Chinese physician perception on the treatment of chemotherapy-induced anemia: online cross-section survey study.

BACKGROUND: The management of chemotherapy induced anemia (CIA) remains challenging. The potential risk and benefits in providing patient-centered care need to be balanced; the disease is multifactorial; and the major treatments including red blood cell (RBC) transfusions, erythropoiesis-stimulating agents (ESAs) and intravenous injection (i.v.)iron supplementation have a unique set of strengths and limitations. Also, most previous survey based on the patient data could not reveal the process of evaluation and decision-making for CIA treatment from a physician's perspective. As the comparison of China Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines, the standard of CIA treatment in China will vary from United States and Europe, for example, the initial hemoglobin (Hb) for RBC transfusions. In order to understand the diagnosis, treatment, and unmet medical needs of CIA patients, the China Medical Education Association (CMEA), in conjunction with Cancer Hope Medium, initiated the first national survey of Chinese physicians regarding the diagnosis and treatment of CIA. METHODS: The CMEA sent an online, 12-item questionnaire (via wjx.cn) to physicians across China from September 1, 2022 to October 22, 2022. Two hundred and sixty-five samples were calculated usingsurveyplanet.com. The questionnaire evaluated the impact of anemia on chemotherapy interruption, initial treatment, the target Hb level of CIA in, and the current status of ESAs prescription in clinical practice. Respondents were asked to score their reasons for not using ESAs (including safety issues, drug access in practice or adherence) and the risk options of the current treatment including ESAs, RBC transfusion, and i.v.iron. RESULTS: A total of 331 questionnaires among 5,000 web visits were gathered, covering 247 hospitals in 29 provinces across China, of which 130 (53%) were tier IIIA hospitals, 50 (20%) were tier III B hospitals, 59 (24%) were tier IIA hospitals, and 8 (3%) were tier II B hospitals. The frequency of chemotherapy dose delay/reduction due to anemia was 24% [standard deviation (SD) 49%]. Most responding physicians rated an initial Hb level for ESAs treatment to be 80 g/L, with a favorable Hb level for chemotherapy being 100 g/L (60%), which would not limit treatment availability. The majority (67.6%, n=221) of physicians who responded indicated that they had used ESAs for anemia correction, while the others (32.4%, n=106) reported never using them. CONCLUSIONS: This is the first study in conducting a large-scale survey on the diagnosis and treatment of CIA in China from a physicians' perspective. We found that in China, nearly one-quarter of patients undergoing chemotherapy with concurrent anemia may experience interruption of chemotherapy and that the initiation of anemia treatment is not adequately timed. In treating CIA, most physicians prioritize the completion of chemotherapy via Hb level over treating the symptoms of anemia.

Compassionate use of roxadustat for treatment of refractory renal anemia in an infant.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) have played an important role in the treatment of renal anemia in children, but cannot improve hemoglobin to target level in some cases. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, can stimulate endogenous erythropoietin production and regulate iron metabolism even in patients with kidney failure. However, roxadustat has not yet been approved for use in children. CASE-DIAGNOSIS/TREATMENT: We report a case of refractory renal anemia in an 80-day-old boy, who was hyporesponsive to ESAs even in combination with iron supplementation and transfusion. Compassionate use of roxadustat successfully corrected the intractable anemia. Hyperkalemia is a manageable adverse event of concern during follow-up. CONCLUSION: The successful experience in this case may inform the clinical utility of roxadustat for refractory renal anemia in children, which should be further confirmed by well-designed prospective clinical trials.

Fatigue visual analogue scale score correlates with quality of life in cancer patients receiving epoetin alfa (Sandoz) for chemotherapy-induced anaemia: The CIROCO study.

PURPOSE: Available tools to measure fatigue and health-related quality of life (HRQoL) in cancer patients are often difficult to use in clinical practice. The fatigue visual analogue scale (VAS) provides a simple method to assess fatigue. This study evaluated the correlation between HRQoL and fatigue perceived by cancer patients undergoing chemotherapy. METHODS: This was a non-interventional prospective study of adult cancer patients in France presenting with chemotherapy-induced anaemia (CIA) treated with epoetin alfa (Sandoz). Data were collected using an electronic case report form at study inclusion (T0), after 2-3 chemotherapy cycles (T1) and after 4-6 cycles (T2). RESULTS: The study included 982 patients from September 2015 to October 2017. Overall, there was a negative correlation between fatigue VAS and HRQoL. The overall haemoglobin (Hb) change between T0 and T2 was +17.8 % (± 18.1 %). Fatigue assessed by both patients and physicians showed a clinically significant improvement during the study. Global HRQoL also increased. CONCLUSION: Treatment of CIA with epoetin alfa (Sandoz) improved Hb levels, fatigue, and HRQoL, with a correlation observed between fatigue VAS score and HRQoL. Fatigue VAS could act as a simple alternative to more complex methods to measure HRQoL; however, further analyses are required to confirm this association.

Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients: a systematic review.

BACKGROUND: Iron supplementation and erythropoiesis-stimulating agent (ESA) administration represent the hallmark therapies in preoperative anemia treatment, as reflected in a set of evidence-based treatment recommendations made during the 2018 International Consensus Conference on Patient Blood Management. However, little is known about the safety of these therapies. This systematic review investigated the occurrence of adverse events (AEs) during or after treatment with iron and/or ESAs. METHODS: Five databases (The Cochrane Library, MEDLINE, Embase, Transfusion Evidence Library, Web of Science) and two trial registries (ClinicalTrials.gov, WHO ICTRP) were searched until 23 May 2022. Randomized controlled trials (RCTs), cohort, and case-control studies investigating any AE during or after iron and/or ESA administration in adult elective surgery patients with preoperative anemia were eligible for inclusion and judged using the Cochrane Risk of Bias tools. The GRADE approach was used to assess the overall certainty of evidence. RESULTS: Data from 26 RCTs and 16 cohort studies involving a total of 6062 patients were extracted, on 6 treatment comparisons: (1) intravenous (IV) versus oral iron, (2) IV iron versus usual care/no iron, (3) IV ferric carboxymaltose versus IV iron sucrose, (4) ESA+iron versus control (placebo and/or iron, no treatment), (5) ESA+IV iron versus ESA+oral iron, and (6) ESA+IV iron versus ESA+IV iron (different ESA dosing regimens). Most AE data concerned mortality/survival (n=24 studies), thromboembolic (n=22), infectious (n=20), cardiovascular (n=19) and gastrointestinal (n=14) AEs. Very low certainty evidence was assigned to all but one outcome category. This uncertainty results from both the low quantity and quality of AE data due to the high risk of bias caused by limitations in the study design, data collection, and reporting. CONCLUSIONS: It remains unclear if ESA and/or iron therapy is associated with AEs in preoperatively anemic elective surgery patients. Future trial investigators should pay more attention to the systematic collection, measurement, documentation, and reporting of AE data.

Hypoxia-inducible factor prolyl hydroxylase inhibitors for anemia in heart failure patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Anemia is common in heart failure (HF) patients with chronic kidney disease (CKD) and is associated with worse outcomes. Iron supplementation improves symptoms and is associated with reduced risk of hospitalization for HF in iron-deficiency HF patients. However, iron deficiency is present in <30% of anemic HF patients. Erythropoiesis stimulating agents (ESAs) improve symptoms but are associated with increased risk of thromboembolic events in anemic HF patients with CKD. Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are a new class of agents for the treatment of anemia. These agents work by stabilizing the HIF complex, thereby stimulating endogenous erythropoietin production. We hypothesized that HIF-PH inhibitors may be associated with reduced risk of cardiovascular outcomes compared with ESAs in anemic HF patients with CKD. Accordingly, we aim to perform the meta-analysis of studies on the efficacy and safety of HIF-PH inhibitors compared with ESAs in anemic HF patients with CKD. METHODS: This meta-analysis will include prospective cohort studies and randomized controlled trials on the effect of HIF-PH inhibitors compared with ESAs in anemic HF patients with CKD. Information of studies will be collected from PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov. The primary outcome will be cardiovascular death. The secondary outcomes will be all-cause death, hospitalization for HF, HF symptoms, exercise capacity, health-related quality of life, and hemoglobin levels. DISCUSSION: This meta-analysis will evaluate the effect of HIF-PH inhibitors in anemic HF patients with CKD, providing evidence regarding the use of HIF-PH inhibitors in these patients. SYSTEMATIC REVIEW REGISTRATION: INPLASY202230103.

