Sex Differential in 15-Hydroxyprostaglandin Dehydrogenase Levels in the Lumen of Human Intracranial Aneurysms.

BACKGROUND: Aspirin is a promising medical therapy for the prevention of intracranial aneurysm (IA) rupture. Recently, we found that men have a better response to aspirin than women. The purpose of this study was to determine whether a sex differential exists in the level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the lumen of human IAs. METHODS AND RESULTS: Consecutive patients undergoing coiling or stent-assisted coiling for a saccular IA at our institution were enrolled. Two samples (A and B) were collected from IA lumens, and the plasma level of 15-PGDH was measured using an ELISA-based method. The study included 38 patients, with 20 women and 18 men. Women and men were comparable on baseline characteristics. The mean plasma concentration of 15-PGDH did not differ statistically between sample A (62.8±16.2 ng/mL) and sample B (61.8±17.9 ng/mL; 95% confidence interval -6.6 to 9.4). The mean plasma concentration of 15-PGDH in IA lumens of samples A and B was significantly higher in men (73.8±13.5 ng/mL) than women (49.6±7.8 ng/mL; P\u3c0.0001). CONCLUSIONS: Higher enzyme levels of 15-PGDH exist in the lumen of IAs of men compared with women. This observation could explain why aspirin confers better protection against IA rupture in men than in women. The susceptibility of an individual to aspirin may differ according to the level of 15-PGDH

Effectiveness of an Intersection Violation Warning System

People age 65 years and older are the fastest growing segment of the U.S. population and the fastest growing sector of the driving population. When compared to other age groups, older drivers are overrepresented in intersection crashes (Subramanian & Lombardo, 2007; Braitman et al., 2006), and approximately half of the charges in fatal intersection crashes are for failure to obey the traffic control device. This project explored an in-vehicle warning system for failure-to-obey (running a stop sign or stop light) violations. Participants who were not using the system made nearly three times as many didnot-stop errors (27%) than participants who were using the system (10%). This effect was most pronounced in older drivers with more risk factors associated with crashes; however, the effect of age group was not statistically significant

Association of walking cadence to changes in knee pain and physical function: The multicenter osteoarthritis study.

OBJECTIVE: Determine the association of walking cadence to incident and worsening knee pain and physical function over 2 years in adults with or at risk for knee OA. DESIGN: Participants from the Multicenter Osteoarthritis study were included.Cadence was measured using a GAITRite walkway. Incident and worsening knee symptoms, pain with walking, and functional limitations were assessed at baseline and 2 years later. The association of cadence to each outcome was analyzed using log binomial regression. Cadence was assessed continuously as a 10-unit change and categorically using quartiles. Analyses were adjusted for age, sex, race, BMI, presence of tibiofemoral OA, depression, and history of knee injury. Sensitivity analyses were conducted for all outcomes adjusted for gait speed and stratified by sex. RESULTS: Among 1600 participants (60.3 ​% female, age 67.1 ​± ​7.7 years), lower cadence was not significantly associated with incident or worsening knee symptoms, pain with walking, or functional limitations. For every 10-step/min decrease in cadence, the risk of incident knee symptoms increased by 10 ​% (RR ​= ​1.10, 95%CI [0.97, 1.25]), though this was not statistically significant and was attenuated after adjusting for gait speed (RR ​= ​0.95, 95%CI [0.80, 1.12]). No significant associations were observed for incident or worsening pain with walking or functional limitations. Sex-stratified analyses revealed inconsistent findings, including an increased risk for incident functional limitations in females (RR ​= ​1.45, 95%CI [1.02, 2.08]), which was attenuated after adjusting for gait speed. CONCLUSION: Lower cadence was not significantly associated with pain and function, suggesting that the interplay between cadence, gait speed, and clinical outcomes warrants further investigation

