A prospective,randomized clinical trial of universal WBC reduction

BACKGROUND: Recipient exposure to allogeneic donor WBCs results in transfusion complications for selected populations of recipients. Whether or not WBC reduction should be universally applied is highly controversial. STUDY DESIGN AND METHODS: In a general hospital, a randomized, controlled clinical trial of conversion to universal WBC reduction was conducted. Patients (11%) with established medical indications for WBC-reduced blood were not eligible. All other patients who required transfusion were assigned at random to receive either unmodified blood components or stored WBC-reduced RBCs and platelets. Analysis for each patient was restricted to the first hospitalization. RESULTS: All eligible patients (n = 2780) were enrolled. Three specified primary outcome measures were not different between the two groups: 1) in-hospital mortality (8.5% control; 9.0% WBC-reduced; OR, 0.94 [95% CI, 0.72-1.22]; p = 0.64); 2) hospital length of stay (LOS) after transfusion (median number of days, 6.4 for control and 6.3 for WBC-reduced; p = 0.21); and 3) total hospital costs (median, $19,500 for control and $19,200 for WBC-reduced, p = 0.24). Secondary outcomes (intensive care LOS, postoperative LOS, antibiotic usage, and readmission rate) were not different between the two groups. Subgroup analysis based on patient age, sex, amount of blood transfused, or category of surgical procedure showed no effect of WBC reduction. Patients who received WBC-reduced blood had a lower incidence of febrile reactions (p = 0.06). CONCLUSION: A beneficial effect of conversion from selective to universal WBC reduction was not demonstrated.     

Cardiac effects of granisetron in a prospective crossover randomized dose comparison trial

Purpose

Cardiac side effects of granisetron have been studied mostly in adult patients that are using cardiotoxic chemotherapeutics. There is limited evidence in pediatric age group and no information in pediatric oncology patients with non-cardiotoxic chemotherapeutics.

Methods

In this prospective, crossover randomized study, the cardiac side effects of granisetron are compared in pediatric oncology patients who had carboplatin based chemotherapy. They were randomized to receive either 10 or 40 μg kg^?1 dose^?1 of granisetron before each cycle of chemotherapy. We drew blood for creatine phosphokinase (CPK), CPK-muscle band (MB) and Troponin-T before and 24?h after administering granisetron. Electrocardiography (ECG) tracings were taken at 0, 1, 2, 3, 6 and 24?h of granisetron. Twenty-four hours Holter ECG monitorisation was performed after each granisetron infusion.

Results

A total of 16 patients (median 8.7?years of age) were treated with weekly consecutive courses of carboplatin. There was bradycardia (p?=?0.000) in patients that had granisetron at 40 μg/kg and PR interval was shortened in patients that had granisetron at 10 μg/kg dose (p?=?0.021). At both doses of granisetron, QTc interval and dispersion were found to be similar. CPK, CK-MB and Troponin-T values were found to be normal before and 24?h after granisetron infusion.

Conclusions

As the first study that has studied cardiac side effects of granisetron in patients that are not using cardiotoxic chemotherapeutics, we conclude that granisetron at 40 μg kg^?1 dose^?1 causes bradycardia only. We have also demonstrated that granisetron does not cause any clinically cardiac side effects either at 10 or 40 μg kg^?1 dose^?1. However, our results should be supported by prospective randomized studies with larger samples of patient groups.     

AAIR versus DDDR pacing in the bradycardia tachycardia syndrome: a prospective, randomized, double-blind, crossover trial

