Unexplained Discrepancies Research Articles

Retraction of Gino et al. (2020).

Reports the retraction of "Why connect? Moral consequences of networking with a promotion or prevention focus" by Francesca Gino, Maryam Kouchaki and Tiziana Casciaro (Journal of Personality and Social Psychology, 2020[Dec], Vol 119[6], 1221-1238). This retraction is at the request of the Research Integrity Officer at Harvard Business School after the results of a review into data for Study 3a collected and analyzed by Francesca Gino. The review identified unexplained discrepancies between (a) the data associated with Study 3a in the Open Science Framework platform and (b) the original, raw data collected in Qualtrics. These discrepancies, which involved 28% of the total data from Study 3a, biased the published results in the direction of the study hypothesis. A reanalysis of the original data invalidated the previous conclusion from the study. The report of the investigation did not concern either Maryam Kouchaki or Tiziana Casciaro, who agree with the retraction. (The following abstract of the original article appeared in record 2020-42384-001.) Networks are a key source of social capital for achieving goals in professional and personal settings. Yet, despite the clear benefits of having an extensive network, individuals often shy away from the opportunity to create new connections because engaging in instrumental networking can make them feel morally impure. In this article, we explore how the motives people have when engaging in networking impact these feelings and, as result, change how frequently they engage in networking and their job performance. Across a correlational survey study, a laboratory experiment (with samples from the United States and Italy), two online studies, an organizational network survey study, and a field experiment with professionals (total N = 2,551), we examine how self-regulatory focus, whether promotion or prevention, affects people's experience of and outcomes from networking. We find that a promotion focus, as compared to a prevention focus or a control condition, is beneficial to professional networking, as it lowers feelings of moral impurity from instrumental networking. As such, networking with a promotion focus increases the frequency of instrumental networking as compared to a control condition, whereas networking with a prevention focus decreases frequency of instrumental networking as compared to a control condition. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Maternal and new-born health policy indicators for low-resourced countries: The example of Liberia

Aim: Over the past two decades, two catastrophic events caused a steep decline in health services in Liberia: the long-lasting civil war (1989-2003) and the weak response of the health system to the Ebola Viral Disease (EVD) outbreak (2013-2015). In early 2015 The Liberian Government reacted and developed a strategic health policy framework. This paper reviews that framework with a focus on maternal and newborn health. Methods: The study is designed as a narrative review executed during the second half of 2017 in Monrovia. It takes advantage of triangulation, derived from recent international and national documents, relevant literature, and available information from primary and secondary sources and databases. Results: In 2015 the severely compromised health system infrastructure included lack of functional refrigerators, low availability of vaccines and child immunization guidelines, high stock-out rates, and an absence of the cold chain minimum requirements in 46% of health facilities. The public health workforce on payroll during 2014/15 included only 117 physicians. Skilled birth attendance as an indicator of maternal health services performance was 61%. Presently, approximately 4.5 women die each day in Liberia due to complications of pregnancy, delivery, and during the post-partum period, equalling about 1,100 women per 100,000 live births. Of particular note is the adolescent birth rate of 147 per 1000 women aged 15-19 years, three times higher than the world average of 44. Additionally, with a neonatal mortality rate of 19.2 neonatal deaths per 1,000 live births, Liberia stands higher than the world average as well. The high mortality rates are caused by multiple factors, including a delay in recognition of complications and the need for medical care, the time it takes to reach a health facility due to a lack of suitable roads and transportation, and a delay in receiving competent care in the health facilities. Conclusions: The fact that performance is above average for some indicators and far below for other points to unexplained discrepancies and a mismatch of international and national definitions or validity of data. Therefore, it is recommended to concentrate on the core of tracer indicators adopted at the global level for Universal Health Coverage and the Sustainable Development Goals to enable a permanent update of relevant information for policymaking and adjustment. At present all health policy documents miss a thorough application of the SMART objectives (Specific, Measurable, Attainable, Relevant and Timely), notably missing in most documents are realistic and detailed budgeting and obligatory timelines for set targets.

