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Data from: Burden of scrub typhus among patients with acute febrile illness attending tertiary care hospital in Chitwan, Nepal
<p><span><b>Objectives: </b>Scrub typhus is an emerging neglected tropical disease, reported from many parts of Asia including Nepal. This study aims to determine the seroepidemiology of scrub typhus among febrile patients attending Chitwan Medical College Teaching Hospital (CMCTH), Bharatpur, Nepal.</span></p> <p><span><b>Study design and setting: </b>This was a hospital laboratory based prospective study conducted in CMC-TH (a 600-bed hospital) located in Bharatpur, Chitwan district of Nepal.</span></p> <p><b>Participants</b><b>: </b> A total of 1797 patients visiting CMC-TH with acute febrile illness (temperature more than 38<sup>0</sup>C) were enrolled in this study.</p> <p><span><b>Methods: </b>A total of 1797 blood samples were collected from patients presenting with acute febrile illness. The samples were processed for detection of antibody for scrub typhus by Enzyme Linked Immunosorbent Assay (ELISA) for specific immunoglobulin M (IgM) antibody and Weil-Felix test. </span></p> <p><span><b>Results: </b>Out of 1797 serum sample of febrile patients, 524 (29.2%) were scrub typhus positive. Maximum seropositive cases were from Chitwan district 271 (51.7%) with predominance among females 314 (35.9%). Scrub typhus was common among age group 51-60 years (37.2%) and farmers 182 (37.8%). Highest<b> </b>seropositivity was found in July 60 (57.7%). Fever was common clinical symptom. Thrombocytopenia was seen in 386 (73.7%) and raised transaminase AST 399 (76.1%) among seropositive cases. Weil-Felix test positive were 397 (22.1%) and IgM ELISA 524 (29.2%). The correlation between IgM ELISA and Weil-Felix test showed statistically significant association (r = 0.319, p<0.001).</span></p> <p><span><b>Conclusion: </b>High prevalence of scrub typhus implies that acute febrile patients should be investigated for scrub typhus with high priority. There is utmost need of reliable diagnostic facilities at all level of health care system in Nepal. Infection with scrub typhus was found high and this calls for an urgent need to introduce vaccine against scrub typhus. More sustain and vigorous awareness programs need to be promoted for early diagnosis, treatment and control. </span></p>
Data from: A virtual molecular tumor board platform to improve efficiency and scalability of delivering precision oncology to physicians and their patients
OBJECTIVES: Scalable informatics solutions that provide molecularly-tailored treatment recommendations to clinicians are needed to streamline Precision Oncology in care settings. MATERIALS AND METHODS: We developed a cloud-based virtual molecular tumor board (VMTB) platform that included a knowledgebase, scoring model, rules engine, an asynchronous virtual chat room and a reporting tool that generated a treatment plan for each of the 1725 patients based on their molecular profile, previous treatment history, structured trial eligibility criteria, clinically relevant cancer gene-variant assertions, biomarker-treatment associations, and current treatment guidelines. The VMTB systematically allows clinician users to combine expert-curated data and structured data from clinical charts along with molecular testing data to develop consensus on treatments, especially those that require off-label and clinical trial considerations. RESULTS: The VMTB was used as part of the cancer care process for a focused subset of 1725 patients referred by advocacy organizations wherein resultant personalized reports were successfully delivered to treating oncologists. Median turnaround time from data receipt to report delivery decreased from 14 days to 4 days over 4 years while the volume of cases increased nearly twofold each year. Using a novel scoring model for ranking therapy options, oncologists chose to implement the VMTB-derived therapies over others, except when pursuing immunotherapy options without molecular support. DISCUSSION: VMTBs will play an increasingly critical role in precision oncology as the compendium of biomarkers and associated therapy options available to a patient continues to expand. CONCLUSION: Further development of such clinical augmentation tools that systematically combine patient-derived molecular data, real world evidence from electronic health records, and expert curated knowledgebases on biomarkers with computational tools for ranking best treatments can support care pathways at point of care.
