Measures Of Clinical Severity Research Articles

Using secondary cases to characterize the severity of an emerging or re-emerging infection

The methods to ascertain cases of an emerging infectious disease are typically biased toward cases with more severe disease, which can bias the average infection-severity profile. Here, we conducted a systematic review to extract information on disease severity among index cases and secondary cases identified by contact tracing of index cases for COVID-19. We identified 38 studies to extract information on measures of clinical severity. The proportion of index cases with fever was 43% higher than for secondary cases. The proportion of symptomatic, hospitalized, and fatal illnesses among index cases were 12%, 126%, and 179% higher than for secondary cases, respectively. We developed a statistical model to utilize the severity difference, and estimate 55% of index cases were missed in Wuhan, China. Information on disease severity in secondary cases should be less susceptible to ascertainment bias and could inform estimates of disease severity and the proportion of missed index cases.

Psychometric evaluation of the Norwegian Toronto Alexithymia Scale (TAS-20) in a multisite clinical sample of patients with personality disorders and personality problems.

Psychometric properties of 20-item Toronto Alexithymia Scale (TAS-20) have been widely analyzed, but the validity and psychometric qualities of the TAS-20 in populations with personality disorders are still poorly understood. The aim of the current study was to analyze the factor structure and validity of TAS-20. Data were extracted from a multisite clinical sample of patients with personality disorders or personality-related problems referred to specialist mental health services in Norway. With one exception, TAS-20 revealed acceptable psychometric properties. Variations of TAS-20 are associated with other clinical measures of distress and severity. Anxiety disorders, borderline, and avoidant personality disorders were all highly related to levels of TAS-20. The TAS-20 also revealed unique variance not accounted for by subjective distress, symptom disorders, or dysfunctional personality traits. The TAS-20 is a relevant instrument for use in assessment of personality disorders, but one subscale should be improved.

Neurofilament light chain and \u03b1-synuclein RT-QuIC as differential diagnostic biomarkers in parkinsonisms and related syndromes

Neurofilament light chain (NfL) and α-synuclein oligomeric seeds (α-syn-s) are promising biomarkers for patients with parkinsonism. We assessed their performance in discriminating Parkinson disease (PD) from atypical parkinsonisms (APDs) and evaluated the association between NfL levels and clinical measures of disease severity. We measured NfL in cerebrospinal fluid (CSF) and/or plasma by immunoassays and α-syn-s in CSF by real-time quaking-induced conversion (RT-QuIC) in patients with PD (n = 153), multiple system atrophy (MSA) (n = 80), progressive supranuclear palsy/cortico-basal syndrome (PSP/CBS) (n = 58), dementia with Lewy bodies (n = 64), isolated REM-sleep behaviour disorder (n = 19), and isolated autonomic failure (n = 30). Measures of disease severity included disease duration, UPDRS-III score, Hoehn and Yahr stage, orthostatic hypotension, MMSE score, and CSF amyloid-beta profile. Both CSF NfL (cNfL) and plasma NfL (pNfL) levels were markedly elevated in APDs, and allowed differentiation with PD (vs. APDs, cNfL AUC 0.96; pNfL AUC 0.95; vs. MSA cNfL AUC 0.99; pNfL AUC 0.97; vs. PSP/CBS cNfL AUC 0.94; pNfL AUC 0.94). RT-QuIC detected α-syn-s in 91.4% of PD, but only 2.5% of APDs (all MSA). In PD/PDD, motor scales significantly correlated with cNfL levels. Although pNfL and both cNfL and α-syn-s accurately distinguished PD from APDs, the combined assessment of CSF markers provided a higher diagnostic value (PD vs. APDs AUC 0.97; vs. MSA AUC 0.97; vs. PSP/CBS AUC 0.99) than RT-QuIC alone (p = 0.047 vs. APDs; p = 0.002 vs MSA; p = 0.007 vs PSP/CBS), or cNfL alone (p = 0.011 vs. APDs; p = 0.751 vs MSA; p = 0.0001 vs. PSP/CBS). The results support the use of these assays in specialised clinics.

