UNASSIGNED: Parkinson\'s Disease (PD) is a progressive, chronic neurodegenerative disease, representing significant economic and social burdens. It is typically defined by motor symptoms (MSs), however, this does not reflect the full patient burden. Non-motor symptoms (NMSs) are increasingly recognized as central characteristics of PD. Despite these recent developments, NMSs still lack recognition in research among patients and clinicians, possibly leading to wrong diagnoses and medical treatment. Therefore, this study employs a scoping review to identify relevant NMSs, their prevalence, and the effect they have on Quality-of-Life (QoL) and Cost-of-Illness (COI). Secondly, this study aims to identify gaps in the current body of knowledge surrounding NMSs of PD and propose possible ways future research could bridge those gaps.
UNASSIGNED: This scoping review identified 60 records for inclusion, using PubMed and Web of Science. It included studies from Spain or Italy, including data on People with Parkinson\'s Disease. A comparative analysis was performed using Microsoft Excel.
UNASSIGNED: It showed that the body of evidence relevant to NMSs, their prevalence, QoL, and COI is limited, or that estimates vary to an extent where interpretation is difficult.
UNASSIGNED: Most studies suffer from generalization, representation, and standardization issues, stemming from their designs and methodological decisions. Although the findings of this study should be interpreted with caution due to the scoping review design, several recommendations are made for future research to generate more robust data.

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UNASSIGNED: Hypomethylating agents (HMAs) are guideline-recommended treatment for higher-risk myelodysplastic syndromes/neoplasms (MDS). However, a prior survey of patients with MDS reported challenges with intravenous (IV) and subcutaneous (SC) HMA therapies, including pain related to treatment administration and interference with daily activities; most patients also indicated a preference to switch to an oral therapy if one were available.
UNASSIGNED: This study evaluated the perspectives of US patients with MDS receiving oral decitabine/cedazuridine (DEC-C), an alternative to IV/SC HMAs.
UNASSIGNED: An online survey was conducted among adult patients with MDS in the United States (10 November 2022 to 5 December 2022) who had filled a prescription for oral DEC-C between 2021 and 2022.
UNASSIGNED: A total of 150 patients completed the survey; 61% were aged ⩾60 years and 63% were male. Of these, 123 (82%) were still receiving oral DEC-C, and 27 (18%) had stopped oral DEC-C treatment. Half (50%) of patients had received oral DEC-C for ⩾6 months. The majority reported that treatment was convenient (83%) and that they were satisfied with treatment (86%). Most patients also reported very little/no interference with regular daily activities (82%), social activities (78%), and productivity (78%). When queried about negative impacts on quality of life (QOL), treatment side effects were the most commonly reported (30% of respondents). Among patients who had previously received IV/SC HMAs (n = 91), most agreed that oral DEC-C interfered less with daily life (91%) and had experienced improvement in QOL (85%) compared with previous treatment; 91% reported that oral DEC-C reduced the number of times they needed to travel to a healthcare facility.
UNASSIGNED: Survey results suggest very little/no impact on regular daily activities and improved QOL with oral DEC-C relative to IV/SC HMAs, highlighting the potential for oral DEC-C to reduce the treatment burden associated with parenteral HMA therapy.

UNASSIGNED: Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, conducting a QOL survey with patients is difficult. Therefore, we conducted a QOL survey with physicians. Specifically, this study aimed to clarify how physicians assess QOL in patients with pancreatic cancer by conducting a survey and comparing the results between physicians and the general public.
UNASSIGNED: A survey was conducted by interviewing physicians administering chemotherapy to patients for recurrent/metastatic pancreatic cancer. This method is similar to that of the QOL survey conducted among the general public. Responses were evaluated using the composite time trade-off (cTTO) and the visual analog scale (VAS) for 11 pancreatic cancer status scenarios (survey scenarios). These scenarios consisted of patients\' health states as well as the types and grades of adverse events (AEs). Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). In addition, we conducted a survey using the EuroQol 5 Dimensions 5-Level (EQ-5D-5l) as reference values.
UNASSIGNED: Twenty physicians responded to the survey. SD had the highest mean QOL value for both assessment methods (Physicians: 0.78, General public: 0.63), whereas PD had the lowest mean QOL value (Physicians: 0.15, General public: -0.12). The physicians assigned higher QOL values on both the VAS and cTTO than the general public did in all survey scenarios.
UNASSIGNED: The QOL values obtained from physicians were consistent with the degree of status in any assessment scenarios. Based on the differences in the QOL survey results between physicians and the general public, physicians tended to assign higher QOL values than the general public in cTTO and VAS assessments.