Patient or family perceived deterioration in functional status and outcome after Intensive Care admission: a retrospective cohort analysis of routinely collected data
<p><span><span><span><span><span><span><span><span><span><span><span>Objective: To explore the association of patient or family reported functional deterioration (defined by a single question) in the preceding year, with mortality outcome for those admitted to the Intensive Care Unit (ICU).</span></span></span></span></span></span></span></span></span></span></span></p> <p> </p> <p><span><span><span><span><span><span><span><span><span><span><span>Design: Retrospective observational analysis of a routinely collected data source.</span></span></span></span></span></span></span></span></span></span></span></p> <p> </p> <p><span><span><span><span><span><span><span><span><span><span><span>Participants: Patients that were admitted to the ICU at Northwick Park Hospital, London North West University Healthcare NHS Trust between 1/10/2017 to 15/6/2019 were included. Patients were excluded if they had a prior ICU admission during the existing hospital episode or if information on functional deterioration could not be retrieved from either the patient or their advocate.</span></span></span></span></span></span></span></span></span></span></span></p> <p> </p> <p><span><span><span><span><span><span><span><span><span><span><span>Primary Outcomes: Mortality at the point of hospital discharge and 1 year following admission to the ICU.</span></span></span></span></span></span></span></span></span></span></span></p> <p> </p> <p><span><span><span><span><span><span><span><span><span><span><span>Results: Of the 1006 patients who were admitted to the ICU during the study period, information on functional deterioration was available for 621 patients who were included in the analysis. From these, 251 (40.4%) patients had patient or family reported functional deterioration in the preceding year, whilst 370 (59.6%) patients had a perceived stable functional baseline. Comparing the two groups, mortality was significantly higher in those who had functionally deteriorated compared to those with stable baseline function, at the point of hospital discharge (45.4% versus 25.9%; P<0.0001) and at 1 year (59.4% versus 33.0%; P<0.0001). </span></span></span></span></span></span></span></span></span></span></span></p> <p> </p> <p><span><span><span><span><span><span><span><span><span><span><span>Conclusion: Patient or family reported functional deterioration was significantly associated with higher mortality at the point of hospital discharge and at 1 year. The concept of functional deterioration in the lead up to ICU admission warrants further exploration.</span></span></span></span></span></span></span></span></span></span></span></p>
Data from: Cerebellar Damage Affects Contextual Priors for Action Prediction in Patients with Childhood Brain Tumor
<p>Raw data used for the article: Cerebellar Damage Affects Contextual Priors for Action Prediction in Patients with Childhood Brain Tumor</p> <p>Predictive coding accounts of action perception sustain that kinematics information is compared with contextual top-down predictions (i.e., priors) to understand actions in conditions of perceptual ambiguity. It has been previously shown that the cerebellum contributes to motor simulation of observed actions. Here, we tested the hypothesis that a specific contribution of the cerebellum to action perception is to provide contextual priors that guide the sampling of perceptual kinematic information. To this aim, we compared the performance of 42 patients with childhood brain tumor affecting infratentorial (ITT) or supratentorial (STT) areas with that of peers with typical development in an action prediction task. First, participants were<br> exposed to videos depicting a child performing different reaching-to-grasp actions, which were associated with contextual cues in a probabilistic fashion. Then, they were presented with shortened versions of the same videos and asked to infer the action outcome; since kinematics was ambiguous, we expected their responses would be biased toward the previously learned contextual priors. We found that patients with brain tumor were impaired in predicting actions when compared to healthy controls. However, STT patients presented a reliable probabilistic effect, while ITT patients, who had cerebellar damage, did not rely on contextual priors in predicting actions. Furthermore, we found an association between the use of contextual priors and the ability<br> to infer others’ mental states as assessed by a standardized test. These results suggest that the cerebellum provides contextual priors to understand others’ actions and this predictive function might underlie complex social cognition abilities.</p>
Data from: Corneal laser procedure for vision improvement in patients with late stage dry age-related macular degeneration
