Community screening for iron deficiency in reproductive aged women: Lessons learnt from Australia.

BACKGROUND AND OBJECTIVES: Reproductive-aged women are at an increased risk of developing iron deficiency (ID). We aimed to develop a non-invasive screening tool to identify ID in women and assess the acceptability of screening. STUDY DESIGN AND METHODS: We screened women (age 18-49 years) in the community of Western Australia. PRIMARY OUTCOME: acceptability of screening, assessed by the feasibility of recruiting the required sample size (n = 323). SECONDARY OUTCOMES: Hand grip strength, finger prick haemoglobin concentration (Hb), prevalence of heavy menstrual bleeding (HMB), diet, pregnancy history, blood donation, symptoms of ID and history of ID or anaemia (Hb < 120 g/L). Those with Hb <130 g/L and no history of iron therapy in the past 2 years were given referrals for venous full blood count and ferritin sampling. RESULTS: Across 5 days, we recruited 640 eligible women. Of which, 178 (28%) had HMB and 79 (12%) were anaemic. Mean age was 33.5 ± 9.2 years, and mean Hb was 132.4 ± 11.9 g/L. In the past 2 years: 335 (52%) were diagnosed with ID or anaemia; 322 (50%) had taken oral iron; and 210 (33%) had an intravenous iron infusion. Vegetarian diets were followed by 89 (14%); 40 (6%) were regular blood donors; 290 (45%) had a previous pregnancy. HMB increased the risk of symptoms of ID and having prior ID/anaemia diagnosis (67% vs. 47%) or treatment (p < 0.022). Hand grip strength showed a positive relationship with both Hb (adjusted R2 = 0.012, p = 0.004) and ferritin (adjusted R2 = 0.135, p = 0.005). CONCLUSION: ID screening was well accepted by women in the community, with high recruitment rates over a short period. Future screening tool development may consider incorporating hand grip strength and HMB assessment.

Associations between non-anaemic iron deficiency and outcomes following elective surgery for colorectal cancer: a prospective cohort study.

BACKGROUND: Iron deficiency is present in up to 75% of patients presenting for colorectal cancer surgery. It is unclear whether iron deficiency without anaemia is associated with worse postoperative outcomes. We hypothesised that, in adults without anaemia undergoing surgery for colorectal cancer, iron deficiency would be associated with worse postoperative outcomes relative to an iron-replete state. METHODS: We performed a prospective, observational study, recruiting adults (aged ≥ 18 y) without anaemia who were undergoing surgery for colorectal cancer in 16 hospitals across Australia and Aotearoa/New Zealand. Anaemia was defined as a haemoglobin concentration < 130 g.l-1 for men and < 120 g.l-1 for women. Iron deficiency was defined primarily as transferrin saturation < 20%. The primary endpoint was days alive and at home on postoperative day 90. The primary endpoint analysis was adjusted for surgical risk based on recruiting institution; sex; Charlson comorbidity index; CR-POSSUM score; surgical approach; and requirement for neoadjuvant therapy. RESULTS: Of 420 patients, 170 were iron deficient and 250 were iron replete. The median (IQR [range]) days alive and at home in the iron-deficient group was 84.0 (80.7-85.9 [0-88.2]) days and in the iron-replete group was 83.1 (78.7-85.1 [0-88.9]) days. The unadjusted difference in medians between groups was 0.9 (95%CI 0-1.8, p = 0.047) days and the adjusted difference was 0.9 (95%CI 0-1.80, p = 0.042) days, favouring the iron-deficient group. CONCLUSIONS: In adult patients without anaemia undergoing surgery for colorectal cancer, iron deficiency defined by transferrin saturation < 20% was not associated with worse patient outcomes and appeared to be associated with more days alive and at home on postoperative day 90.

Nutcracker syndrome (a Delphi consensus).