Sexuality in Persons With Hidradenitis Suppurativa: Factors Associated With Sexual Desire and Functioning Impairment.

Hidradenitis Suppurativa (HS) is a chronic skin disease involving intimate and sensitive areas and affecting physical and mental health. We investigated the prevalence of sexual desire and functioning impairment, and their associations with quality of life, anxiety, depression, minor psychiatric disorders (MPD), and clinical features (e.g., disease severity) in 77 patients with HS who completed self-report measures and answered to questions assessing socio-demographic characteristics, lifestyle habits, and hindered sexuality due to HS. The majority of patients reported hindered sexuality, and poor sexual functioning, while showing good levels of dyadic and solitary sexual desire. No associations were found between clinical severity and sexuality measures. Multivariate analyses showed significant associations of sexual outcome measures with alcohol consumption, low Body Mass Index, family history of HS, and severe skin symptoms. Moreover, we found that the presence of negative psychological factors (i.e., MPD, anxiety, poor mental status) increased the risk of sexual impairment. These findings underline the important role of psychological and sexual aspects in HS patients and suggest that physicians should consider the effect of disease burden on patients' sexual health.

Association between the Degree of Pre-Synaptic Dopaminergic Pathway Degeneration and Motor Unit Firing Behavior in Parkinson's Disease Patients.

The relationship between motor unit (MU) firing behavior and the severity of neurodegeneration in Parkinson’s disease (PD) is not clear. This study aimed to elucidate the association between degeneration with dopaminergic pathways and MU firing behavior in people with PD. Fourteen females with PD (age, 72.6 ± 7.2 years, disease duration, 3.5 ± 2.1 years) were enrolled in this study. All participants performed a submaximal, isometric knee extension ramp-up contraction from 0% to 80% of their maximal voluntary contraction strength. We used high-density surface electromyography with 64 electrodes to record the muscle activity of the vastus lateralis muscle and decomposed the signals with the convolution kernel compensation technique to extract the signals of individual MUs. We calculated the degree of degeneration of the central lesion-specific binding ratio by dopamine transporter single-photon emission computed tomography. The primary, novel results were as follows: (1) moderate-to-strong correlations were observed between the degree of degeneration of the central lesion and MU firing behavior; (2) a moderate correlation was observed between clinical measures of disease severity and MU firing behavior; and (3) the methods of predicting central nervous system degeneration from MU firing behavior abnormalities had a high detection accuracy with an area under the curve >0.83. These findings suggest that abnormalities in MU activity can be used to predict central nervous system degeneration following PD.

Real-World Treatment Patterns and Outcomes from an Electronic Medical Records Database for Patients with Rheumatoid Arthritis Treated with Repository Corticotropin Injection.

PurposeRepository corticotropin injection (RCI; Acthar® Gel) is a naturally sourced mixture of adrenocorticotropic hormone analogs and other pituitary peptides that exerts anti-inflammatory and immunomodulatory properties via melanocortin receptors. RCI is approved as a short-term adjunctive therapy for rheumatoid arthritis (RA) and is typically used in patients with refractory RA. The objective of this study was to describe real-world outcomes of RA patients treated with RCI by retrospective analysis of an electronic medical records (EMR) database.Patients and MethodsEMR data were obtained from the United Rheumatology-Normal Integrated Community Evidence (UR-NICETM) data repository for patients who used RCI for the treatment of RA. Demographics, comorbidities, disease history, medications, and laboratory evaluations 365 days prior to and 365 days after initiation of RCI were examined.ResultsThe patient cohort was predominantly White females with a mean age of 60 years and high RA activity prior to RCI therapy. Clinical measures of disease severity indicated that patients had high RA activity before starting RCI therapy. Clinical Disease Activity Index (CDAI) scores were significantly reduced 365 days post-initiation of RCI. Swollen and tender joint counts and patient-reported outcomes, including Routine Assessment of Patient Index Data 3 (RAPID3), Physician Global Assessment, and patient assessment of pain severity were also significantly lower. The number of patients taking conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), biologic (b) DMARDs, nonsteroidal anti-inflammatory drugs (NSAIDS), and opioids decreased, as did the number of drugs tried within each class for csDMARDs, bDMARDs, NSAIDs, and glucocorticoids.ConclusionsThese findings suggest that RCI significantly improves clinical outcomes of RA and decreases the need for concomitant medications for up to 1 year following initiation of therapy. The study provides valuable insights into the use of RCI and management of these difficult-to-treat RA patients during routine clinical practice.

