Treatment Efficacy Score-continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials.

BACKGROUND: Difference in pathologic complete response (pCR) rate after neoadjuvant chemotherapy does not capture the impact of treatment on downstaging of residual cancer in the experimental arm. We developed a method to compare the entire distribution of residual cancer burden (RCB) values between clinical trial arms to better quantify the differences in cytotoxic efficacy of treatments. PATIENTS AND METHODS: The Treatment Efficacy Score (TES) reflects the area between the weighted cumulative distribution functions of RCB values from two trial arms. TES is based on a modified Kolmogorov-Smirnov test with added weight function to capture the importance of high RCB values and uses the area under the difference between two distribution functions as a statistical metric. The higher the TES the greater the shift to lower RCB values in the experimental arm. We developed TES from the durvalumab + olaparib arm (n = 72) and corresponding controls (n = 282) of the I-SPY2 trial. The 11 other experimental arms and control cohorts (n = 947) were used as validation sets to assess the performance of TES. We compared TES to Kolmogorov-Smirnov, Mann-Whitney, and Fisher's exact tests to identify trial arms with higher cytotoxic efficacy and assessed associations with trial arm level survival differences. Significance was assessed with a permutation test. RESULTS: In the validation set, TES identified arms with a higher pCR rate but was more accurate to identify regimens as less effective if treatment did not reduce the frequency of high RCB values, even if the pCR rate improved. The correlation between TES and survival was higher than the correlation between the pCR rate difference and survival. CONCLUSIONS: TES quantifies the difference between the entire distribution of pathologic responses observed in trial arms and could serve as a better early surrogate to predict trial arm level survival differences than pCR rate difference alone.

A comparison of buprenorphine and psychosocial treatment outcomes in psychosocial and medical settings.

BACKGROUND: Facing an epidemic of opioid-related mortality, many government health departments, insurers, and treatment providers have attempted to expand patient access to buprenorphine in psychosocial substance use disorder (SUD) programs and medical settings. METHODS: With Missouri Medicaid data from 2008 to 2015, we used Cox proportional hazard models to estimate the relative hazards for treatment attrition and SUD-related emergency department (ED) visits or hospitalizations associated with buprenorphine in psychosocial SUD programs and medical settings. We also tested the association of buprenorphine with hours of psychosocial treatment during the first 30 days of psychosocial SUD treatment. The analytic sample included claims from 7606 individuals with an OUD diagnosis. RESULTS: Compared to psychosocial treatment without buprenorphine (PSY), the addition of buprenorphine (PSY-B) was associated with a significantly reduced hazard for treatment attrition (adjusted hazard ratio: 0.67, 95% CI: 0.62-0.71). Among buprenorphine episodes, office-based (B-OBOT), outpatient hospital (B-OPH), and no documented setting (B-PHA) were associated with reduced hazards for treatment attrition when compared to the psychosocial SUD setting (B-PSY) (adjusted hazard ratios: 0.27, 95% CI: 0.24-0.31; 0.46, 95% CI: 0.39-0.54; 0.70, 95% CI: 0.61-0.81). Compared to B-PSY, B-OBOT and B-PHA were associated with significantly reduced hazards for a SUD-related ED visits or hospitalization (adjusted hazard ratios: 0.59, 95% CI: 0.41-0.85; 0.53, 95% CI: 0.36-0.78). There was no significant difference between B-PSY and B-OPH or B-PSY and PSY in hazard for an SUD-related ED visit or hospitalization. CONCLUSIONS: Our findings support the conclusion that adding buprenorphine to Medicaid-covered psychosocial SUD treatment reduces patient attrition and SUD-related ED visits or hospitalizations but that buprenorphine treatment in office-based medical settings is even more effective in reducing these negative outcomes. Policy-makers should consider ways to expand buprenorphine access in all settings, but particularly in office-based medical settings. Buprenorphine treatment in an unbilled setting was associated with an increased hazard for patient attrition when compared to treatment in billed medical settings, indicating the importance of Medicaid-covered provider visits for patient retention.