Prescription rate of erythropoietin-stimulating agents is low for patients with renal impairment under non-nephrology care in a tertiary-level academic medical center in Japan.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) and iron supplements may be prescribed appropriately under nephrology care. However, there are few reports detailing the differences in prescription rates of these therapies among clinical departments. METHODS: A total of 39,585 patients with renal impairment were enrolled from a database of 914,280 patients. Patients were selected based on an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m2. There were eight clinical departments from internal medicine, including nephrology. We defined a hemoglobin level less than 11.0 g/dL as anemia and set 20% of transferrin saturation and 100 ng/mL of serum ferritin as cutoff points. We compared the prescription rates of ESAs and iron supplementation based on the hemoglobin level and iron status among the patients seen across the eight clinical departments. RESULTS: The lower the eGFR, the more the number of patients seen under nephrology care. The rates of patients with no prescription were 52.3, 39.9, 45.9, and 54.3% among those with hemoglobin levels of < 8, 8 ≤ < 9, 9 ≤ < 10, and 10 ≤ < 11 g/dL, respectively. Of the patients with less than 11.0 g/dL of hemoglobin, 77.3% were prescribed ESAs under nephrology care. Meanwhile, only 18.5 and 8.2% of patients were prescribed ESAs in clinical departments of internal medicine, other than nephrology, and non-internal medicine care, respectively. CONCLUSION: Treatment for anemia has not been sufficiently performed in patients with renal impairment under non-nephrology care in a real-world clinical setting.

Retacrit®, Biosimilar of Epoetin Alfa, in Chemotherapy-Induced Anemia in Routine Practice: Impact of Iron Supplementation.

INTRODUCTION: The aim of the study was to evaluate in real-life conditions the effectiveness and safety of a biosimilar of epoetin alfa (Retacrit®) in chemotherapy-induced anemia and the impact of iron supplementation. METHODS: This was a longitudinal, observational, prospective study of 12-16 weeks conducted in 195 French centers. The primary endpoint was the achievement of target Hb (with an increase of Hb ≥1 g/dL) or an increase of Hb ≥2 g/dL, in the absence of transfusion in the previous 3 weeks. RESULTS: 2,076 patients (women, 50.6%; mean age, 67.0 years) with malignant diseases (solid tumors, 79.8%; lymphomas, 12.7%; multiple myeloma, 6.6%) were analyzed. A total of 655 patients received oral iron (40.5%), intravenous iron (58.9%), or both (0.6%). At inclusion, 10.0% and 18.2% of patients without and with iron supplementation had serum ferritin <100 µg/L, respectively. Transferrin saturation (TSAT) ≤20% was more frequent in patients with supplementation (76.6%) than without supplementation (33.9%). The mean weekly doses of epoetin alfa biosimilar and planned duration of treatment were comparable regardless of iron supplementation. The primary endpoint was achieved in 70.5% and 70.2% of patients without and with iron supplementation, respectively. Three (0.1%) serious thromboembolic events related to treatment with epoetin alfa biosimilar were reported. CONCLUSION: Epoetin alfa biosimilar was effective and well tolerated for treating chemotherapy-induced anemia. Patients in subgroup with iron supplementation had lower TSAT at inclusion compared to subgroup without supplementation. Comparable mean Hb levels were achieved in both subgroups. The rate of patients with iron supplementation through the intravenous route was however insufficient.

High-dose versus low-dose iron sucrose in individuals undergoing maintenance haemodialysis: a retrospective study.

BACKGROUND: Intravenous iron sucrose is becoming a prevailing treatment for individuals undergoing maintenance haemodialysis, but comparisons of dosing regimens are lacking. The aim of this retrospective review was to evaluate the safety and efficacy of proactively administered high-dose iron sucrose versus reactively administered low-dose iron sucrose in patients undergoing maintenance haemodialysis. METHODS: We analysed the data of 1500 individuals with maintenance haemodialysis who were treated with either high-dose iron sucrose that was proactively administered (Group HD) or low-dose iron sucrose that was reactively administered (Group LD) at the First Affiliated Hospital of Chongqing Medical University from Jan 1, 2008, to Dec 31, 2020. The primary endpoints were the cumulative doses of iron and erythropoiesis-stimulating agent; the secondary endpoints were the events of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, infection rate, and death from any cause. RESULTS: Of the 2124 individuals, 624 individuals were excluded because they met one or more of the exclusion criteria, thus resulting in 1500 individuals who were eligible for inclusion in the study (Group HD, n = 760 and Group LD, n = 740). The median follow-up for the two cohorts was 32 months (range: 25-36). A significant median difference was detected in the monthly iron dose between the groups (1121 mg [range: 800-1274] in the HD group vs. 366 mg [range: 310-690] in the LD group; p < 0.05). The median dose of an erythropoiesis-stimulating agent was 26,323 IU/month (range: 17,596-44,712) in the HD group and 37,934 IU/month (range: 22,402-59,380) in the LD group (median difference: - 7901 IU/month; 95% CI: - 9632--5013; p = 0.000). A significant difference was detected in the secondary endpoints (266 events in 320 cases in the HD group vs. 344 events in 385 cases in the LD group) (HR: 0.62; 95% CI: 0.51-0.79; p < 0.001). A significant difference was not observed in death from any cause (HR: 0.57; 95% CI: 0.48-1.00; p = 0.361). CONCLUSIONS: For individuals undergoing maintenance haemodialysis, high-dose iron sucrose that was proactively administered may be superior to low-dose iron sucrose that was reactively administered with low doses of erythropoiesis-stimulating agent.

