Determining predictive metabolomic biomarkers of meniscal injury in dogs with cranial cruciate ligament rupture.

OBJECTIVES: This study used hydrogen nuclear magnetic resonance spectroscopy for the first time to examine differences in the metabolomic profile of stifle joint synovial fluid from dogs with cranial cruciate ligament rupture with and without meniscal injuries, in order to identify biomarkers of meniscal injury. Identifying a biomarker of meniscal injury could then ultimately be used to design a minimally invasive diagnostic test for meniscal injuries in dogs. MATERIALS AND METHODS: Stifle joint synovial fluid was collected from dogs undergoing stifle joint surgery or arthrocentesis for lameness investigations. We used multi-variate statistical analysis using principal component analysis and univariate statistical analysis using one-way analysis of variance and analysis of co-variance to identify differences in the metabolomic profile between dogs with cranial cruciate ligament rupture and meniscal injury, cranial cruciate ligament rupture without meniscal injury, and neither cranial cruciate ligament rupture nor meniscal injury, taking into consideration clinical variables. RESULTS: A total of 154 samples of canine synovial fluid were included in the study. Sixty-four metabolites were annotated to the hydrogen nuclear magnetic resonance spectroscopy spectra. Six spectral regions were found to be significantly altered (false discovery rate adjusted P-value <0.05) between groups with cranial cruciate ligament rupture with and without meniscal injury, including three attributed to nuclear magnetic resonance mobile lipids [mobile lipid -CH3 (P=0.016), mobile lipid -n(CH3 )3 (P=0.017), mobile unsaturated lipid (P=0.031)]. CLINICAL SIGNIFICANCE: We identified an increase in nuclear magnetic resonance mobile lipids in the synovial fluid of dogs with meniscal injury which are of interest as potential biomarkers of meniscal injury.

Characterization of the public transit air microbiome and resistome reveals geographical specificity.

BACKGROUND: The public transit is a built environment with high occupant density across the globe, and identifying factors shaping public transit air microbiomes will help design strategies to minimize the transmission of pathogens. However, the majority of microbiome works dedicated to the public transit air are limited to amplicon sequencing, and our knowledge regarding the functional potentials and the repertoire of resistance genes (i.e. resistome) is limited. Furthermore, current air microbiome investigations on public transit systems are focused on single cities, and a multi-city assessment of the public transit air microbiome will allow a greater understanding of whether and how broad environmental, building, and anthropogenic factors shape the public transit air microbiome in an international scale. Therefore, in this study, the public transit air microbiomes and resistomes of six cities across three continents (Denver, Hong Kong, London, New York City, Oslo, Stockholm) were characterized. RESULTS: City was the sole factor associated with public transit air microbiome differences, with diverse taxa identified as drivers for geography-associated functional potentials, concomitant with geographical differences in species- and strain-level inferred growth profiles. Related bacterial strains differed among cities in genes encoding resistance, transposase, and other functions. Sourcetracking estimated that human skin, soil, and wastewater were major presumptive resistome sources of public transit air, and adjacent public transit surfaces may also be considered presumptive sources. Large proportions of detected resistance genes were co-located with mobile genetic elements including plasmids. Biosynthetic gene clusters and city-unique coding sequences were found in the metagenome-assembled genomes. CONCLUSIONS: Overall, geographical specificity transcends multiple aspects of the public transit air microbiome, and future efforts on a global scale are warranted to increase our understanding of factors shaping the microbiome of this unique built environment.

Identification of tissue-dependent proteins in knee OA synovial fluid.