Female autonomy, the family, and industrialization in Java.

PIP: It is generally argued that industrialization has an adverse affect on the position of women due to their exclusion from industrial employment and the resulting erosion of their status. This article addresses a case study of the question of gender stratification and industrialization by analyzing the relationship between factory daughters and their families in Java, Indonesia. From an initial 1-month daily survey of income and expenditures conducted among 14 workers in Nuwun, Wolf found that although they contributed 28% of their wages to the family, in cash or in kind, they overspent their wages by 40%. She then designed a more extensive survey, including questions about access to other income, debts, and savings. To determine if the relationship between daughters and family economy was related to residence, she expanded the survey to include 3 different groups of workers: commuters, migrants, and residents. Commuters lived with their parents in the agricultural village, Nuwan, and were the sole focus of the 1st income survey. Migrants were boarders in an industrialized village, Pamit, and residents walked to work. Single women are the focus of this paper due to the very different contribution daughters can potentially make to the family's welfare. The case study suggests that industrialization at the very least maintains, and may even enhance, female status within the family. To summarize, if a family can release a daughter for factory employment and can forgo the returns from her labor, there are eventual benefits for both the worker and her family. Worker-daughters are less of a financial burden on families. The savings provide surplus income that is not used for subsistence needs. Families gain tangible status goods that are displayed in the house and, at the same time, have access to insurance for crises and cash needs. Daughters, on the other hand, choose what to purchase and for whom. They gain prestige as donors of thoughtful gifts to family members, and gifts are symbols of independence. They also gain prestige as providers of emergency aid. These contributions bring them higher status than would remitting a steady but tiny flow of cash to the family economy. Wolf compares this Southeast Asian case with the East Asian experience to demonstrate the important role family systems play in mediating the effects of industrialization upon women and family change.^ieng

The CHOICE trial: adalimumab demonstrates safety, fistula healing, improved quality of life and increased work productivity in patients with Crohn's disease who failed prior infliximab therapy.

BACKGROUND: Adalimumab induces and maintains remission in adults with Crohn's disease. AIM: To evaluate safety, fistula healing, quality of life and work productivity in adalimumab-treated patients who failed infliximab, including primary nonresponders. METHODS: After a ≥8-week infliximab washout, patients with moderate-to-severe Crohn's disease received open-label adalimumab as induction (160/80 mg at weeks 0/2) and maintenance (40 mg every other week) therapies. At/after 8 weeks, patients with flare/nonresponse could receive weekly therapy. Minimum study duration was 8 weeks, continuing until the commercial availability of adalimumab for Crohn's disease. RESULTS: Of 673 patients enrolled, 17% were infliximab primary nonresponders and 83% were initial responders. Three percent of patients had serious infections (mainly abscesses). Complete fistula healing was achieved by 34/88 (39%) patients with baseline fistulas. Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients, as well as the subgroup of primary nonresponders. CONCLUSIONS: Blinded clinical trials have shown adalimumab to be both an effective first-line therapy for anti-TNF-naïve patients and an important treatment option for infliximab-refractory or -intolerant patients. This trial presents open-label experience to support further the safety and effectiveness of adalimumab in patients who failed infliximab therapy, including primary nonresponders (NCT00338650).

Selecting plants and nitrogen rates to vegetate crude-oil-contaminated soil.