Use of non-contrast MR in diagnosing secondary lymphedema of the upper extremities

PurposeThe purpose of the study is to determine if a combination of dermal thickening and subcutaneous fluid honeycombing on non-contrast MRI, termed the dermal rim sign (DRS), can be diagnostically analogous to dermal backflow seen on lymphoscintigraphy in patients with secondary upper extremity lymphedema. Materials and methodsUpper extremity MRI and lymphoscintigraphy were performed on patients referred to a multidisciplinary lymphedema clinic for suspicion of secondary lymphedema. Sensitivity, specificity, and positive and negative predictive values of DRS on MRI in detecting dermal backflow on lymphoscintigraphy and the correlation between DRS, Indocyanine Green (ICG) lymphography, bioimpedence L-Dex® ratio and MRI Lymphedema Staging were calculated. Weighted interobserver agreements on the presence and location of DRS on MRI were calculated. ResultsOf the 45 patients in the study, 91.1% (41/45) of patients had history of breast cancer. The average age was 58.4 ± 10.5 years, with a mean symptom duration of 4.7 ± 4.4 years. The mean BMI was 30.5 ± 7.0 kg/m2. Interobserver agreement on the presence and the extent of DRS on MRI was 0.93 [95% confidence-interval: 0.80–1]. DRS was present in 97% (32/33) of patients who demonstrated dermal backflow on lymphoscintigraphy. Sensitivity, specificity, PPV, and NPV of DRS were 96.6% [81.7%–99.9%], and 75.0% [47.6%–92.7%], 87.5% [74.9%–94.3%], and 92.3% [63.1%–98.8%]. DRS was associated with severity on ICG lymphography and bioimpedance (both p < 0.001). ConclusionsDRS on non-contrast MRI is highly predictive of dermal backflow and correlates with clinical measures of lymphedema severity. DRS may be used as an independent diagnostic biomarker to identify patients who would benefit from dedicated exams.

HERV-K Modulates the Immune Response in ALS Patients

Human endogenous retrovirus (HERV)-K env-su glycoprotein has been documented in amyotrophic lateral sclerosis (ALS), where HERV-K env-su 19–37 antibody levels significantly correlated with clinical measures of disease severity. Herein, we investigated further the humoral and cell-mediated immune response against specific antigenic peptides derived from HERV-K in ALS. HERV-K env glycoprotein expression on peripheral blood mononuclear cells (PBMCs) membrane and cytokines and chemokines after stimulation with HERV-K env 19–37 and HERV-K env 109–126 were quantified in patients and healthy controls (HCs). HERV-K env glycoprotein was more expressed in B cells and NK cells of ALS patients compared to HCs, whereas HERV-K env transcripts were similar in ALS and HCs. In ALS patients, specific stimulation with HERV-K env 109–126 peptide showed a higher expression of IL-6 by CD19/B cells. Both peptides, however, were able to induce a great production of IFN-γ by stimulation CD19/B cells, and yielded a higher expression of MIP-1α and a lower expression of MCP-1. HERV-K env 19–37 peptide induced a great production of TNF-α in CD8/T cells. In conclusion, we observed the ability of HERV-K to modulate the immune system, generating mediators mainly involved in proinflammatory response.

