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Loss of ambulation is common and highly variable in Parkinson’s disease (PD), and poorly understood from the perspectives of those with PD. Gaining insights to the anticipated perceived trajectories and their drivers, will facilitate patient-centered care. Latent class growth analysis, a person-centered mixture modelling approach, was applied to 16,863 people with PD stratified by early (N = 8612; < 3 years), mid (N = 6181; 3–10 years) and later (N = 2070; > 10 years) disease to discern clusters with similar longitudinal patterns of self-reported walking difficulty, measured by EuroQoL 5D-5L that is validated for use in PD. There were four clusters in early and mid-disease strata, with a fifth identified in later disease. Trajectories ranged from none to moderate walking difficulty, with small clusters with severe problems. The percentage of subjects with moderate (early = 17.5%, mid = 26.4%, later = 32.5%) and severe (early = 3.8%, mid = 7.4%, later = 15.4%) walking difficulty at baseline increased across disease duration groups. The trajectories tended to be stable with variability in moderate and severe groups. Across strata, clusters with moderate to severe problems were associated with more severe impairment, depression, anxiety, arthritis, higher BMI, lower income, and lower education, but no consistent race or gender differences. The findings reveal distinct longitudinal patterns in perceived difficulties in walking in PD.

Pain is a common and complex non-motor symptom in people with Parkinson’s disease (PWP). Little is known about the genetic drivers of pain in PWP, and progress in its study has been challenging. Here, we conducted two genome-wide association studies (GWAS) to identify genetic variants associated with pain experienced during the earliest stages of Parkinson’s disease. The study population consisted of 4,159 PWP of European ancestry who were mapped to five previously-described, longitudinal pain trajectories. In the first GWAS, the extreme pain trajectories (highest burden versus no significant pain over time) were compared, and in the second GWAS, a multinomial approach was undertaken. While no variant reached genome-wide significance, we identified promising associations, such as rs117108018 (OR GWAS−Extreme =8.96, p GWAS−Extreme =2.5 × 10 − 7 ), a brain/nerve eQTL for L3MBTL3 and EPB41L2 , and rs61881484 (p GWAS−Multinomial =2 × 10 − 7 ), which intersects a transcription factor peak targeting CREB1 , critical in sensory neuron synaptic plasticity and neuropathic pain regulation. Gene-based tests implicated CTNNB1 (p GWAS−Extreme =3.2 × 10 − 5 ), KLK7 (p GWAS−Extreme =7 × 10 − 5 ), and SLITRK3 (p GWAS−Multinomial =3.2 × 10 − 5 ), which have been associated with neurodevelopment. At the pathway-level, there was an enrichment for genes involved in neurotransmitter regulation and opioid dependence. This study implicates neuropathic pain mechanisms as prominent drivers of elevated pain in PWP, suggests potential therapeutic genetic targets for further research.

Screening for depression can be challenging among hemodialysis patients due to the overlap of depressive symptoms with dialysis or kidney disease related symptoms. The aim of this study was to understand these overlapping symptoms and develop a depression screening tool for better clinical assessment of depressive symptoms in dialysis patients. We surveyed 1,085 dialysis patients between March 1, 2018 and February 28, 2023 at 15 dialysis facilities in Northeast Ohio with the 9-item patient health questionnaire (PHQ-9) and kidney disease quality of life (KDQOL) instrument. To evaluate overlap across questionnaire items, we used structural equation modeling (SEM). We predicted and transformed factor scores to create a hemodialysis-adjusted PHQ-9 (hdPHQ-9). In exploratory analysis (  = 173), we evaluated the performance of the hdPHQ-9 relative to the PHQ-9 that also received a Mini-International Neuropsychiatric Interview. Our study sample included a high percentage of Black patients (74.6%) and 157 (14.5%) survey participants screened positive for depression (PHQ-9 ≥ 10). The magnitude of overlap was small for (respectively, PHQ-9 item with KDQOL item) fatigue with washed out, guilt with burden on family, appetite with nausea and movement with lightheaded. The hdPHQ-9 showed reasonably high sensitivity (0.81 with 95% confidence interval [CI] 0.58, 0.95) and specificity (0.84 with 95% CI 0.77, 0.89); however, this was not a significant improvement from the PHQ-9. There is little overlap between depressive symptoms and dialysis or kidney disease symptoms. The PHQ-9 was found to be an appropriate depression screening instrument for dialysis patients.

