To develop a simple clinical decision rule (CDR) to identify people with knee osteoarthritis who are likely or unlikely to benefit from bone marrow aspirate concentrate (BMAC) injection.
A total of ...92 people with clinical and radiographic evidence of refractory knee osteoarthritis received a single intra-articular (IA) BMAC injection. Multiple logistic regression analysis was used to determine which combination of risk factors predicted BMAC responsiveness. A responder was defined as a person whose knee pain improved more than 15% from baseline 6 months post procedure.
The CDR demonstrated that those with lower pain levels, or high pain levels with previous surgery, could be predicted to benefit from a single IA BMAC injection.
A simple CDR containing three variables predicted responsiveness to a single IA knee BMAC injection with high accuracy. Further validation of the CDR is required prior to routine use in clinical practice.
Clostridium difficile (C. difficile) is an anaerobic gram-positive pathogen that is the leading cause of nosocomial bacterial infection globally. C. difficile infection (CDI) typically occurs after ...ingestion of infectious spores by a patient that has been treated with broad-spectrum antibiotics. While CDI is a toxin-mediated disease, transmission and pathogenesis are dependent on the ability to produce viable spores. These spores must become metabolically active (germinate) in order to cause disease. C. difficile spore germination occurs when spores encounter bile salts and other co-germinants within the small intestine, however, the germination signaling cascade is unclear. Here we describe a signaling role for Ca2+ during C. difficile spore germination and provide direct evidence that intestinal Ca2+ coordinates with bile salts to stimulate germination. Endogenous Ca2+ (released from within the spore) and a putative AAA+ ATPase, encoded by Cd630_32980, are both essential for taurocholate-glycine induced germination in the absence of exogenous Ca2+. However, environmental Ca2+ replaces glycine as a co-germinant and circumvents the need for endogenous Ca2+ fluxes. Cd630_32980 is dispensable for colonization in a murine model of C. difficile infection and ex vivo germination in mouse ileal contents. Calcium-depletion of the ileal contents prevented mutant spore germination and reduced WT spore germination by 90%, indicating that Ca2+ present within the gastrointestinal tract plays a critical role in C. difficile germination, colonization, and pathogenesis. These data provide a biological mechanism that may explain why individuals with inefficient intestinal calcium absorption (e.g., vitamin D deficiency, proton pump inhibitor use) are more prone to CDI and suggest that modulating free intestinal calcium is a potential strategy to curb the incidence of CDI.
Background
The Substance Abuse and Mental Health Administration awarded State Targeted Response grants to support states’ efforts to address the opioid epidemic. In Nevada, one component of this ...grant was mobile recovery outreach teams (MROTs) that utilized peer recovery support specialists to provide care for qualifying patients in emergency departments (EDs). The Mobile Emergency Recovery Intervention Trial (MERIT) is a mixed methods study to assess the feasibility/acceptability and effectiveness of the MROT intervention. This protocol mainly describes the R33 research activities and outcomes. The full protocol can be found protocols.io.
Methods
Data will be derived from state-level data sets containing de-identified emergency department visits, substance use disorder treatment records, and mortality files; in-person mixed methods interviews; participant observation; and self-report process evaluation forms. Primary outcomes include Medication Assisted Treatment (MAT) initiation and non-fatal overdose; secondary outcomes include MAT retention and fatal overdose. Quantitative hypotheses will be tested using generalized linear mixed effects models, Bayesian hierarchical models, and marginal Cox models. Qualitative interview data will be analyzed using an inductive thematic analysis procedure.
Discussion
It is impossible to conduct a randomized controlled trial of the effectiveness of the MROTs, given the ethical and logistical considerations of this intervention.
This study’s innovative design employs a mixed methods formative phase to examine feasibility and acceptability, and a quasi-experimental outcomes evaluation phase employing advanced statistical methods to mitigate bias and suggest causal inference regarding the effectiveness of the MROTs.
Innovative interventions have been deployed in many states; evidence regarding their effectiveness is lacking, but critical to informing an effective public health response to the opioid epidemic.
