Method used to identify adenomyosis and potentially undiagnosed adenomyosis in a large, U.S. electronic health record database.

BACKGROUND: The prevalence of adenomyosis is underestimated due to lack of a specific diagnostic code and diagnostic delays given most diagnoses occur at hysterectomy. OBJECTIVES: To identify women with adenomyosis using indicators derived from natural language processing (NLP) of clinical notes in the Optum Electronic Health Record database (2014-2018), and to estimate the prevalence of potentially undiagnosed adenomyosis. METHODS: An NLP algorithm identified mentions of adenomyosis in clinical notes that were highly likely to represent a diagnosis. The anchor date was date of first affirmed adenomyosis mention; baseline characteristics were assessed in the 12 months prior to this date. Characteristics common to adenomyosis cases were used to select a suitable pool of women from the underlying population, among whom undiagnosed adenomyosis might exist. A random sample of this pool was selected to form the comparator cohort. Logistic regression was used to compare adenomyosis cases to comparators; the predictive probability (PP) of being an adenomyosis case was assessed. Comparators having a PP ≥ 0.1 were considered potentially undiagnosed adenomyosis and were used to calculate the prevalence of potentially undiagnosed adenomyosis in the underlying population. RESULTS: Among 11 456 347 women aged 18-55 years in the underlying population, 19 503 were adenomyosis cases. Among 332 583 comparators, 22 696 women were potentially undiagnosed adenomyosis cases. The prevalence of adenomyosis and potentially undiagnosed adenomyosis was 1.70 and 19.1 per 1000 women aged 18-55 years, respectively. CONCLUSIONS: Considering potentially undiagnosed adenomyosis, the prevalence of adenomyosis may be 10x higher than prior estimates based on histologically confirmed adenomyosis cases only.

Morbidity and Mortality of Locally Advanced Prostate Cancer: A Population Based Analysis Comparing Radical Prostatectomy versus External Beam Radiation.

PURPOSE: The management of locally advanced prostate cancer remains controversial. We compared the effect of primary external beam radiation therapy vs radical prostatectomy for locally advanced prostate cancer. MATERIALS AND METHODS: We retrospectively analyzed the records of 2,935 elderly men 65 years old or older in the SEER (Surveillance, Epidemiology and End Results)-Medicare linked database who underwent external beam radiation therapy or radical prostatectomy for locally advanced prostate cancer. Propensity adjusted Cox proportional hazard and regression models were fit to examine urinary and gastrointestinal toxicities, the use of androgen deprivation therapy, and overall and prostate cancer specific mortality. RESULTS: A total of 1,429 men (48.69%) underwent radical prostatectomy and had a median followup of 11.47 years (IQR 6.17-17.17) years. A total of 1,506 men (51.31%) received external beam radiation therapy and had a median followup of 7.04 years (IQR 4.11-10.51, p <0.001). Patients treated with radical prostatectomy were at significantly higher risk for urinary and sexual toxicities (HR 1.93, 95% CI 1.66-2.24 and HR 5.50, 95% CI 3.59-8.42, respectively). However, they were at lower risk for gastrointestinal toxicities (HR 0.75, 95% CI 0.65-0.86) than those treated with external beam radiation therapy. Radical prostatectomy was associated with lower odds of androgen deprivation therapy 5 years after primary treatment (OR 0.53, 95% CI 0.41-0.69, p <0.001). External beam radiation therapy was associated with higher overall and prostate specific mortality (HR 1.41, 95% CI 1.09-1.82 and HR 2.35, 95% CI 1.85-2.98, respectively). CONCLUSIONS: We found significant toxicity and survival differences in elderly men who underwent primary external beam radiation therapy vs radical prostatectomy for locally advanced prostate cancer. While our findings must be interpreted within the limitations of studies that rely on administrative claims, they may yet help tailor individual therapies for elderly men who present with locally advanced prostate cancer.

Association between androgen deprivation therapy and anxiety among 78 000 patients with localized prostate cancer.

