Long-term statin use and risk of cancers: a target trial emulation study.

BACKGROUND AND OBJECTIVES: Controversy exists regarding potential cancer risks associated with long-term statin use. This study aimed to use real-world data to investigate the association between cancer incidence and sustained statin use over a 10-year period. METHODS: Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of nested target trials on patients who met indications for statin initiation in each calendar month from January 2009 to December 2011. Statin initiators and noninitiators were matched in a 1:1 ratio to mimic the randomization of eligible person-trials at baseline. Pooled logistic regression was applied to obtain the hazard ratios for the cancer incidence of statin initiation in intention-to-treat analysis, with the adjustment of baseline confounders and the inverse probability weighting accounting for the postbaseline confounders in per-protocol analysis. RESULTS: Among 8,560,051 eligible person-trials, 119,715 noninitiators were matched to 119,715 initiators for analysis. Over the 10-year study period, the estimated hazard ratio of overall cancer incidence was 0.96 (0.87, 1.05), and the standardized 10-year risk difference was -0.4% (-1.3%, 0.4%) in the per-protocol analysis. For the cancer subtypes of interest (ie, breast cancer, colorectal cancer, hematological cancer, pancreatic cancer, prostate cancer, urothelial carcinoma, and lung cancer), the 10-year risk differences ranged from -0.3% to 0.2% in the per-protocol analysis. No observable risk change for cancer was found in all patient subgroups with regards to their sex, age (<70/≥70 years), Charlson Comorbidity Index (≤4/>4), and statin indication. CONCLUSION: Statin use has no impact on cancer incidence over a 10-year follow-up period, including all cancer subtypes of interest and patient subgroups with regards to sex, age, comorbidities, and statin indications.

Students' interaction anxiety and social phobia in interprofessional education in Hong Kong: mapping a new research direction.

BACKGROUND: Interprofessional education (IPE) has been promoted as a breakthrough in healthcare because of the impact when professionals work as a team. However, despite its inception dating back to the 1960s, its science has taken a long time to advance. There is a need to theorize IPE to cultivate creative insights for a nuanced understanding of IPE. This study aims to propose a research agenda on social interaction by understanding the measurement scales used and guiding researchers to contribute to the discussion of social processes in IPE. METHOD: This quantitative research was undertaken in a cross-institutional IPE involving 925 healthcare students (Medicine, Nursing, Social Work, Chinese Medicine, Pharmacy, Speech Language Pathology, Clinical Psychology, Food and Nutritional Science and Physiotherapy) from two institutions in Hong Kong. Participants completed the Social Interaction Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6). We applied a construct validation approach: within-network and between-network validation. We performed confirmatory factors analysis, t-test, analysis of variance and regression analysis. RESULTS: CFA results indicated that current data fit the a priori model providing support to within-network validity [RMSEA=.08, NFI=.959, CFI=.965, IFI=.965, TLI=.955]. The criteria for acceptable fit were met. The scales were invariant between genders, across year levels and disciplines. Results indicated that social interaction anxiety and social phobia negatively predicted behavioural engagement (F = 25.093, p<.001, R2=.065) and positively predicted behavioural disaffection (F = 22.169, p<.001, R2=.057) to IPE, suggesting between-network validity. CONCLUSIONS: Our data provided support for the validity of the scales when used among healthcare students in Hong Kong. SIAS-6 and SPS-6 have sound psychometric properties based on students' data in Hong Kong. We identified quantitative, qualitative and mixed methods research designs to guide researchers in getting involved in the discussion of students' social interactions in IPE.Key MessagesThe Social Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6) scales have sound psychometric properties based on the large-scale healthcare students' data in IPE in Hong Kong.Social interaction anxiety and social phobia negatively predicted students' behavioural engagement with IPE and positively predicted behavioural disaffection. The scales are invariant in terms of gender, year level and discipline.Quantitative, qualitative and mixed methods studies are proposed to aid researchers to contribute in healthcare education literature using the SIAS-6 and SPS-6.

Infectious eccrine hidradenitis: sweat glands as the portal of entry for cellulitis.

