Culture of periprosthetic tissue specimens in blood culture bottles is more sensitive than conventional techniques, but the impact on laboratory workflow has yet to be addressed. Herein, we examined ...the impact of culture of periprosthetic tissues in blood culture bottles on laboratory workflow and cost. The workflow was process mapped, decision tree models were constructed using probabilities of positive and negative cultures drawn from our published study (T. N. Peel, B. L. Dylla, J. G. Hughes, D. T. Lynch, K. E. Greenwood-Quaintance, A. C. Cheng, J. N. Mandrekar, and R. Patel, mBio 7:e01776-15, 2016, https://doi.org/10.1128/mBio.01776-15), and the processing times and resource costs from the laboratory staff time viewpoint were used to compare periprosthetic tissues culture processes using conventional techniques with culture in blood culture bottles. Sensitivity analysis was performed using various rates of positive cultures. Annualized labor savings were estimated based on salary costs from the U.S. Labor Bureau for Laboratory staff. The model demonstrated a 60.1% reduction in mean total staff time with the adoption of tissue inoculation into blood culture bottles compared to conventional techniques (mean ± standard deviation, 30.7 ± 27.6 versus 77.0 ± 35.3 h per month, respectively;
< 0.001). The estimated annualized labor cost savings of culture using blood culture bottles was $10,876.83 (±$337.16). Sensitivity analysis was performed using various rates of culture positivity (5 to 50%). Culture in blood culture bottles was cost-effective, based on the estimated labor cost savings of $2,132.71 for each percent increase in test accuracy. In conclusion, culture of periprosthetic tissue in blood culture bottles is not only more accurate than but is also cost-saving compared to conventional culture methods.
The transforming growth factor
(TGF
) superfamily includes TGF
, activins, inhibins, and bone morphogenetic proteins (BMPs). These extracellular ligands have essential roles in normal tissue ...homeostasis by coordinately regulating cell proliferation, differentiation, and migration. Aberrant signaling of superfamily members, however, is associated with fibrosis as well as tumorigenesis, cancer progression, metastasis, and drug-resistance mechanisms in a variety of cancer subtypes. Given their involvement in human disease, the identification of novel selective inhibitors of TGF
superfamily receptors is an attractive therapeutic approach. Seven mammalian type 1 receptors have been identified that have context-specific roles depending on the ligand and the complex formation with the type 2 receptor. Here, we characterize the biologic effects of two transforming growth factor
receptor 1 (TGFBR1) kinase inhibitors designed to target TGF
signaling. AZ12601011 2-(2-pyridinyl)-4-(1H-pyrrolo3,2-cpyridin-1-yl)-6,7-dihydro-5H-cyclopentadpyrimidine; structure previously undisclosed and AZ12799734 4-({4-(2,6-dimethyl-3-pyridinyl)oxy-2-pyridinyl}amino)benzenesulfonamide (IC
= 18 and 47 nM, respectively) were more effective inhibitors of TGF
-induced reporter activity than SB-431542 4-4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-ylbenzamide (IC
= 84 nM) and LY2157299 4-2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo1,2-bpyrazol-3-ylquinoline-6-carboxamide monohydrate (galunisertib) (IC
= 380 nM). AZ12601011 inhibited phosphorylation of SMAD2 via the type 1 receptors activin A receptor type 1B (ALK4), TGFBR1, and activin A receptor type 1C (ALK7). AZ12799734, however, is a pan TGF/BMP inhibitor, inhibiting receptor-mediated phosphorylation of SMAD1 by activin A receptor type 1L, bone morphogenetic protein receptor type 1A, and bone morphogenetic protein receptor type 1B and phosphorylation of SMAD2 by ALK4, TGFBR1, and ALK7. AZ12601011 was highly effective at inhibiting basal and TGF
-induced migration of HaCaT keratinocytes and, furthermore, inhibited tumor growth and metastasis to the lungs in a 4T1 syngeneic orthotopic mammary tumor model. These inhibitors provide new reagents for investigating in vitro and in vivo pathogenic processes and the contribution of TGF
- and BMP-regulated signaling pathways to disease states.
Self-care incorporates a range of activities undertaken by patients including health protection and maintenance, treatment of minor ailments and the self-management of chronic conditions.. The ...present study aimed to explore patients’ perceptions of self-care, including factors which might promote, or hinder, patients' engagement with self-care strategies.