Hypoxia-inducible factor-prolyl hydroxylase inhibitors for renal anemia in chronic kidney disease: Advantages and disadvantages.

Anemia is a common feature and complication of chronic kidney disease (CKD). Erythropoiesis-stimulating agents (ESAs) and recombinant human erythropoietin have been used widely in renal anemia treatment. Recently, hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs) that may improve the treatment of renal anemia patients were launched. Previous studies indicated that HIF-PHIs may decrease hepcidin levels and modulate iron metabolism, thereby increasing total iron-binding capacity and reducing the need for iron supplementation. Furthermore, HIF-PHIs can reduce inflammation and oxidative stress in CKD. Recombinant erythropoietin has become a routine treatment for patients with CKD and end-stage renal disease with relatively few adverse effects. However, higher doses of recombinant erythropoietin have been demonstrated to be an independent predictor of mortality in patients under hemodialysis. Phase III clinical trials of HIF-PHIs in patients with anemia and dialysis-dependent CKD have shown their efficacy and safety in both non-dialysis and dialysis CKD patients. However, HIFα binds to specific hypoxia-response elements in the vascular endothelial growth factor or retinoic acid-related orphan receptor gamma t (RORγt) promoter, which may be involved in the progression of cancer, psoriasis, and rheumatoid arthritis. In this paper, we have summarized the mechanism, clinical application, and clinical trials of HIF-PHIs in the treatment of renal anemia and aimed to provide an overview of the new drugs in clinical practice, as well as reconsider the advantages and disadvantages of HIF-PHIs and ESAs. Presently, there are not enough clinical studies examining the effects of long-term administration of HIF-PHIs. Therefore, further studies will be needed.

Comparison of Iron Dosing Strategies in Patients Undergoing Long-Term Hemodialysis: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Whether iron supplementation in patients on hemodialysis could be delivered by less frequent but higher single doses compared with the currently more common higher-frequency schedules of lower single iron doses is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We carried out an open-label, randomized, controlled noninferiority trial over 40 weeks in patients on prevalent hemodialysis (n=142). We administered in total 2 g iron as 100 mg iron sucrose biweekly in a continuous (20 × 100 mg) fashion or 500 mg ferric carboxymaltose every 10 weeks in a periodic (4 × 500 mg) fashion. The primary end point was the change in hemoglobin at week 40 from baseline with a noninferiority margin of -0.8 g/dl. Secondary end points were changes in ferritin, transferrin, transferrin saturation, and erythropoiesis-stimulating agent use. RESULTS: In total, 108 patients completed the study. At 40 weeks, hemoglobin changed by -0.27 g/dl (95% confidence interval, -0.64 to 0.09) in the iron sucrose arm and by -0.74 g/dl (95% confidence interval, -1.1 to -0.39) in the ferric carboxymaltose arm compared with baseline. Noninferiority was not established in the per-protocol population as hemoglobin changes compared with baseline differed by -0.47 g/dl (95% confidence interval, -0.95 to 0.01) in the ferric carboxymaltose arm compared with the iron sucrose arm. Proportional changes from baseline to week 40 differed by -31% (98.3% confidence interval, -52 to -0.1) for ferritin, by 1% (98.3% confidence interval, -7 to 10) for transferrin, and by -27% (98.3% confidence interval, -39 to -13) for transferrin saturation in the ferric carboxymaltose arm compared with the iron sucrose arm. Erythropoiesis-stimulating agent dosing did not differ between groups. The overall number of adverse events was similar; however, more infections were observed in the iron sucrose arm. CONCLUSIONS: An equal cumulative dose of ferric carboxymaltose administered less frequently did not meet noninferiority for maintaining hemoglobin levels compared with iron sucrose administered more frequently. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Comparison Study of Two Iron Compounds for Treatment of Anemia in Hemodialysis Patients (COPEFER), NCT02198495.

Drug safety in thalassemia: lessons from the present and directions for the future.

