C.E.R.A. maintains stable hemoglobin in Latin American patients on dialysis

Background

C.E.R.A. is a continuous erythropoietin receptor activator with characteristics that permit a once-monthly schedule of administration for the maintenance treatment for chronic kidney disease (CKD) patients. The main objective of this study was to assess the maintenance of Hb concentration with once-monthly intravenous and/or subcutaneous C.E.R.A. therapy in Latin American dialysis patients with chronic renal anemia previously treated with epoetin alfa s.c or i.v 1–3 times per week.

Methods

This was a single-arm, open-label, multicenter, 32-week study of anemic patients with CKD previously treated with epoetin alfa sc or iv 1–3 times per week. After a 4-week screening period, during which mean Hb levels were maintained between 10.5 and 12.5 g/dL on their previous erythropoiesis stimulating agent, eligible patients entered a 16-week C.E.R.A. dose titration period followed by a 4-week efficacy evaluation period (EEP) and a 28-week safety follow-up. The starting dose of C.E.R.A. was based on the previous dose of epoetin alfa. Doses of C.E.R.A. were then adjusted to maintain Hb levels within ±1.0 g/dL of the reference concentration and between 10.5 and 12.5 g/dL. The Hb reference concentration was defined as the mean of all Hb levels during screening. The primary end point was the proportion of patients maintaining a mean Hb concentration (g/dL) within ±1 g/dL of their reference Hb and between 10.5 and 12.5 g/dL during the EEP.

Results

A total of 163 patients from 27 centers in Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, Uruguay, and Venezuela entered the treatment period and 102 completed the prescribed course of C.E.R.A. Forty-five patients (43.7 %) maintained a mean Hb concentration within ±1 g/dL of their reference Hb value and between 10.5 and 12.5 g/dL during the EEP. The median monthly dose remained constant at 120 μg during the titration period and during the EEP. On the average, there were only 2.3 dose changes per patient in 28 weeks of treatment, covering 7 C.E.R.A. scheduled administrations. 53 % of all dose changes were dose decreases, 47 % increases. A total of 10 AEs and 4 SAEs were considered to be related to the study treatment.

Conclusions

Once-monthly C.E.R.A. treatment effectively maintains stable Hb concentrations in patients with chronic renal anemia undergoing dialysis with a good safety and tolerability profile.     

The efficacy of long-term psychodynamic psychotherapy,fluoxetine and their combination in the outpatient treatment of depression

Abstract

Objective: There are few randomized controlled trials examining the efficacy of long-term psychodynamic psychotherapy (LTPP) in depression treatment. LTPP was compared with fluoxetine treatment and their combination; Methods: 272 depressed patients (aged 26–34, 72% with a first episode of depression) were randomized to receive LTPP (one session/week), fluoxetine treatment (20–60 mg/day) or their combination for 24 months. Beck Depression Inventory (BDI) was the outcome measure. The psychotherapy was not manualized and the treatment took place under real-life conditions in an outpatient psychiatric clinic. Results: Intention-to-treat analyses indicated that all the treatments were associated with significant reductions in the BDI scores (mean reduction of 18.88 BDI points). Furthermore, LTPP and combination therapy were more effective in reducing BDI scores than fluoxetine alone (22.08 and 22.04 vs. 12.53 BDI points). Conclusions: LTPP, pharmacological treatment with fluoxetine and their combination are effective in reducing symptoms of patients with moderate depression. LTPP and combined treatment were more effective compared to fluoxetine alone. These findings have implications for patients with depression who may benefit from long-term psychotherapy or combined treatment, or for depressed patients who do not wish to take medications such as fluoxetine.     

Piperazine designer drugs elicit toxicity in the alternative in vivo model Caenorhabditis elegans

Piperazine designer drugs are a group of synthetic drugs of abuse that have appeared on the illicit market since the second half of the 1990s. The most common derivatives are 1-benzylpiperazine (BZP), 1-(4-methoxyphenyl)piperazine (MeOPP) and 1-(3,4-methylenedioxybenzyl)piperazine (MDBP). They can be consumed as capsules, tablets, but also in powder or liquid forms. Generally, although less potent than amphetamines, piperazines have dopaminergic and serotonergic activities. The aim of this work was to evaluate the toxic effects of BZP, MeOPP and MDBP using Caenorhabditis elegans as in vivo model for acute toxicity, development, reproduction and behavior testing. The LC₅₀ for BZP, MeOPP and MDBP were 52.21, 5.72 and 1.22 mm , respectively. All concentrations induced a significant decrease in the body surface of the worms, indicating developmental alterations, and decrease in the brood size. Worms exposed to piperazine designer drugs also presented a decrease in locomotor activity and mechanical sensitivity, suggesting the possible dysfunction of the nervous system. Neuronal damage was confirmed through the decrease in fluorescence of BY200 strains, indicating loss of dopaminergic transporters. In conclusion, we suggest that piperazine designer drugs lead to neuronal damage, which might be the underlying cause of the altered behavior observed in humans.     