OBJECTIVES: To examine whether any androgen deprivation therapy use or longer duration is associated with an increased risk of anxiety in patients with prostate cancer. METHODS: We identified 78 552 men aged ≥66 years with stage I-III prostate cancer using the Surveillance, Epidemiology, and End Results-Medicare linked database from 1992 to 2006, excluding patients with psychiatric diagnoses within the year prior or 6 months after prostate cancer diagnosis. Multivariable Cox regression was used to examine the association between pharmacological androgen deprivation therapy and diagnosis of anxiety. RESULTS: The 43.1% (33 882) of patients who received androgen deprivation therapy experienced a higher 3-year cumulative incidence of anxiety compared with men who did not (4.1% vs 3.5%, P < 0.001). Any androgen deprivation therapy use was associated with a nearly significant increased risk of anxiety (adjusted hazard ratio 1.08, 95% confidence interval 1.00-1.17, P = 0.054). There was a significant trend between a longer duration of therapy and increased risk of anxiety (P-trend = 0.012), with a 16% higher risk for ≥12 months (adjusted hazard ratio 1.16, 95% confidence interval 1.04-1.29, P = 0.010). CONCLUSIONS: Androgen deprivation therapy was associated with an elevated risk of anxiety in this cohort of elderly men with localized prostate cancer, with the risk higher with a longer duration of treatment. Anxiety should be considered among the possible psychiatric effects of androgen deprivation therapy and discussed before initiating treatment, particularly if a long course is anticipated.

Risk Prediction Accuracy Differs for Emergency Versus Elective Cases in the ACS-NSQIP.

BACKGROUND: Accurate risk estimation is essential when benchmarking surgical outcomes for reimbursement and engaging in shared decision-making. The greater complexity of emergency surgery patients may bias outcome comparisons between elective and emergency cases. OBJECTIVE: To test whether an established risk modelling tool, the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) predicts mortality comparably for emergency and elective cases. METHODS: From the ACS-NSQIP 2011-2012 patient user files, we selected core emergency surgical cases also common to elective scenarios (gastrointestinal, vascular, and hepato-biliary-pancreatic). After matching strategy for Common Procedure Terminology (CPT) and year, we compared the accuracy of ACS-NSQIP predicted mortality probabilities using the observed-to-expected ratio (O:E), c-statistic, and Brier score. RESULTS: In all, 56,942 emergency and 136,311 elective patients were identified as having a common CPT and year. Using a 1:1 matched sample of 37,154 emergency and elective patients, the O:E ratios generated by ACS-NSQIP models differ significantly between the emergency [O:E = 1.031; 95% confidence interval (CI) = 1.028-1.033] and elective populations (O:E = 0.79; 95% CI = 0.77-0.80, P < 0.0001) and the c-statistics differed significantly (emergency c-statistic = 0.927; 95% CI = 0.921-0.932 and elective c-statistic = 0.887; 95% CI = 0.861-0.912, P = 0.003). The Brier score, tested across a range of mortality rates, did not differ significantly for samples with mortality rates of 6.5% and 9% (eg, emergency Brier score = 0.058; 95% CI = 0.048-0.069 versus elective Brier score = 0.057; 95% CI = 0.044-0.07, P = 0.87, among 2217 patients with 6.5% mortality). When the mortality rate was low (1.7%), Brier scores differed significantly (emergency 0.034; 95% CI = 0.027-0.041 versus elective 0.016; 95% CI = 0.009-0.023, P value for difference 0.0005). CONCLUSION: ACS-NSQIP risk estimates used for benchmarking and shared decision-making appear to differ between emergency and elective populations.

Determinants of cancer screening in Asian-Americans.

