VA Med Research Articles

7440 Both GLP-1RA and SGLT2i medications are associated with lower depression scores in veterans compared to metformin and insulin

Abstract Disclosure: S.D. Ubalde: None. H. Cann: None. L. Esper: None. J. Powell: None. K. Meyer: None. S. Sen: None. Background: Type 2 diabetes (T2DM) and depression are considered bidirectional. Depression and mental health issues are often co-morbidities and present with management challenges in veterans with T2DM. With the advent of novel meds for T2DM, it is important to choose appropriate T2DM medication in this context.Glucagon-like-peptide-1 receptor agonists (GLP-1RA) act on the hypothalamus to reduce weight and glycemic indices in T2DM patients which may play a positive role on the amygdala and help improve mood and depression. We hypothesized that patients taking the GLP1-RA (+/-insulin) regimen would have lower PHQ-9 depression scores compared to patients taking SGLT2i (+/-insulin), metformin (+/- insulin), or insulin (ins) alone. Methods: We conducted a retrospective chart review of patients from the Diabetes Clinic at VA Med Center over 10 months to find an association between PHQ9 depression scores and anti-diabetic regimen. We reviewed 200 patient charts and decided to analyze 88 subjects that had bonafide depression that is PHQ-9 score of at least 5 or above including mild, moderate, and severe depression as per the PHQ9 scoring system. Results: Our cohort had a mean age of 64.16±1.18 years. All patients were either overweight or had obesity (BMI 25-45). Percentage prescriptions of different diabetes medications show that most patients are on insulin alone with 35 patients (39.77%), while Metformin (+/- ins) had 23 (26.14%), GLP-1RA (+/- ins) had 17 (19.32%), and with the lowest use in SGLT2i (+/- ins) had 13 (14.77%). The mean BMI was 32.29±0.80, which was similar across the groups with the SGLT2i (+/- ins) group having a slightly lower BMI of 27.80±1.28. Mean A1C was 8.0±0.2 with no difference found between groups. Comparing depression scores between all groups the Brown-Forsythe ANOVA test analysis showed significance of p = 0.0383 among all groups. Contrary to our hypothesis, both GLP-1RA and SGLT2i groups (rather than GLP1RA alone) had a significantly lower mean PHQ-9 score of 8.824±0.81(p = 0.0486, using unpaired t-test) and 8.077±0.91 (p = 0.0311) respectively, compared to the metformin group with a score of 12.04±1.2. Insulin-only group score was slightly lower than metformin at 11.03±0.95, and there was no statistical difference when compared to other groups. Conclusion: In a real-life setting of T2DM clinic subjects that were overweight or obese, depression scores were lower in patients taking the GLP1RA and SGLT2i. This effect was independent of differences in BMI or A1C metrics between the groups. The majority of T2DM veteran patients were prescribed insulin alone indicating under-utilization of novel T2DM meds such as SGLT2i and GLP1A agents. Continuing this research, particularly in a VAMC cohort, may provide insight into the choice of appropriate T2DM medications that may help veterans with concomitant T2DM and depression. Presentation: 6/2/2024

734 Prevalence and Correlates of Insomnia in Veterans with and without Military Sexual Trauma Receiving Care within a VA Med Center

Abstract Introduction A prior study showed a higher prevalence of insomnia among younger Veterans with military sexual trauma (MST) before receiving care at a VA Medical Center (VAMC). We extend the literature to investigate the prevalence and correlates of insomnia in male Veterans with and without MST currently receiving care within a VAMC. Methods We evaluated cross-sectional data from a survey within the Philadelphia VAMC (N=138) using the following instruments: Insomnia Severity Index (ISI) total score for insomnia; Sexual Harassment Scale (DRRI-2) to screen for MST; PTSD checklist for DSM-5 (PCL-5) PTSD symptoms; Quick Inventory of Depressive Symptomatology-Self report (QIDS-SR) to evaluate depressive symptoms; Alcohol Use Disorder Identification Test (AUDIT-C) to assess for harmful drinking; and, the nightmare question from the PCL-5 scale to screen for persistent nightmares. The association between ISI total score and variables were assessed separately in individuals with and without MST, using bivariate and multivariable analyses. Results The mean(SD) age was 55.2(12.8) years. They were likely to identify themselves as African-American (44.2%), and had a high school diploma (39.1%). MST was endorsed by 31.9% of the Veterans. Insomnia was more prevalent in those with MST [N=42(95.4%)] than those without [N=77(81.9%)]. Individuals with MST had higher ISI (19.9±5.0 Vs 16.7±7.2) and PCL-5 (48.4±14.4 Vs 38.1±19.7) total scores, than individuals without. Among those with MST, the bivariate analysis showed significant associations with PCL-5 (β=0.2, p<0.0001), QIDS (β=0.5, p=0.01), AUDIT-C (β=0.5, p=0.008), and nightmares (β=3.9, p=0.03). In the multivariable model, ISI total score was only associated with the PCL-5 total score (β=0.3, R2=0.18, p=0.0005). Among those without MST, the bivariate analysis showed significant associations between ISI total score and age (β=-0.1, p=0.02), total scores on the PCL-5 (β=0.2, p<0.0001), QIDS (β=0.9, p<0.00001), and nightmare (β=6.7, p<0.0001). In the multivariable model (R2=0.5, p<0.00001), the ISI total score was associated with PCL-5 (β=0.1, p=0.01), and QIDS (β=0.7, p=<0.0001) total scores. Conclusion There is a higher prevalence of insomnia among Veterans with MST currently receiving care within the VHA. Treatment of insomnia and PTSD is critical to improve their well-being and prevent complications. Support (if any) The study was supported by VA grant IK2CX000855 (S.C.).

