Postoperative education, discharge instructions, and follow-up appointments provide a foundation for new ostomates after discharge, but a gap in care remains. New ostomates utilize resources twice as much as other colorectal patients. Virtual visits allow visual inspection of the patient while providing verbal support. The purposes of this project were to determine the feasibility of Virtual Postoperative Visits, to define specific issues patients want addressed, and to assess patient satisfaction with a virtual format. In this pilot project, 10 patients attended two outpatient virtual visits following hospital discharge. The virtual visits were conducted using video conferencing software. Descriptive statistics were used to analyze data from a survey assessing patient satisfaction; content analysis described video interactions. All patients successfully completed two virtual visits from their homes. Ninety percent felt these visits helped with ostomy management and agreed they should be part of a discharge plan. All patients felt comfortable with a virtual format. Common themes discussed included pouching and skin irritation. We found that virtual visits are feasible, and patients are satisfied with this format to address goals of care. Future work will focus on large-scale implementation of virtual visits for new ostomates. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Corresponding author: Tracie White, DNP, CRNP, ACNP-BC, CRNFA, School of Nursing, University of Alabama at Birmingham, 1701 University Blvd, Birmingham, AL 35294 (twhite220@uab.edu). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2GqXuBm
Τρίτη 18 Δεκεμβρίου 2018
MDSCs in infectious diseases: regulation, roles, and readjustment
Abstract
Many pathogens, ranging from viruses to multicellular parasites, promote expansion of MDSCs, which are myeloid cells that exhibit immunosuppressive features. The roles of MDSCs in infection depend on the class and virulence mechanisms of the pathogen, the stage of the disease, and the pathology associated with the infection. This work compiles evidence supported by functional assays on the roles of different subsets of MDSCs in acute and chronic infections, including pathogen-associated malignancies, and discusses strategies to modulate MDSC dynamics to benefit the host.
https://ift.tt/2ED2ocU
Fatigue After Aneurysmal Subarachnoid Hemorrhage Is Highly Prevalent in the First-Year Postonset and Related to Low Physical Fitness: A Longitudinal Study
Objective The aim of the study was to investigate whether low physical fitness and inactive and sedentary lifestyles play a role in the severity of fatigue in patients with aneurysmal subarachnoid hemorrhage (a-SAH). Design This is a prospective 1-yr follow-up study, including a total of 52 patients with a-SAH. Outcome measures included the Fatigue Severity Scale score, peak oxygen uptake (VO2peak), isokinetic knee muscle strength (peak torque), physical activity (% 24-hr period), and sedentary behavior (% waking hours) and were evaluated at 6 and 12 mos after onset. Results Fatigue was highly prevalent in the first year and reported by 48% of the patients at 6 mos and by 52% at 12 mos after a-SAH. Fatigue was associated with the knee extension (Phttps://ift.tt/2CmK5Gn
Maximizing Recovery From Concussions for Youth Participating in Sports and Recreational Activities
Concussions have become a public health issue. This public health concern has drawn the attention of many states in which laws were created to address concussions safety, recognition of signs and symptoms, immediate removal, medical clearance, and return-to-play protocols. Most state legislation focused on student athletes participating in organized sports. However, the rise in concussion can be directly attributed to children, youth, and adolescents participating in nonsports-related events. Maximizing recovery from a concussion involves implementing education programs that focus on recognition of symptoms, treatment, and return-to-learn options. Treatment strategies used to address concussed youth include physical and cognitive rest and minimizing external stimuli that can increase symptoms. Because learning is a direct outcome for all youth, a return-to-learn protocol based on a collaborative school-based team approach is suggested.https://ift.tt/2SZbrbb
More Than Just a Game: The Public Health Impact of Sport and Physical Activity for People With Disabilities (The 2017 DeLisa Lecture)
Although people with disabilities make up a large proportion of our global population and are known to be disproportionately impacted by sedentary lifestyles leading to chronic disease, programs promoting physical activity often fail to address their unique needs. Both environmental and attitudinal factors also act as barriers to full participation. In this context, increasing evidence shows the positive impact of physical activity and sport on outcomes related to physical health, mental health, community participation, and, in some cases, neurorecovery for people with disabilities. Thus, participation should be seen not only as a medical intervention but also as a rights-based issue. We, as physiatrists, can be agents of change by promoting concepts of universal design and inclusion in physical activity and sport programs.https://ift.tt/2SZbpjz
The Impact of Introducing a Physical Medicine and Rehabilitation Trauma Consultation Service to an Academic Level 1 Trauma Center
Objective Previous retrospective studies suggest that early physical medicine and rehabilitation (PM&R) consultation for trauma patients improves outcome and reduces acute care length of stay (LOS). There have not been controlled studies to evaluate this impact. This study assesses the impact of PM&R consultations on acute trauma patients. Design This study compared measured outcomes before and after the introduction of a PM&R consultation service to the trauma program at a large academic hospital. The primary outcome measure was acute care LOS. Results The 274 historical controls and 76 patients who received a PM&R consultation were not different in injury severity score, age, or sex. Length of stay was not different between the two groups. However, when early (≤8 days after injury) versus late (>8 days) consults were compared, the early group had a markedly lower LOS (12 vs. 30 days, Phttps://ift.tt/2CmrY3y
Individual and Environmental Determinants of Late-Life Community Disability for Persons Aging With Cardiovascular Disease
Objective The aim of the study was to estimate the prevalence of late-life community disability for adults 65 yrs and older with cardiovascular disease versus those without. This study also investigated the contributions of environmental and individual risk factors on late-life community disability for persons with cardiovascular disease. Design This is a secondary data analysis of the 2016 round of the National Health and Aging Trends Study. The study sample included community-dwelling Americans with cardiovascular disease (n = 1490) and without (n = 4819). Logistic regression was used to estimate associations between individual risk factors, environmental factors, and community disability for those with cardiovascular disease. Results Individuals with cardiovascular disease had a significantly higher prevalence of late-life community disability than those without (44.8% vs. 29.0%). For persons with cardiovascular disease, lack of transportation, home modification, and needing assistance with mobility increased the odds of community disability. Younger age and lower comorbidity were associated with decreased odds of community disability. When accounting for environmental factors in multivariate analyses, sex, race, and education were not significantly associated with community disability. Conclusion Late-life community disability is highly prevalent for persons aging with cardiovascular disease. Intervention strategies to deter late-life community disablement should focus on improving access to transportation and improving the community environment in which older adults live.https://ift.tt/2CnQXDv
Paroxysmal Sympathetic Hyperactivity and Clinical Considerations for Patients With Acquired Brain Injuries: A Narrative Review
The term "storming" has often been used colloquially to characterize patients with brain injury who showed signs and symptoms of elevated heart rate, blood pressure, respiratory rate, temperature, and motor posturing. Recently, the term paroxysmal sympathetic hyperactivity has been used as the unifying term to describe these acute episodes of elevated sympathetic hyperactivity. Various pharmaceutical and management options are available, but no single drug or protocol has been deemed superior to the others. Data on prognosis and recovery in relation to paroxysmal sympathetic hyperactivity are limited but point toward poorer functional outcome and increased mortality. Overall, the phenomenon of paroxysmal sympathetic hyperactivity requires further research to aid rehabilitative efforts so that patients can effectively participate in therapy. A review of the literature has revealed sparse information on the management of sympathetic storming within rehabilitation facilities. This narrative review seeks to provide an up-to-date synopsis and recommendations on the management of rehabilitation inpatients with paroxysmal sympathetic hyperactivity.https://ift.tt/2SVf7dS
Extracellular Matrix and Adhesion Molecule Gene Expression in the Normal and Injured Murine Intervertebral Disc
Objective The aim of the study was to determine the transcription profile of the mouse nucleus pulposus and annulus fibrosus with an unbiased method. Furthermore, pathophysiological relevance of selected genes was demonstrated in the mouse tail intervertebral disc injury model. Design Paired normal mouse nucleus pulposus and annulus fibrosus tissue from C57BL/6j mice was examined by a polymerase chain reaction array. Key gene expression in the normal and injured intervertebral discs was confirmed by real-time polymerase chain reaction. Results Among the 84 genes studied, 63 were expressed higher in annulus fibrosus than in nucleus pulposus; only four genes were expressed higher in nucleus pulposus than in annulus fibrosus (n = 4, P ≤ 0.05). Real-time polymerase chain reaction confirmed that cadherin (cdh) 2 gene expression was higher in nucleus pulposus than in annulus fibrosus, and type I collagen (col1) gene expression was higher in the annulus fibrosus than in nucleus pulposus (n = 8, Phttps://ift.tt/2CmP5Lh
A Tale of Confusion From Overlapping Confidence Intervals
In clinical research presentations, study results are commonly reported in the form of P values and confidence intervals as an estimate of association and treatment effect. The interpretation of confidence intervals that overlap can be confusing and difficult for the reader to draw clinically meaningful conclusions. In this brief report, we describe the basics of confidence intervals and present an example from a recently published randomized control trial to illustrate a common confusion that overlapping confidence intervals between the means of two independent groups may not necessarily reject the true significant difference of effect. It is recommended that investigators use the direct difference of means between groups for confidence interval estimation to reduce type II errors. Clinicians should interpret overlapping confidence intervals with caution and avoid the assumption that overlapping confidence intervals always implies a lack of difference of treatment effect to decide application of treatment.https://ift.tt/2SYeqR8
Complete Restoration of Respiratory Muscle Function in Three Subjects With Spinal Cord Injury: Pilot Interventional Clinical Trial
Objectives The aim of this study was to assess the safety and efficacy of complete restoration of respiratory muscle function in subjects with spinal cord injury. Methods This was an interventional study investigating three subjects maintained on a diaphragm pacing system who were implanted with the spinal cord stimulation system to restore cough. Peak expiratory airflow and airway pressure generation were the primary physiologic outcome measures; an assessment of the degree of difficulty in raising secretions was the primary clinical outcome measure. Results Mean peak expiratory airflow and airway pressure generation during spontaneous efforts were 1.7 ± 0.2 L/s and 31 ± 7 cmH2O, respectively. When spinal cord stimulation was applied after pacing volume associated with the subject's maximum inspiratory effort and synchronized with the subject's maximum expiratory effort, peak expiratory airflow and airway pressure generation were 9.0 ± 1.9 L/s and 90 ± 6 cmH2O, respectively (Phttps://ift.tt/2CmJV1J
Huge Bursitis and Bursal Synovial Osteochondromatosis Associated With Scapular Osteochondroma Mimicking a Giant Calcific Mass of the Chest Wall
Osteochondroma is the most common benign bone tumor, but it rarely arises from the scapula. Scapulothoracic bursitis is quite rare and osteochondroma is one of the unusual causes of this condition. Synovial chondromatosis may occur extremely uncommonly in this bursa. We reported an unusual case of scapulothoracic bursitis with synovial chondromatosis, which is caused by osteochondroma. To the best of our knowledge, there is no defined chondromatosis in the scapulothoracic bursa secondary to scapular osteochondroma in the literature.https://ift.tt/2SX50VQ
