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Background and Purpose— Gait impairment is common in the elderly, especially those with stroke and white matter hyperintensities on conventional brain MRI. Diffusion tensor imaging (DTI) is more sensitive to white matter damage than conventional MRI. The relationship between DTI measures and gait has not been previously evaluated. Our purpose was to investigate the relationship between the integrity of white matter in the corpus callosum as determined by DTI and quantitative measures of gait in the elderly. Methods— One hundred seventy-three participants of a community-dwelling elderly cohort had neurological and neuropsychological examinations and brain MRI. Gait function was measured by Tinetti gait (0 to 12), balance (0 to 16) and total (0 to 28) scores. DTI assessed fractional anisotropy in the genu and splenium of the corpus callosum. Conventional MRI was used to evaluate for brain infarcts and white matter hyperintensity volume. Results— Participants with abnormal gait had low fractional anisotropy in the genu of the corpus callosum but not the splenium. Multiple regressions analyses showed an independent association between these genu abnormalities and all 3 Tinetti scores ( P Conclusions— The independent association between quantitative measures of gait function and DTI findings shows that white matter integrity in the genu of corpus callosum is an important marker of gait in the elderly. DTI analyses of white matter tracts in the brain and spinal cord may improve knowledge about the pathophysiology of gait impairment and help target clinical interventions.

Given the potential morbidity of whole brain radiation therapy (WBRT), there has been an increasing trend to defer WBRT and deliver Gamma Knife stereotactic radiosurgery (GKS) to cerebral metastatic lesions. We analyzed our experience delivering GKS to the tumor cavity following surgical resection of brain metastases and compared our results to patients receiving WBRT after surgical resection of a metastatic lesion. We performed a retrospective review of patients undergoing surgical resection of at least one brain metastasis between December 1999 and December 2008. Both univariate and multivariate Cox proportional hazards regression were utilized to analyze the influence of various prognostic factors on survival. Twenty-five patients had a metastatic lesion resected followed by adjuvant GKS to the resection cavity while another 18 had surgical resection followed by WBRT. Aside from a disparity in gender distribution (72% of GKS patients were female while women only constituted 28% of the WBRT group), no significant differences existed between groups. The median survival for patients receiving GKS was 15.00 months as compared to 6.81 months among those receiving WBRT (P = 0.08). Univariate Cox regression analysis identified the number of metastases (HR 1.65, 95% CI 1.07-2.54, P = 0.02) and regional recurrence (RR 5.23, 95% CI 1.78-15.38, P = 0.003) as poor prognostic factors. Multivariate regression analysis showed that regional recurrence (HR 5.17, 95% CI 1.69-15.78, P = 0.004) was again strongly associated with worse survival. Although limited by the retrospective nature of our study and lack of some clinical measures, patients undergoing GKS to the resection cavity had a trend towards longer median survival.

Object Trigeminal neuralgia (TN) is a disorder of the trigeminal nerve that results in intense episodic pain. Primary treatment with Gamma Knife surgery (GKS) is well established; however, a significant number of patients experience recurrence of TN over time. Repeat GKS can be performed, but the retreatment dose has not been well established. In this study, the authors present their institutional retreatment results and compare them with other series. Methods Between December 2003 and January 2006, 28 patients were treated at Tufts Medical Center with repeat GKS for recurrence of TN. All patients had been initially treated with GKS at this institution, and only those with significant pain improvement were offered retreatment. The maximum dose was prescribed using a single isocenter; the 4-mm collimator was used. The initial median GKS dose was 80 Gy, the median retreatment dose was 45 Gy, and the median cumulative dose was 125 Gy. The median time between GKS procedures was 18.1 months. Facial pain outcomes were defined using the Marseille scale. Excellent outcome was defined as no pain (with or without medications), and good outcome was defined as > 50% pain relief. Toxicity was categorized as none, mild, or bothersome. The median clinical follow-up after the second GKS was 19.7 months. Our clinical outcomes were compared with 8 previously reported retreatment series (including 1 abstract), both for rate of pain control and for rate of complications. Results Outcomes after the second GKS were excellent in 29% (8 patients), good in 32% (9), and poor in 39% (11). Four patients (14%) experienced no improvement after repeat GKS. Eight patients (29%) experienced new trigeminal nerve dysfunction, including numbness (11%), paresthesia (14%), dysesthesia (4%), taste alteration (11%), and bite weakness (4%). None of these were bothersome. No patient developed corneal numbness. Univariate analysis failed to reveal any significant predictors of pain control or complications. Seven published peer-reviewed retreatment series and the authors' data (total 215 patients) were analyzed. There was a cumulative dose-response relationship for both pain control (p = 0.04) and new trigeminal dysfunction (p = 0.08). Successful pain control was strongly correlated with development of new dysfunction (p = 0.02). A cumulative dose > 130 Gy was more likely to result in successful (> 50%) pain control, but was also more likely (> 20%) to result in development of new dysfunction. Conclusions Successful retreatment of patients in whom the initial GKS treatment fails is feasible. Patients who respond initially may be at a higher risk of retreatment-related complications. There appears to be a dose-response relationship for both pain control and development of new side effects. It is important to counsel and treat patients individually based on this dose-response relationship.

Background Albuminuria, a kidney marker of microvascular disease, may herald microvascular disease elsewhere, including in the brain. Study Design Cross sectional. Setting & Participants Boston, MA, elders receiving home health services to maintain independent living who consented to brain magnetic resonance imaging. Predictor Urine albumin-creatinine ratio (ACR). Outcome Performance on a cognitive battery assessing executive function and memory by using principal components analysis and white matter hyperintensity volume on brain imaging, evaluated in logistic and linear regression models. Results In 335 participants, mean age was 73.4 ± 8.1 years and 123 participants had microalbuminuria or macroalbuminuria. Each doubling of ACR was associated with worse executive function (β = −0.05; P = 0.005 in univariate and β = −0.07; P = 0.004 in multivariable analyses controlling for age, sex, race, education, diabetes, cardiovascular disease, hypertension, medications, and estimated glomerular filtration rate [eGFR]), but not with worse memory or working memory. Individuals with microalbuminuria or macroalbuminuria were more likely to be in the lower versus the highest tertile of executive functioning (odds ratio, 1.18; 95% confidence interval, 1.06 to 1.32; odds ratio, 1.19; 95% confidence interval, 1.05 to 1.35 per doubling of ACR in univariate and multivariable analyses, respectively). Albuminuria was associated with qualitative white matter hyperintensity grade (odds ratio, 1.13; 95% confidence interval, 1.02 to 1.25; odds ratio, 1.15; 95% confidence interval, 1.02 to 1.29 per doubling of ACR) in univariate and multivariable analyses and with quantitative white matter hyperintensity volume (β = 0.11; P = 0.007; β = 0.10; P = 0.01) in univariate and multivariable analyses of log-transformed data. Results were similar when excluding individuals with macroalbuminuria. Limitations Single measurement of ACR, indirect creatinine calibration, and reliance on participant recall for elements of medical history. Conclusions Albuminuria is associated with worse cognitive performance, particularly in executive functioning, as well as increased white matter hyperintensity volume. Albuminuria likely identifies greater brain microvascular disease burden.

OBJECTIVES. The goals were to determine how frequently primary care clinicians reported suspected physical child abuse, the levels of suspicion associated with reporting, and what factors influenced reporting to child protective services. METHODS. In this prospective observational study, 434 clinicians collected data on 15003 child injury visits, including information about the injury, child, family, likelihood that the injury was caused by child abuse (5-point scale), and whether the injury was reported to child protective services. Data on 327 clinicians indicating some suspicion of child abuse for 1683 injuries were analyzed. RESULTS. Clinicians reported 95 (6%) of the 1683 patients to child protective services. Clinicians did not report 27% of injuries considered likely or very likely caused by child abuse and 76% of injuries considered possibly caused by child abuse. Reporting rates were increased if the clinician perceived the injury to be inconsistent with the history and if the patient was referred to the clinician for suspected child abuse. Patients who had an injury that was not a laceration, who had >1 family risk factor, who had a serious injury, who had a child risk factor other than an inconsistent injury, who were black, or who were unfamiliar to the clinician were more likely to be reported. Clinicians who had not reported all suspicious injuries during their career or who had lost families as patients because of previous reports were more likely to report suspicious injuries. CONCLUSIONS. Clinicians had some degree of suspicion that ∼10% of the injuries they evaluated were caused by child abuse. Clinicians did not report all suspicious injuries to child protective services, even if the level of suspicion was high (likely or very likely caused by child abuse). Child, family, and injury characteristics and clinician previous experiences influenced decisions to report.