A qualitative approach was adopted. A sample of 20 patients with chronic conditions participated in the study. Seventeen interviews and one focus group were audio recorded and transcribed verbatim. Transcripts were analysed thematically using Framework methodology.
Participants identified five dimensions to the concept of self-care (1) taking responsibility for one's health and lifestyle choices, (2) reflecting on own needs, (3) being an expert of oneself, (4) doing things for oneself (self-agency), and (5) adopting lifestyle activities to support health and wellbeing. Participants identified a number of factors which had facilitated the initiation of their self-care activities. These included having accurate advice/information to inform decision making; having encouragement from treating healthcare professionals; having the right attitude and outlook; and having the motivation to initiate self-care. Factors which could hinder the initiation of self-care included symptoms of their chronic condition, and socioeconomic, cultural, and environmental factors.
Patients appear to have a complex and multifaceted understanding of self-care. The identified factors which facilitated or hindered participants in adopting self-care activities have important implications for the provision of self-care advice by treating health care workers, and the delivery of self-care services more widely.
Objective:
Palatoplasty outcome measurements vary widely among institutions. A standardized outcome metric would help provide quality benchmarks.
Design:
Retrospective review of primary palatoplasty ...patients from 2007 to 2013.
Setting:
Tertiary care children’s hospital.
Main Outcome Measures:
We created a novel conceptual quality metric called “OOR” (Optimal Outcome Reporting). Optimal Outcome Reporting is designed to reflect the percentage of patients with cleft palate who experience the best outcomes: one operation, velar competence by age 5 years, and no unintended palatal fistula.
Results:
Optimal Outcome Reporting was 72.3% (68/94). Eight patients had “suboptimal” outcomes for having undergone more than one operation. Eighteen patients failed for velar incompetence. No additional patients fell out of the algorithm for fistula. A significantly higher proportion of nonsyndromic patients demonstrated an “optimal” result compared to syndromic patients (61/80, 76.3% vs 7/14, 50.0%; P = .04). Patients who required more than one procedure had significantly more clinic visits (32.6 vs 14.9; P < .01) and accrued higher costs compared to “optimal” patients (US$34 019.88 vs US$15 357.25; P < .01).
Conclusions:
Optimal Outcome Reporting represents a novel quality metric that can provide meaningful information for patients with cleft palate. Optimal Outcome Reporting utilization can help cleft centers adopt changes that matter to patients and their families. By allowing for cross-institutional comparisons in a clear and objective manner, OOR can promote competition, innovation, and value in cleft palate care.
Background
Acceptance of basic surgical care as an essential element of any properly functioning health system is growing. To justify investment in surgical interventions, donors require estimates of ...the economic benefit of treating surgical disease. The present study aimed to establish a methodology for valuing the potential economic benefit of surgical intervention using cleft lip and palate (CLP) in sub-Saharan Africa (SSA) as a model.
Methods
Economic modeling of cleft lip and cleft palate (CLP) in SSA was performed with retrospective demographic and economic data from 2008. The total number of Disability-Adjusted Life-Years (DALYs) secondary to CLP in 2008 was calculated from accepted clefting incidence rates and disability weights taken from the Global Burden of Disease Project. DALYs were then converted to monetary terms ($US), using both a human capital approach and Value of a Statistical Life (VSL) approach.
Results
With the human capital approach, the potential economic benefit if all incident cases of CLP in SSA in 2008 were repaired at birth ranged from $252 million to $441 million. With VSL, the potential economic benefit of the same CLP repair would range from $5.4 billion to $9.7 billion.
Conclusions
Cleft lip and cleft palate can have a substantial impact on the economic health of countries in the developing world. Further studies should be directed at quantifying the economic benefit of surgical interventions and quantifying their costs with an economically sound approach.
Introduction:
There has been a burgeoning of research evaluating acupuncture for various symptoms of cancer and the side-effects associated with its treatment. A systematic review was conducted to ...examine the quality of reporting in published studies of acupuncture in cancer according to the STRICTA (STandards for Reporting Interventions in Clinical Trials of Acupuncture) guidelines.
