Safety and outcomes of short-term use of peripheral vasoactive infusions in critically ill paediatric population in the emergency department.

Early restoration of oxygen delivery to end organs in paediatric patients experiencing shock states is critical to optimizing outcomes. However, obtaining central access in paediatric patients may be challenging in non-intensive care settings. There is limited literature on the use of peripheral vasoactive infusions in the initial resuscitation of paediatric patients in the emergency department. The aims of this study were to report the associated complications of peripheral vasoactive infusions and describe our local experience on its use. This was a single-centre, retrospective study on all paediatric patients who received peripheral vasoactive infusions at our paediatric emergency department from 2009 to 2016. 65 patients were included in this study. No patients had any local or regional complications. The mean patient age was 8.29 years old (± 5.99). The most frequent diagnosis was septic shock (45, 69.2%). Dopamine was the most used peripheral vasoactive agent (71.2%). The median time to central agents was 2 h (IQR 1-4). 16(24.2%) received multiple peripheral infusions. We reported no complications of peripheral vasoactive infusions. Its use could serve as a bridge till central access is obtained. Considerations on the use of multiple peripheral vasoactive infusions in the emergency department setting needs further research.

An adapted mindfulness intervention for people with dementia in care homes: feasibility pilot study.

OBJECTIVE: Depression and anxiety are common in dementia. There is a need to develop effective psychosocial interventions. This study sought to develop a group-based adapted mindfulness programme for people with mild to moderate dementia in care homes and to determine its feasibility and potential benefits. METHODS: A manual for a 10-session intervention was developed. Participants were randomly allocated to the intervention plus treatment as usual (n = 20) or treatment as usual (n = 11). Measures of mood, anxiety, quality of life, cognitive function, stress and mindfulness were administered at baseline and 1 week post-intervention. RESULTS: There was a significant improvement in quality of life in the intervention group compared to controls (p = 0.05). There were no significant changes in other outcomes. CONCLUSIONS: The intervention was feasible in terms of recruitment, retention, attrition and acceptability and was associated with significant positive changes in quality of life. A fully powered randomised controlled trial is required. Copyright © 2017 John Wiley & Sons, Ltd.

Monocyte cell membrane-derived nanoghosts for targeted cancer therapy.

Core-shell type 'nanoghosts' were synthesized with a drug-loaded biodegradable PLGA core and a monocyte cell membrane-derived shell. The nanoghosts were monodisperse with an average size <200 nm, and showed good serum stability for 120 h. Doxorubicin-loaded nanoghosts showed greater cellular uptake and cytotoxicity compared to non-coated nanoparticle controls in metastatic MCF-7 breast cancer cell lines.

Immediate versus deferred initiation of androgen deprivation therapy in prostate cancer patients with PSA-only relapse. An observational follow-up study.

BACKGROUND: The optimal timing to start androgen deprivation therapy (ADT) in prostate cancer patients with rising prostate-specific antigen (PSA) as the only sign of relapse is unknown. METHODS: We identified men with prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavour (CaPSURE) study who would have been eligible (⩽ cT3aN0M0, primary radical prostatectomy or radiotherapy, PSA relapse as the only evidence of recurrence) for a randomised trial comparing 'immediate' versus 'deferred' ADT initiation. We emulated such trial by assigning patients to the 'immediate' strategy if they initiated ADT within 3 months of PSA relapse and to the 'deferred' strategy if they initiated ADT when they presented with metastasis, symptoms or a short PSA doubling time. We censored patients when they deviated from the assigned strategy and adjusted for this censoring via inverse probability weighting. RESULTS: Of 2096 eligible patients (median age 69, interquartile range 63-75 years), 88% were white, 35% had a Gleason score ⩾ 7, 69% were treated with radical prostatectomy and 31% received radiotherapy only as primary treatment. The mean time from primary treatment to PSA relapse was 37.4 (standard deviation [SD] 34.2) months. Mean follow-up from primary treatment was 91.4 (SD 48.4) months. The adjusted mortality hazard ratio for immediate versus deferred ADT was 0.91 (95% confidence interval (CI), 0.52-1.60), which would be translated into a similar 5-year survival (difference between groups: -2.0% (95% CI: -10.0 to 5.9%). CONCLUSION: Our analysis suggests that prostate cancer patients undergoing immediate ADT initiation within three months after PSA-only relapse had similar survival to those who deferred ADT initiation within 3 months after clinical progression.