OBJECTIVE: For many proteins from osteoarthritic synovial fluid, their intra-articular tissue of origin remains unknown. In this study we performed comparative proteomics to identify osteoarthritis-specific and joint tissue-dependent secreted proteins that may serve as candidates for osteoarthritis biomarker development on a tissue-specific basis. DESIGN: Protein secretomes of cartilage, synovium, Hoffa's fat pad and meniscus from knee osteoarthritis patients were determined using liquid chromatography tandem mass spectrometry, followed by label-free quantification. Validation of tissue-dependent protein species was conducted by ELISA on independent samples. Differential proteomes of osteoarthritic and non-osteoarthritic knee synovial fluids were obtained via similar proteomics approach, followed by ELISA validation. RESULTS: Proteomics revealed 64 proteins highly secreted from cartilage, 94 from synovium, 37 from Hoffa's fat pad and 21 from meniscus. Proteomic analyses of osteoarthritic vs non-osteoarthritic knee synovial fluid revealed 70 proteins with a relatively higher abundance and 264 proteins with a relatively lower abundance in osteoarthritic synovial fluid. Of the 70 higher abundance proteins, 23 were amongst the most highly expressed in the secretomes of a specific intra-articular tissue measured. Tissue-dependent release was validated for SLPI, C8, CLU, FN1, RARRES2, MATN3, MMP3 and TNC. Abundance in synovial fluid of tissue-dependent proteins was validated for IGF2, AHSG, FN1, CFB, KNG and C8. CONCLUSIONS: We identified proteins with a tissue-dependent release from intra-articular human knee OA tissues. A number of these proteins also had an osteoarthritis-specific abundance in knee synovial fluid. These proteins may serve as novel candidates for osteoarthritis biomarker development on a tissue-specific basis.

PM2.5 on the London Underground.

INTRODUCTION: Despite the London Underground (LU) handling on average 2.8 million passenger journeys per day, the characteristics and potential health effects of the elevated concentrations of metal-rich PM2.5 found in this subway system are not well understood. METHODS: Spatial monitoring campaigns were carried out to characterise the health-relevant chemical and physical properties of PM2.5 across the LU network, including diurnal and day-to-day variability and spatial distribution (above ground, depth below ground and subway line). Population-weighted station PM2.5 rankings were produced to understand the relative importance of concentrations at different stations and on different lines. RESULTS: The PM2.5 mass in the LU (mean 88 µg m-3, median 28 µg m-3) was greater than at ambient background locations (mean 19 µg m-3, median 14 µg m-3) and roadside environments in central London (mean 22 µg m-3, median 14 µg m-3). Concentrations varied between lines and locations, with the deepest and shallowest submerged lines being the District (median 4 µg m-3) and Victoria (median 361 µg m-3 but up to 885 µg m-3). Broadly in agreement with other subway systems around the world, sampled LU PM2.5 comprised 47% iron oxide, 7% elemental carbon, 11% organic carbon, and 14% metallic and mineral oxides. Although a relationship between line depth and air quality inside the tube trains was evident, there were clear influences relating to the distance from cleaner outside air and the exchange with cabin air when the doors open. The passenger population-weighted exposure analysis demonstrated a method to identify stations that should be prioritised for remediation to improve air quality. CONCLUSION: PM2.5 concentrations in the LU are many times higher than in other London transport Environments. Failure to include this environment in epidemiological studies of the relationship between PM2.5 and health in London is therefore likely to lead to a large exposure misclassification error. Given the significant contribution of underground PM2.5 to daily exposure, and the differences in composition compared to urban PM2.5, there is a clear need for well-designed studies to better understand the health effects of underground exposure.

How contraceptive use patterns differ by pregnancy intention: implications for counseling.

To increase awareness of issues to include in contraceptive counseling-the objectives of this study were to evaluate: 1) how contraceptive use patterns (eg, non-use), level of effectiveness of contraceptive method, and sociodemographic characteristics may be associated with the occurrence of unintended pregnancy; 2) patterns of health care use for women with intended and unintended pregnancy; and 3) the association between contraceptive use patterns and sociodemographic characteristics. In-person interviews were conducted with 279 women enrolled in a Medicaid managed care health plan who had been pregnant in the last 5 years. Self-reported measures of pregnancy intention, contraceptive use, and health care use were collected. The relationships of pregnancy intention with contraceptive use patterns, level of effectiveness of contraceptive method used, and patterns of recent health care use were assessed. Differences in contraceptive use patterns by sociodemographic groups were assessed. Seventy-eight percent of women reported an unintended pregnancy. Non-use of birth control the month before conception was reported by 57% of women with unintended pregnancies and 84% of women with intended pregnancies. Use of birth control of low effectiveness was reported by 20% of women with unintended pregnancies and 8% of women with intended pregnancies. Non-use or use of contraceptive methods of low effectiveness did not differ for women in different sociodemographic groups regardless of pregnancy intention status. A majority of women reported recent health care use. Health care providers should be aware that women who have no intention for pregnancy may not be using an effective contraceptive method NOR have an effective pattern of contraceptive use.

