Interprofessional diagnostic management teams: a scoping review protocol.

BACKGROUND: Diagnostic errors are a major problem in healthcare. In 2015, the report "Improving Diagnosis in Health Care" by the National Academies of Sciences, Engineering, and Medicine (NASEM) stated that it is likely that most people will experience at least one diagnostic error in their lifetime. The report suggests implementing diagnostic management teams, including patients and their relatives, diagnosticians, and healthcare professionals who support the diagnostic process, to limit diagnostic error and improve patient safety. Implementing interprofessional diagnostic management teams (IDMT), however, is not an easy task due to the complexity of the diagnostic processes and the traditional organization of healthcare with divided departments and healthcare professional who operate in different geographic locations. As this topic is still emerging, a scoping review is ideal to determine the scope of the body of literature on IDMT, indicate the volume of literature and studies available and identify any gaps in knowledge. In a long-term perspective, this scoping review will contribute to prevent diagnostic errors and improve patient safety, for adults and children with physical health issues. METHODS: We will conduct this scoping review in accordance with the JBI methodology and report it based on the PRISMA-ScR. We will systematically search six databases (EMBASE, PubMed, CINAHL, Academic Search Premier, SCOPUS and Web of Science) for papers published between 1985 and 2023 that describe the use of interprofessional diagnostic management teams. The participants included will be adults and children seeking diagnostic care for physical health issues. The concept studied will be interprofessional diagnostic management teams, and the context will be the diagnostic process in the healthcare system. Studies examining the diagnostic process in psychiatry, odontology or complementary medicine will be excluded. Data extraction, including key study characteristics and findings, will be done by two reviewers independently. Any disagreement will be resolved by discussion and eventually by including the two remainder reviewers. DISCUSSION: To our knowledge, this will be the first scoping review regarding IDMT and the derived effects on diagnostic safety and can therefore be a very important contribution to improve patient safety significantly during the diagnostic process. PROTOCOL REGISTRATION: The project is registered at Open Science Framework (OSF) with ID: osf.io/kv2n6.

Standardised Resting Time Prior to Blood Sampling and Diurnal Variation Associated with Risk of Patient Misclassification: Results from Selected Biochemical Components.

BACKGROUND: According to current recommendations, blood samples should be taken in the morning after 15 minutes' resting time. Some components exhibit diurnal variation and in response to pressures to expand opening hours and reduce waiting time, the aims of this study were to investigate the impact of resting time prior to blood sampling and diurnal variation on biochemical components, including albumin, thyrotropin (TSH), total calcium and sodium in plasma. METHODS: All patients referred to an outpatient clinic for blood sampling were included in the period Nov 2011 until June 2014 (opening hours: 7am-3pm). Each patient's arrival time and time of blood sampling were registered. The impact of resting time and the time of day for all components was analysed using simple linear regression. The "maximum allowable bias" was used as quality indicator for the change in reference interval. RESULTS: Significant diurnal variation was found for albumin (n = 15,544; p<2×10-16), TSH (n = 20,019; p<2×10-16), calcium (n = 13,588; p = 2.8×10-12) and sodium (n = 51,917; p<2×10-16). Further significant influence for resting time was found for albumin (p = 2.6×10-4), TSH (p = 0.004), calcium (p = 8.9×10-7) and sodium (p = 8.7×10-16). Only TSH and albumin were clinically significantly influenced by diurnal variation. Resting time had no clinically significant effect. CONCLUSIONS: We found no need for resting 15 minutes prior to blood sampling. However, diurnal variation was found to have a significant and considerable impact on TSH and, to a minor degree, albumin. This has to be taken into account to ensure that reference intervals provided by the laboratory are valid on a 24-hour basis.

Inhibitory effect of oral contraceptives on CYP2C19 activity is not significant in carriers of the CYP2C19*17 allele.

