Victims of sexual offences: aspects impacting on participation, cooperation and engagement with the interview process.

The way in which police officers interview sexual offence victims is pivotal to how their cases proceed through the criminal justice system (CJS). However, such interviews have previously been found to be lacking in overall quality, with some interviewers finding them technically difficult and stressful to conduct. In addition, victims often feel disbelieved, unsafe and/or uncomfortable during their police interview. The present study provides insight into the personal experiences of five female adult rape/sexual assault victims regarding their police interviews and the aspects that encouraged them to cooperate and engage during the interview process. Following semi-structured interviews, interpretative phenomenological analysis (IPA) was used to identify three key themes: (i) heading into the unknown, (ii) difficulty of talking about the crime and (iii) helpful and unhelpful interviewer approaches. Implications for practice are discussed, together with the need to further our understanding of this specialist area of police work.

The Effect of Dofetilide on the Heart Rate of GD11 and GD13 Rat Embryos, in vivo, Using Ultrasound.

BACKGROUND: There are a wide range of drugs including antidepressants, anticonvulsants and antipsychotics that cause embryonic bradycardia in vitro but it is unknown if they have a similar effect in vivo. One way to verify whether these in vitro findings are replicated in vivo is by the use of ultrasound examination of dosed pregnant rats. We tested this by examining the effect of dofetilide on embryonic heart rate (HR) in vivo using ultrasound. METHODS: Rats were dosed with dofetilide (4 or 2.5 mg/kg) on GD11 or (5 or 2.5 mg/kg) on GD13 and embryonic HR assessed by ultrasound, 2 and 24 hr later. Fetuses were examined for malformations on GD20. RESULTS: HR of control rat embryos showed a wide range at each gestational day. Dosing with dofetilide on GD11 caused severe bradycardia (∼ 60% reduction) 2 hours after dosing with recovery after 24 h of >60% of LD but death and slow HR among the HD embryos. At term, 32% of the LD surviving fetuses had hypoplastic upper lip while >90% of HD embryos had died. On GD13, embryonic HR was reduced in a dose-dependent manner with >85% of LD and HD recovered by 24 hr. At term, all LD fetuses were normal while 29% of HD fetuses had limb defects. CONCLUSIONS: Ultrasound is a useful technique to investigate the effect of maternally administered drugs on the embryonic HR in the rat. The results may provide more information about the safety of these drugs in pregnancy leading to better risk assessment for the human.

Effects of macrolide antibiotics on rat embryonic heart function in vitro.

The Swedish Medical Product Agency (MPA) has listed erythromycin as a suggested human teratogen, causing cardiovascular malformations. It is further suggested that this may be a class effect of macrolide antibiotics. The proposed teratogenic mechanism is blockade of the human ether-á-go-go-related (hERG)/IKr current in the embryonic heart causing bradycardia and arrhythmia resulting in altered cardiac blood flow and/or embryonic hypoxia. To test this hypothesis, we examined the effect of three macrolide antibiotics on the function of the rat embryonic heart. Gestational day 13 rat embryos in vitro were exposed to erythromycin (25-500 µM), clarithromycin (25-500 µM), or azithromycin (100 µM to 1 mM) for 3 hr. The effect on the embryonic heart was monitored every hour. The results showed that erythromycin and clarithromycin caused a concentration-dependent bradycardia. Twenty-five micromolar was a no-effect concentration for erythromycin and was close to a no-effect concentration for clarithromycin. Azithromycin only caused significant bradycardia at 1 mM. Additional studies were performed with the embryos cultured at 40°C instead of 38°C, to mimic fever. The increased temperature increased the number of arrhythmias but did not worsen the drug-induced bradycardia. The results support the concept that erythromycin and clarithromycin can adversely affect the embryonic heart but only at concentrations well outside expected embryonic exposure in the human.

Evaluation of the diagnostic utility of metagenomic next-generation sequencing testing for pathogen identification in infected hosts: a retrospective cohort study.