<p><span>Purpose: To determine the safety and efficacy of corneal photovitrification (CPV), a new corneal laser procedure, for vision improvement in patients with late-stage dry age-related macular degeneration (AMD).</span></p> <p><span>Design: Retrospective observational cohort study</span></p> <p><span>Participants: 32 eyes of 17 patients with late-stage dry AMD; each eye received a single CPV corneal laser procedure and had 12 months (12m) post-treatment (Tx) follow-up.</span></p> <p><span>Methods: Pre- and post-Tx examinations included slit-lamp biomicroscopy, subjective manifest refraction, best corrected distance and near visual acuity (BCDVA and BCNVA), and potential visual acuity (PVA). Additional examinations including contrast sensitivity (CS), corneal topography (CT), ray tracing aberrometry (RTA) and microperimetry (MP) were obtained for a subgroup (n=12) of eyes.</span></p> <p><span>Main Outcome Measures: BCDVA, BCNVA, PVA, CS, CT, RTA and MP measurements</span></p> <p><span>Results: Safety - There were no complications or adverse events. Efficacy – Mean (± SD) BCDVA improved significantly (p < 0.004) from 20/238 (1.08 logMAR) at baseline to 20/144 (0.86 logMAR) at 12m post-Tx corresponding to 11.0 (± 13.1) letters gained. Mean contrast sensitivity improved significantly (p < 0.05) by a factor of 1.86 from baseline at 12m post-Tx. </span></p> <p><span>Conclusions: Subject to the limitation of a small sample size, this pilot study indicates that the CPV corneal laser procedure is safe and efficacious for vision improvement in patients with late-stage dry AMD. The CPV Tx mechanism of action involves retinal irradiance distribution modifications that may stimulate patient use of functional, rather than atrophied, retinal regions. </span></p>
Data from: Vitamin D status and COVID-19 clinical outcomes in hospitalized patients
<p><span><span><span><span><span><span><span><span><span><span><span><b>Context:</b> Populations severely affected by COVID-19 are also at risk for vitamin D deficiency. Common risk factors include older age, chronic illness, obesity, and non-Caucasian race. Vitamin D deficiency has been associated with risk for respiratory infections and failure, susceptibility and response to therapy for enveloped virus infection, and immune-mediated inflammatory reaction.</span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span><b>Objective:</b> To test the hypothesis that 25-hydroxyvitamin D[25(OH)D] deficiency is a risk factor for severity of COVID-19 respiratory and inflammatory complications.</span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span><b>Design:</b> We examined the relationship between retrospectively obtained prehospitalization 25(OH)D levels and COVID-19 clinical outcomes in 700 COVID-19 positive hospitalized patients.</span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span><b>Primary Outcomes:</b> Discharge status, mortality, length of stay, intubation status, renal replacement</span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span><b>Secondary Outcomes: </b>Inflammatory markers</span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span><b>Results:</b> 25(OH)D levels were available in 93 patients [25(OH)D:25(IQR:17–33)ng/mL]. Compared to those without 25(OH)D levels, those with measurements did not differ in age, BMI or distribution of sex and race, but were more likely to have comorbidities. Those with 25(OH)D<20ng/mL (n=35) did not differ from those with 25(OH)D³20ng/mL in terms of age, sex, race, BMI, or comorbidities. Low 25(OH)D tended to be associated with younger age and lower frequency of preexisting pulmonary disease. There were no significant between-group differences in any outcome. Results were similar in those ³50years, in male/female-only cohorts, and when differing 25(OH)D thresholds were used (<15ng/ml and <30ng/ml). There was no relationship between 25(OH)D as a continuous variable and any outcome, even after controlling for age and pulmonary disease. </span></span></span></span></span></span></span></span></span></span></span></p> <p><span><span><span><span><span><span><span><span><span><span><span><b>Conclusions:</b> These preliminary data do not support a relationship between vitamin D status and COVID-19 clinical outcomes. </span></span></span></span></span></span></span></span></span></span></span></p>
Data from: Use of isotretinoin and risk of depression in patients with acne: a systematic review and meta-analysis
Objective: This study aimed to investigate the association between the use of isotretinoin and the risk of depression in patients with acne. Design: This was a meta-analysis in which the standardized mean difference (SMD) and the relative risk (RR) were used for data synthesis employed the random-effects model. Setting: Studies were identified via electronic searches of PubMed, Embase, and the Cochrane Library up to December 28, 2017. Participants: Patients with acne. Interventions: Studies comparing isotretinoin with other interventions in patients with acne were included. Results: Twenty studies were selected. The analysis of 17 studies showed a significant association of the use of isotretinoin with improved symptoms compared with the baseline before treatment [SMD = −0.33, 95% confidence interval (CI) −0.51 to −0.15, P < 0.05; I2 = 76.6%, P < 0.05)]. Four studies were related to the analysis of the risk of depression. The pooled data indicated no association of the use of isotretinoin with the risk of depressive disorders (RR = 1.15, 95% CI 0.60–2.21, P = 0.14). The association of the use of isotretinoin with the risk of depressive disorders was statistically significant on pooling retrospective studies (RR = 1.39, 95% CI 1.05–1.84, P = 0.02), but this association was not evident on pooling prospective studies (RR = 0.85, 95% CI 0.60–2.21, P = 0.86). Conclusions: This study suggested an association of the use of isotretinoin in patients with acne with significantly improved depression symptoms. Future randomized controlled trials are needed to verify the present findings.
