Effect of a price display intervention on laboratory test ordering behavior of general practitioners.

BACKGROUND: Redundant use of diagnostic tests in primary care has shown to be a contributor to rising Dutch healthcare costs. A price display in the test ordering system of the electronic health records (EHRs) could potentially be a low-cost and easy to implement intervention to a decrease in test ordering rate in the primary care setting by creating more cost-awareness among general practitioners (GPs). The aim of this study was to assess the effect of a price display for diagnostic laboratory tests in the EHR on laboratory test ordering behavior of GPs in the Westelijke Mijnstreek region in the Netherlands. METHODS: A pre-post intervention study among 154 GPs working in 57 general practices was conducted from September 2019, until March 2020, in the Netherlands. The intervention consisted of displaying the costs of 22 laboratory tests at the time of ordering. The primary outcome was the mean test ordering rate per 1.000 patients per month, per general practice. RESULTS: Test ordering rates were on average rising prior to the intervention. The total mean monthly test order volume showed a non-statistically significant interruption in this rising trend after the intervention, with the mean monthly test ordering rate levelling out from 322.4 to 322.2 (P = 0.86). A subgroup analysis for solely individually priced tests showed a statistically significant decrease in mean monthly test ordering rate after implementation of the price display for the sum of all tests from 67.2 to 63.3 (P = 0.01), as well as for some of these tests individually (i.e. thrombocytes, ALAT, TSH, folic acid). Leucocytes, ESR, vitamin B12, anti-CCP and NT-proBNP also showed a decrease, albeit not statistically significant (P > 0.05). CONCLUSIONS: Our study suggests that a price display intervention is a simple tool that can alter physicians order behavior and constrain the expanding use of laboratory tests. Future research might consider alternative study designs and a longer follow-up period. Furthermore, in future studies, the combination with a multitude of interventions, like educational programs and feedback strategies, should be studied, while potentially adverse events caused by reduced testing should also be taken into consideration.

Inflammation rather than nutritional depletion determines glutamine concentrations and intestinal permeability.

AIM: Nutritional depletion has been correlated with low plasma and mucosal glutamine concentrations and with increased intestinal permeability. Since nutritional depletion often is associated with (chronic) inflammatory stress, this study was designed to establish the influence of depletion and inflammation on glutamine concentrations and gut barrier function. METHODS: Anthropometric parameters were calculated from 26 patients who required artificial nutrition. Glutamine concentrations in plasma and gut mucosa, gut permeability and mucosal morphology were assessed. For determination of the degree of inflammation erythrocyte sedimentation rates and (pre)albumin concentrations were measured. On the basis of these parameters patients were divided into two groups having significant inflammatory stress or not. Similarly, a depleted and a non-depleted group was formed based on percentage ideal body weight, fat-free mass index (FFMI) and percentage weight loss. Glutamine concentrations, gut permeability and villus morphology were compared between the groups. RESULTS: The presence of inflammatory activity had significant negative effects on glutamine concentrations in contrast to the presence or absence of nutritional depletion. Similarly, intestinal permeability increased during active inflammation but not in depleted patients. FFMI but not inflammation was related to villus height. CONCLUSIONS: The presence of inflammation significantly affects glutamine concentrations and gut permeability, in contrast to the presence of depletion of body cell mass per se. On the other hand, villus morphology is not influenced by changes in systemic inflammatory activity whereas nutritional status possibly does affect villus height.

Does glutamine-enriched parenteral nutrition really affect intestinal morphology and gut permeability?

BACKGROUND: Nutritional depletion has been related to low glutamine levels in plasma and gut mucosa. This study was set up to investigate the effects of glutamine-enriched total parenteral nutrition on intestinal morphology and permeability. METHODS: Twenty-three depleted patients were randomized and after stabilization baseline measurements were performed. Plasma glutamine concentrations, gut morphology (including proliferation and lymphocyte markers) and intestinal permeability were measured. After administration during 8-10 days of a glutamine enriched total parenteral nutrition or an isonitrogenous control solution the measurements were repeated. RESULTS: No significant changes in glutamine concentrations, intestinal permeability, mucosal morphology or gut mucosal inflammation were observed between groups. CONCLUSIONS: Glutamine enriched total parenteral nutrition in a depleted patient population does not result in improvements in gut morphology and gut barrier function.