In 19 patients paced and medicated for bradycardia tachycardia syndrome (BTS), AAIR and DDDR pacing were compared with regard to quality of life (QoL), atrial tachyarrhythmia (AFib), exercise tolerance, and left ventricular (LV)function. Patients had a PQ interval < or = 240 ms during sinus rhythm, no second or third degree AV block, no bundle branch block, or bifascicular block. In DDDR mode, AV delay was optimized using the aortic time velocity integral. After 3 months, QoL was assessed by questionnaires, patients were investigated by 24-hour Holter, cardiopulmonary exercise testing (CPX) was performed, and LV function was determined by echocardiography. QoL was similar in all dimensions, except dizziness, showing a significantly lower prevalence in AAIR mode. The incidence of AFib was 12 episodes in 2 patients with AAIR versus 22 episodes in 7 patients with DDDR pacing (P = 0.072). In AAIR mode, 164 events of second and third degree AV block were detected in 7 patients (37%) with pauses between 1 and 4 seconds. During CPX, exercise duration and work load were higher in AAIR than in DDDR mode (423+/-127 vs 402+/-102 s and 103+/-31 vs 96+/-27 Watt, P < 0.05). Oxygen consumption (VO2), was similar in both modes. During echocardiography, only deceleration of early diastolic flow velocity and early diastolic closure rate of the anterior mitral valve leaflet were higher in DDD than in AAI pacing (5.16+/-1.35 vs 3.56+/-0.95 m/s2 and 69.2+/-23 vs 54.1+/-26 mm/s, P < 0.05). As preferred pacing mode, 11 patients chose DDDR, 8 patients chose AAIR. Hence, AAIR and DDDR pacing seem to be equally effective in BTS patients. In view of a considerable rate of high degree AV block during AAIR pacing, DDDR mode should be preferred for safety reasons.     

Prophylactic granulocyte transfusions: results of a randomized controlled trial in patients with acute myelogenous leukemia

A prospective randomized and controlled clinical trial of prophylactic granulocyte transfusions was conducted in an attempt to reduce the mortality from infection in newly diagnosed adults with acute myelogenous leukemia. Granulocytes were harvested from normal donors by cytapheresis, and transfused patients received a median of 1.45 × 10(10) granulocytes (range 0.28–3.45 × 10(10)) on alternate days during marrow aplasia caused by initial induction chemotherapy. Transfusion were started if the absolute peripheral granulocyte count was less than 500 microliters. Thirteen patients received from one to 12 granulocyte transfusions, and 11 control patients received no granulocytes. No significant advantage was demonstrated in the transfused patients compared with controls with regard to the following: 1) deaths due to infection, 2) reduction in the frequency of febrile episodes, 3) delay in the onset of fever, 4) reduction in the length of febrile episodes, or 5) reduction in the frequency of proven infection.     

Efficacy of cell saver in reducing homologous blood transfusions during OPCAB surgery: a prospective randomized trial

Despite the refinements in surgical technique, rates of homologous blood transfusion (HBT) in cardiac surgery remain high. The adverse effects of blood transfusion are well documented. Retransfusion of shed mediastinal blood reduces the requirement for HBTs during conventional coronary artery bypass grafting. However, some studies have found that autotransfusion leads to bleeding diathesis and paradoxical increase in blood transfusions. Through this prospective randomized trial, we have studied the safety and efficacy of this modality in patients undergoing off-pump coronary artery bypass grafting (OPCAB). Fifty patients enrolled in the study and 49 fulfilled the study criteria. They were randomly divided into group C (cell saver) and group N (non-cell saver). Whereas the cell saver group received processed shed autologous blood and homologous blood if necessary, the non-saver group was transfused homologous blood only. The threshold for transfusion was haemoglobin of 9 g dL(-1) in both the groups. The cell saver group required significantly less number of HBTs (1.6 +/- 1.2 vs. 2.4 +/- 1.3 units). The incidence of re-exploration was zero in both the groups. The mean mediastinal drainage in both the groups was not significantly different (355 +/- 196 vs. 316 +/- 119.8 mL). The number of patients requiring any blood transfusion however was very high. All the patients in the non-saver group and 20 (83%) of the patients in the saver group received homologous blood. During OPCAB surgery, the use of cell saver reduced the requirement for HBT. Its use is not associated with any clinically significant bleeding diathesis.     