Neutrophilic eccrine hidradenitis (NEH) is a rare neutrophilic dermatosis involving the eccrine glands. It is commonly associated with haematological malignancy and administration of chemotherapy. An infective aetiology for NEH is termed infectious eccrine hidradenitis (IEH). Pathogens that have been associated with IEH include Nocardia, Serratia, Enterobacter sp., Staphylococcus aureus and Mycobacterium chelonae We describe a case of IEH in a patient with prolonged use of a compression sleeve for their upper limb lymphoedema. The histopathological findings of NEH and IEH are almost identical. Skin tissue culture and rapid clinical improvement with antibiotic therapy are keys in delineating the two subtypes.

Factors influencing primary care provider referral for bariatric surgery: Systematic review.

OBJECTIVE: To identify barriers to and facilitators of primary care provider (PCP) referral for bariatric surgery in patients with obesity. DATA SOURCES: MEDLINE, EMBASE, and PsycINFO databases were searched and reference lists of included articles were screened to identify additional relevant articles. Two reviewers independently reviewed citations and full-text articles, and appraised the quality of the included articles using the Critical Appraisal Skills Programme Tool Qualitative Checklist and the Appraisal Tool for Cross-Sectional Studies. They extracted data on the study characteristics and the barriers to and facilitators of PCP referral for bariatric surgery. Appraisal discrepancies were resolved through consensus among authors. STUDY SELECTION: Overall, 882 citations were identified and 18 articles were then selected for this review. SYNTHESIS: Barriers included fear of surgery complications and side effects, cost, lack of availability, perception that surgery is a quick fix or a last resort, and prior negative experiences. Facilitators included direct requests from patients, patient motivation, previously failed weight-loss interventions, and obesity-related comorbidities. Those PCPs who were knowledgeable about the risks and benefits of bariatric surgery were more likely to refer their patients. CONCLUSION: Education and continuing professional development programs regarding bariatric surgery are needed to improve PCP knowledge and capacity to manage patients with obesity. Also, educating the general public on obesity, weight management, and available treatment options can empower patients and families to manage their weight and pursue evidence-informed treatments.

Survey of perceptions and educational needs of primary care providers regarding management of patients with class II and III obesity in Ontario, Canada.

BACKGROUND: Primary care providers (PCPs) are typically the primary contact for patients with obesity seeking medical and surgical weight loss interventions; however, previous studies suggest that fewer than 7% of eligible adult patients are referred to publically funded medical and surgical weight loss interventions (MSWLI). METHODS: We performed an anonymous survey study between October 2017 and June 2018 to explore the knowledge, experiences, perceptions, and educational needs of PCPs in Southeastern Ontario in managing patients with class II and III obesity. RESULTS: Surveys were distributed to 591 PCPs (n = 538 family physicians; n = 53 nurse practitioners) identified as practicing in the Southeastern Ontario and 92 (15.6%) participated. PCPs serving a rural population estimated that 14.2 ± 10.9% of patients would qualify for MSWLI compared to 9.9 ± 8.5% of patients of PCPs serving an urban population (p = .049). Overall, 57.5% of respondents did not feel competent prescribing MSWLI to patients with class II/III obesity, while 69.8% stated they had 'good' knowledge of the referral criteria for MSWLI. 22.2% of respondents were hesitant to refer patients for bariatric surgery (BS) due to concerns about postoperative surgical complications and risks associated with surgery. Only 25% of respondents were comfortable providing long-term follow up after BS, and only 39.1% had participated in continuing education on management of patients with class II/III obesity in the past 5 years. CONCLUSION: The majority of PCPs believe there is a need for additional education about MSWLI for patients with class II/III obesity. Future studies are needed to develop and compare the effectiveness of additional education and professional development around risks of contemporary BS, indications to consider referral for MSWLI, management and long-term follow-up of patients after BS.

Survival and prognosis of individuals receiving programmed cell death 1 inhibitor with and without immunologic cutaneous adverse events.