PURPOSE: Recent data suggest that Asian-Americans (AsAs) are more likely to present with advanced disease when diagnosed with cancer. We sought to determine whether AsAs are under-utilizing recommended cancer screening. METHODS: Cross-sectional analysis of the 2012 Behavioral Risk Factor Surveillance System comprising of AsAs and non-Hispanic White (NHW) community-dwelling individuals (English and Spanish speaking) eligible for colorectal, breast, cervical, or prostate cancer screening according to the United States Preventive Services Task Force recommendations. Age, education and income level, residence location, marital status, health insurance, regular access to healthcare provider, and screening were extracted. Complex samples logistic regression models quantified the effect of race on odds of undergoing appropriate screening. Data were analyzed in 2015. RESULTS: Weighted samples of 63.3, 33.3, 47.9, and 30.3 million individuals eligible for colorectal, breast, cervical, and prostate cancer screening identified, respectively. In general, AsAs were more educated, more often married, had higher levels of income, and lived in urban/suburban residencies as compared to NHWs (all p < 0.05). In multivariable analyses, AsAs had lower odds of undergoing colorectal (odds ratio [OR] 0.78, 95 % confidence interval [CI] 0.63-0.96), cervical (OR 0.45, 95 % CI 0.36-0.55), and prostate cancer (OR 0.55, 95 % CI 0.39-0.78) screening and similar odds of undergoing breast cancer (OR 1.29, 95 % CI 0.92-1.82) screening as compared to NHWs. CONCLUSIONS: AsAs are less likely to undergo appropriate screening for colorectal, cervical, and prostate cancer. Contributing reasons include limitations in healthcare access, differing cultural beliefs on cancer screening and treatment, and potential physician biases. Interventions such as increasing healthcare access and literacy may improve screening rates.

Surgeon and Hospital Level Variation in the Costs of Robot-Assisted Radical Prostatectomy.

PURPOSE: We assessed surgeon and hospital level variation in robot-assisted radical prostatectomy costs and predictors of high and low cost surgery. MATERIALS AND METHODS: The study population consisted of a weighted sample of 291,015 men who underwent robot-assisted radical prostatectomy for prostate cancer by 667 surgeons at 197 U.S. hospitals from 2003 to 2013. We evaluated 90-day direct hospital costs (2014 USD) in the Premier Hospital Database. High costs per robot-assisted radical prostatectomy were those above the 90th percentile and low costs were those below the 10th percentile. RESULTS: Mean hospital cost per robot-assisted radical prostatectomy was $11,878 (95% CI $11,804-$11,952). Mean cost was $2,837 (95% CI $2,805-$2,869) in the low cost group vs $25,906 (95% CI $24,702-$25,490) in the high cost group. Nearly a third of the variation in robot-assisted radical prostatectomy cost was attributable to hospital characteristics and more than a fifth was attributable to surgeon characteristics (R-squared 30.43% and 21.25%, respectively). High volume surgeons and hospitals (90th percentile or greater) had decreased odds of high cost surgery (surgeons: OR 0.24, 95% CI 0.11-0.54; hospitals: OR 0.105, 95% CI 0.02-0.46). The performance of robot-assisted radical prostatectomy at a high volume hospital was associated with increased odds of low cost robot-assisted radical prostatectomy (OR 839, 95% CI 122-greater than 999). CONCLUSIONS: This study provides insight into the role of surgeons and hospitals in robot-assisted radical prostatectomy costs. Given the substantial variability, identifying and remedying the root cause of outlier costs may yield substantial benefits.

Dose-dependent effect of androgen deprivation therapy for localized prostate cancer on adverse cardiac events.