Antibacterial drugs in the treatment of osteoarthrosis: results of a prospective randomized trial

65 patients with knee and hip joints osteoarthrosis with concomitant urinary infection and/or irritable colon syndrome were randomized into three groups: group 1 (21 patients) received doxicyclin 200 mg/day with nistatine for three weeks with 3-week interval between the courses and bifidum-bacterin administration between the courses and after the treatment; group 2 (22 patients) received biseptol 1920 mg for 3 weeks then 960 mg 10 days a month; group 3 (22 patients) consisted of controls who received no antibacterial drugs. The effect was assessed upon randomization, 3 weeks, 3, 6 and 12 months after the treatment. It was established that antibacterial treatment not only attenuated dysuria and dyspepsia but also had a significant positive effect on osteoarthrosis especially in patients with x-ray stage II, allowed to reduce doses of nonsteroid antiinflammatory drugs. Further studies will help specify the role of the infection factor in development of osteoarthrosis and potential of antibacterial treatment.     

Nutrition intervention for migraine: a randomized crossover trial

Background

Limited evidence suggests that dietary interventions may offer a promising approach for migraine. The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency.

Methods

Forty-two adult migraine sufferers were recruited from the general community in Washington, DC, and divided randomly into two groups. This 36-week crossover study included two treatments: dietary instruction and placebo supplement. Each treatment period was 16 weeks, with a 4-week washout between. During the diet period, a low-fat vegan diet was prescribed for 4 weeks, after which an elimination diet was used. Participants were assessed at the beginning, midpoint, and end of each period. Significance was determined using student’s t-tests.

Results

Worst headache pain in last 2 weeks, as measured by visual analog scale, was initially 6.4/10 cm (SD 2.1 cm), and declined 2.1 cm during the diet period and 0.7 cm during the supplement period (p=0.03). Average headache intensity (0–10 scale) was initially 4.2 (SD 1.4) per week, and this declined by 1.0 during the diet period and by 0.5 during the supplement period (p=0.20). Average headache frequency was initially 2.3 (SD 1.8) per week, and this declined by 0.3 during the diet period and by 0.4 during the supplement period (p=0.61). The Patient’s Global Impression of Change showed greater improvement in pain during the diet period (p<0.001).

Conclusions

These results suggest that a nutritional approach may be a useful part of migraine treatment, but that methodologic issues necessitate further research.

Trial registration

Clinicaltrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01699009","term_id":"NCT01699009"}}NCT01699009 and {"type":"clinical-trial","attrs":{"text":"NCT01547494","term_id":"NCT01547494"}}NCT01547494.     

Prospective monitoring of plasma and platelet transfusions in a large teaching hospital results in significant cost reduction

BACKGROUND: Plasma and platelets (PLTs) are often transfused to correct mild to moderately abnormal laboratory values. Our objective was to reduce unnecessary plasma and PLT transfusions to nonbleeding patients by prospective triage and education of end users in evidence‐based hemostasis and transfusion medicine practices. STUDY DESIGN AND METHODS: Using the Parkland Memorial Hospital's transfusion service and admission database as the data source, this study comprises the comparison of transfusion data on plasma and PLT use between pre‐ (2000‐2002) and posttriage (2003‐2006) periods. Yearly transfusion and wastage data on red blood cells (RBCs), plasma, and PLTs and yearly hospital admissions, trauma visits, and surgical procedures were extracted retrospectively for the study. RESULTS: The study revealed that implementation of triage resulted in a significant reduction of plasma (60%) and PLT (25%) transfusions, saving more than $3,000,000 over 4 years. CONCLUSIONS: Prospective triage and evidence‐based transfusion practice education reduced unnecessary plasma and PLT transfusions and health care costs.     