Since its discovery in the early 2000s, methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) has become a rapidly emerging cause of human infections, most often associated ...with livestock exposure. We applied whole-genome sequence typing to characterize a diverse collection of CC398 isolates (n = 89), including MRSA and methicillin-susceptible S. aureus (MSSA) from animals and humans spanning 19 countries and four continents. We identified 4,238 single nucleotide polymorphisms (SNPs) among the 89 core genomes. Minimal homoplasy (consistency index = 0.9591) was detected among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage. Phylogenetic analyses revealed that MSSA from humans formed the most ancestral clades. The most derived lineages were composed predominantly of livestock-associated MRSA possessing three different staphylococcal cassette chromosome mec element (SCCmec) types (IV, V, and VII-like) including nine subtypes. The human-associated isolates from the basal clades carried phages encoding human innate immune modulators that were largely missing among the livestock-associated isolates. Our results strongly suggest that livestock-associated MRSA CC398 originated in humans as MSSA. The lineage appears to have undergone a rapid radiation in conjunction with the jump from humans to livestock, where it subsequently acquired tetracycline and methicillin resistance. Further analyses are required to estimate the number of independent genetic events leading to the methicillin-resistant sublineages, but the diversity of SCCmec subtypes is suggestive of strong and diverse antimicrobial selection associated with food animal production.
Modern food animal production is characterized by densely concentrated animals and routine antibiotic use, which may facilitate the emergence of novel antibiotic-resistant zoonotic pathogens. Our findings strongly support the idea that livestock-associated MRSA CC398 originated as MSSA in humans. The jump of CC398 from humans to livestock was accompanied by the loss of phage-carried human virulence genes, which likely attenuated its zoonotic potential, but it was also accompanied by the acquisition of tetracycline and methicillin resistance. Our findings exemplify a bidirectional zoonotic exchange and underscore the potential public health risks of widespread antibiotic use in food animal production.
Background Prolonged air leaks after pulmonary resection lead to patient discomfort, increased hospital length of stay, greater health care costs, and increased morbidity. A standardized approach to ...air leak reduction (STAR) after lung resection was developed and studied. Methods A retrospective review was conducted of a prospective database from 1 surgeon who had adopted STAR as standard of care. Three independent factors shown to reduce air leaks are incorporated in STAR: fissureless operative technique, staple line buttressing, and protocol-driven chest tube management. Patient characteristics and outcomes were compared against aggregate data from The Society of Thoracic Surgeons National Database (2012–2014). Results From June 2010 through May 2015, 475 patients met the study criteria. Of these, 264 (55.6%) had lobectomies, 198 (41.7%) had wedge resections, and 13 (2.7%) had segmentectomies. Prolonged air leaks were reduced in the STAR lobectomy group by 52% (5.7% versus 10.9%; p = 0.0079) and in the STAR wedge group by 40% (2.5% versus 4.2%; p = 0.38). Hospital length of stay for lobectomies (3.2 versus 6.3 days; p = 0.0001), wedge resections (3.3 versus 4.5 days; p = 0.0152), and segmentectomies (3.2 versus 5.2 days; p = 0.0001) was significantly reduced. Readmission rate was 4% and none were related to air leak. No difference was seen in mortality rates. Conclusions Use of STAR for pulmonary resection, particularly for lobectomies, shows decreased postoperative prolonged air leaks when compared with The Society of Thoracic Surgeons National Database. This aggressive approach did not lead to air leak–related hospital readmissions nor compromise postoperative mortality. The STAR protocol is an innovative strategy that has the potential to improve postoperative pulmonary resection outcomes.
Abstract
Objective
Autonomic nervous system dysfunction has been implicated in chronic whiplash-associated disorder (WAD). However, the relationship between autonomic variables (e.g., resting heart ...rate and blood pressure) and clinical factors in chronic WAD is not well understood. This study sought to examine the associations between resting heart rate, resting blood pressure, pain processing and psychological variables in chronic WAD and in pain-free controls.
Design
Secondary analysis of a cross-sectional study.
Setting
University clinical research laboratory.
Subjects
Thirty-six people with chronic WAD Grade II (mean SD age 40.1 14.6 years, 28 females) and 25 pain-free controls (35.6 13.0 years, 17 females).
Methods
Participants had resting heart rate, systolic and diastolic blood pressure measured. Pain processing measures comprised: (i) pain pressure threshold at the cervical spine, hand and leg, (ii) temporal summation at the cervical spine and hand, and (iii) conditioned pain modulation. Psychological outcomes included measures of kinesiophobia, pain catastrophizing and post-traumatic stress symptoms. Correlations between autonomic variables, pain processing and psychological variables were determined (P < .05, 5% FDR).
Results
No significant correlations between autonomic and pain processing variables, or autonomic and psychological variables were found in the chronic WAD group. In the control group, diastolic blood pressure was positively correlated with cervical spine pressure pain threshold (r = 0.53, P = .007).
Conclusions
An association between blood pressure and pain sensitivity was observed in the control group but not the chronic WAD group. Such an association appears to be disrupted in chronic WAD, which may infer involvement of autonomic pathways in the pathophysiology of this condition.