Introduction: Beta-thalassemia is an autosomal recessive hereditary anemia characterized by reduced or absent ß-globin chain synthesis, affecting about 60,000 people peryear. Management for ß-thalassemia major includes regular blood transfusions followed by iron chelating therapy and drug targeting ineffective erythropoiesis.Areas covered: The safety of licensed drugs for the management of ß-thalassemia is reviewed, using evidence from clinical trials and observational research. Such drugs include the iron chelators and the erythrocyte maturation agent luspatercept. The safety of emerging treatment, such as hydroxyurea and thalidomide is also reviewed.Expert opinion: Beta-thalassemia is arare disease, and is not surprising that there are limited studies investigating the safety of drugs used in this disease. Indeed, although observational studies are the main source of drug safety information in areal-world setting, only eleven studies were identified for iron-chelators and none of these estimated the risk of agiven safety outcome. Future work should aim to better leverage existing sources of real-world datato investigate drug safety in thalassemia.

SEOM clinical guidelines for anaemia treatment in cancer patients (2020).

Anaemia is defined by the presence of haemoglobin (Hb) levels < 13 g/dL in men and 12 g/dL in women. Up to 39% of cancer patients present it at the time of diagnosis and up to 40% have iron deficiency. Anaemia causes fatigue, functional deterioration and a reduction in the quality of life; it has also been associated with a poorer response to anti-tumour treatment and lower survival. Basic diagnostic tests for anaemia are simple and should be a routine part of clinical practice. These guidelines review the available evidence on the use of different therapies for treating anaemia: erythropoiesis-stimulating agents, iron supplements, and transfusion of blood products.

Long-term efficacy and safety of hypoxia-inducible factor prolyl hydroxylase inhibitors in anaemia of chronic kidney disease: A meta-analysis including 13,146 patients.

WHAT IS KNOWN AND OBJECTIVE: Previous studies based on small-sample clinical data proved that short-term use of hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) inhibitors increased haemoglobin levels in anaemic patients with chronic kidney disease (CKD). However, these studies reached conflicting conclusions on iron parameters and adverse event profiles. Our meta-analysis aimed to evaluate the long-term efficacy and safety of HIF-PHD inhibitors in renal anaemia. METHODS: Randomized controlled trials comparing treatment with HIF-PHD inhibitors versus placebo or erythropoiesis-stimulating agents (ESAs) were thoroughly searched in the PubMed, Embase, Cochrane Library and international clinical trial registries. Meta-analysis was performed on main outcomes with random effects models. RESULTS AND DISCUSSION: A total of 30 studies comprising 13,146 patients were included. The HIF-PHD inhibitors used included roxadustat, daprodustat, vadadustat, molidustat, desidustat and enarodustat. HIF-PHD inhibitors significantly increased haemoglobin levels in comparison with placebo [weighted mean difference (WMD) 1.53, 95% confidence interval (CI) 1.39 to 1.67] or ESAs (WMD 0.13, 95% CI 0.03 to 0.22). Hepcidin, ferritin and serum iron levels were decreased, while total iron binding capacity and transferrin levels were increased in the HIF-PHD inhibitor group versus those in placebo or ESAs group. Additionally, HIF-PHD inhibitors medication was associated with cholesterol-lowering effects. As for safety, the risk of serious adverse events in the HIF-PHD inhibitor group was increased in comparison with placebo group [risk ratio (RR) 1.07, 95% CI 1.01 to 1.13], but comparable to the ESAs group (RR 1.02, 95% CI 0.94 to 1.10). Compared with placebo, the agents increased the risk of diarrhoea (1.21, 1.00 to 1.47), nausea (1.46, 1.09 to 1.97), oedema peripheral (1.32, 1.01 to 1.59), hyperkalemia (1.27, 1.05 to 1.54) and hypertension (1.34, 1.02 to 1.76). Compared with ESAs, the drugs increased the risk of vomiting (1.30, 1.02 to 1.65), headache (1.27, 1.05 to 1.53) and thrombosis events (1.31, 1.05 to 1.63). WHAT IS NEW AND CONCLUSION: HIF-PHD inhibitors treatment effectively increased haemoglobin levels and promoted iron utilization in anaemic patients with CKD, and they were well tolerated for long-term use. In order to avoid unfavourable effects of excessive iron consumption, it was appropriate to administer HIF-PHD inhibitors in combination with iron supplements for long-term treatment.

Stroke in Hemodialysis Patients Randomized to Different Intravenous Iron Strategies: A Prespecified Analysis from the PIVOTAL Trial.