Cryotherapy Reduces Muscle Spasticity But Does Not Affect Proprioception in Ischemic Stroke: A Randomized Sham-Controlled Crossover Study
Objective The aim of the study was to evaluate the immediate effects of cryotherapy (using an ice pack) on ankle joint position sense and the degree of spasticity after chronic hemiparetic stroke. Design We used a sham-controlled crossover design. Sixteen chronic hemiparetic patients were randomly assigned to two groups: (1) those who received cryotherapy followed by a control intervention 15 days later (cryotherapy group) and (2) those who received the control intervention followed by cryotherapy 15 days later (control intervention group). Ankle joint position sense was measured on the paretic side using a Biodex Multi-joint System 3 dynamometer before and after 20 mins of either application on the calf muscles. Lower absolute error scores were calculated for data analyses and were used to determine joint position sense. The degree of spasticity of the plantar flexor muscles was scored according to the Modified Ashworth Scale. Results Sixteen patients completed the crossover experiment; however, data analysis was successfully conducted in 15 participants. Cryotherapy reduced the degree of spasticity of the plantar flexor muscles without altering ankle joint position sense. Conclusions Cryotherapy (using an ice pack) may reduce plantar flexor spasticity without influencing proprioception.https://ift.tt/2CmThKM
Comparative Effects of Different Assistance Force During Robot-Assisted Gait Training on Locomotor Functions in Patients With Subacute Stroke: An Assessor-Blind, Randomized Controlled Trial
Objective The aim of the study was to compare the effects of progressive reducing assistance force versus full assistance force controlled robot-assisted gait training combined with conventional physiotherapy on locomotor functions in patients with subacute stroke. Design Inpatients with subacute stroke (N = 29; 16 men; Functional Ambulation Category score = 1 ± 0.9) were randomly assigned to one of two groups: a progressive reducing assistance force group (n = 15) or a full assistance force group (n = 14). The progressive reducing assistance force group performed robot-assisted gait training sessions from 100% assistance force at the outset to 60% assistance force at the end of the robot-assisted gait training, whereas the full assistance force group received 100% assistance force throughout the robot-assisted gait training sessions. Both groups performed robot-assisted gait training combined with conventional physiotherapy 5 days a week for 4 wks. After intervention, all patients then underwent only conventional physiotherapy 5 days a week for 4 wks of follow-up. Results The Mann–Whitney U test between-group comparisons showed that improvements were significantly greater in the progressive reducing assistance force group for the Functional Ambulation Category, knee extensors torque, and Berg Balance Scale relative to the full assistance force group, both at postintervention and at follow-up. Conclusions Progressive reducing assistance force control during robot-assisted gait training combined with conventional physiotherapy may be more beneficial for improving locomotor functions in patients with subacute stroke.https://ift.tt/2CmJPHp
The Dodo Bird Is Not Extinct: Ultrasound Imaging for Supraspinatus Tendinosis
No abstract availablehttps://ift.tt/2SYHo3w
The Perception of Psychosocial Risks and Work-Related Stress in Relation to Job Insecurity and Gender Differences: A Cross-Sectional Study
Introduction. The perception of psychosocial risks exposes workers to develop work-related stress. Recently the attention of scientific research has focused on a psychosocial risk already identified as "job insecurity" that regards the "overall concern about the continued existence of the job in the future" and that also depends on worker's perception, different for each gender. Aim of the Study. The aim of this cross sectional study is to show if job insecurity, in the form of temporary contracts, can influence the perception of psychosocial risks and therefore increase worker's vulnerability to work-related stress and how the magnitude of this effect differs between genders. Materials and Methods. 338 administrative technical workers (113 males and 225 females) were administered a questionnaire, enquiring contract typology (permanent or temporary contracts), and the Health Safety Executive questionnaire to assess work-related stress. The Health Safety Executive Analysis Tool software was used to process collected questionnaires and the Wilcoxon rank-sum test was used to evaluate the statistical significance of the differences obtained. Results. Workers with temporary contracts obtained lower scores than workers with permanent contracts in all the domains explored by the Health Safety Executive Analysis questionnaire, statistically significant (P
https://ift.tt/2ED922C
Lethal silicone embolization syndrome complicating penile, scrotal and breast self-augmentation
Abstract
A 62-year-old man died following injection of liquid silicone into his external genitalia and chest wall. The body was discovered naked, apart from a pair of black women's high-heeled shoes, black ankle restraints, which were chained together, and disposable medical gloves. Medical items in the house included syringes, needles, alcohol wipes and unmarked/labelled empty brown glass medical bottles. At autopsy the external genitalia were markedly enlarged with white dressings over injection sites in the scrotum, penis and above the left nipple. Histological examination of the scrotum, penis and breast showed a florid granulomatous foreign body giant cell reaction and scarring surrounding numerous optically clear vacuoles. The lungs also showed numerous vacuoles within the interstitium in keeping with embolization of injected material. Death was due to silicone embolization. Despite the dangers of liquid silicone injections for soft tissue augmentation, and the ban on its use for medical cosmetic procedures, this practice continues.
https://ift.tt/2RclU61
Independent predictors for longer radiographic resolution in patients with refractory Mycoplasma pneumoniae pneumonia: a prospective cohort study
Objectives
To examine prospectively the radiographic clearance of refractory Mycoplasma pneumoniae pneumonia (RMPP) in immunocompetent children, and to identify independent predictors of time to complete radiographic resolution in patients with RMPP.
DesignA prospective cohort study.
SettingChildren's Hospital of Soochow University, China.
ParticipantsA total of 187 patients with RMPP treated with bronchoscopy were prospectively enrolled in the study between January 2012 and December 2015.
MethodsSerial chest radiographs were obtained after discharge every 4 weeks up to a maximum of 24 weeks after diagnosis or until large infiltration on chest radiographs had resolved. Multivariate logistic regression was performed to identify independent predictors of time to complete radiographic resolution.
ResultsOf the 187 patients with RMPP, bronchial mucus plug formation was detected in 73 (39.0%). C reactive protein (CRP) ≥50 mg/L, lactate dehydrogenase (LDH) ≥480 U/L, total fever duration ≥10 days and presence of mucus plugs were associated with longer time to radiographic clearance (all p<0.01). Compared with children without mucus plugs, those with mucus plugs were significantly more likely to have longer time to radiographic clearance (adjusted OR: 11.5; 95% CI 2.5 to 45.7; p<0.01).
ConclusionClinicians might use duration of fever, CRP, LDH and presence of mucus plugs as parameters to identify children at a longer time to radiographic clearance in patients with RMPP.
https://ift.tt/2EzaFxo
Impact of abolishing prescription fees in Scotland on hospital admissions and prescribed medicines: an interrupted time series evaluation
Objectives
To identify whether the abolition of prescription fees in Scotland resulted in: (1) Increase in the number (cost to NHS) of medicines prescribed for which there had been a fee (inhaled corticosteroids). (2) Reduction in hospital admissions for conditions related to those medications for which there had been a fee (asthma or chronic obstructive pulmonary disease (COPD))—when both are compared with prescribed medicines and admissions for a condition (diabetes mellitus) for which prescriptions were historically free.
DesignNatural experimental retrospective general practice level interrupted time series (ITS) analysis using administrative data.
SettingGeneral practices, Scotland, UK.
Participants732 (73.6%) general practices across Scotland with valid dispensed medicines and hospital admissions data during the study period (July 2005–December 2013).
InterventionReduction in fees per dispensed item from April 2008 leading to the abolition of the fee in April 2011, resulting in universal free prescriptions.
Primary and secondary outcomesHospital admissions recorded in the Scottish Morbidity Record – 01 Inpatient (SMR01) and dispensed medicines recorded in the Prescribing Information System (PIS).
ResultsThe ITS analysis identified marked step reductions in adult (19–59 years) admissions related to asthma or COPD (the intervention group), compared with older or young people with the same conditions or adults with diabetes mellitus (the counterfactual groups). The prescription findings were less coherent and subsequent sensitivity analyses found that both the admissions and prescriptions data were highly variable above the annual or seasonal level, limiting the ability to interpret the findings of the ITS analysis.
ConclusionsThis study did not find sufficient evidence that universal free prescriptions was a demonstrably effective or ineffective policy, in terms of reducing hospital admissions or reducing socioeconomic inequality in hospital admissions, in the context of a universal, publicly administered medical care system, the National Health Service of Scotland.
https://ift.tt/2ED00CY
Direct inpatient costs and influencing factors for patients with rectal cancer with low anterior resection: a retrospective observational study at a three-tertiary hospital in Beijing, China
Objectives
The aim of the study was to investigate the direct inpatient cost and analyse influencing factors for patients with rectal cancer with low anterior resection in Beijing, China.
DesignA retrospective observational study.
SettingThe study was conducted at a three-tertiary oncology institution.
ParticipantsA total of 448 patients who underwent low anterior resection and were diagnosed with rectal cancer from January 2015 to December 2016 at Peking University Cancer Hospital were retrospectively identified. Demographic, clinical and cost data were determined.
ResultsThe median inpatient cost was89 064, with a wide range (46 711–191 329) due to considerable differences in consumables. The material cost accounted for 52.19% and was the highest among all the cost components. Colostomy (OR 4.17; 95% CI 1.79 to 9.71), complications of hypertension (OR 5.30; 95% CI 1.94 to 14.42) and combined with other tumours (OR 2.92; 95% CI 1.12 to 7.60) were risk factors for higher cost, while clinical pathway (OR 0.10; 95% CI 0.03 to 0.35), real-time settlement (OR 0.26; 95% CI 0.10 to 0.68) and combined with cardiovascular disease (OR 0.09; 95% CI 0.02 to 0.52) were protective determinants.
ConclusionsThis approach is an effective way to relieve the economic burden of patients with cancer by promoting the clinical pathway, optimising the payment scheme and controlling the complication. Further research focused on the full-cost investigation in different stages of rectal cancer based on a longitudinal design is necessary.
https://ift.tt/2Ezapyq
Differences in the outcomes of adjuvant chemotherapy for colon cancer prescribed by physicians in different disciplines: a population-based study in Taiwan
Objectives
One feature unique to the Taiwanese healthcare system is the ability of physicians other than oncologists to prescribe systemic chemotherapy. This study investigated whether the care paths implemented by oncologists and non-oncologists differ with regard to patient outcomes.
SettingData from the Taiwan Cancer Registry and National Health Insurance Database were linked to identify patients with colon cancer who underwent colectomy as first treatment within 3 months of diagnosis and adjuvant chemotherapy between 2005 and 2009.
Participants and methodsPostoperative patients who underwent adjuvant chemotherapy were included in this study. The exclusion criteria included patients with stage IV disease, a positive surgical margin and early disease recurrence. Among the patients presenting with multiple primary cancers, we also excluded patients who were diagnosed with colon cancer but for whom this was not the first primary cancer. The variables included sex, age, comorbidities, disease stage, chemotherapy cycle and changes in treatment regimen as well as the specialty of treatment providers and their case volume. Cox regression models and Kaplan-Meier analysis were used to examine differences in outcomes in the matched cohorts.