Leg-length inequality is not associated with greater trochanteric pain syndrome

INTRODUCTION. Greater trochanteric pain syndrome (GTPS) is a common condition, the pathogenesis of which is incompletely understood. Although leg-length inequality has been suggested as a potential risk factor for GTPS, this widely held assumption has not been tested. METHODS. A cross-sectional analysis of greater trochanteric tenderness to palpation was performed in subjects with complaints of hip pain and no signs of hip osteoarthritis or generalized myofascial tenderness. Subjects were recruited from one clinical center of the Multicenter Osteoarthritis Study, a multicenter population-based study of community-dwelling adults aged 50 to 79 years. Diagnosis of GTPS was based on a standardized physical examination performed by trained examiners, and technicians measured leg length on full-limb anteroposterior radiographs. RESULTS. A total of 1,482 subjects were eligible for analysis of GTPS and leg length. Subjects' mean ± standard deviation age was 62.4 ± 8.2 years, and 59.8% were female. A total of 372 lower limbs from 271 subjects met the definition for having GTPS. Leg-length inequality (difference ≥ 1 cm) was present in 37 subjects with GTPS and in 163 subjects without GTPS (P = 0.86). Using a variety of definitions of leg-length inequality, including categorical and continuous measures, there was no association of this parameter with the occurrence of GTPS (for example, for ≥ 1 cm leg-length inequality, odds ratio = 1.17 (95% confidence interval = 0.79 to 1.73)). In adjusted analyses, female sex was significantly associated with the presence of GTPS, with an adjusted odds ratio of 3.04 (95% confidence interval = 2.07 to 4.47). CONCLUSION. The present study found no evidence to support an association between leg-length inequality and greater trochanteric pain syndrome.National Institutes of Health and National Institute of Child Health and Human Development (5K12HD001097-08); National Insititues of Health and National Institue on Aging (1 U01 AG18832; 1 U01 AG18820; 1 U01 AG19069, 1 U01 AG18947

The unruptured intracranial aneurysm treatment score A multidisciplinary consensus

Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (v(r)*) (v(r)* 5 0 indicating excellent agreement and v(r)* = 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (v(r)*) for both cohorts was 0.026 (95% CI 0.019-0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.Peer reviewe

Relation of Temporal Asymmetry During Walking to Two-Year Knee Pain Outcomes in Those With Mild-to-Moderate Unilateral Knee Pain: An Exploratory Analysis From the Multicenter Osteoarthritis Study.

OBJECTIVE: We aimed to explore the cross-sectional relation of unilateral knee pain severity and temporal asymmetry during walking and to determine relations of temporal asymmetry during walking to 2-year changes in ipsilateral and contralateral knee pain in those with mild-to-moderate unilateral knee pain. METHODS: The Multicenter Osteoarthritis Study is a prospective cohort study of adults with or at risk for knee osteoarthritis. The current study included participants with unilateral knee pain. Gait was assessed during self-selected and fast walking at baseline. Knee pain was assessed at baseline and 2 years. We calculated limb symmetry indices (LSIs; nonpainful limb/painful limb × 100) for stance, single-limb support time, and double-limb support time, then examined their relations to unilateral knee pain severity, incident contralateral knee pain, and persistent ipsilateral knee pain. RESULTS: Unilateral knee pain severity was not associated with temporal asymmetry during self-selected or fast walking. At 2 years, 17.1% of participants had incident contralateral knee pain and 51.4% had persistent ipsilateral knee pain. For self-selected walking, greater LSIs (i.e., longer time on the nonpainful limb) for stance and single-limb support time were associated with decreased odds of incident contralateral knee pain. Measures of temporal asymmetry were not associated with persistent ipsilateral knee pain, except for single-limb support time during fast walking. CONCLUSION: For those with unilateral knee pain, temporal asymmetry during walking is not associated with pain severity. However, select measures of stance and single-limb support time during self-selected and fast walking relate to longitudinal knee pain outcomes

Multidisciplinary Consensus on Assessment of Unruptured Intracranial Aneurysms Proposal of an International Research Group

Peer reviewe

Comparison of definitions of early knee osteoarthritis for likelihood of progression at 2-year and 5-year follow-up: the Multicenter Osteoarthritis Study.