OBJECTIVES. Primary care clinicians participating in the Child Abuse Reporting Experience Study did not report all suspected physical child abuse to child protective services. This evaluation of study data seeks (1) to identify factors clinicians weighed when deciding whether to report injuries they suspected might have been caused by child abuse; (2) to describe clinicians’ management strategies for children with injuries from suspected child abuse that were not reported; and (3) to describe how clinicians explained not reporting high-suspicion injuries. METHODS. From the 434 pediatric primary care clinicians who participated in the Child Abuse Reporting Experience Study and who indicated they had provided care for a child with an injury they perceived as suspicious, a subsample of 75 of 81 clinicians completed a telephone interview. Interviewees included 36 clinicians who suspected child abuse but did not report the injury to child protective services (12 with high suspicion and 24 with some suspicion) and 39 who reported the suspicious injury. Interviews were analyzed for major themes and subthemes, including decision-making regarding reporting of suspected physical child abuse to child protective services and alternative management strategies. RESULTS. Four major themes emerged regarding the clinicians’ reporting decisions, that is, familiarity with the family, reference to elements of the case history, use of available resources, and perception of expected outcomes of reporting to child protective services. When they did not report, clinicians planned alternative management strategies, including active or informal case follow-up management. When interviewed, some clinicians modified their original opinion that an injury was likely or very likely caused by abuse, to explain why they did not report to child protective services. CONCLUSIONS. Decisions about reporting to child protective services are guided by injury circumstances and history, knowledge of and experiences with the family, consultation with others, and previous experiences with child protective services.

Purpose To present an updated analysis of survival, recurrence rate, and toxicity for a cohort of women with early-stage breast cancer treated with high-dose-rate interstitial brachytherapy for accelerated partial breast irradiation. Methods and materials From August 1997 to July 2001, a total of 32 women with 33 breast cancers were treated with interstitial high-dose-rate brachytherapy after breast-conserving surgery as part of a Phase I/II protocol. All patients had T1–2 tumors with ≤3 axillary nodes positive, nonlobular histology, negative surgical margins, and no evidence of extracapsular lymph node extension. Multiple brachytherapy catheters were used and radiation was delivered with a high activity (3–10 Ci) 192Ir source placed via remote after loader. Dose was prescribed to the tumor bed plus a 2 cm margin. A total of 3400 cGy was delivered in 10 fractions of 340 cGy each given twice daily over 5 days. Toxicities (skin, subcutaneous tissue, pain, fat necrosis) were evaluated by Radiation Therapy Oncology Group criteria; cosmesis was assessed using a previously published scale. Toxicity scores were separated into four followup intervals: ≤6 months, >6 months and ≤2 years, >2 and ≤5 years, and >5 years. Results The actuarial local recurrence rate was 6.1% at 5 years with the last measured event at 70.5 months. A total of three treatment failures were observed at 25.8, 39.9, and 70.5 months of followup. All three were elsewhere failures within the treated breast. One patient died after 90.0 months of followup secondary to a subsequently diagnosed small-cell lung cancer. For the purpose of analysis, toxicity scores were assigned to each of four followup intervals: ≤6 months, >6 but ≤24 months, >24 but ≤60 months, and >60 months. Fat necrosis was not seen in the first 6 months after treatment, then appeared in 27.3% of patients from 6 to 24 months, 28.1% from 24 to 60 months, and 17.9% beyond 60 months. Skin toxicity appeared to stabilize with longer followup: the percentage of patients showing any degree of skin toxicity was 69.7%, 33.3%, 40.6%, and 28.6% at each successive time interval. Subcutaneous toxicity increased beyond 60 months: moderate to severe subcutaneous toxicity was seen in 15.2%, 18.2%, 18.8%, and 35.7% of patients successively. The percentage of patients with less than excellent cosmetic outcome improved beyond 60 months (21.2%, 21.2%, 21.9%, and 11.1% successively). Only 1 patient experienced more than mild pain at any time. The percentage of patients experiencing any degree of pain improved over time (30.3%, 33.3%, 18.8%, 17.9%). Conclusions Our series showed a local recurrence rate of 6.1% at 5 years, which is comparable to that seen in conventional whole breast series. Fat necrosis was found in more than half the cohort. Fat necrosis, pain, and cosmesis appeared to improve with longer followup, whereas subcutaneous toxicity worsened and skin toxicity stabilized.

BACKGROUND: Selection of cancer treatment fundamentally relies on staging of the underlying malignancy. The aim of this study was to evaluate the feasibility and effectiveness of laparoscopic narrow band imaging (NBI) for operative staging and detection of occult peritoneal cancer metastases. METHODS: A randomized, controlled feasibility trial with crossover design evaluating adult patients with gastrointestinal or gynecologic malignancies who have a clinical indication for diagnostic laparoscopy was conducted. Twenty-three patients were randomized to white-light followed by NBI laparoscopy (n = 11) or NBI followed by white-light laparoscopy (n = 12) using the Olympus Evis Exera II system. Three patients were excluded from analysis. RESULTS: In all 20 study patients, the abdominal cavity was sufficiently illuminated. An enhanced contrast of microvasculature and organ surface pattern was appreciated. Eight of the 20 patients (40 %) were found to have metastases of the peritoneal surface. While NBI did not show any additional peritoneal lesions, 2 of the 63 suspicious-appearing nodules seen on white-light imaging were not visible on NBI (p = 0.50). The median diameter of all the nodules identified was 2 mm (range 1–50 mm) and was identical with each method. CONCLUSIONS: The information from this feasibility study demonstrated that NBI provides adequate illumination of the abdominal cavity and a unique contrast that enhances microvasculature and architectural surface pattern. The results suggest that NBI laparoscopy is not superior in detecting peritoneal metastases compared to standard white-light laparoscopy, but might provide a technology that could be applied for other abdominal pathologies.

Background Fibromyalgia is a chronic musculoskeletal pain syndrome that causes substantial physical and psychological impairment and costs the US healthcare system over $25 billion annually. Current pharmacological therapies may cause serious adverse effects, are expensive, and fail to effectively improve pain and function. Finding new and effective non-pharmacological treatments for fibromyalgia patients is urgently needed. We are currently conducting the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise (a recommended component of the current standard of care) in a large fibromyalgia population. This article describes the design and conduct of this trial. Methods/design A single-center, 52-week, randomized controlled trial of Tai Chi versus aerobic exercise is being conducted at an urban tertiary medical center in Boston, Massachusetts. We plan to recruit 216 patients with fibromyalgia. The study population consists of adults ≥21 years of age with fibromyalgia who meet American College of Rheumatology 1990 and 2010 diagnostic criteria. Participants are randomized to one of four Tai Chi intervention groups: 12 or 24 weeks of supervised Tai Chi held once or twice per week, or a supervised aerobic exercise control held twice per week for 24 weeks. The primary outcome is the change in Revised Fibromyalgia Impact Questionnaire total score from baseline to 24 weeks. Secondary outcomes include measures of widespread pain, symptom severity, functional performance, balance, muscle strength and power, psychological functioning, sleep quality, self-efficacy, durability effects, and health-related quality of life at 12, 24, and 52 week follow-up. Discussion This study is the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise in a large fibromyalgia population with long-term follow up. We present here a robust and well-designed trial to determine the optimal frequency and duration of a supervised Tai Chi intervention with regard to short- and long-term effectiveness. The trial also explores multiple outcomes to elucidate the potential mechanisms of Tai Chi and aerobic exercise and the generalizability of these interventions across instructors. Results of this study are expected to have important public health implications for patients with a major disabling disease that incurs substantial health burdens and economic costs. Trial registration ClinicalTrials.gov identifier: NCT01420640, registered 18 August 2011. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-0548-x) contains supplementary material, which is available to authorized users.

The purpose of this study was to expand and validate the cartilage damage index (CDI) to detect cartilage damage in thelateraltibiofemoral compartment. We used an iterative 3-step process to develop and validate the lateral CDI: development (100 knees), testing (80 knees), and validation (100 knees). The validation set included 100 knees from the Osteoarthritis Initiative that was enriched to include all grades of lateral joint space narrowing (JSN, 0–3). Measurement of the CDI was rapid at 7.4 (s.d. 0.73) minutes per knee pair (baseline and follow-up of one knee). The intratester reliability is good (intraclass correlation coefficient (3, 1 model) = 0.86 to 0.98). At baseline, knees with greater KL grade and lateral JSN had a lower mean CDI (i.e., greater cartilage damage). Baseline lateral CDI is associated with both lateral JSW (r=0.81to 0.85,p<0.01) and HKA (r=-0.30to −0.33,p<0.05). The SRM is good (lateral femur SRM = −0.76; lateral tibia SRM = −0.73; lateral tibiofemoral total SRM = −0.87). The lateral tibiofemoral CDI quantification allows for rapid evaluation and is reliable and responsive, with good construct validity. It may be an efficient method to measure lateral tibiofemoral articular cartilage in large clinical and epidemiologic studies.

