Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double-blind, randomised, placebo-controlled trial.

OBJECTIVE: To evaluate whether maintenance treatment with vaginal progesterone after an arrested preterm labour reduces the incidence of preterm delivery. DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING: Twelve tertiary care centres in Spain. POPULATION: A total of 265 women with singleton pregnancy, preterm labour successfully arrested with tocolytic treatment, and cervical length of <25 mm. METHODS: Randomisation was stratified by gestational age (from 24.0 to <31.0 weeks of gestation and from 31.0 to <34.0 weeks of gestation) and centre. Patients were randomly assigned, in a 1 : 1 ratio, to either daily vaginal capsules of 200 mg progesterone or placebo until delivery or 36.6 weeks of gestation, whichever occurred first. MAIN OUTCOME MEASURES: Primary outcome was delivery before 34.0 and 37.0 weeks of gestation. Secondary outcomes were discharge-to-delivery time, readmissions because of preterm labour, emergency service use, and neonatal morbidity and mortality. RESULTS: From June 2008 through June 2012, 1419 women were screened: 472 met the inclusion criteria and 265 were randomised. The final analysis included 258 women: 126 in the progesterone group and 132 in the placebo group. There were no significant differences between the progesterone and placebo groups in terms of delivery at <34 weeks of gestation [9/126 (7.1%) versus 10/132 (7.6%), P = 0.91] or <37 weeks of gestation [36/126 (28.6%) versus 29/132 (22.0%), P = 0.22]. There were no differences observed between groups when considering the two strata of gestational age at inclusion. CONCLUSIONS: A maintenance treatment of 200 mg of daily vaginal progesterone capsules in women discharged home after an episode of arrested preterm labour did not significantly reduce the rate of preterm delivery. TWEETABLE ABSTRACT: Maintenance progesterone in 258 women after arrested PTL showed no benefit.

Important role of microglia in HIV-1 associated neurocognitive disorders and the molecular pathways implicated in its pathogenesis.

The development of effective combined anti-retroviral therapy (cART) led to a significant reduction in the death rate associated with human immunodeficiency virus type 1 (HIV-1) infection. However, recent studies indicate that considerably more than 50% of all HIV-1 infected patients develop HIV-1-associated neurocognitive disorder (HAND). Microglia are the foremost cells infected by HIV-1 in the central nervous system (CNS), and so, are also likely to contribute to the neurotoxicity observed in HAND. The activation of microglia induces the release of pro-inflammatory markers and altered secretion of cytokines, chemokines, secondary messengers, and reactive oxygen species (ROS) which activate signalling pathways that initiate neuroinflammation. In turn, ROS and inflammation also play critical roles in HAND. However, more efforts are required to understand the physiology of microglia and the processes involved in their activation in order to better understand the how HIV-1-infected microglia are involved in the development of HAND. In this review, we summarize the current state of knowledge about the involvement of oxidative stress mechanisms and role of HIV-induced ROS in the development of HAND. We also examine the academic literature regarding crucial HIV-1 pathogenicity factors implicated in neurotoxicity and inflammation in order to identify molecular pathways that could serve as potential therapeutic targets for treatment of this disease. KEY MESSAGES Neuroinflammation and excitotoxicity mechanisms are crucial in the pathogenesis of HAND. CNS infiltration by HIV-1 and immune cells through the blood brain barrier is a key process involved in the pathogenicity of HAND. Factors including calcium dysregulation and autophagy are the main challenges involved in HAND.

The role of dopamine receptors in lymphocytes and their changes in schizophrenia.