Background: People with kidney failure treated with hemodialysis (HD) are at increased risk of stroke compared with similarly aged people with normal kidney function. One concern is that treatment of renal anemia might increase stroke risk. We studied risk factors for stroke in a prespecified secondary analysis of a randomized, controlled trial of intravenous iron treatment strategies in HD. Methods: We analyzed data from the Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial, focusing on variables associated with risk of stroke. The trial randomized 2141 adults who had started HD <12 months earlier and who were receiving an erythropoiesis-stimulating agent (ESA) to high-dose IV iron administered proactively or low-dose IV iron administered reactively in a 1:1 ratio. Possible stroke events were independently adjudicated. We performed analyses to identify variables associated with stroke during follow-up and assessed survival following stroke. Results: During a median 2.1 years of follow-up, 69 (3.2%) patients experienced a first postrandomization stroke. Fifty-seven (82.6%) were ischemic strokes, and 12 (17.4%) were hemorrhagic strokes. There were 34 postrandomization strokes in the proactive arm and 35 postrandomization strokes in the reactive arm (hazard ratio, 0.90; 95% confidence interval, 0.56 to 1.44; P=0.66). In multivariable models, women, diabetes, history of prior stroke at baseline, higher baseline systolic BP, lower serum albumin, and higher C-reactive protein were independently associated with stroke events during follow-up. Hemoglobin, total iron, and ESA dose were not associated with risk of stroke. Fifty-eight percent of patients with a stroke event died during follow-up compared with 23% without a stroke. Conclusions: In patients on HD, stroke risk is broadly associated with risk factors previously described to increase cardiovascular risk in this population. Proactive intravenous iron does not increase stroke risk.Clinical Trial registry name and registration number: Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL), 2013-002267-25.

The use of intravenous iron in pregnancy: for whom and when? A survey of Australian and New Zealand obstetricians.

BACKGROUND: Iron deficiency anaemia in pregnancy (IDAP) affects 11-18% of Australian pregnancies and is associated with adverse perinatal outcomes. National prescribing data suggests the use of intravenous iron in pregnancy is increasingly common. This study aimed to: 1) Establish the current patterns of intravenous iron use by Fellows of the Royal Australian and New Zealand College of Obstetricians (FRANZCOG) when treating iron deficiency and IDAP including immediately postpartum and; 2) Assess FRANZCOG opinions regarding potential trial of intravenous iron for first-line treatment of IDAP. METHODS: An online survey of RANZCOG Fellows practicing obstetrics was distributed in September 2018. Results were analysed descriptively and responses compared by clinician demographics using Chi-squared testing. RESULTS: Of 484 respondents (21% of FRANZCOG), 457 were currently practicing obstetrics. Most prescribed intravenous iron in pregnancy (96%) and/or postpartum (85%). Most intravenous iron was prescribed for IDAP (98%) rather than iron deficiency without anaemia (53%), and for IDAP most commonly second-line to failed oral iron supplementation and first-line in special circumstances (59%). Intravenous iron prescribing was associated with shorter time since FRANZCOG completion (p = 0.01), public hospital practice (p = 0.008) and higher hospital birth numbers (p = 0.01). Most respondents (90%) would consider a randomised controlled trial of first-line intravenous iron for IDAP, although views on appropriate thresholds differed. CONCLUSIONS: Almost all respondents prescribed intravenous iron for IDAP, and while mostly used for second-line treatment over half sometimes used it first-line. With accelerating intravenous iron use, further research is required into its optimal use in pregnancy, recognizing important clinical outcomes and cost effectiveness.

Successful Treatment of Iatrogenic Cutaneous Siderosis with Pigment Lasers: A Retrospective Study in 15 Consecutive Patients.

Intravenous ferric carboxymaltose is increasingly used to treat iron deficiency. However, a common side-effect is paravenous extravasation of iron preparations, resulting in cutaneous siderosis. Quality-switched (QS) lasers and, recently, picosecond (PS) lasers have been used to treat these hyperpigmentations with variable success. The optimal treatment protocol remains unclear. The aims of this study were to assess the response of cutaneous siderosis to treatment with pigment lasers and to determine the optimal wavelength, number of treatment sessions and pulse duration. Fifteen patients with cutaneous siderosis on the arms were included. The effectiveness of laser treatment was evaluated using a 5-point standard Physician Global Assessment (PGA) grading system. Differences in continuous variables between distinct groups of patients were assessed with a Mann-Whitney U test. In all 15 patients clearance of at least 50% was obtained. In 12 patients, at least 75% of pigment was removed. In conclusion, pigment lasers are an effective and safe method to treat cutaneous siderosis.

