Transfusion-associated circulatory overload prevention: a retrospective observational study of diuretic use.

BACKGROUND AND OBJECTIVES: Approaches to preventing transfusion-associated circulatory overload (TACO) include the use of diuretics. The purpose of this study was to determine how commonly diuretics are prescribed in patients receiving a red-blood-cell (RBC) transfusion. MATERIALS AND METHODS: This was a retrospective study of 200 adult inpatient RBC transfusion orders, 50 consecutive at each of four academic institutions. Only the first transfusion order for each patient was included. Only 1 or 2 unit orders were included. The primary outcome was the percentage of patients receiving furosemide peri-transfusion. Secondary objectives included the dose, route, and timing of furosemide and the association of clinical factors with ordering furosemide. RESULTS: The median age was 62·5 years (IQR 53, 73), and 52% were female. Peri-transfusion furosemide was ordered in 16% (95% CI 11-21%). The most common dose was 20 mg (55%), the route intravenous (90%) and timing post-transfusion (74%). At least one risk factor for TACO was present in 55% of patients: renal dysfunction (33%), older than 70 years (28%), history of congestive heart failure (18%), ejection fraction <60% (16%) and diastolic dysfunction (5%). Low haemoglobin as an indication for transfusion (OR 4·2; 95% CI 1·4-12·8) and diuretics on admission (OR 3·5; 95% CI 1·5-8·0) were associated with ordering furosemide peri-transfusion. CONCLUSIONS: Furosemide is not routinely ordered for RBC transfusion, even in patients with risk factors for TACO. Studies assessing the safety, efficacy, optimal dose, and timing of furosemide in preventing TACO are justified.

Audit of appropriate use of platelet transfusions: validation of adjudication criteria.

BACKGROUND AND OBJECTIVES: Platelet (PLT) transfusions must be used appropriately, as they are in chronic short supply, costly and risky to patients. The goals of this audit were to: (1) validate preset adjudication criteria through an audit of appropriateness at four large academic hospitals; (2) identify variability in appropriateness across medical services, physician specialties or hospital locations; and (3) inform logistical or educational interventions that may reduce inappropriate use. MATERIALS AND METHODS: A chart review of two hundred patients receiving PLT transfusions was performed. Fifty consecutive transfusion episodes per site were audited in detail. Each transfusion episode was independently adjudicated as appropriate or inappropriate by two transfusion specialists based on predetermined criteria. RESULTS: The adjudication criteria performed well with simple agreement of 95% (kappa statistic 0·83) between reviewers. Overall, 78% (95% CI: 72-84%) of PLT transfusions were adjudicated as appropriate, with results varying significantly by hospital site (range 62-94%). Prophylactic transfusions for non-bleeding patients had the highest proportion of appropriateness (85%, n = 80), and therapeutic transfusions for bleeding patients had the lowest (73%, n = 99). The lowest levels of appropriate platelet transfusions were observed in the operating rooms (60%) and when ordered by the general surgery service (55%). CONCLUSIONS: One in five platelet transfusions may be unnecessary, suggesting that interventions to improve PLT transfusion practice are warranted.

Reactivity to unpredictable threat as a treatment target for fear-based anxiety disorders.

BACKGROUND: Heightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT). METHODS: Participants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding. RESULTS: Across both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable. CONCLUSIONS: Together, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.

The association of fever with transfusion-associated circulatory overload.

BACKGROUND: Fever is described in transfusion-associated circulatory overload (TACO), reflecting either comprehensive haemovigilance or an inflammatory pathobiology (such as congestion-associated atheroma disruptions). METHODS: Hospital haemovigilance data (1/1/2010-31/12/2012) were reviewed for TACO cases (frequency and mode of referral). TACO with or without fever (TACO+F/-F) was examined for its association with patient age (as a surrogate for atheroma burden) and product age (as a surrogate for storage-related pyrogens). Fever in allergic transfusion reactions was also compared. RESULTS: Of 972 reactions, 107 suspected cases of TACO (11%) were seen. TACO+F vs. TACO-F occurred in 42·1 vs. 57·9%, respectively. TACO+F cases were discovered in referrals to investigate either a fever (in 47·1%) or dyspnoea (in 52·9%). Among TACO+F cases, 24·4% had already been febrile, whereas 75·6% exhibited a new reaction-associated fever. After excluding preexisting fevers, TACO+F occurred in 31·8% of TACO, compared with 8·2% of allergic reactions with fever, for an odds ratio of 5·2 (2·9-9·4 [95% CI]), P < 0·001. TACO+F/TACO-F showed no difference in median host age (69 vs. 64 years, P = 0·3), RBC age (22 days +F/-F, P = 0·9) or severity. CONCLUSION: Transfusion-associated circulatory overload disproportionately exhibits fever compared with allergic reactions. However, TACO+F did not associate with patient or product age, nor reflect severity. To better understand TACO+F, the fever-congestion sequence merits attention. Further study is needed to see whether TACO+F occurs as reproducibly elsewhere, and in association with atherosclerosis in a better characterized cohort.