ResultsWe examined 3534 patients who were prescribed adjuvant chemotherapy by physicians from different disciplines. In terms of 5-year disease-free survival, no significant difference was observed between the groups of oncologists or surgeons among patients with stage II (90.02%vs88.99%) or stage III (77.64%vs79.99%) diseases. Patients who were subjected to changes in their chemotherapy regimens presented recurrence rates higher than those who were not.
ConclusionsThe discipline of practitioners is seldom taken into account in most series. This is the first study to provide empirical evidence demonstrating that the outcomes of patients with colon cancer do not depend on the treatment path, as long as the selection criteria for adjuvant chemotherapy is appropriate. Further study will be required before making any further conclusions.
https://ift.tt/2ECZV28
Effects of food items and related nutrients on metabolic syndrome using Bayesian multilevel modelling using the Tehran Lipid and Glucose Study (TLGS): a cohort study
Objectives
Diet and nutrition might play an important role in the aetiology of metabolic syndrome (MetS). Most studies that examine the effects of food intake on MetS have used conventional statistical analyses which usually investigate only a limited number of food items and are subject to sparse data bias. This study was undertaken with the goal of investigating the concurrent effect of numerous food items and related nutrients on the incidence of MetS using Bayesian multilevel modelling which can control for sparse data bias.
DesignProspective cohort study.
SettingThis prospective study was a subcohort of the Tehran Lipid and Glucose Study. We analysed dietary intake as well as pertinent covariates for cohort members in the fourth (2008–2011) and fifth (2011–2014) follow-up examinations. We fitted Bayesian multilevel model and compared the results with two logistic regression models: (1) full model which included all variables and (2) reduced model through backward selection of dietary variables.
Participants3616 healthy Iranian adults, aged ≥20 years.
Primary and secondary outcome measuresIncident cases of MetS.
ResultsBayesian multilevel approach produced results that were more precise and biologically plausible compared with conventional logistic regression models. The OR and 95% confidence limits for the effects of the four foods comparing the Bayesian multilevel with the full conventional model were as follows: (1) noodle soup (1.20 (0.67 to 2.14) vs 1.91 (0.65 to 5.64)), (2) beans (0.96 (0.5 to 1.85) vs 0.55 (0.03 to 11.41)), (3) turnip (1.23 (0.68 to 2.23) vs 2.48 (0.82 to 7.52)) and (4) eggplant (1.01 (0.51 to 2.00) vs 1 09 396 (0.152x10–6 to 768x1012)). For most food items, the Bayesian multilevel analysis gave narrower confidence limits than both logistic regression models, and hence provided the highest precision.
ConclusionsThis study demonstrates that conventional regression methods do not perform well and might even be biased when assessing highly correlated exposures such as food items in dietary epidemiological studies. Despite the complexity of the Bayesian multilevel models and their inherent assumptions, this approach performs superior to conventional statistical models in studies that examine multiple nutritional exposures that are highly correlated.
https://ift.tt/2Ez9RZo
Feasibility and validity of the Health Status Classification System-Preschool (HSCS-PS) in a large community sample: the Generation R study
Objectives
To evaluate the feasibility, discriminant validity and concurrent validity of the Health Status Classification System-Preschool (HSCS-PS) in children aged 3 years in a large community sample in the Netherlands.
Design/settingA prospective population-based cohort in Rotterdam, the Netherlands.
ParticipantsA questionnaire was administrated to a sample of parents of 4546 children (36.7±1.5 months).
Outcome measuresHealth-related quality of life (HRQOL) of children was measured by HSCS-PS. The HSCS-PS consists of 10 original domains. Two single-item measures of 'General health' and 'Behavior' were added. A disability score was calculated by summing up all 10 original domains to describe the overall health status. Feasibility was assessed by the response rate, percentages of missing answers, score distributions and the presence of floor/ceiling effects. Discriminant validity was analysed between subgroups with predefined conditions: low birth weight, preterm birth, wheezing, Ear-Nose-Throat surgical procedures and behaviour problems. In the absence of another HRQOL measure, this study uses the single-items 'General health' and 'Behavior' as a first step to evaluate concurrent validity of the HSCS-PS.
ResultsFeasibility: response rate was 69%. Ceiling effects were observed in all domains. Discriminant validity: the disability score discriminated clearly between subgroups of children born with a 'very low birth weight', 'very preterm birth', with 'four or more than four times wheezing', 'at least one ear-nose-throat surgical procedures', 'behaviour problems present' and the 'reference' group. Concurrent validity: HSCS-PS domains correlated better with hypothesised parallel additional domains than with other non-hypothesised original domains.
ConclusionsThis study supports the feasibility and validity of the HSCS-PS among preschoolers in community settings. We recommend developing a utility-based scoring algorithm for the HSCS-PS. Further empirical studies and repeated evaluations in varied populations are recommended.
https://ift.tt/2ECZOne
Trends of socioeconomic equality in mortality amenable to healthcare and health policy in 1992-2013 in Finland: a population-based register study
Objective
To study trends in socioeconomic equality in mortality amenable to healthcare and health policy interventions.
DesignA population-based register study.
SettingNationwide data on mortality from the Causes of Death statistics for the years 1992–2013.
ParticipantsAll deaths of Finnish inhabitants aged 25–74.
Outcome measuresYearly age-standardised rates of mortality amenable to healthcare interventions, alcohol-related mortality, ischaemic heart disease mortality and mortality due to all the other causes by income. Concentration index (C) was used to evaluate the magnitude and changes in income group differences.
ResultsSignificant socioeconomic inequalities favouring the better-off were observed in each mortality category among younger (25–64) and older (65–74) age groups. Inequality was highest in alcohol-related mortality, C was –0.58 (95% CI –0.62 to –0.54) among younger men in 2008 and –0.62 (–0.72 to –0.53) among younger women in 2013. Socioeconomic inequality increased significantly during the study period except for alcohol-related mortality among older women.
ConclusionsThe increase in socioeconomic inequality in mortality amenable to healthcare and health policy interventions between 1992 and 2013 suggests that either the means or the implementation of the health policies have been inadequate.
https://ift.tt/2EwjKr2
Clinical, neurocognitive and demographic factors associated with functional impairment in the Australian Brain and Mind Youth Cohort Study (2008-2016)
Objectives
We sought to determine the unique and shared contributions of clinical, neurocognitive and demographic factors to functional impairment in a large, transdiagnostic, clinical cohort of adolescents and young adults.
DesignCross-sectional baseline data from a prospective, cohort study.
SettingHelp-seeking youth referred from outpatient services were recruited to the Brain and Mind Youth Cohort (2008–2016) in Sydney, Australia.
ParticipantsIn total, 1003 outpatients were recruited, aged between 12 and 36 years (mean= 20.4 years, 54% female), with baseline diagnoses of affective, psychotic, developmental or behavioural disorders.
InterventionsTreatment as usual.
Primary outcome measuresSocial and occupational functioning was used to index level of functional impairment. Structural equation modelling was used to examine associations between neurocognition, core clinical symptoms and alcohol and substance use, and clinician-rated and researcher-rated functional impairment. Moderator analyses were conducted to determine the potential influence of demographic and clinical factors (eg, medication exposure).
ResultsIndependent of diagnosis, we found that neurocognitive impairments, and depressive, anxiety and negative symptoms, were significantly associated with functioning. The association of neurocognition with social and occupational functioning remained significant even when constraining for age (15–25-year-olds only) or diagnosis (affective disorders only) in the final model.
ConclusionsThis study demonstrated that, in a clinically representative sample of youth, the key determinants of functioning may not be disorder specific. Further, evidence of neurocognitive dysfunction suggests that interventions that target cognition and functioning should not necessarily be reserved just for older adults with established illness.
https://ift.tt/2ECZQeG
Cast versus functional brace in the rehabilitation of patients treated for an ankle fracture: protocol for the UK study of ankle injury rehabilitation (AIR) multicentre randomised trial
Introduction
Each year in the UK over 120 000 people fracture their ankle. It is not known what the best rehabilitation strategy is for these people. Traditionally standard care has involved immobilisation in a plaster cast but an alternative is a functional brace, which can be removed to allow early movement. This paper details the protocol for a multicentre randomised trial of plaster cast immobilisation versus functional bracing for patients with an ankle fracture.
Methods and analysisWe will recruit adults with a fractured ankle, for which the treating clinician would consider plaster cast to be a reasonable management option. Randomisation will be on a 1:1 basis, stratified by centre, operative or non-operative management and age. Participants will be allocated to either plaster cast or a functional brace, both treatments are widely used. To have 90% power to detect a difference of 10 points on the primary outcome (Olerud and Molander Ankle Score) at the primary outcome time point (16 weeks), we need to randomise a minimum of 478 people. Quality of life and resource use will be collected at 6, 10, 16, 24 weeks and 12, 18, 24 months. The differences between treatment groups will be assessed on an intention-to-treat basis. The economic evaluation will adhere to the recommendations of the National Institute for Health and Care Excellence reference case.
Ethics, registration and disseminationNational Research Ethic Committee approved this study on 4 July 2017 (17/WM/0239). The first site opened to recruitment 9 October 2017. The results of this trial will be submitted to a peer-reviewed journal and will inform clinical practice.
Trial registration numberISRCTN15537280; Pre-results.
https://ift.tt/2Ezq69K
Evaluation of lung transplant perfusion using iodine maps from novel spectral detector computed tomography
p. 436
Nils Große Hokamp, Amit Gupta
DOI:10.4103/ijri.IJRI_35_18
We report the case of a 51-year-old patient who underwent bilateral lung transplantation and presented with an unstable condition and sepsis 6 days after transplantation. The performed contrast enhanced spectral detector computed tomography (CT) using a dual-layer detector showed absence of perfusion in the left lung on iodine maps, although branches of the pulmonary artery were patent. This prompted retrospective evaluation of CT images and total venous occlusion of the left pulmonary veins was found. Here, iodine maps helped in raising conspicuity of loss of lung perfusion.
http://www.ijri.org/currentissue.asp?sabs=y
Nils Große Hokamp, Amit Gupta
DOI:10.4103/ijri.IJRI_35_18
We report the case of a 51-year-old patient who underwent bilateral lung transplantation and presented with an unstable condition and sepsis 6 days after transplantation. The performed contrast enhanced spectral detector computed tomography (CT) using a dual-layer detector showed absence of perfusion in the left lung on iodine maps, although branches of the pulmonary artery were patent. This prompted retrospective evaluation of CT images and total venous occlusion of the left pulmonary veins was found. Here, iodine maps helped in raising conspicuity of loss of lung perfusion.