BACKGROUND: Nutcracker syndrome (NCS) describes the symptomatic compression of the left renal vein between the aorta and superior mesenteric artery. Whereas asymptomatic compression is a common radiological finding, patients with NCS can report a range of symptoms. There are no specific diagnostic criteria and interventions include a range of open surgical and endovascular procedures. Therefore, we wished to develop an international consensus document covering aspects of diagnosis, management, and follow-up for patients with NCS. METHODS: A three-stage modified Delphi consensus was performed. A steering committee developed 37 statements covering 3 categories for patients with NCS: diagnosis, management, and follow-up. These statements were reported individually by 20 international experts in the management of venous disease, using a 5-point Likert scale. Consensus was defined if ≥70% of respondents rated the statement between 1 and 2 (agreement) and between 4 and 5 (disagreement). Those statements without consensus were recirculated in a second round of voting. A third round of the questionnaire was performed with 14 additional statements to clarify diagnostic values of NCS. RESULTS: Responses were returned by 20 of 20 experts (100%) in round one and 17 of 20 (85%) in round two. Initial consensus was reached in 24 of 37 statements (65%) spread over all categories. Round two achieved a further consensus on 5 out of 10 statements (50%). No categories reported consensus on all statements. In round two consensus was reached in the category of follow-up (4/5 statements [80%]). The final round reached consensus on 5 out of 14 statements (36%). Experts agreed that imaging is obligated to confirm NCS. Experts did not agree on specific diagnostic cut-off values. There was a consensus that the first choice of operative treatment is left renal vein transposition and that the risk of stent migration outweighs the advantages of a percutaneous procedure. CONCLUSIONS: Consensus was achieved on most statements concerning the assessment and management of NCS. This Delphi consensus identified those areas in which further research is needed, such as antiplatelet therapy, endovascular treatment, and renal autotransplantation. A rare disease registry to improve data and reports of patient outcomes is warranted.

Evaluating diagnostic tools, outcome measures and antibiotic approach in diabetic foot osteomyelitis: a scoping review and narrative synthesis.

INTRODUCTION: Diabetic foot osteomyelitis (DFO) is a significant complication of diabetic foot disease; however, diagnosis remains challenging and treatment success is difficult to ascertain. Literature in this space that has utilized varying diagnostic criteria and ideal outcome measures for success is unclear. AREAS COVERED: This scoping review assesses methods of diagnosis of DFO and definitions of treatment outcomes in the literature assessing antibiotic therapy for treatment of DFO. EXPERT OPINION: There is a lack of consensus in the design of diabetic foot trials, resulting in difficulty for clinicians to assess and manage serious conditions such as DFO. The cure for DFO is challenging to ascertain and treatment failure may be a better approach to assess outcomes in research assessing the efficacy of antibiotic therapy. In the absence of gold-standard diagnostic tools, practical approaches to outcome assessment may allow for greater clinical applicability of available data.

Efficacy of iron supplementation on physical capacity in non-anaemic iron-deficient individuals: protocol for an individual patient data meta-analysis.

BACKGROUND: A deficiency in iron stores is associated with various adverse health complications, which, if left untreated, can progress to states of anaemia, whereby there is significant detriment to an individual's work capacity and quality of life due to compromised erythropoiesis. The most common methods employed to treat an iron deficiency include oral iron supplementation and, in persistent and/or unresponsive cases, intravenous iron therapy. The efficacy of these treatments, particularly in states of iron deficiency without anaemia, is equivocal. Indeed, both randomised control trials and aggregate data meta-analyses have produced conflicting evidence. Therefore, this study aims to assess the efficacy of both oral and intravenous iron supplementation on physical capacity, quality of life, and fatigue scores in iron-deficient non-anaemic individuals using individual patient data (IPD) meta-analysis techniques. METHODS: All potential studies, irrespective of design, will be sourced through systematic searches on the following databases: Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, Web of Science: Science Citation Index Expanded, Web of Science: Conference Proceedings Citation Index-Science, ClinicalTrials.gov, and World Health Organization (WHO) International Clinical Trials Registry Platform. Individual patient data from all available trials will be included and subsequently analysed in a two-stage approach. Predetermined subgroup and sensitivity analyses will be employed to further explain results. DISCUSSION: The significance of this IPD meta-analysis is one of consolidating a clear consensus to better inform iron-deficient individuals of the physiological response associated with iron supplementation. The IPD approach, to the best of our knowledge, is novel for this research topic. As such, the findings will significantly contribute to the current body of evidence. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020191739.

The relationship between menorrhagia, iron deficiency, and anaemia in recreationally active females: An exploratory population based screening study.

