Efficacy of three BCG strains (Connaught, TICE and RIVM) with or without secondary resection (re-TUR) for intermediate/high-risk non-muscle-invasive bladder cancers: results from a retrospective single-institution cohort analysis

Purpose: (I) To evaluate the clinical efficacy of three different BCG strains in patients with intermediate-/high-risk non-muscle-invasive bladder cancer (NMIBC). (II) To determine the importance of performing routine secondary resection (re-TUR) in the setting of BCG maintenance protocol for the three strains. Methods: NMIBCs who received an adjuvant induction followed by a maintenance schedule of intravesical immunotherapy with BCG Connaught, TICE and RIVM. Only BCG-naïve and those treated with the same strain over the course of follow-up were included. Cox proportional hazards model was developed according to prognostic factors by the Spanish Urological Oncology Group (CUETO) as well as by adjusting for the implementation of re-TUR. Results: n = 422 Ta-T1 patients (Connaught, n = 146; TICE, n = 112 and RIVM, n = 164) with a median (IQR) follow-up of 72 (60-85) were reviewed. Re-TUR was associated with improved recurrence and progression outcomes (HRRFS: 0.63; 95% CI 0.46-0.86; HRPFS: 0.55; 95% CI 0.31-0.86). Adjusting for CUETO risk factors and re-TUR, BGC TICE and RIVM provided longer RFS compared to Connaught (HRTICE: 0.58, 95% CI 0.39-0.86; HRRIVM: 0.61, 95% CI 0.42-0.87) while no differences were identified between strains for PFS and CSS. Sub-analysis of only re-TUR cases (n = 190, 45%) showed TICE the sole to achieve longer RFS compared to both Connaught and RIVM. Conclusion: Re-TUR was confirmed to ensure longer RFS and PFS in intermediate-/high-risk NMIBCs but did not influence the relative single BCG strain efficacy. When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to the other strains for RFS outcomes

Protocol for: Sheffield Obesity Trial (SHOT): A randomised controlled trial of exercise therapy and mental health outcomes in obese adolescents [ISRCNT83888112]

Background While obesity is known to have many physiological consequences, the psychopathology of this condition has not featured prominently in the literature. Cross-sectional studies have indicated that obese children have increased odds of experiencing poor quality of life and mental health. However, very limited trial evidence has examined the efficacy of exercise therapy for enhancing mental health outcomes in obese children, and the Sheffield Obesity Trial (SHOT) will provide evidence of the efficacy of supervised exercise therapy in obese young people aged 11–16 years versus usual care and an attention-control intervention. Method/design SHOT is a randomised controlled trial where obese young people are randomised to receive; (1) exercise therapy, (2) attention-control intervention (involving body-conditioning exercises and games that do not involve aerobic activity), or (3) usual care. The exercise therapy and attention-control sessions will take place three times per week for eight weeks and a six-week home programme will follow this. Ninety adolescents aged between 11–16 years referred from a children's hospital for evaluation of obesity or via community advertisements will need to complete the study. Participants will be recruited according to the following criteria: (1) clinically obese and aged 11–16 years (Body Mass Index Centile > 98th UK standard) (2) no medical condition that would restrict ability to be active three times per week for eight weeks and (3) not diagnosed with insulin dependent diabetes or receiving oral steroids. Assessments of outcomes will take place at baseline, as well as four (intervention midpoint) and eight weeks (end of intervention) from baseline. Participants will be reassessed on outcome measures five and seven months from baseline. The primary endpoint is physical self-perceptions. Secondary outcomes include physical activity, self-perceptions, depression, affect, aerobic fitness and BMI

Interprofessional communication with hospitalist and consultant physicians in general internal medicine : a qualitative study

This study helps to improve our understanding of the collaborative environment in GIM, comparing the communication styles and strategies of hospitalist and consultant physicians, as well as the experiences of providers working with them. The implications of this research are globally important for understanding how to create opportunities for physicians and their colleagues to meaningfully and consistently participate in interprofessional communication which has been shown to improve patient, provider, and organizational outcomes

Behavioral Inhibition and Attentional Control in Adolescents: Robust Relationships with Anxiety and Depression