http://www.ijri.org/currentissue.asp?sabs=y
Gujarati hypertensives
: A cross-sectional study p. 153
Jayesh Dalpatbhai Solanki, Hemant B Mehta, Sunil J Panjwani, Hirava B Munshi, Chinmay J Shah
DOI:10.4103/jpp.JPP_59_18
Objective: To study the effect of different classes and combinations of antihypertensive agents on arterial stiffness and central hemodynamic parameters. Materials and Methods: A cross-sectional study was conducted in 446 treated apparently healthy hypertensives. Oscillometric PWA was performed by Mobil-o-Graph (IEM, Germany) to derive cardiovascular parameters that were further analyzed in groups stratified by antihypertensive used. Study parameters were brachial hemodynamics (blood pressure (BP), heart rate, and rate pressure product); arterial stiffness (augmentation pressure, augmentation index, pulse wave velocity, total arterial stiffness, and pulse pressure amplification); and central hemodynamics (central BP, cardiac output, and stroke work). Statistical significance was kept at P < 0.05. Results: All groups were selected by matching of age, gender, and body mass index. They were comparable with major confounding factors. There was no difference between study parameters in hypertensives taking exclusive angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), or angiotensin II receptor blocker. Multitherapy showed better hemodynamics and monotherapy showed better stiffness parameters. Addition of CCB to ACEI did not make a difference except with diastolic BP. For most comparisons, most of the results lacked statistical significance. Conclusion: Discrete PWA parameters showed no class difference in hypertensives, treated by conventional monotherapy or combination, ACEI appears to be the best drug. This also indicates that early diagnosis and blood pressure control are more important than antihypertensive used.
http://www.jpharmacol.com/currentissue.asp?sabs=y
Jayesh Dalpatbhai Solanki, Hemant B Mehta, Sunil J Panjwani, Hirava B Munshi, Chinmay J Shah
DOI:10.4103/jpp.JPP_59_18
Objective: To study the effect of different classes and combinations of antihypertensive agents on arterial stiffness and central hemodynamic parameters. Materials and Methods: A cross-sectional study was conducted in 446 treated apparently healthy hypertensives. Oscillometric PWA was performed by Mobil-o-Graph (IEM, Germany) to derive cardiovascular parameters that were further analyzed in groups stratified by antihypertensive used. Study parameters were brachial hemodynamics (blood pressure (BP), heart rate, and rate pressure product); arterial stiffness (augmentation pressure, augmentation index, pulse wave velocity, total arterial stiffness, and pulse pressure amplification); and central hemodynamics (central BP, cardiac output, and stroke work). Statistical significance was kept at P < 0.05. Results: All groups were selected by matching of age, gender, and body mass index. They were comparable with major confounding factors. There was no difference between study parameters in hypertensives taking exclusive angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), or angiotensin II receptor blocker. Multitherapy showed better hemodynamics and monotherapy showed better stiffness parameters. Addition of CCB to ACEI did not make a difference except with diastolic BP. For most comparisons, most of the results lacked statistical significance. Conclusion: Discrete PWA parameters showed no class difference in hypertensives, treated by conventional monotherapy or combination, ACEI appears to be the best drug. This also indicates that early diagnosis and blood pressure control are more important than antihypertensive used.
http://www.jpharmacol.com/currentissue.asp?sabs=y
Phosphodiesterase 7B1 as therapeutic target for treatment of cognitive dysfunctions in multiple sclerosis
p. 126
Arthi Balsundaram, Darling Chellathai
DOI:10.4103/jpp.JPP_77_18
Multiple sclerosis (MS) is an autoimmune, chronic degenerative neuroinflammatory disorder affecting younger age groups of the United States of America and Europe. MS prevalence studies in India have shown that India is no longer a low-risk zone. Many studies have shown the seriousness of cognitive impairments (CIs) and its types caused in MS. In this review, the pathological basis for CI in various stages of MS was reviewed and revealed to provide a basis for the treatment. Role of phosphodiesterase 7B1 (PDE7B1) inhibitors in treating CI related to MS were also stated in this review. The literature for this review was collected from PubMed and Embase.
http://www.jpharmacol.com/currentissue.asp?sabs=y
DOI:10.4103/jpp.JPP_77_18
Multiple sclerosis (MS) is an autoimmune, chronic degenerative neuroinflammatory disorder affecting younger age groups of the United States of America and Europe. MS prevalence studies in India have shown that India is no longer a low-risk zone. Many studies have shown the seriousness of cognitive impairments (CIs) and its types caused in MS. In this review, the pathological basis for CI in various stages of MS was reviewed and revealed to provide a basis for the treatment. Role of phosphodiesterase 7B1 (PDE7B1) inhibitors in treating CI related to MS were also stated in this review. The literature for this review was collected from PubMed and Embase.
http://www.jpharmacol.com/currentissue.asp?sabs=y
Healthcare Costs of Smokers Using Varenicline Versus Nicotine-Replacement Therapy Patch in the United States: Evidence from Real-World Practice
Abstract
Introduction
Varenicline (VAR) is an effective smoking-cessation therapy compared to the commonly used nicotine-replacement therapy patch (NRT-P). However, comparative real-world evidence on smoking-cessation therapies is limited, especially for economic outcomes.
Methods
Using national claims databases (2012–2016) in the United States (US), adults initiating VAR or NRT-P without use of any other smoking-cessation products were followed for up to 1 year on a quarterly basis. Outcomes included smoking-attributable (SA) (cardiovascular, diabetes, pulmonary diseases, and smoking cessation) and all-cause costs (2017 US dollars). Adjusted mean costs were estimated from multivariable regressions, with baseline characteristics and propensity scores as covariates. Annual adjusted costs were calculated from quarterly averages.
Results
The VAR cohort (n = 209,284) was younger (mean age 46.7 vs. 49.0 years) and had fewer comorbidities [mean Charlson Comorbidity Index (CCI): 0.8 vs. 1.6] than the NRT-P cohort (n = 34,593). After adjustment, VAR cohort had lower SA and all-cause medical costs than NRT-P cohort in Quarters 1–4 (Q1–Q4) of follow-up, and had lower SA and all-cause total costs in Q2–Q4. Annually, VAR cohort had higher SA total costs ($307) and lower all-cause costs (− $2089) than NRT-P cohort. Annual medical costs were lower in VAR cohort (− $640 for SA and − $2876 for all-cause), and pharmacy costs were higher ($762 for SA and $777 for all-cause). In adherent patients (VAR: n = 38,744; NRT-P: n = 2702), VAR patients had lower annual medical costs (− $794 for SA and − $1636 for all-cause) and higher pharmacy costs ($1175 for SA and $1269 for all-cause); differences in SA and all-cause total costs were not statistically significant between treatment groups.
Conclusions
Lower SA and all-cause medical costs associated with the use of VAR versus NRT-P resulted in savings in all-cause total costs and, among adherent patients, potentially offset the high pharmacy costs of VAR.
Funding
Pfizer, Inc.
https://ift.tt/2Bu0uY5
Clostridium difficile colitis in the setting of subacute thyroiditis: the chicken or the egg
Subacutethyroiditis is a self-limited inflammatory condition commonly of viral aetiology, that manifests through phases of thyroid hormone changes over a 6–8 month period. A 24-year-old active duty military man, undergoing treatment for recurrent Clostridiumdifficile infection, presented for clinical evaluation and was found to have a thyroid stimulating hormone level of 0.003 mg/dL. Further labs revealed a normal T4, elevated T3 at 5.0 pg/mL and elevated C reactive protein at 3.69 mg/L. The patient was followed with monthly labs and the abnormal thyroid stimulating hormone and triiodothyronine levels resolved after the completion of his C. difficile treatment. While subacute thyroiditis has historically been due to viral causes, rarely do we see this condition associated with an intestinal bacterial source.
https://ift.tt/2ExydCP
Splenectomy for breast carcinoma diffusely metastatic to the spleen presenting as severe transfusion-dependent anaemia and thrombocytopaenia
We report a 48-year-old woman with metastatic infiltrating lobular carcinoma of the breast. Though her metastatic disease remained stable, she was repeatedly admitted for symptomatic anaemia and treated by red blood cell and platelet transfusions with increasing frequency as time elapsed. Abdominal examination and ultrasound revealed splenomegaly (27 cm span). A bone marrow biopsy showed fibrosis and foci of metastatic carcinoma. Splenectomy ameliorated her transfusion-dependent anaemia and thrombocytopaenia. Histopathology revealed multiple foci of metastatic carcinoma and scattered foci of extramedullary haematopoiesis. Differential diagnosis of anaemia and thrombocytopaenia in patients with cancer include bone morrow involvement by cancer cells, iron-deficiency anaemia, microangiopathies and chemotherapy suppression of haematopoiesis. Splenic involvement with cancer is common in patients with multivisceral disease. Many may regard transfusion-dependent severe anaemia and thrombocytopaenia as an end-stage disease in these patients. Nevertheless, palliative splenectomy should be considered in patients with possible hypersplenism who will otherwise survive for a relatively prolonged period of time.
https://ift.tt/2EtOBV6
Role of the body mass index in the genesis of ascites in ovarian cancer: a forensic case and review of the literature
The ovarian tumour is the seventh female cancer for incidence. In the advanced stages of cancer, tumour cells nourish on the peritoneal serous causing carcinomatosis and peritoneal function abnormalities with liquid build-up inside it. Ascites from peritoneal carcinomatosis is common in patients with ovarian cancer. An obese woman suffering from ovarian cancer was found dead in her home from secondary cardio-respiratory arrest due to Multiple Organ Failure (MOF). An autopsy was performed. The abdominal incision showed an ascitic fluid outflow about 20 litres in volume and a flood about one metre and half. An association between obesity and intraperitoneal fluid volume secondary to peritoneal carcinomatosis has been demonstrated. This finding could improve the prognosis of patients through actions aimed to reduce body weight.
https://ift.tt/2EDciej
Prenatal diagnosis of cervical ribs by three-dimensional ultrasound in a foetus with a herniated Dandy-Walker cyst
We present a case report of a foetus with a herniated Dandy-Walker cyst and bilateral rudimentary cervical ribs. The cervical ribs were visualised prenatally by three-dimensional ultrasound and confirmed by post-termination radiography. The prevalence of cervical ribs is higher in deceased fetuses and neonates with or without structural abnormalities compared with healthy individuals and might be regarded as a marker of disadvantageous fetal development. We demonstrate that evaluation of the fetal vertebral pattern by three-dimensional ultrasonography, including the cervical region, is feasible and could provide valuable information regarding fetal and neonatal prognosis.
https://ift.tt/2EtOqco
Complication of dislodged gastrostomy Foley catheter: antegrade migration into small bowel
A 65-year-old man with dysphagia underwent placement of a percutaneous endoscopic gastrostomy tube. He was cared for at a nursing facility where the tube became dislodged and was replaced with similar size Foley catheter. Patient was brought to the hospital with dislodged feeding Foley but none was found at the bedside. Diagnostic workup revealed antegrade migration of the catheter into the small bowel. Push enteroscopy was unsuccessful in retrieving the catheter because it was too far distal. Patient was observed for a total of 7 days. Due to lack of progress with conservative measures, a colonoscopy was performed to extract the catheter, thus avoiding the need for more invasive surgical measures. If a Foley catheter is used as a gastrostomy tube, it should be replaced with a dedicated feeding tube as quickly as possible and should always be affixed to the skin to prevent antegrade migration and associated complications.