BACKGROUND: The treatment response to new immunotherapy in advanced melanoma patients remains varied between individuals. Immune-related cutaneous side effects might have prognostic value. OBJECTIVE: To determine whether development of ≥1 of the 3 immune-mediated cutaneous events (eczema, lichenoid reaction, or vitiligo-like depigmentation) is associated with improved progression-free survival. METHODS: A cohort study of adults with stage IIIC-IV melanoma treated with pembrolizumab or nivolumab during May 1, 2012-February 1, 2018, at Westmead Hospital, Sydney, Australia. Treatment response was based on iRECIST version 1.1. RESULTS: In total, 82 patients of an average age of 59.9 years were included. Median follow-up was 40.7 months; 33 patients had ≥1 target skin reaction. Skin reactions developed in one-third of individuals by 6 months. At any given time, the instantaneous risk of disease progression and death was lower for individuals who had ≥1 cutaneous adverse event (CAE) develop. Compared with individuals with no CAE, the hazard ratio for disease progression and death for individuals who had ≥1 CAE develop was 0.46 (95% confidence interval 0.23-0.91; P = .025) by the time-dependent Cox proportional hazards model. LIMITATIONS: Single-center study. CONCLUSION: This study demonstrates an association between the development of ≥1 of 3 CAEs and improved progression-free survival in this cohort of patients.

A 30 kDa polyethylene glycol-enfuvirtide complex enhances the exposure of enfuvirtide in lymphatic viral reservoirs in rats.

HIV therapy with anti-retroviral drugs is limited by the poor exposure of viral reservoirs, such as lymphoid tissue, to these small molecule drugs. We therefore investigated the effect of PEGylation on the anti-retroviral activity and subcutaneous lymphatic pharmacokinetics of the peptide-based fusion inhibitor enfuvirtide in thoracic lymph duct cannulated rats. Both the peptide and the PEG were quantified in plasma and lymph via ELISA. Conjugation to a single 5 kDa linear PEG decreased anti-HIV activity three-fold compared to enfuvirtide. Whilst plasma and lymphatic exposure to peptide mass was moderately increased, the loss of anti-viral activity led to an overall decrease in exposure to enfuvirtide activity. A 20 kDa 4-arm branched PEG conjugated with an average of two enfuvirtide peptides decreased peptide activity by six-fold. Plasma and lymph exposure to enfuvirtide, however, increased significantly such that anti-viral activity was increased two- and six-fold respectively. The results suggest that a multi-enfuvirtide-PEG complex may optimally enhance the anti-retroviral activity of the peptide in plasma and lymph.

A 10-year retrospective cohort study of the management of toxic epidermal necrolysis and Stevens-Johnson syndrome in a New South Wales state referral hospital from 2006 to 2016.

IMPORTANCE: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening severe cutaneous drug reactions. There have been no Australian data published since 2007. OBJECTIVE: To explore whether there is an association between prognosis and the type of systemic immune-modulation treatment administered in a cohort of patients with SJS, SJS-TEN overlap, and TEN at the New South Wales State SJS/TEN referral center - Concord Repatriation General Hospital. METHODS: This is a retrospective, single center, cohort study of patients admitted with SJS/TEN from January 1, 2006, to December 31, 2016, at Concord Repatriation General Hospital. Data on demographic information, the causative agent, treatment, and final survival outcome were analyzed. RESULTS: Forty-two patients included: 26 (62%) with TEN, six (14%) with SJS/TEN overlap, and 10 (24%) with SJS. Overall mortality was 19% (n = 8), and seven suffered TEN. The average age of those who died was 60 years. Eighty-one percent of patients were managed within the burn unit. Twenty-nine patients (70%) received IVIG within this group; 13 individuals also received systemic corticosteroids. Seven (17%) were managed with corticosteroid therapy alone. The incidence of death was 0% in the combined IVIG and corticosteroid group. CONCLUSION: This series of 42 patients contributes valuable information to a serious condition with low global incidence and high mortality. There appears to be an apparent reduced mortality in the group of SJS/TEN patients managed with combined IVIG and corticosteroid. Larger cohorts are required to validate this relationship due to the risk of bias inherent to the retrospective study design and small sample size.