Imaging of the vulnerable carotid plaque: biological targeting of inflammation in atherosclerosis using iron oxide particles and MRI.

OBJECTIVES: Identification of those patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque destabilization and the propensity of atherosclerotic lesions to cause clinical sequelae. There is currently no clinical imaging technique available to assess the degree of inflammation associated with plaques. This study aims at visualizing and characterizing atherosclerosis using antibody-conjugated superparamagnetic iron oxide (SPIO) particles as an MRI probe to assess inflammation in human atherosclerotic plaques. METHODS: Atherosclerotic plaques were collected from 20 consecutive patients (n=10 from symptomatic patients, n=10 from asymptomatic patients) undergoing carotid endarterectomy (CEA) for extracranial high-grade internal carotid artery (ICA) stenosis (>70% luminal narrowing). Inflammatory markers on human atherosclerotic plaques were detected and characterized by ex vivo magnetic resonance imaging (MRI) using anti-VCAM-1 antibody and anti-E-selectin antibody-conjugated SPIO with confirmatory immunohistochemistry. RESULTS: Inflammation associated with human ex vivo atherosclerotic plaques could be imaged using dual antibody-conjugated SPIO by MRI. Symptomatic plaques could be distinguished from asymptomatic ones by the degree of inflammation, and the MR contrast effect was significantly correlated with the degree of plaque inflammation (r=.64, p<.001). The asymptomatic plaque population exhibited heterogeneity in terms of inflammation. The dual-targeted SPIO-induced MR signal not only tracked closely with endothelial activation (i.e. endothelial expression of VCAM-1 and E-selectin), but also reflected the macrophage burden within plaque lesions, offering a potential imaging tool for quantitative MRI of inflammatory activity in atherosclerosis. CONCLUSIONS: These functional molecular MRI probes constitute a novel imaging tool for ex vivo characterization of atherosclerosis at a molecular level. Further development and translation into the clinical arena will facilitate more accurate risk stratification in carotid artery disease in the future.

Free hernia surgery for the underserved is possible in the United States.

INTRODUCTION: Inguinal hernia is one of the most common ailments known to mankind. When symptomatic it can severely affect the patient's quality of life. Nevertheless, the vast majority of inguinal herniorrhaphies are elective and, therefore, not available to uninsured patients who do not have the financial wherewithal to pay for the operation. Using the Surgery on Sunday model developed in Kentucky, hernia repair for the underserved developed a free clinic for hernia surgery, based on institutional commitment to the poor as well as the volunteer efforts of medical students and hospital personnel at all levels. METHODS: After consulting with Surgery on Sunday personnel, HRFU determined the number of in need patients by consulting with local free clinic physicians. Second, and most time consuming, was the application for the Federal Tort Claims Act (FTCA) medical legal protection. Under this law, all in hospital credentialed volunteer professionals are medico-legally protected if the surgery is performed in an associated free clinic. After FTCA application re-writes and committee meetings to work out logistics of the pre-op clinic, the follow-up clinic, enlistment of other volunteers such as transporters, translators, housekeeping for the ORs, a pharmacist, registration personnel and creation of HRFU hospital forms we established a surgery date. A memorandum of understanding was drafted and an agreement letter with the hospital system was co-signed. Fourteen patients were seen in the pre-operative clinic and two were placed on waiting list. Patients were operated upon using 3 operating rooms and a volunteer staff of 4 surgeons, 4 anesthesia personnel and 13 nurses. RESULTS: No surgical complications were encountered intra-operatively or in the recovery room, and all patients were discharged by 2:30 p.m. 1 week post-operatively one patient had severe incisional pain, two had operative site swelling, but there was no evidence of infection or hematoma, and one had a distal sac fluid collection. All patients returned for follow-up and were appreciative of the care provided. The enthusiasm and participation of the patients and staff both pre-operatively, the day of surgery and postoperatively was outstanding. CONCLUSION: On the basis of this result HRFU is prepared to assist other US hernia specialists and their respective hospitals to make Surgery on Sunday a possibility in their community.