Subchondral bone marrow lesions (BMLs) are related to structural and symptomatic osteoarthritis progression. However, it is unclear how sequence selection influences a quantitative BML measurement and its construct validity. We compared quantitative assessment of BMLs on intermediate-weighted fat suppressed (IW FS) turbo spin echo and 3-dimensional dual echo steady state (3D DESS) sequences. We used a customized software to measure 30 knees’ (24- and 48-month MR images) BMLs on both sequences. The results showed that the IW FS sequences have much larger BML volumes (median: IW FS = 1840 mm3; DESS = 191 mm3) and BML volume change (between 24 and 48 months) than DESS sequence and demonstrate more BML volume change. The 24-month BML volume on IW FS is correlated with BML volume on DESS (rs= 0.83). BML volume change on IW FS is not significantly correlated with change on DESS. The 24-month WOMAC pain is correlated with the 24-month BMLs on IW FS (rs= 0.39) but not DESS. The change in WOMAC pain is correlated with BML volume change on IW FS (rs= 0.37) but not DESS. Overall, BML quantification on IW FS offers better validity and statistical power than BML quantification on a 3D DESS sequence.

Background Personnel in Armed Forces entities such as the US Coast Guard (USCG) engage in strenuous tasks requiring high levels of physiological and psychological fitness. Previous reports have found increased prevalence of dietary supplement (DS) use by military personnel to meet the demands of their occupation. Objective This study assessed DS prevalence and patterns of use in USCG personnel and compared these findings to reports from other Armed Forces personnel. Design Use of DS by USCG personnel (n = 1059) was assessed by survey at USCG installations. Data were weighted by age, sex, and rank to be representative of total USCG demographics. Results Seventy percent of USCG personnel reported using a DS at least 1 time/wk. Thirty-three percent used 1–2 DS ≤ 1 time/wk, 18% 3–4 DS ≥ 1 time/wk, and almost 19% ≥ 5 DS ≥ 1 time/wk. Average expenditure on DSs by UCSG personnel was $40/mo. More than 47% of USCG personnel used a multivitamin and mineral, 33% consumed protein supplements, 22% used individual vitamins and minerals, 23% reported taking combination products, and 9% consumed herbal supplements. Increased use of DS use was associated with high intensity operational occupations, participating in high volumes of aerobic exercise and strength training. Use of DS was not associated with age, education or body mass index. Conclusion Occupation is an important determinate of DS use. Prevalence of DS use by USCG personnel is greater than reported for other Armed Forces personnel and reflects high levels of participation in aerobic and strength training activities.

Pediatrician experience with child protective services (CPS) and factors associated with identifying and reporting suspected child physical abuse were examined by a survey of members of the American Academy of Pediatrics (AAP). Respondents provided information about their demographics and experience, attitudes and practices with child abuse. They indicated their diagnosis and management of a child in a purposely ambiguous clinical vignette. Pediatricians who had received recent child abuse education were more confident in their ability to identify and manage child abuse. High confidence in ability to manage child abuse and positive attitude about domestic violence screening and value of anticipatory guidance predicted that pediatricians would have high suspicion that the child in the vignette was abused and that they would report the child to CPS. Future efforts to improve medical intervention in child abuse should focus on physician attitudes and experience, as well as cognitive factors.

OBJECTIVES: To describe patterns of cognitive deficits and activities of daily living (ADLs) in older people with diabetes mellitus. DESIGN: Cross-sectional, population-based study. SETTING: Three homecare agency areas in Boston, Massachusetts. PARTICIPANTS: Two hundred ninety-one homebound people aged 60 and older; 40% with diabetes mellitus. MEASUREMENTS: Demographic data; evidence of diabetes mellitus and other diseases; Mini-Mental State Examination and tests of memory and executive function; ADLs. RESULTS: Executive and visuospatial functions were more impaired in individuals with diabetes mellitus than in those without, as assessed using Block Design (mean score±standard deviation 17.1±8.6 vs 20.5±9.6, P=.003) and Trails B (median seconds to accomplish the task: 255 vs 201, P=.03). For memory, word retention score was lower in those with diabetes mellitus than without (39.1±28.9 vs 48.0±29.7, P=.01), but the other memory tests did not show a difference between these two subgroups. More individuals with diabetes mellitus suffered from depressive symptoms than those without (55% vs 42%, P=.03). The ADL scores of those with diabetes mellitus were higher than those without. CONCLUSION: The pattern of cognitive deficits in people with diabetes mellitus suggests frontal-subcortical dysfunction, as seen in microvascular disease of the brain. The impairment in ADLs may be associated with this executive dysfunction, which cerebral microvascular disease in diabetes mellitus may cause.

Background Micronutrient status can affect cognitive function in the elderly; however, there is much to learn about the precise effects. Understanding mediating factors by which micronutrient status affects cognitive function would contribute to elders' quality of life and their ability to remain in the home. Objectives The Nutrition, Aging, and Memory in Elders (NAME) Study is designed to advance the current level of knowledge by investigating potential mediating factors by which micronutrient status contributes to cognitive impairment and central nervous system abnormalities in the elderly. NAME targets homebound elders because they are understudied and particularly at risk for poor nutritional status. Methods Subjects are community-based elders aged 60 and older, recruited through area Aging Services Access Points. The NAME core data include demographics; neuropsychological testing and activities of daily living measures; food frequency, health and behavioral questionnaires; anthropometrics; gene status; plasma micronutrients, homocysteine, and other blood determinants. A neurological examination, psychiatric examination, and brain MRI and volumetric measurements are obtained from a sub-sample. Results Preliminary data from first 300 subjects are reported. These data show that the NAME protocol is feasible and that the enrolled subjects are racially diverse, at-risk, and had similar basic demographics to the population from which they were drawn. Conclusion The goal of the NAME study is to evaluate novel relationships between nutritional factors and cognitive impairment. These data may provide important information on potential new therapeutic strategies and supplementation standards for the elderly to maintain cognitive function and potentially reduce the public health costs of dementia. Copyright © 2006 John Wiley & Sons, Ltd.

Neutropenia after orthotopic liver transplantation (LT) is relatively common, but the factors associated with its development remain elusive. We assessed possible predictors of neutropenia (absolute neutrophil count [ANC] ≤ 1000/mm(3) ) within the first year of LT in a cohort of 304 patients at a tertiary medical center between 1999 and 2009 using time-dependent survival analysis to identify risk factors for neutropenia. In addition, we analyzed neutropenia as a predictor of the clinical outcomes of death, bloodstream infection (BSI), invasive fungal infection, cytomegalovirus (CMV) disease, and graft rejection within the first year of LT. Of the 304 LT recipients, 73 (24%) developed neutropenia, 5 (7%) of whom had grade 4 neutropenia (ANC < 500/mm(3) ). The following were independent predictors for neutropenia: Child-Turcotte-Pugh score (hazard ratio [HR] 1.15; 95% confidence interval [CI], 1.03-1.30; P = 0.02), BSI (HR, 2.89; 95% CI, 1.63-5.11; P < 0.001), CMV disease (HR, 4.28; 95% CI, 1.55-11.81; P = 0.005), baseline tacrolimus trough level (HR, 1.02; 95% CI, 1.01-1.03; P = 0.007), and later era LT (2004-2009 versus 1999-2003; HR, 2.28; 95% CI, 1.43-3.65; P < 0.001). Moreover, neutropenia was found to be an independent predictor for mortality within the first year of LT (HR, 3.76; 95% CI, 1.84-7.68; P < 0.001). In conclusion, our data suggest that neutropenia within a year after LT is not unusual and is an important predictor of mortality.

