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Background: The impact of peripheral artery disease (PAD) on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is not well studied., Methods: We analyzed the association of PAD with CTO-PCI outcomes using data from the PROGRESS-CTO registry of procedures performed at 47 centers between 2012 and 2023., Results: The prevalence of PAD among 12 961 patients who underwent CTO PCI during the study period was 13.9% (1802). PAD patients were older, more likely to be current smokers, and had higher rates of dyslipidemia, diabetes, cerebrovascular disease, hypertension, prior myocardial infarction, PCI, and coronary artery bypass graft surgery. Their PROGRESS-CTO (1.35 vs 1.22; P < .001) and J-CTO (2.63 vs 2.33; P < .001) scores were higher, lesion length was longer, and angiographic characteristics were more complex. Their access site was more likely to be bifemoral (33.6% vs 30.9%; P = .024) compared with patients with no PAD. Technical (82.9% vs 87.7%; P < .001) and procedural (80.5% vs 86.6%; P < .001) success rates were lower in patients with PAD, while the incidence of major adverse cardiovascular events (MACE) was higher (3.1% vs 1.8%; P < .001), with higher mortality (0.8% vs 0.4%; P = .034), acute myocardial infarction rate (0.9% vs 0.4%; P = .010), and perforations rate (6.6% vs 4.5%; P < .001). In multivariable analysis, PAD was associated with higher MACE (odds ratio [OR]: 1.53; 95% CI, 1.01-2.26; P = .038) and lower technical success (OR: 0.82; 95% CI, 0.69-0.99; P = .039)., Conclusions: PAD patients undergoing CTO PCI have higher comorbidity burden, more complex CTOs, higher MACE, and lower technical success.

Background: Fatal opioid-involved overdose rates increased precipitously from 5.0 per 100,000 population to 33.5 in Massachusetts between 1999 and 2022., Methods: We used spatial rate smoothing techniques to identify persistent opioid overdose-involved fatality clusters at the ZIP Code Tabulation Area (ZCTA) level. Rate smoothing techniques were employed to identify locations of high fatal opioid overdose rates where population counts were low. In Massachusetts, this included areas with both sparse data and low population density. We used Local Indicators of Spatial Association (LISA) cluster analyses with the raw incidence rates, and the Empirical Bayes smoothed rates to identify clusters from 2011 to 2021. We also estimated Empirical Bayes LISA cluster estimates to identify clusters during the same period. We constructed measures of the socio-built environment and potentially inappropriate prescribing using principal components analysis. The resulting measures were used as covariates in Conditional Autoregressive Bayesian models that acknowledge spatial autocorrelation to predict both, if a ZCTA was part of an opioid-involved cluster for fatal overdose rates, as well as the number of times that it was part of a cluster of high incidence rates., Results: LISA clusters for smoothed data were able to identify whether a ZCTA was part of a opioid involved fatality incidence cluster earlier in the study period, when compared to LISA clusters based on raw rates. PCA helped in identifying unique socio-environmental factors, such as minoritized populations and poverty, potentially inappropriate prescribing, access to amenities, and rurality by combining socioeconomic, built environment and prescription variables that were highly correlated with each other. In all models except for those that used raw rates to estimate whether a ZCTA was part of a high fatality cluster, opioid overdose fatality clusters in Massachusetts had high percentages of Black and Hispanic residents, and households experiencing poverty. The models that were fitted on Empirical Bayes LISA identified this phenomenon earlier in the study period than the raw rate LISA. However, all the models identified minoritized populations and poverty as significant factors in predicting the persistence of a ZCTA being part of a high opioid overdose cluster during this time period., Conclusion: Conducting spatially robust analyses may help inform policies to identify community-level risks for opioid-involved overdose deaths sooner than depending on raw incidence rates alone. The results can help inform policy makers and planners about locations of persistent risk., (© 2024. The Author(s).)

Objective: In this study, we explored key prescription drug monitoring program-related outcomes among clinicians from a broad cohort of Massachusetts healthcare facilities following prescription drug monitoring program (PDMP) and electronic health record (EHR) data integration., Methods: Outcomes included seven-day rolling averages of opioids prescribed, morphine milligram equivalents (MMEs) prescribed, and PDMP queries. We employed a longitudinal study design to analyze PDMP data over a 15-month study period which allowed for six and a half months of pre- and post-integration observations surrounding a two-month integration period. We used longitudinal mixed effects models to examine the effect of EHR integration on each of the key outcomes., Results: Following EHR integration, PDMP queries increased both through the web-based portal and in total (0.037, [95% CI = 0.017, 0.057] and 0.056, [95% CI = 0.035, 0.077]). Both measures of clinician opioid prescribing declined throughout the study period; however, no significant effect following EHR integration was observed. These results were consistent when our analysis was applied to a subset consisting only of continuous PDMP users., Conclusions: Our results support EHR integration contributing to PDMP utilization by clinicians but do not support changes in opioid prescribing behavior., (Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Ranolazine is an anti-anginal medication given to patients with chronic angina and persistent symptoms despite medical therapy. We examined 11 491 chronic total occlusion (CTO) percutaneous coronary interventions (PCI) that were performed at 41 US and non-US centers between 2012 and 2023 in the PROGRESS-CTO Registry. Patients on ranolazine at baseline had more comorbidities, more complex lesions, lower procedural and technical success (based on univariable but not multivariable analysis), and higher incidence of major adverse cardiac events (MACE) (on both univariable and multivariable analysis).

Background: Recent studies indicate that COVID-19 has had a significant impact on access and continuity to opioid and benzodiazepine medications; little is known about its effect on access to and utilization of stimulant medications., Objective: To investigate trends of dispensed stimulant medications in relation to the COVID-19 pandemic response., Methods: Stimulant prescriptions dispensed during 2011-2021 were analyzed using the Massachusetts Prescription Drug Monitoring Program (PDMP), the state's data repository for all controlled substance medications dispensed to residents from retail pharmacies and out of state mail-order pharmacies. Statewide trends were estimated by age group, sex, and stimulant-naïve patients (individuals with no stimulant prescription in the prior one-year period)., Results: Overall, stimulant prescriptions increased 70% from 2011 to 2021. Wide differences by sex and age groups were found pre and post COVID response periods. Between 2019 and 2021, stimulant prescriptions for males 12-18 years old decreased 14.6% compared to 0.9% for females. Female stimulant-naïve patients ages 25-34 increased more than males between 2019 and 2021 (11.6% compared to <1%, respectively) and females ages 35-44 increased 4.1% while males decreased by 2.7%., Conclusions: Administrators, clinicians, and policy makers should closely monitor stimulant prescribing trends, a critical step in improving access to and quality of care., Competing Interests: The Authors declare that they have no conflicts of interest to disclose., (© 2023 The Authors.)