Dopamine and its 5 receptors, which are grouped into two families (D1-like and D2-like), modulate functions at a systemic level in both the central nervous system and periphery. The central nervous system and the immune system are the main adaptive systems, which participate in a continuous and functional crosstalk to guarantee homeostasis. On binding to its 5 dopamine receptors, dopamine acts as a co-regulator of the immune system, contributing to the interaction of the central nervous system and inflammatory events and as a source of communication between the different immune cells. Dopaminergic perturbations in the central nervous system are observed in several neurological and psychiatric disorders. Schizophrenia is one of the most common mental disorders with a poorly understood pathoaetiology that includes genetic and environmental components that promote alterations in the dopaminergic system. Interestingly, abnormalities in dopamine receptors expression in lymphocytes of schizophrenia patients have been reported, often significantly correlating with the severity of the psychotic illness. Here, we review the current literature regarding the dopaminergic system in human lymphocytes and its alterations in schizophrenia.

Long-term outcomes in patients with schizophrenia treated with risperidone long-acting injection or oral antipsychotics in Spain: results from the electronic Schizophrenia Treatment Adherence Registry (e-STAR).

BACKGROUND: The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice. METHODS: Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n=1345) or a new oral antipsychotic (AP) (n=277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review. RESULTS: At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p<0.0001) and reduction in Clinical Global Impression Severity scores (-1.14 for RLAI versus -0.94 for APs, p=0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p<0.05) and days (18.74 versus 13.02, p<0.01) of hospitalizations at 24 months than oral AP patients. CONCLUSIONS: This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.

[Urogenitals prolapse: revision of concepts]. / Prolapsos urogenitales: revisión de conceptos.

The prolapse is the exteriorization of the pelvic organs through the vagina, this condition may affect the quality of life. The prolapse was diagnosed in 50% of multiparous women. It is estimated that a woman throughout her life, has 11% risk of needing surgery for correction of pelvic organ prolapse or urinary incontinence. The prolapse may occur at the anterior vaginal wall (cystocele) at the vaginal, uterus (histerocele) or at the posterior wall (or rectocele enterocele). For the unfit patient obliteratives procedures may be indicated and recontructives for pacients wih good performance status. It is important for reconstructive surgery a correct diagnosis, for the specific defect repair. When indicated, meshes can be used to add strength to the poor quality tissues.

[Treatment of post-surgical complications antiincontinence with "sling"]. / Tratamiento de complicaciones post-cirugías antiincontinencia con "sling".

Reports on postoperative complications of anti-incontinence surgery followed the widespread use of synthetic slings. In this paper we describe the more frequent complications, such as obstruction, pelvic hematoma, bladder and urethral injuries, to facilitate the management of these complications.

The neurobiological hypothesis of neurotrophins in the pathophysiology of schizophrenia: A meta-analysis.

BACKGROUND: Schizophrenia is associated with patterns of aberrant neurobiological circuitry. The disease complexity is mirrored by multiple biological interactions known to contribute to the disease pathology. One potential contributor is the family of neurotrophins which are proteins involved in multiple functional processes in the nervous system, with crucial roles in neurodevelopment, synaptogenesis and neuroplasticity. With these roles in mind, abnormal neurotrophin profiles have been hypothesized to contribute to the pathology of schizophrenia. METHODS: We performed a systematic review and a meta-analysis to scrutinize the neurobiological hypothesis of neurotrophins in schizophrenia, examining the correlation between peripheral levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3) and neurotrophin 4/5 (NT-4/5) associated with schizophrenia. RESULTS: Fifty-two studies were reviewed and twenty-two studies were included in this meta-analysis. Using a random effects model, we confirmed that decreased levels of neurotrophins (BDNF, NGF and NT-4/5) were associated with schizophrenia (Hedges's g = -0.846; SE = 0.058; 95% confidence interval: -0.960 to -0.733; Z-value = -14.632; p-value = 0.000). Subgroup analysis indicated that neurotrophin levels are significantly decreased in both medicated and drug-näive patients. Meta-regression of continuous variables such as mean age, duration of illness and PANSS total score did not show significant effects (p > 0.05) in relation to neurotrophins levels. DISCUSSION: We confirm that decreased peripheral neurotrophin levels are significantly associated with schizophrenia, thereby confirming the neurobiological hypothesis of neurotrophins in schizophrenia. Low levels of neurotrophins in peripheral blood of patients with schizophrenia may explain, in part, the pathophysiology of schizophrenia.

