Mean Change In Hemoglobin Level Research Articles

Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis

BackgroundIron deficiency anemia is a common public health issue among women of reproductive age (WRA) because it can result in adverse maternal and birth outcomes. Although studies are undertaken to assess iron efficacy, some gaps and limitations in the existing literature need to be addressed. To fill the gaps, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the role of iron in reducing anemia among WRA in low-middle-income countries (LMICs).MethodsA comprehensive search strategy was used to search Medline through PubMed, Embase, and Science Direct for RCTs published between 2000 and 2020. The primary outcome was the mean change in hemoglobin level. We used standardized mean differences and their respective 95% CI to estimate the pooled effect. We used I2 statistics and Egger’s test to assess heterogeneity and publication bias, respectively. This review was carried out in accordance with revised guidelines based on the Preferred Reporting Items for Systematic Review and Meta-analysis.ResultsThe findings showed that iron therapy improved hemoglobin and ferritin levels, though the results varied across studies. An overall pooled effect estimate for the role of iron therapy in improving the hemoglobin levels among WRA was -0.71 (95% CI: -1.27 to -0.14) (p = 0.008). Likewise, the overall pooled effect estimate for the role of iron therapy in improving the ferritin levels among WRA was -0.76 (95% CI: -1.56 to 0.04) (p = 0.04). The heterogeneity (I2) across included studies was found to be statistically significant for studies assessing hemoglobin (Q = 746.93, I2 = 97.59%, p = 0.000) and ferritin level (Q = 659.95, I2 = 97.88%, p = 0.000).ConclusionIron therapy in any form may reduce anemia’s burden and improve hemoglobin and ferritin levels, indicating improvement in iron-deficiency anemia. More evidence is required, however, to assess the morbidity associated with iron consumption, such as side effects, work performance, economic outcomes, mental health, and adherence to the intervention, with a particular focus on married but non-pregnant women planning a pregnancy in the near future.Trial registrationRegistered with PROSPERO and ID is CRD42020185033.

Ascorbic Acid for Prevention of Intraoperative Blood Loss and Related Complications During Myomectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Leiomyomas are inherently well-vascularized neoplasms; thus, they are very vulnerable to bleeding-associated complications during myomectomy. Ascorbic acid has well-established functions in tissue healing and the prevention of bleeding tendencies. Several randomized controlled trials (RCTs) have explored the antihemorrhagic utility of ascorbic acid administration during myomectomy. This research aimed to systematically and meta-analytically summarize the clinical antihemorrhagic efficacy of ascorbic acid (i.e., the intervention arm) versus placebo/no treatment (i.e., the control arm) during myomectomy. We electronically searched six sources, i.e., PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar. Our search was from inception until October 2022. We used the Cochrane Risk of Bias Scale (version 2) to assess the quality of the included studies. We summarized the effect sizes as the mean difference (MD) or risk ratio (RR) with a 95% confidence interval (CI) in a fixed-effects or random-effects model. Overall, three RCTs met the inclusion criteria, comprising a total of 193 patients: 99 patients were allocated to the ascorbic acid arm, whereas 94 patients were allocated to the control arm. The overall study quality was "low" and "some concerns" risk of bias in two and one RCT(s), respectively. There was no significant difference between the ascorbic acid and control arms regarding the mean intraoperative blood loss (n=2 RCTs, MD = -190.29 ml, 95% CI [-626.62, 246.05], p=0.39) and mean change in hemoglobin level (n=3 RCTs, MD = -0.26 mg/dl, 95% CI [-0.56, 0.04], p=0.09), respectively. Conversely, the ascorbic acid arm had statistically significant reductions in the mean operative time (n=3 RCTs, MD = -24.10 min, 95% CI [-30.67, -17.53], p<0.001) and the rate of blood transfusion (n=3 RCTs, RR=0.36, 95% CI [0.15, 0.87], p=0.02) compared with the control arm. No serious adverse events related to ascorbic acid were identified. In conclusion, ascorbic acid administration was associated with several beneficial effects, including reductions in mean operative time and rate of blood transfusion, but without affecting the mean intraoperative blood loss and mean change in hemoglobin level. In view of the limitations of the present meta-analysis, the use of ascorbic acid as an antihemorrhagic additive among patients undergoing myomectomy is not strongly recommended.