Phytoremediation can be effective for remediating contaminated soils in situ and generally requires the addition of nitrogen (N) to increase plant growth. Our research objectives were to evaluate seedling emergence and survival of plant species and to determine the effects of N additions on plant growth in crude-oil-contaminated soil. From a preliminary survival study, three warm-season grasses--pearlmillet (Pennisetum glaucum [L.] R. Br.), sudangrass (Sorghum sudanense [Piper] Stapf [Piper]), and browntop millet (Brachiaria ramosa L.)--and one warm-season legume--jointvetch (Aeschynomene americana L.)--were chosen to determine the influence of the N application rate on plant growth in soil contaminated with weathered crude oil. Nitrogen was added based on total petroleum hydrocarbon-C:added N ratios (TPH-C:TN) ranging from 44:1 to 11:1. Plant species were grown for 7 wk. Root and shoot biomass were determined and root length and surface area were analyzed. Pearlmillet and sudangrass had higher shoot and root biomass when grown at a TPH-C:TN (inorganic) ratio of 11:1 and pearlmillet had higher root length and surface area when grown at 11:1 compared with the other species. By selecting appropriate plant species and determining optimum N application rates, increased plant root growth and an extended rhizosphere influence should lead to enhanced phytoremediation of crude-oil-contaminated soil.

Adenosine-tri-phosphate treatment for supraventricular tachycardia in infants.

Adenosine is an endogenous nucleoside acting on coronary perfusion and myocardial conduction. Although the anti-arrhythmic effects of adenosine have been known for decades, interest in the use of adenosine or adenosine-triphosphate (ATP) (a precursor of adenosine) in termination of supraventricular tachycardia (SVT) has been renewed. We studied the use of striadyne (ATP and a mixture of other nucleosides including adenosine) in 22 infants younger than 6 months in order to evaluate efficiency and safety of the drug in this particular age group. Striadyne stopped SVT in 17 cases and was diagnostic in another 4 cases. Ten out of 17 successfully converted infants showed one or more reinitiations of SVT, which were easily controlled. The results support the efficiency of ATP for the termination of re-entry types of tachycardia, as well as its diagnostic value and its lack of serious side-effects.

Adenosine triphosphate treatment for supraventricular tachycardia in infants.

UNLABELLED: Adenosine is an endogenous nucleoside acting on coronary perfusion and myocardial conduction. Although the anti-arrhythmic effects of adenosine have been known for decades, interest in the use of adenosine or adenosine triphosphate (ATP- a precursor of adenosine) in termination of supraventricular tachycardia (SVT) has been renewed. We studied the use of Striadyne (ATP and a mixture of other nucleosides including adenosine) in 22 infants younger than 6 months in order to evaluate efficacy and safety of the drug in this particular age group. Striadyne stopped SVT in 17 cases and was diagnostic in another 4 cases. Ten out of 17 successfully converted infants showed one or more reinitiations of SVT, which were easily controlled. The results support the efficacy of ATP for the termination of re-entry types of tachycardia, as well as its diagnostic value and its lack of serious side-effects. CONCLUSION: Adenosine or ATP could be the drug of choice for the treatment of junctional tachycardia in infants after vagal manoeuvres have failed. Provided continuous ECG monitoring is performed during injection, adenosine or ATP may be diagnostic in other types of supraventricular tachycardia and even in wide-complex tachycardia. We suggest a bolus injection of 0.5-1.0 mg/kg to be used prior to transport to the paediatric cardiology unit.

Promoting hospital discharge of infants in safety seats.

In 1990, the American Academy of Pediatrics (AAP) Committee on Injury and Poison Prevention issued a policy statement, "Safe Transportation of Newborns Discharged from the Hospital," recommending that hospitals adopt comprehensive policies, procedures and education programs for the discharge of newborns in child safety seats (CSSs). The purpose of this project was to determine if a statewide educational intervention based on the AAP statement would be effective in bringing about those recommendations in Nebraska hospitals. All hospitals providing newborn services in Nebraska were surveyed prior to and after the intervention to determine the nature and extent of their CSS discharge policies, patient education programs and loan programs. Post-intervention data indicate significant increases in the percentage of hospitals having formal infant CSS discharge policies (from 25.9% to 88%), providing CSS patient education (from 51% to 95%), and having safety seat loan/give-away programs (from 59% to 76%). It is concluded that a comprehensive, statewide educational program can influence hospitals to promote usage of, access to, and education with infant CSSs.