SA59 Is There Life for Pre-Prints After COVID-19?

During the COVID-19 pandemic, pre-prints were widely used to accelerate data dissemination. Advantages of using such material in a crisis are compelling but should still be balanced against potential limitations (e.g., the lack of peer-review and possible unexplained data discrepancies between pre-prints and corresponding journal publications). We aimed to assess recently published pre-prints on non-COVID-19 treatments, for insights into the utility of such material in the absence of related peer-reviewed publications. The pre-print databases SSRN and MedRXiv were systematically searched for records posted in 2021 and reporting randomised trials of any pharmacological or surgical interventions for non-COVID-19 indications. MEDLINE and Embase were also searched for corresponding peer-reviewed articles published by May 2022. Data gathered and analysed included posting/publication date, sample size and any differences in definition/reporting of primary outcomes between pre-pint and peer-reviewed publication. Overall, 41 (of 688 screened) pre-prints were included, with 22 having a corresponding peer-reviewed publication. The median time from pre-print posting to journal publication was 4.35 months (range: 1–13.4 months), over a median follow-up (i.e., time from pre-print posting to database search) of 9.9 months (range: 1.8–15.5 months). For the 19 pre-prints without a peer-reviewed publication, the median follow-up was 7.4 months (range: 4.6–14.9 months). There were no discrepancies in the reporting of primary outcomes in 18 out of the 19 pre-print/peer-reviewed-publication dyads. In one of the dyads, the pre-print reported only the per-protocol results, while the peer-reviewed publication reported only the intention-to-treat analysis. Nevertheless, the overall conclusions were similar in both publications. Our study suggests that pre-prints can be a reliable source of evidence, often accessible several months before any corresponding peer-reviewed publication. While the findings need confirmation in further research, they raise questions about whether pre-prints should be considered routinely in settings where early availability of data may be crucial, such as reimbursement decision-making.

In-beam γ -ray spectroscopy of Mg32 via direct reactions

Background: The nucleus $^{32}$Mg ($N=20$ and $Z=12$) plays a central role in the so-called "island of inversion" where in the ground states $sd$-shell neutrons are promoted to the $fp$-shell orbitals across the shell gap, resulting in the disappearance of the canonical neutron magic number $N=20$. Purpose: The primary goals of this work are to extend the level scheme of $^{32}$Mg, provide spin-parity assignments to excited states, and discuss the microscopic structure of each state through comparisons with theoretical calculations. Method: In-beam $\gamma$-ray spectroscopy of $^{32}$Mg was performed using two direct-reaction probes, one-neutron (two-proton) knockout reactions on $^{33}$Mg ($^{34}$Si). Final-state exclusive cross sections and parallel momentum distributions were extracted from the experimental data and compared with eikonal-based reaction model calculations combined with shell-model overlap functions. Results: Owing to the remarkable selectivity of the one-neutron and two-proton knockout reactions, a significantly updated level scheme for $^{32}$Mg, which exhibits negative-parity intruder and positive-parity normal states, was constructed. The experimental results were confronted with four different nuclear structure models. Conclusions: In some of these models, different aspects of $^{32}$Mg and the transition into the island of inversion are well described. However, unexplained discrepancies remain, and even with the help of these state-of-the-art theoretical approaches, the structure of this key nucleus is not yet fully captured.

Deciphering metformin action in obese mice: A critical re-evaluation of established protocols

