Cognitive improvement in patients with carotid stenosis is independent of treatment type

Treatment of carotid artery stenosis decreases the long-term risk of stroke and may enhance cerebral blood flow. It is therefore expected to have the potential to prevent cognitive decline or even improve cognition over the long-term. However, intervention itself can cause peri-interventional cerebral infarcts, possibly resulting in a decline of cognitive performance, at least for a short time. We investigated the long-term effects of three treatment methods on cognition and the emotional state one year after intervention. In this prospective observational cohort study, 58 patients with extracranial carotid artery stenosis (≥70%) underwent magnetic resonance imaging and assessment of cognition, mood and motor speed before carotid endarterectomy (n = 20), carotid stenting (n = 10) or best medical treatment (n = 28) (i.e., time-point 1 [TP1]), and at one-year follow-up (TP2). Gain scores, reflecting cognitive change after treatment, were built according to performance as (TP2 -TP1)/TP1. Independent of the treatment type, significant improvement in frontal lobe functions, visual memory and motor speed was found. Performance level, motor speed and mood at TP1 were negatively correlated with gain scores, with greater improvement in patients with low performance before treatment. Active therapy, whether conservative or interventional, produces significant improvement of frontal lobe functions and memory in patients with carotid artery disease, independent of treatment type. This effect was particularly pronounced in patients with low cognitive performance prior to treatment.

Do clinicians understand the size of treatment effects? A randomized survey across 8 countries.

BACKGROUND Meta-analyses of continuous outcomes typically provide enough information for decision-makers to evaluate the extent to which chance can explain apparent differences between interventions. The interpretation of the magnitude of these differences - from trivial to large - can, however, be challenging. We investigated clinicians' understanding and perceptions of usefulness of 6 statistical formats for presenting continuous outcomes from meta-analyses (standardized mean difference, minimal important difference units, mean difference in natural units, ratio of means, relative risk and risk difference). METHODS We invited 610 staff and trainees in internal medicine and family medicine programs in 8 countries to participate. Paper-based, self-administered questionnaires presented summary estimates of hypothetical interventions versus placebo for chronic pain. The estimates showed either a small or a large effect for each of the 6 statistical formats for presenting continuous outcomes. Questions addressed participants' understanding of the magnitude of treatment effects and their perception of the usefulness of the presentation format. We randomly assigned participants 1 of 4 versions of the questionnaire, each with a different effect size (large or small) and presentation order for the 6 formats (1 to 6, or 6 to 1). RESULTS Overall, 531 (87.0%) of the clinicians responded. Respondents best understood risk difference, followed by relative risk and ratio of means. Similarly, they perceived the dichotomous presentation of continuous outcomes (relative risk and risk difference) to be most useful. Presenting results as a standardized mean difference, the longest standing and most widely used approach, was poorly understood and perceived as least useful. INTERPRETATION None of the presentation formats were well understood or perceived as extremely useful. Clinicians best understood the dichotomous presentations of continuous outcomes and perceived them to be the most useful. Further initiatives to help clinicians better grasp the magnitude of the treatment effect are needed.

Guidance of treatment decisions in risk-adapted primary radiotherapy for prostate cancer using multiparametric magnetic resonance imaging: a single center experience.

BACKGROUND Magnetic resonance imaging (MRI) of the prostate is considered to be the most precise noninvasive staging modality for localized prostate cancer. Multiparametric MRI (mpMRI) dynamic sequences have recently been shown to further increase the accuracy of staging relative to morphological imaging alone. Correct radiological staging, particularly the detection of extraprostatic disease extension, is of paramount importance for target volume definition and dose prescription in highly-conformal curative radiotherapy (RT); in addition, it may affect the risk-adapted duration of additional antihormonal therapy. The purpose of our study was to analyze the impact of mpMRI-based tumor staging in patients undergoing primary RT for prostate cancer. METHODS A total of 122 patients admitted for primary RT for prostate cancer were retrospectively analyzed regarding initial clinical and computed tomography-based staging in comparison with mpMRI staging. Both tumor stage shifts and overall risk group shifts, including prostate-specific antigen (PSA) level and the Gleason score, were assessed. Potential risk factors for upstaging were tested in a multivariate analysis. Finally, the impact of mpMRI-based staging shift on prostate RT and antihormonal therapy was evaluated. RESULTS Overall, tumor stage shift occurred in 55.7% of patients after mpMRI. Upstaging was most prominent in patients showing high-risk serum PSA levels (73%), but was also substantial in patients presenting with low-risk PSA levels (50%) and low-risk Gleason scores (45.2%). Risk group changes occurred in 28.7% of the patients with consequent treatment adaptations regarding target volume delineation and duration of androgen deprivation therapy. High PSA levels were found to be a significant risk factor for tumor upstaging and newly diagnosed seminal vesicle infiltration assessed using mpMRI. CONCLUSIONS Our findings suggest that mpMRI of the prostate leads to substantial tumor upstaging, and can considerably affect treatment decisions in all patient groups undergoing risk-adapted curative RT for prostate cancer.