Role of IL28B and inosine triphosphatase polymorphisms in the treatment of chronic hepatitis C virus genotype 6 infection.

IL28B and inosine triphosphatase (ITPA) polymorphisms are able to predict treatment response and degree of ribavirin-related anaemia, respectively, in the treatment of chronic hepatitis C virus (HCV) infection. However, their roles in the treatment of chronic HCV genotype 6 remain undetermined. Sixty patients who were infected with HCV genotype 6 were commenced on 48 weeks of combination pegylated interferon and ribavirin therapy. Response to therapy, profiles of haemoglobin changes and platelet counts during therapy and their associations with IL28B rs8099917 and ITPA rs1127354 polymorphisms were analysed. The overall sustained virologic response (SVR) rate was 91.7%. 18 patients (30.0%) required a reduction in ribavirin dosage. The distribution of IL28B rs8099917 TT/TG genotypes and ITPA rs1127354 CC/CA genotypes were in Hardy-Weinberg equilibrium. IL28B rs8099917 TT genotype, when compared to TG genotype, was significantly associated with an increased SVR rate (96.2% and 62.5%, respectively) and was the only clinical parameter that predicted SVR (P = 0.014). The same significant association was observed when analysing allelic frequencies (T vs G, P = 0.001). ITPA rs1127354 CA genotype, when compared to CC genotype, was associated with lesser degree of anaemia throughout therapy (P < 0.05 for all time points). ITPA polymorphisms showed no association with changes in platelet count throughout therapy (P > 0.05 for all time points) and was not associated with SVR (P = 0.640). In chronic HCV genotype 6 infection, IL28B polymorphisms were associated with response to therapy. ITPA polymorphisms influenced the degree of anaemia but not thrombocytopenia during therapy.

Active surveillance: does serial prostate biopsy increase histological inflammation?

BACKGROUND: Active surveillance (AS) is an appropriate management strategy for men with low-risk prostate cancer. Most protocols recommend repeated prostate biopsy every 12-24 months. The purpose of this paper is to describe histological inflammation patterns in men on AS who underwent serial prostate biopsy for disease monitoring. METHODS: We reviewed records of men on AS from January 1999 through February 2011 who had a diagnostic plus ≥1 repeat transrectal ultrasound-guided biopsies performed at our institution. The type and degree of inflammatory infiltrate were grossly reviewed and scored for each patient's biopsy by a single pathologist. Relationship of inflammation severity and number of serial biopsies was assessed using a repeated measures mixed model. Unpaired t-test and χ(2)-square analysis assessed variance in degree of inflammation and location of inflammation relative to cancer grade progression defined as Gleason sum increase. RESULTS: Fifty-six men met study inclusion criteria. Mean age was 62.1 (6.5) years, 71% were stage cT1c, 79% had a PSA level <10 ng ml(-1), and 98% had diagnostic Gleason sum ≤6. A small, statistically significant increase in maximum chronic inflammation (CI) scores with greater number of repeat biopsies was observed. CI scores were not associated with number of biopsies based on upgrade status. The main limitation to our study is our small sample size. Potential unmeasured confounders, such as unreported antibiotic use or symptomatic prostatitis, may have also affected our findings. CONCLUSIONS: In this pilot study of 56 men on AS for localized prostate cancer, degree of chronic histological inflammation increased with greater number of prostate biopsies, but was not associated with subsequent risk of grade progression.

Emergence of fatal avian influenza in New England harbor seals.