Behavioral inhibition (BI) has been associated with the development of internalizing disorders in children and adolescents. It has further been shown that attentional control (AC) is negatively associated with internalizing problems. The combination of high BI and low AC may particularly lead to elevated symptomatology of internalizing behavior. This study broadens existing knowledge by investigating the additive and interacting effects of BI and AC on the various DSM-IV based internalizing dimensions. A sample of non-clinical adolescents (N = 1806, age M = 13.6 years), completed the Behavioral Inhibition System/Behavioral Activation System Scales (BIS/BAS), the attentional control subscale of the Adult Temperament Questionnaire (ATQ) and the Revised Child Anxiety and Depression Scale (RCADS). As expected, BI was positively, and AC was negatively related to internalizing dimensions, with stronger associations of BI than of AC with anxiety symptoms, and a stronger association of AC than of BI with depressive symptoms. AC moderated the association between BI and all measured internalizing dimensions (i.e., symptoms of generalized anxiety disorder, social phobia, separation anxiety disorder, panic disorder, obsessive–compulsive disorder, and major depressive disorder). Since high AC may reduce the impact of high BI on the generation of internalizing symptoms, an intervention focused on changing AC may have potential for prevention and treatment of internalizing disorders

A new method for determining physician decision thresholds using empiric, uncertain recommendations

<p>Abstract</p> <p>Background</p> <p>The concept of risk thresholds has been studied in medical decision making for over 30 years. During that time, physicians have been shown to be poor at estimating the probabilities required to use this method. To better assess physician risk thresholds and to more closely model medical decision making, we set out to design and test a method that derives thresholds from actual physician treatment recommendations. Such an approach would avoid the need to ask physicians for estimates of patient risk when trying to determine individual thresholds for treatment. Assessments of physician decision making are increasingly relevant as new data are generated from clinical research. For example, recommendations made in the setting of ocular hypertension are of interest as a large clinical trial has identified new risk factors that should be considered by physicians. Precisely how physicians use this new information when making treatment recommendations has not yet been determined.</p> <p>Results</p> <p>We derived a new method for estimating treatment thresholds using ordinal logistic regression and tested it by asking ophthalmologists to review cases of ocular hypertension before expressing how likely they would be to recommend treatment. Fifty-eight physicians were recruited from the American Glaucoma Society. Demographic information was collected from the participating physicians and the treatment threshold for each physician was estimated. The method was validated by showing that while treatment thresholds varied over a wide range, the most common values were consistent with the 10-15% 5-year risk of glaucoma suggested by expert opinion and decision analysis.</p> <p>Conclusions</p> <p>This method has advantages over prior means of assessing treatment thresholds. It does not require physicians to explicitly estimate patient risk and it allows for uncertainty in the recommendations. These advantages will make it possible to use this method when assessing interventions intended to alter clinical decision making.</p

?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of ?2-microglobulin (?2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which ?2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of ?2m monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibril-induced membrane damage. We show that ?2m fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between ?2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of ?2m amyloid-associated osteoarticular tissue destruction in DRA

In Vivo, Multimodal Imaging of B Cell Distribution and Response to Antibody Immunotherapy in Mice

BACKGROUND: B cell depletion immunotherapy has been successfully employed to treat non-Hodgkin's lymphoma. In recent years, increasing attention has been directed towards also using B-cell depletion therapy as a treatment option in autoimmune disorders. However, it appears that the further development of these approaches will depend on a methodology to determine the relation of B-cell depletion to clinical response and how individual patients should be dosed. Thus far, patients have generally been followed by quantification of peripheral blood B cells, but it is not apparent that this measurement accurately reflects systemic B cell dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Cellular imaging of the targeted population in vivo may provide significant insight towards effective therapy and a greater understanding of underlying disease mechanics. Superparamagnetic iron oxide (SPIO) nanoparticles in concert with near infrared (NIR) fluorescent dyes were used to label and track primary C57BL/6 B cells. Following antibody mediated B cell depletion (anti-CD79), NIR-only labeled cells were expeditiously cleared from the circulation and spleen. Interestingly, B cells labeled with both SPIO and NIR were not depleted in the spleen. CONCLUSIONS/SIGNIFICANCE: Whole body fluorescent tracking of B cells enabled noninvasive, longitudinal imaging of both the distribution and subsequent depletion of B lymphocytes in the spleen. Quantification of depletion revealed a greater than 40% decrease in splenic fluorescent signal-to-background ratio in antibody treated versus control mice. These data suggest that in vivo imaging can be used to follow B cell dynamics, but that the labeling method will need to be carefully chosen. SPIO labeling for tracking purposes, generally thought to be benign, appears to interfere with B cell functions and requires further examination

The Assembly of Individual Chaplin Peptides from Streptomyces coelicolor into Functional Amyloid Fibrils