Accurate prediction of anastomotic leakage after colorectal surgery using plasma markers for intestinal damage and inflammation.

BACKGROUND: Anastomotic leakage is a frequent and life-threatening complication after colorectal surgery. Early recognition of anastomotic leakage is critical to reduce mortality. Because early clinical and radiologic signs of anastomotic leakage are often nonspecific, there is an urgent need for accurate biomarkers. Markers of inflammation and gut damage might be suitable, as these are hallmarks of anastomotic leakage. STUDY DESIGN: In 84 patients undergoing scheduled colorectal surgery with primary anastomosis, plasma samples were collected preoperatively and daily after surgery. Inflammatory markers, C-reactive protein; calprotectin; and interleukin-6, and intestinal damage markers, intestinal fatty acid binding protein; liver fatty acid binding protein; and ileal bile acid binding protein, were measured. Diagnostic accuracy of single markers or combinations of markers was analyzed by receiver operating characteristic curve analysis. RESULTS: Anastomotic leakage developed in 8 patients, clinically diagnosed at median day 6. Calprotectin had best diagnostic accuracy to detect anastomotic leakage postoperatively. Highest diagnostic accuracy was obtained when C-reactive protein and calprotectin were combined at postoperative day 3, yielding sensitivity of 100%, specificity of 89%, positive likelihood ratio = 9.09 (95% CI, 4.34-16), and negative likelihood ratio = 0.00 (95% CI, 0.00-0.89) (p < 0.001). Interestingly, preoperative intestinal fatty acid binding protein levels predicted anastomotic leakage at a cutoff level of 882 pg/mL with sensitivity of 50%, specificity of 100%, positive likelihood ratio = infinite (95% CI, 4.01-infinite), and negative likelihood ratio = 0.50 (95% CI, 0.26-0.98) (p < 0.0001). CONCLUSIONS: Preoperative intestinal fatty acid binding protein measurement can be used for anastomotic leakage risk assessment. In addition, the combination of C-reactive protein and calprotectin has high diagnostic accuracy. Implementation of these markers in daily practice deserves additional investigation.

Evaluation of the diagnostic accuracy of plasma markers for early diagnosis in patients suspected for acute appendicitis.

OBJECTIVES: The main objective of this study was to evaluate the diagnostic accuracy of two novel biomarkers, calprotectin (CP) and serum amyloid A (SAA), along with the more traditional inflammatory markers C-reactive protein (CRP) and white blood cell count (WBC), in patients suspected of having acute appendicitis (AA). The secondary objective was to compare diagnostic accuracy of these biomarkers with a clinical scoring system and radiologic imaging. METHODS: A total of 233 patients with suspected AA, presenting to the emergency department (ED) between January 2010 and September 2010, and 52 healthy individuals serving as controls, were included in the study. Blood was drawn and CP and SAA-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). CRP and WBC concentrations were routinely measured and retrospectively abstracted from the electronic health record, together with physical examination findings and radiologic reports. The Alvarado score was calculated as a clinical scoring system for AA. Final diagnosis of AA was based on histopathologic examination. The Mann-Whitney U-test was used for between-group comparisons. Receiver operating characteristic (ROC) curves were used to measure the diagnostic accuracy for the tests and to determine the best cutoff points. RESULTS: Seventy-seven of 233 patients (33%) had proven AA. Median plasma levels for CP and SAA-1 were significantly higher in patients with AA than in those with another final diagnosis (CP, 320.9 ng/mL vs. 212.9 ng/mL; SAA-1, 30 mg/mL vs. 0.6 mg/mL; p < 0.001). CRP and WBC were significantly higher in patients with AA as well. The Alvarado score was helpful at the extremes (<3 or >7). Ultrasound (US) had a sensitivity of 84% and a specificity of 94%. Computed tomography (CT) had a sensitivity of 100% and a specificity of 91%. The area under the ROC (95% confidence interval [CI]) was 0.67 (95% CI = 0.60 to 0.74) for CP, 0.76 (95% CI = 0.70 to 0.82) for SAA, 0.71 (95% CI = 0.64 to 0.78) for CRP, and 0.79 (95% CI = 0.73 to 0.85) for WBC. No cutoff points had high enough sensitivity and specificity to accurately diagnose AA. However, a high sensitivity of 97% was shown at 7.5 × 10(9) /L for WBC and 0.375 mg/mL for SAA. CONCLUSIONS: CP, SAA-1, CRP, and WBC were significantly elevated in patients with AA. None had cutoff points that could accurately discriminate between AA and other pathology in patients with suspected AA. A WBC < 7.5 × 10(9) /L, with a low level of clinical suspicion for AA, can identify a subgroup of patients who may be sent home without further evaluation, but who should have available next-day follow-up.

