The reciprocal relationship between sexual victimization and sexual assertiveness

Low sexual assertiveness has been proposed as a possible mechanism through which sexual revictimization occurs, yet evidence for this has been mixed. In this study, prospective path analysis was used to examine the relationship between sexual refusal assertiveness and sexual victimization over time among a community sample of women. Results provide support for a reciprocal relationship, with historical victimization predicting low sexual assertiveness and low sexual assertiveness predicting subsequent victimization. The effect of recent sexual victimization on subsequent sexual assertiveness also was replicated prospectively. These findings suggest that strengthening sexual assertiveness may help reduce vulnerability to future victimization.     

Research on severe maternal morbidities and near-misses in Brazil: what we have learned

The occurrence of complications during pregnancy depends less on the degree of human development than differences in the way complications in pregnancy are detected and managed. It is the quick diagnosis and correct management that really contribute to the enormous differences in maternal mortality ratios between countries and regions. Understanding of the determinants of maternal mortality may be improved by studying cases of severe maternal morbidity. In this paper, various approaches to the concept of severe maternal morbidity and near-misses are discussed, and the relationship between these and maternal deaths. Although no consensus has been reached on a strict definition of near-miss or severe maternal morbidity, we show that the definitions used may be tailored to support diverse objectives, including monitoring progress, epidemiological surveillance and auditing of health care. We conclude that the versatility of the concept, the greater frequency of cases available for study and the possibility of interviewing the survivors of severe complications all support the value of studying severe maternal morbidity to help guide local efforts to reduce maternal mortality. Although this may almost be a reality in developed countries, it continues to represent an important and difficult challenge to overcome in places where its benefits would be most evident.     

Tocolysis and delayed delivery versus emergency delivery in cases of non-reassuring fetal status during labor

AIM: To determine whether fetal intrauterine resuscitation using tocolysis and delayed delivery is better for the fetus than emergency delivery when fetal hypoxia is suspected because of a non-reassuring fetal heart-rate (FHR) pattern using conventional heart rate monitoring. METHODS: This was a prospective and randomized study, conducted between 2001 and 2004 at Pereira Rossell Hospital, Montevideo, Uruguay. The population consisted of 390 fetuses, in which intrauterine distress was diagnosed using electronic FHR monitoring. Of these, 197 were randomly assigned to the emergency delivery group and 193 to the fetal intrauterine resuscitation group. The inclusion criteria were: term singleton pregnancy, in labor, cephalic presentation, and no placental accidents. RESULTS: The time between randomization and birth was 16.9 +/- 7.6 min (mean +/- SD) for the emergency delivery group, and 34.5 +/- 11.7 min (mean +/- SD) for the resuscitation group. The relative risk (RR) of acidosis in the umbilical artery (pH < 7.1) in the emergency delivery group was 1.47 (0.95-2.27). The RR of base deficit < or =12 mEq/L in the emergency delivery group was higher than in the resuscitation group (RR = 1.48 [1.0-2.2], P = 0.04). When considering the need for admission to the neonatal care unit, the relative risk was higher in the emergency delivery group than in the resuscitation group (RR = 2.14 [1.23.3.74], P = 0.005). No maternal adverse effects were reported. CONCLUSION: Tocolysis and delayed delivery renders better immediate neonatal results than emergency delivery when fetal distress is suspected because of a non-reassuring fetal heart pattern. In addition, it may decrease the need for emergency delivery without increasing maternal and fetal adverse side-effects.     

Iatrogenic ureteral lesions and repair: a review for gynecologists

Ureter injuries are a well-known complication of gynecologic surgery and a frequent cause of medicolegal problems. Because there are no randomized, controlled trials and the available studies are small series and case reports, the evidence on which to base treatment is weak. We therefore reviewed the complete English-language literature of ureter repair since 1990. In total, 608 ureter injuries were reported. Although it is widely believed that for laceration or section the prognosis is affected by a delay in diagnosis, we could not find evidence to substantiate this. An obstruction requires stenting only. For a laceration, stenting with suturing was more effective than stenting only (p = .006). A ureter anastomosis was successful in over 94% of cases either by laparotomy or laparoscopy. In conclusion, the literature data are scanty and heterogeneous and do not permit solid conclusions. Evidence, however, is emerging that a laceration should be treated by stenting and suturing. A ureter anastomosis over a stent could become a valid option especially when performed by laparoscopy.     