Effect of low-level laser intervention on dermatitis symptoms and cytokine changes in DNCB-induced atopy mouse model: A randomized controlled trial.

The incidence of atopic dermatitis (AD) has recently increased due to various factors. Its prevalence is higher among children and teenagers than in other age groups. Numerous methods to treat AD are available, including light ray therapy, which has been proposed as an alternative therapy for the treatment of AD. The present study aimed to evaluate the curative mechanism and optimal energy level of energy irradiation from a low-level laser (LLL) toward AD. AD was induced in BALB/c mice with dinitrochlorobenzene (DNCB) solution. The mice were divided into six groups, including one normal control (n=8), one AD control (n=10) and four AD experimental groups with LLL irradiation at 2 J/cm2 (n=10), 4 J/cm2 (n=10), 6 J/cm2 (n=9) and 8 J/cm2 (n=10). Following AD induction, an LLL was applied to the four AD experimental groups for 2, 4, 6, and 8 min, for two weeks (14 times in total) at a wavelength of 650 nm and an output of 50 mW. The effects of irradiation on AD were evaluated using a scratch test, a clinical skin severity test, immunoglobulin-E (IgE) analysis and measurements of numerous cytokine levels, including interleukin (IL)-4, IL-6, tumor necrosis factor (TNF)-α, and interferon-γ (IFN-γ), tissue thickness and mast cell count. The results demonstrated that serum IgE level in all irradiated groups was significantly decreased compared with that of the AD control group, and IL-4 level was significantly decreased in all irradiated groups apart from the 8 J/cm2 LLL irradiated group. IL-6 and TNF-α levels were also significantly decreased in all irradiated groups. The results from histological analysis revealed diminished epidermal thickness and mast cell counts in irradiated mice compared with those mice in the AD control group. In summary, these findings suggested that LLL irradiation may alleviate symptoms of AD and may be useful for restoring cytokines levels and tissues features to normal levels.

Cystatin C, COVID-19 severity and mortality: a systematic review and meta-analysis.

BackgroundCombined markers of renal dysfunction and inflammation, e.g., cystatin C, might assist with risk stratification and clinical decisions in patients with coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis with meta-regression of serum cystatin C in COVID-19.MethodsWe searched PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting serum cystatin C concentrations, measures of clinical severity and survival outcomes in hospitalized COVID-19 patients (PROSPERO registration number: CRD42021245295).ResultsThirteen studies in 2510 COVID-19 patients, 1972 with low severity or survivor status and 538 with high severity or non-survivor status during follow up, were included in the meta-analysis. The pooled results showed that serum cystatin C concentrations were higher in patients with high disease severity or non-survivor status (standard mean deviation, SMD, 1.71, 95% CI 0.95 to 2.46, p < 0.001). Extreme between-study heterogeneity was observed (I2 = 97.5%, p < 0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not substantially modified. The Begg’s and Egger’s t tests did not show publication bias. In meta-regression, the SMD of serum cystatin C was not associated with age, proportion of males, C-reactive protein, neutrophils, lymphocytes, aspartate aminotransferase, alanine aminotransferase, albumin, creatinine, creatine kinase-MB, lactate dehydrogenase, and proportion of patients with diabetes or hypertension.ConclusionsHigher concentrations of serum cystatin C were associated with higher COVID-19 severity and mortality.Graphic abstract

Using computerized spiral analysis to evaluate deep brain stimulation outcomes in Parkinson disease