Data from: Time-dependent decline of body-specific attention to the paretic limb in chronic stroke patients
Objective: To examine whether reduced body-specific attention to paretic limb is found in chronic stroke patients in the time-dependent manner. Methods: Twenty-one patients with chronic hemiparesis (10 left and 11 right hemiparesis) after subcortical stroke and 18 age-matched healthy controls were recruited in this study. Standard neuropsychological examinations showed no clear evidence of spatial neglect in all patients. In order to quantitatively measure the spatial attention to paretic hand, a visual detection task for detecting a target appearing on the surface of either a paretic or dummy hand was used. This task can measure the body facilitation effect, which makes faster detection of a target on the body compared with one far from the body. Results: In stroke patients, there was no difference in the reaction time for visual target between on the paretic and the dummy hands, while the healthy participants showed faster detection for the visual target on the real hand than that on dummy one. The Index of the body facilitation effect, subtracting the reaction time for the target-on-paretic hand from that for the target-on-dummy one, was correlated with the duration since onset and with finger function test on the Stroke Impairment Assessment Set. Conclusions: The reduction of the body facilitation effect in paretic limb suggests the decline of body-specific attention to the paretic one in patients with chronic hemiparesis. This decline of the body-specific attention, leading to neglect for paretic limb, will be one of the most serious problems for rehabilitation based on use-dependent plasticity.
Data from: A consensus study to define appropriate inaction and inappropriate inertia in the management of hypertensive patients in primary care
Objectives. To elaborate and validate operational definitions for appropriate inaction and for inappropriate inertia in the management of hypertensive patients in primary care. Design. A two-step approach was used to reach a definition consensus. First, nominal groups provided practice-based information on the two concepts. Second, a Delphi procedure was used to modify and validate the two definitions created from the nominal groups results. Participants. 14 French practicing GPs participated in each of the two nominal groups, held in two different areas in France. For the Delphi procedure, 30 academics, international experts in the field, were contacted; 20 agreed to participate, and 19 completed the procedure. Results. Inappropriate inertia was defined as: to not initiate or intensify an antihypertensive treatment for a patient who is not at the blood pressure goals defined for this patient in the guidelines when all following conditions are fulfilled: (1) elevated blood pressure has been confirmed by self-measurement or ambulatory BP monitoring, (2) there is no legitimate doubt on the reliability of the measurements, (3) there is no observance issue regarding pharmacological treatment, (4) there is no specific iatrogenic risk (which alters the risk-benefit balance of treatment for this patient), in particular orthostatic hypotension in the elderly, (5) there is no other medical priority more important and more urgent, (6) access to treatment is not difficult. Appropriate inaction was defined as the exact mirror, i.e. when at least one of the above conditions is not met. Conclusion. Definitions of appropriate inaction and inappropriate inertia in the management of hypertensive patients have been established from empirical practice-based data and validated by an international panel of academics as useful for practice and research.
Data from: Early sitting in ischemic stroke patients (SEVEL): a randomized controlled trial
Background: Extended immobility has been associated with medical complications during hospitalization. However no clear recommendations are available for mobilization of ischemic stroke patients. Objective: As early mobilization has been shown to be feasible and safe, we tested the hypothesis that early sitting could be beneficial to stroke patient outcome. Methods: This prospective multicenter study tested two sitting procedures at the acute phase of ischemic stroke, in a randomized controlled fashion (clinicaltrials.org registration number NCT01573299). Patients were eligible if they were above 18 years of age and showed no sign of massive infarction or any contra-indication for sitting. In the early-sitting group, patients were seated out of bed at the earliest possible time but no later than one calendar day after stroke onset, whereas the progressively-sitting group was first seated out of bed on the third calendar day after stroke onset. Primary outcome measure was the proportion of patients with a modified Rankin score [0–2] at 3 months post stroke. Secondary outcome measures were a.) prevalence of medical complications, b.) length of hospital stay, and c.) tolerance to the procedure. Results: One hundred sixty seven patients were included in the study, of which 29 were excluded after randomization. Data from 138 patients, 63 in the early-sitting group and 75 in the progressively-sitting group were analyzed. There was no difference regarding outcome of people with stroke, with a proportion of Rankin [0–2] score at 3 months of 76.2% and 77.3% of patients in the early- and progressive-sitting groups, respectively (p = 0.52). There was also no difference between groups for secondary outcome measures, and the procedure was well tolerated in both arms. Conclusion: Due to a slow enrollment, fewer patients than anticipated were available for analysis. As a result, we can only detect beneficial/detrimental effects of +/- 15% of the early sitting procedure on stroke outcome with a realized 37% power. However, enrollment was sufficient to rule out effect sizes greater than 25% with 80% power, indicating that early sitting is unlikely to have an extreme effect in either direction on stroke outcome. Additionally, we were not able to provide a blinded assessment of the primary outcome. Taking these limitations into account, our results may help guide the development of more effective acute stroke rehabilitation strategies, and the design of future acute stroke trials involving out of bed activities and other mobilization regimens.