The anhedonias: a conceptual history.

BACKGROUND: The term and concept of 'anhedonia' refer to a group of clinical phenomena whose common denominator is the complaint of a putative incapacity to 'experience pleasure". Linked to disorders such as schizophrenia and depression, anhedonia remains difficult to define and measure. METHOD: This paper explores the historical frames in which anhedonia was originally constructed; and is fully based on primary sources. It makes use of the 'conceptual method', i.e. it differentiates the history of the word from that of the behaviours and concepts involved. RESULTS: Historical analysis shows that the boundaries of 'anhedonia' have been fuzzy since the time of Ribot, and that this has made it conceptually unstable. One reason for this instability pertains to the fact that from the start its definition has been parasitical upon the (itself evolving) concept of 'pleasure'. Another that it is defined negatively, i.e. as a reduction or abolition in a putative unitary function. Yet another, that there is little evidence that anhedonia itself is a unitary phenomenon. CONCLUSIONS: It is concluded that at this stage it might be advisable to refer to the concept in the plural (the anhedonias); that a definition should be formulated that it is less dependent upon the ongoing concept of pleasure; and that far more empirical research is needed to find out whether anhedonia is more than a final common pathway.

[Impact of sacrospinous vaginal vault suspension on the anterior compartment]. / Impacto de la suspensión de la cúpula vaginal al ligamento sacroespinoso sobre el compartimiento anterior.

OBJECTIVES: A prospective study was conducted to assess the efficacy of sacrospinous vaginal vault fixation and its impact on the anterior compartment. The Pelvic Organ Prolapse Quantification (POP-Q) system was used to quantify pelvic organ prolapse in the apical and anterior vaginal compartments. METHODS: Fifty-eight patients underwent a procedure to correct apical prolapse from March 2003 to February 2006. Mean preoperative and postoperative POP-Q scores were respectively: Aa (+0.74; -1.45); Ba (+3.17; -1.36); C (+3.41; -7.71) (p<0.001). RESULTS: Cure rate was 93.1%. Preoperative and postoperative evaluation of the anterior vaginal compartment was respectively: stage 1 (5.2%; 48.3%), stage 2 (6.9%; 34.5%), stage 3 (74.1%; 5.2%), and stage 4 (13.8%; 0%). De novo cystocele occurred in 87.9% of cases. An improvement was seen in lower urinary tract symptoms of urgency, nocturia, and urge incontinence. CONCLUSIONS: Sacrospinous vaginal vault suspension is effective for the treatment of apical prolapse and leads to formation of cystocele in most cases.

Treatment retention with risperidone long-acting injection: 24-month results from the Electronic Schizophrenia Treatment Adherence Registry (e-STAR) in six countries.