Background: Metagenomic next-generation sequencing (mNGS) testing identifies thousands of potential pathogens in a single blood test, though data on its real-world diagnostic utility are lacking. Objectives: Determine the diagnostic utility of mNGS testing in practice and factors associated with high clinical utility. Design: Retrospective cohort study of mNGS tests ordered from June 2018 through May 2020 at a community teaching hospital. Methods: Tests were included if ordered for diagnostic purposes in patients with probable or high clinical suspicion of infection. Exclusions included patient expiration, hospice care, or transfer outside of the institution. Utility criteria were established a priori by the research team. Two investigators independently reviewed each test and categorized it to either high or low diagnostic utility. Reviewer discordance was referred to a third investigator. The stepwise multiple regression method was used to identify clinical factors associated with high diagnostic utility. Results: Among 96 individual tests from 82 unique patients, 80 tests met the inclusion criteria for analysis. At least one potential pathogen was identified in 58% of tests. Among 112 pathogens identified, there were 74 bacteria, 25 viruses, 12 fungi, and 1 protozoon. In all, 46 tests (57.5%) were determined to be of high diagnostic utility. Positive mNGS tests were identified in 36 (78.3%) and 11 (32.4%) of high and low diagnostic utility tests, respectively (p < 0.001). Antimicrobials were changed after receiving test results in 31 (67.4%) of high utility tests and 4 (11.8%) of low utility tests (p < 0.0001). In the multiple regression model, a positive test [odds ratio (OR) = 10.9; 95% confidence interval (CI), 3.2-44.4] and consultation with the company medical director (OR = 3.6; 95% CI, 1.1-13.7) remained significantly associated with high diagnostic utility. Conclusion: mNGS testing resulted in high clinical utility in most cases. Positive mNGS tests were associated with high diagnostic utility. Consultation with the Karius® medical director is recommended to maximize utility.

Evaluating the real world utility of using a diagnostic test that uses cell-free DNA to identify bacteria, viruses, fungi and protozoa from blood in hospitalized adult and pediatric patients Our institution has utilized a meta-genomic test that identifies bacteria, DNA-based viruses, fungi and protozoa from blood sample in hospitalized patients to support diagnostics in select clinical cases. We evaluated the utility of these tests in an adult and pediatric population. We found that 58% of the 96 tests from 82 unique patients produced a pathogen. Overall, a majority (58%) of tests were deemed to be of high utility which directly resulted in changes in antimicrobial therapy, selection of duration of therapy, direction for new diagnostics, or avoidance of further need for diagnostics. Positive tests and consultation with the medical director of the laboratory were both associated with high utility of the tests.

Comparative effects of sodium channel blockers in short term rat whole embryo culture.

This study was undertaken to examine the effect on the rat embryonic heart of two experimental drugs (AZA and AZB) which are known to block the sodium channel Nav1.5, the hERG potassium channel and the l-type calcium channel. The sodium channel blockers bupivacaine, lidocaine, and the l-type calcium channel blocker nifedipine were used as reference substances. The experimental model was the gestational day (GD) 13 rat embryo cultured in vitro. In this model the embryonic heart activity can be directly observed, recorded and analyzed using computer assisted image analysis as it responds to the addition of test drugs. The effect on the heart was studied for a range of concentrations and for a duration up to 3h. The results showed that AZA and AZB caused a concentration-dependent bradycardia of the embryonic heart and at high concentrations heart block. These effects were reversible on washout. In terms of potency to cause bradycardia the compounds were ranked AZB>bupivacaine>AZA>lidocaine>nifedipine. Comparison with results from previous studies with more specific ion channel blockers suggests that the primary effect of AZA and AZB was sodium channel blockage. The study shows that the short-term rat whole embryo culture (WEC) is a suitable system to detect substances hazardous to the embryonic heart.

Efficacy and safety evaluation of a large niacin therapeutic interchange program.