(1) The purpose of the present study was to examine whether cytochrome P450 2C19 (CYP2C19) in carriers of the CYP2C19*17 allele is inhibited in vivo by oral contraceptives (OC). (2) Retrospective CYP2C19 phenotyping according to omeprazole : 5-OH-omeprazole molar 3 h plasma metabolic ratios (MR) from a population (n = 222) genotyped as CYP2C19*1/*1, CYP2C19*1/*17 and CYP2C19*17/*17 was analysed. Furthermore, 30 women genotyped as CYP2C19*1/*1 (n = 11), CYP2C19*1/*17 (n = 11) and CYP2C19*17/*17 (n = 8) were prospectively CYP2C19 phenotyped during the administration of OC and again after a minimum 5 days break from OC. (3) We found a significantly higher MR in the CYP2C19*1/*1 genotype group that took OC (n = 48) compared with women who did not take OC (n = 31; geometric mean 1.37 vs. 0.83, respectively; P < 0.05). However, in the CYP2C19*1/*17 genotype group, the geometric means of the MR in the 37 women taking OC and the 20 women not taking OC were 0.67 and 0.46, respectively (P > 0.05). In the CYP2C19*1/*1 panel of the prospective cross-over study, we found a significantly higher MR while women were taking the OC compared with the MR during the OC break (geometric mean 1.21 vs. 0.91, respectively; P = 0.0123). However, in the CYP2C19*1/*17 group, the geometric means of the MR with and without OC were 0.77 and 0.65, respectively, compared with 1.05 and 0.79, respectively, in the CYP2C19*17/*17 group (P = 0.20 and 0.17, respectively). (4) In conclusion, we have shown that OC intake inhibits CYP2C19 in homozygous carriers of the CYP2C19 wild type but that the inhibition is not significant in heterozygous and homozygous carriers of the CYP2C19*17 allele.

Two separate dose-dependent effects of paroxetine: mydriasis and inhibition of tramadol's O-demethylation via CYP2D6.

PURPOSE: To investigate paroxetine's putative dose-dependent impact on pupil reaction and inhibition of the O-demethylation of tramadol. METHODS: Twelve healthy CYP2D6 extensive metabolizers participated in this double-blinded randomized five-way placebo controlled cross-over study; they received placebo, 10, 20, 30, and 50 mg paroxetine as single oral doses at bedtime. Next morning the pupil was measured followed by oral intake of 50 mg of tramadol, and urine was collected for 8 h. Three hours after ingestion of tramadol a second measurement of the pupil was performed. Enantioselective urine concentrations of (+/-)-tramadol and (+/-)-O-desmethyltramadol (M1) were determined. RESULTS: With placebo, the median maximum pupil diameter was 6.43 mm (range 5.45-7.75 mm) before tramadol and 6.22 mm (4.35-7.65 mm) after 50 mg of tramadol (P = 0.4935). Paroxetine resulted in a statistically significant, dose-dependent dilatation of the pupil with a geometric mean difference of 1.17 (95% CI 1.10-1.24) after ingestion of 50 mg paroxetine (P < 0.001). Likewise, a reduction in the relative constriction amplitude with a geometric mean difference of 0.81 (95% CI 0.71-0.92) (P < 0.001) was seen. A dose-dependent inhibition of the metabolism of tramadol by an increase in the two urinary metabolic ratios (+)-tramadol / (+)-M1 [geometric mean difference 9.09, 95% CI 5.60-14.73 (P < 0.001)] and (-)-M1 / (+)-M1 [geometric mean difference 2.84, 95% CI 2.15-3.77 (P < 0.001)] was also observed. CONCLUSIONS: Paroxetine is a dose-dependent dilator of the pupil and as expected a dose-dependent inhibitor of (+)-tramadol's O-demethylation.

The antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes.

The aim of this study was to search for a possible association between the variant allele of the single nucleotide polymorphisms A118G in the OPRM1 gene and C3435T and G2677T/A in the ABCB1 gene and altered antinociceptive effect and adverse drug reactions of oxycodone. Thirty-three healthy subjects exposed to experimental pain including electrical stimulation and the cold pressor test were included. A118G: We found that the variant G allele was associated with reduced antinociceptive effect as measured by pain tolerance thresholds to single electrical nerve stimulation (8% increase vs. 25% for the wild-type carriers, P = 0.007). C3435T: The carriers of the variant T allele generally had less adverse drug reactions on oxycodone than the carriers of the wild-type genotype. G2677T/A: The carriers of the variant T allele had a better antinociceptive effect of oxycodone than the carriers of the wild-type genotype in the cold pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25% reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug reactions. The combined wild-type genotype 3435CC-2677GG was associated with less antinociceptive effect of oxycodone in the discomfort rating of the cold pressor test (13% reduction vs. 23%, P = 0.019) and more severe adverse drug reactions than the carriers of the variant alleles. We found a moderate association between less antinociceptive effect of oxycodone and the variant allele of A118G. There was strong association between less adverse drug reactions of oxycodone and the variant alleles of C3435T and G2677T/A.