The self-association of proteins into amyloid fibrils offers an alternative to the natively folded state of many polypeptides. Although commonly associated with disease, amyloid fibrils represent the natural functional state of some proteins, such as the chaplins from the soil-dwelling bacterium Streptomyces coelicolor, which coat the aerial mycelium and spores rendering them hydrophobic. We have undertaken a biophysical characterisation of the five short chaplin peptides ChpD-H to probe the mechanism by which these peptides self-assemble in solution to form fibrils. Each of the five chaplin peptides produced synthetically or isolated from the cell wall is individually surface-active and capable of forming fibrils under a range of solution conditions in vitro. These fibrils contain a highly similar cross-β core structure and a secondary structure that resembles fibrils formed in vivo on the spore and mycelium surface. They can also restore the growth of aerial hyphae to a chaplin mutant strain. We show that cysteine residues are not required for fibril formation in vitro and propose a role for the cysteine residues conserved in four of the five short chaplin peptides

Use of dietary supplements by female seniors in a large Northern California health plan

BACKGROUND: Women aged ≥ 65 years are high utilizers of prescription and over-the-counter medications, and many of these women are also taking dietary supplements. Dietary supplement use by older women is a concern because of possible side effects and drug-supplement interactions. The primary aim of this study was to provide a comprehensive picture of dietary supplement use among older women in a large health plan in Northern California, USA, to raise awareness among health care providers and pharmacists about the need for implementing structural and educational interventions to minimize adverse consequences of self-directed supplement use. A secondary aim was to raise awareness about how the focus on use of herbals and megavitamins that has occurred in most surveys of complementary and alternative therapy use results in a significant underestimate of the proportion of older women who are using all types of dietary supplements for the same purposes. METHODS: We used data about use of different vitamin/mineral (VM) supplements and nonvitamin, nonmineral (NVNM) supplements, including herbals, from a 1999 general health survey mailed to a random sample of adult members of a large Northern California health plan to estimate prevalence of and characteristics associated with supplement use among women aged 65–84 (n = 3,109). RESULTS: Based on weighted data, 84% had in the past 12 months used >1 dietary supplement, 82% a VM, 59% a supplement other than just multivitamin or calcium, 32% an NVNM, and 25% an herbal. Compared to white, nonHispanic women, African-Americans and Latinas were significantly less likely to use VM and NVNM supplements and Asian/Pacific Islanders were less likely to use NVNM supplements. Higher education was strongly associated with use of an NVNM supplement. Prevalence did not differ by number of prescription medications taken. Among white, nonHispanic women, multiple logistic regression models showed that college education, good health, belief that health practices have at least a moderate effect on health, and having arthritis or depression significantly increased likelihood of NVNM use, while having diabetes decreased likelihood. CONCLUSIONS: An extremely high proportion of older women are using dietary supplements other than multivitamins and calcium, many in combination with multiple prescription medications. Increased resources should be devoted to helping clinicians, pharmacists, supplement vendors, and consumers become more aware of the safety, effectiveness, and potential side effects of dietary supplements

Enhanced Eyelashes: Prescription and Over-the-Counter Options

Women have long strived to possess long, thick, and dark eyelashes. Prominent eyes and eyelashes are often considered a sign of beauty and can be associated with increased levels of attractiveness, confidence, and well-being. Numerous options may improve the appearance of eyelashes. Mascara aims to temporarily darken, lengthen, and thicken eyelashes using a combination of waxes, pigments, and resins. Artificial eyelashes can be adhered either to the dermal margin or to individual eyelashes. Individuals may even use eyelash transplantations to improve the appearance of their eyelashes. The unique properties of eyelashes (e.g., relatively long telogen and short anagen phases compared with scalp hairs, slow rate of growth, and a lack of influence by androgens) may allow for specific aesthetic interventions to improve the appearance of natural eyelashes. Some over-the-counter (OTC) products may contain prostaglandin analogs that can affect eyelash growth, but neither the safety nor efficacy of these OTC cosmetics has been fully studied. Originally indicated for the reduction of intraocular pressure, the synthetic prostaglandin analog bimatoprost was recently approved for the treatment of hypotrichosis of the eyelashes. In a double-blinded, randomized, vehicle-controlled trial, bimatoprost safely and effectively grew natural eyelashes, making them longer, thicker, and darker. Bimatoprost was generally safe and well tolerated and appears to provide an additional option for individuals looking to improve the appearance of their eyelashes