BACKGROUND: An extended-release niacin product (Niaspan, Abbott Laboratories) was identified as a product with a less costly therapeutic alternative; a therapeutic product interchange was implemented. OBJECTIVE: To evaluate the efficacy and safety of a product therapeutic interchange from Niaspan to a controlled-release niacin product (Slo-Niacin, Upsher-Smith Laboratories) among patients at a large US Department of Veterans Affairs health care facility. METHODS: Patients with active prescriptions for Niaspan underwent a therapeutic product interchange to Slo-Niacin; following conversion of the product, the medical record for each patient was reviewed and pre- and postconversion clinical information and conversion details were transcribed into a database for subsequent analysis and study. The primary efficacy end point was pre- and postconversion level of low-density lipoprotein cholesterol; secondary efficacy end points were levels of serum total cholesterol, high-density lipoprotein cholesterol, and triglycerides. Abnormal serum liver enzyme levels greater than 3 times the upper limits of normal was the primary safety end point; blood hemoglobin A1c was assessed as a secondary safety end point. RESULTS: A total of 5321 patients' medical records were reviewed; for the efficacy evaluation, 539 patients were maintained on a daily dose of Slo-Niacin that was the same as the previous Niaspan dose. The dosage of any other concurrently prescribed dyslipidemia medication was unchanged. Analysis of these cases indicated that the conversion of Niaspan to Slo-Niacin was not associated with a difference in serum lipids over a mean (SD) of 503.9 (98.0) postconversion observation days with the exception of a decrease in mean serum triglyceride concentration of 19.8 mg/dL (p = 0.0003). Evaluation of all 5321 patients given Slo-Niacin for up to 724 days did not detect any safety differences between Slo-Niacin and Niaspan. Local facility cost avoidance exceeded $800,000 in the first postconversion year. CONCLUSIONS: Data from a medication use evaluation of modified-release niacin products therapeutic interchange in a large US Department of Veterans Affairs health care facility show that the switch from Niaspan to Slo-Niacin had no negative effects on lipid-altering efficacy or safety but generated significant cost avoidance.

The effect on rat embryonic heart rate of Na+, K+, and Ca2+ channel blockers, and the human teratogen phenytoin, changes with gestational age.

In this study, we compared the effects of four ion channel blockers on rat embryonic heart function during the organogenic period from gestational day (GD) 10 to 15, to determine the changes in dependence on ion channels during rat cardiac development. Rat embryos in culture were exposed to either the human ether-á-go-go-related gene potassium channel blocker, dofetilide (400 nM); the sodium channel blocker, lidocaine (250 µM); the L-type calcium channel blocker, nifedipine (1.8 µM); or the multichannel blocker, phenytoin (200 µM). Lidocaine slowed the heart rate (HR) with the effect becoming more severe with increasing GD. Dofetilide slowed the embryonic HR and caused arrhythmias with the most severe effect on GD 11 to 13. Nifedipine primarily caused a negative inotropic effect except on GD 10 when it stopped the heart in most embryos. Phenytoin stopped the heart of most GD 10 to 12 embryos while on GD 13 to 15 phenytoin slowed the heart. The results demonstrate that as the rat heart develops during the organogenic period its functional dependence on ion channels changes markedly. These changes are important for understanding drug effects on the embryo during pregnancy and the methodology used provides a simple procedure for assessing drug effects on the developing heart.

The teratogenic effect of dofetilide during rat limb development and association with drug-induced bradycardia and hypoxia in the embryo.

BACKGROUND: Dofetilide is an antiarrhythmic drug that blocks the cardiac repolarizing current IKr ((IKr, rapid component of the delayed rectifying potassium current). Previous studies have shown that (a) IKr is essential for normal cardiac function of the embryonic heart and (b) dofetilide is teratogenic in rodents. This study was undertaken to examine the mechanism by which dofetilide causes limb defects on gestational day 13 (GD 13) in the rat. METHODS: Rats were treated with dofetilide (single oral dose, 5 mg/kg) on GD 13 and embryonic heart rates assessed by ultrasound (Vevo770, VisualSonics, Toronto, Ontario, Canada) 2 hr later. Fetuses were examined for malformations on GD 20. In a separate experiment, dofetilide treatment of GD 13 rats was followed 2, 4, 12, or 24 hr with iv dosing with the hypoxia marker, pimonidazole (60 mg/kg). Embryos were collected and heart rates were assessed in vitro and hypoxia in embryo limbs analyzed. RESULTS: A teratogenic dose of dofetilide at a susceptible stage of development (GD 13) resulted in a period of bradycardia and arrhythmia of the embryonic heart and hypoxia in the developing limbs (GD 13) resulting in limb malformations (GD 20). CONCLUSIONS: Drugs that induce periods of bradycardia and/or arrhythmia of the embryonic heart and cause the embryo to become hypoxic are potential human teratogens.

