Characteristics of Unscheduled and Scheduled Outpatient Palliative Care Clinic Patients at a Comprehensive Cancer Center

Context

There is limited literature regarding outpatient palliative care and factors associated with unscheduled clinic visits.

Effect of transfusion of fresh frozen plasma on parameters of endothelial condition and inflammatory status in non-bleeding critically ill patients: a prospective substudy of a randomized trial

IntroductionMuch controversy exists on the effect of a fresh frozen plasma (FFP) transfusion on systemic inflammation and endothelial damage. Adverse effects of FFP have been well described, including acute lung injury. However, it is also suggested that a higher amount of FFP decreases mortality in trauma patients requiring a massive transfusion. Furthermore, FFP has an endothelial stabilizing effect in experimental models. We investigated the effect of fresh frozen plasma transfusion on systemic inflammation and endothelial condition.MethodsA prospective predefined substudy of a randomized trial in coagulopathic non-bleeding critically ill patients receiving a prophylactic transfusion of FFP (12 ml/kg) prior to an invasive procedure. Levels of inflammatory cytokines and markers of endothelial condition were measured in paired samples of 33 patients before and after transfusion. The statistical tests used were paired t test or the Wilcoxon signed-rank test.ResultsAt baseline, systemic cytokine levels were mildly elevated in critically ill patients. FFP transfusion resulted in a decrease of levels of TNF-α (from 11.3 to 2.3 pg/ml, P = 0.01). Other cytokines were not affected. FFP also resulted in a decrease in systemic syndecan-1 levels (from 675 to 565 pg/ml, P = 0.01) and a decrease in factor VIII levels (from 246 to 246%, P <0.01), suggestive of an improved endothelial condition. This was associated with an increase in ADAMTS13 levels (from 24 to 32%, P <0.01) and a concomitant decrease in von Willebrand factor (vWF) levels (from 474 to 423%, P <0.01).ConclusionsA fixed dose of FFP transfusion in critically ill patients decreases syndecan-1 and factor VIII levels, suggesting a stabilized endothelial condition, possibly by increasing ADAMTS13, which is capable of cleaving vWF.

Trial registrations

Trialregister.nl NTR2262, registered 26 March 2010 and Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01143909","term_id":"NCT01143909"}}NCT01143909, registered 14 June 2010.     

Prospective study of erythropoietin use on quality of life and cost effectiveness in acute myeloid leukemia and allogeneic hematopoietic stem cell transplantation patients

BACKGROUND:

Despite frequent anemia and multiple transfusions in patients undergoing chemotherapy and allogeneic hematopoietic stem cell transplantation (allo‐HSCT) for acute myeloid leukemia , recommendations for use of erythropoiesis‐stimulating agents (ESAs) in these populations are still missing. The primary objective was the effect of ESA administration on patient's quality of life (QoL). Secondary objectives were hemoglobin (Hb) recovery, red blood cell (RBC) transfusions, overall survival, and event‐free survival.

METHODS:

Adult patients with Hb ≤ 11 g/dL after consolidation chemotherapy for acute myeloid leukemia (group 1), or after allo‐HSCT for any hematological diseases (group 2), were prospectively included. ESA was administered subcutaneously once per week during a maximum period of 6 months and was stopped when Hb level reached 12 g/dL. A paired‐matched analysis using a historical control group was performed for secondary endpoints. Fifty‐two patients were included in group 1, and 55 patients were in group 2.

RESULTS:

For the global population, a significant improvement of QoL was noticed with ESA use; 83% (group 1) and 71% (group 2) of patients achieved an Hb level ≥ 12 g/dL without transfusion requirement. The pair‐matched analysis showed a reduction of 4 RBC units per patient in group 1 (P = .0002) and 3 RBC units per patient in group 2 (P = .04). No significant difference in terms of thromboembolic events, overall survival, and event‐free survival was observed between ESA and control groups. A RBC transfusion median savings of €1712 per patient was estimated in each group.

CONCLUSIONS:

ESAs have a clinical and economic benefit on Hb recovery, could improve a patient's QoL, and lead to a significant reduction in number of RBC transfusions with no effect on survival. Cancer 2013. © 2012 American Cancer Society.     