Purpose: Oral-maxillofacial surgeons (OMSs) are frequent prescribers of opioid analgesics. It remains unclear if prescription patterns differ for urban versus rural patients, given potential differences in access to and delivery of care. This study aimed to characterize urban-rural differences in opioid analgesic prescriptions to patients in Massachusetts by OMSs from 2011 to 2021., Methods: This retrospective cohort study used the Massachusetts Prescription Monitoring Program database to identify Schedule II and III opioid prescriptions by providers with specialty of oral and maxillofacial surgery from 2011 to 2021. The primary predictor variable was patient geography (urban/rural) and secondary predictor was year (2011-2021). The primary outcome variable was milligram morphine equivalent (MME) per prescription. Secondary outcome variables were days' supply per prescription and number of prescriptions received per patient. Descriptive and linear regression statistics were performed to analyze differences in prescriptions to urban and rural patients each year and throughout the study period., Results: The study data, which includes OMS opioid prescriptions (n = 1,057,412) in Massachusetts from 2011 to 2021, ranged annually between 63,678 and 116,000 prescriptions to between 58,000 and 100,000 unique patients. The cohorts each year ranged between 48 and 56% female with mean ages between 37 and 44 years. There were no differences in the mean number of patients per provider in urban and rural populations in any year. The study sample had a large majority of urban patients (>98%). MME per prescription, days' supply per prescription, and prescriptions received per patient were all generally similar between urban and rural patients each year, with the largest MME per prescription difference in 2019 (87.3 for rural to 73.9 for urban patients, P < .01). From 2011 to 2021, all patients had a steady decrease in MME per prescription (β = -6.64, 95% confidence interval: -6.81, -6.48; R 2  = 0.39) and day's supply per prescription (β = -0.1, 95% confidence interval: -0.1, -0.09; R 2  = 0.37)., Conclusion: In Massachusetts, there were similar opioid prescribing patterns by oral and maxillofacial surgeons to urban and rural patients from 2011 to 2021. There has also been a steady decrease in the duration and total dosage of opioid prescriptions to all patients. These results are consistent with multiple statewide policies over the last several years aimed at curbing opioid overprescribing., (Copyright © 2023 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Although buprenorphine/naloxone has been demonstrated to be an effective treatment for patients with opioid use disorder (OUD), treatment retention has been a challenge. This study extends what is presently a limited literature regarding patients' experiences with this medication and the implications for treatment retention. Methods: The study was conducted as a qualitative investigation of patients in treatment for OUD at the time of the study. Forty-three patients (27 men, 15 women, mean age 34.7) were recruited from three clinical settings, a community health center, an academically-based treatment site, and an independent substance abuse treatment facility. Most patients had returned to use in the past after attempts to become abstinent. Results: Patients generally reported positive experiences with this medication noting it helped to reduce opioid cravings quickly. As important considerations for treatment retention, patients emphasized a firm commitment to achieving abstinence when beginning treatment and a prescriber who is informed about and attentive to their emotional state. Diverging attitudes did exist regarding treatment duration as some patients were accepting of long-term treatment while others desired a relatively brief option. Among patients who had returned to use, potentially important issues emerged pertaining to the absence of patient outreach for missed medication appointments and inadequate discharge planning following stays at rehabilitation facilities. Conclusions: While results regarding the importance of patient motivation and strong patient-prescriber relationships have been noted in previous studies, other findings regarding opportunities to improve patient outreach and coordination of care have received relatively less attention and warrant further consideration.

Background: The use of intravascular lithotripsy (IVL) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study., Methods: We analyzed the baseline clinical and angiographic characteristics and procedural outcomes of 82 CTO PCIs that required IVL at 14 centers between 2020 and 2022., Results: During the study period, IVL was used in 82 of 3301 (2.5%) CTO PCI procedures (0.4% in 2020 and 7% in 2022; p for trend < 0.001). Mean patient age was 69 ± 11 years and 79% were men. The prevalence of hypertension (95%), diabetes mellitus (62%), and prior PCI (61%) was high. The most common target vessel was the right coronary artery (54%), followed by the left circumflex (23%). The mean J-CTO and PROGRESS-CTO scores were 2.8 ± 1.1 and 1.3 ± 1.0, respectively. Antegrade wiring was the final successful crossing strategy in 65% and the retrograde approach was used in 22%. IVL was used in 10% of all heavily calcified lesions and 11% of all balloon undilatable lesions. The 3.5 mm lithotripsy balloon was the most commonly used balloon (28%). The mean number of pulses per lithotripsy run was 33 ± 32 and the median duration of lithotripsy was 80  (interquartile range: 40-103) seconds. Technical and procedural success was achieved in 77 (94%) and 74 (90%) cases, respectively. Two (2.4%) Ellis Class 2 perforations occurred after IVL use and were managed conservatively., Conclusion: IVL is increasingly being used in CTO PCI with encouraging outcomes., (© 2022 Wiley Periodicals LLC.)

Background: While buprenorphine/naloxone (buprenorphine) has been demonstrated to be an effective medication for treating opioid use disorder (OUD), an important question exists about how long patients should remain in treatment. Objective: To examine the relationship between treatment duration and patient outcomes for individuals with OUD who have been prescribed buprenorphine. Methods: We conducted a retrospective, longitudinal study using the Massachusetts All Payer Claims Database, 2013 to 2017. The study comprised over 2,500 patients, approximately one-third of whom were female, who had been prescribed buprenorphine for OUD. The outcomes were hospitalizations and emergency room (ER) visits at 36 months following treatment initiation and 12 months following treatment discontinuation. Patients were classified into four groups based on treatment duration and medication adherence: poor adherence, duration <12 months; good adherence, duration <6 months; good adherence, duration 6 to 12 months, and good adherence, duration >12 months. We conducted analyses at the patient level of the relationship between duration and outcomes. Results: Better outcomes were observed for patients whose duration was greater than 12 months. Patients in the other groups had higher odds of hospitalization at 36 months following treatment initiation: poor adherence (2.71), <6 months (1.53), and 6 to 12 months (1.42). They also had higher odds of ER visits: poor adherence (1.69), <6 months (1.51), and 6 to 12 months (1.30). Similar results were observed following treatment discontinuation. Conclusions: OUD treatment with buprenorphine should be continued for at least 12 months to reduce hospitalizations and ED visits.

Introduction: In response to the opioid overdose crisis, providers were urged to taper and discontinue patients from long-term opioid therapy; however, abrupt discontinuation may lead to poor health outcomes. This study aims to determine abrupt and tapered discontinuation rates and identify the patient and provider characteristics associated with abrupt discontinuation., Methods: Data were from the Massachusetts Prescription Monitoring Program, 2015-2018. Patients discontinued from long-term opioid therapy were included in the analysis. Differences between abrupt and tapered discontinuations were identified with bivariate correlations, and variables independently associated with abrupt discontinuation were identified using multivariable Poisson regression analyses. Data were analyzed during 2019-2021., Results: In total, 277,485 patients experienced 359,320 discontinuations, of which 33.7% (n=120,964) were abrupt. Of all discontinuations, 55.7% were among female patients, and 57.9% were among patients aged >55 years. The ratio of abrupt to tapered discontinuations increased from 1:2.11 in 2015 to 1:1.75 in 2018. In bivariate analysis, prescribers with more patients receiving monthly opioid prescriptions were less likely to abruptly discontinue patients (29.0, IQR=13.9, 55.3 vs 18.8, IQR=5.84, 43.9, p<0.001), as were prescribers who wrote more monthly opioid prescriptions (36.0, IQR=16.8, 70.8 vs 25.4, IQR=7.40, 58.3, p<0.001). Multivariable results indicated that abrupt discontinuation was independently associated with male sex (RR=1.31, 95% CI=1.29, 1.1.32), younger age (RR=0.872, 95% CI=0.869, 0.874), greater distance between patient and prescriber (RR=1.0075, 95% CI=1.0072, 1.0078), and longer long-term opioid therapy duration (RR=1.021, 95% CI=1.021, 1.0122 for every month increase)., Conclusions: Among all long-term opioid therapy discontinuations, abrupt discontinuation is increasing. Evidence-based approaches to managing and tapering long-term opioid therapy are urgently needed., (Copyright © 2021 American Journal of Preventive Medicine. All rights reserved.)