Data from: The proportion of clinically relevant alarms decreases as patient clinical severity decreases in intensive care units: a pilot study
Objectives: To determine (1) the proportion and number of clinically relevant alarms based on the type of monitoring device; (2) whether patient clinical severity, based on the sequential organ failure assessment (SOFA) score, affects the proportion of clinically relevant alarms and to suggest; (3) methods for reducing clinically irrelevant alarms in an intensive care unit (ICU). Design: A prospective, observational clinical study. Setting: A medical ICU at the University of Tokyo Hospital in Tokyo, Japan. Participants: All patients who were admitted directly to the ICU, aged ≥18 years, and not refused active treatment were registered between January and February 2012. Methods: The alarms, alarm settings, alarm messages, waveforms and video recordings were acquired in real time and saved continuously. All alarms were annotated with respect to technical and clinical validity. Results: 18 ICU patients were monitored. During 2697 patient-monitored hours, 11 591 alarms were annotated. Only 740 (6.4%) alarms were considered to be clinically relevant. The monitoring devices that triggered alarms the most often were the direct measurement of arterial pressure (33.5%), oxygen saturation (24.2%), and electrocardiogram (22.9%). The numbers of relevant alarms were 12.4% (direct measurement of arterial pressure), 2.4% (oxygen saturation) and 5.3% (electrocardiogram). Positive correlations were established between patient clinical severities and the proportion of relevant alarms. The total number of irrelevant alarms could be reduced by 21.4% by evaluating their technical relevance. Conclusions: We demonstrated that (1) the types of devices that alarm the most frequently were direct measurements of arterial pressure, oxygen saturation and ECG, and most of those alarms were not clinically relevant; (2) the proportion of clinically relevant alarms decreased as the patients' status improved and (3) the irrelevance alarms can be considerably reduced by evaluating their technical relevance.
Data from: Patients' experiences with and attitudes towards a diabetes patient web portal
Objective: A diabetes patient web portal allows patients to access their personal health record and may improve diabetes outcomes; however, patients' adoption is slow. We aimed to get insight into patients' experiences with a web portal to understand how the portal is being used, how patients perceive the content of the portal and to assess whether redesign of the portal might be needed. Materials and Methods: A survey among 1500 patients with type 1 and type 2 diabetes with a login to a patient portal. Setting: 62 primary care practices and one outpatient hospital clinic, using a combined patient portal. We compared patients who requested a login but never used it or once ('early quitters') with patients who used it at least two times ('persistent users'). Results: 632 patients (42.1%) returned the questionnaire. Their mean age was 59.7 years, 63.1% was male and 81.8% had type 2 diabetes. 413 (65.3%) people were persistent users and 34.7% early quitters. In the multivariable analysis, insulin use (OR2.07; 95%CI[1.18–3.62]), experiencing more frequently hyperglycemic episodes (OR1.30;95%CI[1.14–1.49]) and better diabetes knowledge (OR1.02, 95%CI[1.01–1.03]) do increase the odds of being a persistent user. Persistent users perceived the usefulness of the patient portal significantly more favorable. However, they also more decisively declared that the patient portal is not helpful in supporting life style changes. Early quitters felt significantly more items not applicable in their situation compared to persistent users. Both persistent users (69.8%) and early quitters (58.8%) would prefer a reminder function for scheduled visits. About 60% of both groups wanted information about medication and side-effects in their portal. Conclusions: The diabetes patient web portal might be improved significantly by taking into account the patients' experiences and attitudes. We propose creating separate portals for patients on insulin or not.
Data from: High reproducibility of adenosine stress cardiac magnetic resonance myocardial perfusion imaging in patients with nonischemic dilated cardiomyopathy
Objective: To evaluate the reproducibility of first-pass contrast-enhanced cardiac MR (CMR) myocardial perfusion imaging in patients with non-ischaemic dilated cardiomyopathy (NIDCM). Design: Prospective observational study. Setting: Single centre, tertiary care hospital. Participants: 6 outpatient participants with NIDCM. Outcome: Reproducibility of semiquantitative myocardial perfusion analysis by CMR. Method: 6 patients with NIDCM were studied twice using first-pass of contrast transit through the left ventricular (LV) myocardium with a saturation-recovery gradient echo sequence at rest and during adenosine-induced hyperaemia. The anterior wall was divided into endocardial (Endo) and epicardial (Epi) segments. The Myocardial Perfusion Index (MPI) was calculated as the myocardial signal augmentation rate normalised to the LV cavity rate. The Myocardial Perfusion Reserve Index (MPRI) was calculated as hyperaemic/resting MPI. Results: Between study 1 and 2, median MPI was similar for resting Endo (0.076 vs 0.077), hyperaemic Endo (0.143 vs 0.143), resting Epi (0.073 vs 0.074), and hyperaemic Epi (0.135 vs 0.134). Median MPRI was similar for Endo (1.84 vs 1.87) and Epi (1.90 vs 2.00). Combining Endo and Epi MPI (N=12), there was excellent agreement between Study 1 and 2 for resting MPI (r=0.998, intraclass correlation coefficient (ICC) 0.998, coefficients of variation (CoV) 1.4%), hyperaemic MPI (r=0.979, ICC 0.963, CoV 3.3%) and MPRI (r=0.989, ICC 0.94, CoV 3.8%). Conclusions: Resting and hyperaemic myocardial perfusion using a normalised upslope analysis during adenosine CMR is a highly reproducible technique in patients with NIDCM. Trial registration number: Clinical Trials.Gov ID NCT00574119.