WBC reduction of RBC transfusions is associated with a decreased incidence of RBC alloimmunization

BACKGROUND: Allogeneic transfusion stimulates Th2 (humoral) immunity. A hypothesis was developed that WBC reduction, by reducing the Th2 stimulus associated with transfusions, might reduce RBC alloimmunization. STUDY DESIGN AND METHODS: The first retrospective cohort study involved determining the prevalence of newly detected alloimmunization in transfused patients with acute myeloid leukemia (AML) in our hospital in the period before WBC reduction and after its introduction for this particular group of patients. The second study involved determining the incidence of newly detected RBC alloimmunization in all transfused hospital patients during three annual periods with WBC-reduction prevalences ranging from 0 to 100 percent. RESULTS: The alloimmunization prevalence rate in AML patients was 8.2 percent in those receiving non-WBC-reduced RBCs and platelets (n=195) and 2.8 percent in those receiving only WBC-reduced components (n=215) (p=0.016). In all patients, the alloimmunization incidence rate decreased from 3.47 per 1000 antibody screens in 1987 (no WBC reduction) to 2.97 per 1000 in 1999 (40% of transfusions WBC-reduced) to 2.38 per 1000 in 2001 (100% of transfusions WBC-reduced) (p=0.0298). A decrease in alloimmunization was observed in both males and females, with the decrease more clearly evident in males. CONCLUSION: These preliminary data support the hypothesis that WBC reduction may be associated with a reduced frequency of RBC alloimmunization. These findings require confirmation and further investigation.     

Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, double-blind, crossover trial.

Amitriptyline (AT) relieves some patients with postherpetic neuralgia (PHN). Many patients suffer side effects and better therapies are necessary. The aim of this study was to evaluate the efficacy of maprotiline (MT) (noradrenergic) compared to AT (mixed noradrenergic and serotonergic) in this disorder. Thirty-five patients entered a randomized, double-blind, crossover trial of these two agents. We found that MT relieved PHN in many patients but was not as effective as AT. Side effects were troublesome with both agents. Relief of steady pain, brief pain and pain on tactile stimulation occurred. Four groups of responses were identified. Some patients reported relief with both agents, some with neither agent and others with only one of the drugs. Most patients were not depressed and analgesia was observed to occur without change in depression ratings in most patients who responded. This result provides evidence that in some patients AT may act via a selective noradrenergic mechanism in relieving PHN and that individuals may differ in the balance and type of neurotransmitters inhibiting pain. Selective noradrenergic agents may be effective if AT fails.     

A randomized controlled trial comparing plasma removal with white cell reduction to prevent reactions to platelets

BACKGROUND: Recent data suggest that most reactions to platelets are caused by white cell (WBC)-derived cytokines that accumulate in the plasma portion of the component during storage. On the basis of this theory, the effectiveness of two interventions to prevent reactions, poststorage WBC reduction and plasma depletion, were compared. STUDY DESIGN: A multiple crossover design was used, in which platelet components for transfusion to a patient randomly were WBC reduced after storage, or the plasma supernatant was removed. Adults >17 years of age, with a hematologic disease requiring platelet transfusion support, were eligible for the study. Patients were assessed for signs and symptoms characteristic of a reaction during, immediately after, and 1 hour after transfusion. Reactions were graded as mild, moderate, or severe. Interleukin 6 levels were also measured in the transfused platelet components. RESULTS: There were 380 analyzable platelet transfusions to 30 patients. The frequency of reactions was 25.8 percent (48/186) in the transfusions of poststorage WBC-reduced platelets and 17.0 percent (33/194) in the transfusions of plasma-depleted platelets (p<0.008). The severity of the reaction was graded by the patient. Severe reactions occurred more frequently in connection with poststorage WBC-reduced platelets than with plasma-depleted platelets: 33.4 percent (16/48) versus 18.2 percent (6/33), respectively (p = 0.048). Regression analysis identified interleukin 6 as the most significant of the evaluated factors in its correlation with the risk of reaction. CONCLUSION: Plasma removal is more effective than poststorage WBC reduction in preventing reactions, especially severe reactions to platelets.     

