PRimary Care Opioid Use Disorders treatment (PROUD) trial protocol: a pragmatic, cluster-randomized implementation trial in primary care for opioid use disorder treatment

BACKGROUND: Most people with opioid use disorder (OUD) never receive treatment. Medication treatment of OUD in primary care is recommended as an approach to increase access to care. The PRimary Care Opioid Use Disorders treatment (PROUD) trial tests whether implementation of a collaborative care model (Massachusetts Model) using a nurse care manager (NCM) to support medication treatment of OUD in primary care increases OUD treatment and improves outcomes. Specifically, it tests whether implementation of collaborative care, compared to usual primary care, increases the number of days of medication for OUD (implementation objective) and reduces acute health care utilization (effectiveness objective). The protocol for the PROUD trial is presented here. METHODS: PROUD is a hybrid type III cluster-randomized implementation trial in six health care systems. The intervention consists of three implementation strategies: salary for a full-time NCM, training and technical assistance for the NCM, and requiring that three primary care providers have DEA waivers to prescribe buprenorphine. Within each health system, two primary care clinics are randomized: one to the intervention and one to Usual Primary Care. The sample includes all patients age 16-90 who visited the randomized primary care clinics from 3 years before to 2 years after randomization (anticipated to be \u3e 170,000). Quantitative data are derived from existing health system administrative data, electronic medical records, and/or health insurance claims ( electronic health records, [EHRs]). Anonymous staff surveys, stakeholder debriefs, and observations from site visits, trainings and technical assistance provide qualitative data to assess barriers and facilitators to implementation. The outcome for the implementation objective (primary outcome) is a clinic-level measure of the number of patient days of medication treatment of OUD over the 2 years post-randomization. The patient-level outcome for the effectiveness objective (secondary outcome) is days of acute care utilization [e.g. urgent care, emergency department (ED) and/or hospitalizations] over 2 years post-randomization among patients with documented OUD prior to randomization. DISCUSSION: The PROUD trial provides information for clinical leaders and policy makers regarding potential benefits for patients and health systems of a collaborative care model for management of OUD in primary care, tested in real-world diverse primary care settings

Regulation of Progranulin Expression in Human Microglia and Proteolysis of Progranulin by Matrix Metalloproteinase-12 (MMP-12)

Background: The essential role of progranulin (PGRN) as a neurotrophic factor has been demonstrated by the discovery that haploinsufficiency due to GRN gene mutations causes frontotemporal lobar dementia. In addition to neurons, microglia in vivo express PGRN, but little is known about the regulation of PGRN expression by microglia. Goal: In the current study, we examined the regulation of expression and function of PGRN, its proteolytic enzyme macrophage elastase (MMP-12), as well as the inhibitor of PGRN proteolysis, secretory leukocyte protease inhibitor (SLPI), in human CNS cells. Methods: Cultures of primary human microglia and astrocytes were stimulated with the TLR ligands (LPS or poly IC), Th1 cytokines (IL-1/IFNc), or Th2 cytokines (IL-4, IL-13). Results were analyzed by Q-PCR, immunoblotting or ELISA. The roles of MMP-12 and SLPI in PGRN cleavage were also examined. Results: Unstimulated microglia produced nanogram levels of PGRN, and PGRN release from microglia was suppressed by the TLR ligands or IL-1/IFNc, but increased by IL-4 or IL-13. Unexpectedly, while astrocytes stimulated with proinflammatory factors released large amounts of SLPI, none were detected in microglial cultures. We also identified MMP-12 as a PGRN proteolytic enzyme, and SLPI as an inhibitor of MMP-12-induced PGRN proteolysis. Experiments employing PGRN siRNA demonstrated that microglial PGRN was involved in the cytokine and chemokine production following TLR3/4 activation