Book Review

Hunter Holmes McGuire VA Med Center Richmond, Virginia The author declares no conflicts of interest.One of the editors of this book is the chair of the department in which I am currently completing a fellowship in traumatic brain injury. I am currently training with or have previously trained with a number of authors of individual chapters of this book. Although my opinion may logically be a reflection of my training, I have attempted to give an honest appraisal of the text.

699. Relationship Between Klebsiella pneumoniae Antimicrobial Resistance and Biofilm Formation

Background Klebsiella pneumoniae is a frequently multidrug-resistant organism with a high propensity to form biofilm. K. pneumoniae is the most common carbapenem-resistant Enterobacteriaceae (CRE), and labeled an urgent threat by the CDC. The relationship between K. pneumoniae biofilm formation and specific antimicrobial resistance patterns has not been well defined.Methods K. pneumoniae isolates (n = 139) were evaluated for antimicrobial resistance and biofilm formation (CDC, Providence VA Med. Ctr., Rhode Island Hosp., BEI, and ATCC). Susceptibility was based predominantly on 2017 CLSI (Clinical and Laboratory Standards Institute) breakpoints. Isolates were categorized as multidrug-resistant (MDR: resistant to ≥ 1 antimicrobial in ≥ 3 out of 16 antimicrobial categories) or extensively drug-resistant (XDR: resistant to ≥ 1 antimicrobial in all but ≤ 2 out of 16 antimicrobial categories) based on expert consensus criteria for Enterobacteriaceae (European CDC (ECDC)/CDC, 2012). We collapsed antimicrobial categories described by the ECDC/CDC consensus group into nine categories: penicillins, cephalosporins, monobactam, carbapenems, protein synthesis inhibitors, fluoroquinolones, folate pathway inhibitors, fosfomycin, and colistin. Biofilm formation was assessed using a modified crystal violet method (OD570) and defined by tertile cut-points. Antimicrobial resistance was compared for weak (n = 47) vs. strong (n = 46) biofilm formation by chi-square or Fisher’s exact test. Predictors of strong biofilm formation were identified using logistic regression.ResultsMDR isolates were more common among weak (n = 46/47, 97.9%) vs. strong biofilm formers (n = 35/46, 76.1%; P = 0.002), whereas XDR was similar between groups (n = 12/47, 25.5% vs. n = 13/46, 28.3% P = 0.77). Resistance to penicillins, cephalosporins, monobactams, carbapenems, protein synthesis, or fluoroquinolones was more common among weak biofilm formers (P < 0.05). Carbapenem resistance was inversely associated with strong biofilm formation (odds ratio 0.09; 95% confidence interval 0.02–0.33).ConclusionCarbapenem-resistant K. pneumoniae was 91% less likely to form strong biofilm. Potential trade-off mechanisms between antimicrobial resistance and biofilm formation require further exploration.Disclosures A. Caffrey, Merck: Grant Investigator, Research grant. The Medicine’s Company: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. K. LaPlante, Merck: Grant Investigator, Research grant. Pfizer Pharmaceuticals: Grant Investigator, Research grant. Allergan: Scientific Advisor, Honorarium. Ocean Spray Cranberries, Inc.: Grant Investigator and Scientific Advisor, Honorarium and Research grant. Achaogen, Inc.: Scientific Advisor, Honorarium. Zavante Therapeutics, Inc.: Scientific Advisor, Honorarium.