https://ift.tt/2EDp8JU
Role of Single-Agent Methotrexate as a Neoadjuvant Chemotherapy in Oral Cavity Cancers
Abstract
Oral cancers are the most common cancer in India due to tobacco abuse in the form of chewing, smoking, and inhalation. Majority of these patients present late at advanced disease stage. Such patients have significant morbidity irrespective of the intent of treatment; the survival rate is very poor. To improve loco-regional control and survival, neoadjuvant chemotherapy has been started in many centers all over the world. To study the effect of injecting methotrexate as a single agent in (1) down-staging and increasing operability of oral cancers, (2) need for reconstructive surgery, and (3) recurrence. A total of 50 patients with biopsy-proven oral malignancy were selected over a period of 2 years from August 2014 to August 2016 for the study. Patients were subjected to weekly dose of injecting methotrexate 1 mg/kg given intravenously for 6 weeks. All patients underwent surgery after completing 6 cycles of methotrexate. A total 50 patients were started on inj. methotrexate of which 9 patients did not complete neoadjuvant chemotherapy. 53.7% of patients showed more than 50% decrease in tumor size. 29.26% of patients showed complete disappearance of cervical lymph nodes and 31.7% of patients showed more than 50% decrease in size of cervical lymph nodes. 48.78% of patients were managed with wide local excision with primary closure, decreasing the need of reconstructive surgery. 94.74% of patients did not show any recurrence in follow-up period of 1 year. Single agent methotrexate is effective in down-staging oral cancers, improving operability and decreasing morbidity and recurrence among patients.
https://ift.tt/2URn45T
Slower alpha rhythm associates with poorer seizure control in epilepsy
Abstract
Objective
Slowing and frontal spread of the alpha rhythm have been reported in multiple epilepsy syndromes. We investigated whether these phenomena are associated with seizure control.
Methods
We prospectively acquired resting‐state electroencephalogram (EEG) in 63 patients with focal and idiopathic generalized epilepsy (FE and IGE) and 39 age‐ and gender‐matched healthy subjects (HS). Patients were divided into good and poor (≥4 seizures/12 months) seizure control groups based on self‐reports and clinical records. We computed spectral power from 20‐sec EEG segments during eyes‐closed wakefulness, free of interictal abnormalities, and quantified power in high‐ and low‐alpha bands. Analysis of covariance and post hoc t‐tests were used to assess group differences in alpha‐power shift across all EEG channels. Permutation‐based statistics were used to assess the topography of this shift across the whole scalp.
Results
Compared to HS, patients showed a statistically significant shift of spectral power from high‐ to low‐alpha frequencies (effect size g = 0.78 [95% confidence interval 0.43, 1.20]). This alpha‐power shift was driven by patients with poor seizure control in both FE and IGE (g = 1.14, [0.65, 1.74]), and occurred over midline frontal and bilateral occipital regions. IGE exhibited less alpha power shift compared to FE over bilateral frontal regions (g = −1.16 [−0.68, −1.74]). There was no interaction between syndrome and seizure control. Effects were independent of antiepileptic drug load, time of day, or subgroup definitions.
Interpretation
Alpha slowing and anteriorization are a robust finding in patients with epilepsy and might represent a generic indicator of seizure liability.
https://ift.tt/2GqEwuE
Immune cell infiltration as a biomarker for the diagnosis and prognosis of stage I–III colon cancer
Abstract
Tumour-infiltrating immune cells are a source of important prognostic information for patients with resectable colon cancer. We developed a novel immune model based on systematic assessments of the immune landscape inferred from bulk tumor transcriptomes of stage I–III colon cancer patients. The "Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)" algorithm was used to estimate the fraction of 22 immune cell types from six microarray public datasets. The random forest method and least absolute shrinkage and selection operator model were then used to establish immunoscores for diagnosis and prognosis. By comparing immune cell compositions in samples of 870 colon cancer patients and 70 normal controls, we constructed a diagnostic model, designated the diagnostic immune risk score (dIRS), that showed high specificity and sensitivity in both the training [area under the curve (AUC) = 0.98, p < 0.001] and validation (AUC 0.96, p < 0.001) sets. We also established a prognostic immune risk score (pIRS) that was found to be an independent prognostic factor for relapse-free survival in every series (training: HR 2.23; validation: HR 1.65; entire: HR 2.01; p < 0.001 for all), which showed better prognostic value than TNM stage. In addition, integration of the pIRS with clinical characteristics in a composite nomogram showed improved accuracy of relapse risk prediction, providing a higher net benefit than TNM stage, with well-fitted calibration curves. The proposed dIRS and pIRS models represent promising novel signatures for the diagnosis and prognosis prediction of colon cancer.
https://ift.tt/2S7EhpN
Hydrocephalus in cblC type methylmalonic acidemia
Abstract
Methylmalonic acidemia (MMA) is a typical type of organic acidemia caused by defects in methylmalonyl-CoA mutase or adenosyl-cobalamin synthesis. Hydrocephalus (HC), results from an imbalance between production and absorption of cerebrospinal fluid (CSF), causeing enlarged cerebral ventricles and increased intracranial pressure, is a condition that requires urgent clinical decision-making. MMA without treatment could result in brain damage. However, HC in MMA was rarely reported. In this study, 147 MMA were identified from 9117 high risk children by gas chromatography mass spectrometry (GC/MS) for organic acidurias screening in urine samples and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for amino acids detection in blood samples. Totally 10 cases with MMA and HC were determined by brain MRI/CT, as well as gene mutation testing either by high throughput sequencing or Sanger sequencing. Besides, homocysteine was also analyzed for the 10 MMA with HC. Out of them, 9 cases carry out compound heterozygous mutations or homozygous mutation in MMACHC gene, and 1 case has MUTmutation. The mutation c.609G > A in MMACHC was the most common in the cbl type patients. Although MMA has a high incidence in Shandong province of China, especially cblC type. All of the 10 patients were not correctly diagnosed before developing HC. As a result, when a child develops progressive and refractory HC, the screening for inherited metabolic diseases should be immediately conducted.
https://ift.tt/2EAU6SF
Immune cell infiltration as a biomarker for the diagnosis and prognosis of stage I–III colon cancer
Abstract
Tumour-infiltrating immune cells are a source of important prognostic information for patients with resectable colon cancer. We developed a novel immune model based on systematic assessments of the immune landscape inferred from bulk tumor transcriptomes of stage I–III colon cancer patients. The "Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)" algorithm was used to estimate the fraction of 22 immune cell types from six microarray public datasets. The random forest method and least absolute shrinkage and selection operator model were then used to establish immunoscores for diagnosis and prognosis. By comparing immune cell compositions in samples of 870 colon cancer patients and 70 normal controls, we constructed a diagnostic model, designated the diagnostic immune risk score (dIRS), that showed high specificity and sensitivity in both the training [area under the curve (AUC) = 0.98, p < 0.001] and validation (AUC 0.96, p < 0.001) sets. We also established a prognostic immune risk score (pIRS) that was found to be an independent prognostic factor for relapse-free survival in every series (training: HR 2.23; validation: HR 1.65; entire: HR 2.01; p < 0.001 for all), which showed better prognostic value than TNM stage. In addition, integration of the pIRS with clinical characteristics in a composite nomogram showed improved accuracy of relapse risk prediction, providing a higher net benefit than TNM stage, with well-fitted calibration curves. The proposed dIRS and pIRS models represent promising novel signatures for the diagnosis and prognosis prediction of colon cancer.
https://ift.tt/2S7EhpN
Efficacy and safety of EUS-guided liver biopsy: a systematic review and meta-analysis
EUS-guided liver biopsy (LB) is an emerging technique over conventional percutaneous (PC) or transjugular (TJ) approaches. Recent studies have reported that EUS-guided LB may have a better safety profile than PC LB or TJ LB without compromising diagnostic yield, and the outcomes are varied with respect to the types of biopsy needles. We performed a systematic review and meta-analysis to estimate the diagnostic yield, specimen adequacy, and adverse events associated with EUS-guided LB.
https://ift.tt/2rJjNrF
Re: “Drug Use and Misuse in the Mountains: A UIAA MedCom Consensus Guide for Medical Professionals” by Donegani et al. (High Alt Med Biol 17:157–184)
High Altitude Medicine &Biology, Ahead of Print.
https://ift.tt/2Ls9YaA
Long-term risk of screen-detected and interval breast cancer after false-positive results at mammography screening: joint analysis of three national cohorts
Long-term risk of screen-detected and interval breast cancer after false-positive results at mammography screening: joint analysis of three national cohorts
Long-term risk of screen-detected and interval breast cancer after false-positive results at mammography screening: joint analysis of three national cohorts, Published online: 19 December 2018; doi:10.1038/s41416-018-0358-5
Long-term risk of screen-detected and interval breast cancer after false-positive results at mammography screening: joint analysis of three national cohortshttps://ift.tt/2QCARi1
Kidney stones and the risk of renal cell carcinoma and upper tract urothelial carcinoma: the Netherlands Cohort Study
Kidney stones and the risk of renal cell carcinoma and upper tract urothelial carcinoma: the Netherlands Cohort Study
Kidney stones and the risk of renal cell carcinoma and upper tract urothelial carcinoma: the Netherlands Cohort Study, Published online: 19 December 2018; doi:10.1038/s41416-018-0356-7
Kidney stones and the risk of renal cell carcinoma and upper tract urothelial carcinoma: the Netherlands Cohort Studyhttps://ift.tt/2Bx56Nc
Whole-colon investigation vs. flexible sigmoidoscopy for suspected colorectal cancer based on presenting symptoms and signs: a multicentre cohort study
Whole-colon investigation vs. flexible sigmoidoscopy for suspected colorectal cancer based on presenting symptoms and signs: a multicentre cohort study
Whole-colon investigation vs. flexible sigmoidoscopy for suspected colorectal cancer based on presenting symptoms and signs: a multicentre cohort study, Published online: 19 December 2018; doi:10.1038/s41416-018-0335-z
Whole-colon investigation vs. flexible sigmoidoscopy for suspected colorectal cancer based on presenting symptoms and signs: a multicentre cohort studyhttps://ift.tt/2QGqMk0
Alterations in serum amino-acid profile in the progression of colorectal cancer: associations with systemic inflammation, tumour stage and patient survival
Alterations in serum amino-acid profile in the progression of colorectal cancer: associations with systemic inflammation, tumour stage and patient survival
Alterations in serum amino-acid profile in the progression of colorectal cancer: associations with systemic inflammation, tumour stage and patient survival, Published online: 19 December 2018; doi:10.1038/s41416-018-0357-6
Alterations in serum amino-acid profile in the progression of colorectal cancer: associations with systemic inflammation, tumour stage and patient survivalhttps://ift.tt/2BwVfqj
Molecular characterisation of aromatase inhibitor-resistant advanced breast cancer: the phenotypic effect of ESR1 mutations
Molecular characterisation of aromatase inhibitor-resistant advanced breast cancer: the phenotypic effect of ESR1 mutations
Molecular characterisation of aromatase inhibitor-resistant advanced breast cancer: the phenotypic effect of <i>ESR1</i> mutations, Published online: 19 December 2018; doi:10.1038/s41416-018-0345-x
Molecular characterisation of aromatase inhibitor-resistant advanced breast cancer: the phenotypic effect of ESR1 mutationshttps://ift.tt/2QGU7Li
A Strategy To Exploit Surrogate Sire Technology in Livestock Breeding Programs
In this work, we performed simulations to develop and test a strategy for exploiting surrogate sire technology in animal breeding programs. Surrogate sire technology allows the creation of males that lack their own germline cells, but have transplanted spermatogonial stem cells from donor males. With this technology, a single elite male donor could give rise to huge numbers of progeny, potentially as much as all the production animals in a particular time period. One hundred replicates of various scenarios were performed. Scenarios followed a common overall structure but differed in the strategy used to identify elite donors and how these donors were used in the product development part. The results of this study showed that using surrogate sire technology would significantly increase the genetic merit of commercial sires, by as much as 6.5 to 9.2 years' worth of genetic gain compared to a conventional breeding program. The simulations suggested that a strategy involving three stages (an initial genomic test followed by two subsequent progeny tests) was the most effective of all the strategies tested. The use of one or a handful of elite donors to generate the production animals would be very different to current practice. While the results demonstrate the great potential of surrogate sire technology there are considerable risks but also other opportunities. Practical implementation of surrogate sire technology would need to account for these.