OBJECTIVES: To investigate the dose-dependent effect of androgen deprivation therapy (ADT) on adverse cardiac events in elderly men with non-metastatic prostate cancer (PCa) stratified according to life expectancy. PATIENTS AND METHODS: A total of 50 384 men diagnosed with localized PCa between 1992 and 2007 were identified within the Surveillance, Epidemiology, and End Results registry areas. We compared those who received ADT within 2 years of PCa diagnosis with those who did not, calculated as monthly equivalent doses of GnRH agonists (<8, ≥8 doses), or orchiectomy. Men were further stratified according to life expectancy (<5 years, 5-10 years and >10 years). Adjusted Cox hazard models assessed the risk of new-onset coronary heart disease (CHD), acute myocardial infarction (AMI), sudden cardiac death (SCD) and cardiac-related interventions, as well as any of these events. RESULTS: Overall, patients receiving GnRH agonists were more likely to experience a cardiac event, with the most pronounced effect among those receiving ≥8 doses (hazard ratio [HR] <8 doses: 1.13, 95% confidence interval [CI] 1.09-1.16, and HR ≥8 doses: 1.18, 95% CI 1.14-1.22; both P < 0.001). The effect of prolonged (≥8 doses) GnRH agonist use on cardiac events was sustained across all strata of life expectancy; however, there was no effect among men with a life expectancy of <5 years and when use of GnRH agonists was limited to <8 doses (HR 0.99, 95% CI 0.67-1.46; P = 0.964). The use of GnRH agonists was associated with a higher risk of CHD (HR <8 doses: 1.13, 95% CI 1.09-1.17 and HR ≥8 doses: 1.17, 95% CI 1.13-1.21; both P < 0.001). Conversely, the use of GnRH was generally not associated with an increased risk of AMI or SCD, except for men who received ≥8 doses of GnRH agonists and had a life expectancy of ≥5 years, who were at a significantly higher risk of SCD (HR for life expectancy 5-10 years: 1.19, 95% CI 1.06-1.33; P = 0.003 and HR for life expectancy >10 years: 1.16, 95% CI 1.04-1.29; P = 0.006). Finally, orchiectomy was not associated with overall cardiac events, AMI or SCD, and was protective with regard to cardiac-related interventions (HR 0.78, 95% CI 0.68-0.90, P = 0.001). CONCLUSION: Exposure to ADT with GnRH agonists is associated with an increased risk of cardiac events in elderly men with localized PCa and a decent life expectancy. Clinicians should carefully weigh the risks and benefits of ADT in patients with a prolonged life expectancy. Routine screening and lifestyle interventions are warranted in at-risk subpopulations treated with ADT.

Suicide and accidental deaths among patients with non-metastatic prostate cancer.

OBJECTIVE: To determine if American men with prostate cancer are at increased risk of suicide/accidental death compared with other cancers and if the receipt of definitive treatment alters this association, as patients with cancer are at increased risk of suicide and evidence suggests a relationship between suicides and deaths due to accidents and externally caused injuries. PATIENTS AND METHODS: Demographic, socio-economic and tumour characteristics of men with prostate cancer and men with other solid malignancies were extracted from the Surveillance, Epidemiology and End Results (SEER) database (1988-2010). Poisson regression models were fitted to compare the incidence of suicidal and accidental deaths in prostate cancer vs other solid cancers. Multivariate Cox regression was used to determine if receipt of definitive primary treatment impacted the risk of suicide or accidental death in men with localised/regional prostate cancer. RESULTS: Risk of suicidal and accidental death was significantly lower in men with prostate cancer (1 165 [0.2%] and 3 199 [0.6%]) than men with other cancers (2 232 [0.2%] and 4 501 [0.5%], respectively), except within the first year of diagnosis (adjusted relative risk [ARR] 3.98, 95% confidence interval [CI] 3.02-5.23 and ARR 4.22, 95% CI 3.24-5.51, respectively, 0-3 months after diagnosis). Men with non-metastatic prostate cancer who were White, uninsured, or recommended but did not receive treatment (hazard ratio vs treated 1.44, 95% CI 1.20-1.72, and 1.44, 95% CI 1.30-1.59, both P < 0.001) were at increased risk of suicidal and accidental mortality, respectively. Absence of data about previous co-morbidities and drug addictions in the SEER dataset was an important limitation. CONCLUSIONS: Relative to other cancers, men with prostate cancer were at increased risk of suicide and accidental deaths within the first year of diagnosis and when definitive treatment was recommended but not received, suggesting the need for close monitoring and coordination with mental health professionals in at-risk men with potentially curable disease.

Variation in National Use of Long-Term ADT by Disease Aggressiveness Among Men With Unfavorable-Risk Prostate Cancer.