Reactivity to uncertain threat as a familial vulnerability factor for alcohol use disorder.

BACKGROUND: When sober, problematic drinkers display exaggerated reactivity to threats that are uncertain (U-threat). Since this aversive affective state can be alleviated via acute alcohol intoxication, it has been posited that individuals who exhibit heightened reactivity to U-threat at baseline are motivated to use alcohol as a means of avoidance-based coping, setting the stage for excessive drinking. To date, however, no study has attempted to characterize the dispositional nature of exaggerated reactivity to U-threat and test whether it is a vulnerability factor or exclusively a disease marker of problematic alcohol use. METHOD: The current investigation utilized a family study design to address these gaps by examining whether (1) reactivity to U-threat is associated with risk for problematic alcohol use, defined by family history of alcohol use disorder (AUD) and (2) reactivity to U-threat is correlated amongst adult biological siblings. A total of 157 families, and 458 individuals, participated in the study and two biological siblings completed a threat-of-shock task designed to probe reactivity to U-threat and predictable threat (P-threat). Startle potentiation was collected as an index of aversive responding. RESULTS: Within biological siblings, startle potentiation to U-threat [intraclass correlation (ICC) = 0.35] and P-threat (ICC = 0.63) was significantly correlated. In addition, independent of an individuals' own AUD status, startle potentiation to U-threat, but not P-threat, was positively associated with risk for AUD (i.e. AUD family history). CONCLUSION: This suggests that heightened reactivity to U-threat may be a familial vulnerability factor for problematic drinking and a novel prevention target for AUD.

Consent for blood transfusion: do patients understand the risks and benefits?

BACKGROUND AND OBJECTIVES: Blood transfusion is a frequent medical intervention in hospitals. The benefits of, risks of and alternatives to blood transfusions are not consistently understood by patients. The objective of this study was to assess gaps in knowledge and comfort with the current process of consenting patients for blood transfusions. A standardised video regarding the risk and benefits of blood transfusions was developed and feedback regarding this tool was assessed. METHODS: After informed consent had been obtained, 25 patients receiving their first transfusion at a single academic centre were asked to complete a survey, watch a standardised educational video and complete a follow-up survey. RESULTS: The patient survey revealed that the information recollected from informed consent discussions was variable and incomplete. After the informed consent discussion, the majority of patients were comfortable with having a blood transfusion, although one-third did express concerns or worry about having a blood transfusion. After viewing the video, patients felt that the video improved their understanding of the risks (7·3 of 10), benefits (6·9 of 10) and alternatives (7·1 of 10) to transfusion, but it did not change their comfort with blood transfusion consent. CONCLUSION: Patients experienced a variable informed consent process prior to blood transfusion. Although the video improved their understanding of risks, it did not improve patient comfort towards giving consent for transfusion as the level of comfort was already high. The video is available online (http://www.youtube.com/watch?v=RxaPnLkgh-0) as an optional resource for patients (and physicians) who wish to receive standardised and accurate information about blood transfusions.

Efficacy and safety of hydrokinesitherapy in patients with dystrophinopathy.

Duchenne muscular dystrophy (DMD) is one of the most common forms of hereditary muscular dystrophies in childhood and is characterized by steady progression and early disability. It is known that physical therapy can slow down the rate of progression of the disease. According to global recommendations, pool exercises, along with stretching, are preferable for children with DMD, as these types of activities have a balanced effect on skeletal muscles and allow simultaneous breathing exercises. The present study aimed to evaluate the effectiveness of regular pool exercises in patients with Duchenne muscular dystrophy who are capable of independent movement during 4 months of training. 28 patients with genetically confirmed Duchenne muscular dystrophy, who were aged 6.9 ± 0.2 years, were examined. A 6-min distance walking test and timed tests, namely, rising from the floor, 10-meter running, and stair climbing and descending, muscle strength of the upper and lower extremities were assessed on the baseline and during dynamic observation at 2 and 4 months. Hydrorehabilitation course lasted 4 months and was divided into two stages: preparatory and training (depend on individual functional heart reserve (IFHR)). Set of exercises included pool dynamic aerobic exercises. Quantitative muscle MRI of the pelvic girdle and thigh was performed six times: before training (further BT) and after training (further AT) during all course. According to the results of the study, a statistically significant improvement was identified in a 6-min walking test, with 462.7 ± 6.2 m on the baseline and 492.0 ± 6.4 m after 4 months (p < 0.001). The results from the timed functional tests were as follows: rising from the floor test, 4.5 ± 0.3 s on the baseline and 3.8 ± 0.2 s after 4 months (p < 0.001); 10 meter distance running test, 4.9 ± 0.1 s on the baseline and 4.3 ± 0.1 s after 4 months (p < 0.001); 4-stair climbing test, 3.7 ± 0.2 s on the baseline and 3.2 ± 0.2 s after 4 months (p < 0.001); and 4-stair descent test, 3.9 ± 0.1 s on the baseline and 3.2 ± 0.1 s after 4 months (p < 0.001). Skeletal muscle quantitative MRI was performed in the pelvis and the thighs in order to assess the impact of the procedures on the muscle structure. Muscle water T2, a biomarker of disease activity, did not show any change during the training period, suggesting the absence of deleterious effects and negative impact on disease activity. Thus, a set of dynamic aerobic exercises in water can be regarded as effective and safe for patients with DMD.