UNLABELLED: From September to December 2011, 162 New England harbor seals died in an outbreak of pneumonia. Sequence analysis of postmortem samples revealed the presence of an avian H3N8 influenza A virus, similar to a virus circulating in North American waterfowl since at least 2002 but with mutations that indicate recent adaption to mammalian hosts. These include a D701N mutation in the viral PB2 protein, previously reported in highly pathogenic H5N1 avian influenza viruses infecting people. Lectin staining and agglutination assays indicated the presence of the avian-preferred SAα-2,3 and mammalian SAα-2,6 receptors in seal respiratory tract, and the ability of the virus to agglutinate erythrocytes bearing either the SAα-2,3 or the SAα-2,6 receptor. The emergence of this A/harbor seal/Massachusetts/1/2011 virus may herald the appearance of an H3N8 influenza clade with potential for persistence and cross-species transmission. IMPORTANCE: The emergence of new strains of influenza virus is always of great public concern, especially when the infection of a new mammalian host has the potential to result in a widespread outbreak of disease. Here we report the emergence of an avian influenza virus (H3N8) in New England harbor seals which caused an outbreak of pneumonia and contributed to a U.S. federally recognized unusual mortality event (UME). This outbreak is particularly significant, not only because of the disease it caused in seals but also because the virus has naturally acquired mutations that are known to increase transmissibility and virulence in mammals. Monitoring the spillover and adaptation of avian viruses in mammalian species is critically important if we are to understand the factors that lead to both epizootic and zoonotic emergence.

PSA screening: determinants of primary-care physician practice patterns.

BACKGROUND: The effect of practice guidelines and the European Randomised Screening for Prostate Cancer (ERSPC) and Prostate, Lung, Colorectal and Ovarian (PLCO) trials on PSA screening practices of primary-care physicians (PCPs) is unknown. METHODS: We conducted a national cross-sectional on-line survey of a random sample of 3010 PCPs from July to August 2010. Participants were queried about their knowledge of prostate cancer, PSA screening guidelines, the ERSPC and PLCO trials, and about their PSA screening practices. Factors associated with PSA screening were identified using multivariable linear regression. RESULTS: A total of 152 (5%) participants opened and 89 completed the on-line survey, yielding a response rate of 58% for those that viewed the invitation. Eighty percent of respondents correctly identified prostate cancer risk factors. In all, 51% and 64% reported that they discuss and order PSA screening for men aged 50-75 years, respectively. Fifty-four percent were most influenced by the US Preventative Services Task Force (USPSTF) guidelines. Also, 21% and 28% of respondents stated that their PSA screening practices were influenced by the ERSPC and PLCO trials, respectively. Medical specialty was the only variable associated with propensity to screen, with family medicine physicians more likely to use PSA screening than internists (ß=0.21, P=0.02). CONCLUSIONS: Half of the physicians surveyed did not routinely discuss PSA screening with eligible patients. The impact of the ERSPC and PLCO trials on PSA screening practices was low among US PCPs. USPSTF recommendations for PSA screening continue to be the strongest influence on PCPs' propensity to use PSA screening.

Nanoparticles in medicine: therapeutic applications and developments.

Nanotechnology is the understanding and control of matter generally in the 1-100 nm dimension range. The application of nanotechnology to medicine, known as nanomedicine, concerns the use of precisely engineered materials at this length scale to develop novel therapeutic and diagnostic modalities. Nanomaterials have unique physicochemical properties, such as ultra small size, large surface area to mass ratio, and high reactivity, which are different from bulk materials of the same composition. These properties can be used to overcome some of the limitations found in traditional therapeutic and diagnostic agents.

Demographic factors associated with the diet quality of older US men: baseline data from the Osteoporotic Fractures in Men (MrOS) study.

OBJECTIVE: Throughout the world, the proportion of the male population aged 65 years and older is increasing. Yet, we have limited information regarding diet quality and predictors of diet quality in this segment of the population. The objectives of the current analyses are to describe the diet quality of a cohort of men >65 years of age, and identify lifestyle factors associated with poor diet quality. METHODS: We present a cross-sectional analysis of the diet quality of 5928 men, aged 65-100 years, who are participants in the Osteoporotic Fractures in Men (MrOS) cohort study. Dietary intake was determined using a modified Block 98 food-frequency questionnaire. Diet quality was calculated using the previously validated Diet Quality Index-Revised (DQI-R). Univariate and multivariate modelling was used to estimate the variance in diet quality predicted by a number of sociodemographic factors, including age, race/ethnicity, body mass index (BMI), marital status, education, smoking status, physical activity, self-perceived health and nutritional supplement use. RESULTS: Overall, we found that in this geographically diverse group of older men, diet quality was low, with a mean modified DQI-R for the entire study population of 62.5 (standard deviation 13.1) out of an ideal of 100. Further, younger age, very low total calorie intake (< or = 1187 kcal day- 1), higher BMI, residence in a North or Southeast community, being of African-American or Hispanic race, being less educated, not using dietary supplements and smoking were each significant independent predictors of a poorer diet. CONCLUSION: These data may prove useful in both understanding the dietary intake of older US men as it relates to published dietary guidelines, and for targeting future dietary intervention programmes.