Cultivating grassroots IPE: the Dalhousie University experience.

A bottom-up and menu-based approach to embedding interprofessional education (IPE) into the curricula of more than 20 health profession programs at Dalhousie University is described. In addition to adopting an IPE graduation requirement and a common time for IPE activities, progress appears to have been facilitated by placing responsibility directly with the schools that own the curricula rather than with a central office for IPE.

Effect of vinpocetine on embryonic heart rate in vitro.

Vinpocetine is a readily available nutritional supplement claimed to improve memory and weight loss. However, it blocks the Ikr current essential for cardiac action potential repolarisation and Ikr inhibition can cause "torsade de pointes" arrhythmias and sudden death. Moreover, Ikr blockers have exhibited teratogenic effects in reproductive toxicology studies, leading to increased birth defects and embryonic mortality. The FDA advises against vinpocetine use in pregnant and prospective mothers based on animal studies showing dose-dependent fetal mortality in rats and rabbits, and cardiovascular malformations in surviving fetuses. However, the mechanisms responsible for vinpocetine's fetal toxicity remain unclear. The present study used rat embryo culture to evaluate vinpocetine and its major metabolite, apovincaminic acid, on embryonic heart rate, a possible causative factor behind its adverse effects. Both compounds induced embryonic bradycardia in a concentration-dependent manner, with vinpocetine proving more potent. The minimum vinpocentine concentration to induce bradycardia was 100 nM, a level unlikely to be reached in humans following typical doses. Embryonic arrhythmias were also observed at the highest concentrations. These results suggest that the FDA's cautionary statement may generate undue anxiety, although re-evaluation of teratogenicity risk associated with vinpocetine should be revisited if a link to cardiac arrhythmias in adults is established.

Antidepressants cause bradycardia and heart block in GD 13 rat embryos in vitro.

This study investigated the effects of a range of antidepressant drugs on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the drugs would adversely affect the function of the embryonic heart since they all have some cardiac ion channel blocking activity in addition to their main pharmacological effect on neurotransmitters. The results showed that all the tested drugs caused bradycardia in a generally concentration-dependent manner. At higher concentrations most of the drugs caused some degree of heart block consistent with sodium channel blockade and some drugs also showed negative inotropy associated with blockade of the L-type calcium channel. One drug, trazodone, caused arrhythmia consistent with blockade of the hERG (human ether-a-go-go related gene) potassium channel. In general the effects on the embryonic rat heart were only seen at "free drug" concentrations much greater than those likely to occur in pregnant women taking antidepressant medication. The least margin of safety was seen with the tricyclic antidepressants and the serotonin antagonist and reuptake inhibitor trazodone.

The effect of drugs with ion channel-blocking activity on the early embryonic rat heart.

This study investigated the effects of a range of pharmaceutical drugs with ion channel-blocking activity on the heart of gestation day 13 rat embryos in vitro. The general hypothesis was that the blockade of the I(Kr)/hERG channel, that is highly important for the normal functioning of the embryonic rat heart, would cause bradycardia and arrhythmia. Concomitant blockade of other channels was expected to modify the effects of hERG blockade. Fourteen drugs with varying degrees of specificity and affinity toward potassium, sodium, and calcium channels were tested over a range of concentrations. The rat embryos were maintained for 2 hr in culture, 1 hr to acclimatize, and 1 hr to test the effect of the drug. All the drugs caused a concentration-dependent bradycardia except nifedipine, which primarily caused a negative inotropic effect eventually stopping the heart. A number of drugs induced arrhythmias and these appeared to be related to either sodium channel blockade, which resulted in a double atrial beat for each ventricular beat, or I(Kr)/hERG blockade, which caused irregular atrial and ventricular beats. However, it is difficult to make a precise prediction of the effect of a drug on the embryonic heart just by looking at the polypharmacological action on ion channels. The results indicate that the use of the tested drugs during pregnancy could potentially damage the embryo by causing periods of hypoxia. In general, the effects on the embryonic heart were only seen at concentrations greater than those likely to occur with normal therapeutic dosing.