https://ift.tt/2SexT08
Repeats of Unusual Size in Plant Mitochondrial Genomes: Identification, Incidence and Evolution
Plant mitochondrial genomes have excessive size relative to coding capacity, a low mutation rate in genes and a high rearrangement rate. They also have abundant non-tandem repeats often including pairs of large repeats which cause isomerization of the genome by recombination, and numerous repeats of up to several hundred base pairs that recombine only when the genome is stressed by DNA damaging agents or mutations in DNA repair pathway genes. Early work on mitochondrial genomes led to the suggestion that repeats in the size range from several hundred to a few thousand base pair are underrepresented. The repeats themselves are not well-conserved between species, and are not always annotated in mitochondrial sequence assemblies. We systematically identified and compared these repeats, which are important clues to mechanisms of DNA maintenance in mitochondria. We developed a tool to find and curate non-tandem repeats larger than 50bp and analyzed the complete mitochondrial sequences from 157 plant species. We observed an interesting difference between taxa: the repeats are larger and more frequent in the vascular plants. Analysis of closely related species also shows that plant mitochondrial genomes evolve in dramatic bursts of breakage and rejoining, complete with DNA sequence gain and loss. We suggest an adaptive explanation for the existence of the repeats and their evolution.
https://ift.tt/2A8hx1R
Composition of the Survival Motor Neuron (SMN) Complex in Drosophila melanogaster
Spinal Muscular Atrophy (SMA) is caused by homozygous mutations in the human survival motor neuron 1 (SMN1) gene. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. SMN is part of an oligomeric complex with core binding partners, collectively called Gemins. Biochemical and cell biological studies demonstrate that certain Gemins are required for proper snRNP assembly and transport. However, the precise functions of most Gemins are unknown. To gain a deeper understanding of the SMN complex in the context of metazoan evolution, we investigated its composition in Drosophila melanogaster. Using transgenic flies that exclusively express Flag-tagged SMN from its native promoter, we previously found that Gemin2, Gemin3, Gemin5, and all nine classical Sm proteins, including Lsm10 and Lsm11, co-purify with SMN. Here, we show that CG2941 is also highly enriched in the pulldown. Reciprocal co-immunoprecipitation reveals that epitope-tagged CG2941 interacts with endogenous SMN in Schneider2 cells. Bioinformatic comparisons show that CG2941 shares sequence and structural similarity with metazoan Gemin4. Additional analysis shows that three other genes (CG14164, CG31950 and CG2371) are not orthologous to Gemins 6-7-8, respectively, as previously suggested. In D. melanogaster, CG2941 is located within an evolutionarily recent genomic triplication with two other nearly identical paralogous genes (CG32783 and CG32786). RNAi-mediated knockdown of CG2941 and its two close paralogs reveals that Gemin4 is essential for organismal viability.
https://ift.tt/2SexPNW
ER translocation of the MAPK pathway drives therapy resistance in BRAF mutant melanoma [Research Articles]
Resistance to BRAF and MEK inhibitor (BRAFi+MEKi) in BRAF mutant tumors occurs through heterogeneous mechanisms, including ERK reactivation and autophagy. Little is known about the mechanisms by which ERK reactivation, or autophagy are induced by BRAFi+MEKi. Here we report that in BRAF mutant melanoma cells, BRAFi+MEKi induced SEC61-dependent ER translocation of the MAPK pathway via GRP78 and KSR2. Inhibition of ER translocation prevented ERK reactivation and autophagy. Following ER translocation, ERK exited the ER and was rephosphorylated by PERK. Reactivated ERK phosphorylated ATF4, which activated cytoprotective autophagy. Upregulation of GRP78 and phosphorylation of ATF4 was detected in tumors of patients resistant to BRAFi+MEKi. ER translocation of the MAPK pathway was demonstrated in therapy-resistant patient-derived xenografts. Expression of a dominant negative ATF4 mutant conferred sensitivity to BRAFi+MEKi in vivo. This mechanism reconciles two major targeted therapy resistance pathways and identifies druggable targets, whose inhibition would likely enhance the response to BRAFi+MEKi.
https://ift.tt/2EC9Wwj
Binimetinib plus Gemcitabine and Cisplatin Phase I/II Trial in Patients with Advanced Biliary Cancers
Purpose: Mutations in the RAS/RAF/MEK/ERK signaling pathway are commonly found in biliary tract cancer (BTC). Binimetinib, a selective inhibitor of MEK1/2, has single-agent activity. Preclinical data support binimetinib combination with chemotherapy, when given in an interrupted dosing schedule.
Experimental Design: A phase I/II trial evaluated binimetinib in combination with gemcitabine and cisplatin in patients with untreated advanced BTC. The primary endpoints were to determine the MTD (phase I), and PFS 6 and RR (phase II). Tumor tissue for targeted gene sequencing and blood samples for peripheral blood pERK expression were evaluated. Patients received oral binimetinib twice daily with gemcitabine and cisplatin on day 8 and 15 of a 21-day cycle. Binimetinib was held for 2 days prior to and on day of each chemotherapy treatment.
Results: Twelve patients enrolled in the phase I showed the MTD of binimetinib at 45 mg orally twice daily with gemcitabine 800 and cisplatin 20 mg/m2. Twenty-nine patients were treated in the phase II. Six patients treated at MTD in phase I were evaluable as part of phase II. PFS 6 months was 54% and RR was 36%. Median overall survival was 13.3 months (95% CI, 9.8–16.5). MSK-IMPACT 410-gene panel showed aberrations in the RAS–RAF–MEK–ERK pathway and mutations in PIK3CA, AKT2, PIK3CG, BRAF, and MAP3K1 in responding patients.
Conclusions: Binimetinib with gemcitabine and cisplatin did not show an improvement in PFS 6 and RR. Molecular profiling may help select patients who may benefit from this triplet therapy, which is not planned at this time.
https://ift.tt/2Ev7cQv
Arylsulfonamide 64B inhibits hypoxia/HIF-induced expression of c-Met and CXCR4 and reduces primary tumor growth and metastasis of uveal melanoma
Purpose: Uveal melanoma (UM) is the most prevalent and lethal intraocularmalignancy in adults. Here, we examined the importance of hypoxia in UM growth and tested the anti-tumor effects of arylsulfonamide 64B, an inhibitor of the hypoxia-induced factor (HIF) pathway in animal models of UM and investigated the related mechanisms. Experimental Design: UM cells were implanted in the uvea of mice eyes and mice systemically treated with 64B. Drug effect on primary eye tumor growth, circulating tumor cells, metastasis formation in liver and survival were examined. 64B effects on UM cell growth, invasion and hypoxia-induced expression of C-X-C chemokine receptor type 4 (CXCR4) and mesenchymal-epithelial transition factor (c-Met)were measured. Luciferase reporter assays, chromatin immunoprecipitation, co-immunoprecipitation and cellular thermal shift assays were used to determine how 64B interferes with the HIF transcriptional complex. Results: Systemic administration of 64B had potent anti-tumor effects against UM in several orthotopic mouse models, suppressing UM growth in the eye (~70% reduction) and spontaneous liver metastasis (~50% reduction), and extending mice survival (p< 0.001) while being well tolerated. 64B inhibited hypoxia-induced expression of CXCR4 and c-Met,two key drivers of tumor invasion and metastasis. 64B disrupted HIF-1 complex by interfering with HIF-1α binding to p300/CBP co-factors, reducing p300 recruitment to the METand CXCR4gene promoters. 64B could thermo-stabilize p300, supporting direct 64B binding to p300. Conclusions: Our pre-clinical efficacy studies support the further optimization of the 64B chemical scaffold towards a clinical candidate for the treatment of UM.
https://ift.tt/2EE67XE
A Phase II Study of Talazoparib After Platinum or Cytotoxic Nonplatinum Regimens in Patients With Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO)
Purpose: To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast cancer (aBC). Experimental Design: ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of talazoparib (1 mg/day) in germline BRCA mutation carriers with a response to prior platinum with no progression on or within 8 weeks of the last platinum dose (cohort 1) or ≥3 platinum-free cytotoxic regimens (cohort 2) for aBC. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment. Results: We enrolled 84 patients (cohort 1, n = 49; cohort 2, n = 35) from May 2014 to February 2016. Median age was 50 (range, 31-75) years. Triple-negative breast cancer incidence was 59% (cohort 1) and 17% (cohort 2). Median number of prior cytotoxic regimens for aBC was two and four, respectively. Confirmed ORR was 21% (95% CI, 10 to 35) (cohort 1) and 37% (95% CI, 22 to 55) (cohort 2). Median duration of response was 5.8 and 3.8 months, respectively. Confirmed ORR was 23% (BRCA1), 33% (BRCA2), 26% (TNBC) and 29% (hormone receptor positive). The most common allgrade adverse events (AEs) included anemia (52%), fatigue (45%), and nausea (42%). Talazoparib-related AEs led to drug discontinuation in three (4%) patients. In an exploratory analysis, longer platinum-free interval was associated with higher response rate in cohort 1 (0% ORR with interval <8 weeks; 47% ORR with interval >6 months). Conclusions: Talazoparib exhibited promising antitumor activity in patients with aBC and germline BRCA mutation.