252 Chemoprevention of basal and squamous cell carcinoma with a single course of 5-flourouracil 5% cream

252 Chemoprevention of basal and squamous cell carcinoma with a single course of 5-flourouracil 5% cream MAWeinstock, K Marcolivio and S Thwin, V Trial Group 1 VA Med Ctr, Providence, RI, 2 Brown Univ, Providence, RI and 3 VA Healthcare Syst, Boston, MA Keratinocyte carcinoma (KC; basal cell and squamous cell carcinoma of the skin, i.e. BCC and SCC) is the most common cancer in the United States and throughout the world’s lightskinned population, with over 5 million cases per year in the US alone, and its incidence is increasing. Topical 5% 5-fluorouracil (5-FU) has been used for decades for the treatment of actinic keratosis, a known precursor of SCC. We sought to test whether topical application of 5-FU could be an effective regimen for the prevention of BCC and SCC of the face and ears that require surgery. We recruited a high-risk population of 932 veterans at 12 Veterans Affairs Medical Centers who had a history of at least 2 KCs during the prior 5 years, at least one of which was on the face or ears. They were randomized to apply a standard course of 28 to 56 applications (twice daily for 2 to 4 weeks) of 5-FU 5% cream or vehicle control cream to the face and ears. Investigators were blinded to randomization group and did not examine study participants during the first 6 months after initiating application of the study cream. All lesions biopsied from the face or ears were reviewed by a board-certified study dermatopathologist who was blinded to group assignment. During this 4 year trial (median follow-up 2.6 years), 299 participants developed a BCC on the face or ears requiring surgery and 108 developed an SCC that met the same criteria. Over the 4 year trial period, there was no difference in risk of KC, BCC, or SCC. However, during the first year of follow-up, there was a 74% reduction in SCCs requiring surgery in the 5-FU group compared to vehicle control (HR1⁄40.25, 95% CI 0.09-0.68, p1⁄40.003), whereas there was no difference in BCC or overall KC. These data demonstrate that a conventional course of 5-FU to the face and ears substantially reduces surgery for SCC on the face and ears for at least 1 year without affecting the corresponding risk for BCC. 253 Sirolimus for the treatment of venolymphatic and lymphatic malformations in children: A volumetric analysis JH Tu, HI Cohn, HM Do, K Yeom, A Marqueling, M Sofilos, M Jeng and J Teng 1 Vascular Anomalies Clinic, Stanford University, Stanford, CA, 2 Columbia University College of Physicians and Surgeons, New York, NY and 3 3DQ Lab, Stanford University, Stanford, CA The purpose of this study was to (i) evaluate the clinical and radiological outcomes of venolymphatic (VLM) and lymphatic malformations (LM) in children treated with systemic sirolimus; (ii) explore the benefit of sirolimus as an adjuvant therapy. Retrospective chart review was performed on 6 children treated with sirolimus for VLM or LM in our institution for the past three years. Volumetric analysis using 3D reconstructive software was completed using preand post-treatment MRI data. All 6 subjects were refractory to previous surgical and medical therapies prior to systemic sirolimus treatment. The subjects’ ages range from 3 to 16. Median duration of treatment was 16 (7-35) months. All six patients had notable clinical response evident by reduced swelling or pain. Average weight-adjusted post-treatment change in volume was -12.8%, with a cumulative decrease of 281.5 cm. The most significant change was a decrease of 57.9%. All patients had a greater than 10% decrease in volume. There is no clear correlation between duration of treatment and extent or response to sirolimus (p1⁄40.9). Sirolimus was well-tolerated by all patients with no significant adverse events; minor side effects included abdominal pain and vomiting at treatment initiation in one patient, and oral ulceration in one other. All six patients are still on treatment. All patients experienced clinical improvement and volume reduction in 3D reconstruction. This study concludes that sirolimus can be beneficial for both the symptomatic and volumetric improvement of VLMs and LMs, especially in children. Further molecular and genetic characterization of these patients may improve our understanding in the management of vascular anomalies using mTOR inhibitors.

211 Genetic variants in the Wnt pathway genes NFATC1 and PLCB1 predict melanoma survival

208 Multiple primary melanomas: Prevalence and outcomes A Nosrati, S Goel, J McGuire, B Grimes, RK Singh, K Lee, VB Morhenn, A Griffin and ML Wei 1 University of California, San Francisco, CA and 2 Veterans Affairs Medical Center, San Francisco, CA We investigated the characteristics and outcomes of individuals with multiple primary melanomas (MPM) compared with individuals with a single primary melanoma (SPM) to identify risk factors for developing MPM and whether outcomes differed between these groups. 7,268 individuals diagnosed with melanoma from 1983-2013 were identified at a tertiary referral academic center for a retrospective observational study. 6963 individuals (95.8%) had a SPM and 305 (4.2%) had MPM. Mean follow-up interval was 17 y (median 14.6, CI 95%13.715.4). MPM patients were more likely to be older (mean age 60.2 vs 55.8 y; P 1 mm. Overall survival was significantly better for patients with MPM when calculated by designating the index tumor as either the first occurring tumor (HR1⁄40.73, 95%CI 0.599-0.891) or the first invasive tumor (HR1⁄40.8, 95%CI 0.652-0.992). Overall survival was also increased when the thickest tumor was designated as the index tumor (HR1⁄40.86, 95%CI 0.7-1.06), however this did not reach significance. Melanoma specific survival was increased in MPM patients, but not significantly. In summary, MPM patients are more frequently older, white, male individuals with family history of melanoma. MPM patients have an increased rate of selected internal malignancies and overall survival but similar melanoma-specific survival rate compared with those with SPM. 209 No psychological harm from melanoma screening by PCPs: Preliminary results PM Risica, L Dionne, J Mello, LK Ferris, G Alan, M Saul, J Kirkwood and MA Weinstock 1 Brown University, Providence, RI, 2 VA Med CTR, Providence, RI, 3 University of Pittsburgh, Pittsburgh, PA and 4 Harvard University, Cambridge, MA Screening for melanoma may save lives, but may also cause patient distress. In January 2014, the University of Pittsburgh Medical Center launched a melanoma screening program for primary care providers (PCPs) offering INFORMED, a validated web-based training for detection of skin cancers, especially melanoma, to all PCPs and promoting annual skin screening of all patients age 35. We report the results of the first 139 telephone surveys of UPMC patients indicated by e medical record to having been screened to identify potential effects of the screening process. Measures of anxiety, depression and other distress were queried in addition to questions about screening activities, resources provided, and future intentions regarding skin cancer prevention. Patients surveyed were mostly white, non-Latino, female, with college or higher education, and of higher household income. Of those surveyed 42% were determined to have been thoroughly screened by their PCP as indicated by selfreport (35%) or by report of level of undress and skin areas examined consistent with thorough examination (6%). The remaining 58% were unaware the PCP screening, but may have been screened by another provider. Low numbers of participants reported potentially concerning anxiety (5 PCP screened of 7 overall) and depression (1 PCP screened of 2 overall). No differences in distress measures were found between screening groups. However, those with PCP screening were more likely to have been counseled to perform regular skin selfexamination (53%) and have been provided with written information (33%) compared to those not screened (27, 6% respectively, all p<.01). These data are subject to limitations including the several months’ time lag between screening and the survey. However, they suggest that screening for melanoma by PCPs occurred without increasing psychological symptoms. The sample will be enlarged to over 200 patients to better understand the impact of PCP screening.