Data from: Impaired T Cell Responsiveness to Interleukin-6 in Hematological Patients with Invasive Aspergillosis
Invasive mold infections (IMI) are among the most devastating complications following chemotherapy and hematopoietic stem cell transplantation (HSCT), with high mortality rates. Yet, the molecular basis for human susceptibility to invasive aspergillosis (IA) and mucormycosis remain poorly understood. Herein, we aimed to characterize the immune profile of individuals with hematological malignancies (n = 18) who developed IMI during the course of chemotherapy or HSCT, and compared it to that of hematological patients who had no evidence of invasive fungal infection (n = 16). First, we measured the expression of the pattern recognition receptors pentraxin 3, dectin-1, and Toll-like receptors (TLR) 2 and 4 in peripheral blood of chemotherapy and HSCT recipients with IMI. Compared to hematological controls, individuals with IA and mucormycosis had defective expression of dectin-1; in addition, patients with mucormycosis had decreased TLR2 and increased TLR4 expression. Since fungal recognition via dectin-1 favors T helper 17 responses and the latter are highly dependent on activation of the signal transducer and activator of transcription (STAT) 3, we next used phospho-flow cytometry to measure the phosphorylation of the transcription factors STAT1 and STAT3 in response to interferon-gamma (IFN-γ) and interleukin (IL)-6, respectively. While IFN-γ/STAT1 signaling was similar between groups, naïve T cells from patients with IA, but not those with mucormycosis, exhibited reduced responsiveness to IL-6 as measured by STAT3 phosphorylation. Furthermore, IL-6 increased Aspergillus-induced IL-17 production in culture supernatants from healthy and hematological controls but not in patients with IA. Altogether, these observations suggest an important role for dectin-1 and the IL-6/STAT3 pathway in protective immunity against Aspergillus.
Data from: Increasing procaspase 8 expression using repurposed drugs to induce HIV infected cell death in ex vivo patient cells
HIV persists because a reservoir of latently infected CD4 T cells do not express viral proteins and are indistinguishable from uninfected cells. One approach to HIV cure suggests that reactivating HIV will activate cytotoxic pathways; yet when tested in vivo, reactivating cells do not die sufficiently to reduce cell-associated HIV DNA levels. We recently showed that following reactivation from latency, HIV infected cells generate the HIV specific cytotoxic protein Casp8p41 which is produced by HIV protease cleaving procaspase 8. However, cell death is prevented, possibly due to low procaspase 8 expression. Here, we tested whether increasing procaspase 8 levels in CD4 T cells will produce more Casp8p41 following HIV reactivation, causing more reactivated cells to die. Screening 1277 FDA approved drugs identified 168 that increased procaspase 8 expression by at least 1.7-fold. Of these 30 were tested for anti-HIV effects in an acute HIVIIIb infection model, and 9 drugs at physiologic relevant levels significantly reduced cell-associated HIV DNA. Primary CD4 T cells from ART suppressed HIV patients were treated with one of these 9 drugs and reactivated with αCD3/αCD28. Four drugs significantly increased Casp8p41 levels following HIV reactivation, and decreased total cell associated HIV DNA levels (flurbiprofen: p = 0.014; doxycycline: p = 0.044; indomethacin: p = 0.025; bezafibrate: P = 0.018) without effecting the viability of uninfected cells. Thus procaspase 8 levels can be increased pharmacologically and, in the context of HIV reactivation, increase Casp8p41 causing death of reactivating cells and decreased HIV DNA levels. Future studies will be required to define the clinical utility of this or similar approaches.