Comparison of the use of intravenous iron sucrose with intravenous ferric Carboxymaltose for treatment of iron deficiency anaemia in pregnant patients

BACKGROUND &amp; OBJECTIVE: Iron deficiency results in major disabilities and death all over the world, about two billion people are suffering from anaemia at the moment. To compare intravenous iron sucrose with intravenous ferric carboxymaltose in terms of mean change in hemoglobin level and mean corpuscular volume (MCV) for treatment of iron deficiency anaemia in pregnant patients.&#x0D; METHODOLOGY: Prospective comparative study was conducted at the department of Obstetrics/ Gynecology of POF Hospital Wah Cantt and HIT Hospital Taxila Cantt. The study duration was 2 years, from January 2017-December 2018. A total of 80 patients were included in the study. Patients were randomly divided into two groups; in Group-A; 40 patients were given intravenous iron sucrose, and in Group B, 40 patients were given intravenous ferric carboxymaltose. Patients were observed for hemoglobin level and mean corpuscular volume (MCV). Data analysis was done with SPSS version 24. An Independent t-test was applied, and results with p-value ≤0.05 were found significant.&#x0D; RESULTS: Post-treatment hemoglobin means level in the iron sucrose group was 9.90±0.4SD, and in the intravenous ferric carboxymaltose group, post-treatment hemoglobin was 10.71±0.9SD (p≤0.001). In the iron sucrose group, the post-treatment mean corpuscular volume mean level was 81.94±6.0SD and in the intravenous ferric carboxymaltose group mean post-treatment mean corpuscular volume was 88.08±7.1SD (p≤0.001)&#x0D; CONCLUSION: Treatment with intravenous iron caboxymaltose is superior to intravenous iron sucrose with respect to hematological response, which seems to be safe, as very few severe side effects were observed.

MDS-254 A Matching-Adjusted Indirect Comparison of the Efficacy of Pegcetacoplan using PRINCE Trial Data versus Ravulizumab and Eculizumab in Complement Inhibitor–Naïve Patients With Paroxysmal Nocturnal Hemoglobinuria

In the phase III randomized, open-label PRINCE trial (NCT04085601), pegcetacoplan demonstrated superior efficacy versus control treatment (excluding complement inhibitors) among treatment-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH); no head-to-head trials comparing pegcetacoplan to complement inhibitors have previously been conducted in this patient population. To indirectly compare the effectiveness of pegcetacoplan versus ravulizumab and eculizumab in complement inhibitor-naïve PNH patients. Cross-trial comparisons were conducted using individual patient data from PRINCE and published aggregate data for ravulizumab and eculizumab from ALXN1210-PNH-301. Propensity score weighting using logistic regression was employed to balance baseline characteristics across studies. Outcomes at 26 weeks were compared using unanchored matching-adjusted indirect comparison (MAIC) and weighted Wald statistical tests. MAIC of clinical trial data. Complement inhibitor-naïve patients with PNH matched on Asian race, age at first infusion, sex, and baseline EORTC-QLQ-C30 General Health score Interventions: N/A. Transfused packed red blood cell (PRBC) units, time to first LDH normalization (<1x ULN [246 U/L] without transfusions during the randomized controlled period), breakthrough hemolysis, major adverse vascular events (MAVEs), mean change in hemoglobin level, and change in FACIT-Fatigue and EORTC-QLQ-C30 scores. Before matching, statistically significant differences existed among pegcetacoplan (n=34), ravulizumab (n=125), and eculizumab (n=121) arms on White and American Indian/Alaska Native race and baseline LDH (all P<0.001). After matching pegcetacoplan to each of the comparator arms, most characteristics were well-balanced (mean age: 44.8-46.2 years, 43.0%-48.0% female, mean hemoglobin: 9.4-9.7 g/dL). At week 26, pegcetacoplan was associated with significantly greater improvements in hemoglobin levels versus ravulizumab (mean: 1.58 g/dL [16.8%]) and eculizumab (1.78 g/dL [19.5%]) and in EORTC-QLQ-C30 General Health scores (mean: 12.9 and 12.5 points, all P<0.05). Significantly fewer units of PRBCs transfused were estimated for pegcetacoplan versus ravulizumab and eculizumab (mean: -4.1 and -4.6 units, respectively, all P<0.0001) and faster LDH normalization (-8.3 and -13.1 days, P<0.0001 and P=0.0095). The proportions with breakthrough hemolysis or MAVEs, and changes in FACIT-Fatigue and EORTC-QLQ-C30 Physical Functioning or Fatigue scores, were similar between arms. This MAIC demonstrates that pegcetacoplan is more efficacious than ravulizumab or eculizumab among complement inhibitor-naïve patients with PNH.