Background and purposeDespite extensive efforts and a plethora of suggested targets and pathways, the mechanism via which metformin lowers blood glucose remains obscure. Obstacles that hamper progress in understanding metformin action include unexplained discrepancies between preclinical models and patients. ProceduresWe treated obese male C57BL/6J mice fed high fat diet with metformin provided in the form of a single dose, daily intraperitoneal injections, admixture to drinking water, or continuous infusion via intraperitoneal minipumps. ResultsThe results suggest several superimposed components, via which metformin acts on blood glucose. These include (i) marked glucose lowering shortly after dosing, which fades rapidly with the decrease in metformin concentrations in plasma and liver, but could, at least to a major extent, rely on the mechanism also accounting for metformin's therapeutic action in humans; (ii) indirect action via reduced weight gain, which might be responsible for glucose lowering observed in many previous rodent studies; and (iii) deterioration of glucose homeostasis by prolonged treatment that can be unmasked by avoidance of dosing shortly before measuring blood glucose in combination with exclusion of weight-related actions via restricted feeding of the control mice. ConclusionsOur work raises the question whether elucidation of metformin's anti-diabetic mechanism(s) in rodent experiments may in the past have been hampered by failure to mimic clinical circumstances, as caused by insufficient consideration of pharmacokinetics and multiplicity of involved actions.

Limitations of Current Approaches for Predicting Groundwater Vulnerability from PFAS Contamination in the Vadose Zone.

Published literature for reported sorption coefficients (Kd) of eight anionic per- and polyfluoroalkyl substances (PFAS) in soil was reviewed. Kd values spanned three to five log units indicating that no single value would be appropriate for use in estimating PFAS impacts to groundwater using existing soil-water partition equations. Regression analysis was used to determine if the soil or solution parameters might be used to predict Kd values. None of the 15 experimental parameters collected could individually explain variability in reported Kd values. Significant associations between Kd and soil calcium and sodium content were found for many of the selected PFAS, suggesting that soil cation content may be critical to PFAS sorption, as previously noted in sources like Higgins and Luthy (2006), while organic carbon content was significant only at elevated levels (>5%). Unexplained discrepancies between the results from studies where PFAS were introduced to soil and desorbed in the laboratory and those that used material from PFAS-impacted sites suggest that laboratory experiments may be overlooking some aspects critical to PFAS sorption. Future studies would benefit from the development and use of standardized analytical methods to improve data quality and the establishment of soil parameters appropriate for collection to produce more complete data sets for predictive analysis.

Uncertainty in East Antarctic Firn Thickness Constrained Using a Model Ensemble Approach

AbstractMass balance assessments of the East Antarctic ice sheet (EAIS) are highly sensitive to changes in firn thickness, causing substantial disagreement in estimates of its contribution to sea‐level. To better constrain the uncertainty in recent firn thickness changes, we develop an ensemble of 54 model scenarios of firn evolution between 1992 and 2017. Using statistical emulation of firn‐densification models, we quantify the impact of firn compaction formulation, differing climatic forcing, and surface snow density on firn thickness evolution. At basin scales, the ensemble uncertainty in firn thickness change ranges between 0.2 and 1.0 cm yr−1 (15%–300% relative uncertainty), with the choice of climate forcing having the largest influence on the spread. Our results show the regions of the ice sheet where unexplained discrepancies exist between observed elevation changes and an extensive set of modeled firn thickness changes estimates, marking an important step toward more accurately constraining ice sheet mass balance.

Fabricated or induced illness: From “Munchausen by proxy” to child and family-oriented action

BackgroundIn fabricated or induced illness (FII), a child is harmed due to caregiver(s) behaviour and actions, carried out to convince mainly doctors that the child’s physical and/or psychological health is more impaired than in reality. Harm is caused directly by the caregivers(s) and also often inadvertently by doctors’ responses. ObjectivesTo describe: dynamics underlying FII; wider definition of FII; alerting signs for early recognition of possible FII; respective responsibilities of health, social care, education. MethodsLiterature review, clinical experience, expert opinion. Results and conclusionsCaregivers are motivated by gain from having their child treated as ill, and/or by erroneous beliefs about their child's health, either way needing medical confirmation about their contentions. Their behaviour is therefore directed primarily towards doctors. Most cases of FII present unexplained discrepancies between caregiver reports/actions and independent observations of the child. More rarely, the child has actual signs of illness, induced by the caregiver, occasionally fatal.Children are harmed in all aspects of life: health, daily functioning including education, and psychologically. Harm emanates directly from the caregiver(s) but also unintentionally from medical responses.Illness induction and clear deception by the caregiver require immediate child protection. Otherwise, the initial focus is on assessing the child’s current health and functioning rather than caregiver's mental health. If, beyond verified illness, there is no medical explanation for the child’s reported ill-health, the family require help to function better. This requires co-ordinated, multidisciplinary rehabilitation and long-term monitoring. If caregivers refuse rehabilitation, child protection is required. Several unanswered questions remain.