149 Predictors of actinic keratosis count

148 A case-control study of the skin manifestations of osteogenesis imperfecta HB Pasieka, J Qi, MS Jang, JA Jefferson, Y Balagula, N Kim, S Leung, D Kuhn, JR Shapiro, S Kang and AL Chien 1 Dermatology, Johns Hopkins University, Baltimore, MD and 2 Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD Osteogenesis imperfecta (OI) is a congenital disorder resulting in brittle bones, associated with collagen deficiency. Despite the important role of collagen as a component of skin, the dermatological manifestations of this disease continue to remain an understudied topic in literature. In this case-control study, 15 participants with OI were recruited, along with 15 controls. Case-control pairs were matched in age (mean1⁄446.5), sex (22 females, 8 males), and race (22 Caucasians, 4 African-Americans, 2 Hispanics, and 2 Asians). Participants underwent a skin exam and answered a survey on medical history and lifestyle factors. Comparison of skin exam findings did not show statistically significant differences in photoaging, chronological aging, non-acne scars, acne scars, or striae. Cases had higher Beighton scores for joint hypermobility (p1⁄40.050). Survey results showed that perceived bruise healing time is longer for cases than controls (p1⁄40.026). Additional complaints more common in cases included flat feet (p1⁄40.016), scoliosis (p1⁄40.006), thin limbs (p1⁄40.031), “double-jointedness” (p1⁄40.016), and blue sclera (p1⁄40.001). Notably, cases reported seeing a dermatologist less frequently than controls (p1⁄40.011). While our study was limited in size, given the rareness of OI, the data provide useful insight into the dermatological issues for this patient group. 149 Predictors of actinic keratosis count JA Siegel, AJ Luber and MAWeinstock 1 VA Med Ctr, Providence, RI and 2 Brown Univ, Providence, RI Actinic keratoses (AKs) are frequently treated in the U.S., impacting an estimated 40 million people in 2004 and costing over $1 billion annually. AKs are a major public health concern because of their high prevalence, substantial cost, and potential for malignant transformation to keratinocyte carcinoma (KC). In this analysis, predictors of AK count were explored using pre-randomization baseline data from two large randomized controlled trials of veterans with two or more KCs in the past 5 years (n1⁄4932 and n1⁄41131). Multivariate analyses were conducted to elucidate associations between AK count and several demographic and health related factors. Increased AK count was strongly associated (p<0.01) with older age, history of 5-flurouracil use, low latitude, and greater sun sensitivity (based on natural hair color, ability to burn, and ability to tan at age 18, as well as current untanned skin color). Greater AK count was also strongly associated with higher numbers of prior KCs, specifically invasive squamous cell carcinoma (SCC), followed by SCC in situ, followed by basal cell carcinoma (BCC). Additionally, baseline AK count on the left side of the face and left ear was significantly higher than baseline AK count on the right side of the face and right ear (p<0.001), which may be explained by increased UV radiation to the left side while driving. These results not only confirm that AKs are associated with chronic sun-damage, but also highlight the relationship between AKs and KCs independent of susceptibility to UV damage. While the relationship between AKs and SCCs is well established, the association of prior BCCs with increased AK count highlights the importance of increased vigilance for all KCs in patients with many AKs, regardless of sun exposure and susceptibility. Recognizing predictors of AK count in individuals at high risk for KC may also help providers tailor AK prevention and treatment efforts. This may in turn lower the risk of KC—perhaps a more important goal—as the keratinocytic dysplasia that gives rise to malignancy, and sometimes appears as an AK, is what actually threatens patient health.