BACKGROUND: DNA methylation integrates environmental signals with transcriptional programs. COVID-19 infection induces changes in the host methylome. While post-acute sequelae of COVID-19 (PASC) is a long-term complication of acute illness, its association with DNA methylation is unknown. No universal blood marker of PASC, superseding single organ dysfunctions, has yet been identified.
METHODS: In this single centre prospective cohort study, PASC, post-COVID without PASC, and healthy participants were enrolled to investigate their symptoms association with peripheral blood DNA methylation data generated with state-of-the-art whole genome sequencing. PASC-induced quality-of-life deterioration was scored with a validated instrument, SF-36. Analyses were conducted to identify potential functional roles of differentially methylated loci, and machine learning algorithms were used to resolve PASC severity.
RESULTS: 103 patients with PASC (22.3% male, 77.7% female), 15 patients with previous COVID-19 infection but no PASC (40.0% male, 60.0% female), and 27 healthy volunteers (48.1% male, 51.9% female) were enrolled. Whole genome methylation sequencing revealed 39 differentially methylated regions (DMRs) specific to PASC, each harbouring an average of 15 consecutive positions, that differentiate patients with PASC from the two control groups. Motif analyses of PASC-regulated DMRs identify binding domains for transcription factors regulating circadian rhythm and others. Some DMRs annotated to protein coding genes were associated with changes of RNA expression. Machine learning support vector algorithm and random forest hierarchical clustering reveal 28 unique differentially methylated positions (DMPs) in the genome discriminating patients with better and worse quality of life.
CONCLUSIONS: Blood DNA methylation levels identify PASC, stratify PASC severity, and suggest that DNA motifs are targeted by circadian rhythm-regulating pathways in PASC.
BACKGROUND: This project has been funded by the following agencies: NIH-AI173035 (A. Jaitovich and R. Alisch); and NIH-AG066179 (R. Alisch).

Irritable bowel syndrome (IBS), a disorder of gut-brain interaction, is often comorbid with somatic pain and psychological disorders. Dysregulated signaling of brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), has been implicated in somatic-psychological symptoms in individuals with IBS. We investigated the association of 10 single-nucleotide polymorphisms (SNPs) in the regulatory 3\' untranslated region of neurotrophic receptor tyrosine kinase-2 (NTRK2) kinase domain-deficient truncated isoform (TrkB.T1) and BDNF Val66Met SNP with somatic and psychological symptoms and quality-of-life (QoL) in a cohort from the United States (IBS, n = 464; healthy controls, n = 156). We found that the homozygous recessive genotype (G/G) of rs2013566 in individuals with IBS is associated with worsened somatic symptoms, including headache, back pain, joint pain, muscle pain, and somatization as well as diminished sleep quality, energy level, and overall QoL. Validation using United Kingdom BioBank data confirmed the association of rs2013566 with an increased likelihood of headache. Several SNPs (rs1627784, rs1624327, and rs1147198) showed significant associations with muscle pain in our U.S. cohort. These 4 SNPs are predominantly located in H3K4Me1-enriched regions, suggesting their enhancer and/or transcription regulation potential. Our findings suggest that genetic variation within the 3\' untranslated region region of the TrkB.T1 isoform may contribute to comorbid conditions in individuals with IBS, resulting in a spectrum of somatic and psychological symptoms impacting their QoL. These findings advance our understanding of the genetic interaction between BDNF/TrkB pathways and somatic-psychological symptoms in IBS, highlighting the importance of further exploring this interaction for potential clinical applications. PERSPECTIVE: This study aims to understand the genetic effects on IBS-related symptoms across somatic, psychological, and quality-of-life (QoL) domains, validated by United Kingdom BioBank data. The rs2013566 homozygous recessive genotype correlates with worsened somatic symptoms and reduced QoL, emphasizing its clinical significance.

UNASSIGNED: Low back pain (LBP) is a debilitating phenomenon that significantly impacts quality-of-life (QoL). The PainDETECT questionnaire (PD-Q) is a screening tool aimed at distinguishing nociceptive pain (NoP) and neuropathic pain (NeP) classifications. Associations between these classifications and patient-reported outcome measures (PROMs) and sociodemographic parameters are yet to be established.
UNASSIGNED: The study aimed to determine the relationship between NeP as assessed by the PD-Q and pain, disability, QoL, and sociodemographic factors.
UNASSIGNED: A retrospective analysis of an ongoing prospectively collected database was conducted involving 512 patients aged >18 years who presented to a tertiary spine clinic for LBP having completed the PainDETECT questionnaire, Oswestry Disability Index (ODI), EuroQol Five-Dimensional (EQ-5D) questionnaire, or answered questions regarding sociodemographic status.
UNASSIGNED: The NeP group had a higher mean numerical rating scale (NRS) score (7.96±1.54 vs. 5.76±2.27, p <.001) and lower age (55±15.6 vs. 59±17.8, p <.05) compared to the NoP group. When confounded for NRS, analysis of covariance demonstrated an 89.5% higher total ODI score (p <.001) and 50.5% lower EQ-5D utility score (p <.001) in the NeP compared to NoP group. Smokers and individuals with a no partner marital status were 2.373 (OR = 2.373, 95% CI = 1.319-4.266, p <.01) and 2.384 times (OR = 2.384, 95% CI = 1.390-4.092, p <.01) more likely to have NeP compared to NoP, respectively. Patients with NeP were also of lower income class compared to patients with NoP (Z = -2.45, p <.05).
UNASSIGNED: NeP was associated with higher levels of disability and lower QoL. Smokers, individuals with a no partner marital status, and individuals with a lower income class were more likely to suffer NeP rather than NoP. These findings have illuminated a crucial notion: in patients with elevated NRS, the detrimental impact of NeP on patient wellbeing underscores the fundamental need to represent pain on a nociceptive-neuropathic continuum, permitting more accurate differentiation of pain components.

