Blood over-testing: impact, ethical issues and mitigating actions.

Plenty of studies demonstrate that hospital-acquired anemia (HAA) can increase transfusion rates, mortality, morbidity and cause unnecessary patient burden, including additional length of hospital stay, sleep disruption and venipuncture harms resulting from blood samples unlikely to change clinical management. Beyond patient costs, community costs should also be considered, such as laboratory time and resources waste, environmental impact, increasing pressure on labs and fewer tests available on time for patients who can benefit from them most. Blood over-testing does not support the principles of non-maleficence, justice and respect for patient autonomy, at the expense dubious beneficence. Reducing the number and frequency of orders is possible, to a certain extent, by adopting nudge strategies and raising awareness among prescribing doctors. However, reducing the orders may appear unsafe to doctors and patients. Therefore, reducing blood volume from each order is a better alternative, which is worth implementing through technological, purchasing and organizational arrangements, possibly combined according to need (smaller tubes, adequate analytic platforms, blind dilution, blood conservative devices, aggregating tests and laboratory units).

C-reactive protein and clinical outcome in COVID-19 patients: the importance of harmonized measurements.

C-reactive protein (CRP) is a cytokine-mediated acute phase reactant with a recognized role in inflammatory conditions and infectious disease. In coronavirus disease 2019 (COVID-19), elevated CRP concentrations in serum were frequently detected and significantly associated with poor outcome in terms of disease severity, need for intensive care, and in-hospital death. For these reasons, the marker was proposed as a powerful test for prognostic classification of COVID-19 patients. In most of available publications, there was however confounding information about how interpretative criteria for CRP in COVID-19 should be derived, including quality of employed assays and optimal cut-off definition. Assuring result harmonization and controlling measurement uncertainty in terms of performance specifications are fundamental to allow worldwide application of clinical information according to specific CRP thresholds and to avoid risk of patient misclassification.

A step towards optimal efficiency of HbA1c measurement as a first-line laboratory test: the TOP-HOLE (Towards OPtimal glycoHemOgLobin tEsting) project.

OBJECTIVES: The TOP-HOLE (Towards OPtimal glycoHemOgLobin tEsting) project aimed to validate the HbA1c enzymatic method on the Abbott Alinity c platform and to implement the HbA1c testing process on the total laboratory automation (TLA) system of our institution. METHODS: Three different measuring systems were employed: Architect c4000 stand-alone (s-a), Alinity c s-a, and Alinity c TLA. Eight frozen whole blood samples, IFCC value-assigned, were used for checking trueness. A comparison study testing transferability of HbA1c results from Architect to Alinity was also performed. The alignment of Alinity TLA vs. s-a was verified and the measurement uncertainty (MU) estimated according to ISO 20914:2019. Turnaround time (TAT) and full time equivalent (FTE) were used as efficiency indicators. RESULTS: For HbA1c concentrations covering cut-offs adopted in clinical setting, the bias for both Architect and Alinity s-a was negligible. When compared with Architect, Alinity showed a mean positive bias of 0.54 mmol/mol, corresponding to a mean difference of 0.87%. A perfect alignment of Alinity TLA to the Alinity s-a was shown, and a MU of 1.58% was obtained, widely fulfilling the desirable 3.0% goal. After the full automation of HbA1c testing, 90% of results were released with a maximum TAT of 1 h, 0.30 FTE resource was also saved. CONCLUSIONS: The traceability of Alinity HbA1c enzymatic assay to the IFCC reference system was correctly implemented. We successfully completed the integration of the HbA1c testing on our TLA system, without worsening the optimal analytical performance. The shift of HbA1c testing from s-a mode to TLA significantly decreased TAT.

Lipase elevation in serum of COVID-19 patients: frequency, extent of increase and clinical value.