High HDL cholesterol does not protect against coronary artery disease when associated with combined cholesteryl ester transfer protein and hepatic lipase gene variants.

Cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are two HDL modifying proteins that have both pro- and anti-atherogenic properties. We hypothesized that CETP and HL synergistically affect HDL cholesterol and atherosclerotic risk. To test our hypothesis, we analysed the genotype frequencies of CETP Taq1B (rs708272) and LIPC-514C/T (rs1800588) polymorphisms in male coronary artery disease patients (CAD; n=792) and non-symptomatic controls (n=539). Cases and controls had similar allele frequencies, but the occurrence of the combined genotypes differed (p=0.027). In CAD patients, 1.3% had the CETP-B2B2/LIPC-TT genotype, with only 0.2% in controls (p=0.033). The presence of the CETP lowering B2 allele and the HL lowering LIPC-T allele synergistically increased HDL cholesterol from 0.87+/-0.19 mmol/L in the B1B1/CC (n=183) to 1.21+/-0.25 mmol/L in the B2B2/TT carriers (n=10). The B1B1/CC carriers had an increased CAD risk (OR 1.4; p=0.025). Despite their high HDL cholesterol, the B2B2/TT individuals also had an increased CAD risk (OR 3.7; p=0.033). In a 2-year follow up, the loss of coronary artery lumen diameter in these patients was higher than in all other patients combined (0.34+/-0.70 versus 0.10+/-0.29 mm; p=0.044). We conclude that a high HDL cholesterol does not protect against coronary artery disease when associated with combined CETP- and HL-lowering gene variants.

Automated analysis of pleural fluid total and differential leukocyte counts with the Sysmex XE-2100.

BACKGROUND: Determination of leukocyte (WBC) counts in pleural fluid is routinely performed by microscopic examination. In this study, we evaluated the performance of automated (differential) WBC counting in comparison with manual counting. METHODS: Pleural fluid samples (n=45) were obtained from patients undergoing diagnostic thoracocentesis. The manual total WBC count was determined after Samson staining in a Fuchs-Rosenthal hemocytometer; microscopic differential counts were performed on May-Grünwald Giemsa-stained cytospin slides. The Sysmex XE-2100 hematology analyzer was used for automated (differential) WBC counting. The functional detection limit was determined by serial dilution of continuous ambulatory peritoneal dialysis (CAPD) fluid and replicate measurements of each dilution. RESULTS: The automated WBC count (x10(6)/L) was highly correlated with that of the microscopic reference method (r(2)=0.95; WBC-analyzer=0.97 x WBC-reference method+16; n=45). Good agreement was also observed for the absolute lymphocyte count (r(2)=0.92; WBC-analyzer=0.99 x WBC-reference method+32; n=36), neutrophil count (r(2)=0.94; WBC-analyzer=0.91 x WBC-reference method+6; n=35), and monocyte count (r(2)=0.73; WBC-analyzer=0.83 x WBC-reference method+6; n=38). The functional detection limit for WBCs was calculated at 50 x 10(6)/L (coefficient of variation 20%). CONCLUSIONS: With some limitations, total and differential WBC counts in pleural fluid can be reliably determined using the Sysmex XE-2100 instrument.