The Effect of Erythropoiesis-Stimulating Agent on the Management of Chemotherapy-Induced Anemia and Tumor Growth in Diffuse Large B-Cell Lymphoma Patients

Bacground : Erythropoiesis stimulating agents (ESA) increase hemoglobin levels, reduce red blood cell (RBC) transfusion requirements and improve the quality of life (QoL) in patients with chemotherapy-associated anemia (CAA). The purpose of this study is to investigate the efficacy and safety of ESA for management of anemia caused by chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). And this study estimated quality of life as measured by Functional Assessment of Cancer Therapy Scales for anemia (FACT-An) additionally. Until now, several studies suggested that ESA can affect the progression of tumors. This study conducted experiments to confirm whether the results of previous studies were also applied to lymphoma cells.Patients and Methods : This prospective, multicenter, phase II study enrolled 50 Histologically confirmed DLBCL patients who were treated with rituximab, cyclophosphamide, doxorubicin, vincristin, and prednisolone (R-CHOP) chemotherapy. This study enrolled patients who were shown hemoglobin < 10.0 g/dL at least 3 cycles after starting R-CHOP, were planning to receive at least 4 times of darbepoetin, could read Quality of life as measured by FACT-An and agreed with informed consent. However, this study excluded patients who combined iron deficiency anemia, received erythropoietin at least one months before starting darbepoetin, serious pre-existing medical condition, and untreated primary or metastatic CNS(central nervous system) malignancy. This study was registered in clinicaltrial.gov, and more information can be found at NCT02890602. All patients received darbepoietin alfa at fixed dose of 360 mg once every 3 weeks and if the hemoglobin level exceeds 12 g/dL, administration of darbepoietin was stopped temporarily. In addition, DLBCL cell lines or primary DLBCL cells were tested in vitro to investigate if there were any adverse effects of ESAs on the cancer cell growth.Results : Fifty patients were enrolled between Sep 2012 and Oct 2016. The median age was 64.5 years (range: 34-79 years). The baseline clinical features were as follows: female sex, 68.0%; ECOG >1, 75.5%; stage III/IV, 80.0% and International Prognostic Index score (IPI) > 2, 53.3%, and mean serum ferritin level, 648.13±982.52. The baseline mean hemoglobin level was 9.24 g/dL and overall mean change in hemoglobin level was 1.54±1.3 g/dL at 16 weeks. 46% of total enrolled patients achieved an increase in Hb levels of at least 2 g/dL after 16 weeks of darbepoietin administration and median time to response was 8 weeks. The change of OoL was not significant from baseline to finish of ESA. Most adverse events were hematologic complications which were attributed to the primary disease or received chemotherapy. Only one patient had a thrombotic event which was Common Terminology Criteria for Adverse Events (CTCAE) grade I. Transfusion necessity was determined by clinical judgment and the transfusion rates were 18%. In in vitro study using DLBCL cells, erythropoietin or darbepoietin did not alter cancer cell viability nor rituximab-mediated cytotoxicity under the conditions we have tested.Conclusions : Our study has demonstrated that ESA is effective and safe for patients suffering from anemia after RCHOP chemotherapy. The use of ESA in patients with DLBCL did not deteriorate the quality of life of the patients during chemotherapy. Finally, our research have also shown that the use of ESA does not affect the growth of lymphoma cells. (EPOMA ClinicalTrials.gov number, NCT02890602) DisclosuresNo relevant conflicts of interest to declare.

Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria

BackgroundParoxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease characterized by chronic complement-mediated hemolysis. C5 inhibition controls intravascular hemolysis in untreated PNH but cannot address extravascular hemolysis. Pegcetacoplan, a pegylated peptide targeting proximal complement protein C3, potentially inhibits both intravascular and extravascular hemolysis.MethodsWe conducted a phase 3 open-label, controlled trial to assess the efficacy and safety of pegcetacoplan as compared with eculizumab in adults with PNH and hemoglobin levels lower than 10.5 g per deciliter despite eculizumab therapy. After a 4-week run-in phase in which all patients received pegcetacoplan plus eculizumab, we randomly assigned patients to subcutaneous pegcetacoplan monotherapy (41 patients) or intravenous eculizumab (39 patients). The primary end point was the mean change in hemoglobin level from baseline to week 16. Additional clinical and hematologic markers of hemolysis and safety were assessed.ResultsPegcetacoplan was superior to eculizumab with respect to the change in hemoglobin level from baseline to week 16, with an adjusted (least squares) mean difference of 3.84 g per deciliter (P<0.001). A total of 35 patients (85%) receiving pegcetacoplan as compared with 6 patients (15%) receiving eculizumab no longer required transfusions. Noninferiority of pegcetacoplan to eculizumab was shown for the change in absolute reticulocyte count but not for the change in lactate dehydrogenase level. Functional Assessment of Chronic Illness Therapy–Fatigue scores improved from baseline in the pegcetacoplan group. The most common adverse events that occurred during treatment in the pegcetacoplan and eculizumab groups were injection site reactions (37% vs. 3%), diarrhea (22% vs. 3%), breakthrough hemolysis (10% vs. 23%), headache (7% vs. 23%), and fatigue (5% vs. 15%). There were no cases of meningitis in either group.ConclusionsPegcetacoplan was superior to eculizumab in improving hemoglobin and clinical and hematologic outcomes in patients with PNH by providing broad hemolysis control, including control of intravascular and extravascular hemolysis. (Funded by Apellis Pharmaceuticals; PEGASUS ClinicalTrials.gov, NCT03500549.)

Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis

BackgroundRoxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis.MethodsIn a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to −1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values.ResultsA total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (±SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7±1.1 g per deciliter) than epoetin alfa (0.5±1.0 g per deciliter) and was statistically noninferior (difference, 0.2±1.2 g per deciliter; 95% confidence interval [CI], −0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 μg per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, −22 mg per deciliter; 95% CI, −29 to −16), as was the decrease in low-density lipoprotein cholesterol (difference, −18 mg per deciliter; 95% CI, −23 to −13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, −64.8 to −13.6), as compared with 2.3 ng per milliliter (95% CI, −51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group.ConclusionsOral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.)

Cesarean Myomectomy: Is it a Safe Procedure?

Objective: To determine whether myomectomy during cesarean section causes an increase in intraoperative and postoperative complications. Materials and methods: A total of 55 patients who had undergone myomectomy during cesarean and a total of 55 patients who undergone only cesarean section in our clinic between January 2010 and December 2013 were retrospectively reviewed. Results: Mean change in hemoglobin level was 1.72±0.56 and 1.59±0.63 in the patients that underwent cesarean myomectomy and the patients that underwent cesarean section only, respectively, and no significant difference was found between the two groups. The incidence of hemorrhage was 5.44% and 5.35%, respectively, and no hysterectomy was required in any patient in both groups. The mean length of postoperative stay was 2.26±0.57 and 2.089±0.34 days, respectively, and no significant difference was found. Blood transfusion was required in 6 patients, with 3 patients in each group. Conclusion: Myomectomy during caesarean section is a safe procedure and does not increase the incidence of intraoperative and postoperative complications.