ObjectiveTo determine whether spiral analysis can monitor the effects of deep brain stimulation (DBS) in Parkinson disease (PD) and provide a window on clinical features that change post-operatively. Clinical evaluation after DBS is subjective and insensitive to small changes. Spiral analysis is a computerized test that quantifies kinematic, dynamic, and spatial aspects of spiral drawing. Validated computational indices are generated and correlate with a range of clinically relevant motor findings. These include measures of overall clinical severity (Severity), bradykinesia and rigidity (Smoothness), amount of tremor (Tremor), irregularity of drawing movements (Variability), and micrographia (Tightness). MethodsWe retrospectively evaluated the effect of subthalamic nucleus (STN) (n = 66) and ventral intermediate thalamus (Vim) (n = 10) DBS on spiral drawing in PD subjects using spiral analysis. Subjects freely drew ten spirals on plain paper with an inking pen on a graphics tablet. Five spiral indices (Severity, Smoothness, Tremor, Variability, Tightness) were calculated and compared pre- and post-operatively using Wilcoxon-rank sum tests, adjusting for multiple comparisons. ResultsSeverity improved after STN and Vim DBS (p < 0.005). Smoothness (p < 0.01) and Tremor (p < 0.02) both improved after STN and Vim DBS. Variability improved only with Vim DBS. Neither STN nor Vim DBS significantly changed Tightness. ConclusionsAll major spiral indices, except Tightness, improved after DBS. This suggests spiral analysis monitors DBS effects in PD and provides an objective window on relevant clinical features that change post-operatively. It may thus have utilization in clinical trials or investigations into the neural pathways altered by DBS. The lack of change in Tightness supports the notion that DBS does not improve micrographia.

Traumatic axonal injury on clinical MRI: association with the Glasgow Coma Scale score at scene of injury or at admission and prolonged posttraumatic amnesia.

The aim in this study was to investigate if MRI findings of traumatic axonal injury (TAI) after traumatic brain injury (TBI) are related to the admission Glasgow Coma Scale (GCS) score and prolonged duration of posttraumatic amnesia (PTA). A total of 490 patients with mild to severe TBI underwent brain MRI within 6 weeks of injury (mild TBI: median 2 days; moderate to severe TBI: median 8 days). The location of TAI lesions and measures of total TAI lesion burden (number and volume of lesions on FLAIR and diffusion-weighted imaging and number of lesions on T2*-weighted gradient echo or susceptibility-weighted imaging) were quantified in a blinded manner for clinical information. The volume of contusions on FLAIR was likewise recorded. Associations between GCS score and the location and burden of TAI lesions were examined with multiple linear regression, adjusted for age, Marshall CT score (which includes compression of basal cisterns, midline shift, and mass lesions), and alcohol intoxication. The predictive value of TAI lesion location and burden for duration of PTA > 28 days was analyzed with multiple logistic regression, adjusted for age and Marshall CT score. Complete-case analyses of patients with TAI were used for the regression analyses of GCS scores (n = 268) and PTA (n = 252). TAI lesions were observed in 58% of patients: in 7% of mild, 69% of moderate, and 93% of severe TBI cases. The TAI lesion location associated with the lowest GCS scores were bilateral lesions in the brainstem (mean difference in GCS score -2.5), followed by lesions bilaterally in the thalamus, unilaterally in the brainstem, and lesions in the splenium. The volume of TAI on FLAIR was the measure of total lesion burden most strongly associated with the GCS score. Bilateral TAI lesions in the thalamus had the largest predictive value for PTA > 28 days (OR 16.2, 95% CI 3.9-87.4). Of the measures of total TAI lesion burden, the FLAIR volume of TAI predicted PTA > 28 days the best. Bilateral TAI lesions in the brainstem and thalamus, as well as the total volume of TAI lesions on FLAIR, had the strongest association with the GCS score and prolonged PTA. The current study proposes a first step toward a modified classification of TAI, with grades ranked according to their relation to these two measures of clinical TBI severity.

New insights into neural networks of error monitoring and clinical implications: a systematic review of ERP studies in neurological diseases.

