved RFS when evaluated in metastatic tumour tissue specimens (HR 0.37). CONCLUSIONS: PD-L1 tumour tissue expression may serve as a predictive biomarker for adjuvant ICI treatment response stratification in melanoma, but caution should be spent on the origin of tumour tissue analysed. The cell-type relevant for the predictive value of PD-L1 expression is tissue-specific with immune cells being important in primary tumours while tumour cells are key in metastases. The present results should be validated in a multicentre cohort.

Tailoring polishing steps for effective removal of polysorbate-degrading host cell proteins in antibody purification.

Ensuring the quality and safety of biopharmaceutical products requires the effective separation of monoclonal antibodies (mAbs) from host cell proteins (HCPs). A major challenge in this field is the enzymatic hydrolysis of polysorbates (PS) in drug products. This study addresses this issue by investigating the removal of polysorbate-degrading HCPs during the polishing steps of downstream purification, an area where knowledge about individual HCP behavior is still limited. We investigated the separation of different mAb formats from four individual polysorbate degrading hydrolases (CES1F, CES2C, LPLA2, and PAF-AH) using cation exchange (CEX) and mixed-mode chromatography (MMC) polishing steps. Our research identified a key challenge: The similar elution behavior of mAbs and HCPs during chromatographic separation. To investigate this phenomenon, we performed high-throughput binding screenings for recombinant polysorbate degrading hydrolases and representative mAb candidates on CEX and MMC chromatography resins. We then employed a three-step strategy that also served as a scale-up process, optimizing separation conditions and leading to the successful removal of specific HCPs while maintaining high mAb recovery rates (>96%). This strategy involved the use of surface response models and miniature columns for screening, followed by validation on larger columns using a chromatography system. Our results highlight the critical role of the inherent properties of mAbs for successful separation from HCPs. These results underscore the need to tailor the purification process to leverage the slight differences in binding behavior and elution profiles between mAbs and specific HCPs. This approach lays the foundation for developing more effective strategies for overcoming the challenge of enzymatic polysorbate degradation, paving the way for improved quality and safety in biopharmaceutical products.

Mogamulizumab-associated rash - Case series and review of the literature.

Mogamulizumab, a monoclonal antibody directed against CC chemokine receptor 4, is approved as a second-line treatment of mycosis fungoides and Sézary syndrome. One of the most common side effects is mogamulizumab-associated rash (MAR), which can present in a variety of clinical and histological types. Clinically, it can be difficult to differentiate between MAR and progression of the underlying disease, so histological examination is crucial for clinicopathological correlation. Current data analyses suggest that MAR is more common in patients with Sézary syndrome and is associated with a significantly better response to treatment, making the distinction from disease progression particularly important. The management of MAR depends on its severity, and therapy may need to be paused. This article presents three cases from our clinic and reviews the current literature on MAR. It emphasizes the importance of understanding MAR in the management of patients with cutaneous lymphomas.

Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma.

Circulating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it requires whole-genome amplification (WGA) of DNA, which might introduce bias. Here, we describe a novel approach based on mass spectrometry for mutation detection from individual CTCs not requiring WGA and complex bioinformatics pipelines. After establishment of our protocol on tumor cell line-derived single cells, it was validated on CTCs of 33 metastatic melanoma patients and the mutations were compared to those obtained from tumor tissue and ctDNA. Although concordance with tumor tissue was superior for ctDNA over CTC analysis, a larger number of mutations were found within CTCs compared to ctDNA (p = 0.039), including mutations in melanoma driver genes, or those associated with resistance to therapy or metastasis. Thus, our results demonstrate proof-of-principle data that CTC analysis can provide clinically relevant genomic information that is not redundant to tumor tissue or ctDNA analysis.

Patient-reported outcomes of topical finasteride/minoxidil treatment for male androgenetic alopecia: A retrospective study using telemedical data.