PBPC mobilization with paclitaxel, ifosfamide, and G-CSF with or without amifostine: results of a prospective randomized trial

BACKGROUND: The impact of amifostine on PBPC mobilization with paclitaxel and ifosfamide plus G-CSF was assessed. STUDY DESIGN AND METHODS: Forty patients with a median age of 34 years (range, 19-53) who had germ cell tumor were evaluated for high-dose chemotherapy. Patients were randomly assigned to receive either a single 500-mg dose of amifostine (Group A, n = 20) or no amifostine (Group B, n = 20) before mobilization chemotherapy with paclitaxel (175 mg/m(2)) given over 3 hours and ifosfamide (5 g/m(2)) given over 24 hours (TI) on Day 1. G-CSF at 10 microg per kg per day was given subsequent to TI with or without amifostine from Day 3 until the end of leukapheresis procedures. RESULTS: In 2 (10%) of 20 patients receiving amifostine and 3 (15%) of 20 patients not receiving it, no PBPC separation was performed because of mobilization failure. No significant differences were observed in the study arms with regard to the time from chemotherapy until first PBPC collection or the number of apheresis procedures needed to harvest more than 2.5 x 10(6) CD34+ cells per kg. Furthermore, leukapheresis procedures yielded comparable doses of CD34+ cells per kg (3.4 x 10(6) vs. 3.6 x 10(6); p = 0.82), MNCs per kg (2.7 x 10(8) vs. 2.6 x 10(8); p = 0.18), and CFU-GM per kg (15.9 x 10(4) vs. 19.3 x 10(4); p = 0.20). Patients in Group A had higher numbers of circulating CD34+ cells on Day 10 (103.0/microL vs. 46.8/microL; p = 0.10) and on Day 11 (63.0/microL vs.14.3/microL; p = 0.04) than did patients in Group B. CONCLUSION: Administration of a single dose of amifostine before chemotherapy with TI mobilized higher numbers of CD34 cells in the circulation, but did not enhance the overall collection efficiency in the present trial.     

A prospective, randomized, sequential, crossover trial of large-volume versus normal-volume leukapheresis procedures: effect on progenitor cells and engraftment

BACKGROUND: The influence of leukapheresis size on the number of harvested peripheral blood progenitor cells is still unclear. A prospective randomized crossover trial was thus performed, to evaluate the effect of large-volume leukapheresis (LVL) versus normal-volume leukapheresis (NVL) on progenitor cells and engraftment in 26 patients with breast cancer and 15 patients with non-Hodgkin's lymphoma who were eligible for peripheral blood progenitor cell transplantation. STUDY DESIGN AND METHODS: Patients were randomly assigned to undergo either LVL on Day 1 and on Day 2 or vice versa. The number of progenitor cells was evaluated in the harvest and before and after leukapheresis in the peripheral blood. RESULTS: The number of harvested CD34+ cells (4.8 x 10(6) vs. 3.4 x 10(6)/kg body weight, p < 0.001) and colony-forming units-granulocyte-macrophage (3.1 x 10(5) vs. 2.4 x 10(5)/kg body weight, p = 0.0026) was significantly higher for LVL procedures than for NVL procedures. The median extraction efficacy, defined as the difference between the yield in the harvest and the decrease in the total number of CD34+ cells in peripheral blood during leukapheresis, was significantly (p < 0.0001) higher for LVL than for NVL (2.6 x 10(8) and 8 x 10(7), respectively). In patients with breast cancer, the median amount of CD34+ cells in the harvest and the median extraction efficacy were higher for LVL than for NVL (p < 0.0001). This was not found for patients with non-Hodgkin's lymphoma. CONCLUSION: LVL results in a higher yield of CD34+ cells and colony-forming units-granulocyte-macrophage than NVL, but only in patients with breast cancer and with high numbers of CD34+ cells in the peripheral blood before leukapheresis.     

Automated versus manual blood pressure measurement: a randomized crossover trial

This study evaluated the accuracy and reliability of the Dinamap 8100 automated blood pressure machine against three internationally recognized criteria. Systolic and diastolic blood pressures were taken concurrently by two nurses using the automated machine and a manual sphygmomanometer. Results demonstrated agreement between automated and manual readings on one set of criteria for both systolic and diastolic pressures, and support for systolic readings only on one other criterion. Comparison of mean differences between automated and manual measures showed the automated machine consistently under-read both systolic and diastolic blood pressures. The conclusion from this study was that the Dinamap 8100 machine can be used with some degree of confidence to assess systolic blood pressures in a general population of adult hospital inpatients, but with caution when taking diastolic readings.     