High-risk drug use and sexual behaviors among out-of-treatment drug users: An aging and life course perspective

High-risk injection drug use and the sexual behaviors that accompany it have large social and financial costs. Tailored treatments have been shown to successfully reduce high-risk behaviors. However, little is known about how age and age at first drug use are related to high-risk injection or sex behaviors. The current study draws on life course theory and hypothesizes that age will have a strong relationship with high-risk behaviors of out-of-treatment drug users. Data from the NIDA Cooperative Agreement was used to analyze the relationship between (1) age, and (2) age at first drug use with seven high-risk injection and sexual behavior variables. Negative binomial regression models revealed that high-risk sexual behavior decreases between 15.8 and 20.9% with each decade of age, while high-risk injection behavior increases between 32 and 67% with each decade of age after the addition of demographic controls. Both high-risk injection and high-risk sex behaviors are significantly reduced with a delayed age at first drug use. Previous research promotes interventions to reduce the high-risk sexual behaviors of older drug users. The current study suggests a refocusing of public health efforts on the high-risk injection habits of older drug users.^

Effects of treatment on orienting in Parkinson disease

Parkinson disease (PD) is a movement disorder affecting over one million Americans, and 1% of our population over 60 years of age. Currently, PD has an unknown cause, no predictive biomarker, and no cure, yet there are effective treatments (medicine and surgery) to chronically manage the motor symptoms. But, PD patients also develop cognitive symptoms (e.g., distractibility, executive dysfunction) that remain untreated or may decline as a result of treating the motor symptoms. To address this important issue, I measured covert orienting of attention and overt eye movements in PD patients to assess the patients' ability to automatically detect stimuli in their visual field, to predict and attend to where the stimuli would appear, and to volitionally look somewhere else. ^ PD patients completed the cognitive tasks under multiple treatment conditions, and their performance was compared to healthy adults. PD patients first completed the tasks after they had withdrawn from medication. Their unmedicated performance revealed exaggerated automatic orienting, poor predictability, and weak volitional orienting. PD patients then repeated the tasks while medication was giving its peak benefit. The medication returned automatic covert orienting toward normal but did not improve volitional covert orienting. Several PD patients completed the tasks a third time after receiving surgery (specifically, implantation of stimulating electrodes in a subcortical brain region to alleviate motor symptoms). The stimulation (without medication) returned automatic orienting toward normal, did not change predictability, and further impaired volitional orienting. Taken together, treatments prescribed to alleviate the motor symptoms (a patient's primary concern) only improve some cognitive functions. Future studies may establish criteria to predict which patients are more likely to have cognitive benefit from medication over surgery, or vice versa. ^ I have also hypothesized an anatomical model relating orienting circuitry to abnormal PD circuitry and the therapeutic targets. My results suggest medication is more effective restoring the orienting circuitry than stimulation. Further, automatic and volitional orienting abilities seem to be modulated independently, which differs from an earlier model proposing a dependent, inverse relationship. My results are further discussed in terms of response inhibition, response selection, and the location of the selection. ^

A study of nurses' perceptions of and participation in the resolution of treatment dilemmas for critically ill newborns

This study was an exploratory investigation of variables which are associated with neonatal intensive care nurses' perceptions of and participation in life-sustaining treatment decisions for critically ill newborns. The primary purpose of the research was to examine the extent to which assessment of infants' physical and mental prognoses, parents' preferences regarding treatment, and legal consequences of non-treatment influence nurses' recommendations about life-saving treatment decisions for handicapped newborns. Secondly, the research explored the extent and nature of nurses' reported participation in the resolution of treatment dilemmas for these critically ill newborns. The framework of the study draws upon the work of Crane (1977), Blum (1980), and Pearlman (1982) who have explored the sociological context of decision-making with critical care patients.^ Participants in the study were a volunteer sample of eighty-three registered nurses who were currently working in neonatal intensive care units in five large urban hospitals in Texas. Data were collected through the use of intensive interviews and case study questionnaires. Results from the study indicate that physical and mental prognoses as well as parent preferences and concerns about legal liability are related to nurses' treatment recommendations, but their levels of significance vary according to the type of handicapping condition and whether the treatment questions are posed in terms of initiating aggressive therapy or withdrawing aggressive therapy.^ The majority of nurses reported that the extent of their participation in formal decision-making regarding handicapped newborns was fairly minimal although they provide much of the definitive data used to make decisions by physicians and parents. There was substantial evidence that nurse respondents perceive their primary role as advocates for critically ill newborns, and believe that their involvement in the resolution of treatment dilemmas should be increased. ^