Clostridium difficile (Cd) infection (CDI) typically occurs after antibiotic usage perturbs the gut microbiota. Mucosa-associated invariant T cells (MAIT) are found in the gut and their development ...is dependent on Major histocompatibility complex-related protein 1 (MR1) and the host microbiome. Here we were interested in determining whether the absence of MR1 impacts resistance to CDI. To this end, wild-type (WT) and MR1-/- mice were treated with antibiotics and then infected with Cd spores. Surprisingly, MR1-/- mice exhibited resistance to Cd colonization. 16S rRNA gene sequencing of feces revealed inherent differences in microbial composition. This colonization resistance was transferred from MR1-/- to WT mice via fecal microbiota transplantation, suggesting that MR1-dependent factors influence the microbiota, leading to CDI susceptibility.
Mobile Lung Screening: Should We All Get on the Bus? Headrick, James R.; Morin, Olivia; Miller, Ashley D. ...
The Annals of thoracic surgery,
October 2020, 2020-10-00, 20201001, Letnik:
110, Številka:
4
Journal Article
Recenzirano
Despite favorable recommendations, national lung screening adoption remains low (2% to 3%). Patients living in rural areas have additional challenges, including access to lung screening programs. We ...initiated a mobile lung screening program to serve the rural patients at risk. This is what we learned from this 12-month feasibility project.
Utilizing a multidisciplinary approach, we began an 8-month design and build schedule. This was the first build of this type. The operational team included a radiology technician, nurse practitioner, driver with a commercial driver’s license, and program developer. Specialized software was used for data mining. Downstream revenue projections were based on previously published Medicare claims data. Generally accepted accounting principles were used.
The prototype bus was delivered January 2018. During the 12-month feasibility period, we performed 548 low-dose lung screenings at 104 sites. Mean patient age was 62 years, mean pack-years of smoking was 41; 258 (47%) were male. Five lung cancers were found in addition to a type B thymoma. Financially, we exceeded the break-even analysis by 28%. The 5-year pro forma using 1 year of actual data and 4 additional years of projected data demonstrated a net present value of 1 million, internal rate of return of 34.6%, and profitability index of 2.2—all highly dependent on downstream revenue.
Although challenges exist, a commercially viable bus and a financially sound mobile program can be developed. However, without a centralized approach for incidental findings, the downstream revenue may be at risk as well as the financial viability of the project.
Background
There is uncertainty regarding the clinical significance of findings on MRI in patients with whiplash associated disorder (WAD) or nonspecific neck pain (NSNP).
Purpose
To compare the ...presence of cervical spine MRI findings in people with WAD or NSNP with pain‐free controls.
Study Type
Systematic review and meta‐analysis.
Population
Adults with WAD (n = 994), NSNP (n = 715), or pain‐free controls (n = 2323).
Field Strength
0.5T, 1.5T, and 3.0T.
Assessment
Medline, EMBASE, CINAHL, Web of Science, SCOPUS, and Cochrane CENTRAL databases were searched. Two independent reviewers identified studies for inclusion and extracted data. Risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross‐Sectional Studies. Overall quality of the evidence from meta‐analysis was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation approach.
Statistical Tests
Meta‐analysis was performed using a random‐effects model to calculate odds ratios or standard mean differences (SMDs) for binary and continuous data.
Results
In total, 31 studies were included (eight comparing acute WAD to controls, 14 comparing chronic WAD to controls, 12 comparing chronic NSNP to controls) comprising 4032 participants. Rectus capitis posterior major cross‐sectional area was smaller in people with chronic NSNP than controls (two studies: SMD –1.18 95% confidence interval CI –1.65, –0.71). The remaining meta‐analysis comparisons showed no group differences in MRI findings. The quality of evidence was mostly low due to small sample sizes and high heterogeneity.
Data Conclusion
Given the typically low‐quality evidence, definitive conclusions cannot be drawn on the presence of MRI findings in individuals with WAD or NSNP compared with pain‐free controls.
Level of Evidence: 3
Technical Efficacy: Stage 3
J. Magn. Reson. Imaging 2018.
In the last decade, as the biopsychosocial model of patient health care has expanded, there has been an increased focus on the influence of psychological manifestations on patient symptoms and ...health-related outcomes. This Viewpoint explores the scientific underpinnings of psychological manifestations in chronic whiplash-associated disorders (WADs)-where opinions vary widely concerning the reason for persistent symptoms and nonrecovery. It also provides an epidemiological and scientific foundation for the management of chronic WAD, incorporating the spectrum of the biopsychosocial model. J Orthop Sports Phys Ther 2019;49(3):118-121. doi:10.2519/jospt.2019.0603.
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