Error monitoring allows for the efficient performance of goal-directed behaviors and successful learning. Furthermore, error monitoring as a metacognitive ability may play a crucial role for neuropsychological interventions, such as rehabilitation. In the past decades, research has suggested two electrophysiological markers for error monitoring: the error-related negativity (ERN) and the error positivity (Pe), thought to reflect, respectively, error detection and error awareness. Studies on several neurological diseases have investigated the alteration of the ERN and the Pe, but these findings have not been summarized. Accordingly, a systematic review was conducted to understand what neurological conditions present alterations of error monitoring event-related potentials and their relation with clinical measures. Overall, ERN tended to be reduced in most neurological conditions while results related to Pe integrity are less clear. ERN and Pe were found to be associated with several measures of clinical severity. Additionally, we explored the contribution of different brain structures to neural networks underlying error monitoring, further elaborating on the domain-specificity of error processing and clinical implications of findings. In conclusion, electrophysiological signatures of error monitoring could be reliable measures of neurological dysfunction and a robust tool in neuropsychological rehabilitation.

Inflammation resolution circuits are uncoupled in acute sepsis and correlate with clinical severity.

Sepsis is a critical illness characterized by dysregulated inflammatory responses lacking counter-regulation. Specialized proresolving mediators are agonists for antiinflammation and for promoting resolution, and they are protective in preclinical sepsis models. Here, in human sepsis, we mapped resolution circuits for the specialized proresolving mediators resolvin D1 and resolvin D2 in peripheral blood neutrophils and monocytes, their regulation of leukocyte activation and function ex vivo, and their relationships to measures of clinical severity. Neutrophils and monocytes were isolated from healthy subjects and patients with sepsis by inertial microfluidics and resolvin D1 and resolvin D2 receptor expression determined by flow cytometry. The impact of these resolvins on leukocyte activation was determined by isodielectric separation and leukocyte function by stimulated phagolysosome formation. Leukocyte proresolving receptor expression was significantly higher in sepsis. In nanomolar concentrations, resolvin D1 and resolvin D2 partially reversed sepsis-induced changes in leukocyte activation and function. Principal component analyses of leukocyte resolvin receptor expression and responses differentiated sepsis from health and were associated with measures of sepsis severity. These findings indicate that resolvin D1 and resolvin D2 signaling for antiinflammation and resolution are uncoupled from leukocyte activation in early sepsis and suggest that indicators of diminished resolution signaling correlate with clinical disease severity.

Bacterial colonization of bladder urothelial cells in women with refractory Detrusor Overactivity: the effects of antibiotic therapy

Bacterial infection may have a pathophysiological role in refractory Detrusor Overactivity (DO). The aim of this study was to observe any impact of antibiotic therapy upon bacterial colonization of urothelial cells, and to determine whether a relationship existed between colonization and symptom severity. Mid-stream urine samples were collected as part of a clinical trial of antibiotics in women with refractory DO. Wright stained urothelial cells were categorized according to the degree of bacterial colonization as; 'clear' (free of bacteria), or as associated with bacteria that were 'adjacent' to the cell or 'intracellular' at low or high density. The average percentages were compared with routine microbiology cultures, over the 26 week trial, and with patient clinical outcome measures of DO severity. In patients receiving placebo, 'high-density intracellular bacteria' significantly increased during urinary tract infection (P = 0.0008). In antibiotic patients, 'clear' cells were more prevalent. Amoxicillin & Clavulanic Acid significantly decreased bacterial colonization within urothelial cells, suggesting that these antibiotics possess the greatest intracellular efficacy. 'High-density intracellular bacteria' positively correlated with symptom severity, measured by leakage on pad test (P = 0.014), leaks per day (P = 0.004), and voids per day (P = 0.005). Thus, by decreasing high density intracellular bacteria, antibiotic treatment may improve the refractory DO condition.

Comparing treatment outcomes and patient satisfaction among individuals presenting to psychiatric care with and without recent suicidal ideation.