Background: Research has shown buprenorphine/naloxone to be an effective medication for treating individuals with opioid use disorder. At the same time, treatment discontinuation rates are reportedly high though much of the extant evidence comes from studies of the Medicaid population., Objectives: To examine the pattern and determinants of buprenorphine/naloxone treatment discontinuation in a population of commercially insured individuals., Research Design: We performed a retrospective observational analysis of Massachusetts All Payer Claims Data (MA APCD) covering years 2013 through 2017. We defined treatment discontinuation as a gap of 60 consecutive days without a prescription for buprenorphine/naloxone within a time frame of 24 months from the initiation of treatment. A mixed-effect Cox proportional hazard model examined the associated risk of discontinuing treatment with baseline predictors., Subjects: A total of 5134 individuals who were commercially insured during the study period., Measures: Buprenorphine/naloxone treatment discontinuation., Results: Overall 75% of individuals had discontinued treatment within two years of initiating treatment, and median time to discontinuation was 300 days. Patients aged between 18 and 24 years (HR = 1.436, 95%, CI = 1.240-1.663) and receiving treatment from prescribers with high panel-size (HR = 1.278, 95% CI = 1.112-1.468) had higher risk of discontinuing treatment. On the contrary, patients receiving treatment from multiple prescribers had lower associated risk of treatment discontinuation., Conclusions: A substantial percentage of patients discontinue treatment well before they can typically meet criteria for sustained remission. Further investigations should assess the clinical outcomes following premature discontinuation and identify strategies for retaining patients in treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Buprenorphine is a widely used treatment option for patients with opioid use disorder (OUD). Premature discontinuation from this treatment has many negative health and societal consequences., Objective: To develop and evaluate a machine learning based two-stage clinical decision-making framework for predicting which patients will discontinue OUD treatment within less than a year. The proposed framework performs such prediction in two stages: (i) at the time of initiating the treatment, and (ii) after two/three months following treatment initiation., Methods: For this retrospective observational analysis, we utilized Massachusetts All Payer Claims Data (MA APCD) from the year 2013 to 2015. Study sample included 5190 patients who were commercially insured, initiated buprenorphine treatment between January and December 2014, and did not have any buprenorphine prescription at least one year prior to the date of treatment initiation in 2014. Treatment discontinuation was defined as at least two consecutive months without a prescription for buprenorphine. Six machine learning models (i.e., logistic regression, decision tree, random forest, extreme-gradient boosting, support vector machine, and artificial neural network) were tested using a five-fold cross validation on the input data. The first-stage models used patients' demographic information. The second-stage models included information on medication adherence during the early phase of treatment based on the proportion of days covered (PDC) measure., Results: A substantial percentage of patients (48.7%) who started on buprenorphine discontinued the treatment within one year. The area under receiving operating characteristic curve (C-statistic) for the first stage models varied within a range of 0.55 to 0.59. The inclusion of knowledge regarding patients' adherence at the early treatment phase in terms of two-months and three-months PDC resulted in a statistically significant increase in the models' discriminative power (p-value < 0.001) based on the C-statistic. We also constructed interpretable decision classification rules using the decision tree model., Conclusion: Machine learning models can predict which patients are most at-risk of premature treatment discontinuation with reasonable discriminative power. The proposed machine learning framework can be used as a tool to help inform a clinical decision support system following further validation. This can potentially help prescribers allocate limited healthcare resources optimally among different groups of patients based on their vulnerability to treatment discontinuation and design personalized support systems for improving patients' long-term adherence to OUD treatment., (© 2021. The Author(s).)

Objectives: To determine the effect of one-click integration of a state's prescription drug monitoring program (PDMP) on the number of PDMP searches and opioid prescriptions, stratified by specialty., Methods: Our large health system worked with the state department of public health to integrate the PDMP with the electronic health record (EHR), which enabled providers to query the data with a single click inside the EHR environment. We evaluated Schedule II or III opioid prescriptions reported to the Massachusetts PDMP 6 months before (November 15, 2017-May 15, 2018) and 6 months after (May 16, 2018, to November 16, 2018) integration. Search counts, prescriptions, patients, morphine milligram equivalents, as well as prescriber specialty were compared., Results: There were 3,185 unique prescribers with a record of a Schedule II and/or III opioid prescription in both study periods that met inclusion criteria. After integration, the number of PDMP searches increased from 208,684 in the pre-integration phase to 298,478 searches in the post-integration phase (+43.0%). The number of opioid prescriptions dispensed decreased by 4.8%, the number of patients receiving a prescription decreased by 5.1%, and the mean morphine milligram equivalents (MMEs) per prescriber decreased by 5.4%. There were some notable specialty-specific differences in these measures., Conclusions: Integration of the PDMP into the EHR markedly increased the number of searches but was associated with modest decreases in opioids prescribed and patients receiving a prescription. Single click EHR integration of the PDMP, if implemented broadly, may be a way for states to significantly increase PDMP utilization., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives. To develop an imputation method to produce estimates for suppressed values within a shared government administrative data set to facilitate accurate data sharing and statistical and spatial analyses. Methods. We developed an imputation approach that incorporated known features of suppressed Massachusetts surveillance data from 2011 to 2017 to predict missing values more precisely. Our methods for 35 de-identified opioid prescription data sets combined modified previous or next substitution followed by mean imputation and a count adjustment to estimate suppressed values before sharing. We modeled 4 methods and compared the results to baseline mean imputation. Results. We assessed performance by comparing root mean squared error (RMSE), mean absolute error (MAE), and proportional variance between imputed and suppressed values. Our method outperformed mean imputation; we retained 46% of the suppressed value's proportional variance with better precision (22% lower RMSE and 26% lower MAE) than simple mean imputation. Conclusions. Our easy-to-implement imputation technique largely overcomes the adverse effects of low count value suppression with superior results to simple mean imputation. This novel method is generalizable to researchers sharing protected public health surveillance data. ( Am J Public Health . 2021; 111(10):1830-1838. https://doi.org/10.2105/AJPH.2021.306432).

Background : In 2016, Massachusetts passed the first-in-the-nation law limiting opioid naïve adults and all minors to a 7-day supply of opioids when prescribed in the outpatient setting. Objective : We hypothesized this policy would be associated with declines in the percent of opioid prescriptions with more than a 7-day supply among opioid naïve adults and minors for select prescriber groups. Methods : Interrupted time series analyses were conducted using measures from the Massachusetts Prescription Monitoring Program database for 2015 through 2017 (n = 13,672,325 opioid prescriptions; 54% to females). Outcomes were the monthly percent of opioid prescriptions greater than 7 days' supply in opioid naïve adults and in minors among select prescriber groups. Model estimates of the pre-policy trend, the average changes in the level pre/post-implementation, and the trend changes post-implementation were assessed. Results : Pre-policy trends showed significant monthly declines in the percent of opioid prescriptions greater than 7 days' supply for all prescriber groups. Policy implementation was associated with significant reduction in the level for opioid naïve adults among surgeons (-2.92%, p < .01), dentists (-0.23%, p < .01), and general medical providers (-2.22%, p = .04), and for minors among all-included prescribers (-2.97%, p < .01) and surgeons (-3.8%, p < .01). Post-implementation changes in trends were not significant except among opioid naïve adults for dentists (0.02%, p = .04). Conclusion : Within a context of significant reductions occurring in opioid prescriptions greater than 7 days' supply during this period, the Massachusetts policy was associated with further declines for opioid naïve adults and minors among select prescriber groups.

