A Statement on the Role and Qualifications of Health Care Chaplains for Research and Quality.

CONTEXT: This statement fills a significant gap in the efforts to demonstrate outcomes of the chaplaincy role in health care and to provide direction for quality measurement related to spiritual care as a key domain of serious illness care. OBJECTIVES: The objective of this project was to develop the first major consensus statement on the role and qualifications of health care chaplains in the Unites States. METHODS: The statement was developed by a diverse panel of highly regarded professional chaplains and nonchaplain stakeholders. RESULTS: The document provides guidance to chaplains and other spiritual care stakeholders as they further integrate spiritual care in health care and conduct research and quality improvement efforts to strengthen the evidence base for practice. The consensus statement is in Fig. 1 and available at https://www.spiritualcareassociation.org/role-of-the-chaplain-guidance.html. CONCLUSION: This statement can potentially drive the standardization and alignment of all phases of health care chaplaincy preparation and practice.

The economic burden of poor glycemic control associated with therapeutic inertia in patients with type 2 diabetes in Denmark.

OBJECTIVE: To evaluate the economic burden associated with therapeutic inertia in patients with type 2 diabetes mellitus (T2D) in Denmark. METHODS: The economic burden for a newly diagnosed Danish T2D population was estimated using a validated diabetes model (The Swedish Institute for Health Economics (IHE) Cohort model), based on achieving varying levels of glycemic control. The analyses were based on clinical data from the Danish Centre for Strategic Research (DD2) and supplemented with relevant Swedish data where variables were missing. The analysis estimated the economic burden for populations achieving different guideline-recommended targets for glycated hemoglobin (HbA1c) and for a number of therapeutic inertia scenarios. To estimate the population-level burden Danish specific epidemiology data were incorporated. All costs are reported in 2020 Danish kroner (DKK) and 2020 Euros (€). RESULTS: The baseline HbA1c level used for this analysis was 7.9% (63 mmol/mol), which was observed in newly diagnosed Danish T2D patients prior to their first anti-diabetic treatment. Therapeutic inertia was associated with substantial economic burden compared to achieving immediate glycemic control (target < 6.5% (< 48 mmol/mol)). Per patient burdens were between 3562 DKK and 20,160 DKK (€477- €2701) dependent on the duration of therapeutic inertia (1-7 years), with this further increased when indirect costs were included (9649 DKK to 51,585 DKK [€1393-€6912]). The economic burden at a population level was between 27 million DKK to 150 million DKK (€3.6 million to €20 million), dependent on the duration of therapeutic inertia, rising to 72 million DKK to 384 million DKK (€9.6 million to €51.4 million) when indirect costs were included. CONCLUSION: Achieving early and intensive glycemic control, thereby minimizing therapeutic inertia can lead to substantial savings for the Danish society, ranging between 72 million DKK and 384 million DKK (€9.6 million to €51.4 million) (1-7 years of therapeutic inertia). This study highlights that efforts to minimize therapeutic inertia, by securing timely intensification before individual HbA1c targets are exceeded, results in significant long-term cost savings in Denmark.

Earliest complete hominin fifth metatarsal-Implications for the evolution of the lateral column of the foot.

StW 114/115, from Sterkfontein, South Africa, is the earliest complete hominin fifth metatarsal. Comparisons of StW 114/115 to modern humans, extant apes, and partial hominin metatarsals AL 333-13, AL 333-78, SKX 33380, OH 8, and KNM-ER 803f reveal a similar morphology in all six fossils consistent with habitual bipedality. Although StW 114/115 possesses some primitive characters, the proximal articular morphology and internal torsion of the head are very human-like, suggesting a stable lateral column and the likely presence of lateral longitudinal and transverse tarsal arches. We conclude that, at least in the lateral component of the foot of the StW 114/115 individual, the biomechanical pattern is very similar to that of modern humans. This, however, may not have been the case in the medial column of the foot, as a mosaic pattern of hominin foot evolution and function has been suggested. The results of this study may support the hypothesis of an increased calcaneo-cuboid stability having been an early evolutionary event in the history of terrestrial bipedalism.

