Cost benefit and cost effectiveness of antifungal prophylaxis in immunocompromised patients treated for haematological malignancies:reviewing the available evidence

There has been a large increase in the incidence of invasive fungal infections (IFIs) over the past decades, largely because of the increasing size of the population at risk. One of the major risk groups for IFIs are patients with haematological malignancies treated with cytotoxic chemotherapy or undergoing haematopoietic stem cell transplantation. These IFIs are associated with high morbidity and mortality rates. Consequently, as the diagnosis of IFIs is difficult, antifungal prophylaxis is desirable in high-risk patients. Furthermore, as the economic impact of IFIs is also significant, it is important to assess the cost benefit and cost effectiveness of each prophylactic agent in order to aid decisions concerning which prophylactic agent provides the best value for limited healthcare resources. This article systematically reviews the available pharmacoeconomic evidence regarding antifungal prophylaxis in immunocompromised patients treated for haematological malignancies. Furthermore, specific points of interest concerning economic analyses of antifungal prophylaxis are briefly discussed. Considering the available evidence, antifungal prophylaxis in immunocompromised patients treated for haematological malignancies seems to be an intervention with favourable cost-benefit, cost-effectiveness and cost-saving potential. Furthermore, recently introduced antifungal agents seem to be attractive alternatives to fluconazole from a pharmacoeconomic point of view. However, due to wide heterogeneity in patient characteristics, underlying diseases, hospital settings and study methods in the included economic studies, as well as the lack of 'head-to-head' trials, it is difficult to find clear evidence of the economic advantages of a single prophylactic agent. Furthermore, we show that the results of cost-effectiveness analyses are highly dependent on several crucial factors that influence the baseline IFI incidence rates and, therefore, differ per patient population or region

6-Mercaptopurine, still valuable for the palliative treatment of acute myeloid leukaemia

Although 6-mercaptopurine (6-MP) is frequently used in the treatment of acute myeloid leukaemia (AML), its effect on disease progression has not been studied systematically. In a small retrospective analysis, we found that 6-MP could induce marked haematological improvement in a considerable number of AML patients who were not treated with intensive remission induction courses. Due to the inherent limitations of retrospective analyses, we then investigated prospectively in 51 consecutive patients over a 3-year period in a single centre, to what extent, oral 6-MP 250 mg twice a week could be beneficial to AML patients who were not-or no longer-eligible for intensive chemotherapy. Clinical response was scored according to changes in blood cell counts and dependency on blood transfusions. Thirteen patients (25%) were considered responders since they showed an increased platelet count from the first month after initiation of 6-MP onwards and they became independent of blood transfusions after 3 months. This effect lasted for 13 (range 7-30+) months. Median overall survival of this subgroup was 16.5 (6-33+) months. Ten patients (20%) had a shorter or incomplete response and a survival of 12 (6-30) months. Seven patients were lost to follow-up. Twenty-one (41%) failed to respond and survived for 4 (1.5-17) months. The response seemed not to be affected by previous chemotherapy, history of myelodysplasia, or karyotype abnormalities, but high leukocyte count initially was unfavourable. 6-MP thus can induce marked improvement of blood cell counts in a considerable proportion of AML patients who are not eligible for intensive chemotherapy, leading to good quality of life and a significant prolongation of survival.</p

Rhodococcus equi Infection after Alemtuzumab Therapy for T-cell Prolymphocytic Leukemia

Rhodococcus equi, mainly known from veterinary medicine as a pathogen in domestic animals, can also cause infections in immunocompromised humans, especially in those with defects in cellular immunity. Alemtuzumab, an anti-CD52 monoclonal antibody, causes lymphocytopenia by eliminating CD52-positive cells. We report a patient in whom Rhodococcus equi infection developed after alemtuzumab therapy

Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia

BACKGROUND: Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). METHODS: In a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only. Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect. The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups. RESULTS: After induction chemotherapy, the rates of response were not significantly different in the two groups. After a median follow-up of 55 months, patients in complete remission after induction chemotherapy plus G-CSF had a higher rate of disease-free survival than patients who did not receive G-CSF (42 percent vs. 33 percent at four years, P=0.02), owing to a reduced probability of relapse (relative risk, 0.77; 95 percent confidence interval, 0.61 to 0.99; P=0.04). G-CSF did not significantly improve overall survival (P=0.16). Although G-CSF did not improve the outcome in the subgroup with an unfavorable prognosis, the 72 percent of patients with standard-risk AML benefited from G-CSF therapy (overall survival at four years, 45 percent, as compared with 35 percent in the group that did not receive G-CSF [relative risk of death, 0.75; 95 percent confidence interval, 0.59 to 0.95; P=0.02]; disease-free survival, 45 percent vs. 33 percent [relative risk, 0.70]; 95 percent confidence interval, 0.55 to 0.90; P=0.006). CONCLUSIONS: Sensitization of leukemic cells with growth factors is a clinically applicable means of enhancing the efficacy of chemotherapy in patients with AML

Moving in an environment of induced sensorimotor incongruence does not influence pain sensitivity in healthy volunteers: A randomised within-subject experiment