BackgroundKnee osteoarthritis causes functional limitation and disability in the elderly. Vitamin D has biological functions on multiple knee joint structures and can play important roles in the progression of knee osteoarthritis. The metabolism of vitamin D is regulated by parathyroid hormone (PTH).ObjectiveThe objective was to investigate whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] and PTH, individually and jointly, predict the progression of knee osteoarthritis.MethodsSerum 25(OH)D and PTH were measured at the 30- or 36-mo visit in 418 participants enrolled in the Osteoarthritis Initiative (OAI) who had ≥1 knee with both symptomatic and radiographic osteoarthritis. Progression of knee osteoarthritis was defined as any increase in the radiographic joint space narrowing (JSN) score between the 24- and 48-mo OAI visits.ResultsThe mean concentrations of serum 25(OH)D and PTH were 26.2 μg/L and 54.5 pg/mL, respectively. Approximately 16% of the population had serum 25(OH)D < 15 μg/L. Between the baseline and follow-up visits, 14% progressed in JSN score. Participants with low vitamin D [25(OH)D < 15 μg/L] had >2-fold elevated risk of knee osteoarthritis progression compared with those with greater vitamin D concentrations (≥15 μg/L; OR: 2.3; 95% CI: 1.1, 4.5). High serum PTH (≥73 pg/mL) was not associated with a significant increase in JSN score. However, participants with both low vitamin D and high PTH had >3-fold increased risk of progression (OR: 3.2; 95%CI: 1.2, 8.4).ConclusionOur results suggest that individuals deficient in vitamin D have an increased risk of knee osteoarthritis progression.

Background and Purpose— Women experience worse outcomes after stroke compared with men. Prior work has suggested sex-based differences in coagulation and fibrinolysis markers in subjects with acute stroke. We explored whether sex might modify the effect of recombinant tissue plasminogen activator (rtPA) on outcomes in patients with acute ischemic stroke. Methods— Using a combined database including subjects from the National Institute of Neurological Disorders and Stroke (NINDS), Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) A and B, and the Second European Cooperative Acute Stroke Study (ECASS II) trials, we examined 90-day outcomes in patients randomized to rtPA versus placebo by sex. We used logistic regression to control for potential confounders. Results— Among 988 women treated between 0 and 6 hours from symptom onset, patients receiving rtPA were significantly more likely than those receiving placebo to have a modified Rankin Score ≤1 (40.5% versus 30.3%, P P =0.52). An unadjusted analysis showed that women were significantly more likely to benefit from rtPA compared with men ( P =0.04). Controlling for age, baseline National Institutes of Health Stroke Scale, diabetes, symptom onset to treatment time, prior stroke, systolic blood pressure, extent of hypoattenuation on baseline computed tomography scan and several significant interaction terms (including onset to treatment time–by-treatment and systolic blood pressure–by treatment) did not substantially change the strength of the interaction between gender and rtPA treatment ( P =0.04). Conclusions— In this pooled analysis of rtPA in acute ischemic stroke, women benefited more than men, and the usual gender difference in outcome favoring men was not observed in the thrombolytic therapy group. For patients presenting at later time intervals, when the risks and benefits of rtPA are more finely balanced, sex may be an important variable to consider for patient selection.

Primary biliary cirrhosis frequently progresses despite treatment with ursodeoxycholic acid (UDCA), the only approved therapy. Previous studies suggested that colchicine and methotrexate may improve biochemical tests of liver function, symptoms, and liver histology. The aim of the present study was to determine if the addition of colchicine or methotrexate to UDCA would improve survival free of liver transplantation. Eighty-five patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase levels were at least twice the normal level and who were not yet candidates for liver transplantation were randomly assigned to receive colchicine or methotrexate in a double-blind study. UDCA was administered to all patients after 2 years. The primary end point was survival free of liver transplantation. Patients were followed up for a total of up to 10 years or until treatment failure. Data were analyzed on an intention-to-treat basis. Transplant-free survival was similar in both groups: 0.57 for colchicine plus UDCA and 0.44 for methotrexate plus UDCA, results that are similar to those predicted by the Mayo prognostic model. Significant improvement in liver biochemical tests and liver histology was observed in a subset of patients in both treatment groups who remained in the study for all 10 years. In conclusion, neither colchcine plus UDCA nor methotrexate plus UDCA improved survival beyond that predicted by the Mayo prognostic model. However, clinical, histologic, and biochemical improvement observed among those who remained in the study for 10 years suggests a possible benefit of these drugs in a subset of patients.

Purpose To compare computer-assisted planimetry using the Discam system (Marcher Enterprises Ltd., Hereford, UK), confocal scanning laser ophthalmoscopy (CSLO), and stereoscopic disc photography with respect to optic nerve head (ONH) measurements and glaucoma status.

Objective To examine the association between baseline mindfulness and response from exercise interventions in knee osteoarthritis (OA). Design Cohort study; responder analysis of a clinical trial subset. Setting Urban tertiary care academic hospital. Participants Participants with symptomatic, radiographic knee OA (N=86; mean age, 60y; 74% female; 48% white). Interventions Twelve weeks (twice per week) of Tai Chi or physical therapy exercise. Main Outcome Measures Treatment response was defined using Osteoarthritis Research Society International criteria indicating meaningful improvements in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, WOMAC function, or Patient Global Assessment scores. At baseline, participants completed the Five Facet Mindfulness Questionnaire (mean total score, 142±17) and were grouped into 3 categories of total mindfulness: higher, medium, or lower. Relative risk (RR) ratios were used to compare treatment response across groups. Results Participants with higher total mindfulness were 38% (95% confidence interval [CI], 1.05–1.83) more likely to meet responder criteria than those with lower mindfulness. We found no significant difference between medium and lower mindfulness groups (RR=1.0; 95% CI, 0.69–1.44). Among the 5 mindfulness facets, medium acting-with-awareness was 46% (95% CI, 1.09–1.96) more likely to respond than lower acting-with-awareness, and higher acting-with-awareness was 34% more likely to respond, but this did not reach significance (95% CI, 0.97–1.86). Conclusions In this study, higher mindfulness, primarily driven by its acting-with-awareness facet, was significantly associated with a greater likelihood of response to nonpharmacologic exercise interventions in knee OA. This suggests that mindfulness-cultivating interventions may increase the likelihood of response from exercise.

Importance Synovitis is common and is associated with progression of structural characteristics of knee osteoarthritis. Intra-articular corticosteroids could reduce cartilage damage associated with synovitis but might have adverse effects on cartilage and periarticular bone. Objective To determine the effects of intra-articular injection of 40 mg of triamcinolone acetonide every 3 months on progression of cartilage loss and knee pain. Design, setting, and participants Two-year, randomized, placebo-controlled, double-blind trial of intra-articular triamcinolone vs saline for symptomatic knee osteoarthritis with ultrasonic features of synovitis in 140 patients. Mixed-effects regression models with a random intercept were used to analyze the longitudinal repeated outcome measures. Patients fulfilling the American College of Rheumatology criteria for symptomatic knee osteoarthritis, Kellgren-Lawrence grades 2 or 3, were enrolled at Tufts Medical Center beginning February 11, 2013; all patients completed the study by January 1, 2015. Interventions Intra-articular triamcinolone (n = 70) or saline (n = 70) every 12 weeks for 2 years. Main outcomes and measures Annual knee magnetic resonance imaging for quantitative evaluation of cartilage volume (minimal clinically important difference not yet defined), and Western Ontario and McMaster Universities Osteoarthritis index collected every 3 months (Likert pain subscale range, 0 [no pain] to 20 [extreme pain]; minimal clinically important improvement, 3.94). Results Among 140 randomized patients (mean age, 58 [SD, 8] years, 75 women [54%]), 119 (85%) completed the study. Intra-articular triamcinolone resulted in significantly greater cartilage volume loss than did saline for a mean change in index compartment cartilage thickness of -0.21 mm vs -0.10 mm (between-group difference, -0.11 mm; 95% CI, -0.20 to -0.03 mm); and no significant difference in pain (-1.2 vs -1.9; between-group difference, -0.6; 95% CI, -1.6 to 0.3). The saline group had 3 treatment-related adverse events compared with 5 in the triamcinolone group and had a small increase in hemoglobin A1c levels (between-group difference, -0.2%; 95% CI, -0.5% to -0.007%). Conclusions and relevance Among patients with symptomatic knee osteoarthritis, 2 years of intra-articular triamcinolone, compared with intra-articular saline, resulted in significantly greater cartilage volume loss and no significant difference in knee pain. These findings do not support this treatment for patients with symptomatic knee osteoarthritis. Trial registration ClinicalTrials.gov Identifier: NCT01230424.