https://ift.tt/2EE65Pw
Phase IB Dose-Escalation and Expansion Study of AKT kinase inhibitor Afuresertib with Carboplatin and Paclitaxel in Recurrent Platinum-Resistant Ovarian Cancer
Purpose: Preclinically, AKT kinase inhibition restores drug sensitivity in platinum-resistant tumors.Here the pan-AKT kinase inhibitor afuresertib was given in combination with paclitaxel and carboplatin (PC) in patients with recurrent platinum-resistant epithelial ovarian cancer (PROC) and primary platinum refractory ovarian cancer (PPROC). Experimental Design: Part I was a combination 3+3 dose-escalation study for recurrent ovarian cancer. Patients received daily continuous oral afuresertib at 50-150 mg/day with three-weekly intravenous paclitaxel (175 mg/m2) and carboplatin (AUC5) for 6 cycles followed by maintenance afuresertib at 125mg/day until progression or toxicity. Part II was a single arm evaluation of the clinical activity of this combination in recurrent PROC (Cohort A) or PPROC (Cohort B). Patients received oral afuresertib at the maximum tolerated dose (MTD) defined in Part I in combination with PC for 6 cycles, followed by maintenance afuresertib. Primary endpoints were safety and tolerability of afuresertib in combination with PC (Part I, dose-escalation), and investigator-assessed overall response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Part II). Results: Twenty-nine patients enrolled into Part I, and 30 into Part II. Three dose-limiting toxicities (DLTs) of grade 3 rash were observed, one at 125mg and two at 150mg afuresertib. The MTD of afuresertib in combination with PC was therefore identified as 125 mg/day. (etc -see manuscript for full version)
https://ift.tt/2EE63Ho
YAP1-mediated CDK6 Activation Confers Radiation Resistance in Esophageal Cancer - Rationale for the combination of YAP1 and CDK4/6 inhibitors in Esophageal Cancer
Purpose: Esophageal cancer (EC) is a lethal disease that is often resistant to therapy. Alterations of YAP1 and CDK6 are frequent in EC. Deregulation of both molecules may be responsible for therapy resistance. Experimental Design: Expression of YAP1 and CDK6 were examined in EC cells and tissues using immunoblotting and immunohistochemistry. YAP1 expression was induced in EC cells to examine YAP1-mediated CDK6 activation and its association with radiation resistance. Pharmacological and genetic inhibitions of YAP1 and CDK6 were performed to dissect the mechanisms and assess the antitumor effects in vitro and in vivo. Results: YAP1 expression was positively associated with CDK6 expression in resistant EC tissues and cell lines. YAP1 overexpression upregulated CDK6 expression, transcription, and promoted radiation resistance; whereas treatment with the YAP1 inhibitor, CA3, strongly suppressed YAP1 and CDK6 overexpression, reduced Rb phosphorylation as well as sensitized radiation resistant/YAP1high EC cells to irradiation. CDK4/6 inhibitor, LEE011, and knock down of CDK6 inhibited expression of YAP1 and sensitized resistant EC cells to irradiation indicating a positive feed-forward regulation of YAP1 by CDK6. Additionally, suppression of both the YAP1 and CDK6 pathways by the combination of CA3 and LEE011 significantly reduced EC cell growth, CSC population (ALDH1+ and CD133+), sensitized cells to irradiation and showed a strong anti-tumor effect in vivo against radiation resistant EC cells. Conclusions: Our results document that a positive crosstalk of YAP1 and CDK6 confers radiation resistance to EC cells. Targeting both YAP1 and CDK6 pathways could be novel therapeutic strategies to overcome resistance in EC.
https://ift.tt/2Ev7bvV
PRE-surgical Metformin In Uterine Malignancy (PREMIUM): a multi-center, randomized double-blind, placebo-controlled phase 3 trial
Purpose Endometrioid endometrial cancer is strongly associated with obesity and insulin resistance. Metformin, an insulin sensitizer, reduces endometrial tumor growth in vitro. Pre-surgical window studies allow rapid in vivo assessment of anti-tumor activity. Previous window studies found metformin reduced endometrial cancer proliferation but these lacked methodological rigor. PREMIUM measured the anti-proliferative effect of metformin in vivo using a robust window study design. Patients and Methods: A multicenter, double-blind, placebo-controlled trial randomized women with atypical hyperplasia or endometrioid endometrial cancer to receive metformin (850mg daily for three days, and twice daily thereafter) or placebo for 1-5 weeks until surgery. The primary outcome was post-treatment immunohistochemical expression of Ki-67. Secondary outcomes investigated the effect of metformin on markers of the PI3K-Akt-mTOR and insulin signaling pathways and obesity. Results: Eighty-eight women received metformin (n=45) or placebo (n=43) and completed treatment. There was no overall difference in post-treatment Ki-67 between the metformin and placebo arms, in an ANCOVA analysis adjusting for baseline Ki-67 expression (mean difference -0·57%, 95% CI -7·57%, 6·42%, p=0·87). Metformin did not affect expression of markers of the PI3K-Akt-mTOR or insulin signaling pathways, and did not result in weight loss. Conclusions: Short-term treatment with standard diabetic doses of metformin does not reduce tumor proliferation in women with endometrioid endometrial cancer awaiting hysterectomy. This study does not support a biological effect of metformin in endometrial cancer and casts doubt on its potential application in the primary and adjuvant treatment settings.
https://ift.tt/2EE62TQ
5 tips to successfully train EMS staff on updated patient care guidelines
Effective training will ensure you and your field personnel are ready to implement the new patient treatment protocols
https://ift.tt/2S6yfFO
Doxycycline Added to Prednisolone in Outpatient-Treated Acute Exacerbations of COPD: A Cost-Effectiveness Analysis Alongside a Randomised Controlled Trial
Abstract
Background
Most patients with mild to severe chronic obstructive pulmonary disease (COPD) experience exacerbations, which are also associated with increased healthcare costs. Despite limited evidence of antibiotics' benefits for exacerbations in outpatients, antibiotics are frequently prescribed. The aim of this study was to investigate whether doxycycline added to prednisolone is cost-effective compared to placebo plus prednisolone for the treatment of COPD acute exacerbations.
Methods
An economic evaluation from the societal perspective was performed alongside a 2-year randomised trial in 301 COPD patients in the Netherlands. The primary outcome was cost per quality-adjusted life year (QALY). The secondary outcome was cost per exacerbation prevented. Healthcare utilisation and loss of productivity were measured using retrospective questionnaires and clinical report forms. Missing data were imputed using multiple imputations by chained equations. Bootstrapping was employed to estimate statistical uncertainty surrounding cost-effectiveness outcomes. A sensitivity analysis from the healthcare perspective was performed.
Results
On average, costs in the doxycycline group were €898 higher than in the placebo group [95% confidence interval (CI) − 2617 to 4409] for the 2 years of follow-up. QALY values were higher in the doxycycline group (0.03; 95% CI − 0.00 to 0.06), but patients in this group suffered 0.01 more exacerbations than patients in the placebo group (95% CI − 0.14 to 0.11). Cost-effectiveness acceptability curves showed that the probability of doxycycline being cost-effective compared to placebo was 61% and 43% at a willingness-to-pay threshold of €34,000 per QALY and per exacerbation avoided, respectively. The sensitivity analysis showed similar results from the healthcare system perspective.
Conclusions
In patients with mild to severe COPD treated for exacerbations in an outpatient setting, doxycycline added to prednisolone is not cost-effective compared to prednisolone plus placebo over a 2-year period.
https://ift.tt/2QH4HC8
Hospitalizations Up for Homeless From 2007 to 2013
TUESDAY, Dec. 18, 2018 -- From 2007 to 2013, hospitalizations among homeless individuals increased and were most frequently for mental illness and substance use disorder, according to a study published in the January issue of Medical Care. Rishi K....
https://ift.tt/2SUMcGX
Delivery Mode Tied to Pelvic Floor Disorder Risk Post-Childbirth
TUESDAY, Dec. 18, 2018 -- After childbirth, the risk for pelvic floor disorders varies by delivery mode, according to a study published in the Dec. 18 issue of the Journal of the American Medical Association. Joan L. Blomquist, M.D., from the...
https://ift.tt/2CmmDJe
Opioids Offer Small Improvement in Pain, Physical Function
TUESDAY, Dec. 18, 2018 -- Opioid use is associated with small improvements in pain and physical functioning in patients with chronic noncancer pain, according to research published in the Dec. 18 issue of the Journal of the American Medical...
https://ift.tt/2SXfkgC
Exercise Linked to Reduced Mortality for Patients With Cancer
TUESDAY, Dec. 18, 2018 -- For patients with cancer, participation in prediagnosis and postdiagnosis recreational physical activity is associated with reduced mortality, according to a study published online Nov. 28 in Cancer Causes &...
https://ift.tt/2ClhWiZ
'Aggressive Steps' Needed to Stop Adolescent Use of E-Cigarettes
TUESDAY, Dec. 18, 2018 -- "Aggressive steps" must be taken by parents, teachers, health providers, and government officials to prevent children and teens from using electronic cigarettes, U.S. Surgeon General Jerome Adams, M.D., M.P.H., said in an...
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5 tips to successfully train EMS staff on updated patient care guidelines
Effective training will ensure you and your field personnel are ready to implement the new patient treatment protocols
https://ift.tt/2EBNkw0
Classified 2019 Advertising Rates & Information
Ads and complete payments must be received in writing by the issue's deadline date. These deadlines apply to insertions, cancellations, and changes.
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Calendar
▮ Health Care Coalition Response Leadership Course – 5. January 8–10, 2019. Anniston, AL. Contact: Rick Murray. Email: rmurray@acep.org. Url: www.acep.org. (23.50)
https://ift.tt/2rLozFo
Global Research Highlights
Editor's note: Annals has partnered with a small group of selected journals of international emergency medicine societies to share from each a highlighted research study, as selected monthly by their editors. Our goals are to increase awareness of our readership to research developments in the international emergency medicine literature, promote collaboration among the selected international emergency medicine journals, and support the improvement of emergency medicine world-wide, as described in the WAME statement at https://ift.tt/2dmKsCb.
https://ift.tt/2Ls1yQw
Commentary
Contact lens–related eye infections appear to be greatly underreported.1 Although there were approximately 1 million outpatient and ED visits for keratitis in 2010, only 1,075 reports of contact-related corneal infections were provided from any source to MedWatch, the official FDA Safety Information and Adverse Event Reporting Program.2 Microbial keratitis can require prolonged treatment courses and may lead to permanent visual impairment.3 This issue of the Morbidity and Mortality Weekly Report reports a case series of 6 patients with corneal infections for which sleeping in lenses was the primary risk factor for infection.
https://ift.tt/2Ls1vEk
Corneal Infections Associated With Sleeping in Contact Lenses—Six Cases, United States, 2016-2018
[Centers for Disease Control and Prevention. Corneal infections associated with sleeping in contact lenses—six cases, United States, 2016-2018. MMWR Morb Mortal Wkly Rep. 2018;67:877-881.]
https://ift.tt/2rM5K4R
A Balancing Act
As the nation watches helplessly each time a mass shooting takes place, emergency physicians jump into action, caring for the wounded. Once it's over, they are among those trying to make sense of gun violence, wondering what physicians could possibly do to help stop the carnage.
https://ift.tt/2Ls1sZa
Keeping Your Patients Alive—for Better or Worse—Until They Reach the Emergency Department
Wang HE, Schmicker RH, Daya MR, et al. Effect of a strategy of initial laryngeal tube insertion vs endotracheal intubation on 72-hour survival in adults with out-of-hospital cardiac arrest: a randomized clinical trial. JAMA. 2018;320:769-778.
