A Randomized Controlled Trial on the Effect of Standardized Video Education on Prenatal Genetic Testing Choices: Uptake of Genetic Testing.

OBJECTIVE: This study aimed to assess the use of a standardized prenatal genetic testing educational video and its effects on patient uptake of prenatal testing, patient knowledge, decisional conflict, and decisional regret. STUDY DESIGN: This was an Institutional Review Board-approved randomized controlled trial. Patients were randomized to intervention (standardized video education) or control (no video education). The video education group viewed a 5-minute educational video on genetic testing options, and the control group did not review the video. Both groups answered validated questionnaires to assess maternal knowledge (Maternal Serum Screening Knowledge Questionnaire [MSSK]), conflict (Decisional Conflict Scale [DCS]), and regret (Decisional Regret Scale [DRS]). The primary outcome was genetic testing uptake; secondary outcomes were knowledge-based test score, and level of decisional conflict and regret. RESULTS: We enrolled 210 patients between 2016 and 2020, with 208 patients randomized, 103 patients in the video education group and 105 patients in the control group. Four patients were excluded from the video education group for missing data. Video education was associated with a 39% lower chance of prenatal testing compared with patients who did not receive video education, (odds ratio 0.39, 95% confidence interval 0.16-0.92). Patients in the video education group had higher mean MSSKQ scores by 2.9 points (8.5 vs. 5.7, p < 0.001), lower Decisional Conflict Scores by 7.3 points (31.5 vs. 38.8, p < 0.001), lower Decisional Regret Scores by 5.4 points (23.8 vs. 29.2, p < 0.001). CONCLUSION: We found that video education on prenatal genetic testing improved patients' knowledge, decreased testing and decisional conflict and regret regarding testing. This may indicate improved understanding of testing options and more informed decisions that align with their personal values and beliefs. This standardized video can be easily implemented in clinical practice to increase patient understanding and support decisions that align with patient's values. KEY POINTS: · A standardized educational video improves patient knowledge about prenatal testing options in pregnancy.. · Video education decreases testing and decisional conflict and decisional regret in pregnancy.. · A standardized educational video may be used in the clinical setting to educate patients on testing options and help them make informed decisions about testing..

Bedside method to estimate actual body weight in the Emergency Department.

BACKGROUND: Actual body weight (ABW) is important for accurate drug dosing in emergency settings. Oftentimes, patients are unable to stand to be weighed accurately or clearly state their most recent weight. OBJECTIVE: Develop a bedside method to estimate ABW using simple anthropometric measurements. METHODS: Prospective, blinded, cross-sectional convenience sampling of adult Emergency Department (ED) patients. A multiple linear regression equation from Derivation Phase (n = 208: 121 males, 87 females) found abdominal and thigh circumferences (AC and TC) had the best fit and an inter-rater correlation of 0.99 and 0.96, respectively: Male ABW (kg) = -47.8 + 0.78 ∗ (AC) + 1.06 ∗ (TC); Female ABW = -40.2 + 0.47 ∗ (AC) + 1.30 ∗ (TC). RESULTS: Derivation phase: Number of patients (%) with a body weight estimation (BWE) > 10 kg from ABW for males/females were: 7 (6%)/1 (1%) for Patients, 46 (38%)/28 (32%) for Doctors, 38 (31%)/24 (27%) for Nurses, 75 (62%)/43 (49%) for 70 kg/60 kg convention, and 14 (12%)/8 (9%) using the anthropometric regression model. For validation phase (55 males, 44 females): Gold standard ABW mean (SD) male/female = 83.6 kg (14.3)/71.5 kg (18.9) vs. anthropometric regression model = 86.3 kg (14.7)/73.3 kg (15.1). R(2) = 0.89, p < 0.001. The number (%) for males/females with a BWE > 10 kg using the anthropometric regression model = 8 (15%)/11 (27%). CONCLUSIONS: For male patients, a regression model using supine thigh and abdominal circumference measurements seems to provide a useful and more accurate alternative to physician, nurse, or standard 70-kg male conventional estimates, but was less accurate for use in female patients.

Bedside estimation of patient height for calculating ideal body weight in the emergency department.