208 Multiple primary melanomas: Prevalence and outcomes

208 Multiple primary melanomas: Prevalence and outcomes A Nosrati, S Goel, J McGuire, B Grimes, RK Singh, K Lee, VB Morhenn, A Griffin and ML Wei 1 University of California, San Francisco, CA and 2 Veterans Affairs Medical Center, San Francisco, CA We investigated the characteristics and outcomes of individuals with multiple primary melanomas (MPM) compared with individuals with a single primary melanoma (SPM) to identify risk factors for developing MPM and whether outcomes differed between these groups. 7,268 individuals diagnosed with melanoma from 1983-2013 were identified at a tertiary referral academic center for a retrospective observational study. 6963 individuals (95.8%) had a SPM and 305 (4.2%) had MPM. Mean follow-up interval was 17 y (median 14.6, CI 95%13.715.4). MPM patients were more likely to be older (mean age 60.2 vs 55.8 y; P 1 mm. Overall survival was significantly better for patients with MPM when calculated by designating the index tumor as either the first occurring tumor (HR1⁄40.73, 95%CI 0.599-0.891) or the first invasive tumor (HR1⁄40.8, 95%CI 0.652-0.992). Overall survival was also increased when the thickest tumor was designated as the index tumor (HR1⁄40.86, 95%CI 0.7-1.06), however this did not reach significance. Melanoma specific survival was increased in MPM patients, but not significantly. In summary, MPM patients are more frequently older, white, male individuals with family history of melanoma. MPM patients have an increased rate of selected internal malignancies and overall survival but similar melanoma-specific survival rate compared with those with SPM. 209 No psychological harm from melanoma screening by PCPs: Preliminary results PM Risica, L Dionne, J Mello, LK Ferris, G Alan, M Saul, J Kirkwood and MA Weinstock 1 Brown University, Providence, RI, 2 VA Med CTR, Providence, RI, 3 University of Pittsburgh, Pittsburgh, PA and 4 Harvard University, Cambridge, MA Screening for melanoma may save lives, but may also cause patient distress. In January 2014, the University of Pittsburgh Medical Center launched a melanoma screening program for primary care providers (PCPs) offering INFORMED, a validated web-based training for detection of skin cancers, especially melanoma, to all PCPs and promoting annual skin screening of all patients age 35. We report the results of the first 139 telephone surveys of UPMC patients indicated by e medical record to having been screened to identify potential effects of the screening process. Measures of anxiety, depression and other distress were queried in addition to questions about screening activities, resources provided, and future intentions regarding skin cancer prevention. Patients surveyed were mostly white, non-Latino, female, with college or higher education, and of higher household income. Of those surveyed 42% were determined to have been thoroughly screened by their PCP as indicated by selfreport (35%) or by report of level of undress and skin areas examined consistent with thorough examination (6%). The remaining 58% were unaware the PCP screening, but may have been screened by another provider. Low numbers of participants reported potentially concerning anxiety (5 PCP screened of 7 overall) and depression (1 PCP screened of 2 overall). No differences in distress measures were found between screening groups. However, those with PCP screening were more likely to have been counseled to perform regular skin selfexamination (53%) and have been provided with written information (33%) compared to those not screened (27, 6% respectively, all p<.01). These data are subject to limitations including the several months’ time lag between screening and the survey. However, they suggest that screening for melanoma by PCPs occurred without increasing psychological symptoms. The sample will be enlarged to over 200 patients to better understand the impact of PCP screening.