Background Cytomegalovirus (CMV) is a major contributor to morbidity and mortality in solid organ transplant recipients (SOTRs). Ganciclovir and valganciclovir are highly effective antiviral drugs with a well-established role in primary prophylaxis and treatment of CMV disease. Our objective in this study was to examine the effect of secondary prophylaxis (SP) on the risk of relapse in SOTRs following an episode of CMV disease. Methods We performed a retrospective cohort study of SOTRs from 1995 to 2015 and used propensity score-based inverse probability of treatment weighting methodology to control for confounding by indication. A weighted Cox model was created to determine the effect of SP on time to relapse within 1 year of treatment completion. Results Fifty-two heart, 34 liver, 79 kidney, and 5 liver-kidney transplant recipients who completed treatment for an episode of CMV infection/disease were included. A total of 120 (70.6%) received SP (median duration, 61 days; range, 5-365) and 39 (23%) relapsed. SP was protective against relapse from 0 to 6 weeks following treatment completion (hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.05-0.69). However, after 6 weeks, risk of relapse did not significantly differ between the 2 groups (HR, 1.18; 95% CI, 0.46-2.99). Conclusions Our findings demonstrate that use of SP following treatment of CMV disease did not confer long-term protection against relapse, although it did delay relapse while patients were receiving antivirals. This suggests that SP has limited clinical utility in the overall prevention of recurrent CMV disease.

Background Knee osteoarthritis (OA) causes pain and long-term disability with annual healthcare costs exceeding $185 billion in the United States. Few medical remedies effectively influence the course of the disease. Finding effective treatments to maintain function and quality of life in patients with knee OA is one of the national priorities identified by the Institute of Medicine. We are currently conducting the first comparative effectiveness and cost-effectiveness randomized trial of Tai Chi versus a physical-therapy regimen in a sample of patients with symptomatic and radiographically confirmed knee OA. This article describes the design and conduct of this trial. Methods/Design A single-center, 52-week, comparative effectiveness randomized controlled trial of Tai Chi versus a standardized physical-therapy regimen is being conducted at an urban tertiary medical center in Boston, Massachusetts. The study population consists of adults ≥ 40 years of age with symptomatic and radiographic knee OA (American College of Rheumatology criteria). Participants are randomly allocated to either 12 weeks of Tai Chi (2x/week) or Physical Therapy (2x/week for 6 weeks, followed by 6 weeks of rigorously monitored home exercise). The primary outcome measure is pain (Western Ontario and McMaster Universities WOMAC) subscale at 12 weeks. Secondary outcomes include WOMAC stkiffness and function domain scores, lower extremity strength and power, functional balance, physical performance tests, psychological and psychosocial functioning, durability effects, health related quality of life, and healthcare utilization at 12, 24 and 52 weeks. Discussion This study will be the first randomized comparative-effectiveness and cost-effectiveness trial of Tai Chi versus Physical Therapy in a large symptomatic knee OA population with long-term follow up. We present here a robust and well-designed randomized comparative-effectiveness trial that also explores multiple outcomes to elucidate the potential mechanisms of mind-body effect for a major disabling disease with substantial health burdens and economic costs. Results of this study are expected to have important public health implications for the large and growing population with knee OA. Trial registration ClinicalTrials.gov identifier: NCT01258985 Electronic supplementary material The online version of this article (doi:10.1186/1472-6882-14-333) contains supplementary material, which is available to authorized users.

Infection after liver transplantation (LT) remains a leading cause of morbidity and mortality. The risk of infection after LT is highest in those who are most immunosuppressed, but to date, no standard blood marker of one's degree of immunosuppression or risk index has been established. The purpose of this study was to determine whether pretransplant lymphopenia (absolute lymphocyte count

To determine whether the presence of spontaneous echocardiographic contrast (SEC) in cats with cardiomyopathy is associated with increased mortality. To establish whether specific types of cardiomyopathy are more often associated with SEC in an attempt to provide a risk-stratification scheme for cats with increased risk of thromboembolic events.Retrospective study 2006-2011.Tertiary referral and teaching hospital.Seven hundred twenty-five client-owned cats undergoing echocardiographic evaluation.Patient characteristics, including age, breed, clinical signs, type of cardiovascular disease, presence of SEC, and survival time were recorded. Thyroxine, HCT, and blood pressure were recorded when available. Among cats diagnosed with cardiac abnormalities based on echocardiographic findings, those with SEC were at significantly increased risk of death as compared to those without SEC. Cats with dilated cardiomyopathy, unclassified cardiomyopathy, and hypertrophic cardiomyopathy were significantly more likely to have SEC compared to cats with other types of cardiac disease.Cats with cardiomyopathy and SEC have an increased risk of death compared to cats without SEC, although other previously identified factors such as the presence of congestive heart failure and increased left atrium to aorta ratio remain important determinants of mortality. Cats with hypertrophic cardiomyopathy, unclassified cardiomyopathy, and dilated cardiomyopathy may benefit from anticoagulant therapy due to the increased risk of SEC in these subpopulations.

Background In the knee, high-resolution magnetic resonance (MR) imaging has demonstrated that increased apparent bone volume fraction (trabecular bone volume per total volume; BV/TV) in the peri-articular proximal medial tibia is associated with joint space narrowing and the presence of bone marrow lesions. However, despite evidence of construct validity, MR-based apparent BV/TV has not yet been cross-validated in the proximal medial tibia by comparison with a gold standard (e.g., micro-computed tomography [microCT]). In this cadaveric validation study we explored the association between MR-based apparent BV/TV and microCT-based BV/TV in the proximal peri-articular medial tibia. Methods Fresh cadaveric whole knee specimens were obtained from individuals 51 to 80 years of age with no knee pathology other than osteoarthritis. Ten knees were collected from five cadavers within 10 hours of death and underwent a 3-Tesla MR exam including a coronal-oblique 3-dimensional fast imaging with steady state precession (3D FISP) sequence within 36 hours of death. The specimens were placed in a 4% paraformaldehyde in phosphate buffer within 58 hours of death. After preservation, a subchondral region from the tibial plateau was collected and underwent microCT imaging with a voxel size of 9 μm x 9 μm x 9 μm. A single reader analyzed the microCT images in a similar volume of interest as selected in the MR measures. A different reader analyzed the MR-based trabecular morphometry using a custom analysis tool. To analyze the MR-based trabecular morphometry, a rectangular region of interest (ROI) was positioned on the 20 central images in the proximal medial tibial subchondral bone. The primary outcome measures were MR-based and microCT-based trabecular BV/TV in the proximal medial tibia. Results The MR-based apparent BV/TV was strongly correlated with microCT-based BV/TV (r = 0.83, confidence interval = 0.42 to 0.96), despite the MR-based apparent BV/TV being systematically lower than measured using microCT. Conclusions MR-based apparent BV/TV in the proximal peri-articular medial tibia has good construct validity and may represent an alternative for CT-based BV/TV.

This study is designed to measure the impact of orthotopic liver transplantation (OLT) on patients' health-related quality of life. Two types of health-related quality-of-life questionnaires were administered at baseline and after OLT: generic (Medical Outcomes Study Short Form 36) and liver specific (Chronic Liver Disease Questionnaire). We also recorded clinical, demographic, and laboratory data. Pre-OLT scores of liver transplant candidates were compared with those of the general population and patients with congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD). Thirty-seven liver transplant candidates were evaluated: 25 men and 12 women; age, 50.2 ± 12 years; Child's class A, 3 patients; class B, 30 patients; class C, 4 patients; and galactose elimination capacity, 277 ± 81. Health-related quality-of-life scores for patients awaiting liver transplants were significantly lower than those for patients with COPD and CHF and those in the general population. Sex and cause of liver disease did not affect the scores. There was a weak but significant inverse correlation between some aspects of health-related quality of life and both age ( r = –0.31 to –0.34) and worsening of the Child-Pugh score ( r = –0.32 to –0.43). All measured aspects of health-related quality of life significantly improved after OLT, and mental health scores were indistinguishable from the population norms. Similar improvements were evident in physical and disease-specific aspects of health-related quality of life, but some residual dysfunction persisted. (Liver Transpl 2000;6:779-783.)

Introduction: The current emphasis on providing holistic competent and efficient healthcare has revealed a need to nurture providers' compassionate and relationship-centred care throughout the continuum of medical education. Methods: Our resident-as-teacher programme trained 41 residents from core clerkships at six clinical sites in the United States of America (USA) to teach and practice compassionate care through role-modelling. The programme focused on resident's demonstrations or failures to demonstrate compassionate care with peers, students and healthcare providers, and engaged residents in disseminating their experience to their colleagues. A mixed-method evaluation assessed short-term outcomes at multiple levels through the collection of resident's: pre- and post-programme scores on empathy scale, performance on standardised patient (SP) exercise, and self-assessment of their performance on relationship-centred care skills; journal reflections; presentations delivered at their site and attendees' evaluation; evaluation of the programme. Quantitative data was analysed calculating descriptive statistics and paired sample t -tests, using SAS. Qualitative data was analysed performing open coding and code frequency counts to identify emergent themes. Results: Residents had empathy scores within the average range, and high scores on SP assessments throughout the programme. The programme had a positive impact on resident's perceptions of their relationship-centred skills. Residents found the programme useful, and emphasised the importance of mindfulness, active presence and slowing down-and were concerned with addressing these needs in daily practice. Eighteen presentations were delivered across sites. Attendees found the presentations useful and necessary in their training. Conclusions: Residents successfully reflected on, embodied and disseminated the programme's core concepts on their rotations. This group required validation of their commitment to compassionate care, and sought strategies to embody their commitment while inspiring other providers, residents and students.