Physician incentives and disclosure of payment methods to patients.

OBJECTIVE: There is increasing public discussion of the value of disclosing how physicians are paid. However, little is known about patients' awareness of and interest in physician payment information or its potential impact on patients' evaluation of their care. DESIGN: Cross-sectional survey SETTING: Managed care and indemnity plans of a large, national health insurer. PARTICIPANTS: Telephone interviews were conducted with 2,086 adult patients in Atlanta, Ga; Baltimore, Md/Washington DC; and Orlando, Fla (response rate, 54%). MEASUREMENTS AND MAIN RESULTS: Patients were interviewed to assess perceptions of their physicians' payment method, preference for disclosure, and perceived effect of different financial incentives on quality of care. Non-managed fee-for-service patients (44%) were more likely to correctly identify how their physicians were paid than those with salaried (32%) or capitated (16%) physicians. Just over half (54%) wanted to be informed about their physicians' payment METHOD: Patients of capitated and salaried physicians were as likely to want disclosure as patients of fee-for-service physicians. College graduates were more likely to prefer disclosure than other patients. Many patients (76%) thought a bonus paid for ordering fewer than the average number of tests would adversely affect the quality of their care. About half of the patients (53%) thought a particular type of withhold would adversely affect the quality of their care. White patients, college graduates, and those who had higher incomes were more likely to think that these types of bonuses and withholds would have a negative impact on their care. Among patients who believed that these types of bonuses adversely affected care, those with non-managed fee-for-service insurance and college graduates were more willing to pay a higher deductible or co-payment in order to get tests that they thought were necessary. CONCLUSIONS: Most patients were unaware of how their physicians are paid, and only about half wanted to know. Most believed that bonuses or withholds designed to reduce the use of services would adversely affect the quality of their care. Lack of knowledge combined with strong attitudes about various financial incentives suggest that improved patient education could clarify patient understanding of the nature and rationale for different types of incentives. More public discussion of this important topic is warranted.

Health literacy among Medicare enrollees in a managed care organization.

CONTEXT: Elderly patients may have limited ability to read and comprehend medical information pertinent to their health. OBJECTIVE: To determine the prevalence of low functional health literacy among community-dwelling Medicare enrollees in a national managed care organization. DESIGN: Cross-sectional survey. SETTING: Four Prudential HealthCare plans (Cleveland, Ohio; Houston, Tex; south Florida; Tampa, Fla). PARTICIPANTS: A total of 3260 new Medicare enrollees aged 65 years or older were interviewed in person between June and December 1997 (853 in Cleveland, 498 in Houston, 975 in south Florida, 934 in Tampa); 2956 spoke English and 304 spoke Spanish as their native language. MAIN OUTCOME MEASURE; Functional health literacy as measured by the Short Test of Functional Health Literacy in Adults. RESULTS: Overall, 33.9% of English-speaking and 53.9% of Spanish-speaking respondents had inadequate or marginal health literacy. The prevalence of inadequate or marginal functional health literacy among English speakers ranged from 26.8% to 44.0%. In multivariate analysis, study location, race/language, age, years of school completed, occupation, and cognitive impairment were significantly associated with inadequate or marginal literacy. Reading ability declined dramatically with age, even after adjusting for years of school completed and cognitive impairment. The adjusted odds ratio for having inadequate or marginal health literacy was 8.62 (95% confidence interval, 5.55-13.38) for enrollees aged 85 years or older compared with individuals aged 65 to 69 years. CONCLUSIONS: Elderly managed care enrollees may not have the literacy skills necessary to function adequately in the health care environment. Low health literacy may impair elderly patients' understanding of health messages and limit their ability to care for their medical problems.