The effects of nifedipine and ivabradine on the functionality of the early rat embryonic heart. Are these drugs a risk in early human pregnancy?

BACKGROUND: When the human heart begins its earliest contractions from day 21, it lacks a functional autonomic nerve supply. Instead, contractions are generated by regular calcium transients later augmented by the funny current (If ) produced by sinoatrial-like cells. This study examined effects of blocking these currents in the early rat embryonic heart. METHODS: Rat embryos were incubated in vitro with either the calcium channel blocker nifedipine and/or the funny current (If ) blocker ivabradine for 1 hr to examine the effects of these drugs on the activity of the embryonic heart. RESULTS: On gestational day (GD) 10, nifedipine (0.45-1.8 µM) caused asystole at high concentrations (8/10 embryos at 1.8 µM and 3/10 embryos at 0.9 µM) and markedly increased embryonic heart rate (EHR) in all surviving embryos but likely reduced blood flow due to weak contractions. Ivabradine (1.5 µM) caused a 29% reduction in EHR in GD 10 embryos and a greater than 50% reduction in EHR for GD 11-14 embryos. Combined exposure to both nifedipine and ivabradine resulted in an additive effect. The increased EHR due to nifedipine was reduced by the ivabradine. CONCLUSION: The results suggest that exposure to nifedipine in human pregnancy 3-4 weeks postfertilization may cause a direct effect on the embryonic heart resulting in reduced blood flow leading to abnormal heart and/or blood vessel development and/or embryonic death. Accidental exposure to ivabradine in the organogenic period would be expected to cause embryonic bradycardia, hypoxia, malformations, and embryonic death. This drug is currently contraindicated in pregnancy.

The effect of anti-emetic drugs on rat embryonic heart activity.

Nausea and vomiting of pregnancy (NVP) is the most common medical complaint during pregnancy affecting up to 70% of pregnant women worldwide. Some antiemetic medications (AEM) (droperidol, domperidone, granisetron, metoclopramide and trifluoperazine) used to treat NVP have the unwanted side effect of hERG blockade. The hERG potassium channel is essential for normal heart rhythm in both the adult human and the human and rat embryo. Animal studies show hERG blockade in the embryo causes bradycardia and arrhythmia leading to cardiovascular malformations and other birth defects. Whole rat embryo in vitro culture was used to determine the effect of the above listed AEM and meclizine on the heart rate of Gestational day 13 rat embryos. These embryos are similar in size and heart development to 5-6-week human embryo. The results showed that all of the AEMs caused a concentration-dependent bradycardia. Droperidol had the lowest margin of safety.

Acardiac fetus: evidence in support of a vascular/hypoxia pathogenesis for isolated oral clefting.

BACKGROUND: The acardiac human fetus represents an accident of monozygotic twinning or higher multiple births due to an artery-to-artery and a vein-to-vein anastomosis in the monochorial placenta. Blood returning to the placenta through the umbilical artery of a normal cotwin is directed into the umbilical artery of the acardiac twin such that blood reaching the cranial end of the embryo is likely to be poorly oxygenated resulting in a number of structural defects including oral clefts. Although retrograde perfusion as a cause of hypoxia is unique to the acardiac fetus, there is ample evidence from animal studies that hypoxia is associated with facial clefting. METHODS: Twenty-six acardiac fetuses were examined at UCSD Medical Center between 1974 and 2003. RESULTS: In 12 of the 26, the cephalic end of the fetus was sufficiently intact to document the structures of the face. Of these, cleft lip +/- palate was present in five and cleft palate alone was present in one. In all six, the oral cleft followed the normal planes of facial closure. The cotwin in all six cases was normal. CONCLUSIONS: This article suggests that decreased blood flow/hypoxia to the cephalic end of the fetus may be an important contributor to the development of cleft lip +/- palate and cleft palate alone in the acardiac fetus and raises the possibility that this may also be a mechanism responsible for oral clefting in singletons.

Ondansetron and teratogenicity in rats: Evidence for a mechanism mediated via embryonic hERG blockade.