Public availability and adherence to prespecified statistical analysis approaches was low in published randomized trials

Background and ObjectivePrespecification of statistical methods in clinical trial protocols and statistical analysis plans can help to deter bias from p-hacking but is only effective if the prespecified approach is made available. Study Design and SettingFor 100 randomized trials published in 2018 and indexed in PubMed, we evaluated how often a prespecified statistical analysis approach for the trial's primary outcome was publicly available. For each trial with an available prespecified analysis, we compared this with the trial publication to identify whether there were unexplained discrepancies. ResultsOnly 12 of 100 trials (12%) had a publicly available prespecified analysis approach for their primary outcome; this document was dated before recruitment began for only two trials. Of the 12 trials with an available prespecified analysis approach, 11 (92%) had one or more unexplained discrepancies. Only 4 of 100 trials (4%) stated that the statistician was blinded until the SAP was signed off, and only 10 of 100 (10%) stated the statistician was blinded until the database was locked. ConclusionFor most published trials, there is insufficient information available to determine whether the results may be subject to p-hacking. Where information was available, there were often unexplained discrepancies between the prespecified and final analysis methods.

Evidence of unexplained discrepancies between planned and conducted statistical analyses: a review of randomised trials

BackgroundChoosing or altering the planned statistical analysis approach after examination of trial data (often referred to as ‘p-hacking’) can bias the results of randomised trials. However, the extent of this issue in practice is currently unclear. We conducted a review of published randomised trials to evaluate how often a pre-specified analysis approach is publicly available, and how often the planned analysis is changed.MethodsA review of randomised trials published between January and April 2018 in six leading general medical journals. For each trial, we established whether a pre-specified analysis approach was publicly available in a protocol or statistical analysis plan and compared this to the trial publication.ResultsOverall, 89 of 101 eligible trials (88%) had a publicly available pre-specified analysis approach. Only 22/89 trials (25%) had no unexplained discrepancies between the pre-specified and conducted analysis. Fifty-four trials (61%) had one or more unexplained discrepancies, and in 13 trials (15%), it was impossible to ascertain whether any unexplained discrepancies occurred due to incomplete reporting of the statistical methods. Unexplained discrepancies were most common for the analysis model (n = 31, 35%) and analysis population (n = 28, 31%), followed by the use of covariates (n = 23, 26%) and the approach for handling missing data (n = 16, 18%). Many protocols or statistical analysis plans were dated after the trial had begun, so earlier discrepancies may have been missed.ConclusionsUnexplained discrepancies in the statistical methods of randomised trials are common. Increased transparency is required for proper evaluation of results.

Diffusion multiple study of the Co-Fe-Ni system at 800 °C

The Co-Fe-Ni system is a key system in a wide range of industrial applications. Knowledge of the thermodynamic and kinetic properties of the system is crucial for the alloy and process design. Although the system has been studied extensively, there remain several unexplained discrepancies between different literature data and, for mediate low temperatures, the information is scarce. In this work, a high throughput diffusion multiple approach was applied. The isothermal phase diagram section at 800 °C was determined using the Co-Fe-Ni multiple. The interdiffusion coefficients of the binary Co-Fe, Co-Ni, Fe-Ni systems and their composition dependence were calculated using the Sauer-Freise method based on the compositional profiles obtained from the diffusion multiple. Different from previous experimental results for mediate low temperature, our results coincide with the extrapolated Arrhenius temperature dependence from diffusion coefficient data at high temperature range. These observations are important for a better understanding and modelling of the interdiffusion behavior in this key alloy system.