Highly elevated PSA and dietary PhIP intake in a prospective clinic-based study among African Americans.

African-American men die from prostate cancer (PC) nearly twice as often as white US men and consume about twice as much of the predominant US dietary heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a genotoxic rat-prostate carcinogen found primarily in well-cooked chicken and beef. To investigate the hypothesis that PhIP exposure increases PC risk, an ongoing prospective clinic-based study compared PC screening outcomes with survey-based estimates of dietary PhIP intake among 40-70-year-old African-American men with no prior PC in Oakland, CA. They completed food-frequency and meat-cooking/consumption questionnaires and had a prostate-specific antigen (PSA) test and digital-rectal exam. Results for 392 men indicated a 17 (+/-17) ng/kg day mean (+/-1 s.d.) daily intake of PhIP, about twice that of white US men of similar age. PhIP intake was attributable mostly to chicken (61%) and positively associated (R(2)=0.32, P<0.0001) with saturated fat intake. An odds ratio (95% confidence interval) of 31 (3.1-690) for highly elevated PSA > or =20 ng/ml was observed in the highest 15% vs lowest 50% of estimated daily PhIP intake (> or =30 vs < or =10 ng/kg day) among men 50+ years old (P=0.0002 for trend) and remained significant after adjustment for self-reported family history of (brother or father) PC, saturated fat intake and total energy intake. PSA measures were higher in African-American men with positive family history (P=0.007 all men, P<0.0001 highest PSA quartile). These preliminary results are consistent with a positive association between PhIP intake and highly elevated PSA, supporting the hypothesis that dietary intervention may help reduce PC risk.

Total and specific complementary and alternative medicine use in a large cohort of men with prostate cancer.

OBJECTIVES: To assess specific complementary and alternative medicine (CAM) use in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a large, community-based national registry of men with prostate cancer. METHODS: We examined more than 50 types of CAM use in a large, national, community-based registry of men with prostate cancer (CaPSURE). Participants completed biannual surveys within 2 years of diagnosis and treatment. We analyzed associations of CAM use with sociodemographic and clinical features, using chi-square tests and multivariate logistic regression. RESULTS: One third of 2582 respondents reported using CAM. Common practices included vitamin and mineral supplements (26%), herbs (16%), antioxidants (13%), and CAM for prostate health (12%; eg, saw palmetto, selenium, vitamin E, lycopene). In multivariate analyses, users were more likely to have other comorbid conditions, worse cancer grade at diagnosis, higher incomes, more education, and to live in the West. CONCLUSIONS: Complementary and alternative medicine use was associated with sociodemographic and clinical characteristics in this large sample of men with prostate cancer. These results should be considered by health care professionals counseling men with prostate cancer regarding diet and secondary prevention.

History of diabetes, clinical features of prostate cancer, and prostate cancer recurrence-data from CaPSURE (United States).

OBJECTIVES: There is a growing epidemiologic literature suggesting an inverse association between history of diabetes and risk of incident prostate cancer. To our knowledge, the relationship between diabetes and tumor features and risk of recurrence among men with prostate cancer has not been examined previously. We hypothesized that men with diabetes would present with more favorable prostate cancer and experience lower risk of recurrence. METHODS: We identified 691 men with diabetes at the time of prostate cancer diagnosis, among 6722 men diagnosed with prostate cancer in 1989 to 2002 within CaPSURE(TM), a community-based prostate cancer registry study. We compared clinical and socio-demographic variables by diabetes status, using chi2 tests, t-tests, and multinomial logistic regression. We examined recurrence rates for prostate cancer among patients with and without diabetes using Kaplan-Meier log-rank tests and Cox proportional hazard models. RESULTS: In multivariate analyses, history of diabetes was not associated with any diagnostic clinical parameter, and treatment-specific recurrence rates for prostate cancer generally did not differ by diabetes history. Among men with low-prognostic risk or who were younger at prostate cancer diagnosis, being diabetic (versus not) was associated with an elevated risk of recurrence after radiation therapy, in multivariate analyses. CONCLUSIONS: Contrary to data suggesting that diabetes may be modestly protective against risk of incident prostate cancer, we did not observe any evidence of an inverse association between history of diabetes and aggressiveness at diagnosis or risk of recurrence, in this population of men with prostate cancer.