Frequency of CYP3A4, CYP3A5, CYP2C9, and CYP2C19 variant alleles in patients receiving clopidogrel that experience repeat acute coronary syndrome.

The presence of cytochrome P450 (CYP) variant alleles may reduce the activation of the prodrug clopidogrel to its active state. This research evaluated the frequency of variant alleles in the genes coding for CYP3A4, CYP3A5, CYP2C9, and CYP2C19 enzymes in patients on clopidogrel therapy and experiencing repeat acute coronary syndrome (ACS) compared to a control group with a matching ethnic composition. Real-time polymerase chain reaction was used for allelic discrimination. Complete data were obtained for 92 patients enrolled over a 3-month period. There were no significant differences in the presence of the examined CYP3A4, CYP3A5, CYP2C9, or CYP2C19 variant alleles between the two groups. The present data indicate that patients currently receiving clopidogrel therapy who present with repeat ACS do not have higher frequency of the examined variant alleles compared to a control group.

CYP2C9 genetic polymorphisms and warfarin.

The objective of this study was to report 2 cases of CYP2C9 genetic polymorphism and elevated warfarin S:R ratios in patients taking low doses of warfarin, and compare the observed characteristics with those in published reports. Two patients of different age groups and races were evaluated for CYP2C9 genotype and warfarin S:R ratios. The patients had been stabilized on weekly warfarin doses of 10.5 mg and 10 mg, respectively. Each patient was found to have at least 1 variant CYP2C9 allele. Elevated warfarin S:R ratios in both patients provided evidence for impaired metabolism of S-warfarin. This report of a CYP2C9*3 heterozygous individual taking a low dose of warfarin is consistent with previous reports in the literature. This summary of a CYP2C9*6 homozygous individual taking a low dose of warfarin is the first such published report. CYP2C9 genotyping in these patients provided a likely explanation for their continued low warfarin dosage requirements. Awareness of a patient's CYP2C9 genotype may provide an explanation for low warfarin dosage requirements in stable patients and may help in determining the optimal dose in patients being initiated on warfarin.

High plantar pressure and callus in diabetic adolescents. Incidence and treatment.

This study examined the incidence of high peak plantar pressure and plantar callus in 211 adolescents with diabetes mellitus and 57 nondiabetic controls. The percentage of subjects with these anomalies was the same in both groups. Although diabetic subjects were no more likely than nondiabetic controls to have high peak plantar pressure and callus, these anomalies place individuals with diabetes at greater risk of future foot problems. The effects of orthoses, cushioning, and both in combination were monitored in 17 diabetic subjects with high peak plantar pressure and in 17 diabetic subjects with plantar callus; reductions of up to 63% were achieved. Twelve-month follow-up of diabetic subjects fitted with orthoses showed a significant reduction in peak plantar pressure even when the orthoses were removed. The diabetic subjects who had not received any interventions during the same 12-month period showed no significant change in peak plantar pressure.

Warfarin Dosing in a Patient with CYP2C9(∗)3(∗)3 and VKORC1-1639 AA Genotypes.

Genetic factors most correlated with warfarin dose requirements are variations in the genes encoding the enzymes cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR). Patients receiving warfarin who possess one or more genetic variations in CYP2C9 and VKORC1 are at increased risk of adverse drug events and require significant dose reductions to achieve a therapeutic international normalized ratio (INR). A 74-year-old white female with atrial fibrillation was initiated on a warfarin dose of 2 mg PO daily, which resulted in multiple elevated INR measurements and three clinically significant hemorrhagic events and four vitamin K antidote treatments over a period of less than two weeks. Genetic analysis later revealed that she had the homozygous variant genotypes of CYP2C9∗3∗3 and VKORC1-1639 AA. Warfarin dosing was subsequently restarted and stabilized at 0.5 mg PO daily with therapeutic INRs. This is the first case report of a white female with these genotypes stabilized on warfarin, and it highlights the value of pharmacogenetic testing prior to the initiation of warfarin therapy to maximize efficacy and minimize the risk of adverse drug events.