Racial and ethnic differences in perceptions of campus climate related to sexual violence.

Objective: To assess perceptions of university institutional climate related to sexual violence and whether these differed by race/ethnicity. Participants: Matriculated undergraduates > age 18 (n = 1028). Methods: Students were invited via campus email to participate in an online survey. Results: Overall, only 20% agreed that the university is creating an environment in which unwanted sexual experiences seemed common or normal, but these findings differed by race. Black students were more likely than their white peers to feel the university is creating an environment in which unwanted sexual experiences seem common or normal (37.3% vs. 19.7%, p < .001) and creating an environment in which such instances were more likely to occur (33.3% vs. 13.4%, p < .001). Conclusions: Data suggest that while students generally perceive that the university is working to create a positive and safe climate, these perceptions vary by race. Further investigation is necessary to better understand the concerns of students of color.

The role of taste and appetite regulation in the understanding of overweight and obesity. Proceedings of the 16th Aschauer Soiree, 26th April 2008.

Overweight and obesity have developed into major illnesses in most Western societies and significantly contribute to the financial burden of modern public health systems. Almost daily, new therapeutic proposals are published in the lay press, and also the scientific literature has increased dramatically in recent years. E.g., when searching MEDLINE (1966 - May 2008 (1)), the key word "obesity" meanwhile appears in more than 108,000 articles. Primary focus however, is put upon aspects of treatment, neglecting the role of taste and appetite regulation. Combining keywords like "obesity + treatment" results in over 50.000 citations, "obesity + diet" in over 23.000, "obesity + energy + expenditure" in over 13.000 citations (even "obesity + gastric + bypass" still evoke 2.600 citations), whereas "obesity + appetite + regulation" result in some 3.000, "obesity + NPY" - neuropeptid Y being one of the major chemical stimulators of appetite - evoke some 500 and "obesity + Arc + nucleus" - the arcuate nucleus being the anatomical centre of appetite regulation - no more than 370 scientific publications. The apparent scarcity of literature about taste and appetite regulation and the amazing lack of interest in neuronal information processing in overweight and obesity, has prompted the authors to brainstorm new aspects of the world-wide derailment of weight control.

Anxiety-potentiated amygdala-medial frontal coupling and attentional control.

Anxiety disorders can be treated both pharmacologically and psychologically, but many individuals either fail to respond to treatment or relapse. Improving outcomes is difficult, in part because we have incomplete understanding of the neurobiological mechanisms underlying current treatments. In a sequence of studies, we have identified 'affective bias-related' amygdala-medial cortical coupling as a candidate substrate underlying adaptive anxiety (that is, anxiety elicited by threat of shock in healthy individuals) and shown that it is also chronically engaged in maladaptive anxiety disorders. We have provided evidence that this circuit can be modulated pharmacologically, but whether this mechanism can be shifted by simple psychological instruction is unknown. In this functional magnetic resonance imaging study, we extend a previously used translational anxiety induction (threat of shock) in healthy subjects (N=43) and cognitive task to include an element of instructed attentional control. Replicating our previous findings, we show that induced anxiety engages 'affective bias-related' amygdala-dorsal medial frontal coupling during the processing of emotional faces. By contrast, instructing subjects to attend to neutral shapes (and ignore faces) disengages this circuitry and increases putative 'attentional control-related' coupling between the amygdala and a more rostral prefrontal region. These neural coupling changes are accompanied by corresponding modulation of behavioural performance. Taken together, these findings serve to further highlight the potential role of amygdala-medial frontal coupling in the pathogenesis of anxiety and highlight a mechanism by which it can be modulated via psychological instructions. This, in turn, generates hypotheses for future work exploring the mechanisms underlying psychological therapeutic interventions for anxiety.

A prospective evaluation of thallium-201 single photon emission computerized tomography for brain tumor burden.