BACKGROUND: Oral finasteride and topical minoxidil are the current standard of care for male androgenetic alopecia and a combination of the two treatments can be considered for greater efficacy. Clinical trials of topical finasteride have also yielded promising results, but routine care data are lacking. AIMS: To examine patient-reported outcomes of men with androgenetic alopecia who received topical finasteride admixed with minoxidil compared to the current standard of care (oral finasteride). METHODS: Retrospective, cross-sectional study with data from a German direct-to-consumer teledermatology platform between December 2021 and January 2023. Patient-reported outcomes were collected through voluntary follow-up questionnaires provided after 6 weeks on topical finasteride/minoxidil or oral finasteride treatment. RESULTS: A total of 1545 patients who received topical finasteride/minoxidil treatment were included; 238 (15.4%) participated in the follow-up questionnaire. At week six, 62.2% (148/238) reported positive changes in their hair appearance, and 44.1% (105/238) reported an improvement of self-esteem. Treatment-related adverse events were reported in 11.8% (28/238). Full treatment adherence was observed in 74.4% (177/238). Comparing the topical treatment group to those receiving oral finasteride, lower treatment adherence was reported, along with higher rates of local adverse events; no difference was found in the incidence of sexual adverse events. CONCLUSION: Based on patient-reported outcomes, topical finasteride/minoxidil seems to be effective and well tolerated, but not superior to oral finasteride. Lower treatment adherence for topical usage must be considered when considering treatment options. Additional real-world data are needed to further evaluate the efficacy and safety of topical finasteride/minoxidil.

532-nm potassium titanyl-phosphate laser versus 595-nm pulsed dye laser for port-wine birthmarks: A prospective, randomized, split-side study.

BACKGROUND: Pulsed dye lasers (PDL) are currently the first-line treatment of port-wine birthmarks (PWB). Due to high maintenance costs and instable technology, alternative methods are needed. OBJECTIVES: To compare clinical outcomes of a variable-sequenced, long-pulsed 532-nm potassium titanyl-phosphate (KTP) laser and PDL on treating PWB. METHODS: A prospective, randomized, split-side study. Patients were treated with a KTP laser and PDL with 1 to 5 sessions at intervals of 6-8 weeks. A follow-up visit was scheduled 6 weeks post-treatment. Efficacy was evaluated through colorimetric analysis, area reduction measurements and clinical evaluations by two blinded investigators based on photo documentation. Subjects provided rating of pain intensity during treatment, post-treatment reactions and satisfaction. Safety was measured by adverse events. Maintenance issues of the laser systems were documented. RESULTS: A total of 35 patients (mean age 42.1 years) were enrolled. 63% were female. Patients received 2.4 (SD 1.4; 1-5) treatment sessions. Colorimetric analysis indicated a comparable clearance effect in PWB of both KTP laser and PDL. Independent investigators rated clinical appearance to be significantly improved compared to baseline. No significant difference was observed between both laser systems. Regarding post-treatment reactions, the KTP laser caused less swelling, purpura and crusts. 96% would recommend both treatment modalities. Patients were satisfied with both laser systems. During the study, PDL systems malfunctioned for 6.6 months in total. For the KTP laser, we did not observe any system failures. CONCLUSION: Our data indicate that the KTP laser of the latest generation with large-spot sizes, subpulse technology and cryogen cooling has a comparable efficacy to the PDL in treating PWB. In addition, KTP laser is associated with greater tolerability, fewer technical failures and lower repair costs. Further prospective studies are required to determine the true effectiveness of the KTP laser in PWB treatment. This study was preregistered in Clinicaltrials.gov (NCT05771298).

High Serum Levels of CCL20 Are Associated with Recurrence and Unfavorable Overall Survival in Advanced Melanoma Patients Receiving Immunotherapy.