UNASSIGNED: Craniopharyngiomas (CPs) are rare, low-grade tumors characterized by a range of debilitating symptoms. Most of the existing literature reports postoperative outcomes of the different treatment modalities of childhood CP. However, few studies have reported the impact of these different treatment methods on the quality of life (QoL) of survivors of childhood CP. Therefore, we aim to assess the correlation between different surgical modalities on the QoL of patients with childhood CP from a lower-middle-income country.
UNASSIGNED: Twenty-nine survivors who underwent treatment for CP were included in the study. The selected patients had either been managed with complete resection, debulking, or placement of an Ommaya reservoir. QoL was assessed by the pediatric quality of life (PedsQL) questionnaire. The effect of the different treatment modalities on the QoL was assessed.
UNASSIGNED: Mean follow-up was 4.4 ± 2.19 years. The type of surgery was significantly related to the mean PedsQL scores for the total score as well as each of the individual domain scores (P < 0.001). Complete resection of the tumor resulted in the lowest mean (standard deviation) PedsQL total score of 56.6 ± 7.12 compared to the Ommaya reservoir with biopsy (83.3 ± 5.69) and debulking (93.8 ± 3.37) (P < 0.001).
UNASSIGNED: There was a significant effect of the type of surgical treatment on the QoL of the survivors of childhood CP. It is important to consider the long-term outcomes in addition to immediate postoperative outcomes when deciding on a treatment strategy while managing children with CP.

BACKGROUND: Selenoprotein P (SELENOP) transports selenium to extrahepatic tissues and is a biomarker of selenium status. Low soil selenium leads to low dietary selenium intake. A consequence is an increased risk of cardiovascular disease.
OBJECTIVE: To investigate clinical aspects associated with SELENOP deficiency, including biomarkers of inflammation, quality of life, and mortality within 12 years, and the effect of dietary selenium and coenzyme Q10 supplementation on SELENOP.
METHODS: SELENOP was determined at inclusion and after four years of supplementation in 403 elderly community-living participants low in selenium receiving selenium yeast (200 μg/day) and coenzyme Q10 (200 mg/day), or placebo. Pre-intervention, the average serum selenium level was 67 μg/L. T-tests, repeated measures of variance, Cox proportional regressions analyses, Kaplan-Meier graphs and ANCOVA analyses were applied. Associations with biomarkers of inflammation, telomere length, quality of life and mortality were investigated. Benchmark modelling was used to determine the serum selenium concentration at which the saturation levels of SELENOP and GPx3 was achieved. Comparison with GPx3 and serum selenium to identify increased mortality risk was performed, and the effect of supplementation on SELENOP levels were evaluated.
RESULTS: Inverse associations were observed between the level of SELENOP at inclusion and biomarkers for inflammation. At follow-up, shorter telomere lengths were seen in those with low levels of SELENOP at inclusion, whereas high levels of SELENOP were associated with better quality of life and decreased mortality. SELENOP had increased prognostic power compared to GPx3 and selenium. Saturation of SELENOP was achieved at a serum selenium level of 146 μg/L, and for GPx3 at 99 μg/L. Supplementation induced higher levels of SELENOP.
CONCLUSIONS: Significant associations between SELENOP and inflammation, length of telomeres, quality of life, and mortality were observed. Thus, selenium supplementation improved SELENOP expression, thereby facilitating systemic selenium bioavailability and resulting in the observed positive health effects.

The highly heterogeneous population of elderly with epilepsy continues to increase as the incidence of epilepsy rises with increasing life expectancy. There are many aspects to consider in the treatment of elderly with epilepsy, e g comorbidities and the complexity of polypharmacy. The literature on quality-of-life (QoL) and patient-centered outcomes in elderly in general as well as in elderly with epilepsy is limited, most of the existing studies report results from quality-of-life surveys. No such QoL questionnaires have, however, in the validation process explored issues specific to the elderly. Seizure frequency, co-morbidities and depression predicted QoL in elderly with epilepsy and the energy/fatigue domain scored worst when QOLIE-31 was used. In the handful of qualitative interview studies identified in this review, a number of topics specific for elderly with epilepsy were explored. Some of these were difficulties with information gathering, the importance of maintaining normalcy, incongruence with provider goals and wanting to be more involved in the treatment. There is a need for further exploration of the specific concerns of elderly with epilepsy. This review provides a comprehensive overview of the studies and emphasizes the importance of involving elderly people with epilepsy in their own care.