BACKGROUND: Ideal body weight (IBW), which can be calculated using the variables of true height and sex, is important for drug dosing and ventilator settings. True height often cannot be measured in the emergency department (ED). OBJECTIVES: Determine the most accurate method to estimate IBW using true height-based IBW that uses true height estimated by providers or patients compared to true height estimated by a regression formula using measured tibial length, and compare all to the conventional 70 kg male/60 kg female standard IBW. METHODS: Prospective, observational, double-blind, convenience sampling of stable adult patients in a tertiary care ED from September 2004 to April 2006. Derivation set (215 patients) had blinded provider and patient true height estimates and tibial length measurements compared to gold-standard standing true height. A validation set (102 patients) then compared the accuracy of IBW using true height calculated from the regression formula vs. IBW using gold-standard true height. Regression formula for men tibial length-IBW (kg) = 25.83 + 1.11 × tibial length; for women tibial length-IBW = 7.90 + 1.20 × tibial length; R(2) = 0.89, p < 0.001. Inter-rater correlation of tibial length was 0.94. RESULTS: Derivation set: percent within 5 kg of true height-based IBW for men/women = PATIENT: 91.1%:/85.7%; Physician: 66.1%/45.1%; Nurse: 65.7%/ 47.3%; tibial length: 66.1%/63.7%; and 70 kg male/60 kg female standard 46%/75%. Validation set: tibial length-IBW estimates were within 5 kg of true height-ideal body weight in only 56.2% of men and 42.2% of women. CONCLUSIONS: PATIENT-reported height is the best bedside method to estimate true height to calculate ideal body weight. Physician and nurse estimates of true height are substantially less accurate, as is true height obtained from a regression formula that uses measured tibial length. All methods were more accurate than using the conventional 70 kg male/60 kg female IBW standard.

Nucleotide dependent packing differences in helical crystals of the ABC transporter MsbA.

Bacterial ATP binding cassette (ABC) exporters fulfill a wide variety of transmembrane transport roles and are homologous to the human multidrug resistance P-glycoprotein. Recent X-ray structures of the exporters MsbA and Sav1866 have begun to describe the conformational changes that accompany the ABC transport cycle. Here we present cryo-electron microscopy structures of MsbA reconstituted into a lipid bilayer. Using ATPase inhibitors, we captured three nucleotide transition states of the transporter that were subsequently reconstituted into helical arrays. The enzyme-substrate complex (trapped by ADP-aluminum fluoride or AMPPNP) crystallized in a different helical lattice than the enzyme-product complex (trapped by ADP-vanadate). Approximately 20A resolution maps were calculated for each state and revealed MsbA to be a dimer with a large channel between the membrane spanning domains, similar to the outward facing crystal structures of MsbA and Sav1866. This suggests that while there are likely structural differences between the nucleotide transition states, membrane embedded MsbA remains in an outward facing conformation while nucleotide is bound.

Fragment-based identification of determinants of conformational and spectroscopic change at the ricin active site.

BACKGROUND: Ricin is a potent toxin and known bioterrorism threat with no available antidote. The ricin A-chain (RTA) acts enzymatically to cleave a specific adenine base from ribosomal RNA, thereby blocking translation. To understand better the relationship between ligand binding and RTA active site conformational change, we used a fragment-based approach to find a minimal set of bonding interactions able to induce rearrangements in critical side-chain positions. RESULTS: We found that the smallest ligand stabilizing an open conformer of the RTA active site pocket was an amide group, bound weakly by only a few hydrogen bonds to the protein. Complexes with small amide-containing molecules also revealed a switch in geometry from a parallel towards a splayed arrangement of an arginine-tryptophan cation-pi interaction that was associated with an increase and red-shift in tryptophan fluorescence upon ligand binding. Using the observed fluorescence signal, we determined the thermodynamic changes of adenine binding to the RTA active site, as well as the site-specific binding of urea. Urea binding had a favorable enthalpy change and unfavorable entropy change, with a DeltaH of -13 +/- 2 kJ/mol and a DeltaS of -0.04 +/- 0.01 kJ/(K*mol). The side-chain position of residue Tyr80 in a complex with adenine was found not to involve as large an overlap of rings with the purine as previously considered, suggesting a smaller role for aromatic stacking at the RTA active site. CONCLUSION: We found that amide ligands can bind weakly but specifically to the ricin active site, producing significant shifts in positions of the critical active site residues Arg180 and Tyr80. These results indicate that fragment-based drug discovery methods are capable of identifying minimal bonding determinants of active-site side-chain rearrangements and the mechanistic origins of spectroscopic shifts. Our results suggest that tryptophan fluorescence provides a sensitive probe for the geometric relationship of arginine-tryptophan pairs, which often have significant roles in protein function. Using the unusual characteristics of the RTA system, we measured the still controversial thermodynamic changes of site-specific urea binding to a protein, results that are relevant to understanding the physical mechanisms of protein denaturation.