OBJECTIVES: Previous studies reported lipase elevations in serum of COVID-19 patients trying to establish a causal link between SARS-CoV-2 infection and pancreatic damage. However, the degree and prevalence of hyperlipasemia was not uniform across studies. METHODS: We retrospectively evaluated 1,092 hospitalized patients with COVID-19 and at least one available lipase result. The number and frequency of patients with lipase above the upper reference limit (URL), >3 URL, and >6 URL were estimated. Correlations between lipase values and other biomarkers of organ or tissue damage were performed to identify possible extra-pancreatic sources of lipase release. The potential prognostic role of lipase to predict death and intensive care unit (ICU) admission during hospitalization was also evaluated. RESULTS: Lipase was >URL in 344 (31.5%) of COVID-19 patients. Among them, 65 (5.9%) and 25 (2.3%) had a peak lipase >3 URL and >6 URL, respectively. In the latter group, three patients had acute pancreatitis of gallstone or drug-induced etiology. In others, the etiology of lipase elevations appeared multifactorial and could not be directly related to SARS-CoV-2 infection. No correlation was found between lipase and other tested biomarkers of organ and tissue damage. Lipase concentrations were not different between survivors and non-survivors; however, lipase was significantly increased (p<0.001) in patients admitted to the ICU, even if the odds ratio for lipase as predictor of ICU admission was not significant. CONCLUSIONS: Lipase was elevated in ∼1/3 of COVID-19 patients, but the clinical significance of this finding is unclear and irrelevant to patient prognosis during hospitalization.

Pursuing appropriateness of laboratory tests: a 15-year experience in an academic medical institution.

Appropriateness in Laboratory Medicine has been the object of various types of interventions. From published experiences, it is now clear that to effectively manage the laboratory test demand it is recommended to activate evidence-based preventative strategies stopping inappropriate requests before they can reach the laboratory. To guarantee appropriate laboratory test utilization, healthcare institutions should implement and optimize a computerized provider order entry (CPOE), exploiting the potential of electronic requesting as "enabling factor" for reinforcing appropriateness and sustaining its effects over time. In our academic institution, over the last 15 years, our medical laboratory has enforced various interventions to improve test appropriateness, all directly or indirectly based on CPOE use. The following types of intervention were implemented: (1) applying specific recommendations supported by monitoring by CPOE as well as a continuous consultation with clinicians (tumour markers); (2) removing outdated tests and avoiding redundant duplications (cardiac markers, pancreatic enzymes); (3) order restraints to selected wards and gating policy (procalcitonin, B-type natriuretic peptide, homocysteine); (4) reflex testing (bilirubin fractions, free prostate-specific antigen, aminotransferases, magnesium in hypocalcemia); and (5) minimum retesting interval (D-Dimer, vitamin B12, C-reactive protein, γ-glutamyltranspeptidase). In this paper, we reviewed these interventions and summarized their outcomes primarily related to the changes in total test volumes and cost savings, without neglecting patient safety. Our experience confirmed that laboratory professionals have an irreplaceable role as "stewards" in designing, implementing, evaluating, and maintaining interventions focused to improving test appropriateness.

Cellular dehydration acutely degrades mood mainly in women: a counterbalanced, crossover trial.

It is unclear if mild-to-moderate dehydration independently affects mood without confounders like heat exposure or exercise. This study examined the acute effect of cellular dehydration on mood. Forty-nine adults (55 % female, age 39 (sd 8) years) were assigned to counterbalanced, crossover trials. Intracellular dehydration was induced with 2-h (0·1 ml/kg per min) 3 % hypertonic saline (HYPER) infusion or 0·9 % isotonic saline (ISO) as a control. Plasma osmolality increased in HYPER (pre 285 (sd 3), post 305 (sd 4) mmol/kg; P < 0·05) but remained unchanged in ISO (pre 285 (sd 3), post 288 (sd 3) mmol/kg; P > 0·05). Mood was assessed with the short version of the Profile of Mood States Questionnaire (POMS). The POMS sub-scale (confusion-bewilderment, depression-dejection, fatigue-inertia) increased in HYPER compared with ISO (P < 0·05). Total mood disturbance score (TMD) assessed by POMS increased from 10·3 (sd 0·9) to 16·6 (sd 1·7) in HYPER (P < 0·01), but not in ISO (P > 0·05). When TMD was stratified by sex, the increase in the HYPER trial was significant in females (P < 0·01) but not in males (P > 0·05). Following infusion, thirst and copeptin (surrogate for vasopressin) were also higher in females than in males (21·3 (sd 2·0), 14·1 (sd 1·4) pmol/l; P < 0·01) during HYPER. In conclusion, cellular dehydration acutely degraded specific aspects of mood mainly in women. The mechanisms underlying sex differences may be related to elevated thirst and vasopressin.