BACKGROUND: Immune checkpoint inhibition has revolutionized melanoma therapy, but many patients show primary or secondary resistance. Biomarkers are, therefore, urgently required to predict response prior to the initiation of therapy and to monitor disease progression. METHODS: In this prospective study, we analyzed the serum C-C motif chemokine ligand 20 (CCL20) concentration using an enzyme-linked immunosorbent assay. Blood was obtained at baseline before the initiation of immunotherapy with anti-PD-1 monotherapy or Nivolumab and Ipilimumab in advanced melanoma patients (stages III and IV) enrolled at the University Medical Center Hamburg-Eppendorf. The CCL20 levels were correlated with clinico-pathological parameters and disease-related outcomes. RESULTS: An increased C-C motif chemokine ligand 20 (CCL20) concentration (≥0.34 pg/mL) at baseline was associated with a significantly impaired progression-free survival (PFS) in the high-CCL20 group (3 months (95% CI: 2-6 months) vs. 11 months (95% CI: 6-26 months)) (p = 0.0033) and could be identified as an independent negative prognostic factor for PFS in univariate (Hazard Ratio (HR): 1.98, 95% CI 1.25-3.12, p = 0.004) and multivariate (HR: 1.99, 95% CI 1.21-3.29, p = 0.007) Cox regression analysis, which was associated with a higher risk than S100 (HR: 1.74). Moreover, high CCL20 levels were associated with impaired overall survival (median OS not reached for low-CCL20 group, p = 0.042) with an HR of 1.85 (95% CI 1.02-3.37, p = 0.043) in univariate analysis similar to the established prognostic marker S100 (HR: 1.99, 95% CI: 1.02-3.88, p = 0.043). CONCLUSIONS: CCL20 may represent a novel blood-based biomarker for the prediction of resistance to immunotherapy that can be used in combination with established strong clinical predictors (e.g., ECOG performance score) and laboratory markers (e.g., S100) in advanced melanoma patients. Future prospective randomized trials are needed to establish CCL20 as a liquid biopsy-based biomarker in advanced melanoma.

Shades of gravity - effects of planetary gravity levels on electrocortical activity and neurocognitive performance.

The plans of international space agencies to return to the Moon and explore deep space, including Mars, highlight the challenges of human adaptation and stress the need for a thorough analysis of the factors that facilitate, limit and modify human performance under extreme environments. This study investigates the influence of partial gravity on behavioural (error rate and reaction time) and neuronal parameters (event-related potentials) through parabolic flights. Brain cortical activity was assessed using EEG from 18 participants who solved a neurocognitive task, consisting of a mental arithmetic task and an auditory oddball paradigm, during Earth (1G), Lunar (0.16G + 0.25G) and Martian gravity (0.38G + 0.5G) for 15 consecutive parabolas. Data shows higher electrocortical activity in Earth gravity compared to Lunar and Martian gravity in the parietal lobe. No differences in participants' performance were found among the gravity levels. Event-related potentials displayed gravity-dependent variations, though limited stimuli recording suggests caution in interpretation. Data suggests a threshold between Earth and Martian gravity within the different gravities responsible for physiological changes, but it seems to vary greatly between individuals. The altered neuronal communication could be explained with a model developed by Kohn and Ritzmann in 2018. The increasing intracranial pressure in weightlessness changes the properties of the cell membrane of neurons and leads to a depolarisation of the resting membrane potential. The findings underscore the individuality of physiological changes in response to gravity alterations, signalling the need for further investigations in future studies.

Rosacea treatment with 532 nm KTP versus 595 nm pulsed dye laser-A prospective, controlled study.

BACKGROUND: Pulsed-dye lasers (PDL) are one of the standard therapies for rosacea, but alternatives are needed. AIMS: To compare the efficacy and safety of the variable-sequenced, large-spot 532 nm KTP laser to the 595 nm PDL in treating rosacea. MATERIALS AND METHODS: A prospective, controlled, evaluator-blinded study. Patients were treated with either a KTP or PDL with 1-3 sessions at intervals of 6-8 weeks. A follow-up visit was scheduled on Week 6 post-treatment. Clinical outcome was assessed by computer-assisted analysis and by patients and two blinded dermatologists. Pain intensity during treatment and adverse events were documented. RESULTS: Forty-five patients (mean age 51 years) were allocated in a 2:1 ratio to either the KTP or PDL. Erythema in both treatment arms decreased significantly (p < 0.01). Clinical evaluation revealed high improvement. Mean pain intensity was significantly lower with the KTP (2.5/10) than with the PDL (4.1/10). Both lasers showed a good safety profile. Relevant purpura was only seen in the PDL group. CONCLUSIONS: Both the variable-sequenced, large-spot KTP and the PDL demonstrated comparable efficacy in treatment of rosacea. Regarding safety, the KTP exhibited fewer post-treatment reactions. The KTP might serve as a potential alternative to PDL in the treatment of rosacea.