Robotic Single-Site Myomectomy: Clinical Analysis of 61 Consecutive Cases

Study ObjectivesTo report 61 consecutive cases of successful robotic single-site myomectomy (RSSM), and to evaluate the feasibility and safety of RSSM. DesignRetrospective analysis of 61 cases involving RSSM (Canadian Task Force classification III). SettingDepartment of Obstetrics and Gynecology, College of Medicine, Robot Surgery Center, Ewha Womans University, Seoul, Republic of Korea. PatientsSixty-one patients who underwent RSSM performed by 3 gynecologic surgeons at Ewha Womans University between December 2014 and May 2016. InterventionsWe analyzed the patients' baseline characteristics and surgical variables and the trends in operation-related variables according to surgeon's level of experience with RSSM. Measurements and Main ResultsThere were no cases of conversion to laparotomy or robotic multisite myomectomy. RSSM was successful for multiple uterine myomas up to 12 in number and for large myomas up to 12.8 cm in longest diameter. In terms of myoma location, RSSM was successful for all types of myomas, including subserosal, intramural, and intraligamentary. The mean docking time was 5.45 ± 2.84 minutes (2.0∼12.0 minutes), mean total operation time was 135.98 ± 59.62 minutes (60∼295 minutes), mean estimated blood loss was 182.62 ± 153.02 mL (10∼600 mL), and mean skin incision length was 2.70 ± 0.19 cm (2.4∼3.10 cm). The mean time to postoperative gas passage was 28.71 ± 12.99 hours (3.33∼76.50 hours), and the mean duration of hospitalization was 4.21 ± 0.84 days (3∼6 days). No patient required additional analgesics other than applied intravenous patient-controlled analgesia. The mean change in hemoglobin level was 2.43 ± 0.87 g/dL, and the incidence of postoperative anemia requiring blood transfusion was only 3.3% (2 cases). No intraoperative or perioperative complications were noted. ConclusionRSSM is a feasible and safe procedure even in cases large, multiple, and intramural type myomas. Therefore, this option could be extended to appropriately selected patients.

Intravenous iron monotherapy for the treatment of non-iron-deficiency anemia in cancer patients undergoing chemotherapy: a pilot study

BackgroundAnemia in patients with cancer who are undergoing active therapy is commonly encountered and may worsen quality of life in these patients. The effect of blood transfusion is often temporary and may be associated with serious adverse events. Erythropoiesis-stimulating agents are not effective in 30%–50% of patients and may have a negative effect on overall survival.AimsTo assess the efficacy and feasibility of intravenous iron therapy in patients with cancer who have non-iron-deficiency anemia and who are undergoing treatment with chemotherapy without the use of erythropoiesis-stimulating agents.MethodsAdult patients with solid cancers and non-iron-deficiency anemia were included. Ferric sucrose at a dose of 200 mg was given in short intravenous infusions weekly for a total of 12 weeks. Hemoglobin level was measured at baseline, every 3 weeks, and 2 weeks after the last iron infusion (week 14). Adverse events related to intravenous iron were prospectively reported.ResultsOf 25 patients included, 19 (76.0%) completed at least three iron infusions and 14 (56.0%) finished the planned 12 weeks of therapy. The mean hemoglobin level of the 25 patients at baseline was 9.6 g/dL (median, 9.9 g/dL; range, 6.9 g/dL 10.9 g/dL). The mean change in hemoglobin level for the 15 patients who completed at least 9 treatments was 1.7 g/dL (median, 1.1 g/dL; range, −1.9 g/dL to 3.2 g/dL); it reached 2.1 g/dL (median, 1.3 g/dL; range, −0.2 g/dL to 4.6 g/dL; P = 0.0007) for the 14 patients who completed all 12 weekly treatments. Five (20.0%) patients were transfused and considered as treatment failures. No treatment-related adverse events were reported.ConclusionIntravenous iron treatment alone is safe and may reduce blood transfusion requirements and improve hemoglobin level in patients with cancer who are undergoing anticancer therapy. Further randomized studies are needed to confirm these findings.