Mortality in patients with STEMI-associated cardiogenic shock (CS) is increasing. Whether a comprehensive ST-elevation myocardial infarction (STEMI) protocol (CSP) can improve their care delivery and mortality is unknown. We evaluated the impact of a CSP on incidence and outcomes in patients with STEMI-associated CS. We implemented a 4-step CSP including: (1) Emergency Department catheterization lab activation; (2) STEMI Safe Handoff Checklist; (3) immediate catheterization lab transfer; (4) and radial-first percutaneous coronary intervention (PCI). We studied 1,272 consecutive STEMI patients who underwent PCI and assessed for CS incidence per National Cardiovascular Data Registry definitions within 24-hours of PCI, care delivery, and mortality before (January 1, 2011, to July 14, 2014; n = 723) and after (July 15, 2014, to December 31, 2016; n = 549) CSP implementation. Following CSP implementation, CS incidence was reduced (13.0% vs 7.8%, p = 0.003). Of 137 CS patients, 43 (31.4%) were in the CSP group. CSP patients had greater IABP-Shock II risk scores (1.9 ± 1.8 vs 2.8 ± 2.2, p = 0.014) with otherwise similar hemodynamic and baseline characteristics, cardiac arrest incidence, and mechanical circulatory support use. Administration of guideline-directed medical therapy was similar (89.4% vs 97.7%, p = 0.172) with significant improvements in trans-radial PCI (9.6% vs 44.2%, p < 0.001) and door-to-balloon time (129.0 [89:160] vs 95.0 [81:116] minutes, p = 0.001) in the CSP group, translating to improvements in infarct size (CK-MB 220.9 ± 156.0 vs 151.5 ± 98.5 ng/ml, p = 0.005), ejection fraction (40.8 ± 14.5% vs 46.7 ± 14.6%, p = 0.037), and in-hospital mortality (30.9% vs 14.0%, p = 0.037). In conclusion, CSP implementation was associated with improvements in CS incidence, infarct size, ejection fraction, and in-hospital mortality in patients with STEMI-associated CS. This strategy offers a potential solution to bridging the historically elusive gap in their care., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The brand name Suboxone and its generic formulation buprenorphine/naloxone is a medication for treating opioid use disorder. While this medication has been shown to be effective, little research has examined the extent to which it is being prescribed and under what circumstances. Objective: This study examined patterns of prescription claims for buprenorphine/naloxone in terms of volume and associated clinical conditions. Methods: The study was conducted using a statewide database comprising pharmacy and medical claims that were covered by commercial health insurance plans in Massachusetts between 2011 and 2015. Trends in prescription volume for buprenorphine/naloxone were assessed based on the annual number of patients with a prescription for buprenorphine/naloxone. To examine clinical conditions associated with buprenorphine/naloxone prescriptions, patients' pharmacy claims were linked to their medical claims within the prior three months. For patients with common pain-related conditions, the odds they were prescribed buprenorphine/naloxone rather than oxycodone, a widely used opioid for pain management, were also examined. Results: The number of patients with a buprenorphine/naloxone prescription increased substantially during the study period, from approximately 25,000 in 2011 to over 39,000 in 2015. The most common clinical condition associated with buprenorphine/naloxone prescribing was opioid use disorder, but a substantial percentage of prescriptions were preceded by diagnoses that included pain or were for pain alone. Conclusion: A substantial increase in the number of patients with a prescription for buprenorphine/naloxone was observed. While buprenorphine/naloxone is most frequently prescribed for opioid use disorder, clinicians also appear to prescribe it for pain, particularly for patients who may be at elevated risk for opioid use disorder.

Objective: State prescription drug monitoring programs (PDMPs) can help detect individuals with multiple provider episodes (MPEs; also referred to as doctor/pharmacy shopping), an indicator of prescription drug abuse and/or diversion. Although unsolicited reporting by PDMPs to prescribers of opioid analgesics is thought to be an important practice in reducing MPEs and the potential harm associated with them, evidence of its effectiveness is mixed. This exploratory research evaluates the impact of unsolicited reports sent by Massachusetts' PDMP to the prescribers of persons with MPEs., Methods: Individuals with MPEs were identified from PDMP records between January 2010 and July 2011 as individuals having Schedule II prescriptions (at least one prescription being an opioid) from four or more distinct prescribers and four or more distinct pharmacies within six months. Based on available MA-PDMP resources, an unsolicited report containing the patient's 12-month prescription history was sent to prescribers of a subset of patients who met the MPE threshold; a comparison group closely matched on demographics and baseline prescription history, whose prescribers were not sent a report, was generated using propensity score matching. The prescription history of each group was examined for 12 months before and after the intervention., Results: There were eighty-four patients (intervention group) whose prescribers received an unsolicited report and 504 matched patients (comparison group) whose prescribers were not sent a report. Regression analyses indicated significantly greater decreases in the number of Schedule II opioid prescriptions (P < 0.01), number of prescribers visited (P < 0.01), number of pharmacies used (P < 0.01), dosage units (P < 0.01), total days' supply (P < 0.01), total morphine milligram equivalents (MME; P < 0.01), and average daily MME (P < 0.05) for the intervention group relative to the comparison group. A post hoc analysis suggested that the observed intervention effects were greater for individuals with an average daily dose of less than 100 MMEs., Conclusions: This study suggests that PDMP unsolicited reporting to prescribers can help reduce risk measures in patients' prescription histories, which may improve health outcomes for patients receiving opioid analgesics from multiple providers.

As modern society ages rapidly, the number of people with dementia is sharply increasing. Direct medical costs and indirect social costs for dementia patients are also increasing exponentially. However, the lack of social awareness about dementia results in difficulties to dementia patients and their families. So, understanding dementia is the first step to remove or reduce the stigma of dementia patients and promote the health of our community. Alzheimer's disease is the most common form of dementia. The term, 'Alzheimer's disease' has been used for over 100 years since first used in 1910. With the remarkable growth of science and medical technologies, the techniques for diagnosis and treatment of dementia have also improved. Although the effects of the current symptomatic therapy are still limited, dramatic improvement is expected in the future through the continued research on disease modifying strategies at the earlier stage of disease. It is important to look at the past to understand the present and obtain an insight into the future. In this article, we review the etymology and history of dementia and previous modes of recognizing dementia. We also review the historical developments leading to the terminology of Alzheimer's disease., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development., (Copyright © 2014 Roy et al.)

Purpose: While intralesional injections improve penile curvature and decrease plaque volume, the exact mechanism of action on Peyronie disease is unknown. We evaluated penile curvature, immunohistology and erectile function outcomes after intralesional injections of verapamil and normal saline in a previously described Peyronie disease animal model., Materials and Methods: Peyronie plaque was induced in 12 adult male rats using an established Peyronie disease animal model. At 4 weeks the rats were divided into group 1-5 with 0.1 mg/0.1 ml intralesional verapamil injected every second day for 2 weeks, group 2-5 with 0.1 ml intralesional normal saline injection and group 3-2 that served as controls. At weeks 6 and 8 penile pressure was measured and serial immunohistochemical staining of penile tissue sections was done., Results: Intralesional injection of verapamil and normal saline resulted in macroscopic and microscopic changes to penile curvature and Peyronie plaque size. Decreased collagen and elastin fibers were measured with a significant reduction in smooth muscle α-actin (p <0.05). Changes were greater in group 1 than group 2 (p <0.05). Intralesional verapamil injection was associated with greater recovery of electrostimulated penile pressure, a surrogate of erectile function, than in the saline and control groups., Conclusions: To our knowledge this novel study offers for the first time histological evidence of cellular changes and improvement in penile pressure studies in rats with Peyronie plaque after intralesional verapamil injection therapy in a Peyronie disease animal model., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