PURPOSE: The follow-up of patients with malignant brain tumors after surgery, radiation, and/or chemotherapy has been inadequate for evaluating brain tumor burden using computerized tomography (CT) or magnetic resonance imaging (MRI). Thallium-201 has been shown to concentrate in viable tumor, and Tl-201 single photon emission computerized tomography (SPECT) imaging can identify tumor burden more accurately than CT. METHODS AND MATERIALS: Thirty-one patients with glioblastoma and three patients with low grade astrocytoma were studied with Tl-201 SPECT. Histololgic diagnosis was obtained in all patients by biopsy and all patients had CT scans within 2 weeks of the SPECT study. Seventeen patients were followed with one or more SPECT and CT evaluations. RESULTS: Single photon emission computerized tomography studies, after surgery, radiotherapy, and/or chemotherapy, were more accurate than CT in identifying progression or regression of disease. Twenty-three patients had evidence of disease and 11 patients had no evidence of recurrent disease in the initial Tl-201 SPECT study following therapy. Computerized tomography identified 20 of the 23 patients with disease and 6 of 11 patients with no recurrent disease. Follow-up with Tl-201 SPECT in 17 patients suggested progression of disease in 9 patients, while CT showed progression in only 3 patients. Clinical examinations and repeat CT studies confirmed the accuracy of Tl-201 SPECT images. CONCLUSION: We found Tl-201 SPECT more accurate than CT scans in a prospective evaluation of 34 patients with brain tumor. Follow-up studies with both Tl-201 SPECT and CT imaging in 17 patients demonstrated that SPECT was more reliable than CT in identifying progression, improvement, or no change in brain tumor burden.

Tissue distribution of copper-labeled 3-ethoxy-2-oxobutyraldehyde bis (thiosemicarbazone) (Cu-64 KTS) in mice and rats: concise communication.

The antitumor activity of, 3-ethoxy-2-oxobutyraldehyde bis (thiosemicarbazone) (KTS), is related to the presence of copper(II) ion. We have studied the tissue distribution of Cu-64-labeled KTS in rats and mice carrying transplanted tumors to evaluate whether the uptake of the radioactivity in the tumor is adequate to warrant further investigation of the tracer as a tumor-seeking agent in patients. Four groups of three of four animals each were studied: (a) mice with fibrosarcoma; (b) mice with mammary adenocarcinoma; (c) rats with fibrosarcoma; and (d) rats with squamous cell carcinoma of the lung. The animals were killed at intervals of 0.25, 1, 4, 24, and 48 hr after i.v. injection of 1.6 X 10(-3) M Cu.KTS containing 3 to 18 muCi Cu-64. Blood, tumor, and six to ten additional tissues were counted for radioactivity. The mouse fibrosarcoma concentrated Cu-64, reaching 15% of the administered dose/g at 48 hr after injection. This suggests that for tumor scanning, the 61.7-hr Cu-67 might be more suitable as a label for KTS than the 12.7-hr Cu-64.

[131I]iodocholesterol scintiscan and a rare "functional" black adenoma of the adrenal cortex.

A rare functional black adenoma (FBA) of the adrenal cortex was found to be the cause of hypertension and cushingold features in a 34-yr-old white female. Preoperative studies included [131I]iodocholesterol scanning (ICS) of the adrenal glands, which demonstrated the increased release of cortisol from the affected adrenal gland, with the failure of the opposite adrenal gland to record. This is evidence that cortisol was suppressing adrenocorticotropin (ACTH) output by the pituitary gland. This case documents the clinical utility of "functional" imaging techniques in this clinical setting.

The in vivo distribution of indium-111 labeled in vitro alloactivated syngeneic lymphocytes in a patient with relapsed acute myelomonocytic leukemia: implications for adoptive chemoimmunotherapy.

A single patient who had a leukemic relapse six months after receiving a syngeneic bone marrow transplant was given "adoptive chemoimmunotherapy." Lymphocytes from the patients identical twin were alloactivated and grown in T cell growth factor in vitro. After receiving chemotherapy to reduce the number of relapsed leukemia cells, he received 1.1 X 10(10) in vitro alloactivated twin lymphocytes via intravenous and intraperitoneal injections. Although progressive Candidal pneumonia was fatal and prevented analysis of either efficacy or delayed toxicity of this potential form of therapy for this patient, radioactive 111In labelling and scanning showed dissemination of these lymphocytes following either injection route, with no clinical evidence of immediate toxicity.

Radionuclide scintiphotography in defining postoperative pulmonary vasoconstriction. Succesful results after tolazoline administration in a four-month-old infant with congenital heart disease.

99mTechnetium macroaggregated albumin has successfully been used to define severe postoperative pulmonary vasoconstriction in a four-month-old boy with D-transposition of the great vessels who had undergone a Blalock-Hanlon surgical atrial septectomy. Radionuclide imaging documented clinically suspected pulmonary vasoconstriction and led to the successful use of tolazoline (Priscoline) to reverse the vasoconstriction with improved pulmonary blood flow patterns.