Intercomparison of midlatitude tropospheric and lower-stratospheric water vapor measurements and comparison to ECMWF humidity data

Abstract. Accurate measurement of water vapor in the climate-sensitive region near the tropopause is very challenging. Unexplained systematic discrepancies between measurements at low water vapor mixing ratios made by different instruments on airborne platforms have limited our ability to adequately address a number of relevant scientific questions on the humidity distribution, cloud formation and climate impact in that region. Therefore, during the past decade, the scientific community has undertaken substantial efforts to understand these discrepancies and improve the quality of water vapor measurements. This study presents a comprehensive intercomparison of airborne state-of-the-art in situ hygrometers deployed on board the DLR (German Aerospace Center) research aircraft HALO (High Altitude and LOng Range Research Aircraft) during the Midlatitude CIRRUS (ML-CIRRUS) campaign conducted in 2014 over central Europe. The instrument intercomparison shows that the hygrometer measurements agree within their combined accuracy (±10 % to 15 %, depending on the humidity regime); total mean values agree within 2.5 %. However, systematic differences on the order of 10 % and up to a maximum of 15 % are found for mixing ratios below 10 parts per million (ppm) H2O. A comparison of relative humidity within cirrus clouds does not indicate a systematic instrument bias in either water vapor or temperature measurements in the upper troposphere. Furthermore, in situ measurements are compared to model data from the European Centre for Medium-Range Weather Forecasts (ECMWF) which are interpolated along the ML-CIRRUS flight tracks. We find a mean agreement within ±10 % throughout the troposphere and a significant wet bias in the model on the order of 100 % to 150 % in the stratosphere close to the tropopause. Consistent with previous studies, this analysis indicates that the model deficit is mainly caused by too weak of a humidity gradient at the tropopause.

Structural differences between single crystal and polycrystalline UBe13

We report on observations of structural and chemical differences between samples of UBe13 that were synthesised using two different methods. Unexplained discrepancies in properties between samples with differing synthesis had previously been found in this heavy fermion superconductor. A polycrystalline UBe13 sample was made by arc-melting the constituents. Single crystals were grown using an aluminium flux and had a consistently slightly larger lattice parameter than the polycrystals, which merited further study. Neutron diffraction data were collected at the Lujan Center at LANSCE on the HIPPO diffractometer. Aluminium was detected by inductively coupled plasma mass spectrometry (ICP-MS) in the flux-grown single crystal (0.803 wt%), and small amounts (~0.2 wt%) of thorium were detected in the UBe13 polycrystalline sample. In order to probe the implications of the presence of Al, calculations by spin-polarised DFT-GGA+U show that the incorporation of Al onto the 96i site (the lowest symmetry site in the structure) is energetically more favourable than on other sites. In general, the trends calculated by DFT for bond lengths and lattice parameter increases are consistent with bond lengths experimentally observed by neutron diffraction, but specific percentage changes with aluminium incorporation may be obscured by the unexpected thorium in the polycrystalline sample. The aggregate of our initial observations suggests that incorporation of aluminium from the flux into single crystal UBe13 is significant.

Circuit-based versus full-wave modelling of active microwave circuits

ABSTRACTModern full-wave computational tools enable rigorous simulations of linear parts of complex microwave circuits within minutes, taking into account all physical electromagnetic (EM) phenomena. Non-linear components and other discrete elements of the hybrid microwave circuit are then easily added within the circuit simulator. This combined full-wave and circuit-based analysis is a must in the final stages of the circuit design, although initial designs and optimisations are still faster and more comfortably done completely in the circuit-based environment, which offers real-time solutions at the expense of accuracy. However, due to insufficient information and general lack of specific case studies, practitioners still struggle when choosing an appropriate analysis method, or a component model, because different choices lead to different solutions, often with uncertain accuracy and unexplained discrepancies arising between the simulations and measurements. We here design a reconfigurable power amplifier, as a case study, using both circuit-based solver and a full-wave EM solver. We compare numerical simulations with measurements on the manufactured prototypes, discussing the obtained differences, pointing out the importance of measured parameters de-embedding, appropriate modelling of discrete components and giving specific recipes for good modelling practices.