OBJECTIVES: Iron deficiency, anaemia, and menorrhagia - or heavy menstrual bleeding - are interrelated conditions that are highly prevalent and commonly underrecognised in exercising females of reproductive age. This study utilised a screening tool to identify risk factors and symptoms associated with heavy menstrual bleeding, iron deficiency, and anaemia in this population. DESIGN: An observational, cross sectional survey study was employed. METHODS: 1042 active females (aged 18-65) completed a comprehensive screening questionnaire and 887 (85 % compliance) provided a fingerprick blood sample for haemoglobin (Hb) concentration measurement. Women that presented as anaemic (defined as a [Hb] < 120 g/L) or deemed to be at risk of iron deficiency (120 < [Hb] < 130 g/L) were asked to complete follow-up blood tests to screen for iron studies. RESULTS: Average [Hb] was 134.2 ±â€¯12.1 g/L, with 94 individuals considered anaemic (10.6 %). Of the sample, 104 underwent follow-up blood tests; 51 (~49 %) presented with iron deficiency (defined as ferritin <30 µg/L). Based on survey responses, 274 (30.9 %) participants were determined to have heavy menstrual bleeding. Those presenting with heavy menstrual bleeding were younger, exercised fewer hours per week, and were more likely to have a history of iron deficiency or anaemia (all p < 0.05). Participants reporting a history of anaemia or iron deficiency were more likely to have heavy menstrual bleeding (anaemia: 39.7 %; iron deficiency; 36.9 %; both p < 0.05). CONCLUSIONS: In this cohort of exercising females of reproductive age, the prevalence of anaemia was 10.6 %. There is a strong association between heavy menstrual bleeding and a self-reported history of iron deficiency and anaemia. Greater awareness of heavy menstrual bleeding and its relationship with iron deficiency and anaemia is needed in this population. Non-invasive screening should be conducted to raise awareness and further understand the associated risk factors and symptomatology.

Urinary Ferritin as a Noninvasive Means of Assessing Iron Status in Young Children.

BACKGROUND: Iron deficiency (ID) is the most common nutritional deficiency affecting young children. Serum ferritin concentration is the preferred biomarker for measuring iron status because it reflects iron stores; however, blood collection can be distressing for young children and can be logistically difficult. A noninvasive means to measure iron status would be attractive to either diagnose or screen for ID in young children. OBJECTIVES: This study aimed to determine the correlation between urinary and serum ferritin concentrations in young children; to determine whether correcting urinary ferritin for creatinine and specific gravity improves the correlation; and to determine a urine ferritin cut point to predict ID. METHODS: Validation study was conducted using paired serum and urine collected from 3-y-old children (n = 142) participating in a longitudinal birth cohort study: the ORIGINS project in Perth, Western Australia. We calculated the sensitivity, specificity, positive, and negative predictive values of urinary ferritin amount in identifying those with ID at the clinical cut point used by the World Health Organization (serum ferritin concentration of <12 ng/mL). RESULTS: Urine ferritin, corrected for creatinine, correlated moderately with serum ferritin [r = 0.53 (0.40-0.64)] and performed well in predicting those with ID (area under the curve: 0.85; 95% confidence interval: 0.75, 0.94). Urine ferritin <2.28 ng/mg creatinine was sensitive (86%) and specific (77%) in predicting ID and had a high negative predictive value of 97%; however, the positive predictive value was low (40%) owing to the low prevalence of ID in the sample (16%). CONCLUSIONS: Urine ferritin shows good diagnostic performance for ID. This noninvasive biomarker maybe a useful screening tool to exclude ID in healthy young children; however, further research is needed in other populations.

Associations between postoperative anaemia and unplanned readmission to hospital after major surgery: a retrospective cohort study†.

BACKGROUND: Anaemia following major surgery may be associated with unplanned readmission to hospital. However, the severity-response relationship between the degree of anaemia at discharge and the risk of unplanned readmission is poorly defined. We aimed to describe the severity-response relationship between haemoglobin concentration at the time of discharge and the risk of unplanned readmission in a cohort of patients undergoing different types of major surgery. METHODS: We performed a retrospective cohort study in a single tertiary health service, including all patients who underwent major surgery (orthopaedic, abdominal, cardiac or thoracic) between 1 May 2011 and 1 February 2022. The primary outcome was unplanned readmission to hospital in the 90 days following discharge after the index surgical procedure. These complex, non-linear relationships were modelled with restricted cubic splines. RESULTS: We identified 22,134 patients and included 14,635 in the primary analysis, of whom 1804 (12%) experienced at least one unplanned readmission. The odds of unplanned readmission rose when the discharge haemoglobin concentration was < 100 g.l-1 (p < 0.001). On subgroup analysis, the haemoglobin threshold below which odds of readmission began to increase appeared to be higher in patients undergoing emergency surgery (110 g.l-1; p < 0.001) compared with elective surgery. Declining discharge haemoglobin concentration was associated with increased odds ratios (95%CI) of unplanned readmission in patients undergoing orthopaedic (1.08 (1.01-1.15), p = 0.03), abdominal (1.13 (1.07-1.19), p < 0.001) and thoracic (1.12 (1.01-1.24), p = 0.03) procedures, but not cardiac surgery (1.09 (0.99-1.19), p = 0.07). CONCLUSIONS: Our findings suggest that a haemoglobin concentration < 100 g.l-1 following elective procedures and < 110 g.l-1 following emergency procedures, at the time of hospital discharge after major surgery, was associated with unplanned readmission. Future interventional trials that aim to treat postoperative anaemia and reduce unplanned readmission should include patients with discharge haemoglobin below these thresholds.