Conversion from Recombinant Human Erythropoietin to Once Every 4 Weeks Darbepoetin Alfa for Treatment of Renal Anemia in CAPD Patients

Background Darbepoetin alfa is a new erythropoietic protein with a three-fold longer half-life than recombinant human erythropoietin (rHuEPO), allowing for an extended dosing interval of once every 2 weeks in patients with chronic renal failure. The objective of this study was to investigate the possibility of further extending the dose interval of this erythropoietic agent to once every 4 weeks in the treatment of renal anemia in dialysis patients. Methods A prospective study was carried out in 14 continuous ambulatory peritoneal dialysis (CAPD) patients stably maintained on subcutaneous rHuEPO with hemoglobin level of 10–13 g/dL. They were switched to subcutaneous darbepoetin alfa administered once every 4 weeks for a period of 24 weeks. The starting dose was 40 [.proportional]g. The dose of darbepoetin alfa was then adjusted to maintain a target hemoglobin level between 10 and 13 g/dL. When darbepoetin alfa was increased by 100%, the dosing interval was shortened to maintain the target hemoglobin. Evaluation was done during the last 4 weeks. Results Of the 14 patients recruited, 11 patients completed the study. Of these 11 patients, 9 (82%) successfully maintained the target hemoglobin with once every 4 weeks darbepoetin alfa. For those successful patients, the mean hemoglobin level during the evaluation period was 11.13 ± 2.04 g/dL (mean ± standard deviation), and the mean change in hemoglobin level from baseline was −1.03 g/dL (95% CI: −2.34, 0.27). The mean weekly darbepoetin alfa dose requirement during the evaluation period was 12.33 ± 4.80 [.proportional]g/week, and the mean change in weekly dose from baseline was +2.33 [.proportional]g/week (95% CI: −1.35, 6.02). No serious adverse event related to darbepoetin alfa occurred during the study. Conclusion Darbepoetin alfa administered once every 4 weeks effectively maintained hemoglobin level in most CAPD patients after conversion from previously stabilized rHuEPO treatment. Darbepoetin alfa is safe and well tolerated, allowing for less frequent dosing. [ Hong Kong J Nephrol 2007;9(2):77–81]

Comparison of Darbepoetin alfa and Epoetin alfa in the Management of Anemia of Critical Illness

To compare the effectiveness of darbepoetin alfa with epoetin alfa (recombinant human erythropoietin [rHuEPO]) for achieving transfusion independence and increasing hemoglobin concentrations in critically ill patients. Retrospective, descriptive study. Level I trauma center intensive care units. Seventy-two patients who spent at least 3 days in the cardio-thoracic, medical, or surgery-trauma intensive care units and received at least one weekly dose of rHuEPO 40,000 units (33 patients) or darbepoetin alfa 100 microg (39 patients). Number of rHuEPO and darbepoetin alfa doses, hemoglobin concentrations, and cumulative number of transfusions were recorded for up to 28 days after the first dose was given, and the data were statistically analyzed. Beginning a median of 10 days after the patients were admitted to the intensive care unit, they received a median of 3.5 doses of darbepoetin alfa or 4 doses of rHuEPO. Mean hemoglobin concentrations at which treatment with darbepoetin alfa and rHuEPO were started were 8 and 8.2 g/dl, respectively (p=0.41). Transfusion independence was achieved in 44% of patients in the darbepoetin alfa group compared with 36% of patients in the rHuEPO group (p=0.63). Patients in both groups received a mean of 2.7 units of packed red blood cells during the 28-day study period. The mean change in hemoglobin levels from baseline over time did not significantly differ between groups (p=0.75). Patients receiving darbepoetin alfa 100 microg/week and those receiving rHuEPO 40,000 units/week for anemia of critical illness achieved similar rates of transfusion independence and increases in hemoglobin concentrations from baseline at 28 days. Compared with previously published studies, erythropoietic agents were administered late in the course of critical illness in response to low hemoglobin concentrations.

Pharmacokinetics and pharmacodynamics of once-weekly subcutaneous epoetin alfa in critically ill patients: Results of a randomized, double-blind, placebo-controlled trial*

To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients. Randomized, double-blind, placebo-controlled study. Medical, surgical, or mixed medical/surgical intensive care units. A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%. Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n=48) or matching placebo (n=25) for up to 4 wks. Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo. Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.