Methods:
Systematic review of published research of acupuncture for symptoms of cancer and the side-effects associated with its treatment. Databases searched were: Medline, CINAHL, Cochrane (all databases), Scopus, and PubMed from their inception to December 2014. Clinical trials, pilot/feasibility studies, observational studies, and case studies were included. Only full journal papers published in English were included. The quality of reporting was evaluated using STRICTA guidelines. Each included paper was assessed by two independent reviewers, with disagreements adjudicated by a third reviewer.
Results:
88 papers were identified which met the inclusion criteria. The median number of STRICTA items reported in trials with a control or comparator arm (n=47) was 14 out of 17 (range 8 to 17, IQR 4). For studies without a control or comparator arm the median was 11 out of a possible 15 (range 5 to 15, IQR 3). Key weaknesses in reporting included details of other components of treatments, and details of the acupuncturist administering treatments.
Conclusions:
Despite the widespread use of the STRICTA guidelines in acupuncture research, adherence remains poor for a few specific items. Further research is required to explore the reasons why authors fail to report those items, and to develop strategies to improve the adherence to the guidelines.
To review and update consensus-based recommendations for medical and public health professionals following a Bacillus anthracis attack against a civilian population.
The working group included 23 ...experts from academic medical centers, research organizations, and governmental, military, public health, and emergency management institutions and agencies.
MEDLINE databases were searched from January 1966 to January 2002, using the Medical Subject Headings anthrax, Bacillus anthracis, biological weapon, biological terrorism, biological warfare, and biowarfare. Reference review identified work published before 1966. Participants identified unpublished sources.
The first draft synthesized the gathered information. Written comments were incorporated into subsequent drafts. The final statement incorporated all relevant evidence from the search along with consensus recommendations.
Specific recommendations include diagnosis of anthrax infection, indications for vaccination, therapy, postexposure prophylaxis, decontamination of the environment, and suggested research. This revised consensus statement presents new information based on the analysis of the anthrax attacks of 2001, including developments in the investigation of the anthrax attacks of 2001; important symptoms, signs, and laboratory studies; new diagnostic clues that may help future recognition of this disease; current anthrax vaccine information; updated antibiotic therapeutic considerations; and judgments about environmental surveillance and decontamination.
Due to the importance of both prostaglandins (PGs) and leukotrienes (LTs) as pro-inflammatory mediators, and the potential for eicosanoid shunting in the presence of pathway target inhibitors, we ...have investigated an approach to inhibiting the formation of both PGs and LTs as part of a multi-targeted drug discovery effort.
We generated ligand-protein X-ray crystal structures of known inhibitors of microsomal prostaglandin E2 synthase-1 (mPGES-1) and the 5-Lipoxygenase Activating Protein (FLAP), with their respective proteins, to understand the overlapping pharmacophores. We subsequently used molecular modeling and structure-based drug design (SBDD) to identify hybrid structures intended to inhibit both targets.
This work enabled the preparation of compounds 4 and 5, which showed potent in vitro inhibition of both targets.
Our findings enhance the structural understanding of mPGES-1 and FLAP's unique ligand binding pockets and should accelerate the discovery of additional dual inhibitors for these two important integral membrane protein drug targets.
Display omitted
•mPGES-1 and FLAP share < 5% of sequence identity and possess distinct binding pockets.•Using structure-based drug design, we explored the possibility of targeting both mPGES-1 and FLAP with a single agent.•Compounds 4 and 5 were designed and prepared. They showed inhibitory activities at both mPGES-1 and FLAP.
Point-of-care (POC) HbA1c is frequently used as a surrogate for serum HbA1c. We aimed to determine if resident management of type 2 diabetes changed after accounting for the + 0.5% margin of error ...associated with POC HbA1c devices.
Residents were surveyed in an outpatient clinic regarding two of their patients with type 2 diabetes for which they had obtained a POC HbA1c. For one patient, the resident was asked if management would change if the POC HbA1c were 0.5% higher (called the positive case), and for another if management would change if POC HbA1c were 0.5% lower (negative case).
Twelve of 58 (21%) cases had a change in management. Of the 27 cases where POC HbA1c was near the glycemic target (defined as POC HbA1c ≥6.0% and <8.0%), 11 (41%) resulted in a change in management while one (3%) of the 31 cases outside that interval had a change in management.
POC HbA1c testing is well-suited for patients with poorly controlled type 2 diabetes while serum HbA1c testing may be more appropriate when near a patient's personalized HbA1c target since small changes in HbA1c can lead to differences in medical management.
PDF