To compare pre- and posttreatment psychological functioning and patient satisfaction among patients with and without recent suicidal ideation receiving care at a partial hospital program. Patients (N = 1295) completed (1) self-report measures of clinical severity, treatment beliefs, and patient satisfaction and (2) a clinician-administered suicidal ideation measure. At admission, patients with past-month ideation reported more severe psychopathology and functional impairment than those without past-month ideation; however, at discharge, both groups reported comparable psychological functioning. Additionally, although patients with past-month ideation reported lower expectations that treatment would be helpful, both groups ultimately reported comparable satisfaction with services. Individuals with recent suicidal ideation may present to care with more severe psychopathology and lower treatment expectations yet may experience comparable treatment benefits and report similar satisfaction with services as patients without recent ideation. Research is needed to identify treatment components that drive perceived benefits and symptom reduction among at-risk individuals.

The relationship between clinical severity and outcome measures in patients with chronic venous insufficiency with or without leg ulcer

PurposeTo evaluate the relationship between clinical severity and functionality, sleep quality, depression, and quality of life (QoL) in patients with CVI with or without leg ulcers. MethodsA total of sixty patients with CVI were enrolled in the study. The patients were C2-6 according to the CEAP classification. All the patients were assessed with Venous Clinical Severity Score (VCSS) for clinical severity, Visual Analog Scale (VAS) for pain, right and left lower limb (RLL and LLL) circumference measurements for edema, 6-min-walk test (6-MWT) for functional capacity, Lower Extremity Functional Scale (LEFS) for functionality, Pittsburg Sleep Quality Index (PSQI) for sleep quality, Beck Depression Inventory version I (BDI-I) for depression, and The Quality of Life Questionnaire for Chronic Venous Diseases-20 (CIVIQ-20) for QoL. ResultsThe mean age of the patients was 45.83 ± 13.25 years, and the mean duration of disease was 8.30 ± 7.42 years. There was a significant association between VCSS and VAS-rest/activity, edema-RLL/LLL, PSQI, BDI-I, LEFS, and CIVIQ-20 in patients without leg ulcers. In addition, a significant association was found between VCSS and VAS-rest/activity and CIVIQ-20 in patients with leg ulcers. ConclusionThe current study showed that an association has been found between clinical severity and pain at rest and during activity, edema, sleep quality, depression, lower extremity function, and QoL in patients without ulcers. However, clinical severity has been correlated with only pain at rest and during activity, and QoL in patients with leg ulcers.

The sputum microbiome and clinical outcomes in patients with bronchiectasis: a prospective observational study

Infection is a key component of bronchiectasis pathophysiology. Characterisation of the microbiome offers a higher degree of sensitivity and resolution than does traditional culture methods. We aimed to evaluate the role of the microbiome in determining the risk of exacerbation and long-term outcomes, including all-cause mortality, in bronchiectasis. We did a prospective observational cohort study of patients with bronchiectasis from eastern Scotland. Patients were enrolled from Sept 11, 2012, to Dec 21, 2015, and followed until Jan 8, 2019, for long-term outcomes. Patients were included if they were aged 18 years or older, and had a high-resolution CT-confirmed diagnosis of bronchiectasis and clinical symptoms consistent with the disease. Sputum samples were obtained when patients were clinically stable. Repeat sputum samples were taken at stable and exacerbation visits during follow-up. The V3-V4 region of the bacterial 16S rRNA gene was sequenced using the Illumina MiSeq platform. The dominant bacterial genus in each sample was assigned on the basis of a previously published method. Microbiome characteristics were analysed for their association with measures of clinical disease severity and long-term outcomes using PERMANOVA, random forest, and survival analyses. Sequencing data were obtained from the sputum samples of 281 patients with bronchiectasis who were included in the stable baseline cohort. 49 (17%) of 281 patients provided more than one sample when clinically stable and were included in the longitudinal analysis. 64 (23%) patients provided both stable and exacerbation samples. In both stable bronchiectasis and during exacerbations, a sputum microbiome dominated by Proteobacteria and Firmicutes was observed. Individual patients' microbiome profiles were relatively stable over time, during exacerbations and at disease stability. Lower microbiome diversity, measured using the Shannon-Wiener diversity index, was associated with more severe bronchiectasis defined by the bronchiectasis severity index, lower FEV1, and more severe symptoms. Random forest analysis of baseline samples identified Pseudomonas, Enterobacteriaceae, and Stenotrophomonas as being associated with severe bronchiectasis (bronchiectasis severity index ≥9) and greater lung inflammation and Pseudomonas and Enterobacteriaceae with more frequent exacerbations. Patients in whom Pseudomonas was dominant (n=35) were at increased risk of all-cause mortality (hazard ratio 3·12, 95% CI 1·33-7·36; p=0·0091) and had more frequent exacerbations (incident rate ratio 1·69, 95% CI 1·07-2·67; p=0·024) during follow-up compared with patients with other dominant genera (n=246). A reduction in microbiome diversity, particularly one associated with dominance of Pseudomonas, is associated with greater disease severity, higher frequency and severity of exacerbations, and higher risk of mortality. The microbiome might therefore identify subgroups of patients at increased risk of poor outcomes who could benefit from precision treatment strategies. Further research is required to identify the mechanisms of reduced microbiome diversity and to establish whether the microbiome can be therapeutically targeted. British Lung Foundation and European Respiratory Society EMBARC2 consortium.