Interventions for fatigue in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is an umbrella term used to describe a group of chronic, progressive inflammatory disorders of the digestive tract. Crohn's disease and ulcerative colitis are the two main types. Fatigue is a common, debilitating and burdensome symptom experienced by individuals with IBD. The subjective, complex nature of fatigue can often hamper its management. The efficacy and safety of pharmacological or non-pharmacological treatments for fatigue in IBD is not yet established through systematic review of studies. OBJECTIVES: To assess the efficacy and safety of pharmacological and non-pharmacological interventions for managing fatigue in IBD compared to no treatment, placebo or active comparator. SEARCH METHODS: A systematic search of the databases Embase, MEDLINE, Cochrane Library, CINAHL, PsycINFO was undertaken from inception to July 2018. A top-up search was run in October 2019. We also searched the Cochrane IBD Group Specialized Register, the Cochrane Central Register of Controlled Trials, ongoing trials and research registers, conference abstracts and reference lists for potentially eligible studies. SELECTION CRITERIA: Randomised controlled trials of pharmacological and non-pharmacological interventions in children or adults with IBD, where fatigue was assessed as a primary or secondary outcome using a generic or disease-specific fatigue measure, a subscale of a larger quality of life scale or as a single-item measure, were included. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results and four authors extracted and assessed bias independently using the Cochrane 'Risk of bias' tool. The primary outcome was fatigue and the secondary outcomes included quality of life, adverse events (AEs), serious AEs and withdrawal due to AEs. Standard methodological procedures were used. MAIN RESULTS: We included 14 studies (3741 participants): nine trials of pharmacological interventions and five trials of non-pharmacological interventions. Thirty ongoing studies were identified, and five studies are awaiting classification. Data on fatigue were available from nine trials (1344 participants). In only four trials was managing fatigue the primary intention of the intervention (electroacupuncture, physical activity advice, cognitive behavioural therapy and solution-focused therapy). Electroacupuncture Fatigue was measured with Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (scores range from 0 to 52). The FACIT-F score at week eight was 8.00 points higher (better) in participants receiving electroacupuncture compared with no treatment (mean difference (MD) 8.00, 95% CI 6.45 to 9.55; 1 RCT; 27 participants; low-certainty evidence). Results at week 16 could not be calculated. FACIT-F scores were also higher with electroacupuncture compared to sham electroacupuncture at week eight (MD 5.10, 95% CI 3.49 to 6.71; 1 RCT; 30 participants; low-certainty evidence) but not at week 16 (MD 2.60, 95% CI 0.74 to 4.46; 1 RCT; 30 participants; low-certainty evidence). No adverse events were reported, except for one adverse event in the sham electroacupuncture group. Cognitive behavioural therapy (CBT) and solution-focused therapy Compared with a fatigue information leaflet, the effects of CBT on fatigue are very uncertain (Inflammatory Bowel Disease-Fatigue (IBD-F) section I: MD -2.16, 95% CI -6.13 to 1.81; IBD-F section II: MD -21.62, 95% CI -45.02 to 1.78; 1 RCT, 18 participants, very low-certainty evidence). The efficacy of solution-focused therapy on fatigue is also very uncertain, because standard summary data were not reported (1 RCT, 98 participants). Physical activity advice One 2 x 2 factorial trial (45 participants) found physical activity advice may reduce fatigue but the evidence is very uncertain. At week 12, compared to a control group receiving no physical activity advice plus omega 3 capsules, FACIT-F scores were higher (better) in the physical activity advice plus omega 3 group (FACIT-F MD 6.40, 95% CI -1.80 to 14.60, very low-certainty evidence) and the physical activity advice plus placebo group (FACIT-F MD 9.00, 95% CI 1.64 to 16.36, very low-certainty evidence). Adverse events were predominantly gastrointestinal and similar across physical activity groups, although more adverse events were reported in the no physical activity advice plus omega 3 group. Pharmacological interventions Compared with placebo, adalimumab 40 mg, administered every other week ('eow') (only for those known to respond to adalimumab induction therapy), may reduce fatigue in patients with moderately-to-severely active Crohn's disease, but the evidence is very uncertain (FACIT-F MD 4.30, 95% CI 1.75 to 6.85; very low-certainty evidence). The adalimumab 40 mg eow group was less likely to experience serious adverse events (OR 0.56, 95% CI 0.33 to 0.96; 521 participants; moderate-certainty evidence) and withdrawal due to adverse events (OR 0.48, 95%CI 0.26 to 0.87; 521 participants; moderate-certainty evidence). Ferric maltol may result in a slight increase in fatigue, with better SF-36 vitality scores reported in the placebo group compared to the treatment group following 12 weeks of treatment (MD -9.31, 95% CI -17.15 to -1.47; 118 participants; low-certainty evidence). There may be little or no difference in adverse events (OR 0.55, 95% CI 0.26 to 1.18; 120 participants; low-certainty evidence) AUTHORS' CONCLUSIONS: The effects of interventions for the management of fatigue in IBD are uncertain. No firm conclusions regarding the efficacy and safety of interventions can be drawn. Further high-quality studies, with a larger number of participants, are required to assess the potential benefits and harms of therapies. Future studies should assess interventions specifically designed for fatigue management, targeted at selected IBD populations, and measure fatigue as the primary outcome.