Social and ecological differences in early SARS-CoV-2 pandemic screening and outcomes have been documented, but the means by which these differences have arisen are not well understood. To characterize socioeconomic and chronic disease-related mechanisms underlying these differences. Observational cohort study. Outpatient and emergency care. 12900 Cleveland Clinic Health System patients referred for SARS-CoV-2 testing between March 17 and April 15, 2020. Nasopharyngeal PCR test for SARS-CoV-2 infection. Test location (emergency department, ED, vs. outpatient care), COVID-19 symptoms, test positivity and hospitalization among positive cases. We identified six classes of symptoms, ranging in test positivity from 3.4% to 23%. Non-Hispanic Black race/ethnicity was disproportionately represented in the group with highest positivity rates. Non-Hispanic Black patients ranged from 1.81 [95% confidence interval: 0.91-3.59] times (at age 20) to 2.37 [1.54-3.65] times (at age 80) more likely to test positive for the SARS-CoV-2 virus than non-Hispanic White patients, while test positivity was not significantly different across the neighborhood income spectrum. Testing in the emergency department (OR: 5.4 [3.9, 7.5]) and cardiovascular disease (OR: 2.5 [1.7, 3.8]) were related to increased risk of hospitalization among the 1247 patients who tested positive. Non-Hispanic Black patients and patients from low-income neighborhoods tended toward more severe and prolonged symptom profiles and increased comorbidity burden. These factors were associated with higher rates of testing in the ED. Non-Hispanic Black patients also had higher test positivity rates.

BackgroundSomatic symptoms frequently occur in haemodialysis patients, whereas depression and anxiety are also common but are often under-recognised issues. This study aims to examine the associations among depression, anxiety and somatic symptoms in haemodialysis patients. These symptoms may be linked together under a general distress construct in haemodialysis patients.MethodsWe surveyed 1085 dialysis patients between 1 March 2018 and 28 February 2023 at 17 dialysis facilities in Northeast Ohio with the 9-item Patient Health Questionnaire (PHQ-9), 7-item Generalized Anxiety Disorder and Kidney Disease Quality of Life instrument somatic questions. To evaluate associations across these multi-item questionnaires, we used latent variables and a structural equation modelling approach. We first compared single-factor, two-factor and three-factor models. We next considered bifactor and higher order factor models. We controlled for race, gender and age in all models.ResultsOur study sample included a high percentage of black patients (75%) and 150 (14.3%) survey participants screened positive for depression (PHQ-9 ≥10). All models fit relatively well, with the three-factor model fitting slightly better than the single and two-factor models. In the three-factor model, the associations for depression and anxiety (r=0.818), depression and somatic (r=0.800) and anxiety and somatic (r=0.784) were all high, potentially indicative of poor discriminant validity. We found that the bifactor model fit the best of the five models tested (comparative fit index=0.957, Tucker-Lewis fit index=0.959, root mean square error of approximation=0.043) and was the most substantively meaningful, with an overall internalising construct and specific domains explaining additional covariance across the questions. Being black (vs all other races), male (vs female) and older age all had significantly (p<0.05) lower levels of reported symptoms on most constructs.ConclusionWe found very strong associations among depression, anxiety and somatic symptoms in our sample of haemodialysis patients. All questionnaire items may be linked together under a common general distress disorder, while each still retains unique features of depression, anxiety and somatic symptoms not fully explained by internalising processes. Patient care approaches should generally consider screening for all three together, rather than only one.

In epidemiology, gerontology, human development and the social sciences, age-period-cohort (APC) models are used to study the variability in trajectories of change over time. A well-known issue exists in simultaneously identifying age, period and birth cohort effects, namely that the three characteristics comprise a perfectly collinear system. That is, since age = period-cohort, only two of these effects are estimable at a time. In this paper, we introduce an alternative framework for considering effects relating to age, period and birth cohort. In particular, instead of directly modeling age in the presence of period and cohort effects, we propose a risk modeling approach to characterize age-related risk (i.e., a hybrid of multiple biological and sociological influences to evaluate phenomena associated with growing older). The properties of this approach, termed risk-period-cohort (RPC), are described in this paper and studied by simulations. We show that, except for pathological circumstances where risk is uniquely determined by age, using such risk indices obviates the problem of collinearity. We also show that the size of the chronological age effect in the risk prediction model associates with the correlation between a risk index and chronological age and that the RPC approach can satisfactorily recover cohort and period effects in most cases. We illustrate the advantages of RPC compared to traditional APC analysis on 27496 individuals from NHANES survey data (2005-2016) to study the longitudinal variability in depression screening over time. Our RPC method has broad implications for examining processes of change over time in longitudinal studies.