Prospective trial of a novel nomogram to achieve updated vancomycin trough concentrations.

Purpose. To determine if the use of a novel vancomycin nomogram predicts dosing regimens that achieve target trough concentrations equal to or more accurate than dosing regimens calculated using traditional pharmacokinetic calculations, evaluate the incidence of subtherapeutic and supratherapeutic troughs, and assess pharmacist's impressions of the nomogram. Methods. Prospective, open-label study in 473 patients who had a new order for vancomycin and were >18 years of age and ≤120 kg. Patients were randomized to the active group, dosed using the nomogram, or to the control group, dosed using traditional pharmacokinetic calculations already in place at our institution. Results. Patients dosed via nomogram were within the appropriate trough range in 44% of cases compared to 33% in the control group (P = 0.014). Vancomycin troughs less than 10 mcg/mL were significantly decreased with the use of nomogram (P = 0.032). Incidence of supratherapeutic troughs, greater than 20 mcg/mL, was not significantly different between groups (P = 0.706), and pharmacists agreed that the nomogram was easy to use and saved their time. Conclusions. A novel vancomycin nomogram was prospectively validated and found to be more effective than traditional pharmacokinetic dosing. The nomogram is being implemented as the standard dosing protocol at our institution.

First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele.

BACKGROUND: Warfarin is the most frequently prescribed anticoagulant in North America and Europe. It is administered as a racemate, but S-warfarin is principally responsible for its anticoagulant activity. Cytochrome P450 (CYP) 2C9 is the enzyme primarily responsible for the metabolism of S-warfarin. Numerous variant alleles of CYP2C9 have been identified. The CYP2C9*12 (rs9332239) allele harbors a P489S substitution in CYP2C9 which has been shown to result in a 40% decline in catalytic activity in vitro. CASES: Four Caucasian patients with a low mean weekly warfarin dose (MWWD) were genotyped for CYP2C9, VKORC1 and APOE variant alleles. None of the four patients carried the common CYP2C9 variant alleles (*2, *3, *5, *6, *7, *8, *9, *11, *13) despite a relatively low MWWD (23.4±7.94 mg) compared to 208 patients carrying the CYP29C9*1 genotype (32.2±12.65 mg). Given that CYP2C9*12 confers decreased in vitro activity to the enzyme, we investigated whether these patients carried this allele. All four patients were CYP2C9*12 CT heterozygotes. Individual comparisons with patients possessing the same VKORC1 and APOE genotypes also demonstrated lower dose requirements in the patients that possessed CYP2C9*12 allele. CONCLUSIONS: There are no reports of the clinical impact of rs9332239 on CYP2C9 substrates. This is the first report of patients with the rare CYP2C9*12 genotype and lower warfarin dose requirements.

Evaluation of genetic variations in organic cationic transporter 3 in depressed and nondepressed subjects.

Organic cationic transporter 3 (OCT3, SLS22A3) has only recently emerged as one of the regulators of monoaminergic neurotransmission, which plays a critical role in the pathogenesis of depression and is a potential new antidepressant drug target. OCT3 single-nucleotide polymorphisms (SNPs) have been investigated for their association with psychiatric disorders such as methamphetamine use disorder and obsessive-compulsive disorder in children and adolescents, but not depression. This study was designed to evaluate the allele frequencies of seven OCT3 SNPs in a US Caucasian depressed population and compare these frequencies with a control group of nondepressed subjects. Informed consent and a DNA sample were obtained from 157 subjects and analysis was performed using real-time PCR. Allele and genotype frequencies were compared using a t-test and the Pearson chi-square analysis, respectively. There were no significant differences in OCT3 allele or genotype frequencies between the depressed and non-depressed groups for all seven SNPs evaluated.

Comparison of the frequency of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in depressed versus nondepressed patients.