BACKGROUND: The current NCCN Clinical Practice Guidelines in Oncology for Prostate Cancer recommend long-term androgen deprivation therapy (ADT) for all men with high-risk prostate cancer treated with external-beam radiation therapy (EBRT). We determined whether the use of long-term ADT varied by the recently defined subcategories of high-risk disease (favorable, other, and very high) versus unfavorable intermediate-risk disease. METHODS: We identified 5,524 patients with unfavorable-risk prostate cancer diagnosed from 2004 to 2007 and managed with EBRT using the SEER-Medicare linked database. Patients were stratified by risk group: unfavorable intermediate-risk, favorable high-risk (previously defined and validated as clinical stage T1c, Gleason score of 4 + 4 = 8, and prostate-specific antigen [PSA] level <10 ng/mL, or clinical stage T1c, Gleason score of 6, and PSA level >20 ng/mL), very-high-risk (clinical stage T3b-T4 or primary Gleason pattern 5), or other high risk (ie, neither favorable nor very high). We used multivariable competing risks regression to estimate the rates of long-term (≥2 years) ADT by group. RESULTS: Men with favorable high-risk prostate cancer were significantly less likely to receive long-term ADT than those with other high-risk disease (15.4% vs 24.6%, adjusted hazard ratio [AHR], 0.68; 95% CI, 0.60-0.76;P<.001), and similarly likely as those with unfavorable intermediate-risk disease (AHR, 1.10; 95% CI, 0.99-1.23;P=.087). Other high-risk disease was less likely to receive long-term ADT than very high-risk cancer (24.6% vs 30.8%; AHR, 0.83; 95% CI, 0.74-0.93;P=.002). CONCLUSIONS: Despite current guidelines, patients with EBRT-managed high-risk prostate cancer received significantly different rates of long-course ADT based on subclassification. Our results suggest that oncologists view these patients as a heterogeneous group with favorable high-risk cancer warranting less aggressive therapy than other high-risk or very high-risk disease.

The impact of Medicare eligibility on cancer screening behaviors.

INTRODUCTION: Lack of health insurance limits access to preventive services, including cancer screening. We examined the effects of Medicare eligibility on the appropriate use of cancer screening services in the United States. METHODS: We performed a cross-sectional analysis of the 2012 Behavioral Risk Factor and Surveillance System (analyzed in 2014). Univariable and logistic regression analyses were performed for participants aged 60-64 and 66-70 to examine the effects of Medicare eligibility on prevalence of self-reported screening for colorectal, breast, and prostate cancers. Sub-analyses were performed among low-income (<$25,000 annual/household) individuals. RESULTS: Medicare-eligible individuals were significantly more likely to undergo all examined preventive services (colorectal cancer OR: 1.90; 95% CI 1.79-2.04; prostate cancer OR: 1.29; 95% CI 1.17-1.43; breast cancer OR: 1.23; 95% CI 1.10-1.37) and the effect was most pronounced among low-income individuals (colorectal cancer OR: 2.04; 95% CI 1.8-2.32; prostate cancer OR: 1.39; 95% CI 1.12-1.72; breast cancer OR: 1.42, 95% CI 1.20-1.67). Access to a healthcare provider was the strongest independent predictor of undergoing appropriate screening, ranging from OR 2.73 (95% CI 2.20-3.39) for colorectal cancer screening in the low-income population to OR 4.79 (95% CI 3.95-5.81) for breast cancer screening in the overall cohort. The difference in screening prevalence was most pronounced when comparing Medicare-eligible participants to uninsured Medicare-ineligible participants (+33.2%). CONCLUSIONS: Medicare eligibility impacts the prevalence of cancer screening, likely as a result of increased access to primary care. Low-income individuals benefit most from Medicare eligibility. Expanded public insurance coverage to these individuals may improve access to preventive services.

Relationship between androgen deprivation therapy and community-acquired respiratory infections in patients with prostate cancer.