Data from: Effect of HIV and malaria parasites co-infection on immune-hematological profiles among patients attending anti-retroviral treatment (ART) clinic in Infectious Disease Hospital Kano, Nigeria
Background Human immunodeficiency virus (HIV) and malaria co-infection may present worse health outcomes in the tropics. Information on HIV/malaria co-infection effect on immune-hematological profiles is critical for patient care and there is a paucity of such data in Nigeria. Objective To evaluate immune-hematological profiles among HIV infected patients compared to HIV/malaria co-infected for ART management improvement. Methods This was a cross sectional study conducted at Infectious Disease Hospital, Kano. A total of 761 consenting adults attending ART clinic were randomly selected and recruited between June and December 2015. Participants' characteristics and clinical details including two previous CD4 counts were collected. Venous blood sample (4ml) was collected in EDTA tube for malaria parasite diagnosis by rapid test and confirmed with microscopy. Hematological profiles were analyzed by Sysmex XP-300 and CD4 count by Cyflow cytometry. Data was analyzed with SPSS 22.0 using Chi-Square test for association between HIV/malaria parasites co-infection with age groups, gender, ART, cotrimoxazole and usage of treated bed nets. Mean hematological profiles by HIV/malaria co-infection and HIV only were compared using independent t-test and mean CD4 count tested by mixed design repeated measures ANOVA. Statistical significant difference at probability of <0.05 was considered for all variables. Results Of the 761 HIV infected, 64% were females, with a mean age of ± (SD) 37.30 (10.4) years. Prevalence of HIV/malaria co-infection was 27.7% with Plasmodium falciparum specie accounting for 99.1%. No statistical significant difference was observed between HIV/malaria co-infection in association to age (p = 0.498) and gender (p = 0.789). A significantly (p = 0.026) higher prevalence (35.2%) of co-infection was observed among non-ART patients compared to (26%) ART patients. Prevalence of co-infection was significantly lower (20.0%) among cotrimoxazole users compared to those not on cotrimoxazole (37%). The same significantly lower co-infection prevalence (22.5%) was observed among treated bed net users compared to those not using treated bed nets (42.9%) (p = 0.001). Out of 16 hematology profiles evaluated, six showed significant difference between the two groups (i) packed cell volume (p = <0.001), (ii) mean cell volume (p = 0.005), (iii) mean cell hemoglobin concentration (p = 0.011), (iv) absolute lymphocyte count (p = 0.022), (v) neutrophil percentage count (p = 0.020) and (vi) platelets distribution width (p = <0.001). Current mean CD4 count cell/μl (349±12) was significantly higher in HIV infected only compared to co-infected (306±17), (p = 0.035). A significantly lower mean CD4 count (234.6 ± 6.9) was observed among respondents on ART compared to non-ART (372.5 ± 13.2), p<0.001, mean difference = -137.9). Conclusion The study revealed a high burden of HIV and malaria co-infection among the studied population. Co-infection was significantly lower among patients who use treated bed nets as well as cotrimoxazole chemotherapy and ART. Six hematological indices differed significantly between the two groups. Malaria and HIV co-infection significantly reduces CD4 count. In general, to achieve better management of all HIV patients in this setting, diagnosing malaria, prompt antiretroviral therapy, monitoring CD4 and some hematology indices on regular basis is critical.
Data from: Patient factors that influence decision-making in self-management support: a clinical vignette study
Background and aim: Self-management support is an integral part of current chronic care guidelines. The success of self-management interventions varies between individual patients, suggesting a need for tailored self-management support. Understanding the role of patient factors in the current decision making of health professionals can support future tailoring of self-management interventions. The aim of this study is to identify the relative importance of patient factors in health professionals' decision making regarding self-management support. Method: A factorial survey was presented to primary care physicians and nurses. The survey consisted of clinical vignettes (case descriptions), in which 11 patient factors were systematically varied. Each care provider received a set of 12 vignettes. For each vignette, they decided whether they would give this patient self-management support and whether they expected this support to be successful. The associations between respondent decisions and patient factors were explored using ordered logit regression. Results: The survey was completed by 60 general practitioners and 80 nurses. Self-management support was unlikely to be provided in a third of the vignettes. The most important patient factor in the decision to provide self-management support as well as in the expectation that self-management support would be successful was motivation, followed by patient-provider relationship and illness perception. Other factors, such as depression or anxiety, education level, self-efficacy and social support, had a small impact on decisions. Disease, disease severity, knowledge of disease, and age were relatively unimportant factors. Conclusion: This is the first study to explore the relative importance of patient factors in decision making and the expectations regarding the provision of self-management support to chronic disease patients. By far, the most important factor considered was patient's motivation; unmotivated patients were less likely to receive self-management support. Future tailored interventions should incorporate strategies to enhance motivation in unmotivated patients. Furthermore, care providers should be better equipped to promote motivational change in their patients.