Comparisons of Self-Report With Objective Measurements Suggest Faster Responding but Little Change in Response Quality Over Time in Ecological Momentary Assessment Studies.

Response times (RTs) to ecological momentary assessment (EMA) items often decrease after repeated EMA administration, but whether this is accompanied by lower response quality requires investigation. We examined the relationship between EMA item RTs and EMA response quality. In one data set, declining response quality was operationalized as decreasing correspondence over time between subjective and objective measures of blood glucose taken at the same time. In a second EMA study data set, declining response quality was operationalized as decreasing correspondence between subjective ratings of memory test performance and objective memory test scores. We assumed that measurement error in the objective measures did not increase across time, meaning that decreasing correspondence across days within a person could be attributed to lower response quality. RTs to EMA items decreased across study days, while no decrements in the mean response quality were observed. Decreasing EMA item RTs across study days did not appear problematic overall.

Two-Drug Regimens Dolutegravir/Lamivudine and Dolutegravir/Rilpivirine Are Effective with Few Discontinuations in US Real-World Settings: Results from the TANDEM Study.

INTRODUCTION: Dolutegravir/lamivudine (DTG/3TC) and dolutegravir/rilpivirine (DTG/RPV) are fixed-dose, complete, single-tablet, two-drug regimens (2DRs) indicated for HIV-1. DTG/3TC is approved for antiretroviral therapy (ART)-naive people with HIV-1 and virologically suppressed individuals to replace current ART; DTG/RPV is indicated for virologically suppressed individuals as a switch option. Virologic efficacy and effectiveness of these DTG-based 2DRs have been demonstrated in phase 3 clinical trials and real-world cohorts, primarily from Europe. This study characterized real-world use of DTG-based 2DRs for HIV-1 treatment in the USA. METHODS: TANDEM was a retrospective medical chart review across 24 US sites. Individuals aged ≥ 18 years who initiated DTG/3TC or DTG/RPV before September 30, 2020, with ≥ 6 months of follow-up were included. One cohort included ART-naive people who initiated DTG/3TC (n = 126), and two other cohorts included virologically suppressed (HIV-1 RNA < 50 copies/mL) people on stable ART regimens for ≥ 3 months before switch to either DTG/3TC (n = 192) or DTG/RPV (n = 151). Clinical characteristics, treatment history, and outcomes are described. RESULTS: Virologically suppressed individuals were older than those who were ART-naive, and the ART-naive cohort had higher proportions of individuals assigned male at birth and of Hispanic ethnicity. The most common healthcare provider-reported reason for choosing a DTG-based 2DR was avoidance of long-term toxicities (25-33% across cohorts), followed by simplification/streamlining of treatment. Among ART-naive people on DTG/3TC, 94% achieved virologic suppression after initiation, and 83% maintained suppression at last follow-up; discontinuation rate was < 1%. Among cohorts who switched to DTG-based 2DRs, 96% maintained virologic suppression on DTG/3TC and 93% on DTG/RPV; 2% on DTG/3TC and 3% on DTG/RPV discontinued. CONCLUSION: Motivation for selecting DTG-based 2DRs was primarily driven by a desire to avoid or manage toxicities and simplify treatment. Results demonstrate that DTG/3TC and DTG/RPV are effective in real-world settings, with few discontinuations, reflecting data from clinical trials.

C-reactive protein flare predicts response to checkpoint inhibitor treatment in melanoma.