OBJECTIVES: To investigate the dose-dependent effect of androgen deprivation therapy on community-acquired respiratory infections in patients with localized prostate cancer. METHODS: We identified 52 905 men diagnosed with localized prostate cancer within the Surveillance, Epidemiology and End Results-Medicare database between 1991 and 2006. We compared those who did not receive androgen deprivation therapy with those who received androgen deprivation therapy within 2 years of diagnosis, calculated as monthly equivalent doses (<7, 7-11, >11 doses), or orchiectomy. Adjusted Cox hazard models were fitted to predict the risk of community-acquired respiratory infections (acute sinusitis, acute bronchitis, [severe] pneumonia) in patients treated with medical androgen deprivation therapy versus orchiectomy versus none. RESULTS: Overall, 43.4% received medical androgen deprivation therapy. These patients more likely experienced respiratory events compared with those who did not receive androgen deprivation therapy or who underwent orchiectomy (62.2% vs 54.5% vs 47.8%, P < 0.001). The risk of experiencing any respiratory event increased with the number of doses received. For example, men receiving >11 doses of androgen deprivation therapy were at greatest risk of acute sinusitis, acute bronchitis and pneumonia (HR 1.13, 1.26 and 1.15, respectively, all P < 0.001), except severe pneumonia. Furthermore, we did not detect any relationship between orchiectomy and respiratory events. Study limitations include the utilization of a retrospective population-based dataset. CONCLUSIONS: Increased exposure to medical androgen deprivation therapy for men with localized prostate cancer is associated with a higher risk of community-acquired respiratory infections. Our results suggest that respiratory complications represent potentially underreported complications of medical androgen deprivation therapy.

Racial Disparities in End-of-Life Care Among Patients With Prostate Cancer: A Population-Based Study.

OBJECTIVE: To examine racial disparities in end-of-life (EOL) care among black and white patients dying of prostate cancer (PCa). METHODS: Relying on the SEER-Medicare database, 3789 patients who died of metastatic PCa between 1999 and 2009 were identified. Information was assessed regarding diagnostic care, therapeutic interventions, hospitalizations, intensive care unit (ICU) admissions, and emergency department visits in the last 12 months, 3 months, and 1 month of life. Logistic regression tested the relationship between race and the receipt of diagnostic care, therapeutic interventions, and high-intensity EOL care. RESULTS: Overall, 729 patients (19.24%) were black. In the 12-months preceding death, laboratory tests (odds ratio [OR], 0.51; 95% CI, 0.36-0.72), prostate-specific antigen test (OR, 0.54; 95% CI, 0.43-0.67), cystourethroscopy (OR, 0.71; 95% CI, 0.56-0.90), imaging procedure (OR, 0.58; 95% CI, 0.41-0.81), hormonal therapy (OR, 0.53; 95% CI, 0.44-0.65), chemotherapy (OR, 0.59; 95% CI, 0.48-0.72), radiotherapy (OR, 0.74; 95% CI, 0.61-0.90), and office visit (OR, 0.38; 95% CI, 0.28-0.50) were less frequent in black versus white patients. Conversely, high-intensity EOL care, such as ICU admission (OR, 1.27; 95% CI, 1.04-1.58), inpatient admission (OR, 1.49; 95% CI, 1.09-2.05), and cardiopulmonary resuscitation (OR, 1.72; 95% CI, 1.40-2.11), was more frequent in black versus white patients. Similar trends for EOL care were observed at 3-month and 1-month end points. CONCLUSIONS: Although diagnostic and therapeutic interventions are less frequent in black patients with end-stage PCa, the rate of high-intensity and aggressive EOL care is higher in these individuals. These disparities may indicate that race plays an important role in the quality of care for men with end-stage PCa.

Trauma systems are associated with increased level 3 trauma centers.