148 A case-control study of the skin manifestations of osteogenesis imperfecta

148 A case-control study of the skin manifestations of osteogenesis imperfecta HB Pasieka, J Qi, MS Jang, JA Jefferson, Y Balagula, N Kim, S Leung, D Kuhn, JR Shapiro, S Kang and AL Chien 1 Dermatology, Johns Hopkins University, Baltimore, MD and 2 Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD Osteogenesis imperfecta (OI) is a congenital disorder resulting in brittle bones, associated with collagen deficiency. Despite the important role of collagen as a component of skin, the dermatological manifestations of this disease continue to remain an understudied topic in literature. In this case-control study, 15 participants with OI were recruited, along with 15 controls. Case-control pairs were matched in age (mean1⁄446.5), sex (22 females, 8 males), and race (22 Caucasians, 4 African-Americans, 2 Hispanics, and 2 Asians). Participants underwent a skin exam and answered a survey on medical history and lifestyle factors. Comparison of skin exam findings did not show statistically significant differences in photoaging, chronological aging, non-acne scars, acne scars, or striae. Cases had higher Beighton scores for joint hypermobility (p1⁄40.050). Survey results showed that perceived bruise healing time is longer for cases than controls (p1⁄40.026). Additional complaints more common in cases included flat feet (p1⁄40.016), scoliosis (p1⁄40.006), thin limbs (p1⁄40.031), “double-jointedness” (p1⁄40.016), and blue sclera (p1⁄40.001). Notably, cases reported seeing a dermatologist less frequently than controls (p1⁄40.011). While our study was limited in size, given the rareness of OI, the data provide useful insight into the dermatological issues for this patient group. 149 Predictors of actinic keratosis count JA Siegel, AJ Luber and MAWeinstock 1 VA Med Ctr, Providence, RI and 2 Brown Univ, Providence, RI Actinic keratoses (AKs) are frequently treated in the U.S., impacting an estimated 40 million people in 2004 and costing over $1 billion annually. AKs are a major public health concern because of their high prevalence, substantial cost, and potential for malignant transformation to keratinocyte carcinoma (KC). In this analysis, predictors of AK count were explored using pre-randomization baseline data from two large randomized controlled trials of veterans with two or more KCs in the past 5 years (n1⁄4932 and n1⁄41131). Multivariate analyses were conducted to elucidate associations between AK count and several demographic and health related factors. Increased AK count was strongly associated (p<0.01) with older age, history of 5-flurouracil use, low latitude, and greater sun sensitivity (based on natural hair color, ability to burn, and ability to tan at age 18, as well as current untanned skin color). Greater AK count was also strongly associated with higher numbers of prior KCs, specifically invasive squamous cell carcinoma (SCC), followed by SCC in situ, followed by basal cell carcinoma (BCC). Additionally, baseline AK count on the left side of the face and left ear was significantly higher than baseline AK count on the right side of the face and right ear (p<0.001), which may be explained by increased UV radiation to the left side while driving. These results not only confirm that AKs are associated with chronic sun-damage, but also highlight the relationship between AKs and KCs independent of susceptibility to UV damage. While the relationship between AKs and SCCs is well established, the association of prior BCCs with increased AK count highlights the importance of increased vigilance for all KCs in patients with many AKs, regardless of sun exposure and susceptibility. Recognizing predictors of AK count in individuals at high risk for KC may also help providers tailor AK prevention and treatment efforts. This may in turn lower the risk of KC—perhaps a more important goal—as the keratinocytic dysplasia that gives rise to malignancy, and sometimes appears as an AK, is what actually threatens patient health.

The associations between disc degeneration and co-existent structural abnormalities in the lumbosacral spine – A 3.0T MRI study of community-based adults

The associations between disc degeneration and co-existent structural abnormalities in the lumbosacral spine – A 3.0T MRI study of community-based adults

Cross-sectional and longitudinal association between types of meniscal pathology and knee pain: Data from the osteoarthritis initiative

Cross-sectional and longitudinal association between types of meniscal pathology and knee pain: Data from the osteoarthritis initiative

The association of comorbid conditions with patient reported outcomes in osteoarthritis

The association of comorbid conditions with patient reported outcomes in osteoarthritis

Perceived barriers and enablers to accessing conservative and surgical care for osteoarthritis

Perceived barriers and enablers to accessing conservative and surgical care for osteoarthritis

Long-term effectiveness of glucosamine and chondroitin in treating knee osteoarthritis: an analysis with marginal structural modeling

Long-term effectiveness of glucosamine and chondroitin in treating knee osteoarthritis: an analysis with marginal structural modeling

Effect of Cannabinoids and MethoxyPolyethylene Glycols on Aqueous Humor Outflow and Vascular Tone

WIN, a cannabinoid, and MPDTE, a methoxy polyethylene glycol are novel drugs to mitigate the increase in intraocular pressure, a major risk factor for glaucoma. However, their mechanism of action is not well studied. We investigate whether WIN or MPDTE reduce IOP by targeting vascular tone or reduced aqueous humor (AH) production and if eNOS is involved. To document AH flow using fluorometry, eyes were treated topically with either 1.0% WIN, 1.0% MPDTE, 0.1% brimonidine or brinzolamide 10 min prior to applying fluorescein. To measure vascular tone, 4mm aortic rings were placed on a weighted hook system and equilibrated in Krebs solution before introducing either 1.0% WIN or 1.0% MPDTE (n=5/group). Changes in the length of the bands were measured with a micrometer. To control for eNOS contribution, endothelial lining on aortic rings was either removed or kept intact. The greatest reduction in fluorescein intensity was observed after WIN treatment (73±13%) followed by brimonidine (55±10%), MPDTE (42±7%) and brinzolamide (39±4%). WIN increased ring length by 15±3% and MPDTE by 6±4% (p=0.01, n=5). In aortic rings without endothelium, WIN increased ring length by 8±4% and MPDTE by 5±3%. Preliminary results suggest that WIN targets AH outflow with some eNOS involvement while MPDTE targets AH production without affecting vascular tone. Supported in part by E. VA Eye Inst. and E. VA Med Sch.