Associations between urinary hydration markers and metabolic dysfunction: a cross-sectional analysis of NHANES data, 2008-2010.

PURPOSE: Growing evidence suggests hydration plays a role in metabolic dysfunction, however data in humans are scarce. This study examined the cross-sectional association between hydration and metabolic dysfunction in a representative sample of the US population. METHODS: Data from 3961 adult NHANES (National Health and Nutrition Examination Survey) participants (49.8% female; age 46.3 ± 0.5 years) were grouped by quartile of urine specific gravity (USG, 2007-2008 cohort) or urine osmolality (UOsm, 2009-2010 cohort) as measures of hydration. Metabolic dysfunction was assessed by glycemic and insulinemic endpoints and by components of the metabolic syndrome. Multivariate-adjusted linear and logistic regression models were used. RESULTS: Increasing quartiles of USG but not UOsm was associated with higher fasting plasma glucose (FPG), glycated hemoglobin (all P < 0.01), HOMA-IR and elevated insulin (all P < 0.05). Compared with the lowest quartile, those with the highest USG but not UOsm had greater risk of metabolic syndrome (Q4 vs. Q1, OR (99% CI): 1.6 (1.0, 2.7), P = 0.01) and diabetes (Q4 vs. Q1, OR: 1.8 (1.0, 3.4), P < 0.05). Additionally, those with USG > 1.013 or UOsm > 500 mOsm/kg, common cut-off values for optimal hydration based on retrospective analyses of existing data, had less favorable metabolic markers. In a subset of participants free from diabetes mellitus, impaired kidney function, hypertension and diuretic medication, USG remained positively associated with FPG (P < 0.01) and elevated FPG (P < 0.05). CONCLUSION: These analyses provide population-based evidence that USG as a proxy for hydration is associated with glucose homeostasis in NHANES 2007-2008. The same association was not significant when UOsm was used as a proxy for hydration in the 2009-2010 wave. CLINICAL TRIAL REGISTRY: Not applicable, as this was a reanalysis of existing NHANES data.

Hydration for health hypothesis: a narrative review of supporting evidence.

PURPOSE: An increasing body of evidence suggests that excreting a generous volume of diluted urine is associated with short- and long-term beneficial health effects, especially for kidney and metabolic function. However, water intake and hydration remain under-investigated and optimal hydration is poorly and inconsistently defined. This review tests the hypothesis that optimal chronic water intake positively impacts various aspects of health and proposes an evidence-based definition of optimal hydration. METHODS: Search strategy included PubMed and Google Scholar using relevant keywords for each health outcome, complemented by manual search of article reference lists and the expertise of relevant practitioners for each area studied. RESULTS: The available literature suggest the effects of increased water intake on health may be direct, due to increased urine flow or urine dilution, or indirect, mediated by a reduction in osmotically -stimulated vasopressin (AVP). Urine flow affects the formation of kidney stones and recurrence of urinary tract infection, while increased circulating AVP is implicated in metabolic disease, chronic kidney disease, and autosomal dominant polycystic kidney disease. CONCLUSION: In order to ensure optimal hydration, it is proposed that optimal total water intake should approach 2.5 to 3.5 L day-1 to allow for the daily excretion of 2 to 3 L of dilute (< 500 mOsm kg-1) urine. Simple urinary markers of hydration such as urine color or void frequency may be used to monitor and adjust intake.

Searching for a role of procalcitonin determination in COVID-19: a study on a selected cohort of hospitalized patients.