Data from: Urgent-start peritoneal dialysis and hemodialysis in ESRD patients: complications and outcomes
Background: Several studies have suggested that urgent-start peritoneal dialysis (PD) is a feasible alternative to hemodialysis (HD) in patients with end-stage renal disease (ESRD), but the impact of the dialysis modality on outcome, especially on short-term complications, in urgent-start dialysis has not been directly evaluated. The aim of the current study was to compare the complications and outcomes of PD and HD in urgent-start dialysis ESRD patients. Methods: In this retrospective study, ESRD patients who initiated dialysis urgently without a pre-established functional vascular access or PD catheter at a single center from January 2013 to December 2014 were included. Patients were grouped according to their dialysis modality (PD and HD). Each patient was followed for at least 30 days after catheter insertion (until January 2016). Dialysis-related complications and patient survival were compared between the two groups. Results: Our study enrolled 178 patients (56.2% male), of whom 96 and 82 patients were in the PD and HD groups, respectively. Compared with HD patients, PD patients had more cardiovascular disease, less heart failure, higher levels of serum potassium, hemoglobin, serum albumin, serum pre-albumin, and lower levels of brain natriuretic peptide. There were no significant differences in gender, age, use of steroids, early referral to a nephrologist, prevalence of primary renal diseases, prevalence of co-morbidities, and other laboratory characteristics between the groups. The incidence of dialysis-related complications during the first 30 days was significantly higher in HD than PD patients. HD patients had a significantly higher probability of bacteremia compared to PD patients. HD was an independent predictor of short-term (30-day) dialysis-related complications. There was no significant difference between PD and HD patients with respect to patient survival rate. Conclusion: In an experienced center, PD is a safe and feasible dialysis alternative to HD for ESRD patients with an urgent need for dialysis.
Data from: Implementation of new standard operating procedures for geriatric trauma patients with multiple injuries: a single level I trauma centre study
<p class="Abstract"><b>Background</b></p> <p class="Abstract">The demographic changes towards ageing of the populations in developed countries impose a challenge to trauma centres, as geriatric trauma patients require specific diagnostic and therapeutic procedures. This study investigated whether the integration of new standard operating procedures (SOPs) for the resuscitation room (ER) has an impact on the clinical course in geriatric patients. The new SOPs were designed for severely injured adult trauma patients, based on the Advanced Trauma Life Support (ATLS) and imply early whole-body computed tomography (CT), damage control surgery, and the use of goal-directed coagulation management.</p> <p class="Abstract"><b>Methods</b></p> <p class="Abstract">Single-centre cohort study. We included all patients ≥ 65 years of age with an Injury Severity Score (ISS) ≥ 9 who were admitted to our hospital primarily via ER. A historic cohort was compared to a cohort after the implementation of the new SOPs.</p> <p class="Abstract"><b>Results</b></p> <p class="Abstract">We enrolled 311 patients who met the inclusion criteria between 2000–2006 (group <i>Pre</i>SOP) and 2010–2012 (group SOP). There was a significant reduction in the mortality rate after the implementation of the new SOPs (<i>P</i> = .001). This benefit was seen only for severely injured patients (ISS ≥ 16), but not for moderately injured patients (ISS 9–15). There were no differences with regard to infection rates or rate of palliative care.</p> <p class="Abstract"><b>Conclusions</b></p> <p class="Abstract">We found an association between implementation of new ER SOPs, and a lower mortality rate in severely injured geriatric trauma patients, whereas moderately injured patients did not obtain the same benefit.</p>
Data from: Jaw biodynamic data for 24 patients with chronic unilateral temporomandibular disorder
This study assessed 24 adult patients, suffering from severe chronic unilateral pain diagnosed as temporomandibular joint (TMJ) disorder (TMD). The full dentate patients had normal occlusion and had never received an occlusal therapy, i.e., were with natural dental evolution/maturation. The following functional and dynamic factors were assessed: (1) chewing function; (2) TMJ remodeling or the condylar path (CP); and (3) lateral jaw motion or lateral guidance (LG). CPs were assessed using conventional axiography, and LG was assessed by K7 jaw tracking. Seventeen (71%) of the 24 (100%) patients consistently showed a habitual chewing side. The mean (standard deviation [SD]) of the CP angles was 47.90 (9.24) degrees. The mean (SD) of the LG angles was 42.95 (11.78) degrees. Data collection emerged from the conception of a new TMD paradigm where the affected side could be the habitual chewing side, the side with flatter lateral jaw motion or the side with an increased CP angle. These data may lead to improved diagnosis, therapy plans and evolution in TMD patients.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.