Predictors for the progression of knee pain in subjects with early symptomatic knee osteoarthritis - five year results from the CHECK study

Predictors for the progression of knee pain in subjects with early symptomatic knee osteoarthritis - five year results from the CHECK study

Predictors of fatigue in patients with hip and knee osteoarthritis

s / Osteoarthritis and Cartilage 21 (2013) S63–S312 S250 Conclusions: Knees that were replaced (KRs) had lower baseline cartilage thickness and greater longitudinal (1 year) cartilage loss than nonKRs, the differences being strongest in both tibiae. Cartilage loss in the weight-bearing femur (a region commonly showing the greatest rate and sensitivity to change), in contrast showed less discrimination. The ability to discriminate between KRs and non-KRs was greater for “earlier” KRs (within 2 years after measurement of cartilage loss) than for those who received KR “later” (year 2-4 after measuring cartilage loss). 474 PREDICTORS OF FATIGUE IN PATIENTS WITH HIP AND KNEE OSTEOARTHRITIS K.D. Allen y,z, H.B. Bosworth y,z, C.J. Coffman y,z, A.S. Jeffreys y, E.Z. Oddone y,z, W.S. Yancy, Jr. y,z. yDurham VA Med. Ctr., Durham, NC, USA; zDuke Univ. Med. Ctr., Durham, NC, USA Purpose: Fatigue is emerging as an important outcome for patients with osteoarthritis (OA), but little is known about factors that predict fatigue severity. This study examined associations of demographic and clinical factors with fatigue in a cohort of patients with hip and / or knee OA. Methods: Participants were n1⁄4291 patients enrolled in a clinical trial of a combined patient and provider intervention for managing OA at the Durham Veterans Affairs Medical Center (mean age 1⁄4 61, SD1⁄49, 90% male, 53% non-white primarily African American). All measures were from baseline assessments. Fatigue was assessed with a 10cm visual analog scale (range 0-10) that asked participants to report how much fatigue has been a problem for them during the past week; anchors were “Fatigue is no problem” and “Fatigue is a major problem.” Potential predictors included participant age, race (white vs. nonwhite), gender, education (some vs. no college), self-rated health (excellent, very good, or good vs. fair or poor), pain severity (Western Ontario and McMasters University Osteoarthritis Index pain subscale), insomnia (Insomnia Severity Index), and depressive symptoms (Patient Health Questionnaire-8). Simple linear regression models examined associations of each individual predictor variable with fatigue, then a multivariable model was fit including all predictors that were significantly associated (p<0.01) with fatigue in simple regression models. Results: The mean fatigue score was 4.8 (SD1⁄43.1). In simple regression models, older age was associated with slightly lower fatigue (b1⁄4 0.07, 95%CI 1⁄4 -0.1, -0.04; p<0.001), and the following were associate with more fatigue: fair / poor self-rated health (b1⁄42.2, 95%CI 1⁄4 1.3, 3.1; p<0.001), greater insomnia severity (b 1⁄4 0.21, 95%CI 1⁄4 0.2, 0.3, p<0.001), greater pain severity (b1⁄4 0.4, 95%CI1⁄4 0.3, 0.5; p<0.001), and greater depressive symptoms (b 1⁄4 0.35, 95%CI 1⁄4 0.3, 0.4; p<0.001). In the multivariable model, variables that remained associated with fatigue were insomnia severity (b 1⁄4 0.06, 95%CI 1⁄4 0.01, 0.1; p1⁄40.0), pain severity (b 1⁄4 0.20, 95%CI 1⁄4 0.1, 0.3; p<0.001), depressive symptoms (b 1⁄4 0.21, 95%CI 1⁄4 0.1, 0.3; p<0.001). Conclusions: Fatigue severity was relatively high in this cohort of patients with OA; mean values on the fatigue visual analog scale were comparable to those seen in patients with rheumatoid arthritis. Demographic factors including age, as well as general health, were not associated with fatigue in the multivariable model. However, key clinical variables related to OA pain, depressive symptoms, and insomnia were associated with more fatigue. These results highlight that fatigue is part of a cluster of OA-related symptoms that generally worsen with greater disease severity. Because of its impact on daily activities and quality of life, fatigue is an important issue to address among patients

Female gender is protective for outcomes after primary total knee arthroplasty: a risk-adjusted analysis