Objectives To (1) determine a reference interval for shock index (SI) [defined as heart rate (HR)/systolic blood pressure (SBP)], in a group of healthy dogs, and (2) compare SI in healthy dogs with dogs presenting to the emergency room (ER) deemed to be in or not in a state of shock. Design Prospective study. Animals Sixty‐eight clinically normal dogs, 18 dogs that were presented to the ER deemed to be in shock and 19 dogs presenting to the ER not deemed to be in shock. Setting University teaching hospital. Interventions Peripheral or central venous blood sampling. Measurements and Main Results Heart rate and SBP were recorded on simulated presentation (healthy dogs), and emergency presentations for both dogs deemed to be in shock and dogs not deemed in shock. Dogs in shock had a median SI of 1.37 (0.87–3.13), which was significantly higher than both other groups; dogs not deemed in shock had median SI 0.73 (0.56–1.20), P < 0.0001 and healthy dogs had median SI 0.78 (0.37–1.30) P < 0.0001), respectively. Receiver operator characteristic curve analysis suggested a SI cut‐off of 1.0, yielding an area under the receiver operator characteristic (AUROC) of 0.89 (Specificity (Sp) 89, Sensitivity (Sn) 90) when comparing dogs deemed in shock with healthy dogs, and 0.92 (Sp 95, Sn 89) when comparing dogs in shock with to dogs not deemed in shock. Conclusions The SI is an easy and noninvasive patient parameter that is higher in dogs that are deemed to be in shock than both healthy dogs and dogs presented as emergencies but not deemed to be in a state of shock. The measurement of SI may have some benefit in clinical assessment of emergency patients.

Lustgarten, MS, Price, LL, Phillips, EM, Kirn, DR, Mills, J, and Fielding, RA. Serum predictors of percent lean mass in young adults. J Strength Cond Res 30(8): 2194-2201, 2016-Elevated lean (skeletal muscle) mass is associated with increased muscle strength and anaerobic exercise performance, whereas low levels of lean mass are associated with insulin resistance and sarcopenia. Therefore, studies aimed at obtaining an improved understanding of mechanisms related to the quantity of lean mass are of interest. Percent lean mass (total lean mass/body weight × 100) in 77 young subjects (18-35 years) was measured with dual-energy x-ray absorptiometry. Twenty analytes and 296 metabolites were evaluated with the use of the standard chemistry screen and mass spectrometry-based metabolomic profiling, respectively. Sex-adjusted multivariable linear regression was used to determine serum analytes and metabolites significantly (p ≤ 0.05 and q ≤ 0.30) associated with the percent lean mass. Two enzymes (alkaline phosphatase and serum glutamate oxaloacetate aminotransferase) and 29 metabolites were found to be significantly associated with the percent lean mass, including metabolites related to microbial metabolism, uremia, inflammation, oxidative stress, branched-chain amino acid metabolism, insulin sensitivity, glycerolipid metabolism, and xenobiotics. Use of sex-adjusted stepwise regression to obtain a final covariate predictor model identified the combination of 5 analytes and metabolites as overall predictors of the percent lean mass (model R = 82.5%). Collectively, these data suggest that a complex interplay of various metabolic processes underlies the maintenance of lean mass in young healthy adults.

Background— Epidemiology data for lower-extremity arterial thromboembolism (LET) are limited and may result from either acute limb ischemia or an acute exacerbation of critical limb ischemia. Given marked changes in both diagnosis and therapy over the last 2 decades, we hypothesized that this time period would have witnessed reductions in both the incidence and in-hospital mortality of LET. Methods and Results— Data from 1988 through 2007 from the National Hospital Discharge Survey were analyzed. All admissions for patients with LET were extracted, and the respective International Classification of Diseases, Ninth Revision, Clinical Modification codes were internally validated for both LET and acute limb ischemia. Descriptive statistics were used. The validity of the codes was good for identifying LET cases but poor for identifying acute limb ischemia cases because many of these acute presentations were attributable to critical limb ischemia. Over the 20-year span, there were 1.76 million cases of LET. The incidence of LET decreased significantly from 42.4 per 100 000 persons between 1988 and 1997 to 23.3 per 100 000 persons between 1998 and 2007. The in-hospital mortality for LET decreased significantly from 8.28% between 1988 and 1997 to 6.34% between 1998 and 2007, and male patients achieved greater mortality reduction compared with female patients. Treatments for acute limb ischemia showed decreasing use of surgical bypass and amputation and increasing rates of catheter-based thrombolysis. Conclusions— Over the 20-year study period, there have been significant reductions in both LET incidence and in-hospital mortality. Unfortunately, LET admissions extracted from an administrative database comprise a diverse group of individuals, including those with acute and chronic forms of limb ischemia and iatrogenic arterial injury, limiting the true assessment of ALI incidence.

Introduction Bone marrow lesion (BML) size may be an important imaging biomarker for osteoarthritis-related clinical trials and reducing BML size may be an important therapeutic goal. However, data on the interrelationships between BML size, pain, and structural progression are inconsistent and rarely examined in the same cohort. Therefore, we evaluated the cross-sectional and longitudinal associations of BML volume with knee pain and joint space narrowing (JSN). Methods A BML volume assessment was performed on magnetic resonance images of the knee collected at the 24- and 48-month Osteoarthritis Initiative visits from a convenience sample of 404 participants in the progression cohort. During the same visits, knee pain was assessed with WOMAC pain scores and knee radiographs were acquired and scored for JSN. BML volume was summed to generate a total knee volume and an index tibiofemoral compartment volume (compartment with greater baseline JSN). Primary analyses included multiple linear regressions (outcome = pain, predictor = total knee BML volume) and logistic regressions (outcome = JSN, predictor = index tibiofemoral compartment BML volume). Results This sample was 49% female with a mean age of 63 (9.2 standard deviation (SD)) years, and 71% had radiographic osteoarthritis in the study knee. Larger baseline BMLs were associated with greater baseline knee pain (P = 0.01), the presence of JSN at baseline (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.23 to 1.83), and JSN progression (OR = 1.27, 95%CI = 1.11 to 1.46). Changes in total knee BML volume had a positive association with changes in knee pain severity (P = 0.004) and this association may be driven by knees that were progressing from no or small baseline BMLs to larger BMLs. In contrast, we found no linear positive relationship between BML volume change and JSN progression. Instead, regression of medial tibiofemoral BML volume was associated with JSN progression compared to knees with no or minimal changes in BML volume (OR = 3.36, 95%CI = 1.55 to 7.28). However, follow-up analyses indicated that the association between JSN progression and BML volume change may primarily be influenced by baseline BML volume. Conclusion Large baseline BMLs are associated with greater baseline knee pain, the presence of JSN at baseline, and disease progression. Additionally, BML regression is associated with decreased knee pain but not a reduced risk of concurrent JSN progression.