Efficacy of barriers and hypoxia-inducible factor inhibitors to prevent CO(2) pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model

STUDY OBJECTIVE: To investigate the effects of hypoxia-inducible factor (HIF) inhibitors, flotation agents, barriers, and a surfactant on pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model. DESIGN: Prospective randomized trial (Canadian Task Force classification I). SETTING: Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Catholic University of Leuven. SUBJECTS: One hundred fourteen female BALB/c mice. INTERVENTIONS: Adhesions were induced during laparoscopy in BALB/c female mice. Pneumoperitoneum was maintained for 60 minutes with humidified CO(2). In 3 experiments the effects of HIF inhibitors such as 17-allylamino 17-demethoxygeldanamycin, radicicol, rapamycin, and wortmanin, flotation agents such as Hyskon and carboxymethylcellulose, barriers such as Hyalobarrier gel and SprayGel, and surfactant such as phospholipids were evaluated. MEASUREMENTS AND MAIN RESULTS: Adhesions were scored after 7 days during laparotomy. Adhesion formation decreased with the administration of wortmannin (p <.01), phospholipids (p <.01), Hyalobarrier Gel (p <.01), and SprayGel (p <.01). CONCLUSIONS: These experiments confirm the efficacy of barriers and phospholipids to separate or lubricate damaged surfaces. They also confirm the role of mesothelial hypoxia in this model by the efficacy of the HIF inhibitor wortmannin.     

BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car...     

Estimation of brain receptor occupancy for trazodone immediate release and once a day formulations

Trazodone is approved for the treatment of major depressive disorders, marketed as immediate release (IR), prolonged release, and once a day (OAD) formulation. The different formulations allow different administration schedules and may be useful to facilitate patients’ compliance to the antidepressant treatment. A previously verified physiologically‐based pharmacokinetic model based on in vitro and in vivo information on trazodone pharmacokinetics was applied, aiming at predicting brain receptor occupancy (RO) after single and repeated dosing of the IR formulation and repeated dosing of the OAD formulation in healthy subjects. Receptors included in the simulations were selected using static calculations of RO based on the maximum unbound brain concentration (C_max,brain,u) of trazodone for each formulation and dosing scheme, resulting in 16 receptors being simulated. Seven receptors were simulated for the IR low dose formulation (30 mg), with similar t _onset and duration of coverage (range: 0.09–0.25 h and 2.1–>24 h, respectively) as well as RO (range: 0.64–0.92) predicted between day 1 and day 7 of dosing. The 16 receptors evaluated for the OAD formulation (300 mg) showed high RO (range: 0.97–0.84 for the receptors also covered by the IR formulation and 0.73–0.48 for the remaining) correlating with affinity and similar duration of time above the target threshold to the IR formulation (range: 2–>24 h). The dose‐dependent receptor coverage supports the multimodal activity of trazodone, which may further contribute to its fast antidepressant action and effectiveness in controlling different symptoms in depressed patients.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

The antidepressant efficacy of trazodone has been shown to be significantly correlated to its steady‐state plasma levels, and previous work has shown some understanding of trazodone range of affinity for different receptors, at different doses, but without considering the different available formulations. Trazodone is commonly available as: immediate release (IR), prolonged release (PR), and once a day (OAD) tablets. The IR formulation has a rapid onset and short duration of action, whereas the PR formulation is characterized by an absorption boost as soon as it is administered and has a comparatively delayed maximum concentration (C_max). Conversely, the OAD formulation provides a controlled release of trazodone over 24 h without the early high peak plasma concentration seen with the IR and PR formulations.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This work aims to identify the brain receptors reaching a threshold occupancy of 50% through static predictions and determine the occupancy versus time profile for those of interest following administration of short‐ and long‐acting trazodone formulations.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Brain receptor occupancy (RO) for key targets were predicted based on free drug concentrations, allowing for a physiologically relevant assessment of the different pathways affected by each formulation and dose.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The presented physiologically‐based pharmacokinetic approach to assess RO can be used to guide formulation selection and dosing in clinical studies.