BACKGROUND: State-supported trauma systems have a proven association with improved mortality, but to date, there are no data reported on what mechanism leads to this benefit. Our hypothesis is that trauma systems with funding support are associated with increased number of trauma centers (TCs). MATERIALS AND METHODS: A retrospective population study: data for the number of American College of Surgeons-verified adult TCs in 2010 were obtained from the American College of Surgeons and for state-designated TCs from state departments of health. Population and gross domestic product (GDP) were obtained from the US Census. The main outcome measure was the number of TCs per population and per GDP. Statistical analysis was carried out using the Mann-Whitney U-test and Poisson regression. RESULTS: There was no association between a trauma system and the numbers of level 1 or 2 centers. In states with funded trauma systems, the numbers of level 3 centers per GDP and per million state population were 4.76 ± 2.37/$100 billion and 1.77 ± 0.51/million people compared with 0.72 ± 1.72/$100 billion and 0.28 ± 0.60/million people for unfunded states (P < 0.05). Poisson multivariate regression identified system funding as an independent predictor of number of level 3 centers. CONCLUSIONS: Our study shows that the number of level 3 TCs significantly and independently correlated with the presence of a funded trauma system. The number of level 1 and 2 centers showed no such correlation. Further study will determine if increased number of level 3 centers leads to improved clinical outcome.

Prolonged nerve blockade delays the onset of neuropathic pain.

Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain. Pharmacological blockade of that activity has been shown to mitigate the onset of associated molecular events in the nervous system. However, results in preventing onset of pain behaviors by providing prolonged nerve blockade have been mixed. Furthermore, the experimental techniques used to date to provide that blockade were limited in clinical potential in that they would require surgical implantation. To address these issues, we have used liposomes (SDLs) containing saxitoxin (STX), a site 1 sodium channel blocker, and the glucocorticoid agonist dexamethasone to provide nerve blocks lasting ~1 wk from a single injection. This formulation is easily injected percutaneously. Animals undergoing spared nerve injury (SNI) developed mechanical allodynia in 1 wk; nerve blockade with a single dose of SDLs (duration of block 6.9 ± 1.2 d) delayed the onset of allodynia by 2 d. Treatment with three sequential SDL injections resulting in a nerve block duration of 18.1 ± 3.4 d delayed the onset of allodynia by 1 mo. This very prolonged blockade decreased activation of astrocytes in the lumbar dorsal horn of the spinal cord due to SNI. Changes in expression of injury-related genes due to SNI in the dorsal root ganglia were not affected by SDLs. These findings suggest that formulations of this kind, which could be easy to apply clinically, can mitigate the development of neuropathic pain.

Enhanced photothermal effect of plasmonic nanoparticles coated with reduced graphene oxide.

We report plasmonic gold nanoshells and nanorods coated with reduced graphene oxide that produce an enhanced photothermal effect when stimulated by near-infrared (NIR) light. Electrostatic interactions between nanosized graphene oxide and gold nanoparticles followed by in situ chemical reduction generated reduced graphene oxide-coated nanoparticles; the coating was demonstrated using Raman and HR-TEM. Reduced graphene oxide-coated gold nanoparticles showed enhanced photothermal effect compared to noncoated or nonreduced graphene oxide-coated gold nanoparticles. Reduced graphene oxide-coated gold nanoparticles killed cells more rapidly than did noncoated or nonreduced graphene oxide-coated gold nanoparticles.

Local toxicity from local anesthetic polymeric microparticles.