The potent hERG channel blocking drug ondansetron is used off-label for treatment of nausea and vomiting in early pregnancy. Some human epidemiological studies have associated ondansetron with fetal cardiovascular defects and orofacial clefts. This study investigated the effects of ondanestron on embryonic heart rhythm of gestational day (GD) 13 rat embryos in vitro and then integrated the results with published animal teratology, and animal and human pharmacokinetic studies to perform a risk evaluation. Ondansetron caused concentration dependent bradycardia and arrhythmia. Cardiovascular malformations in rats occurred at exposures slightly higher than those in early human pregnancy. Together the results suggest that ondansetron can have teratogenic potential in rats and humans mediated via hERG block and severe heart rhythm disturbances in the embryo. The risk may be increased in human pregnancy if additional risk factors are present such as hypokalemia.

Editor's Highlight: Ethylene Glycol Teratogenicity: A Role for Embryonic Acidosis?

Ethylene glycol (EG) is a developmental toxicant in pregnant rats and mice. A suggested mechanism for this toxicity is that the EG metabolite, glycolic acid (GA), causes acidosis which may affect the embryonic heart rate (HR). This inhibition would cause periods of embryonic bradycardia and arrhythmia resulting in increased embryonic death and malformation in surviving embryos. This hypothesis was investigated using gestational day (GD) 11 and 13 rat embryos in vitro. Increasing concentrations of GA or lactic acid in the incubation medium caused a decrease in external pH (pHe) and a concentration-dependent decrease in embryonic HR. Increased concentrations of GA or lactic acid with pHe corrected to normal levels did not affect HR. Severely decreased pHe, caused by reduced NaHCO3 in the incubation medium, had little effect on the HR of GD 13 embryos but substantially reduced the HR of GD 11 embryos. These results suggest that increased monocarboxylate concentration (glycolate or lactate) needs to be in combination with increased H+ concentration (low pHe) to influence the embryonic HR. These results implicate the monocarboxylate transporter reported to be present in the early postnatal rat heart, the chick embryonic heart throughout development, and the chorioallantoic placenta. The results showed some evidence that the adverse effect of GA and reduced pHe on the embryonic HR increased with duration of exposure and hence lends support to the suggested mechanism of embryotoxicity for EG.

Division mental health in the new brigade combat team structure: part I. Predeployment and deployment.

OBJECTIVE: Recent Army transformation has led to significant changes in roles and demands for division mental health (DMH) staff members. This article focuses on predeployment and deployment. METHODS: Surveillance of Combat and Operational Stress Reactions data, review of DMH implementation plans, and observations by staff members, providers, and soldiers were reviewed. RESULTS: During the course of the deployment, the Task Force Baghdad DMH unit had >22,000 soldier encounters with 5,542 clinical encounters. The duration of the deployment and increased levels of threat later in the deployment resulted in increased stress problems but not a substantial or sustained increase in mental health casualties. CONCLUSIONS: Predeployment education and communication probably eliminated some problems during deployment, and communication among mental health and command units during deployment resolved most problems encountered.

Division mental health in the new brigade combat team structure: part II. Redeployment and postdeployment.

OBJECTIVE: Recent Army transformation has led to significant changes in roles and demands for division mental health staff members. This article focuses on redeployment and postdeployment. METHODS: The postdeployment health assessment behavioral health screening and referral process and redeployment plan are reviewed, and data on postdeployment rates of negative events are reported. RESULTS: All soldiers and many of their families participated in an aggressive education program. Of the 19,500 soldiers screened, 2,170 (11.1%) were referred for behavioral health consultation; of those referred, 219 (10.1%) were found to be at moderate or high risk for mental health issues (1.1% of total screened). Of the moderate/highrisk soldiers, 146 (71.9%) accepted follow-up mental health treatment upon return to home station. Fewer cases of driving under the influence, positive drug screens, suicidal gestures/ attempts, crimes, and acts of domestic violence were seen, in comparison with rates seen after an earlier deployment of this unit to Iraq. CONCLUSIONS: A formalized approach with command support and coordination can have a positive impact on successful referral and treatment and reduce negative postdeployment events.