Development and testing of a decision aid for women considering delayed breast reconstruction.

BACKGROUND: The decision to have post-mastectomy breast reconstruction (PMBR) is highly complex and many women feel ill equipped to make this decision. Decision aids have been advocated to promote patient involvement in decision-making by streamlining and standardizing communication between the patient and the health care professional. In this study, we report on the development and testing of a decision aid (DA) for breast cancer survivors considering delayed PMBR. METHODS: The DA was developed and evaluated in three phases. The first phase included the development of the DA with input and review by practitioners and key stakeholders. The second phase involved pilot testing of the feasibility and acceptability of the DA with a convenience sample of women with delayed PMBR. The third phase involved a pretest/post-test evaluation of the DA for women who were making decisions about their PMBR options. RESULTS: The DA was developed using the Ottawa Decision Support Framework. In the second phase of the study, 21 women completed the acceptability survey, of whom 100% reported that they would recommend the DA to other women. In the third phase, decisional conflict decreased significantly (p < 0.001) and knowledge increased significantly (p < 0.001) from prior to using the DA to 1-2 weeks after using the DA. CONCLUSIONS: The DA is feasible and acceptable to women considering delayed PMBR. Furthermore, the DA is effective at reducing decisional conflict and increasing knowledge about delayed PMBR. The DA is an appropriate tool to be used in addition with standard care in women considering PMBR.

An Evaluation of Optimal PEGylation Strategies for Maximizing the Lymphatic Exposure and Antiviral Activity of Interferon after Subcutaneous Administration.

Interferon α2 is an antiviral/antiproliferative protein that is currently used to treat hepatitis C infections and several forms of cancer. Two PEGylated variants of interferon α2 (containing 12 and 40 kDa PEGs) are currently marketed and display longer plasma circulation times than that of unmodified interferon. With increasing realization that the lymphatic system plays an important role in the extrahepatic replication of the hepatitis C virus and in the metastatic dissemination of cancers, this study sought to evaluate PEGylation strategies to optimally enhance the antiviral activity and plasma and lymphatic exposure of interferon after subcutaneous administration in rats. The results showed that conjugation with a linear 20 kDa PEG provided the most ideal balance between activity and plasma and lymph exposure. A linear 5 kDa PEG variant also exhibited excellent plasma and lymph exposure to interferon activity when compared to those of unmodified interferon and the clinically available linear 12 kDa PEGylated construct.

Determination of the True Inclination Angle of the Main Bronchi Relative to the Median Sagittal Plane for Placement of a Left-Sided Double-Lumen Tube.

OBJECTIVES: This study aimed to determine the true inclination angle of the main bronchi relative to the median sagittal plane, using CT imaging to help increase accuracy of double-lumen tube (DLT) placement. DESIGN: In this retrospective study, 2 investigators independently measured normal chest CT scans from 50 male and 50 female patients. To determine the true AP axis, a mid-sagittal plane reference line (MSPRL) was drawn, intersecting the midsternum and the vertebral spinous process at the level of mid-carina. Lines were drawn through the center of each main bronchus to determine the inclination angle with regard to the MSPRL. SETTING: Research was conducted at a single institution, the Los Angeles County and University of Southern California Medical Center. PARTICIPANTS: Normal chest CT images from 50 women and 50 men. MAIN RESULTS: The mean true inclination angle between the main bronchi and trachea in the mid-sagittal plane was 108.4° on the left compared with 96.2° on the right (p<0.0001). INTERVENTIONS: No specific interventions were done because this was a retrospective study and CT scan analysis. CONCLUSION: The data suggested that the trachea does not merely branch in the horizontal plane but branches posteriorly as well, with a true mean anatomic angle between the left main bronchus and trachea of 108.4°. This finding concurred with the authors' suggestion that the DLT be rotated to 110° counterclockwise instead of the routine practice of 90°. The authors suggest clinicians rotate the DLT an additional 20° counterclockwise and direct the top of the DLT to the 11 o'clock position.

Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

A Comparison of the Pharmacokinetics and Pulmonary Lymphatic Exposure of a Generation 4 PEGylated Dendrimer Following Intravenous and Aerosol Administration to Rats and Sheep.

PURPOSE: Cancer metastasis to pulmonary lymph nodes dictates the need to deliver chemotherapeutic and diagnostic agents to the lung and associated lymph nodes. Drug conjugation to dendrimer-based delivery systems has the potential to reduce toxicity, enhance lung retention and promote lymphatic distribution in rats. The current study therefore evaluated the pharmacokinetics and lung lymphatic exposure of a PEGylated dendrimer following inhaled administration. METHODS: Plasma pharmacokinetics and disposition of a 22 kDa PEGylated dendrimer were compared after aerosol administration to rats and sheep. Lung-derived lymph could not be sampled in rats and so lymphatic transport of the dendrimer from the lung was assessed in sheep. RESULTS: Higher plasma concentrations were achieved when dendrimer was administered to the lungs of rats as a liquid instillation when compared to an aerosol. Plasma pharmacokinetics were similar between sheep and rats, although some differences in disposition patterns were evident. Unexpectedly, less than 0.5% of the aerosol dose was recovered in pulmonary lymph. CONCLUSIONS: The data suggest that rats provide a relevant model for assessing the pharmacokinetics of inhaled macromolecules prior to evaluation in larger animals, but that the pulmonary lymphatics are unlikely to play a major role in the absorption of nanocarriers from the lungs.

PEGylation does not significantly change the initial intravenous or subcutaneous pharmacokinetics or lymphatic exposure of trastuzumab in rats but increases plasma clearance after subcutaneous administration.

The lymphatic system plays a major role in the metastatic dissemination of cancer and has an integral role in immunity. PEGylation enhances drainage and lymphatic uptake following subcutaneous (sc) administration of proteins and protein-like polymers, but the impact of PEGylation of very large proteins (such as antibodies) on subcutaneous and lymphatic pharmacokinetics is unknown. This study therefore aimed to evaluate the impact of PEGylation on the sc absorption and lymphatic disposition of the anti-HER2 antibody trastuzumab in rats. PEG-trastuzumab was generated via the conjugation of a single 40 kDa PEG-NHS ester to trastuzumab. PEG-trastuzumab showed a 5-fold reduction in HER2 binding affinity, however the in vitro growth inhibitory effects were preserved as a result of changes in cellular trafficking when compared to native trastuzumab. The lymphatic pharmacokinetics of PEG-trastuzumab was evaluated in thoracic lymph duct cannulated rats after iv and sc administration and compared to the pharmacokinetics of native trastuzumab. The iv pharmacokinetics and lymphatic exposure of PEG-trastuzumab was similar when compared to trastuzumab. After sc administration, initial plasma pharmacokinetics and lymphatic exposure were also similar between PEG-trastuzumab and trastuzumab, but the absolute bioavailability of PEG-trastuzumab was 100% when compared to 86.1% bioavailability for trastuzumab. In contrast to trastuzumab, PEG-trastuzumab showed accelerated plasma clearance beginning approximately 7 days after sc, but not iv, administration, presumably as a result of the generation of anti-PEG IgM. This work suggests that PEGylation does not significantly alter the lymphatic disposition of very large proteins, and further suggests that it is unlikely to benefit therapy with monoclonal antibodies.

Optimal PEGylation can improve the exposure of interferon in the lungs following pulmonary administration.