Patient-, medication- and environment-related factors affecting medication discrepancies in older patients

BackgroundAs patients move across different clinical settings, medication changes are likely to occur. AimTo identify patient-, medication- and environment-related factors associated with unintentional medication discrepancies in older patients, who were admitted to hospital via an emergency department and who had a subacute care admission at some point following hospital admission. MethodsA retrospective clinical audit was undertaken using a stratified random sampling approach over a 14-month period. Medical records of patients aged 65 years or over were collected from five hospitals. FindingsData were collected from 426 older patients. Of these patients, 169 (39.7%) had at least one unexplained medication discrepancy. Patients without social supports had 2.956 greater odds of experiencing an unexplained medication discrepancy (95% CI 1.870–4.671), p<0.0001. As the number of prescribed medications increased upon admission to the emergency department, patients had 1.125 greater odds of experiencing an unexplained medication discrepancy (95% CI 1.035–1.223), p=0.006. Patients discharged to destinations other than their home had 2.714 increased odds (95% CI 1.317–5.594), p=0.007 while those experiencing more than four transition points of care had 2.476 increased odds (95% CI 1.208–5.074), p=0.013, of experiencing an unexplained medication discrepancy. A significant association existed between the prevalence of unexplained medication discrepancies and hospital readmission within six months, χ2=36.496, df=1, p<0.001. ConclusionGreat care is needed in managing complex medication regimens of older people with multiple chronic conditions, especially those who move across several transition points of care.

State-to-State Variation in SSI Enrollment for Children With Mental Disabilities: An Administrative and Ethical Challenge.

The study examined state variation in rates of Supplemental Security Income (SSI) determinations, allowances, and receipt of benefits for ten selected child mental disabilities in 2013. SSI administrative and U.S. Census Bureau data collected by a multidisciplinary consensus committee convened by the National Academies of Science, Engineering, and Medicine in 2015 were examined. Less than 1% of children in 2013 were recipients of SSI for mental disabilities. Determination rates ranged from 1,441 to 251 per 100,000 low-income children, an almost sixfold difference. Allowance rates varied from 16% to 78%, a fivefold difference. Receipt of benefits ranged from .7% to 5.3%, a sevenfold difference. Large unexplained discrepancies across states were found in review and receipt of SSI benefits for low-income children with mental disabilities. Inequities that cannot be explained by disability severity or financial need violate the ethos of equitable access to federally entitled services.

Reconstructing the last interglacial at Summit, Greenland: Insights from GISP2

The Eemian (last interglacial, 130-115 ka) was likely the warmest of all interglacials of the last 800 ka, with summer Arctic temperatures 3-5 °C above present. Here, we present improved Eemian climate records from central Greenland, reconstructed from the base of the Greenland Ice Sheet Project 2 (GISP2) ice core. Our record comes from clean, stratigraphically disturbed, and isotopically warm ice from 2,750 to 3,040 m depth. The age of this ice is constrained by measuring CH4 and δ(18)O of O2, and comparing with the historical record of these properties from the North Greenland Ice Core Project (NGRIP) and North Greenland Eemian Ice Drilling (NEEM) ice cores. The δ(18)Oice, δ(15)N of N2, and total air content for samples dating discontinuously from 128 to 115 ka indicate a warming of ∼6 °C between 127-121 ka, and a similar elevation history between GISP2 and NEEM. The reconstructed climate and elevation histories are compared with an ensemble of coupled climate-ice-sheet model simulations of the Greenland ice sheet. Those most consistent with the reconstructed temperatures indicate that the Greenland ice sheet contributed 5.1 m (4.1-6.2 m, 95% credible interval) to global eustatic sea level toward the end of the Eemian. Greenland likely did not contribute to anomalously high sea levels at ∼127 ka, or to a rapid jump in sea level at ∼120 ka. However, several unexplained discrepancies remain between the inferred and simulated histories of temperature and accumulation rate at GISP2 and NEEM, as well as between the climatic reconstructions themselves.