Binding characteristics of [3H] guanfacine to rat brain α-adrenoceptors: Comparison with [3H]clonidine

The tritium-labeled α-adrenoceptor agonist and antihypertensive drug guanfacine, N-amidino-2-(2,6-dichlorophenyl)-acetamide (sp. act. 24.2 $\text{Ci}\text{mmole}$) was employed for a direct identification and characterization of α-adrenoceptors in rat brain membranes. Its usefulness as a radioligand was studied in comparison with [³H]clonidine (sp. act. 26.7 $\text{Ci}\text{mmole}$). The nonspecific binding of [³H]guanfacine to rat cerebral membranes was considerably more pronounced than that observed for [³H]clonidine. The specific binding of [³H] guanfacine (0.1–20 nM) and [³H]clonidine (0.1–20 nM) as defined as the excess over blanks containing (?)-norepinephrine (10μM) was saturable. Scatchard analyses of these binding data indicated single populations of binding sites for both ligands. K_D values of 3.9 ([³H]guanfacine) and 3.7 nM ([³H]clonidine) were calculated. Maximal number of specific binding sites amounted to 220 and 195 $\text{fmole}\text{mg}$ protein for [³H]guanfacine and [³H]clonidine, respectively. In case unlabeled guanfacine (1 μM) was used to characterize the specific binding of [³H] guanfacine, K_d value and maximal number of binding sites were about twice as high as determined in the presence of excess (?)-norepinephrine. The rate of association of both radioligands was rapid. Binding reached equilibrium by about 10–15 min of incubation. Half-maximal binding was attained at approximately 1–2 min. The rates of dissociation were biphasic. A rapid and a slow component were identified. The specific binding sites of [³H] guanfacine in rat brain possess the general characteristics of α₂-adrenoceptors. Selective antagonists of α₂-adrenoceptors, like yohimbine and rauwolscine strongly interfered with this binding. However, preferential blocking agents of α₁-adrenoceptors, such as prazosin and corynanthine, were weak competitors. The relative potency of agonists and antagonists in displacing [³H]guanfacine was identical to their effectiveness in competing for [³H]clonidine specific binding sites. It is concluded that [³H]guanfacine labels the same α₂-adrenoceptor population in rat brain as [³H]clonidine. However, [³H]guanfacine seems not as suitable as [³H]clonidine for routine use in the direct identification of α₂-adrenoceptors in view of its relatively high nonspecific binding.     

Inhibition of adenovirus infection and adenain by green tea catechins

Green tea catechins have been reported to inhibit proteases involved in cancer metastasis and infection by influenza virus and HIV. To date there are no effective anti-adenoviral therapies. Consequently, we studied the effect of green tea catechins, and particularly the predominant component, epigallocatechin-3-gallate (EGCG), on adenovirus infection and the viral protease adenain, in cell culture. Adding EGCG (100 microM) to the medium of infected cells reduced virus yield by two orders of magnitude, giving and IC(50) of 25 microM and a therapeutic index of 22 in Hep2 cells. The agent was the most effective when added to the cells during the transition from the early to the late phase of viral infection suggesting that EGCG inhibits one or more late steps in virus infection. One of these steps appears to be virus assembly because the titer of infectious virus and the production of physical particles was much more affected than the synthesis of virus proteins. Another step might be the maturation cleavages carried out by adenain. Of the four catechins tested on adenain, EGCG was the most inhibitory with an IC(50) of 109 microM, compared with an IC(50) of 714 microM for PCMB, a standard cysteine protease inhibitor. EGCG and different green teas inactivated purified adenovirions with IC(50) of 250 and 245-3095, respectively. We conclude that the anti-adenoviral activity of EGCG manifests itself through several mechanisms, both outside and inside the cell, but at effective drug concentrations well above that reported in the serum of green tea drinkers.     

Classification of heart failure in population based research: An assessment of six heart failure scores

Several scores based on symptoms and signs have been developed to assess the presence of heart failure. The goal of this study was to compare six heart failure scores in non-hospitalised subjects and to determine their usefulness in population based research. The scores were applied to 54 participants of a population based study. All underwent a complete medical examination, including chest X-ray, electrocardiography and Doppler echocardiography. Using all information available, a cardiologist, unaware of the results of the scores, clinically classified participants as having no, possible or definite heart failure. Sensitivity, specificity, predictive values and receiver operating characteristics were calculated, using the cardiologist's assessment as a gold standard. The cardiologist judged definite or possible heart failure to be present in 17 persons. All scores had a high sensitivity for the detection of definite heart failure, whereas the study of men born in 1913 and Walma's score had the highest sensitivity for the combination of possible and definite heart failure. Gheorgiade's and the Boston score had the highest positive predictive values. In conclusion, five of the six scores we studied are broadly similar in the detection of heart failure. The men born in 1913 score relies heavily on the assessment of dyspnea, resulting in a relatively large number of false positives. Although the scores are useful in detecting manifest heart failure, objective measurements of cardiac function appear necessary to reduce the false positive rate and accurately detect early stages of heart failure.     