The utility of inhaled protein therapeutics to treat lung-resident diseases is limited by protein degradation in the lungs and rapid clearance. This study therefore aimed to evaluate the impact of PEGylation on the lung and systemic exposure of interferon (IFN) α2 after intratracheal administration to rats. An inverse correlation was observed between PEG chain length and systemic exposure, where bioavailability was 5.5% for the 31 kDa PEGylated construct and <0.4% for the 60 kDa PEGylated construct when compared with 15% for native IFN (19 kDa). Retention of PEGylated IFNα within the lungs increased 2.5-fold to threefold when compared with native IFN. When comparing the lung and systemic exposure of PEGylated and native IFN in terms of protein biological activity, the 31 kDa PEGylated construct increased exposure by 50% and 100%, respectively, when compared with native IFN, but the 60 kDa PEG construct offered no benefit. Preliminary work also indicated that the conjugation of IFNγ with 10 kDa PEG significantly increases the retention of the protein within the lung. Optimal PEGylation may therefore be used as a means to improve the exposure of lung-resident diseases to therapeutic cytokines and potentially reduce systemic exposure and side effects as well as dosing frequency.

Analysis of risk factors associated with microvascular free flap failure using a multi-institutional database.

BACKGROUND: There are numerous factors that may contribute to microvascular free flap failure. Although technical issues are dominant factors, patient and clinical characteristics are also contributory. The aim of this study was to investigate non-technical variables associated with microsurgical free flap failure using a multi-institutional dataset. METHODS: Utilizing the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) database, we identified all patients who underwent microvascular free tissue transfer from 2005 through 2009. Univariate analysis was performed to determine the association of flap failure with the following factors: age, gender, ethnicity, body mass index, intraoperative transfusion, diabetes, smoking, alcohol, American Society of Anesthesiologists classification, year of operation, operative time, number of flaps, and type of reconstruction. Factors with a significance of P < 0.2 in the univariate analysis were included in the multivariate logistic regression model to identify independent risk factors. RESULTS: A total of 639 patients underwent microsurgical free flap reconstruction with 778 flaps over the 4-year study period; 139 patients had two free flaps during the same operation. The overall incidence of flap failure was 4.4% (34/778) (95% confidence interval [CI]: 3.0%, 6.2%). Operative time was identified as an independent risk factor for free flap failure. After adjusting for other factors, those whose operative time was equal to or greater than the 75th percentile (625.5 min) were twice as likely to experience flap failure (AOR 2.09; 95% CI: 1.01-4.31; P = 0.045). None of the other risk factors studied were significant contributors. CONCLUSIONS: In this series, the overall flap loss rate of was 4.4%. Operative time was a significant independent risk factor for flap failure.

Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumor-burdened lymph nodes after intravenous and subcutaneous administration in rats.

The current study sought to explore whether the subcutaneous administration of lymph targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumor activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumor-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumor growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumor-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumor activity, possibly suggesting constrained drug release at the site of action.

Effect of community educational interventions on rate of organ donation among Hispanic Americans.

IMPORTANCE: The need for suitable organs for transplantation is especially pronounced in minority populations such as Hispanic Americans owing to disproportionately high rates of diabetes mellitus and kidney disease. Considerable barriers exist for Hispanic Americans consent to donation, resulting in significantly lower donation rates compared with white individuals. OBJECTIVE: To investigate the effect of an aggressive outreach intervention during a 5-year period aimed at improving organ donation rates among Hispanic Americans. DESIGN, SETTING, AND PARTICIPANTS: Prospective longitudinal observation study of organ donors treated at a major metropolitan level I trauma center. The center provides most of the medical care to the 4 Southern California neighborhoods with a high percentage of Hispanic Americans that were included in the study. INTERVENTIONS: Television and radio media campaigns and culturally sensitive educational programs implemented at high schools, churches, and medical clinics in the target neighborhoods. MAIN OUTCOME AND MEASURE: Consent rate for organ donation recorded during the study. RESULTS: Outreach interventions started in 2007 and were completed by 2012. Of 268 potential donors, 155 total donors (106 Hispanic Americans) provided consent during this time. A significant increase in consent rate was noted among Hispanic Americans, from 56% in 2005 to 83%in 2011 (P = .004); this increase was not evident in the population that was not Hispanic (67%in 2005 and 79% in 2011; P = .21). CONCLUSIONS AND RELEVANCE: Aggressive outreach programs can reduce the disparity between organ supply and demand by improving the consent rate among the target group.