BACKGROUND: The treatment of melanoma has been revolutionized by the use of immune checkpoint inhibition (ICI), but many patients do not benefit. Furthermore, immune-related adverse events may occur during therapy. A predictive biomarker is needed to reliably identify patients benefitting. In lung, renal cell and bladder cancer early C-reactive protein (CRP) kinetics were shown to be a predictive biomarker for ICI. OBJECTIVE: Here, we investigate early CRP kinetics as predictive biomarker for ICI in melanoma patients. METHODS: Two independent prospectively collected cohorts were analysed: Cohort 1 (n = 87) with advanced and Cohort 2 (n = 99) with completely resected melanoma. Patients were stratified by in the dynamics of CRP after ICI initiation: A doubling of baseline CRP within 30 days followed by at least a 30% drop within 3 months was classified as a CRP flare. If no doubling of CRP was reported, but a 30% drop within 3 months, patients were classified as CRP responders and all others as CRP non-responders. Analysed factors included clinical characteristics like S100B and LDH. Median follow-up was 1.5 and 1.7 years for Cohorts 1 and 2. RESULTS: In Cohort 1 CRP flare (n = 12), CRP responders (n = 43) and CRP non-responders (n = 32) with a progression-free survival (PFS) of 0.7, 0.6 and 0.2 years (p = 0.017) and an overall survival (OS) of 2.2, 1.5 and 1.0 years (p = 0.014), respectively. Multivariable Cox analysis showed an independent risk reduction of progression for CRP responders by 62% compared to CRP non-responders (p = 0.001). In Cohort 2 CRP flare (n = 13), CRP responders (n = 70) and CRP non-responders (n = 16) the log-rank analysis showed a significant difference between OS and recurrence-free survival (RFS) curves (p = 0.046 and p = 0.049). CONCLUSION: Early CRP kinetics could indicate a response to ICI with improved OS and RFS/PFS. CRP flare and CRP response indicating significantly improved outcomes compared to CRP non-responders.

Telephone follow-up after outpatient nail surgery - a retrospective analysis.

BACKGROUND: One of the areas of care in dermatosurgery is the surgical treatment of diseases of the nail organ. Side effects and complications after nail surgery were investigated by telephone follow-up (TFU), and its suitability for postoperative monitoring and consultation was assessed. PATIENTS AND METHODS: All patients who underwent nail surgery at the Department of Dermatology at the Ludwigshafen City Hospital from October 2019 to December 2021 in outpatient setting were contacted by telephone on the second to third postoperative day and questioned in a standardized manner about postoperative complaints and counselled if necessary. RESULTS: A total of 100 cases were followed up. The most common procedures performed were phenol matricectomy (41%), nail avulsion (16%), and nail matrix biopsies (9%). 50% and 21% of patients reported pain on the day of the procedure and the day after surgery, respectively. After nail avulsion, pain was statistically significantly more frequently reported on the day following the procedure and pain medication was statistically significantly more frequently required (p  =  0.002). Serious adverse events did not occur after nail surgery. 10% of the respondents raised specific questions and needed counseling by TFU. CONCLUSIONS: All nail surgeries were well tolerated in the outpatient setting. Pain was the most common side effect, although only half of all patients reported pain on the day of surgery and only 21% on the day after the procedure. The TFU proved to be an effective and practical as well as easy to establish method for postoperative follow-up and consultation after outpatient nail surgery.

Cognitive Functioning and the Quality of Survey Responses: An Individual Participant Data Meta-Analysis of 10 Epidemiological Studies of Aging.