More plants can be screened for reniform nematode resistance each year if the time involved can be shortened. In this study, the hypothesis that female counts are as efficient as egg counts in identifying resistant genotypes was tested. In two greenhouse experiments Gossypium genotypes which varied from resistant to susceptible to reniform nematode (Rotylenchulus reniformis) were compared to a susceptible control cultivar. Infested field soil served as the inoculum source for the first experiment, and vermiform stages extracted from greenhouse cultures were used to infest soil in the second experiment. Six replicates of each genotype were harvested 25 d after planting and swollen females were counted. The remaining plants were harvested 35 d after planting and eggs extracted from the roots were counted. Processing and counting times recorded in the first experiment were similar for both assessment methods, but 10 additional days were required for egg-based assessment. Contrast analyses showed that assessments based on females per gram of root were equivalent to assessments based on eggs per gram of root for the five genotypes tested in the first experiment and for an expanded set of 13 genotypes tested in the second experiment. The results indicated that either life stage can be used to screen for resistance.

Nine sources of resistance to Rotylenchulus reniformis in Gossypium (cotton) were tested by measuring population density (Pf) and root-length density 0 to 122 cm deep. A Pf in the plow layer less than the autumn sample treatment threshold used by consultants was considered the minimum criterion for acceptable resistance, regardless of population density at planting (Pi). Other criteria were ample roots and a Pf lower than on the susceptible control, as in pot studies. In a Texas field in 2001 and 2002, no resistant accessions had Pf less than the control but all did in microplots into which nematodes from Louisiana were introduced. An environmental chamber experiment ruled out nematode genetic variance and implicated unknown soil factors. Pf in field experiments in Louisiana, Mississippi, and Alabama were below threshold for zero, six and four of the accessions and above threshold in the control. Gossypium arboreum A2-87 and G. barbadense GB-713 were the most resistant accessions. Results indicate that cultivars developed from these sources will suppress R. reniformis populations but less than in pots in a single season.

The possible impact of Rotylenchulus reniformis below plow depth was evaluated by measuring the vertical distribution of R. reniformis and soil texture in 20 symptomatic fields on 17 farms across six states. The mean nematode population density per field, 0 to 122 cm deep, ranged from 0.4 to 63 nematodes/g soil, and in 15 fields more than half of the R. reniformis present were below 30.5 cm, which is the greatest depth usually plowed by farmers or sampled by consultants. In 11 fields measured, root density was greatest in the top 15 cm of soil; however, roots consistently penetrated 92 to 122 cm deep by midseason, and in five fields in Texas and Louisiana the ratio of nematodes to root-length density within soil increased with depth. Repeated sampling during the year in Texas indicated that up to 20% of the nematodes in soil below 60 cm in the fall survived the winter. Differences between Baermann funnel and sugar flotation extraction methods were not important when compared with field-to-field differences in nematode populations and field-specific vertical distribution patterns. The results support the interpretation that R. reniformis below plow depth can significantly impact diagnosis and treatment of cotton fields infested with R. reniformis.

Tests have determined that boots or shoes of individuals at a fire scene do not transport sufficient contaminants ("tracking") through the fire scene to produce a positive laboratory result for the presence of gasoline in a fire scene that was not present at the time of the fire. Questions about the validity of forensic laboratory results have been raised on the basis that low-level gasoline residues detected in the laboratory samples could have been the result of transporting the residue by footwear contaminated from the fire scene ("tracking"). The data collected in this study establish that "tracking" does not lead to false-positive laboratory results. Canines trained and experienced in the detection of trace ignitable liquid residues were also utilized in this study. The canine results confirmed that properly trained canines show a higher sensitivity than do standard ASTM laboratory techniques for fire debris analysis. In a few cases, canines responded to contamination, but laboratory testing (which is the definitive indicator) did not produce positive results.

The host suitability of diverse races and gene pools of common bean (Phaseolus vulgaris) for multiple isolates of Heterodera glycines was studied. Twenty P. vulgaris genotypes, representing three of the six races within the two major germplasm pools, were tested in greenhouse experiments to determine their host suitability to five H. glycines isolates. Phaseolus vulgaris genotypes differed in their host suitability to different H. glycines isolates. While some common bean lines were excellent hosts for some H. glycines isolates, no common bean line was a good host for all isolates. Some bean lines from races Durango and Mesoamerica, representing the Middle America gene pool, were resistant to all five nematode isolates. Other lines, from both the Andean and Middle America gene pools, had differential responses for host suitability to the different isolates of H. glycines.

The primary objective was to estimate breed, heterosis, and recombination effects on growth and carcass traits of two different four-breed composite populations of pigs. Experiment 1 (Exp. 1) included purebred and crossbred pigs originating from Yorkshire, Landrace, Large White, and Chester White breeds, and Experiment 2 (Exp. 2) included pigs from Duroc, Hampshire, Pietrain, and Spot breeds. Data were recorded on purebred pigs, two-breed cross pigs, and pigs from generations F1 through F6, where F1 pigs were the first generation of a four-breed cross. Pig weights were recorded at birth and at 14, 28, 56, 70, and 154 d of age. Average daily gain was calculated for intervals between weights, and ultrasonic backfat measurements (A-mode) were taken at 154 d of age. Feed intake was measured between 70 and 154 d of age on mixed pens of boars and barrows. Carcass backfat, length, and loin muscle area were measured on barrows at slaughter. Mixed-model analyses were done separately by experiment, fitting an animal model. Fixed effects included farrowing group and sex for growth traits and farrowing group for carcass traits. For ADFI, a weighted mixed-model analysis was done fitting farrowing group as a fixed effect, sire nested within farrowing group as a random effect, and weighting each observation by the number of pigs in each pen. To test feed efficiency, a second analysis of ADFI was done adding ADG as a covariate in the previous model. Included as covariates in all models were direct, maternal, and maternal grandam breed effects, direct and maternal heterosis effects, and a direct recombination effect. Recombination is the breakup of additive x additive epistatic effects present in purebreds during gamete formation by crossbred parents. Effects of direct heterosis significantly increased weights at birth, 14, 56, 70, and 154 d of age in Exp. 1. Effects of direct heterosis significantly increased ADG from birth to 14, 28 to 56, and 70 to 154 d of age in Exp. 1. In Exp. 2, effect of direct heterosis significantly increased weights and ADG at all ages. In Exp. 1, recombination significantly reduced loin muscle area. In Exp. 2, recombination significantly increased weights at birth, 14, 28, and 56 d, ADFI from 70 to 154 d, and ADFI adjusted for ADG. The correlation between maternal heterosis and recombination effects for all traits in Exp. 1 and Exp. 2 was approximately -0.90. Maternal heterosis and recombination effects were estimable, but greatly confounded.