Resuscitation of critically ill patients based on the results of gastric tonometry: a prospective, randomized, controlled trial

OBJECTIVE: To determine whether additional therapy aimed at correcting low gastric intramucosal pH (pHi) improves outcome in conventionally resuscitated, critically ill patients. DESIGN: Prospective, randomized, controlled study. SETTING: General intensive care unit (ICU) of a university teaching hospital. PATIENTS: A total of 210 adult patients, with a median Acute Physiology and Chronic Health Evaluation II score of 24 (range, 8-51). INTERVENTIONS: All patients were resuscitated according to standard guidelines. After resuscitation, those patients in the intervention group with a pHi of <7.35 were treated with additional colloid and then dobutamine (5 microg/kg/min then 10 microg/kg min) until 24 hrs after enrollment. MEASUREMENTS AND MAIN RESULTS: There were no significant differences (p > .05) in ICU mortality (39.6% in the control group vs. 38.5% in the intervention group), hospital mortality (45.3% in the control group vs. 42.3% in the intervention group), and 30-day mortality (43.7% in the control group vs. 40.2 in the intervention group); survival curves; median modified maximal multiorgan dysfunction score (10 points in the control group vs. 13 points in the intervention group); median modified duration of ICU stay (12 days in the control group vs. 11.5 days in the intervention group); or median modified duration of hospital stay (60 days in the control group vs. 42 days in the intervention group). A subgroup analysis of those patients with gastric mucosal pH of > or =7.35 at admission revealed no difference in ICU mortality (10.3% in the control group vs. 14.8% in the intervention group), hospital mortality (13.8% in the control group vs. 29.6% in the intervention group), or 30-day mortality (10.3% in the control group vs. 26.9% in the intervention group). CONCLUSIONS: The routine use of treatment titrated against pHi in the management of critically ill patients cannot be supported. Failure to improve outcome may be caused by an inability to produce a clinically significant change in pHi or because pHi is simply a marker of disease rather than a factor in the pathogenesis of multiorgan failure.     

Immediate effects of dry needling and acupuncture at distant points in chronic neck pain: results of a randomized,double-blind,sham-controlled crossover trial

To evaluate immediate effects of two different modes of acupuncture on motion-related pain and cervical spine mobility in chronic neck pain patients compared to a sham procedure. Thirty-six patients with chronic neck pain and limited cervical spine mobility participated in a prospective, randomized, double-blind, sham-controlled crossover trial. Every patient was treated once with needle acupuncture at distant points, dry needling (DN) of local myofascial trigger points and sham laser acupuncture (Sham). Outcome measures were motion-related pain intensity (visual analogue scale, 0-100 mm) and range of motion (ROM). In addition, patients scored changes of general complaints using an 11-point verbal rating scale. Patients were assessed immediately before and after each treatment by an independent (blinded) investigator. Multivariate analysis was used to assess the effects of true acupuncture and needle site independently. For motion-related pain, use of acupuncture at non-local points reduced pain scores by about a third (11.2 mm; 95% CI 5.7, 16.7; P = 0.00006) compared to DN and sham. DN led to an estimated reduction in pain of 1.0 mm (95% CI -4.5, 6.5; P = 0.7). Use of DN slightly improved ROM by 1.7 degrees (95% CI 0.2, 3.2; P = 0.032) with use of non-local points improving ROM by an additional 1.9 degrees (95% CI 0.3, 3.4; P = 0.016). For patient assessment of change, non-local acupuncture was significantly superior both to Sham (1.7 points; 95% CI 1.0, 2.5; P = 0.0001) and DN (1.5 points; 95% CI 0.4, 2.6; P = 0.008) but there was no difference between DN and Sham (0.1 point; 95% CI -1.0, 1.2; P = 0.8). Acupuncture is superior to Sham in improving motion-related pain and ROM following a single session of treatment in chronic neck pain patients. Acupuncture at distant points improves ROM more than DN; DN was ineffective for motion-related pain.