The hypoalgesic effect of oxycodone in human experimental pain models in relation to the CYP2D6 oxidation polymorphism.

Oxycodone is O-demethylated by CYP2D6 to oxymorphone which is a potent micro-receptor agonist. The CYP2D6 oxidation polymorphism divides the Caucasian population in two phenotypes: approximately 8% with no enzyme activity, poor metabolizers (PM) and the remainder with preserved CYP2D6 activity, extensive metabolizers (EM). The objective of the study was to determine if the analgesic effect of oxycodone in human experimental pain depends on its metabolism to oxymorphone. The analgesic effect of oxycodone was evaluated in a randomized, placebo-controlled, double-blinded, crossover experiment including 33 (16 EM and 17 PM) healthy volunteers. Pain tests were performed before and 1, 2, 3 and 4 hr after medication and included pain detection and tolerance thresholds to single electrical sural nerve stimulation, pain summation threshold to repetitive electrical sural nerve stimulation and the cold pressor test with rating of discomfort and pain-time area under curve (AUC(0-2 min.)). For single sural nerve stimulation, there was a less pronounced increase in thresholds on oxycodone in pain detection (9% vs. 20%, P = 0.02, a difference of 11%, CI: 2%-20%) and pain tolerance thresholds (15% vs. 26%, P = 0.037, a difference of 10%, CI: 1%-20%) for PM compared with EM. In the cold pressor test, there was less reduction in pain AUC on oxycodone for PM compared with EM (14% vs. 26%, P = 0.012, a difference of 12%, CI: 3%-22%). The plasma oxymorphone/oxycodone ratio was significantly lower in PM compared with EM (P < 0.001). Oxycodone analgesia seems to depend both on oxycodone itself and its metabolite oxymorphone.

The relative bioavailability of loratadine administered as a chewing gum formulation in healthy volunteers.

OBJECTIVE: The aim of this study was to investigate the pharmacokinetics of loratadine and its active metabolite desloratadine after single-dose administration of loratadine as a conventional tablet, orally disintegrating tablet (smelt tablet) and a chewing gum formulation with and without the collection of saliva. METHODS: Twelve healthy male volunteers participated in a four-period cross-over trial evaluating the effect of dosage forms on the pharmacokinetics of a single dose of loratadine. Loratadine was administered as two 10-mg conventional tablet, two 10-mg smelt tablet, a 30-mg portion of medicated chewing gum without collection of saliva and a 30-mg portion of medicated chewing gum with collection of saliva. Blood samples were taken at predefined sampling points 0-24 h after medication, and the plasma concentrations of loratadine and desloratadine were determined by high-performance liquid chromatography. Each study period was separated by a wash-out period of at least 7 days. RESULTS: The mean dose-corrected area under the plasma concentration-time curve extrapolated to infinity AUC(0-infinity) for the chewing gum formulation was statistically significantly increased compared to the tablet formulation (geometric mean ratio: 2.68; 95%CI: 1.75-4.09). Desloratadine pharmacokinetic parameters from the chewing gum formulation were not statistically significantly different from the conventional tablet. Neither loratadine nor desloratadine pharmacokinetics of the smelt tablet formulation were statistically significantly different from the conventional tablet formulation. Plasma concentrations of desloratadine following the administration of loratadine as chewing gum with saliva collection were very low. CONCLUSION: Our study showed that formulation of loratadine as a medicated chewing gum results in an almost threefold increase in relative bioavailability. This is most likely due to a bypass of first-pass metabolism as this study suggests that approximately 40% of the absorbed loratadine was absorbed via the oral mucosa.