Resting-state connectivity subtype of comorbid PTSD and alcohol use disorder moderates improvement from integrated prolonged exposure therapy in Veterans.

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid and are associated with significant functional impairment and inconsistent treatment outcomes. Data-driven subtyping of this clinically heterogeneous patient population and the associated underlying neural mechanisms are highly needed to identify who will benefit from psychotherapy. In 53 comorbid PTSD/AUD patients, resting-state functional magnetic resonance imaging was collected prior to undergoing individual psychotherapy. We used a data-driven approach to subgroup patients based on directed connectivity profiles. Connectivity subgroups were compared on clinical measures of PTSD severity and heavy alcohol use collected at pre- and post-treatment. We identified a subgroup of patients associated with improvement in PTSD symptoms from integrated-prolonged exposure therapy. This subgroup was characterized by lower insula to inferior parietal cortex (IPC) connectivity, higher pregenual anterior cingulate cortex (pgACC) to posterior midcingulate cortex connectivity and a unique pgACC to IPC path. We did not observe any connectivity subgroup that uniquely benefited from integrated-coping skills or subgroups associated with change in alcohol consumption. Data-driven approaches to characterize PTSD/AUD subtypes have the potential to identify brain network profiles that are implicated in the benefit from psychological interventions - setting the stage for future research that targets these brain circuit communication patterns to boost treatment efficacy.

Disparity vergence differences between typically occurring and concussion-related convergence insufficiency pediatric patients

This study sought to test the hypothesis that significant differences would be observed in clinical measures, symptoms, and objective assessments of vergence eye movements between children with typically developing convergence insufficiency (TYP-CI) and children with persistent post-concussion symptoms with convergence insufficiency (PPCS-CI). Data from age-matched binocularly normal controls (BNC) were used for comparison. Data from three groups of children 11 to 17 years of age are presented: BNC (N = 11), TYP-CI (N = 10), and PPCS-CI (N = 15). Clinical measures of vergence, accommodation, and symptom severity were collected. Symmetrical 4° disparity vergence eye movements were quantified with an eye tracker integrated into a head-mounted display (Oculus DK2). Peak velocity and final response amplitude of convergence and divergence eye movement responses were assessed. The mean near point of convergence (break) was more receded (worse), the amplitude of accommodation more deficient, and convergent and divergent peak velocities slower in the PPCS-CI group compared with the TYP-CI and BNC groups. These results suggest that PPCS-CI may be a different clinical entity than TYP-CI. Hence, more research is warranted to determine whether the therapeutic interventions that are effective for TYP-CI can also be used for PPCS-CI populations.