Identification and management of preoperative anaemia in adults: A British Society for Haematology Guideline update.

This updated British Society for Haematology guideline provides an up-to-date literature review and recommendations regarding the identification and management of preoperative anaemia. This includes guidance on thresholds for the diagnosis of anaemia and the diagnosis and management of iron deficiency in the preoperative context. Guidance on the appropriate use of erythropoiesis-stimulating agents and preoperative transfusion is also provided.

Associations Between Nonanemic Iron Deficiency and Postoperative Outcomes in Cardiac Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Preoperative screening for iron deficiency is a part of patient blood management protocols. This systematic review, meta-analysis, and meta-regression reviews the association between nonanemic iron deficiency and postoperative outcomes in patients undergoing cardiac surgery. We aimed to determine whether preoperative screening for nonanemic iron deficiency should be recommended in patients undergoing cardiac surgery. METHODS: Electronic databases MEDLINE (Ovid), Embase (Ovid), and Scopus were searched from inception until December 9, 2022. Studies were considered for inclusion if they (1) used an observational study design; (2) enrolled adult patients undergoing cardiac surgery; and (3) included an iron-deficient and iron-replete group, defined using serum ferritin and/or transferrin saturation. The primary outcome was the length of acute hospital stay. Secondary outcomes included length of intensive care unit stay, requirement for allogeneic red blood cell transfusion, number of red blood cell units transfused, days alive and at home at postoperative days 30 and 90, all-cause postoperative complications, postoperative infection, mortality, and hospital readmission. Meta-regression was performed to assess the effects of study and patient-level factors on the associations between nonanemic iron deficiency and specific outcomes. Individual study quality was assessed using the Risk of Bias in Non-Randomized Studies of Exposures (ROBINS-E) tool. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to determine the quality of evidence for each outcome. RESULTS: Eight studies (2683 patients) were included. No significant association was observed between nonanemic iron deficiency and any of the primary or secondary outcomes except for an increased requirement for allogeneic red blood cell transfusion (odds ratio [OR], 1.39 [95% confidence interval, CI, 1.16-1.68; P < .001; I2 2.8%]). Meta-regression did not identify any potential sources of heterogeneity to explain variation in individual study results. The quality of evidence was rated as "low" or "very low" for all outcomes. CONCLUSIONS: Few high-quality studies are available to assess associations between nonanemic iron deficiency and outcomes after cardiac surgery. Acknowledging these limitations, the presence of preoperative nonanemic iron deficiency was not associated with a change in the primary outcome of length of hospital stay, or any patient-centered secondary outcome compared to those without iron deficiency. There was an association with increased requirement for allogeneic red blood cell transfusion, but this did not impact the reported patient-centered outcomes.

COVID-19 vaccine hesitancy in rural and metropolitan Western Australia: A mid-rollout cross-sectional analysis of why it exists and potential solutions.

INTRODUCTION: Vaccine hesitancy represents a state of uncertainty before a decision about vaccination is made. It can lead to limited vaccine uptake despite adequate supply and an efficacious product. Western Australia (WA) presents a unique challenge with a population widely spread across metropolitan and rural sites and diverse opinions regarding vaccination. OBJECTIVE: To elicit and compare the common COVID-19 vaccine concerns in rural and metropolitan WA, and to identify proposed solutions to vaccine hesitancy. DESIGN: A voluntary online survey was distributed via social media over a 2-week period in August 2021 during Phase 2A of the National COVID-19 Vaccine Rollout Strategy. General practitioners and members of the public living in rural and metropolitan WA over the age of 18 were surveyed regarding COVID-19 vaccine concerns (blood clots; long- and short-term side effects; lack of testing; and other concerns) and suggested methods to address vaccine hesitancy. Data were analysed with a sequential mixed methods and thematic analysis approach. FINDINGS: There were 468 general population respondents to our survey, of whom 19.0% (n = 89) lived rurally. A majority (52.6% [n = 246]) of general respondents expressed concerns about COVID-19 vaccine safety. The commonest concerns were long- and short-term side effects, blood clots and inadequate testing. There was a positive correlation between rurality and vaccine concerns; an inverse relationship between rurality and vaccine uptake; and an inverse relationship between vaccine concerns and uptake. Improved media coverage was the commonest solution suggested to address COVID-19 vaccine hesitancy. DISCUSSION: A significant proportion of respondents had concerns about vaccine safety; concerns were more common in rural respondents. Rural communities may benefit from location-targeted media campaigns with a focus on breaking down barriers specific to these members of the population. Vaccine access is more challenging, and consistent messaging from trusted sources is of utmost importance to improve uptake. CONCLUSION: COVID-19 vaccine hesitancy is more common in rural populations. Targeted media-based education regarding vaccine safety may improve COVID-19 vaccine uptake.