The objective was to estimate breed, heterosis, and recombination effects on pig reproductive traits in two different four-breed composite populations. Breeds included Yorkshire, Landrace, Large White, and Chester White in Exp. 1 and Duroc, Hampshire, Pietrain, and Spot in Exp. 2. Data were recorded on purebred pigs, two-breed cross pigs, and pigs from generations F1 through F6, where F1 pigs were the first generation of a four-breed cross. Litter traits were considered a trait of the gilt. There were 868 first parity litters in Exp. 1 and 865 in Exp. 2. Direct heterosis significantly increased sow weight at 110 d of gestation and litter weight at 14 and 28 d (weaning) in both experiments. Direct heterosis significantly increased number of nipples, weight at puberty, lactation weight loss, litter size, and litter birth weight in Exp. 2. Gestation length in Exp. 1 and age at puberty in Exp. 1 and Exp. 2 were significantly decreased by direct heterosis. Maternal heterosis significantly increased age at puberty in Exp. 2 and decreased sow weight at 110 d of gestation in Exp. 1. Recombination significantly increased sow weight at 110 d of gestation and tended to increase total number born and litter birth weight in Exp. 1. Recombination significantly decreased age at puberty in Exp. 2. Litter heterosis significantly increased number of pigs at 14 and 28 d; litter weights at birth, 14, and 28 d; and tended to increase lactation weight loss in Exp. 1. Litter heterosis decreased litter size in Exp. 2. Maternal heterosis and recombination effects had a sampling correlation of -0.97 in Exp. 1 and -0.91 in Exp. 2 for number of fully formed pigs. Therefore, maternal heterosis and recombination effects were summed, and their net effect was tested. This net effect tended to increase number of nipples, lactation weight loss, and litter birth weight and significantly increased number of fully formed pigs in Exp. 1. Direct, maternal, and litter heterosis and recombination effects significantly influenced reproductive traits.

Little information is available regarding the safety and efficacy of lipid lowering therapy in the elderly. Records of 80 octogenarians, taken from the database of the LifeHelp Lipid Clinic of the Heart Institute of St. Petersburg, FL, were examined, representing 1863 patient months of treatment. Therapy was effective, lowering low density lipoprotein cholesterol (from 140Â+/-4 to 92Â+/-3 mg/dL), raising high density lipoprotein cholesterol (from 44Â+/-1 to 50Â+/-1 mg/dL), and lowering triglycerides (from 199Â+/-21 to 146Â+/-9 mg/dL). Six patients developed myalgias (without significant creatine phosphokinase rise) or gastrointestinal disturbances. Three of these patients restarted therapy without difficulty. No patient developed rhabdomyolysis (including the 11% of patients on combination therapy). One patient developed an elevation of liver (more than 3 times upper limits of normal), but later restarted therapy without sequelae. We conclude that lipid lowering therapy was effective at modifying hyperlipidemia in the elderly without significant adverse effects. (c) 2000 by CVRR, Inc.

Effects of Dorset, Finnsheep, Romanov, Texel, and Montadale breeds for performance as sires were estimated in the initial phase of a comprehensive evaluation of these breeds as contributors to sheep crossbreeding systems. Objectives were to evaluate the effects of ram breed, ewe breed, season of mating, and two-way interactions. Rams from the five breeds were single-sire-mated with ewes from two breed types to produce lambs over a 3-yr period. Ewes were assigned to one of three distinct 35-d mating seasons initiated each year in August, October, and December. A different sample of six rams per breed was used each year across all three seasons, and each ram was penned with ewes of both breeds. Traits evaluated and number of ewe records were conception rate and litter weaning weight per ewe exposed (n = 3,261) and number born, litter birth weight, average birth weight, number weaned, and litter weaning weight per ewe lambing (n = 2,751). Ram breed and ewe breed interacted (P < .01) for conception rate and litter weaning weight per ewe exposed, implicating mating preferences, particularly of Romanov rams. In mixed groups of ewes exposed to Romanov rams, conception rate was 12.7% lower and litter weight weaned was 8.4 kg lower in the ewe breed presumably less preferred for mating by the rams. On a per ewe exposed basis, Romanov-sired litters produced either the largest or the smallest values for litter weaning weight, depending on the breed of ewe. Effects of ram breed on number born and litter birth weight interacted (P < .05) with season of mating. The largest litters within each ram breed were associated with the October mating season. Montadale and Romanov rams sired larger and heavier litters from August matings than from December matings, whereas the opposite was true for Dorset-sired litters. Texel- and Finnsheep-sired litters were similar in size and weight from August and December matings. Breed of ram differences affected per ewe lambing productivity measurements (P < .01). Differences between ram breeds for ewe productivity were noted, with increased number born and improved survival of crossbred progeny to weaning for Romanov-sired litters. These results may have implications for using these ram breeds as sires in different crossbreeding systems. Structured mating systems or the creation of new composite populations involving these breeds could be used to match the resources, environment, and market of specific production situations.

The mechanisms by which superantigens, such as staphylococcal enterotoxin B (SEB), contribute to microbial pathogenicity have been poorly defined. The study of such pathogenic processes has been hampered by the lack of an adequate animal model. We utilized a previously described murine chimeric model to determine the cytokines and cell populations that might be involved in SEB toxicity. In the absence of bone marrow transplantation (BMT), all total body irradiated (TBI) mice died, while all transplanted mice survived up to 6 months. Compared with non-TBI and non-BMT mice, chimeric mice had an increased percentage of CD11b (Mac-1)-positive splenocytes (17 vs. 59%, P < 0.05) and decreased CD45R-positive (B) cells (33 vs. 6%, P < 0.05) at 6 weeks after BMT. The relative numbers of splenocyte CD4 and CD8 cells were similar in chimeric and normal mice. Susceptibility of chimeric animals to 10 or 100 microg SEB was time-dependent: no mice challenged at 2 weeks post-BMT died, but 15% of mice challenged at 4 weeks and 50% of those challenged at 6-8 weeks died. Compared with TBI and non-BMT C3H/HeJ mice, SEB-challenged chimeric mice at 6-8 weeks had (1) increased splenocyte mRNA expression for: IFN-gamma (3.5 x optimally at 1 h), TNF-alpha (6.5 x at 2 h), IL-6 (4.8 x at 4 h), IL-1beta (8.4 x at 4 h), IL-2 (4.7 x at 4 h), and IL-10 (3 x at 16 h), and (2) increased and earlier peak serum levels of IFN-gamma, IL-6, IL-1beta and IL-2, but no increase in serum TNF-alpha or IL-4. These data support the hypothesis that the decreased percentage of B cells and increased macrophages in chimeric mice lead to enhanced T cell-macrophage interactions after SEB administration and a lethal burst of T cell and macrophage cytokine release. This model will provide insight into cell populations and mechanisms that mediate superantigen-induced toxicity.

Heterodera glycines is an economically important pest of soybean in the United States. The steps necessary to manage this nematode are to sample for inoculum density, identify the race present, and then select appropriate control measures. Planting resistant cultivars is the most widely used management practice, and this tactic has provided enormous economic benefits. However, the nematode has adapted to each source of resistance deployed. The time required for the nematode to adapt to resistant cultivars is lengthened by including nonhost crops and susceptible cultivars in rotations with resistant cultivars. Searching for new sources of resistance and developing more techniques to prolong the effectiveness of resistance genes are necessary to maintain profitability for soybean producers.

The therapeutic potential of recombinant human interleukin-11 (rhIL-11) was tested in a neutropenic rat model that mimics the clinical consequences of myelosuppressive chemotherapy complicated by Pseudomonas aeruginosa sepsis. rhIL-11-treated animals (150 micrograms/kg intravenously every 24 h for 3 days) had reduced endotoxin levels (P < .05) and less pulmonary edema fluid (P < .001) and were protected (P < .01) against thinning and necrosis of the intestinal mucosa compared with the control group. The survival rate in rhIL-11-treated animals was 40% (19/47), whereas it was 0 (0 of 19) in the control group (P < .01). The addition of ciprofloxacin (10 mg/kg every 12 h) resulted in a survival rate of 9 (60%) of 15, while the combination of rhIL-11 and ciprofloxacin resulted in 100% survival (15/15; P < .05). These results indicate that rhIL-11 supports mucous membrane integrity of the alimentary tract and decreases the systemic inflammatory response to experimental gram-negative infection in immunocompromised animals.