s / Osteoarthritis and Cartilage 20 (2012) S54–S296 S294 587 FEMALE GENDER IS PROTECTIVE FOR OUTCOMES AFTER PRIMARY TOTAL KNEE ARTHROPLASTY: A RISK-ADJUSTED ANALYSIS J.A. Singh , C. Kwoh , D. Richardson , W. Chen , S. Ibrahim . Univ. of Alabama and Birmingham VA Med. Ctr., Birmingham, AL, USA; Univ. of Pittsburgh and Pittsburgh VA Med. Ctr., Pittsburgh, PA, USA; Univ. of Pennsylvania and Philadelphia VA Med. Ctr., Philadelphia, PA, USA; Univ. of Pennsylvania and Philadelphia VA Med. Ctr., Philadelphia, AL, USA; Univ. of Pennsylvania and Philadelphia VA Med. Ctr., philadelphia, PA, USA Purpose: Osteoarthritis is more prevalent in women than men. Joint replacement is an effective treatment option for end-stage knee OA and its utilization is increasing rapidly. There are, however, limited data on gender differences in surgical outcomes after total joint arthroplasty. We sought to examine gender differences in overall mortality, major complications, revision rates and re-admission rates after primary total knee arthroplasty.. Methods: The sample consisted of all primary knee total joint arthroplasties performed in the State of Pennsylvania during the fiscal year 2002. Primary knee arthroplasty was identified using the International Classification of Diseases, Ninth revision, Clinical Modification (ICD-9CM) code 81.54 in the Pennsylvania Health Care Cost Containment Council (PHC4) Database. We excluded patients with revision knee arthroplasty or with hip joint related procedures during index hospitalization. PHC4 includes demographic data from all patient discharges from 170 non-governmental (i.e. non-Veterans Administration) acute care hospitals in the State of Pennsylvania. We used ICD-9 codes to identify major complications such as venous thromboembolism (VTE), myocardial infarction (MI), prosthetic device malfunction, surgical wound infection and revision knee arthroplasty (ICD-9 codes, 81.55, 0080, 0081, 0082, 0083, and 0084). We examined the associations between gender and allcause mortality, major surgical complications. risk of surgical revision at 1-year and at 5-years after index arthroplasty. We adjusted for age, race or ethnicity, hospital teaching status (teaching or non-teaching), insurance status (none or unknown, Medicaid, Medicare/ government, or private), hospital procedure volume (0-100 and >100), and length of hospital stay and the 3M[[Unsupported Character ]] All Patient Refined-Diagnosis Related Group Risk of Mortality (APR-ROM) score, a validated surgical risk score. Results: In sample consisting of 19,312 primary total knee arthroplasties, there were 47 deaths (0.2%) at 30 days and 232 (1.2%) at one year. Within 30 days of index TKA, 1076 (5.8%) had major complications. Table 1 shows unadjusted rates of major complications. Compared to women, men had higher adjusted odds of one-year mortality (Odds Ratio (OR), 1.50; 95% CI, [1.22-1.86]), wound infections (1.23 [1.01-1.49]) and 30-day readmission (1.44 [0.80-2.57]) after primary TKA. Men also had significantly higher risk of revision arthroplasty of the primary TKA at 1-year (Hazard Ratio(HR), 1.60; 95% CI1⁄4 1.27-2.03) and 5-years (1.21; 95% CI1⁄4 1.08-1.37). There were no statistically significant gender differences in the rates of short-term complications (i.e., venous thromboembolism, Table 1 Unadjusted rates (n (%)) of surgical outcomes of TKA comparing women to men

Effects of IV Remifentanil (Remi) on the discharge patterns of canine pre‐Botzinger complex (pBC) neurons

Mu‐opioids at clinical doses typically produces bradypnea, which may be mediated by their effects on presynaptic neurons that supply inputs to pBC neurons. This study evaluated the effects of the rapid, short‐acting mu‐opioid Remi (IV) on the discharge patterns of pBC neuron subtypes in decerebrate, vagotomized, mechanically‐ventilated, paralyzed dogs during hyperoxia. A NeuroNexus 16‐electrode microprobe was used to simultaneously record from multiple pBC neurons before, during and after the IV infusion of Remi. Histograms (CTHs) triggered from the phrenic neurogram (PNG) were used to determine peak and time‐averaged discharge frequency (Fn) and profiles. Remi (0.94 mcg/kg/min) increased TI and TE by 3% and 71% respectively, and decreased peak PNG by 55%. Depression (peak Fn) among subtypes was not different: I‐aug (28±10%; n=32), I‐dec (22±10%; n=18), E‐aug (18±10%; n=15), and E‐dec (38±8%; n=26). Depression based on average Fn was similar. The magnitude of neuronal depression was not related to TI and TE or control Fn. Differential depression between simultaneously recorded neurons was common. While the pBC neurons were much less depressed than the peak PNG, the similar degree of depression of neuron subtypes and response variability did not allow bradypnea to be assigned to any pBC neuron subtype. The mechanism for bradypnea may lie outside the pBC. Supported by VA Med. Res. and NIH GM059234 funds.

Depression of respiratory rate by intravenous opioids is not due to direct opioid effects on neurons within the preBotzinger Complex (pBC) region

Clinical doses of i.v. mu‐opioids profoundly depress breathing rate. Mu‐opioid receptors (MORs) on pBC neurons, the putative kernel of rhythmogenesis, are potential targets. The purpose of this study was to determine the contribution of pBC MORs to respiratory depression by i.v. remifentanil (remi), a short‐acting, selective MOR agonist. Multi‐barrel micropipettes were used to record pBC neuronal activity and picoeject naloxone (NAL) in decerebrate, vagotomized, paralyzed and ventilated dogs during isocapnic hyperoxia. Remi was infused i.v. at a rate (0.2–0.4 mcg/kg/min) that produced a marked steady‐state bradypnea as determined from the phrenic neurogram (PNG). In study 1, NAL (5 mM) was picoejected onto single pBC neurons to determine the level of direct remi depression. In study 2, bilateral injections of NAL (100 nl each), 3 each side, centered in the pBC and 1‐mm rostral and caudal were used to locally block MORs. The results show that antagonism of MOR in the pBC region had no effect on neuronal and PNG patterns, but i.v. NAL (0.3 ml; 5 mM) completely reversed bradypnea. We conclude that opioids at plasma concentrations used for profound clinical analgesia depress breathing via MORs outside of the pBC region, which does not exclude that effects may be mediated indirectly via the pBC. Support: VA Med. Res. Funds &amp; NIH R01 GM59234.