The origin of ferritin reference intervals: a systematic review.

Iron deficiency is a highly prevalent condition, which contributes to unnecessary morbidity, mortality, and health inequity. A serum ferritin concentration of less than 30 µg/L has a high specificity and sensitivity for diagnosing iron deficiency in adults, but the laboratory reported lower limit of normal (LLN) is typically lower. These LLNs might not be rooted in rigorous scientific evidence and might be contributing to structural underdiagnosis of iron deficiency. A systematic review was done per systematic reviews and meta-analysis guidelines with the use of medical literature databases from inception of each database to Nov 30, 2021, to identify studies that determined ferritin reference intervals in healthy adults and grey literature search for the five most common ferritin assays (registration number CRD42022268844). The objectives were to systematically summarise the ferritin reference intervals and to do a methodological quality assessment of the included studies. 2306 studies were screened and 61 full texts were included. 37 studies were eligible for analysis of the ferritin LLN in the general population. The population the sample was comprised of was a total of 21 882 females and 23 650 males participants. The ferritin LLN was a median of 8 µg/L (IQR 5-15) and mean of 9 µg/L (SD 11) in females and a median of 25 µg/L (IQR 16-44) and mean of 25 µg/L (SD 29) in males. 30 (49%) of 61 studies did not explicitly screen for patients at risk of iron deficiency, and 32 (52%) did not refer to a reference interval establishment guideline (eg, guideline recommended by Clinical and Laboratory Standards Institute). The five most used commercial ferritin laboratory assays reported reference intervals with a median LLN of 11 (IQR 9-12) and mean of 9 µg/L (SD 4) for females and median of 22 (IQR 22-24) and mean of 23 µg/L (SD 4) for males. In the literature, serum ferritin reference intervals in healthy adults consistently report a LLN of less than 30 µg/L. Data driving these ferritin reference intervals are at high risk of bias, given no exclusion of individuals at risk for iron deficiency in the presumed normal population sample and no adherence to reference interval establishment standards. We suggest the use of evidence-based laboratory clinical decision limits to diagnose iron deficiency.

Defining ferritin clinical decision limits to improve diagnosis and treatment of iron deficiency: A modified Delphi study.

BACKGROUND: Iron deficiency is highly prevalent worldwide and is an issue of health inequity. Despite its high prevalence, uncertainty on the clinical applicability and evidence-base of iron-related lab test cut-offs remains. In particular, current ferritin decision limits for the diagnosis of iron deficiency may not be clinically appropriate nor scientifically grounded. METHODS: A modified Delphi study was conducted with various clinical experts who manage iron deficiency across Canada. Statements about ferritin decision limits were generated by a steering committee, then distributed to the expert panel to vote on agreement with the aim of achieving consensus and acquiring feedback on the presented statements. Consensus was reached after two rounds, which was defined as 70% of experts rating their agreement for a statement as 5 or higher on a Likert scale from 1 to 7. RESULTS: Twenty-six clinical experts across 10 different specialties took part in the study. Consensus was achieved on 28 ferritin decision limit statements in various populations (including patients with multiple comorbid conditions, pediatric patients, and pregnant patients). For example, there was consensus that a ferritin <30 µg/L rules in iron deficiency in all adult patients (age ≥ 18 years) and warrants iron replacement therapy. CONCLUSION: Consensus statements generated through this study corresponded with current evidence-based literature and guidelines. These statements provide clarity to facilitate clinical decisions around the appropriate detection and management of iron deficiency.

Effectiveness of Community Treatment Order in Patients with a First Episode of Psychosis: A Mirror-Image Study.

OBJECTIVE: Poor adherence to antipsychotic medications is strongly associated with psychotic relapses and hospitalizations. This may hinder patients' ability to function, particularly in a first episode of psychosis (FEP). Poor adherence to treatment may be due to poor insight that can alter the capacity to consent to care, including pharmacotherapy. When patients are judged legally lacking the capacity to consent to care, treatment can be mandated through community treatment orders (CTOs). This naturalistic study examines the effects of CTOs in FEP patients. METHOD: This study examines 38 FEP patients legally deemed unable to consent to care during their follow-up. Using a naturalistic mirror-image approach, we compare clinical (Scale for the Assessment of Positive Symptoms [SAPS], Scale for the Assessment of Negative Symptoms [SANS]), functional (Global Assessment of Functioning Scale [GAF], Social and Occupational Functioning Assessment Scale [SOFAS]), and service use (number of emergency room visits, length of hospitalizations) indicators before and after CTO. RESULTS: After the CTO, 37 of 38 patients complied with treatment. Statistically significant improvements in clinical (▵SAPS = -6.3; 95% CI, 4.5 to 8.1 and ▵SANS = -2.2; 95% CI, 0.9 to 3.4, P < 0.01) and functional (▵GAF = +15.0; 95% CI, 8.4 to 21.6, ▵SOFAS = +18.6; 95% CI, 12.8 to 24.4, P < 0.01) outcomes were observed. Significant reduction in emergency room visits ( P = 0.016) and days of hospitalization per month in acute care units ( P < 0.05) were identified with no difference in hospital days per month in short-stay units. Moreover, encounters with case managers ( P = 0.008) and attendance of cognitive therapy sessions ( P = 0.031) were significantly higher. However, patients' weight significantly increased after CTO (▵weight = +8.0 kg, P < 0.01). CONCLUSIONS: In FEP patients, CTOs improve compliance to treatment, which contributes to reducing positive and negative symptoms, shortening hospital stays, and improving functioning.