A rare occurrence of intrauterine death following an allergic reaction to iron sucrose.

During pregnancy, iron-deficiency anemia if untreated can affect the mother and child and hence iron is supplemented. Intolerance to oral iron therapy and malabsorption are common indications for parenteral iron therapy. The regularly used intravenous iron preparations are iron sucrose, sodium ferric gluconate, and iron dextran, of which iron sucrose has a satisfactory safety profile. We report a case of iron sucrose causing rare reaction with generalized edema in the mother, which was followed by intrauterine death. The oxidative stress due to immune-mediated mechanisms or adjuvant used in iron sucrose could cause mild rashes to severe anaphylactic reactions. This case report warns us toward the use of parenteral iron preparations in pregnant women, as one of the safe formulations could lead to an unusual fatal outcome in the fetus.

Efficacy and safety of a low monthly dose of intravenous iron sucrose in peritoneal dialysis patients.

PURPOSE: Scientific data regarding intravenous iron supplementation in peritoneal dialysis (PD) patients are scarce. In attempting to administer the minimum monthly IV iron dose that could improve erythropoiesis, we wanted to assess the safety and efficacy of monthly maintenance intravenous administration of 100 mg iron sucrose in PD patients. METHODS: In a 9-month prospective study, all clinically stable PD patients received intravenously 200 mg of iron sucrose as a loading dose, followed by monthly doses of 100 mg for five consecutive months. Levels of hemoglobin (Hb), ferritin, transferrin saturation (TSAT), reticulocyte hemoglobin content (CHr) and C-reactive protein (CRP) were measured before each administration and 3 months after the last iron infusion. Also, doses of concurrent erythropoietin administration were recorded. RESULTS: Eighteen patients were eligible for the study. Mean levels of Hb and ferritin increased significantly (from 10.0 to 10.9 mg/dL, p = 0.01 and from 143 to 260 ng/mL, p = 0.005), as well as the increase in TSAT levels approached borderline significance (from 26.2 to 33.1%, p = 0.07). During the 6 months of iron administration, the erythropoietin dose was reduced in five patients and discontinued in one. During the 3 months following the last iron infusion, three of them again raised the erythropoietin dose to previous levels. None of the patients experienced any side effects related to IV iron administration. CONCLUSIONS: A monthly maintenance intravenous dose of 100 mg iron sucrose may be a practical, effective, and safe in the short term, treatment of anemia in PD patients resulting in improved hemoglobin levels, iron indices, and erythropoietin response.

Intravenous iron supplementation does not increase infectious disease risk in hemodialysis patients: a nationwide cohort-based case-crossover study.

BACKGROUND: Studies have reported conflicting findings on the infection risk posed by intravenous iron supplementation among hemodialysis (HD) patients. We used a novel study design to assess associations between intravenous iron and infectious diseases. METHODS: Patients initiating HD between 1998 and 2008 were extracted from Taiwan's National Health Insurance Research Database. Their first infectious disease in the period between 1.5 years after dialysis initiation and 2010 was identified and defined as the index date. Through the case-crossover design, the odds of exposure to intravenous iron within the 1-month period immediately preceding the index date (i.e., the case period) were compared with iron exposure in three different matched control periods for the same enrollee, thus possibly reducing some unmeasured confounders. RESULTS: A total of 1410 patients who met our enrollment criteria were extracted from incident HD patients. The odds of intravenous iron exposure during the case period versus total control periods exhibited no significant difference (odds ratio: 1.000, 95% confidence interval: 0.75-1.33). In subgroup analyses, this association remained nonsignificant across patients with diabetes mellitus, heart failure, chronic lung disease, venous catheter for HD, and higher iron load. CONCLUSIONS: We found that intravenous iron supplementation did not increase short-term infection risk among HD patients.