Analysis of interval -censored events in hypertension studies: Evaluation of treatment of coronary heart disease

Many statistical studies feature data with both exact-time and interval-censored events. While a number of methods currently exist to handle interval-censored events and multivariate exact-time events separately, few techniques exist to deal with their combination. This thesis develops a theoretical framework for analyzing a multivariate endpoint comprised of a single interval-censored event plus an arbitrary number of exact-time events. The approach fuses the exact-time events, modeled using the marginal method of Wei, Lin, and Weissfeld, with a piecewise-exponential interval-censored component. The resulting model incorporates more of the information in the data and also removes some of the biases associated with the exclusion of interval-censored events. A simulation study demonstrates that our approach produces reliable estimates for the model parameters and their variance-covariance matrix. As a real-world data example, we apply this technique to the Systolic Hypertension in the Elderly Program (SHEP) clinical trial, which features three correlated events: clinical non-fatal myocardial infarction, fatal myocardial infarction (two exact-time events), and silent myocardial infarction (one interval-censored event). ^

Influencia del tratamiento "a fuego" en las características del estuco tradicional con cal = Influence of treatment "by fire" in the characteristics of traditional lime stucco

Esta investigación avanza en el intento de recuperar la técnica tradicional del estuco a fuego, paradigma de la decoración de espacios interiores hasta la mitad del s. XX por sus imitaciones marmóreas de gran calidad. Para ejecutarlos se utilizaban morteros de cal con áridos de mármol, pigmentos minerales y grasas; con estos materiales se preparaban y tendían las masas, se pintaban al fresco y se terminaban con el paso de una herramienta metálica caliente. Como sucede con otras técnicas, el paso del tiempo ha difuminado los conocimientos sobre la materia, haciendo muy difícil la conservación o restauración de los ejemplos en nuestro patrimonio. A partir de la escasa bibliografía existente se ha recuperado el proceso, sometiendo las muestras elaboradas a diferentes ensayos que han caracterizado el acabado final,tanto en sus características intrínsecas como en las que le son conferidas al proteger finalmente las muestras con una capa de cera, tal y como se realizaba tradicionalmente.---ABSTRACT---This research advances in the attempt to recover the traditional technique of stucco by fire; paradigm of indoor decoration until half of 20th century due to its high quality marbled imitations. On its implementation process, it was used lime mortars with marble aggregates, mineral pigments and greases. With these materials, masses were prepared and extended into the walls, they were painted in fresco and ended with the passage of a heated metal tool. As with any other technique, the time passing over has blurred the knowledge on the subject, making very difficult the preservation or restoration of examples in our heritage. Despite of the limited literature, the process has been recovered; subjecting the samples prepared at different trials that have characterized the finished, both in its merits and its conferred characteristics by finally protecting the samples with a layer of wax, as was done traditionally.

Reduction of HIV-1 in blood and lymph nodes following potent antiretroviral therapy and the virologic correlates of treatment failure

Potent antiretroviral therapy can reduce plasma HIV RNA levels below the threshold of detection for periods of a year or more. The magnitude of HIV RNA reduction in the lymphoid tissue in patients with suppression of HIV RNA levels in plasma beyond 6 months has not been determined. We evaluated levels of HIV RNA and DNA and characterized resistance mutations in blood and inguinal lymph node biopsies obtained from 10 HIV-infected subjects who received 36–52 weeks of indinavir (IDV)/zidovudine (ZDV)/lamivudine (3TC), IDV, or ZDV/3TC. After 1 year of therapy, viral RNA levels in LN of individuals remained detectable but were log10 = 4 lower than in subjects on the triple drug regimen with interruption of therapy or in those treated with ZDV/3TC alone, who had viral loads in their lymph nodes indistinguishable from those expected for untreated patients. In all cases viral DNA remained detectable in lymph nodes and peripheral blood mononuclear cells (PBMC). When plasma virus suppression was incomplete, lymph node and PBMC cultures were positive and drug resistance developed. These studies indicate that pronounced and sustained suppression of plasma viremia by a potent antiretroviral combination is associated with low HIV RNA levels in the lymph nodes 1 year after treatment. Conversely, the persistence of even modest levels of plasma virus after 1 year of treatment reflects ongoing viral replication, the emergence of drug resistance, and the maintenance of high burdens of virus in the lymph nodes.