Objectives: Procalcitonin (PCT) has been proposed for differentiating viral vs. bacterial infections. In COVID-19, some preliminary results have shown that PCT testing could act as a predictor of bacterial co-infection and be a useful marker for assessment of disease severity. Methods: We studied 83 COVID-19 hospitalized patients in whom PCT was specifically ordered by attending physicians. PCT results were evaluated according to the ability to accurately predict bacterial co-infections and death in comparison with other known biomarkers of infection and with major laboratory predictors of COVID-19 severity. Results: Thirty-three (39.8%) patients suffered an in-hospital bacterial co-infection and 44 (53.0%) patients died. In predicting bacterial co-infection, PCT showed a relatively low accuracy (area under receiver-operating characteristic [ROC] curve [AUC]: 0.757; 95% confidence interval [CI]: 0.651-0.845), with a strength for detecting the outcome not significantly different from that of white blood cell count and C-reactive protein (CRP). In predicting patient death, PCT showed an AUC of 0.815 (CI: 0.714-0.892), not better than those of other more common laboratory tests, such as blood lymphocyte percentage (AUC: 0.874, p=0.19), serum lactate dehydrogenase (AUC: 0.860, p=0.47), blood neutrophil count (AUC: 0.845, p=0.59), and serum albumin (AUC: 0.839, p=0.73). Conclusions: Procalcitonin (PCT) testing, even when appropriately ordered, did not provide a significant added value in COVID-19 patients when compared with more consolidated biomarkers of infection and poor clinical outcome. The major application of PCT in COVID-19 is its ability, associated with a negative predictive value >90%, to exclude a bacterial co-infection when a rule-out cut-off (<0.25 µg/L) is applied.

Urinary markers of hydration during 3-day water restriction and graded rehydration.

PURPOSE: This investigation had three purposes: (a) to evaluate changes in hydration biomarkers in response to a graded rehydration intervention (GRHI) following 3 days of water restriction (WR), (b) assess within-day variation in urine concentrations, and (c) quantify the volume of fluid needed to return to euhydration as demonstrated by change in Ucol. METHODS: 115 adult males and females were observed during 1 week of habitual fluid intake, 3 days of fluid restriction (1000 mL day-1), and a fourth day in which the sample was randomized into five different GRHI groups: no additional water, CON; additional 500 mL, G+0.50; additional 1000 mL, G+1.00; additional 1500 mL, G+1.50; additional 2250 mL, G+2.25. All urine was collected on 1 day of the baseline week, during the final 2 days of the WR, and during the day of GRHI, and evaluated for urine osmolality, color, and specific gravity. RESULTS: Following the GRHI, only G+1.50 and G+2.25 resulted in all urinary values being significantly different from CON. The mean volume of water increase was significantly greater for those whose Ucol changed from > 4 to < 4 (+ 1435 ± 812 mL) than those whose Ucol remained ≥ 4 (+ 667 ± 722 mL, p < 0.001). CONCLUSIONS: An additional 500 mL of water is not sufficient, while approximately 1500 mL of additional water (for a total intake between 2990 and 3515 mL day-1) is required to return to a urine color associated with adequate water intake, following 3 days of WR.

Impact of total automation consolidating first-line laboratory tests on diagnostic blood loss.

Background Blood loss for laboratory testing may contribute to hospital-acquired anemia. When implementing the core laboratory (core-lab) section, we consolidated first-line tests decreasing the number of tubes previously dispatched to different sites. Here, hypothesized benefits of the amount of blood volume drawn were explored. Methods We retrieved, using a laboratory information system (LIS), the number of tubes received by laboratories interested in the change from all clinical wards in a year-based period, i.e. 2013 for pre-core-lab and 2015 for core-lab system, respectively. Data were expressed as the overall number of tubes sent to laboratories, the corresponding blood volume, and the number of laboratory tests performed, normalized for the number of inpatients. Results After consolidation, the average number of blood tubes per inpatient significantly decreased (12.6 vs. 10.7, p < 0.001). However, intensive care units (ICUs) did not reduce the number of tubes per patient, according to the needs of daily monitoring of their clinical status. The average blood volume sent to laboratories did not vary significantly because serum tubes for core-lab required higher volumes for testing up to 55 analytes in the same transaction. Finally, the number of requested tests per patient during the new osystem slightly decreased (-2.6%). Conclusions Total laboratory automation does not automatically mean reducing iatrogenic blood loss. The new system affected the procedure of blood drawing in clinical wards by significantly reducing the number of handled tubes, producing a benefit in terms of costs, labor and time consumption. Except in ICUs, this also slightly promoted some blood saving. ICUs which engage in phlebotomizing patients daily, did not take advantage from the test consolidation.

Sucrose and Sodium but not Caffeine Content Influence the Retention of Beverages in Humans Under Euhydrated Conditions.