EMBIO trial study protocol: left gastric artery embolisation for weight loss in patients living with obesity with a BMI 35-50 kg/m2.

INTRODUCTION: Left gastric artery embolisation (LGAE) is a well-established treatment for major upper gastrointestinal (GI) bleeding when control is not established via upper GI endoscopy and recently has shown promising results for weight loss in small single arm studies. LGAE could be a treatment option in between our current tier-3 and tier-4 services for obesity. EMBIO is a National Institute for Health Research funded trial, a multicentre double-blinded randomised controlled trial between Imperial College National Health Service Trust and University College London Hospital, comparing LGAE versus Placebo procedure. The key aims of the trial is to evaluate LGAE efficacy on weight loss, its mechanism of action, safety profile and obesity-related comorbidities. METHODS AND ANALYSIS: 76 participants will be recruited from the existing tier-3 database after providing informed consent. Key inclusion criteria include adults aged 18-70 with a body mass index 35-50 kg/m2 and appropriate anatomy of the left gastric artery and coeliac plexus on CT Angiogram. Key exclusion criteria included previous major abdominal and bariatric surgery, weight >150 kg, type 2 diabetes on any medications other than metformin and the use of weight modifying medications. Participants will undergo mechanistic visits 1 week prior to the intervention and 3, 6 and 12 months postintervention. Informed consent will be received from each participant and they will be randomised in a 1:1 ratio to left gastric artery embolisation and placebo treatment. Blinding strategies include the use of moderate doses of sedation, visual and auditory isolation. All participants will enter a tier-3 weight management programme postintervention. The primary analysis will estimate the difference between the groups in the mean per cent weight loss at 12 months. ETHICS AND DISSEMINATION: This trial shall be conducted in full conformity with the 1964 Declaration of Helsinki and all subsequent revisions. Local research ethics approval was granted by London-Central Research Ethics Committee, (Reference 19/LO/0509) on 11 October 2019. The Medicines and Healthcare products Regulatory Agency (MHRA) issued the Letter of No Objection on 8 April 2022 (Reference CI/2022/0008/GB). The trial's development and progress are monitored by an independent trial steering committee and data monitoring and ethics committee. The researchers plan to disseminate results at conferences, in peer- reviewed journals as well as lay media and to patient organisations. TRIAL REGISTRATION NUMBER: ISRCTN16158402.

Intravenous Iron Therapy to Treat Anemia in Oncology: A Mapping Review of Randomized Controlled Trials.

Anemia is a common problem when patients present with cancer, and it can worsen during treatment. Anemia can directly impact the cognitive and physical quality of life and may impair fitness for oncological therapy. The most common cause of anemia is iron deficiency. Newer intravenous (IV) iron formulations offer a safe and rapidly effective treatment option. We performed a systematic mapping review of randomized controlled trials (RCTs) evaluating intravenous iron therapy in patients with cancer and anemia and their outcomes. A total of 23 RCTs were identified. The median number of patients enrolled was 104 (IQR: 60-134). A total of 5 were focused on surgical outcomes (4 preoperative, 1 postoperative), and 15 were in adjuvant therapies for a variety of tumor types (breast, colorectal, lung, gynecological, myeloid, and lymphomas), 10 of which were in combination with erythropoietin-stimulating agents (ESAs) therapy, 2 in radiotherapy, and 1 in palliative care. Overall, the studies reported that the use of IV iron increased hemoglobin concentration and decreased transfusion rates during different cancer treatment regimes. IV iron can be administered safely throughout the cancer treatment pathway from primary surgery to the palliative setting. More studies are needed to demonstrate net clinical outcomes.