OBJECTIVES: Self-reported survey data are essential for monitoring the health and well-being of the population as it ages. For studies of aging to provide precise and unbiased results, it is necessary that the self-reported information meets high psychometric standards. In this study, we examined whether the quality of survey responses in panel studies of aging depends on respondents' cognitive abilities. METHODS: Over 17 million survey responses from 157,844 participants aged 50 years and older in 10 epidemiological studies of aging were analyzed. We derived 6 common statistical indicators of response quality from each participant's data and estimated the correlations with participants' cognitive test scores at each study wave. Effect sizes (correlations) were synthesized across studies, cognitive tests, and waves using individual participant data meta-analysis methods. RESULTS: Respondents with lower cognitive scores showed significantly more missing item responses (overall effect size ρ^ = -0.144), random measurement error (ρ^ = -0.192), Guttman errors (ρ^ = -0.233), multivariate outliers (ρ^ = -0.254), and acquiescent responses (ρ^ = -0.078); the overall effect for extreme responses (ρ^ = -0.045) was not significant. Effect sizes were consistent across studies, modes of survey administsration, and different cognitive functioning domains, although some cognitive domain specificity was also observed. DISCUSSION: Lower-quality responses among respondents with lower cognitive abilities add random and systematic errors to survey measures, reducing the reliability, validity, and reproducibility of survey study results in aging research.

Can you tell people's cognitive ability level from their response patterns in questionnaires?

Questionnaires are ever present in survey research. In this study, we examined whether an indirect indicator of general cognitive ability could be developed based on response patterns in questionnaires. We drew on two established phenomena characterizing connections between cognitive ability and people's performance on basic cognitive tasks, and examined whether they apply to questionnaires responses. (1) The worst performance rule (WPR) states that people's worst performance on multiple sequential tasks is more indicative of their cognitive ability than their average or best performance. (2) The task complexity hypothesis (TCH) suggests that relationships between cognitive ability and performance increase with task complexity. We conceptualized items of a questionnaire as a series of cognitively demanding tasks. A graded response model was used to estimate respondents' performance for each item based on the difference between the observed and model-predicted response ("response error" scores). Analyzing data from 102 items (21 questionnaires) collected from a large-scale nationally representative sample of people aged 50+ years, we found robust associations of cognitive ability with a person's largest but not with their smallest response error scores (supporting the WPR), and stronger associations of cognitive ability with response errors for more complex than for less complex questions (supporting the TCH). Results replicated across two independent samples and six assessment waves. A latent variable of response errors estimated for the most complex items correlated .50 with a latent cognitive ability factor, suggesting that response patterns can be utilized to extract a rough indicator of general cognitive ability in survey research.

Attrition from longitudinal ageing studies and performance across domains of cognitive functioning: an individual participant data meta-analysis.

OBJECTIVES: This paper examined the magnitude of differences in performance across domains of cognitive functioning between participants who attrited from studies and those who did not, using data from longitudinal ageing studies where multiple cognitive tests were administered. DESIGN: Individual participant data meta-analysis. PARTICIPANTS: Data are from 10 epidemiological longitudinal studies on ageing (total n=209 518) from several Western countries (UK, USA, Mexico, etc). Each study had multiple waves of data (range of 2-17 waves), with multiple cognitive tests administered at each wave (range of 4-17 tests). Only waves with cognitive tests and information on participant dropout at the immediate next wave for adults aged 50 years or older were used in the meta-analysis. MEASURES: For each pair of consecutive study waves, we compared the difference in cognitive scores (Cohen's d) between participants who dropped out at the next study wave and those who remained. Note that our operationalisation of dropout was inclusive of all causes (eg, mortality). The proportion of participant dropout at each wave was also computed. RESULTS: The average proportion of dropouts between consecutive study waves was 0.26 (0.18 to 0.34). People who attrited were found to have significantly lower levels of cognitive functioning in all domains (at the wave 2-3 years before attrition) compared with those who did not attrit, with small-to-medium effect sizes (overall d=0.37 (0.30 to 0.43)). CONCLUSIONS: Older adults who attrited from longitudinal ageing studies had lower cognitive functioning (assessed at the timepoint before attrition) across all domains as compared with individuals who remained. Cognitive functioning differences may contribute to selection bias in longitudinal ageing studies, impeding accurate conclusions in developmental research. In addition, examining the functional capabilities of attriters may be valuable for determining whether attriters experience functional limitations requiring healthcare attention.