BACKGROUND: Local tissue injury from sustained-release formulations for local anesthetics can be severe. There is considerable variability in reporting of that injury. We investigated the influence of the intrinsic myotoxicity of the encapsulated local anesthetic (lidocaine, low; bupivacaine, high) on tissue reaction in rats. METHODS: Cytotoxicity from a range of lidocaine and bupivacaine concentrations was measured in C2C12 myotubes over 6 days. Rats were given sciatic nerve blocks with 4 microparticulate formulations of lidocaine and bupivacaine: 10% (w/w) lidocaine poly(lactic-co-glycolic) acid (PLGA), 10% (w/w) bupivacaine PLGA, 50% (w/w) lidocaine PLGA, and 50% (w/w) bupivacaine PLGA. Effectiveness of nerve blockade was assessed by a modified hotplate test and weightbearing measurements. Myotoxicity was scored in histologic sections of injection sites. Bupivacaine and lidocaine release kinetics from the particles were measured. RESULTS: Median sensory blockade duration for 50% (w/w) lidocaine was 255 (90-540) minutes versus 840 (277-1215) minutes for 50% (w/w) bupivacaine (P = 0.056). All microparticulate formulations resulted in myotoxicity. The choice of local anesthetic did not influence the severity of myotoxicity. Median myotoxicity scores for 50% (w/w) lidocaine compared with 50% (w/w) bupivacaine at 4 days were 3.4 (2.1-4.2) vs 3.3 (2.9-3.5) (P = 0.44) and at 14 days 1.9 (1.8-2.4) vs 1.7 (1.3-1.9) (P = 0.23), respectively. CONCLUSIONS: Lidocaine and bupivacaine PLGA microspheres resulted in similar degrees of myotoxicity, irrespective of drug loading. Intrinsic myotoxicity did not predict tissue injury from sustained release of these anesthetics. Caution is warranted in the use of such devices near muscle and nerve.

Nanocomposite gold-silk nanofibers.

Cell-biomaterial interactions can be controlled by modifying the surface chemistry or nanotopography of the material, to induce cell proliferation and differentiation if desired. Here we combine both approaches in forming silk nanofibers (SNFs) containing gold nanoparticles (AuNPs) and subsequently chemically modifying the fibers. Silk fibroin mixed with gold seed nanoparticles was electrospun to form SNFs doped with gold seed nanoparticles (SNF(seed)). Following gold reduction, there was a 2-fold increase in particle diameter confirmed by the appearance of a strong absorption peak at 525 nm. AuNPs were dispersed throughout the AuNP-doped silk nanofibers (SNFs(Au)). The Young's modulus of the SNFs(Au) was almost 70% higher than that of SNFs. SNFs(Au) were modified with the arginine-glycine-aspartic acid (RGD) peptide. Human mesenchymal stem cells that were cultured on RGD-modified SNF(Au) had a more than 2-fold larger cell area compared to the cells cultured on bare SNFs; SNF(Au) also increased cell size. This approach may be used to alter the cell-material interface in tissue engineering and other applications.

A Randomized Cross-Over Trial Focused on Clinical Breast Exam Skill Acquisition Using High Fidelity versus Low Fidelity Simulation Models in Rwanda.

OBJECTIVE: Breast cancer incidence is rising for women in low and middle income country (LMIC)s. Growing the health care workforce trained in clinical breast exam (CBE) is critical to mitigating breast cancer globally. We developed a CBE simulation training course and determined whether training on a low-fidelity (LF) simulation model results in similar skill acquisition as training on high-fidelity (HF) models in Rwanda. DESIGN: A single-center randomized educational crossover trial was implemented. A preintervention baseline exam (exam 1), followed by a lecture series (exam 2), and training sessions with assigned simulation models was implemented (exam 3)-participants then crossed over to their unassigned model (exam 4). The primary outcome of this study determined mean difference in CBE exam scores between HF and LF groups. Secondary outcomes identified any provider level traits and changes in overall scores. SETTING: The study was implemented at the University Teaching Hospital, Kigali (CHUK) in Rwanda, Africa from July 2014 to March 2015 PARTICIPANTS: Medical students, residents in surgery, obstetrics and gynecology, and internal medicine residents participated in a 1-day CBE simulation training course. RESULTS: A total of 107 individuals were analyzed in each arm of the study. Mean difference in exam scores between HF and LF models in exam 1 to 4 was not significantly different (exam 1 0.08 standard error (SE) = 0.47, p = 0.42; exam 2 0.86, SE = 0.69, p = 0.16; exam 3 0.03, SE = 0.38, p = 0.66; exam 4 0.10 SE = 0.37, p = 0.29). Overall exam scores improved from pre- to post-intervention. CONCLUSIONS: Mean difference in exams scores were not significantly different between participants trained with HF versus LF models. LF models can be utilized as cost effective teaching tools for CBE skill acquisition, in resource poor areas.