Milk intake, circulating levels of insulin-like growth factor-I, and risk of colorectal cancer in men.

BACKGROUND: Milk and dietary calcium may have antiproliferative effects against colorectal cancer, but milk intake also raises serum levels of insulin-like growth factor-I (IGF-I). A high ratio of IGF-I to IGF-binding protein-3 (IGFBP-3) has been linked to an increased risk of colorectal cancer. METHODS: In a case-control study nested in the Physicians' Health Study, plasma samples were collected from the period 1982 through 1983 from 14 916 men, aged 40-84 years, who also answered dietary questionnaires. Circulating levels of IGF-I and IGFBP-3 were assayed among 193 men who developed colorectal cancer during 13 years of follow-up and 318 age- and smoking-matched cancer-free control men. Conditional logistic regression was used to assess relative risks (RRs) of colorectal cancer for tertiles of IGF-I/IGFBP-3 and dietary factors. Statistical tests were two-sided. RESULTS: Overall, there was a moderate but statistically nonsignificant inverse association between intake of low-fat milk or calcium from dairy food and colorectal cancer risk. Intake of dairy food (especially low-fat milk) was also positively and moderately associated with plasma levels of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 among control men. We observed a statistically significant interaction between low-fat milk intake and IGF-I/IGFBP-3 in association with risk of colorectal cancer (P(interaction) =.03). Nondrinkers with IGF-I/IGFBP-3 in the highest tertile had a threefold higher risk than nondrinkers with IGF-I/IGFBP-3 in the lowest tertile (RR = 3.05; 95% confidence interval [CI] = 1.29 to 7.24), but no such increase was seen among frequent low-fat milk drinkers (RR = 1.05; 95% CI = 0.41 to 2.69). Conversely, among men with high IGF-I/IGFBP-3, frequent low-fat milk drinkers had a 60% lower risk (95% CI = 0.17 to 0.87; P(trend) =.02) than nondrinkers. CONCLUSION: Intake of dairy products was associated with a modest increase in circulating IGF-I levels, but intake of low-fat milk was associated with lower risk of colorectal cancer, particularly among individuals with high IGF-I/IGFBP-3. This subpopulation, which is at increased risk of colorectal cancer, might benefit the most from specific dietary intervention.

Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study.

BACKGROUND: A high calcium intake, mainly from dairy products, may increase prostate cancer risk by lowering concentrations of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a hormone thought to protect against prostate cancer. The results of epidemiologic studies of this hypothesis are inconclusive. OBJECTIVE: We investigated the association between dairy product and calcium intakes and prostate cancer risk in the Physicians' Health Study, a cohort of male US physicians. DESIGN: At baseline, the men answered abbreviated dietary questionnaires. During 11 y of follow-up, we documented 1012 incident cases of prostate cancer among 20885 men. We estimated dairy calcium intake on the basis of consumption of 5 major dairy products and used logistic regression to estimate relative risk. RESULTS: At baseline, men who consumed >600 mg Ca/d from skim milk had lower plasma 1,25(OH)(2)D(3) concentrations than did those consuming < or =150 mg Ca/d [71 compared with 85 pmol/L (30.06 compared with 35.64 pg/mL); P = 0.005]. Compared with men consuming < or =0.5 daily servings of dairy products, those consuming >2.5 servings had a multivariate relative risk of prostate cancer of 1.34 (95% CI: 1.04, 1.71) after adjustment for baseline age, body mass index, smoking, exercise, and randomized treatment assignment in the original placebo-controlled trial. Compared with men consuming < or =150 mg Ca/d from dairy products, men consuming >600 mg/d had a 32% higher risk of prostate cancer (95% CI: 1.08, 1.63). CONCLUSIONS: These results support the hypothesis that dairy products and calcium are associated with a greater risk of prostate cancer.