Prenatal care in the first trimester: misleading findings from HEDIS. Health Plan Employer Data and Information Set.

OBJECTIVE: To understand factors influencing Health Plan Employer Data and Information Set (HEDIS) rates for the measure 'Prenatal care in the first trimester'. DESIGN: Telephone survey of a retrospective cohort of women with a live birth. Medical record review of a sample of both responders and non-responders to the telephone survey. Detailed review of HEDIS data collection procedures. SETTING: A managed care plan in California. STUDY PARTICIPANTS: Women aged 18-49 years at date of delivery, who delivered a live birth from 1 October 1995 through 31 March 1996, and who were continuously enrolled in a California managed care plan for 12 months prior to delivery (telephone survey, n= 1,185; medical record review, n= 465). RESULTS: Of the women participating in the telephone survey, 95% indicated that their first prenatal visit occurred during the first 3 months of pregnancy. Using HEDIS 3.0 standards, a review of medical records for a sample of these women indicated that 94% of the women initiated care during the first trimester. These results contrasted sharply with 1995 and 1996 HEDIS rates of 64% and 75%, respectively. CONCLUSION: An investigation of the discrepancy between HEDIS rates and rates from both telephone survey and medical record review led to the finding that the low HEDIS rates were due not to a true low rate of early care, but to data collection problems, including difficulty obtaining medical records. Potential solutions involving health plan activities, revisions to the official HEDIS process and revised reporting of results are proposed.

The relationship between method of physician payment and patient trust.

CONTEXT: Trust is the cornerstone of the patient-physician relationship. Payment methods that place physicians at financial risk have raised concerns about patients' trust in physicians to act in patients' best interests. OBJECTIVE: To evaluate the extent to which methods of physician payment are related to patient trust. DESIGN: Cross-sectional telephone interview survey done between January and June 1997. SETTING: Health plans of a large national insurer in Atlanta, Ga, the Baltimore, Md-Washington, DC, area, and Orlando, Fla. PARTICIPANTS: A total of 2086 adult managed care and indemnity patients. MAIN OUTCOME MEASURE: A 10-item scale (alpha = .94) assessing patients' trust in physicians. RESULTS: More fee-for-service (FFS) indemnity patients (94%) completely or mostly trust their physicians to "put their health and well-being above keeping down the health plan's costs" than salary (77%), capitated (83%), or FFS managed care patients (85%) (P<.001 for pairwise comparisons). In multivariate analyses that adjusted for potentially confounding factors, FFS indemnity patients also had higher scores on the 10-item trust scale than salary (P<.001), capitated (P<.001), or FFS managed care patients (P<.01). The effects of payment method on patient trust were reduced when a measure based on patients' reports about physician behavior (eg, Does your physician take enough time to answer your questions?) was included in the regression analyses, but the differences remained statistically significant, except for the comparison between FFS managed care and FFS indemnity patients (P=.08). Patients' perceptions of how their physicians were paid were not independently associated with trust, but the 37.7% who said they did not know how their physicians were paid had higher levels of trust than other patients (P<.01). A total of 30.2% of patients were incorrect about their physicians' method of payment. CONCLUSIONS: Most patients trusted their physicians, but FFS indemnity patients have higher levels of trust than salary, capitated, or FFS managed care patients. Patients' reports of physician behavior accounted for part of the variation in patients' trust in physicians who are paid differently. The impact of payment methods on patient trust may be mediated partly by physician behavior.

Patients' trust in their physicians: effects of choice, continuity, and payment method.