OBJECTIVE: To assess treatment retention on risperidone long-acting injection (RLAI) and outcomes in schizophrenia patients for whom 24 months of follow-up data in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) were available. RESEARCH DESIGN AND METHODS: e-STAR is an ongoing, international, multicenter, prospective, observational registry assessing use of antipsychotics in patients with schizophrenia or schizoaffective disorder in a normal clinical practice setting. Parameters were assessed prior to and post-initiation of RLAI. Data presented are from six European countries that enrolled patients in e-STAR after they initiated treatment with RLAI. MAIN OUTCOME MEASURES: Clinical and demographic information were collected at baseline and treatment-related data, including RLAI discontinuation, psychiatric hospitalization and medication utilization, were collected prospectively every 3 months. Data collection continued for 24 months, even for patients who discontinued RLAI therapy. Hospitalization and medication utilization were also collected retrospectively by chart review for the 12-month period prior to RLAI initiation. RESULTS: A total of 1659 patients (mean age, 39.2; 18.3% inpatients) completed the study. Twenty-four months after initiating therapy (initial RLAI dose = 33.6 mg) 85% of patients (n = 1410) remained on RLAI (completers) while 15% discontinued therapy. The main reasons for discontinuation were insufficient response (28.5%), patient/family choice (26.1%), adverse events (9.6%) and unacceptable tolerability (6.0%). At baseline, compared to completers, discontinuers were younger (37.4 vs. 39.6 years, p = 0.01), had schizophrenia for a shorter time (10.2 vs. 11.9 years, p = 0.02), had lower Global Assessment of Functioning (GAF) scores (43.5 vs. 48.0, p = 0.0001), higher utilization of benzodiazepines (56.5 vs. 43.3%) and more initiated therapy as inpatients (30 vs. 16%). With RLAI therapy GAF scores improved significantly (p < 0.001) for both groups but the 24-month value for discontinuers was lower than that of completers (55.4 vs. 67.2). Compared to the pre-RLAI initiation period, at 12 months post-initiation completers had greater reductions than discontinuers in the percent of patients hospitalized (66.2% reduction vs. 29.2%) and in the length (68% reduction vs. 0%) and number (80.0 vs. 14.3%) of hospital stays, differences that remained at 24 months. The most common adverse events while patients were taking RLAI were nervous system disorders (6.8%), psychiatric disorders (5.6%), weight increase (3.2%), reproductive system and breast disorders (2.5%) and gastrointestinal disorders (2.1%). CONCLUSIONS: These observational data confirm that RLAI is an effective treatment in schizophrenia and high levels of adherence to therapy offers an opportunity for effective long-term disease management and significant sustained decreases in hospitalization.

Clinical and resource-use outcomes of risperidone long-acting injection in recent and long-term diagnosed schizophrenia patients: results from a multinational electronic registry.

BACKGROUND: Non-adherence to pharmacological treatment leading to frequent relapses and rehospitalizations is a major issue of concern among schizophrenia patients, especially those who are recently diagnosed. Risperidone long-acting injection (RLAI) has been shown to be efficacious, improve compliance, and increase long-term retention rate on therapy. OBJECTIVE: To determine clinical outcomes and hospitalizations before and after the initiation of RLAI among schizophrenia patients with recent (< or =2 years) diagnosis relative to those who had long-term (> 2 years) diagnosis. RESEARCH DESIGN AND METHODS: The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is an observational study of patients with schizophrenia who start treatment with RLAI. Data were recorded at baseline, retrospectively for the 12 months prior to baseline, and prospectively every 3 months for 24 months. Data on patients with a defined length of diagnosis were pooled from eight countries. MAIN OUTCOME MEASURES: Clinical Global Impression of Illness Severity (CGI-S), Global Assessment of Functioning (GAF) scores, and hospitalization data were key outcomes. RESULTS: The magnitude of improvement in CGI-S scores was greater in the recent versus long-term diagnosis group [Delta -1.48 vs. Delta -0.95 (12 months); Delta -1.6 vs. Delta -1.09 (24 months)]. There were parallel improvements in GAF scores [Delta 19.4 vs. Delta 13.7 (12 months); Delta 22.3 vs. Delta 16.8 (24 months)]. The decline in the proportion of patients hospitalized from the retrospective to the prospective period was greater in the recent versus long-term diagnosis group (Delta -36.0 vs. Delta -19%, respectively) at 12 months. This was also true for the number of hospital stays (Delta -0.6 vs. Delta -0.3, respectively) and length of stay (days) (Delta -20.9 vs. Delta -6.9, respectively) at 12 months. Common adverse events in both groups included psychiatric, gastrointestinal, musculoskeletal and reproductive system and breast disorders. CONCLUSIONS: Treatment with RLAI is associated with improved outcomes in recently diagnosed and chronic patients. However, the magnitude of improvement was higher in recently diagnosed patients.