Implementation of FocalPoint GS location-guided imaging system: experience in a clinical setting

Background:

Recently, the Food and Drug Administration approved the use of the location‐guided imaging system FocalPoint GS (FPGS), on SurePath Papanicolaou (Pap) tests for primary screening. The objective of the current study was to evaluate the impact of FPGS on the following: distribution of diagnostic categories; rate of high‐risk human papillomavirus (HR‐HPV)–positive ASC‐US cases; and quality control (QC) data before and after FPGS implementation.

Methods:

A search of the laboratory information system was performed to identify all SurePath Pap tests processed in our laboratory for the first 19 months after FPGS implementation. We also retrieved all SurePath specimens from a 16‐month period prior to FPGS implementation to serve as the control. During the period from Janaury 2008 to April 2009, the FocalPoint Slide Profiler was used.

Results:

Implementation of FPGS resulted in a significantly higher percentage of LSIL and ASC‐US interpretations, as well as a significant increase in the detection of candidiasis and bacterial vaginosis. The ASC‐to‐SIL ratio was 1.4 and 1.9 before and after FPGS implementation, respectively. There was a decrease in the HR‐HPV positive rate in ASC‐US cases, and a decrease in the estimated false‐negative fraction after FPGS implementation.

Conclusions:

In conclusion, our study seems to demonstrate a favorable performance of FPGS in the routine clinical setting. FPGS may have the potential to be a promising screening tool for gynecologic cytology in a low‐risk patient population. Cancer (Cancer Cytopathol) 2012;. © 2011 American Cancer Society.     

Lost workdays in uterine cervical cancer survivors compared to the general population: impact of treatment and relapse

Purpose

The aim of the present study was to examine the risk of lost workdays due to sick leave and disability pension by treatment modality and relapse in a population-based cohort of cervical cancer survivors versus matched comparators.

Methods

We identified 1971 cervical cancer patients aged ≤60 years (median 42) at diagnosis in Sweden 2003–2009 and 9254 population comparators. Information on sociodemographic and clinical characteristics, sick leave, and disability pension was retrieved from nationwide prospective registers. Differences in the annual mean number of lost workdays were calculated by linear regression, and hazard ratios (HRs) of disability pension were calculated by Cox regression analysis, with follow-up through September 2013.

Results

Cervical cancer patients had more lost workdays annually than comparators up to 8 years following diagnosis. Relapse-free patients had more lost workdays than comparators up to 4 years. Risk of disability pension during follow-up was increased among the relapse-free patients treated with hysterectomy (HR 1.8 [95 % confidence interval (CI) 1.1–2.8]), hysterectomy plus chemotherapy and/or radiotherapy (HR 2.5 [95 % CI 1.2–5.4]), or chemotherapy and/or radiotherapy alone (HR 3.0 [95 % CI 1.3–6.8]), compared with the population. Women treated with fertility-sparing surgery did not have more lost workdays than the population beyond the first year and were not at increased risk of disability pension.

Conclusion

We observed a long-standing increased risk of lost workdays among cervical cancer patients, overall, as well as among relapse-free patients.

Implications for Cancer Survivors

Extensive but not limited treatment was associated with increased risk of lost workdays, possibly reflecting an association between treatment side effects and work ability.

     

Rate-difference method proved satisfactory in estimating the influenza burden in primary care visits

OBJECTIVE: To compare different methods to estimate the disease burden of influenza, using influenza and respiratory syncytial virus-(RSV) associated primary care data as an example. STUDY DESIGN AND SETTING: In a retrospective study in the Netherlands over 1997-2003, primary care attended respiratory episodes and national viral surveillance data were used to compare the rate-difference method to other, more complex methods. RESULTS: The influenza-associated excess estimated by the different methods varied. The estimates provided by the rate-difference model lay well within this range. According to the rate-difference method, influenza-associated primary care consultations were present for all ages, including low-risk adults. The highest influenza-associated burden was demonstrated for children below the age of 5 years. The RSV-associated primary care burden was highest in the youngest age category and well above that associated with influenza. Significant RSV-associated excess was also recorded among adults, particularly in high-risk adults and the elderly. CONCLUSION: The straightforward rate-difference model seemed satisfactory to estimate the influenza-associated burden. Significant influenza-associated excess was demonstrated among persons not yet recommended for influenza vaccination in The Netherlands. The RSV-associated burden was highest for the youngest children, but also significant for adults.     

Impact of plasma and intracellular exposure and CYP3A4, CYP3A5, and ABCB1 genetic polymorphisms on vincristine-induced neurotoxicity

Purpose  

The aim of this study was to investigate the impact of plasma and intracellular exposure and CYP3A4, CYP3A5, and ABCB1 polymorphisms on vincristine neurotoxicity. We subsequently assessed the impact of ABCB1 polymorphisms on intracellular vincristine accumulation.