OBJECTIVE: To evaluate the extent to which physician choice, length of patient-physician relationship, and perceived physician payment method predict patients' trust in their physician. DESIGN: Survey of patients of physicians in Atlanta, Georgia. PATIENTS: Subjects were 292 patients aged 18 years and older. MEASUREMENTS AND MAIN RESULTS: Scale of patients' trust in their physician was the main outcome measure. Most patients completely trusted their physicians "to put their needs above all other considerations" (69%). Patients who reported having enough choice of physician (p < .05), a longer relationship with the physician (p < .001), and who trusted their managed care organization (p < .001) were more likely to trust their physician. Approximately two thirds of all respondents did not know the method by which their physician was paid. The majority of patients believed paying a physician each time a test is done rather than a fixed monthly amount would not affect their care (72.4%). However, 40.5% of all respondents believed paying a physician more for ordering fewer than the average number of tests would make their care worse. Of these patients, 53.3% would accept higher copayments to obtain necessary medical tests. CONCLUSIONS: Patients' trust in their physician is related to having a choice of physicians, having a longer relationship with their physician, and trusting their managed care organization. Most patients are unaware of their physician's payment method, but many are concerned about payment methods that might discourage medical use.

Are we underestimating rates of vaginal birth after previous cesarean birth? The validity of delivery methods from birth certificates.

Previous studies of birth certificates have not fully evaluated how accurately they identify delivery methods that have a historical component, such as repeat cesarean and vaginal birth after previous cesarean (VBAC). The authors used linked Georgia birth certificates for first and second deliveries to examine the accuracy of four reported delivery methods in the second pregnancy: vaginal (without previous cesarean), VBAC, primary cesarean, and repeat cesarean, as well as an indicator of a previous cesarean. From the immediate birth certificates, the delivery method for each of the two births was classified as vaginal (V) or cesarean section (CS), which produced possible sequences of V-V, CS-V, V-CS, and CS-CS. The delivery method for the second births to 106,049 women from 1989 through 1992 was reviewed, taking into account the historical information from the linked certificates regarding the first births. Only 42.0% of women with a CS-V sequence were correctly designated on the second birth certificate as a VBAC; 79.3% of women with a V- CS sequence were correctly designated as primary cesarean. From 1980 through 1988, birth certificates contained a check box indicating a previous cesarean (but no VBAC box). During this period, only 75.5% of 25,491 women with a previous cesarean were so designated on the birth certificate. These findings suggest that cross-sectional vital records data substantially underestimate VBAC and primary cesarean rates.

The effect of gas density on glottal vibration and exit jet particle velocity.

Although theoretical studies include a term for gas density in their mathematical descriptions of glottal aerodynamics, the effect of gas density on glottal vibration has not been examined empirically. In this study, an in vivo canine model was used to evaluate the effect of gas density on glottal vibration by comparing phonation with air and helium. With gas flow and nerve stimulation held constant, phonation with helium resulted in an increased exit jet particle velocity for helium (45 m/s) compared to air (34 m/s). However, the measured increase in helium velocity was less than predicted by a proportional relationship between transglottal pressure and dynamic pressure. This difference could be due to a change in the constant of proportionality or in the dynamic pressure loss coefficient associated with the use of helium.

Changes in glottal area associated with increasing airflow.

Laryngeal resistance varies inversely with airflow during phonation. This study evaluated the morphological changes in the glottis that accompany decreases in laryngeal resistance at higher levels of airflow. An in vivo canine model of phonation and a video analysis system were used to assess changes in area. Four animals were examined stroboscopically as airflow increased, with constant recurrent laryngeal nerve stimulation. Glottal dynamics were evaluated by means of photoglottography, electroglottography, and measures of subglottic pressure. Analysis of digitized stroboscopic images indicated that increasing airflow had no obvious effect on the glottal chink (vocal process contact). Increasing airflow was associated with an increase in the area of peak opening and an increase in the glottal area integral.

Effect of tension, stiffness, and airflow on laryngeal resistance in the in vivo canine model.