Objectives: It has been proposed that in the same way that conflict between vestibular and visual inputs leads to motion sickness, conflict between motor commands and sensory information associated with these commands may contribute to some chronic pain states. Attempts to test this hypothesis by artificially inducing a state of sensorimotor incongruence and assessing self-reported pain have yielded equivocal results. To help clarify the effect sensorimotor incongruence has on pain we investigated the effect of moving in an environment of induced incongruence on pressure pain thresholds (PPT) and the pain experienced immediately on completion of PPT testing. Methods: Thirty-five healthy subjects performed synchronous and asynchronous upper-limb movements with and without mirror visual feedback in random order. We measured PPT over the elbow and the pain evoked by testing. Generalised linear mixed-models were performed for each outcome. Condition (four levels) and baseline values for each outcome were within-subject factors. Results: There was no effect of condition on PPT (p = 0.887) or pressure-evoked pain (p = 0.771). A sensitivity analysis using only the first PPT measure after each condition confirmed the result (p = 0.867). Discussion: Inducing a state of movement related sensorimotor incongruence in the upper-limb of healthy volunteers does not influence PPT, nor the pain evoked by testing. We found no evidence that sensorimotor incongruence upregulates the nociceptive system in healthy volunteer

Нейроендокринний супровід поліваріантних ефектів біоактивної води Нафтуся на рівень хронічного стресу у жінок з різним оваріальним статусом

Проанализированы изменения нейроэндокринных показателен, сопутствующие поливариантным эффектам биоактивной воды Нафтуся курорта Трускавец на уровень хронического стресса у женщин детородного возраста с различным овариальным статусом. Обнаружена значительная (R=0,59) каноническая корреляционная связь между динамикой нейро-гормонального индекса стресса, с одной стороны, и вегетативной реактивности, лютеинизирующего гормона, тиреотропного гормона, тироксина и прогестерона - с другой стороны.The changes in neuroendocrine parameters, concomitant multivariate effects of bioactive water Naftussya spa Truskavets to the level of chronic stress in women of childbearing age with different ovarian status. A significant (R=0,59) canonical correlation between the dynamics of the neuro-hormonal index of stress, on the one hand, and autonomic reactivity, luteinizing hormone, thyroid-stimulating hormone, thyroxine and progesterone - the other side

Quality of life of patients with chronic lymphocytic leukaemia in the Netherlands: results of a longitudinal multicentre study

Purpose: To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients. Methods: HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All HRQoL measurements per patient were connected and analysed using area under the curve analysis over the entire study duration. The total patient group was compared with the general population, and three groups of CLL patients were described separately, i.e. patients without any active treatment (“watch and wait”), chlorambucil treatment only, and patients with other treatment(s). Results: HRQoL in the total group of CLL patients was compromised when compared with age- and gender-matched norm scores of the general population. CLL patients scored statistically worse on the VAS and utility score of the EQ-5D, all functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea, sleeping disturbance, appetite loss, and financial difficulties. In untreated patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was compromised considerably. Patients treated with chlorambucil only scored worse on the EORTC QLQ-C30 than patients who were treated with other treatments with regard to emotional functioning, cognitive functioning, bruises, uncomfortable stomach, and apathy. Conclusions: CLL patients differ most from the general population on role functioning, fatigue, concerns about future health, and having not enough energy. Once treatment is indicated, HRQoL becomes considerably compromised. This applies to all treatments, including chlorambucil, which is considered to be a mild treatment

Multitarget Stool DNA Test Performance in an Average-Risk Colorectal Cancer Screening Population

INTRODUCTION: We set out to evaluate the performance of a multitarget stool DNA (MT-sDNA) in an average-risk colonoscopy-controlled colorectal cancer (CRC) screening population. MT-sDNA stool test results were evaluated against fecal immunochemical test (FIT) results for the detection of different lesions, including molecularly defined high-risk adenomas and several other tumor characteristics. METHODS: Whole stool samples (n = 1,047) were prospectively collected and subjected to an MT-sDNA test, which tests for KRAS mutations, NDRG4 and BMP3 promoter methylation, and hemoglobin. Results for detecting CRC (n = 7), advanced precancerous lesions (advanced adenoma [AA] and advanced serrated polyps; n = 119), and non-AAs (n = 191) were compared with those of FIT alone (thresholds of 50, 75, and 100 hemoglobin/mL). AAs with high risk of progression were defined by the presence of specific DNA copy number events as measured by low-pass whole genome sequencing. RESULTS: The MT-sDNA test was more sensitive than FIT alone in detecting advanced precancerous lesions (46% (55/119) vs 27% (32/119), respectively, P < 0.001). Specificities among individuals with nonadvanced or negative findings (controls) were 89% (791/888) and 93% (828/888) for MT-sDNA and FIT testing, respectively. A positive MT-sDNA test was associated with multiple lesions (P = 0.005), larger lesions (P = 0.03), and lesions with tubulovillous architecture (P = 0.04). The sensitivity of the MT-sDNA test or FIT in detecting individuals with high-risk AAs (n = 19) from individuals with low-risk AAs (n = 52) was not significantly different. DISCUSSION: In an average-risk screening population, the MT-sDNA test has an increased sensitivity for detecting advanced precancerous lesions compared with FIT alone. AAs with a high risk of progression were not detected with significantly higher sensitivity by MT-sDNA or FIT