A randomized, active-control, pilot trial of front-loaded dosing regimens of darbepoetin-alfa for the treatment of patients with anemia during chemotherapy for malignant disease

BACKGROUND Anemia in patients receiving chemotherapy can be ameliorated with recombinant human erythropoietin (rHuEPO), which is administered one to three times per week. Darbepoetin α, a new erythropoietic agent, has longer serum residence time, allowing it to be administered less frequently. METHODS Patients (n = 127) were randomized to receive study drug for 12 weeks: either rHuEPO 40,000 U with escalations to 60,000 U for nonresponders or darbepoetin α at doses of 4.5 μg/kg per week until hemoglobin concentration ≥ 12 g/dL, then 1.5 μg/kg per week (Group 1); 4.5 μg/kg per week for 4 weeks, then 2.25 μg/kg per week for 8 weeks (Group 2); or 4.5 μg/kg per week for 4 weeks, then 3.0 μg/kg every 2 weeks (Group 3). Efficacy was measured using the mean change in hemoglobin level, the proportion of patients achieving a hemoglobin response, the time to response, and the mean change in Functional Assessment of Cancer Therapy-Fatigue Scale scores. Safety was assessed by reports of adverse events. RESULTS Overall, after 4 weeks of treatment, the mean change (95% confidence interval [95%CI]) in hemoglobin concentration was 0.53 g/dL (95%CI, 0.05–1.02 g/dL), 0.70 g/dL (95%CI, 0.11–1.29 g/dL), and 0.90 g/dL (95%CI, 0.47–1.33 g/dL) in darbepoetin α Groups 1, 2, and 3, respectively, and 0.39 g/dL (95%CI, − 0.22–1.00 g/dL) in the rHuEPO group. By the end of the study, the mean change (95%CI) in hemoglobin concentration was 1.35 g/dL (95%CI, 0.67–2.02 g/dL), 1.35 g/dL (95%CI, 0.57–2.12 g/dL), and 1.28 g/dL (95%CI, 0.84–1.73 g/dL) in darbepoetin α Groups 1, 2, and 3, respectively, and 1.03 g/dL (95%CI, 0.53–1.53 g/dL) in the rHuEPO group. The early erythropoietic response in patients who were treated with darbepoetin α was associated with an early and maintained reduction in patient-reported fatigue. The adverse event profile was comparable with all doses of darbepoetin α and rHuEPO. CONCLUSIONS Darbepoetin α, given as a front-loaded dose for 4 weeks and followed by lower and/or less frequent doses, appears to be efficacious and may decrease the time to response relative to treatment with rHuEPO. Cancer 2003;97:1312–20. © 2003 American Cancer Society. DOI 10.1002/cncr.11186

Placental metabolism and function after multielemental intoxication by trace elements

To report 61 consecutive cases of successful robotic single-site myomectomy (RSSM), and to evaluate the feasibility and safety of RSSM.Retrospective analysis of 61 cases involving RSSM (Canadian Task Force classification III).Department of Obstetrics and Gynecology, College of Medicine, Robot Surgery Center, Ewha Womans University, Seoul, Republic of Korea.Sixty-one patients who underwent RSSM performed by 3 gynecologic surgeons at Ewha Womans University between December 2014 and May 2016.We analyzed the patients' baseline characteristics and surgical variables and the trends in operation-related variables according to surgeon's level of experience with RSSM.There were no cases of conversion to laparotomy or robotic multisite myomectomy. RSSM was successful for multiple uterine myomas up to 12 in number and for large myomas up to 12.8 cm in longest diameter. In terms of myoma location, RSSM was successful for all types of myomas, including subserosal, intramural, and intraligamentary. The mean docking time was 5.45 ± 2.84 minutes (2.0∼12.0 minutes), mean total operation time was 135.98 ± 59.62 minutes (60∼295 minutes), mean estimated blood loss was 182.62 ± 153.02 mL (10∼600 mL), and mean skin incision length was 2.70 ± 0.19 cm (2.4∼3.10 cm). The mean time to postoperative gas passage was 28.71 ± 12.99 hours (3.33∼76.50 hours), and the mean duration of hospitalization was 4.21 ± 0.84 days (3∼6 days). No patient required additional analgesics other than applied intravenous patient-controlled analgesia. The mean change in hemoglobin level was 2.43 ± 0.87 g/dL, and the incidence of postoperative anemia requiring blood transfusion was only 3.3% (2 cases). No intraoperative or perioperative complications were noted.RSSM is a feasible and safe procedure even in cases large, multiple, and intramural type myomas. Therefore, this option could be extended to appropriately selected patients.