Several soybean (Glycine max) cropping sequences were planted for 12 years in a field that, at the beginning of the test, was infested with race 14 of the soybean cyst nematode, Heterodera glycines. Continuous soybean cropping sequences included H. glycines-susceptible cultivars Forrest, J82-21, Peking × Centennial breeding line, and moderately resistant cultivars Bedford and J81-116. Forrest treated with aldicarb or pentachloronitrobenzene (PCNB) plus metalaxyl and resistant breeding line JS83-236 followed by resistant cultivars Cordell and Hartwig were additional continuous soybean sequences. Rotations included two sequences each of Bedford with J81-116 or J82-21, and three sequences of Bedford with corn (Zea mays) and susceptible Essex soybean. Rotations of Bedford, corn, and Essex had 12-year mean yields significantly greater than continuous Bedford or Forrest. The female index (FI) of H. glycines on five cultivars and lines was used to bioassay changes in parasitic potential in each cropping sequence. The FI on Bedford bioassay plants increased significantly over time for all field treatments involving Bedford. When J82-21 was the bioassay plant, FI decreased significantly in treatments involving Bedford. There were no significant changes in FI for any treatment when Forrest, J81-16, and Peking were used as bioassays. Rotations of soybean cultivars with different sources of resistance and rotations of resistant and susceptible cultivars with a nonhost crop were not successful practices to manage the nematode's ability to parasitize the resistant cultivar Bedford. However, rotation of resistant and susceptible cultivars with a nonhost crop produced greater mean soybean yields and slowed the shift toward greater parasitism of the resistant cultivar sufficiently to warrant adoption of this practice.

Females were either 1/4 Duroc, 1/4 Meishan, 1/4 Fengjing, or 1/4 Minzhu, and the remainder were 3/4 White Composite. A greater percentage of Fengjing crosses reached puberty than Duroc or Minzhu (P < .05), and Meishan crosses were intermediate and not different (P > .05) from other breed types. After adjusting for differences in percentage detected owing to termination of observation for estrus, breed types ranked Fengjing, Meishan, Minzhu, and Duroc from youngest to oldest at puberty with approximately 14 d between adjacent breed types. Meishan and Fengjing crosses had a greater (P < .05) ovulation rate than Minzhu or Duroc crosses. With the exception of number of fetuses at 100 d and average fetal weight at 60 d, differences among breed types were not detected (P > .05) for litter or uterine traits measured on gilts slaughtered at 60 or 100 d of gestation. Total number of pigs born was greater (P < .05) for 1/4 Fengjing than for 1/4 Duroc gilts. Gestation length, number born alive, number weaned, litter birth weight, or litter weaning weight for gilts did not differ (P > .05) among breed types. Duroc crosses were heavier (P < .01) than Chinese crosses at d 1 and 28 after farrowing, but breed types did not differ (P > .05) for backfat thickness at those times. Breed types did not differ (P > .05) for the ratio of litter gain from 0 to 28 d/total Mcal or any of the component traits in the ratio. Postweaning estrus activity, conception rate, and litter and uterine traits of sows bred for second parity were not affected (P > .05) by breed type. These analyses indicate that crossbred gilts containing 1/4 Meishan, 1/4 Fengjing, or 1/4 Minzhu will reach puberty earlier, have larger litters, and weigh less at first parity than gilts containing 1/4 Duroc, but they do not have any significant advantage in litter size at second parity.

Pigs were the progeny of White Composite boars mated to gilts that were either 1/4 Duroc, 1/4 Meishan, 1/4 Fengjing, or 1/4 Minzhu and the remainder 3/4 White Composite. One-eighth Meishan and 1/8 Fengjing pigs averaged approximately .5 more nipples than 1/8 Duroc pigs and .2 more nipples than 1/8 Minzhu pigs (P < .05), respectively. Duroc, Meishan, and Minzhu crosses did not differ (P > .05) for survival at birth or at 14 and 28 d. Fengjing crosses had a lower survival rate (P < .05) at all three ages than Duroc and Meishan crosses. Duroc crosses were heavier (P < .05) than Chinese crosses at birth. At 56 d, Duroc and Meishan crosses did not differ (P > .05) for BW, but both were heavier (P < .05) than Minzhu crosses. Body weight at 70 d did not differ significantly (P > .05) among breed types. Duroc crosses were heavier (P < .05) than any of the Chinese crosses at 98, 126, and 154 d of age. At 154 d, Fengjing crosses were lighter (P < .05) than Meishan or Minzhu crosses. The effect of breed type was not detected for average probe backfat thickness of gilts at 99.7 kg. Duroc crosses consumed the most feed, and Fengjing crosses consumed the least during each interval and during the total period (P < .05). Feed consumption of Meishan and Minzhu crosses was intermediate to and significantly (P < .05) different from that of Duroc and Fengjing crosses. At 184 d of age, breed types did not differ (P > .16) for measures of carcass fat thickness, marbling score, color score, and firmness score. At 184 d of age, weights of all carcass cuts were heavier (P < .05) for Duroc than for Chinese crosses with the exception of untrimmed loin weight of Minzhu crosses. There were few significant differences among breed types when carcass traits were compared at a constant carcass weight, although Duroc crosses generally were superior. Relative to similar Duroc crosses, these results suggest that 1/8 Chinese pigs would grow less rapidly (P < .05) and produce less weight of trimmed lean cuts at a constant carcass weight.

Polymyxin B (PMB) is a cyclic decapeptide antibiotic which also binds and neutralizes endotoxin. Unfortunately, PMB can be considerably nephrotoxic at clinically utilized doses, thereby limiting its utility as a therapeutic antiendotoxin reagent. We sought to change the pharmacokinetics and toxicity profile of PMB by covalently linking it to a human immunoglobulin G (IgG) carrier. Conjugates of PMB with IgG were prepared by EDAC [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide]-mediated amide formation. Analysis by dot enzyme-linked immunosorbent assay with an anti-PMB monoclonal antibody showed that the purified conjugate contained bound PMB. The IgG-PMB conjugate reacted with lipid A and J5 lipopolysaccharide in Western blot assays in a manner comparable to that of whole antiserum with anti-lipid A reactivity; unconjugated IgG had no reactivity. The PMB bound in the conjugate retained its endotoxin-neutralizing activity compared to that of unbound PMB as evidenced by its dose-dependent inhibition of tumor necrosis factor release by endotoxin-stimulated human monocytes in vitro; unconjugated IgG had no activity. By this assay, the PMB-IgG conjugate was determined to have approximately 3.0 microg of bound functional PMB per 100 microg of total protein of conjugate (five molecules of PMB per IgG molecule). The PMB-IgG conjugate was also bactericidal against clinical strains of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae relative to unconjugated IgG with MBCs of <4 microg of conjugate per ml for each of the tested strains. The conjugate appeared to be nontoxic at the highest doses deliverable and provided statistically significant protection from death to galactosamine-sensitized, lipopolysaccharide-challenged mice in a dose-dependent fashion when administered prophylactically 2 h before challenge. However, neither free PMB nor the PMB-IgG conjugate could protect mice challenged with endotoxin 2 h after administration. This suggests that these reagents can play a role in prophylaxis but not in therapy of sepsis. These experiments demonstrated that the PMB-IgG conjugate retains bound yet functional PMB as evidenced by its endotoxin-neutralizing activity both in vitro and in vivo. Further work is required to define the role that this or related conjugate compounds may play in the prophylaxis of endotoxin-mediated disease.