Numerous studies have found an association between low serum folate levels and incidence of depression. Folic acid supplementation has been successfully used as an adjunct to treat depression in these patients. However, some individuals have a genetic deficiency in the methylene tetrahydrofolate reductase (MTHFR) gene that limits conversion of folic acid to its biologically active form, L-methylfolate. Several studies have identified a higher frequency of genetic variations in the MTHFR gene in depressed patients than in nondepressed controls. This study evaluated the frequency of the most common genetic variation MTHFR C667T in a group of depressed U.S. Caucasians and compared results with those of a control group of nondepressed U.S. Caucasians. Subjects were recruited from a psychiatric practice, an ambulatory care clinic, and the community. Informed consent and a cheek swab sample were obtained from each subject for analysis using real-time polymerase chain reaction (PCR). Allele and genotype frequencies were compared using Pearson X2 analysis. Complete data were obtained for 156 subjects. No significant differences were found in frequency of the MTHFR C667T T allele (0.415 vs 0.365; p=0.408) or the MTHFR C667T TT genotype (20.7% vs 17.6%; p=0.619) between the depressed and non-depressed controls, respectively. Therefore, use of L-methylfolate without an additional indication of need does not appear to be warranted in this group of U.S. Caucasians. Some patients may benefit from L-methylfolate, but an evidence-based approach, such as MTHFR genotyping, should be used to identify these specific patients. Additional research is also needed to confirm the benefit of L-methylfolate in specific patient populations (e.g., MTHFR TT genotype).

Student pharmacists' use and perceived impact of educational technologies.

OBJECTIVE: To assess the frequency of use by and perceived impact of various educational technologies on student pharmacists. METHODS: Data were obtained using a validated, Web-based survey instrument designed to evaluate the frequency of use and impact on learning of various technologies used in educating first-, second-, and third-year student pharmacists. Basic demographic data also were collected and analyzed. RESULTS: The majority (89.4%) of the 179 respondents were comfortable with the technology used in the academic program. The most frequently used technologies for educational purposes were in class electronic presentations, course materials posted on the school Web site, and e-mail. The technologies cited as having the most beneficial impact on learning were course materials posted on the Web site and in-class electronic presentations, and those cited as most detrimental were video-teleconferencing and online testing. Compared to the course textbook, students reported more frequent use of technologies such as electronic course materials, presentations, digital lecture recordings, e-mail, and hand-held devices. CONCLUSIONS: Because students' opinions of educational technologies varied, colleges and schools should incorporate educational technologies that students frequently use and that positively impact learning.

The foot and ankle of Australopithecus sediba.

A well-preserved and articulated partial foot and ankle of Australopithecus sediba, including an associated complete adult distal tibia, talus, and calcaneus, have been discovered at the Malapa site, South Africa, and reported in direct association with the female paratype Malapa Hominin 2. These fossils reveal a mosaic of primitive and derived features that are distinct from those seen in other hominins. The ankle (talocrural) joint is mostly humanlike in form and inferred function, and there is some evidence for a humanlike arch and Achilles tendon. However, Au. sediba is apelike in possessing a more gracile calcaneal body and a more robust medial malleolus than expected. These observations suggest, if present models of foot function are correct, that Au. sediba may have practiced a unique form of bipedalism and some degree of arboreality. Given the combination of features in the Au. sediba foot, as well as comparisons between Au. sediba and older hominins, homoplasy is implied in the acquisition of bipedal adaptations in the hominin foot.

Comparison of students' performance in and satisfaction with a clinical pharmacokinetics course delivered live and by interactive videoconferencing.

OBJECTIVES: To compare students' performance in and course evaluations for a clinical pharmacokinetics course taught in a traditional classroom setting, and for the same course taught via interactive videoconferencing. METHODS: The course was taught in a traditional classroom setting to 38 students, and in asynchronous sessions via interactive videoconferencing to 75 students at a distant site. A course evaluation was administered to each group at the conclusion of the courses. RESULTS: The students in the live classroom setting had a higher mean final course grade of 90.7% compared to the mean final course grade (87.8%) of students in the interactive videoconferencing group (P = 0.024). The mean evaluation score for students in the videoconferencing class were higher than for students in the live classroom setting (4.73 vs. 4.58; P < 0.001). CONCLUSIONS: Students in both the classroom setting and interactive videoconferencing setting performed well and had a high overall perception of the course.