Current knowledge on the sensitivity of the <Superscript>68</Superscript>Ga-somatostatin receptor positron emission tomography and the SUV<Subscript>max</Subscript> reference range for management of pancreatic neuroendocrine tumours

Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three ⁶⁸Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these ⁶⁸Ga-sstr-binding peptides in the imaging setting. On ⁶⁸Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUV_max) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and β-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUV_max-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUV_max-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with ⁶⁸Ga-sstr-PET/CT is mandatory in the clinical setting if uptake in the head/uncinate process is observed.     

Labor and birth care by nurse with midwifery skills in Brazil

Background

The participation of nurses and midwives in vaginal birth care is limited in Brazil, and there are no national data regarding their involvement. The goal was to describe the participation of nurses and nurse-midwives in childbirth care in Brazil in the years 2011 and 2012, and to analyze the association between hospitals with nurses and nurse-midwives in labor and birth care and the use of good practices, and their influence in the reduction of unnecessary interventions, including cesarean sections.

Methods

Birth in Brazil is a national, population-based study consisting of 23,894 postpartum women, carried out in the period between February 2011 and October 2012, in 266 healthcare settings. The study included all vaginal births involving physicians or nurses/nurse-midwives. A logistic regression model was used to examine the association between the implementation of good practices and suitable interventions during labor and birth, and whether care was a physician or a nurse/nurse-midwife led care. We developed another model to assess the association between the use of obstetric interventions during labor and birth to the personnel responsible for the care of the patient, comparing hospitals with decisions revolving exclusively around a physician to those that also included nurses/nurse-midwives as responsible for vaginal births.

Results

16.2 % of vaginal births were assisted by a nurse/nurse-midwife. Good practices were significantly more frequent in those births assisted by nurses/nurse-midwives (ad lib. diet, mobility during labor, non-pharmacological means of pain relief, and use of a partograph), while some interventions were less frequently used (anesthesia, lithotomy position, uterine fundal pressure and episiotomy). In maternity wards that included a nurse/nurse-midwife in labour and birth care, the incidence of cesarean section was lower.

Conclusions

The results of this study illustrate the potential benefit of collaborative work between physicians and nurses/nurse-midwives in labor and birth care. The adoption of good practices in managing labor and birth could be the first step toward more effective obstetric and midwifery care in Brazil. It may be easier to introduce new approaches rather than to eliminate old ones, which may explain why the reduction of unnecessary interventions during labor and birth was less pronounced than the adoption of new practices.

     

IN VITRO EVALUATION OF ROOT CANAL PREPARATION USING OSCILLATORY AND ROTARY SYSTEMS IN FLATTENED ROOT CANALS

Objective:

The aim of this study was to evaluate the biomechanical preparation of flattened root canals using the following systems: Endo-Eze AET stainless steel oscillatory instruments (Ultradent) and RaCe rotary NiTi instruments (FKG Dentaire).

Materials and Methods:

Twenty extracted human mandibular incisors were randomly assigned to two groups: Group 1 - Instrumentation with oscillatory Endo-Eze AET files (oscillatory technique); Group 2 - Instrumentation with rotary NiTi RaCe files (rotary technique). The teeth were decoronated, had their apices and coronal openingssealed with sticky wax and were embedded in crystal-clear orthophtalic polyester resin. The roots were sectioned transversally with diamond discs at 10 mm (middle third) and 5 mm (apical third) from the apex and the segments were reassembled for instrumentation. The sections were photographed before and after root canal instrumentation and evaluated with respect to whether the original root canal shape was modified by instrumentation. To evaluate the differences in the root canal shape before and after biomechanical preparation, scores were given regarding the instruments touch on the intracanal walls.

Results:

In middle third of the root canals instrumented with the rotary system, there was a change in the original canal anatomy (p<0.05), with formation of a protuberance in the mesiodistal direction. This protuberance did not occur when the oscillatory instrumentation was used. The oscillatory system had better results in the middle and apical thirds as evaluated by Dunn’s multiple-comparison test (p>0.05).

Conclusion:

Under the tested conditions, Endo-Eze oscillatory system yielded the instrumentation of all flattened root canal walls, maintaining the canal original shape throughout the biomechanical preparation, and was more effective than RaCe rotary system.