https://ift.tt/2rSYCnr
In Shock: My Journey From Death to Recovery and the Redemptive Power of Hope
"We aren't trained to see our patients. We are trained to see pathology…. [T]he true relationship is forged between the doctor and the disease…. [T]he patients carrying the diagnosis are at risk of becoming an accessory to the whole affair, just another vector." (p 26).
https://ift.tt/2LouysE
Safety of a Brief Emergency Department Observation Protocol for Patients With Presumed Fentanyl Overdose
We read with interest the article by Scheuermeyer et al.1 Although the study sought to fulfill a needed gap in regard to the management of patients with fentanyl overdose, we have questions about certain aspects of it.
https://ift.tt/2rL2uGU
In reply:
Our team thanks Santos et al1 for their commentary in regard to the management of emergency department patients with presumed fentanyl overdose. They raise the important point that, because of the low postoverdose mortality risk, any observation window for such patients may be questionable. Boyer2 suggested a 4- to 6-hour observation period after naloxone resuscitation, but this is not supported by clear evidence in patients with fentanyl overdose. In therapeutic doses, fentanyl has a short duration of action because it is quickly redistributed out of the central nervous system into peripheral tissues before being quickly eliminated.
https://ift.tt/2Lnsq4t
In reply:
We appreciate the letter by Tran et al1 and essentially agree with their comments. Their first concern is the use of a decision rule validated in one population of subjects but applied to a population with potentially different characteristics. Although a derivation-validation study conducted with a population with minimal head injury would have been ideal, we neither had the resources to perform such a study nor believed such an effort was necessary. Risk factors for consequential head injury have been explored in many patient populations and clinical settings already2-4 and finding additional factors seemed unlikely.
https://ift.tt/2rLGuvo
Applicability of the Canadian CT Head Rule in Minimal Head Injury
We applaud Davey et al1 for their study describing their use of the Canadian CT Head Rule with patients with minimal head injury. They generated interesting hypotheses in regard to this subgroup of patients (who do not experience loss of consciousness or transient confusion) compared with patients with minor head injury (who do). Although the authors acknowledged a number of study limitations, some were not taken into consideration, and questions remain.
https://ift.tt/2Ls1lNe
Young Male With Abdominal Pain
A 13-year-old boy presented to the emergency department (ED) after 4 days of abdominal pain without fever or bloody stool, although a year ago, he had had a similar episode and was medically treated for presumed appendicitis. He had normal vital signs but periumbilical and right lower quadrant tenderness; his WBC count and urinalysis results were normal. The emergency physician performed bedside ultrasonography, revealing the diagnosis (Figure 1).
https://ift.tt/2rIfA7R
Middle-Aged Man With Rash
A 55-year-old man with a history of hypertension presented to the emergency department (ED) with complaints of a bilateral lower extremity rash for 1 week (Figures 1 and 2). The patient initially noticed a spotted rash around his sock line, which he attributed to "ringworm." During the course of the next week, the lesions spread proximally and coalesced into a palpable rash. He denied preceding illness or use of any new soap or detergents. On review of systems, he did note a red tint to his urine but denied abdominal or joint pain.
https://ift.tt/2Ls1iB2
Elderly Man With Weight Loss and Groin Masses
A 62-year-old man presented to the emergency department with concerns about fatigue, weight loss, and a self-described "boil" on his left lower abdomen. He stated that the lesion appeared and became rapidly progressive during the preceding 3 months. Physical examination revealed a mildly wasted, elderly man with a 4-by-5-cm exophytic mass in the left inguinal fold (Figure 1) and contralateral firm adenopathy (Figure 2). Subsequent complete genitourinary examination revealed a 6-by-3-cm exophytic mass on the posterior, left scrotal wall (Figures 3 and 4) that was not offered in history by the patient.
https://ift.tt/2QCW6R1
Identification of Core Gene Biomarkers in Patients with Diabetic Cardiomyopathy
Diabetic cardiomyopathy (DCM) is a disorder of the myocardium in diabetic patients, which is one of the critical complications of diabetes giving rise to an increased mortality. However, the underlying mechanisms of DCM remain incompletely understood presently. This study was designed to screen the potential molecules and pathways implicated with DCM. GSE26887 involving 5 control individuals and 7 DCM patients was selected from the GEO database to identify the differentially expressed genes (DEGs). DAVID was applied to perform gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein-protein interaction (PPI) network was also constructed to visualize the interactions among these DEGs. To further validate significant genes and pathways, quantitative real-time PCR (qPCR) and Western blot were performed. A total of 236 DEGs were captured, including 134 upregulated and 102 downregulated genes. GO, KEGG, and the PPI network disclosed that inflammation, immune disorders, metabolic disturbance, and mitochondrial dysfunction were significantly enriched in the development of DCM. Notably, IL6 was an upregulated hub gene with the highest connectivity degree, suggesting that it may interact with a great many molecules and pathways. Meanwhile, SOCS3 was also one of the top 15 hub genes in the PPI network. Herein, we detected the protein level of STAT3 and SOCS3 in a mouse model with DCM. Western blot results showed that the protein level of SOCS3 was significantly lower while phosphorylated-STAT3 (P-STAT3) was activated in mice with DCM. In vitro results also uncovered the similar alterations of SOCS3 and P-STAT3 in cardiomyocytes and cardiac fibroblasts induced by high glucose (HG). However, overexpression of SOCS3 could significantly reverse HG-induced cardiomyocyte hypertrophy and collagen synthesis of cardiac fibroblasts. Taken together, our analysis unveiled potential biomarkers and molecular mechanisms in DCM, which could be helpful to the diagnosis and treatment of DCM.
https://ift.tt/2R2jhUe
ICOS/ICOSL upregulation mediates inflammatory response and endothelial dysfunction in type 2 diabetes mellitus
OBJECTIVE: ICOS/ICOSL plays a crucial part in various disease-mediated immune responses. However, the exact role of ICOS/ICOSL in type 2 diabetes mellitus (T2DM) development remains unexplored. This study aims to investigate the role of ICOS/ICOSL in the pathogenesis of T2DM.
MATERIALS AND METHODS: Human peripheral blood T-lymphocytes (CD3) and umbilical vein endothelial cells (HUVECs) were treated with high-glucose (HG) or advanced glycation end products (AGEs). A portion of CD3 cells was co-cultured with HUVECs and treated with different mediums or anti-ICOS mAbs. The ICOS/ICOSL and caspase-3 protein expression was measured by Western blotting. ELISA (enzyme-linked immunosorbent assay), MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and NOx production assays were respectively used to detect cytokines level, cell viability and the production of NOx.
RESULTS: HG and AGEs significantly upregulated ICOS/ICOSL expressions in T cells and HUVECs. T cell contact with HUVECs secreted more IFN-γ, IL-4, and IL-10 compared to non-contact cells, while cytokines from IL-6-, IL-1β-, and CM- (the conditioned medium) treated cells did not differ from the control. A significant increase of IL-8 and IL-6 was found in HUVECs under both contact and non-contact conditions vs. control cells. Similar results were also observed in the comparison between CM1- (T cell condition medium) or CM2- (co-culture condition medium) treated cells and control cells. However, CM1 and CM2 treatment significantly inhibited cell viability and increased caspase-3 and NOx production; blocking ICOS/ICOSL remarkably decreased cytokines secretion, enhanced cell viability and reduced caspase-3 and NOx production.
CONCLUSIONS: HG and AGEs cause T cell inflammatory response and vascular endothelial dysfunction by upregulating ICOS/ICOSL, which may be one of the possible mechanisms of cardiovascular complications development in T2DM patients.
L'articolo ICOS/ICOSL upregulation mediates inflammatory response and endothelial dysfunction in type 2 diabetes mellitus sembra essere il primo su European Review.
https://ift.tt/2Cl8Kvd
MicroRNA-29a enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis by targeting heme oxygenase-1
OBJECTIVE: To evaluate the effects of miR-29a on the high glucose (HG)-induced apoptosis and the correlation between miR-29a and heme oxygenase-1 (HO-1) and the underlying molecular mechanism.
MATERIALS AND METHODS: The cell apoptosis was analyzed by the flow cytometry, and the cells autophagy was evaluated using the transmission electron microscopy. Luciferase reporter assay was carried out to detect the correlation between miR-29a and HO-1. Besides, reverse transcription-PCR and Western blot were applied to detect the mRNA and protein levels.
RESULTS: The expression of miR-29a was significantly decreased in the HG-treated podocytes. Besides, miR-29a overexpression could promote cellular autophagy and significantly reduce HG-induced podocytes apoptosis. Moreover, HO-1 was a direct target of miR-29a and the pre-autophagy and the anti-apoptotic effects of miR-29a on HG-treated podocytes could be significantly reversed by the HO-1 siRNA administration.
CONCLUSIONS: MiR-29a functionally promoted podocytes autophagy and inhibited apoptosis through the HO-1dependent pathway in the HG condition.
L'articolo MicroRNA-29a enhances autophagy in podocytes as a protective mechanism against high glucose-induced apoptosis by targeting heme oxygenase-1 sembra essere il primo su European Review.
https://ift.tt/2T0zRBf
Challenges in Stratifying the Molecular Variability of Patient-Derived Colon Tumor Xenografts
Colorectal cancer (CRC) is the second most common cancer in Europe and a leading cause of death worldwide. Patient-derived xenograft (PDX) models maintain complex intratumoral biology and heterogeneity and therefore remain the platform of choice for translational drug discovery. In this study, we implanted 37 primary CRC tumors and five CRC cell lines into NU/J mice to develop xenograft models. Primary tumors and established xenografts were histologically assessed and surveyed for genetic variants and gene expression using a panel of 409 cancer-related genes and RNA-seq, respectively. More than half of CRC tumors (20 out of 37, 54%) developed into a PDX. Histological assessment confirmed that PDX grading, stromal components, inflammation, and budding were consistent with those of the primary tumors. DNA sequencing identified an average of 0.14 variants per gene per sample. The percentage of mutated variants in PDXs increased with successive passages, indicating a decrease in clonal heterogeneity. Gene Ontology analyses of 4180 differentially expressed transcripts (adj. p value
https://ift.tt/2SUpnmI
Advance directives, medical conditions, and preferences for end-of-life care among physicians: 12-year follow-up of the Johns Hopkins Precursors Study
Stability of preferences for life-sustaining treatment may vary depending on personal characteristics.
https://ift.tt/2R3cjht
Mechanical thrombectomy for Trousseau syndrome in a terminally ill cancer patient
Trousseau syndrome was first described by Armand Trousseau in 1865 and is characterized by hypercoagulation resulting from malignant tumors. This complication can markedly impact quality of life (QOL). This is the first report of a terminally ill patient who developed large-vessel occlusion stroke from Trousseau syndrome and underwent mechanical thrombectomy. A 75-year-old woman presented with stage IV ovarian cancer. Goals of care were transitioned to palliative care. The patient was hospitalized with vertebral compression fracture, and suddenly developed right hemiparesis and total aphasia during admission.
https://ift.tt/2GpT1yQ
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