This study used an in vivo canine model of phonation to determine the effects of airflow on glottal resistance at low, medium, and high levels of recurrent laryngeal nerve (RLN) and superior laryngeal nerve (SLN) stimulation. Static and dynamic trials of changing airflow were used to study the effects of airflow on glottal resistance during phonation. As reported previously, glottal resistance varies inversely as a function of airflow. Increasing levels of RLN stimulation resulted in a statistically significant increase in glottal resistance for each level of airflow evaluated. Variation in SLN stimulation had no statistically effects on the relationship between flow and resistance. At airflow rates greater than 590 milliliters per second (mL/s), glottal resistance approached 0.1 mm Hg per mL/s for all levels of RLN and SLN stimulation tested. These data support the collapsible tube model of phonation.

Point-touch technique of botulinum toxin injection for the treatment of spasmodic dysphonia.

Intralaryngeal injections of botulinum toxin (Botox), under electromyographic guidance, have emerged as an effective treatment for adductor spasmodic dysphonia. To remain effective, these injections must be repeated every 3 to 9 months as the symptoms recur. One drawback to the current method is the need for electromyographic confirmation of needle placement into the thyroarytenoid muscle. This report describes an anatomic approach to Botox injection that requires only flexible nasopharyngeal endoscopy and careful evaluation of the anatomic landmarks. This technique has been used successfully on 13 patients, and objective pretreatment and posttreatment measures are reported.

Physiologic motion after vocal cord reinnervation: a preliminary study.

This study attempted to reestablish physiologic vocal cord motion, rather than synkinesis, to a reinnervated vocal cord. One mongrel dog underwent a division and reanastomosis of the anterior branch of the right recurrent laryngeal nerve and simultaneous separation and reimplantation of a posterior division nerve-muscle pedicle into the posterior cricoarytenoid muscle. After 21 weeks, spontaneous physiologic vocal cord movement and electromyographic (EMG) activity were recorded during respiratory obstruction and laryngeal mechanical stimulation. Acoustic measures and histologic data are also presented from the reinnervated and normal vocalis muscle and from the recurrent laryngeal nerve. This study demonstrated that physiologic vocal cord motion can be achieved after laryngeal reinnervation using this technique.

A functional evaluation of ansa cervicalis nerve transfer for unilateral vocal cord paralysis: future directions for laryngeal reinnervation.

There are a variety of methods for treating unilateral vocal cord paralysis, but to date there are few objective studies that evaluate the functional results of nerve transfer from the ansa cervicalis. Six dogs underwent unilateral recurrent laryngeal nerve section with immediate reanastamosis to the sternothyroid branch of the ansa cervicalis. After 5 to 6 months, measurements of vocal efficiency and acoustic parameters, videolaryngoscopy, videostroboscopy, and evoked electromyography were performed. Identical measurements were made in eight control dogs during normal electrically induced phonation and a simulated unilateral recurrent laryngeal nerve paralysis. Histologic analysis of both vocalis muscles, recurrent laryngeal nerves, ansa cervicalis, and the ansa-recurrent laryngeal nerve anastamosis site was performed. Evidence of reinnervation was found in all of the animals that underwent nerve transfer. The vocal efficiency and acoustic quality after ansa cervicalis nerve transfer were dependent on the degree of electrical stimulation from the transferred nerve to the reinnervated cord during phonation. In the absence of electrical stimulation to the nerve transfer, physiologic vocal cord motion could not be elicited from the reinnervated cord.

Vocal fold medialization by surgical augmentation versus arytenoid adduction in the in vivo canine model.

There are a variety of methods for treating unilateral vocal cord paralysis, but to date there have been few studies that compare these phonosurgical techniques by using objective measures of voice improvement. Vocal efficiency is an objective voice measure that is defined as the ratio of the acoustic power produced by the larynx to the subglottic air power. Vocal efficiency has been found to decrease with glottic disorders such as vocal cord paralysis and carcinoma. This study compared the effects of vocal fold medialization by surgical augmentation to those of arytenoid adduction on the vocal efficiency, videostroboscopy, and acoustics (jitter, shimmer, and signal-to-noise ratio) of a simulated unilateral vocal cord paralysis in an in vivo canine model. Arytenoid adduction was superior to surgical augmentation in vocal efficiency, traveling wave motion, and acoustics.