Systematic review: conservative treatments for secondary lymphedema

<p>Abstract</p> <p>Background</p> <p>Several conservative (i.e., nonpharmacologic, nonsurgical) treatments exist for secondary lymphedema. The optimal treatment is unknown. We examined the effectiveness of conservative treatments for secondary lymphedema, as well as harms related to these treatments.</p> <p>Methods</p> <p>We searched MEDLINE^®, EMBASE^®, Cochrane Central Register of Controlled Trials^®, AMED, and CINAHL from 1990 to January 19, 2010. We obtained English- and non-English-language randomized controlled trials or observational studies (with comparison groups) that reported primary effectiveness data on conservative treatments for secondary lymphedema. For English-language studies, we extracted data in tabular form and summarized the tables descriptively. For non-English-language studies, we summarized the results descriptively and discussed similarities with the English-language studies.</p> <p>Results</p> <p>Thirty-six English-language and eight non-English-language studies were included in the review. Most of these studies involved upper-limb lymphedema secondary to breast cancer. Despite lymphedema's chronicity, lengths of follow-up in most studies were under 6 months. Many trial reports contained inadequate descriptions of randomization, blinding, and methods to assess harms. Most observational studies did not control for confounding. Many studies showed that active treatments reduced the size of lymphatic limbs, although extensive between-study heterogeneity in areas such as treatment comparisons and protocols, and outcome measures, prevented us from assessing whether any one treatment was superior. This heterogeneity also precluded us from statistically pooling results. Harms were rare (< 1% incidence) and mostly minor (e.g., headache, arm pain).</p> <p>Conclusions</p> <p>The literature contains no evidence to suggest the most effective treatment for secondary lymphedema. Harms are few and unlikely to cause major clinical problems.</p

Why Are Some Plant Genera More Invasive Than Others?

Determining how biological traits are related to the ability of groups of organisms to become economically damaging when established outside of their native ranges is a major goal of population biology, and important in the management of invasive species. Little is known about why some taxonomic groups are more likely to become pests than others among plants. We investigated traits that discriminate vascular plant genera, a level of taxonomic generality at which risk assessment and screening could be more effectively performed, according to the proportion of naturalized species which are pests. We focused on the United States and Canada, and, because our purpose is ultimately regulatory, considered species classified as weeds or noxious. Using contingency tables, we identified 11 genera of vascular plants that are disproportionately represented by invasive species. Results from boosted regression tree analyses show that these categories reflect biological differences. In summary, approximately 25% of variation in genus proportions of weeds or noxious species was explained by biological covariates. Key explanatory traits included genus means for wetland habitat affinity, chromosome number, and seed mass

Combined Use of Serum Adiponectin and Tumor Necrosis Factor-Alpha Receptor 2 Levels Was Comparable to 2-Hour Post-Load Glucose in Diabetes Prediction

Background: Adipose tissue inflammation and dysregulated adipokine secretion are implicated in obesity-related insulin resistance and type 2 diabetes. We evaluated the use of serum adiponectin, an anti-inflammatory adipokine, and several proinflammatory adipokines, as biomarkers of diabetes risk and whether they add to traditional risk factors in diabetes prediction. Methods: We studied 1300 non-diabetic subjects from the prospective Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). Serum adiponectin, tumor necrosis factor-alpha receptor 2 (TNF-α R2), interleukin-6 (IL-6), adipocyte-fatty acid binding protein (A-FABP) and high-sensitivity C-reactive protein (hsCRP) were measured in baseline samples. Results: Seventy-six participants developed diabetes over 5.3 years (median). All five biomarkers significantly improved the log-likelihood of diabetes in a clinical diabetes prediction (CDP) model including age, sex, family history of diabetes, smoking, physical activity, hypertension, waist circumference, fasting glucose and dyslipidaemia. In ROC curve analysis, "adiponectin + TNF-α R2" improved the area under ROC curve (AUC) of the CDP model from 0.802 to 0.830 (P = 0.03), rendering its performance comparable to the "CDP + 2-hour post-OGTT glucose" model (AUC = 0.852, P = 0.30). A biomarker risk score, derived from the number of biomarkers predictive of diabetes (low adiponectin, high TNF-α R2), had similar performance when added to the CDP model (AUC = 0.829 [95% CI: 0.808-0.849]). Conclusions: The combined use of serum adiponectin and TNF-α R2 as biomarkers provided added value over traditional risk factors for diabetes prediction in Chinese and could be considered as an alternative to the OGTT. © 2012 Woo et al.published_or_final_versio

Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Fatigue is prevalent in breast cancer survivors and has profound effects on daily life. The interference of fatigue with endocrine therapy may be difficult to separate. This study investigates the prevalence and severity of fatigue and identifies the demographic, clinical, and lifestyle factors associated with cancer-related fatigue (CRF) in breast cancer patients undergoing endocrine therapy in an urban area.</p> <p>Methods</p> <p>Women with stage I-IIIA breast cancer were recruited and asked to participate (n = 371) in the study. The 315 women who responded to the questionnaire (84.9%), 54 (17.1%) had completed endocrine therapy and 261 (82.9%) were still undergoing endocrine therapy. The patients had been diagnosed at an average of 31 months prior to recruitment (range, 7 to 60 months); the average age was 48 (range, 33 to 72) years. The 11-point scale and Visual Analog Scale (VAS) were employed to quantify the level of fatigue experienced by the patients. Logistic regression analyses and a trend test method were performed to evaluate factors associated with CRF.</p> <p>Results</p> <p>Among the 315 patients, 189 (60%) had experienced or were experiencing CRF during endocrine therapy. Logistic regression analysis was performed to identify factors associated with CRF, including BMI (body mass index), clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet. Factors unrelated to CRF were age, marital status, treatment, endocrine therapy drugs, alcohol intake, and smoking. The trend test method revealed an association between physical activity and dietary level and the intensity of CRF.</p> <p>Conclusions</p> <p>The present findings suggest that fatigue is an important problem in the majority of breast cancer patients during endocrine therapy. We found that BMI, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet are associated with fatigue. Future research should focus on the impact factors of CRF and lifestyle in the management of breast cancer patients.</p

The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel

<p>Abstract</p> <p>Background</p> <p>Drinking water contaminated with inorganic arsenic is associated with increased risk for different types of cancer. Paradoxically, arsenic trioxide can also be used to induce remission in patients with acute promyelocytic leukemia (APL) with a success rate of approximately 80%. A comprehensive study examining the mechanisms and potential signaling pathways contributing to the anti-tumor properties of arsenic trioxide has not been carried out.</p> <p>Methods</p> <p>Here we applied a systems biology approach to identify gene biomarkers that underlie tumor cell responses to arsenic-induced cytotoxicity. The baseline gene expression levels of 14,500 well characterized human genes were associated with the GI₅₀ data of the NCI-60 tumor cell line panel from the developmental therapeutics program (DTP) database. Selected biomarkers were tested <it>in vitro</it> for the ability to influence tumor susceptibility to arsenic trioxide.</p> <p>Results</p> <p>A significant association was found between the baseline expression levels of 209 human genes and the sensitivity of the tumor cell line panel upon exposure to arsenic trioxide. These genes were overlayed onto protein-protein network maps to identify transcriptional networks that modulate tumor cell responses to arsenic trioxide. The analysis revealed a significant enrichment for the oxidative stress response pathway mediated by nuclear factor erythroid 2-related factor 2 (NRF2) with high expression in arsenic resistant tumor cell lines. The role of the NRF2 pathway in protecting cells against arsenic-induced cell killing was validated in tumor cells using shRNA-mediated knock-down.</p> <p>Conclusions</p> <p>In this study, we show that the expression level of genes in the NRF2 pathway serve as potential gene biomarkers of tumor cell responses to arsenic trioxide. Importantly, we demonstrate that tumor cells that are deficient for NRF2 display increased sensitivity to arsenic trioxide. The results of our study will be useful in understanding the mechanism of arsenic-induced cytotoxicity in cells, as well as the increased applicability of arsenic trioxide as a chemotherapeutic agent in cancer treatment.</p

A user-centred approach to developing bWell, a mobile app for arm and shoulder exercises after breast cancer treatment

Purpose: The study aim was to develop a mobile application (app) supported by user preferences to optimise self-management of arm and shoulder exercises for upper-limb dysfunction (ULD) after breast cancer treatment. Methods: Focus groups with breast cancer patients were held to identify user needs and requirements. Behaviour change techniques were explored by researchers and discussed during the focus groups. Concepts for content were identified by thematic analysis. A rapid review was conducted to inform the exercise programme. Preliminary testing was carried out to obtain user feedback from breast cancer patients who used the app for 8 weeks post-surgery. Results: Breast cancer patients’ experiences with ULD and exercise advice and routines varied widely. They identified and prioritised several app features: tailored information, video demonstrations of the exercises, push notifications, and tracking and progress features. An evidence-based programme was developed with a physiotherapist with progressive exercises for passive and active mobilisation, stretching and strengthening. The exercise demonstration videos were filmed with a breast cancer patient. Early user testing demonstrated ease of use, and clear and motivating app content. Conclusions: bWell, a novel app for arm and shoulder exercises was developed by breast cancer patients, health care professionals and academics. Further research is warranted to confirm its clinical effectiveness. Implications for Cancer Survivors: Mobile health has great potential to provide patients with information specific to their needs. bWell is a promising way to support breast cancer patients with exercise routines after treatment and may improve future self-management of clinical care