Intrauterine contraception: the pendulum swings back

Intrauterine contraception is the most widely used method of reversible fertility regulation in the world. Finally, IUC is undergoing a renaissance in the US and it's role will expand as new devices and systems are developed and as old biases among clinicians and women are erased. Successful fertility regulation is a defining factor of the overall health of a population; the expanded use of IUC can help achieve that public health success.     

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.     

The biliopancreatic diversion. A comparison of laparoscopic and laparotomic techniques

AIM: Morbid obesity has increased its frequency in the last 20 years in association with the increase of a country's richness. Bariatric surgery has developed a role which is becoming more and more important. The aim of this study, after 10 years of experience with the biliopancreatic diversion, is to compare the laparoscopic versus open technique RESULTS: METHODS: From March 1993 to December 2004, 150 patients were operated by biliopancreatic diversion. We divided our experience into 2 groups: laparotomic and laparoscopic techniques. We compared the following variables in the 2 groups: total operating time, intestinal functions, postoperative pain, patient's discharge and recovery time, major postoperative complications, postoperative mortality, late complications, incisional hernia incidence and anastomotic ulceration. RESULTS: We found a significant difference in both the reduction of the postoperative pain and the recanalization time in the laparoscopic group. Equally, we found a reduction in the incidence of abdominal wall complications, especially the reduction of incisional hernia and infections. The mean operative time was longer in the laparoscopic group, in particular due to the hard learning curve. CONCLUSIONS: The laparoscopic biliopancreatic diversion is a feasible and safe operation with good results: less postoperative discomfort, shorter recanalization and ospedalization time, less incidence of abdominal wall morbidity (incisional hernia). However, the procedure may prove difficult and it needs a highly experienced surgeon in laparoscopic technique.     

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.     

The Effect of a 2-Year Intervention Consisting of Diet,Physical Exercise,Cognitive Training,and Monitoring of Vascular Risk on Chronic Morbidity—the FINGER Randomized Controlled Trial

Objective

To verify whether a multidomain intervention lowers the risk of developing new chronic diseases in older adults.