Knee osteoarthritis (OA), a disorder of cartilage and periarticular bone, is a public health problem without effective medical treatments. Some studies have suggested that vitamin D may protect against structural progression.To determine whether vitamin D supplementation reduces symptom and structural progression of knee OA.A 2-year randomized, placebo-controlled, double-blind, clinical trial involving 146 participants with symptomatic knee OA (mean age, 62.4 years [SD, 8.5]; 57 women [61%], 115 white race [79%]). Patients were enrolled at Tufts Medical Center in Boston between March 2006 and June 2009.Participants were randomized to receive either placebo or oral cholecalciferol, 2000 IU/d, with dose escalation to elevate serum levels to more than 36 ng/mL.Primary outcomes were knee pain severity (Western Ontario and McMaster Universities [WOMAC] pain scale, 0-20: 0, no pain; 20, extreme pain), and cartilage volume loss measured by magnetic resonance imaging. Secondary end points included physical function, knee function (WOMAC function scale, 0-68: 0, no difficulty; 68, extreme difficulty), cartilage thickness, bone marrow lesions, and radiographic joint space width.Eighty-five percent of the participants completed the study. Serum 25-hydroxyvitamin D levels increased by a mean 16.1 ng/mL (95% CI, 13.7 to 18.6) in the treatment group and by a mean 2.1 mg/mL (95% CI, 0.5 to 3.7) (P.001) in the placebo group. Baseline knee pain was slightly worse in the treatment group (mean, 6.9; 95% CI, 6.0 to 7.7) than in the placebo group (mean, 5.8; 95% CI, 5.0 to 6.6) (P = .08). Baseline knee function was significantly worse in the treatment group (mean, 22.7; 95% CI, 19.8 to 25.6) than in the placebo group (mean, 18.5; 95% CI, 15.8 to 21.2) (P = .04). Knee pain decreased in both groups by a mean -2.31 (95% CI, -3.24 to -1.38) in the treatment group and -1.46 (95% CI, -2.33 to -0.60) in the placebo group, with no significant differences at any time. The percentage of cartilage volume decreased by the same extent in both groups (mean, -4.30; 95% CI, -5.48 to -3.12 vs mean, -4.25; 95% CI, -6.12 to -2.39) (P = .96). There were no differences in any of the secondary clinical end points.Vitamin D supplementation for 2 years at a dose sufficient to elevate 25-hydroxyvitamin D plasma levels to higher than 36 ng/mL, when compared with placebo, did not reduce knee pain or cartilage volume loss in patients with symptomatic knee OA.clinicaltrials.gov Identifier: NCT00306774.

Background To determine the validity of a semi-automated segmentation of bone marrow lesions (BMLs) in the knee. Methods Construct validity of the semi-automated BML segmentation method was explored in two studies performed using sagittal intermediate weighted, turbo spine echo, fat-suppressed magnetic resonance imaging sequences obtained from the Osteoarthritis Initiative. The first study (n = 48) evaluated whether tibia BML volume was different across Boston Leeds Osteoarthritis Knee Scores (BLOKS) for tibia BMLs (semiquantitative grades 0 to 3). In the second study (n = 40), we evaluated whether BML volume change was associated with changes in cartilage parameters. The knees in both studies were segmented by one investigator. We performed Wilcoxon signed-rank tests to determine if tibia BML volume was different between adjacent BLOKS BML scores and calculated Spearman correlation coefficients to assess the relationship between 2-year BML volume change and 2-year cartilage morphometry change (significance was p ≤ 0.05). Results BML volume was significantly greater between BLOKS BML score 0 and 1 (z = 2.85, p = 0.004) and BLOKS BML scores 1 and 2 (z = 3.09, p = 0.002). There was no significant difference between BLOKS BML scores 2 and 3 (z = −0.30, p = 0.77). Increased tibia BML volume was significantly related to increased tibia denuded area (Spearman r = 0.42, p = 0.008), decreased tibia cartilage thickness (Spearman r = −0.46, p = 0.004), increased femur denuded area (Spearman r = 0.35, p = 0.03), and possibly decreased femur cartilage thickness (Spearman r = −0.30, p = 0.07) but this last finding was not statistically significant. Conclusion The new, efficient, and reliable semi-automated BML segmentation method provides valid BML volume measurements that increase with greater BLOKS BML scores and confirms previous reports that BML size is associated with longitudinal cartilage loss.

To describe the clinical features and outcomes of critically ill dogs and cats with acute kidney injury (AKI) receiving fenoldopam infusions compared to patients with AKI that did not receive fenoldopam.Retrospective clinical study from May 1, 2008 until June 1, 2012.Private emergency and specialty referral hospital.Client-owned dogs (28) and cats (34) with AKI that received fenoldopam compared with similar patients with AKI (30 dogs and 30 cats) that did not.None.The medical records of 62 critically ill dogs and cats with AKI that received fenoldopam were reviewed. Presenting clinical signs, physical examination findings, and primary and secondary disease processes were identified in all patients. The mean number of days on fenoldopam was 1.5 days (range 0.3-4.0 days) for dogs and 1.9 days (range 1.0-4.0 days) for cats. Eleven of 28 (39%) dogs survived to discharge and 13 of 34 (38%) of the cats survived to discharge. Of the animals in the group receiving fenoldopam that died, the majority (84%) were euthanized. Potential adverse reactions were evaluated, with hypotension being the most commonly encountered adverse effect (7% of fenoldopam group [FG] dogs and 23% of FG cats). When compared with patients with AKI that did not receive fenoldopam, no significant differences were found between the groups with regards to survival, length of hospital stay, adverse effects, or changes in creatinine, BUN, or sodium concentrations except that patients receiving fenoldopam were significantly more likely to have received other renally active medications.In this study of patients with AKI, fenoldopam administration at 0.8 μg/kg/min in dogs and 0.5 μg/kg/min in cats appeared relatively safe but was not associated with improvement in survival to discharge, length of hospital stay, or improvement in renal biochemical parameters when compared to patients with AKI not receiving fenoldopam.

Introduction: This study aims to quantify the radiobiology of the MammoSite applicator and examine whether there is a relationship between equivalent uniform dose (EUD) and radiotherapy-associated toxicity. Methods and materials: A previously-published version of the linear quadratic (LQ) model, designed to address the impact of dose-gradients in brachytherapy applications, was used to determine the biological effective dose (BED), equivalent dose in 2 Gray per fraction (EQD2) and EUD for the most common fractionation scheme for the MammoSite catheter (34 Gy in 10 fractions prescribed to 1 cm from the balloon surface), using a range of balloon sizes in a series of patients treated with single or multiple dwell positions. Toxicity from the MammoSite catheter was assessed and statistical associations with the calculated EUDs were investigated. Results: The acute- and late-toxicity EUDs respectively range from 34.8–39.4 Gy and 33.4–37.6 Gy, with EUD decreasing as balloon diameter increases and/or the number of dwell positions increases. There was a positive association between EUD and hyperpigmentation and telangiectasia. Conclusions: For APBI using the Mammosite applicator, EUD is higher than the marginal prescription dose and, for the dose-fractionation patterns considered here, was associated with acute and late skin toxicity. EUD is a potentially useful parameter to characterize non-uniform dose distributions related to brachytherapy treatments. Further evaluation in future studies is warranted.

Studies aimed at identifying serum markers of cellular metabolism (biomarkers) that are associated at baseline with aerobic capacity (VO₂max) in young, healthy individuals have yet to be reported. Therefore, the goal of the present study was to use the standard chemistry screen and untargeted mass spectrometry (MS)-based metabolomic profiling to identify significant associations between baseline levels of serum analytes or metabolites with VO₂max (77 subjects, age range 18-35 years). Use of multivariable linear regression identified three analytes (standard chemistry screen) and twenty-three metabolites (MS-based metabolomics) containing significant, sex-adjusted associations with VO₂max. In addition, fourteen metabolites were found to contain sex-specific associations with aerobic capacity. Subsequent stepwise multivariable linear regression identified the combination of SGOT, 4-ethylphenylsulfate, tryptophan, γ-tocopherol, and α-hydroxyisovalerate as overall, sex-adjusted baseline predictors of VO₂max (adjusted R(2) = 0.66). However, the results of the stepwise model were found to be sensitive to outliers; therefore, random forest (RF) regression was performed. Use of RF regression identified a combination of seven covariates that explained 57.6 % of the variability inherent in VO₂max. Furthermore, inclusion of significant analytes, metabolites and sex-specific metabolites into a stepwise regression model identified the combination of five metabolites in males and seven metabolites in females as being able to explain 80 and 58 % of the variability inherent in VO₂max, respectively. In conclusion, the evidence presented in the current report is the first attempt to identify baseline serum biomarkers that are significantly associated with VO₂max in young, healthy adult humans.

This study is the first double-blinded, randomized comparison of two absorbable sutures. To better understand product characteristics and surgeon preference, we conducted a study of two similar-appearing FDA-approved sutures, glyconate and poliglecaprone 25. Four dermatologic surgeons were enlisted. A total of 48 patients with 53 surgical sites were examined. One half of each surgical wound was closed with one type of suture and the other half with the other type. Each half was evaluated for product characteristics. There was no statistically significant difference in surgeon preference for glyconate versus poliglecaprone 25 (P=0.64). Of the cohort preferring poliglecaprone 25, there was a correlation with speed of closure (P=0.06). Of the surgeons that preferred glyconate, we found significantly better visibility (P=0.03), reduced suture breakage during knot tying (P=0.05), and correlation with better handling properties (P=0.06) associated with that preference. The data from this study will enable products to be designed towards these needs and allow surgeons to select sutures that more precisely fit their particular requirements.