Repeated records on fertility, litter size, and ovulation rate of Rambouillet ewes and on fertility and litter size of Finnsheep ewes were used to estimate heritabilities and repeatabilities with linear and nonlinear sire and animal models. Linear sire (LSM) and animal models were used with all traits. Nonlinear models were the threshold, Poisson, and negative binomial. Threshold sire (TSM) and animal models were used with all traits. Litter size and ovulation rate were analyzed also with Poisson sire and animal models and with negative binomial sire and animal models. Variance components for linear models were estimated using REML; in the threshold, Poisson, and negative binomial, they were estimated using approximate marginal maximum likelihood. Poisson and negative binomial analyses yielded results difficult to interpret due to problems in variance component estimation. Animal models resulted in slightly greater estimates of heritability for fertility than did sire models, but ovulation rate heritability estimates from sire models were much greater than estimates form animal models. Differences between sire and animal models for heritability estimates for litter size were not consistent. Threshold models resulted in higher heritability estimates for all traits in both breeds and with both sire and animal models. In general, repeatabilities were consistent across models. For example, LSM (TSM) repeatabilities were .10 (.14) for fertility, .20 (.25) for litter size, and .25 (.29) for ovulation rate in the Rambouillet, and .17 (.17) for fertility and .11 (.13 for litter size in the Finnsheep.

The performance of linear and nonlinear sire and animal models in the analyses of reproductive traits (fertility, litter size, and ovulation rate) in two sheep populations (Rambouillet and Finnsheep) was compared in terms of goodness of fit and predictive ability. Linear sire (LSM) and animal (LAM) models were used with all traits. Nonlinear models were the threshold, Poisson, and negative binomial. Threshold sire (TSM) and animal (TAM) models were also used with all traits. Litter size and ovulation rate were analyzed also with Poisson and negative binomial sire (PSM and NBSM, respectively) and animal (PAM and NBAM, respectively) models. Variance components were those reported in the companion article. For PAM a new set of variance components derived from estimates found with the linear animal model also was used (PAM-L). Mean squares error (MSE) and correlations between fitted and observed values were used to assess goodness of fit. Predictive ability was assessed by partitioning the data sets for the different traits into two subsets with the restriction that all levels of fixed effects were represented in each subset. Parameters from one subset were employed to predict observations in the other, and then MSE and correlations between observed and predicted values were used as criteria for model comparison. Within estimation procedure, breed, and trait, goodness of fit of sire and animal models was similar. Linear and threshold models resulted in similar fit, and both outperformed Poisson and negative binomial models. In terms of predictive ability, linear and threshold models performed only slightly better than Poisson and negative binomial models. Goodness of fit and predictive ability generally were better when models included permanent environmental effects.

Yields of four soybean cultivars were measured for 4 years in a field infested with Heterodera glycines race 3 and in a field infested with H. glycines race 14. Cultivars included Hutcheson (susceptible to both races), Deltapine 415 (resistant to race 3 and susceptible to race 14), Asgrow 5979 (resistant to both races), and Harwig (resistant to both races as well as most other known races of H. glycines). Although no above-ground symptoms of nematode infection were visible, mean yield was 16-32% greater for Asgrow 5979 than for Hutcheson. Yield for Dehpiue 415 was similar to that of Asgrow 5979 in the field infested with race 3 and similar to that of Hutcheson in the race 14-infested field. Hartwig produced lower yields than Asgrow 5979 in both fields. Yield differences, particularly between Asgrow 5979 and Hutcheson, were attributed primarily to nematodes because both cultivars have been shown to produce similar yields in the absence of H. glycines. This study illustrates the importance of knowing which race of the nematode is prevalent in a field and demonstrates that the nematode can cause significant yield loss in the absence of visible symptoms of infection.

Female indices were measured on six soybean cultivars with resistance to Heterodera glycines derived from PI 88788. Cultivars were inoculated with four isolates of race 6, 3 of race 9, 2 of race 4, and one of race 14. Changes in female index from slightly < or > 10% of the test cultivars compared to 'Lee' resulted in a change of most of the race designations after at least three generations on 'Essex.' Variation due to race was the greatest source of variation in the analysis of the data and was three to nine times the second largest source of variation. In most cases, female indices for the cultivars within a race were not different (P = 0.05). This study suggests that one cultivar can serve as a type cultivar for a common source ofH. glycines resistance. Value of race designations was demonstrated.

Using an actual infection model of Pseudomonas aeruginosa sepsis in neutropenic rats, the potential utility of a combination anticytokine approach for the treatment of sepsis was tested. A dimeric tumor necrosis factor binding protein (TNF-BP) consisting of two soluble recombinant human TNF type 1 receptors linked with polyethylene glycol was used with recombinant human interleukin-1 receptor antagonist (IL-1ra). Despite having levels of bacteremia and endotoxemia similar to the control group (survivors, 0/18), 30% of IL-1ra-treated animals survived (P < .05); 31% of TNF-BP-treated animals survived (P < .01). Unexpectedly, the combination of IL-1ra plus TNF-BP proved to be uniformly fatal (survivors, 0/20). Endotoxin (P < .0001) and bacteremia (P < .01) levels were >10-fold higher than levels in animals treated with IL-1ra alone, TNF-BP alone, or placebo. Disseminated microabscesses in major organs were found in animals treated with combination immunotherapy. Combination anticytokine therapy may exacerbate systemic infection and worsen outcome in experimental sepsis.

Pigs were the progeny of White Composite (WC) boars mated to F1 Duroc x WC, Meishan x WC, Fengjing x WC, and Minzhu x WC gilts. Meishan and Fengjing crosses had more (P < .05) nipples than Duroc and Minzhu crosses. Meishan and Minzhu crosses had a higher survival rate at birth (P < .05) than Duroc and Fengjing crosses, but breed types did not differ significantly (P approximately .29) for survival to 14 or 28 d of age. Duroc crosses were heavier (P < .05) than Fengjing and Minzhu crosses at 0, 28, 56, 70, 98, 126, and 154 d of age; they were heavier (P < .05) than Meishan crosses at 0, 28, 98, 126, and 154 d of age. Chinese crosses had similar weights at most ages, although Meishan crosses were heavier (P < .05) than Fengjing and Minzhu crosses at 126 and 154 d of age. Breed types did not differ significantly (P approximately .27) for feed efficiency during the nursery period. Over the entire finishing period, Duroc-cross gilts (.3310) were less efficient (P < .05) than Meishan (.3436), Fengjing (.3454), or Minzhu crosses (.3466); among barrows Meishan crosses (.3176) were least efficient (P < .05), Fengjing crosses (.3263) were most efficient (P < .05), and Duroc (.3211) and Minzhu (.3209) were intermediate but not significantly different from the Meishan or Fengjing crosses. At a constant age, Duroc crosses had longer carcasses, greater longissimus muscle area, and heavier slaughter weight, carcass weight, and weight of untrimmed cuts and trimmed cuts than the Chinese crosses (P < .05). There were few significant differences among breed types for carcass traits at a constant carcass weight. Results show that, relative to one-half Duroc females, incorporation of one-half Chinese females into a crossbreeding program will result in progeny with a significant decrease in rate of growth (approximately 9% for weight at 154 d of age) and a small, nonsignificant decrease in yield of trimmed lean cuts (approximately 5%) at a constant carcass weight.