Background Multi-site studies in stroke rehabilitation are important for determining whether a technology and/or treatment can be successfully administered by sites other than the originating site and with similar positive outcomes. This study is the first multi-site clinical trial of a novel intervention for post-stroke upper limb rehabilitation called contralaterally controlled functional electrical stimulation (CCFES). Previous pilot and single-site studies showed positive effects of CCFES on upper limb impairment and hand dexterity in stroke survivors. The main purpose of this study is to confirm and demonstrate the efficacy of CCFES in a larger group of most likely responders across multiple clinical sites. Methods Up to 129 stroke survivors with moderate to severe upper extremity hemiparesis at 4 clinical trial sites will be randomized to CCFES, cyclic neuromuscular electrical stimulation (cNMES), or task-oriented-training (TOT). Participants will receive 12 weeks of group-specific therapy. Blinded assessments of upper limb impairment and activity limitation, quality of life, and neurophysiology will be used to compare outcomes at baseline, after treatment, and up to 6 months post-treatment. The primary endpoint is change in dexterity from baseline to 6 months post-treatment. Discussion Loss of hand function following stroke is a major rehabilitation problem affecting millions of people per year globally. More effective rehabilitation therapies are needed to restore hand function in these individuals. This study will determine whether CCFES therapy produces greater improvements in upper extremity function than cNMES or TOT, and will begin to elucidate the different mechanisms underlying each of the three treatments. This multi-site study is a critical step in advancing a novel method of rehabilitation toward clinical translation and widespread dissemination. Trial registration ClinicalTrials.gov NCT03574623 . Registered prior to first enrollment; July 2, 2018.

Objectives KiloHertz frequency alternating current waveforms produce conduction block in peripheral nerves. It is not clearly known how the waveform shape affects block outcomes, and if waveform effects are frequency dependent. We determined the effects of waveform shape using two types of electrodes. Materials and methods Acute in-vivo experiments were performed on 12 rats. Bipolar electrodes were used to electrically block motor nerve impulses in the sciatic nerve, as measured using force output from the gastrocnemius muscle. Three blocking waveforms were delivered (sinusoidal, square and triangular) at 6 frequencies (10–60 kHz). Bare platinum electrodes were compared with carbon black coated electrodes. We determined the minimum amplitude that could completely block motor nerve conduction (block threshold), and measured properties of the onset response, which is a transient period of nerve activation at the start of block. In-vivo results were compared with computational modeling conducted using the NEURON simulation environment using a nerve membrane model modified for stimulation in the kilohertz frequency range. Results For the majority of parameters, in-vivo testing and simulations showed similar results: Block thresholds increased linearly with frequency for all three waveforms. Block thresholds were significantly different between waveforms; lowest for the square waveform and highest for triangular waveform. When converted to charge per cycle, square waveforms required the maximum charge per phase, and triangular waveforms the least. Onset parameters were affected by blocking frequency but not by waveform shape. Electrode comparisons were performed only in-vivo. Electrodes with carbon black coatings gave significantly lower block thresholds and reduced onset responses across all blocking frequencies. For 10 and 20 kHz, carbon black coating significantly reduced the charge required for nerve block. Conclusions We conclude that both sinusoidal and square waveforms at frequencies of 20 kHz or higher would be optimal. Future investigation of carbon black or other high charge capacity electrodes may be useful in achieving block with lower BTs and onsets. These findings will be of importance for designing clinical nerve block systems.

Introduction Research suggests neighbourhood socioeconomic vulnerability is negatively associated with women's likelihood of receiving adequate prenatal care and achieving desired postpartum permanent contraception. Receiving adequate prenatal care is linked to a greater likelihood of achieving desired permanent contraception, and access to such care may be critical for women with Medicaid insurance given that the federally mandated Medicaid sterilization consent form must be signed at least 30 days before the procedure. We examined whether adequacy of prenatal care mediates the relationship between neighbourhood socioeconomic position and postpartum permanent contraception fulfilment, and examined moderation of relationships by insurance type. Methods This secondary analysis of a retrospective cohort study examined 3012 Medicaid or privately insured individuals whose contraceptive plan at postpartum discharge was permanent contraception. Path analysis estimated relationships between neighbourhood socioeconomic position (economic hardship and inequality, financial strength and educational attainment) and permanent contraception fulfilment by hospital discharge, directly and indirectly through adequacy of prenatal care. Multigroup testing examined moderation by insurance type. Results After adjusting for age, parity, weeks of gestation at delivery, mode of delivery, race, ethnicity, marital status and body mass index, having adequate prenatal care predicted achieving desired sterilization at discharge (β = 0.065, 95% confidence interval [CI]: 0.011, 0.117). Living in neighbourhoods with less economic hardship (indirect effect −0.007, 95% CI: −0.015, −0.001), less financial strength (indirect effect −0.016, 95% CI: −0.030, −0.002) and greater educational attainment (indirect effect 0.012, 95% CI: 0.002, 0.023) predicted adequate prenatal care, in turn predicting achievement of permanent contraception by discharge. Insurance status conditioned some of these relationships. Conclusion Contact with the healthcare system via prenatal care may be a mechanism by which neighbourhood socioeconomic disadvantage affects permanent contraception fulfilment, particularly for patients with Medicaid. To promote reproductive autonomy and healthcare equity, future inquiry and policy might closely examine how neighbourhood social and economic characteristics interact with Medicaid mandates.