This study systematically examined the influence of carbohydrate (sucrose), sodium, and caffeine on the fluid retention potential of beverages under euhydrated conditions, using the beverage hydration index method. Three cohorts, each of 12 young, healthy, active men, ingested 1 L of beverages containing four different concentrations of a single component (sucrose, sodium, or caffeine) in a double-blind, crossover manner. Urine output was collected for the subsequent 4 hr. Cumulative urine output was lower and net fluid balance was higher after 10 and 20% sucrose beverages than 0 and 5% sucrose beverages (p < .05), and after 27 and 52 mmol/L sodium beverages than 7 and 15 mmol/L sodium beverages (p < .05). No difference in urine output or net fluid balance was apparent following ingestion of caffeine at concentrations of 0-400 mg/L (p = .83). Consequently, the calculated beverage hydration index was greater in beverages with higher sucrose or sodium content, but caffeine had no effect. No difference was observed in arginine vasopressin or aldosterone between any trials. These data highlight that the key drivers promoting differences in the fluid retention potential of beverages when euhydrated are energy density, likely through slowed fluid delivery to the circulation (carbohydrate content effect), or electrolyte content through improved fluid retention (sodium content effect). These data demonstrate that beverage carbohydrate and sodium content influence fluid delivery and retention in the 4 hr after ingestion, but caffeine up to 400 mg/L does not. Athletes and others can use this information to guide their daily hydration practices.

Fast track protocols using highly sensitive troponin assays for ruling out and ruling in non-ST elevation acute coronary syndrome.

The introduction of "highly sensitive" cardiac troponin assays (hsTn) has reinforced the evidence that only serial testing incorporated in running algorithms allows a more accurate diagnosis of acute myocardial infarction. In this report, we consider the available evidence supporting the use of fast track protocols for ruling out and ruling in non-ST elevation myocardial infarction (NSTEMI) and compare it with the content of recently released guideline by the European Society of Cardiology, noting some uncomfortable aspects that need urgent clarification and/or revision. Firstly, the guideline drafters have to reconsider the available evidence that does not permit to assign the same class and level of evidence to the very well-validated 0-3 h algorithm and to the 0-1 h algorithm. In agreement with the validity of available data, the limitations of fast track protocols, in particular of the 0-1 h algorithm for NSTEMI rule-in, calls for caution. Secondly, as the current diagnostics guidance by the UK National Institute for Health and Care Excellence recommends, rapid diagnostic protocols should be performed only using well-validated hsTn; recommending the use of an assay before being commercially available is not fair and scientifically sound.

Portable Prehospital Methods to Treat Near-Hypothermic Shivering Cold Casualties.

OBJECTIVE: To compare the effectiveness of a single-layered polyethylene survival bag (P), a single-layered polyethylene survival bag with a hot drink (P+HD), a multi-layered metalized plastic sheeting survival bag (MPS: Blizzard Survival), and a multi-layered MPS survival bag with 4 large chemical heat pads (MPS+HP: Blizzard Heat) to treat cold casualties. METHODS: Portable cold casualty treatment methods were compared by examining core and skin temperature, metabolic heat production, and thermal comfort during a 3-hour, 0°C cold air exposure in 7 shivering, near-hypothermic men (35.4°C). The hot drink (70°C, ~400 ml, ~28 kJ) was consumed at 0, 1, and 2 hours during the cold air exposure. RESULTS: During the cold air exposure, core rewarming and thermal comfort were similar on all trials (P = .45 and P = .36, respectively). However, skin temperature was higher (10%-13%; P < .001; large effect sizes d > 2.7) and metabolic heat production lower (15%-39%; P < .05; large effect sizes d > .9) on MPS and MPS+HP than P and P+HD. The addition of heat pads further lowered metabolic heat production by 15% (MPS+HP vs MPS; P = .05; large effect size d = .9). The addition of the hot drink to polyethylene survival bag did not increase skin temperature or lower metabolic heat production. CONCLUSIONS: Near-hypothermic cold casualties are rewarmed with less peripheral cold stress and shivering thermogenesis using a multi-layered MPS survival bag compared with a polyethylene survival bag. Prehospital rewarming is further aided by large chemical heat pads but not by hot drinks.