The aims of this study were to examine the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and disease activity in juvenile idiopathic arthritis (JIA), to determine the prevalence of vitamin D (VD) deficiency [25(OH)D ≤ 19 ng/ml] and insufficiency [25(OH)D 20-29 ng/ml], and to determine factors associated with lower serum levels of 25(OH)D in this population. In this cross-sectional study, disease activity was measured using JADAS-27, as well as its individual components (physician global assessment of disease activity, parent global assessment of child's well-being, count of joints with active disease, and erythrocyte sedimentation rate). Linear regression models were developed to analyze the association between serum 25(OH)D levels and JADAS-27 and to determine variables associated with serum 25(OH)D levels. A total of 154 patients (61% girls, 88% whites) were included. Mean age was 10.6. VD deficiency was detected in 13% and insufficiency in 42%. In univariate and multivariate analyses, 25(OH)D levels were not associated with JADAS-27, neither with its individual components. However, in a subset analysis including all new-onset JIA patients (n = 27), there was a nonsignificant negative correlation between serum 25(OH)D levels and JADAS-27 (r = -0.29, P = 0.14). In the univariate and multivariate analyses, age, ethnicity, BMI, and season were significantly associated with serum 25(OH)D levels, but not total VD intake. More than 1/2 of JIA patients had serum 25(OH)D levels below 29 ng/ml; however, there was no association between serum 25(OH)D levels and disease activity. Future larger, long-term studies with new-onset JIA patients are needed to further explore the association between serum 25(OH)D levels and disease activity.

To determine corneal sensitivity in 20 healthy adult alpacas (40 eyes) in order to establish reference values.Prospective study.Twenty healthy, adult alpacas.Corneal sensitivity was determined by the corneal touch threshold (CTT) using a Cochet-Bonnet esthesiometer. Five different regions of the cornea were evaluated (nasal, ventral, lateral, dorsal, and central).Corneal touch threshold values (in mm filament length) obtained from five corneal regions demonstrated varying corneal sensitivities. The central region (34.5 ± 7.1 mm) was the most sensitive, followed by the ventral (29.5 ± 7.2 mm), medial (29.3 ± 7.3 mm), dorsal (25.6 ± 6.3 mm), and lateral (21.8 ± 5.7 mm) regions. All pairwise comparisons of regional differences were statistically significant (P0.05), except for the comparison between the ventral and medial regions (P = 0.88). Evaluation of the CCT while controlling for age (2-5 years vs. 6-10 years) demonstrated an increased CTT with an increasing age for the central, ventral, medial and lateral regions. A decrease in the CTT of the dorsal region was noted with increasing age.Corneal touch threshold values in 40 eyes of 20 healthy adult alpacas were determined using a Cochet-Bonnet esthesiometer. This study demonstrated the central corneal region to be most sensitive. Values obtained may serve as reference values in subsequent studies.

To (1) determine a reference interval for shock index (SI) [defined as heart rate (HR)/systolic blood pressure (SBP)], in a group of healthy dogs, and (2) compare SI in healthy dogs with dogs presenting to the emergency room (ER) deemed to be in or not in a state of shock.Prospective study.Sixty-eight clinically normal dogs, 18 dogs that were presented to the ER deemed to be in shock and 19 dogs presenting to the ER not deemed to be in shock.University teaching hospital.Peripheral or central venous blood sampling.Heart rate and SBP were recorded on simulated presentation (healthy dogs), and emergency presentations for both dogs deemed to be in shock and dogs not deemed in shock. Dogs in shock had a median SI of 1.37 (0.87-3.13), which was significantly higher than both other groups; dogs not deemed in shock had median SI 0.73 (0.56-1.20), P0.0001 and healthy dogs had median SI 0.78 (0.37-1.30) P0.0001), respectively. Receiver operator characteristic curve analysis suggested a SI cut-off of 1.0, yielding an area under the receiver operator characteristic (AUROC) of 0.89 (Specificity (Sp) 89, Sensitivity (Sn) 90) when comparing dogs deemed in shock with healthy dogs, and 0.92 (Sp 95, Sn 89) when comparing dogs in shock with to dogs not deemed in shock.The SI is an easy and noninvasive patient parameter that is higher in dogs that are deemed to be in shock than both healthy dogs and dogs presented as emergencies but not deemed to be in a state of shock. The measurement of SI may have some benefit in clinical assessment of emergency patients.

Summary Background and objectives Serum creatinine (sCr) increments currently used to define acute kidney injury (AKI) do not take into consideration the baseline level of kidney function. The objective of this study was to establish whether baseline estimated GFR (eGFR) provides additional risk stratification to sCr-based increments for defining AKI. Design, setting, participants, & measurements 29,645 adults hospitalized at an acute care facility were analyzed. Hospital-acquired AKI was defined by calculating the difference between the nadir and subsequent peak sCr. Results Different thresholds of nadir-to-peak sCr were found to be independently associated with increased in-hospital mortality according to baseline eGFR strata. A nadir-to-peak sCr minimum threshold of 0.2, 0.3, and 0.5 mg/dl was required to be independently associated with increased in-hospital mortality among patients with baseline eGFR 60 ml/min per 1.73 m 2 (odds ratio [OR] 1.67; 95% confidence interval [CI] 1.13 to 2.47), 30 to 59 ml/min per 1.73 m 2 (OR 2.69; 95% CI, 1.82 to 3.97), and 30 ml/min per 1.73 m 2 (OR 2.15; 95% CI 1.02 to 4.51), respectively. There was a significant interaction between the nadir-to-peak sCr and baseline eGFR for in-hospital mortality (P 0.001). Using these thresholds, survivors of AKI episodes had an increased hospital length of stay and were more likely to be discharged to a facility rather than home. Sensitivity analyses showed a significant interaction between baseline eGFR strata and relative increases in sCr, as well as absolute and relative decreases in eGFR for in-hospital mortality (P 0.001). Conclusions This study suggests that future sCr-based definitions of AKI should take into consideration baseline eGFR. Clin J Am Soc Nephrol 6: 1556–1565, 2011. doi: 10.2215/CJN.08470910

Objective This study examined the validity of primary health care providers' (PHCPs) assessment of suspicion that an injury was caused by child abuse and their decision to report suspected child abuse to child protective services (CPS). Methods By using a subsample of injuries drawn from the 15,003 childhood injuries evaluated in the Child Abuse Recognition and Evaluation Study, PHCPs completed telephone interviews concerning a stratified sample (no suspicion of abuse; suspicious but not reported; and suspicious of abuse and reported) of 111 injury visits. Two techniques were used to validate the PHCPs' initial decision: expert review and provider retrospective self-assessment. Five child abuse experts reviewed clinical vignettes created by using data prospectively collected by PHCPs about the patient encounter. The PHCPs' opinions 6 weeks and 6 months after the injury-related visits were elicited and analyzed. Results PHCPs and experts agreed about the suspicion of abuse in 81% of the cases of physical injury. PHCPs did not report 21% of injuries that experts would have reported. Compared with expert reviewers, PHCPs had a 68% sensitivity and 96% specificity in reporting child abuse. A PHCP's decision to report suspected child abuse to CPS did not reduce the frequency of primary care follow-up in the 6 months after the index visit. PCHPs received information from their state CPS in 70% of the reported cases. Conclusions Child abuse experts and PHCPs are in general agreement concerning the assessment of suspected child physical abuse, although experts would have reported suspected abuse to CPS more frequently than the PHCPs. Future training should focus on clear guidance for better recognition of injuries that are suspicious for child abuse and state laws that mandate reporting.

Background The practice patterns and career paths of physicians who are double-boarded in medicine, family practice, or neurology and psychiatry are not well understood. Given increased attention to integrated medical and psychiatric care, these individuals may play an important role. Objective To compare the practice patterns and career paths of physicians who are double-boarded in medicine, family practice, or neurology and psychiatry with physicians who are boarded in general psychiatry, and among double-boarded physicians with various training sequences and specialty types. Method A survey was distributed to all physicians identified by the American Board of Medical Specialties (ABMS) as double-boarded in medicine, family practice, or neurology and psychiatry, and an equal number of physicians who are boarded in general psychiatry. Results Compared with psychiatrists who are not double-boarded, double-boarded psychiatrists are significantly more likely to be older, more likely to be male, to practice in consultation-liaison or inpatient settings, and to assume positions of leadership in departments of psychiatry or in general health care organizations. Among the various groups of double-boarded physicians, 39% continue to practice their medical specialty in addition to their psychiatry practice, although this varies by medical specialty, sequence or type of program, and motivation for double-board training. Conclusion Double-boarded physicians appear to be a distinct group within psychiatry and may serve as an important bridge to the general medical environment because of their leadership roles and medical psychiatric practice patterns. Further understanding of their career development and roles is warranted.