Clinical trials: The mathematics of falling vaccine efficacy with rising disease incidence

Reports of unexplained discrepancies in the efficacy of vaccines, as estimated from randomised controlled trials in different parts of the world, are commonplace in the literature [1], [2], [3], [4]. Moreover, there is a consistent trend for lower vaccine efficacy when measured in settings where the disease of interest has a higher incidence, leading to questions about the appropriateness of pooled estimates. Here, we examine the mathematical basis for such trends and propose a measure of efficacy that is valid across settings. The approach relies on fitting mechanistic models, which specify pathogen exposures and host responses, to global vaccine trial data stratified by local disease incidence. Such models enable the estimation of vaccine protection per exposure to the pathogen. A strategy to estimate per-exposure vaccine efficacy will enable more accurate estimates of vaccine efficacy across a range of disease incidence [5].

The impact of CYP3A5*3 polymorphism on sirolimus pharmacokinetics: insights from predictions with a physiologically-based pharmacokinetic model.

Sirolimus is an mTOR inhibitor metabolized by CYP3A4 and CYP3A5. Reported effects of CYP3A5 polymorphisms on sirolimus pharmacokinetics (PK) have shown unexplained discrepancies across studies. We quantitatively assessed the effect of CYP3A5*3 status on sirolimus PK by in vitro assessment and simulation using a physiologically-based PK (PBPK) model. In addition, we explored designs for an adequately powered pharmacogenetic association study. In vitro metabolism studies were conducted to confirm individual CYP contribution to sirolimus metabolism. PK profiles were simulated in CYP3A5 expressers and non-expressers with a PBPK model. The pre-dose concentration predictions were used as the outcome parameter to estimate the required sample size for a pharmacogenetic association study. Sirolimus metabolism was inhibited by over 90% by ketoconazole, a CYP3A specific inhibitor. The PBPK model developed based on CL(int) of recombinant CYP3A4, CYP3A5 and CYP2C8 predicted a small CYP3A5*3 effect on simulated sirolimus PK profiles. A subsequent power analysis based on these findings indicated that at least 80 subjects in an enrichment design, 40 CYP3A5 expressers and 40 non-expressers, would be required to detect a significant difference in the predicted trough concentrations at 1 month of therapy (P < 0.05, 80% power). This study suggests that CYP3A5 contribution to sirolimus metabolism is much smaller than that of CYP3A4. Observed discrepancies across studies could be explained as the result of inadequate sample size. PBPK model simulations allowed mechanism-based evaluation of the effects of CYP3A5 genotype on sirolimus PK and provided preliminary data for the design of a future prospective study.

Accuracy in the medication history and reconciliation errors in the emergency department

Background and objectiveTo assess the accuracy of pharmaceutical anamnesis obtained at the Emergency Department (ED) of a tertiary referral hospital and to determine the prevalence of medication reconciliation errors (RE). Materials and methodsThis was a single-center, prospective, interventional study. The home medication list obtained by a pharmacist was compared with the one recorded by a doctor to identify inaccuracies. Subsequently, the home medication list was compared with the active prescription at the ED. All unexplained discrepancies were checked with the doctor in charge to evaluate if a RE has occurred. A univariate analysis was performed to identify factors associated with RE. ResultsThe pharmacist identified a higher number of drugs than doctors (6.89 versus 5.70; p<0.05). Only 39% of the drugs obtained by doctors were properly written down in the patient's record. The main cause of discrepancy was omission of information regarding the name of the drug (39%) or its dosage (33%). One hundred and fifty-seven RE were identified and they affected 85 patients (43%), mainly related to information omission (62%). Age and polymedication were identified as main risk factors of RE. The presence of a caregiver or relative in the ED was judged to be a protective factor. No relationship was found between inaccuracies in the registries and RE. ConclusionsThe process of obtaining a proper pharmaceutical anamnesis still needs improvement. The pharmacist may play a role in the process of obtaining a good quality anamnesis and increase patient safety by detecting RE. Better information systems are needed to avoid this type of incidents.