BACKGROUND: Preventing worsening osteoarthritis (OA) in persons with early OA is a major treatment goal. We evaluated if different early OA definitions yielded enough cases of worsening OA within 2-5 years to make trial testing treatments feasible. METHODS: We assessed different definitions of early OA using data from Multicenter Osteoarthritis (MOST) Study participants who were followed up longitudinally. We defined early OA as having at least minimal knee pain (WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain ≥3/20) with different levels of pre-radiographic OA. For MRI, we required knee pain and used MRI definitions with combinations of cartilage damage, osteophytes, bone marrow lesions and meniscus damage. The primary outcome, worsening OA at 2 or 5 years, combined structural (Kellgren and Lawrence grade ≥2 with joint space narrowing ≥1) and symptom (WOMAC pain ≥6 with increase ≥2 from baseline) outcomes. We also examined structural and symptom outcomes separately. RESULTS: For worsening OA at 2 years, we included 750 participants (mean age 65 years, 60% female, 90% white, mean body mass index 29.2 kg/m2). Fewer than 10% of early OA knees had the combined outcome at 2 or 5 years. At 2 years, for several early OA definitions, roughly 20% of knees had either structural or symptom worsening outcomes. Two-year trials of either, but not both, outcomes would need to recruit over 1200 patients. CONCLUSION: Most knees with early OA are stable and do not progress. Some painful knees experience worse pain but not structural progression and vice versa. Trial testing treatments to prevent OA illness or disease will be challenging

The Association of Obesity with Walking Independent of Knee Pain: The Multicenter Osteoarthritis Study

Practice guidelines recommend addressing obesity for people with knee OA, however, the association of obesity with walking independent of pain is not known. We investigated this association within the Multicenter Osteoarthritis Study, a cohort of older adults who have or are at high risk of knee OA. Subjects wore a StepWatch to record steps taken over 7 days. We measured knee pain from a visual analogue scale and obesity by BMI. We examined the association of obesity with walking using linear regression adjusting for pain and covariates. Of 1788 subjects, the mean steps/day taken was 8872.9 ± 3543.4. Subjects with a BMI ≥35 took 3355 fewer steps per day independent of knee pain compared with those with a BMI ≤25 (95% CI −3899, −2811). BMI accounted for 9.7% of the variability of walking while knee pain accounted for 2.9%. BMI was associated with walking independent of knee pain

Psychological and Pain Sensitization Characteristics Are Associated With Patellofemoral Osteoarthritis Symptoms: The Multicenter Osteoarthritis Study

ObjectiveDetermine the relation of symptomatic and structural features of patellofemoral osteoarthritis (PFOA) to psychological characteristics and measures of pain sensitization, in older adults with or at risk of knee osteoarthritis (OA).MethodsThis study included 1112 participants from the Multicenter Osteoarthritis Study (713 females, mean age 66.8 ± SD 7.6 yrs, body mass index 29.5 ± 4.8 kg/m2). Participants were grouped based on the presence of PFOA symptoms (anterior knee pain and pain on stairs) and magnetic resonance imaging (MRI) PFOA (full-thickness cartilage lesion with bone marrow lesion): (1) patellofemoral (PF) symptoms with MRI PFOA; (2) PF symptoms without MRI PFOA; (3) MRI PFOA without PF symptoms; and (4) no PF symptoms or MRI PFOA (no PFOA). Relation of PFOA classification to depressive symptoms, catastrophizing, temporal summation (TS) and pressure pain thresholds (PPT) was evaluated using logistic (categorical variables) and linear regression (continuous variables).ResultsCompared with no PFOA, those with PF symptoms with or without MRI PFOA had significantly greater odds of depressive symptoms, catastrophizing, and patellar TS (OR range 1.5-2.01), and those with PF symptoms without MRI PFOA had significantly greater odds of wrist TS (OR 1.66). Males with PF symptoms without MRI PFOA had significantly lower pressure PPT at the patella compared with no PFOA and those with MRI PFOA only (no symptoms). There were no significant differences at the wrist for males, or the patella or wrist for females.ConclusionPersons with PFOA symptoms, regardless of MRI PFOA status, are more likely to demonstrate depressive symptoms, catastrophizing, and TS. Males with PFOA symptoms without MRI PFOA demonstrate local hyperalgesia