Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients, followed-up a median of 9 years

Objective: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. Methods: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. Results: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/μL, 19% CD4 < 200/μL, 27% ALT grade 1-2, 36% AST grade 1-2. Thirty percent ART-naive, 83%received NVP associated with 2 nucleoside analogues during the study period, and 17% a protease inhibitor. A significant improvement was observed in general health status markers, including hemoglobin, platelets, and albumin, regardless of HCV coinfection. CD4 cell gain was +218 and +322/μL after 6 and 9 years, respectively (+321 and +391 in naive patients). Triglycerides significantly decreased in pretreated patients, whereas the percentage of patients with HDLc < 1.03 mmol/L and LDL-c > 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. Conclusions: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.     

Numerical analysis of the biomechanical behaviour of a weakened root after adhesive reconstruction and post-core rehabilitation

Objectives

The purpose of this study was to perform a finite element analysis to determine whether adhesive reconstruction is able to restore the original biomechanical behaviour of weakened roots, in terms of fracture resistance, when compared with post/crown-restored teeth with intact roots.

Methods

A three-dimensional model of a maxillary central incisor was created. The model simulated an endodontically treated tooth restored with a glass-fibre post, a composite-resin core and a metal crown (Model 1). Based on Model 1, a new volume was created in the root cervical third that represented the area where the dentine structure was lost, resulting in a structurally damaged root (Model 2). A 100 N load was applied to the palatal surface at 130° from the long axis of the tooth. After processing (Ansys^® 10.0 – Canonsburg, PA, USA), the principal normal stress data were analyzed (S1, tensile; S3, compressive).

Results

The models demonstrated a similar S1 distribution concentrated in the lingual cervical region but different S1 levels (Model 1: 28.7 MPa; Model 2: 35.3 MPa). The S3 distribution indicated differences in behaviour between the models (Model 1: −18 to −27 MPa along the buccal root surface; Model 2: −25 to −32 MPa on the post buccal surface and along the buccal root wall).

Conclusions

Although the stress distribution within the root walls remained below the ultimate stress limit of the root dentine, the adhesive reconstruction of the weakened roots did not recover the load resistance of structurally intact roots.

Clinical significance

The decision of when to prosthetically rehabilitate weakened roots with cervical dentine structural tissue loss is a challenge for clinicians. A ‘monoblock’ adhesive reconstruction has been proposed for root reinforcement. During treatment planning, the possibility of restoring the mechanical resistance of the root must be evaluated if successful long-term results are to be achieved.     

Impact of inappropriate lymphadenectomy on lung metastasectomy for patients with metastatic colorectal cancer

Purpose

To evaluate the characteristics of lymph node assessment in the Spanish Colorectal Metastasectomy Registry (GECMP-CCR) and to analyze and compare the survival of patients with pathological absence or presence of lymph node metastases (LNM) with the survival of those with uncertain lymph node status (uLNs).

Methods

A total of 522 patients with lung metastases from colorectal carcinoma were prospectively registered from 2008 to 2010. To confirm the pathologic absence of LNM, systematic nodal dissection or systematic sampling was required, or the lymph node status was coded as uncertain. Disease-specific survival and disease-free survival were calculated by the Kaplan–Meier method with the log-rank test for comparisons.

Results

Lymphadenectomy was performed in 250 (48 %) patients. LNM was found in 25 (10 %) of the patients who had lymph node assessment done. The 3- and 5-year disease-specific survival rates according to lymph node status were 73.5 and 58.3 % in the absence of LNM, 50.5 and 24.8 % when LNM was confirmed, and 69 and 44 % for those with uLNs, respectively (p = 0.006).

Conclusions

The presence of LNM and uLNs is associated with an increased risk of death. The association of nodal assessment at the time of metastasectomy to identify LNM helps us to refine the postoperative prognosis; therefore, its impact should be properly studied in a prospective clinical trial.

     

先天性肠闭锁166例临床分析

目的分析先天性肠闭锁病例的诊断及治疗,以提高治愈率及术后生活质量。方法回顾性分析166例先天性肠闭锁的临床资料。结果治愈142例,治愈率85.5%(142/166),其中包括18例二期手术治愈者;术中10例、术后8例放弃治疗;术后死亡6例。结论早期诊断和选择合理的术式是提高肠闭锁治愈率的关键,基础支持及手术技术改进能促进病情的恢复,改善预后。     

Changes in the serum levels of brain-derived neurotrophic factor in adults with attention deficit hyperactivity disorder after treatment with atomoxetine

Rationale

Atomoxetine (ATX) is a non-stimulant drug approved for the treatment of attention deficit hyperactivity disorder (ADHD). Although animal models have provided evidence that brain-derived neurotrophic factor (BDNF) is involved in the effects of ATX in the brain, there are no studies of BDNF in ADHD patients undergoing treatment with ATX.

Objectives

The aim of this study was to evaluate the possible changes in serum levels of BDNF in adults treated with ATX and its relationship with clinical improvement.

Methods

A total of 54 adults with ADHD (age 33.43?±?8.99 years) without any medical or psychiatric comorbidities were treated with ATX for 3 months; 35 of them completed the protocol. The clinical data for ADHD diagnosis, including Conners’ ADHD Rating Scale and blood samples, were collected at baseline (V1) and at the end of the treatment (V2).

Results

Adults with ADHD who completed ATX treatment for 3 months showed a significant improvement in their clinical symptoms. No significant differences were found in BDNF levels before and after treatment with ATX in the whole group of patients (p?=?0.15). The inattentive subgroup of ATX responders showed a decrease of serum BDNF after 3 months of ATX treatment (p?=?0.05) not present in the combined subtype (p?=?0.82).

Conclusions

These results suggest that BDNF is not directly involved in the neurobiological mechanisms of ATX-induced improvement of clinical symptoms of ADHD. The differences between the combined and inattentive subtypes in serum BDNF changes suggest selective ATX-induced effects in the function of brain circuitry.     

One-step preparation of novel 1-(N-indolyl)-1,3-butadienes by base-catalysed isomerization of alkynes as an access to 5-(N-indolyl)-naphthoquinones

A series of novel 1-(N-indolyl)-1,3-butadienes, as (1 : 1) mixtures of the (E) and (Z) dienes, was prepared in one step by base-catalysed isomerization of N-alkylindoles with a terminal butyne chain. The reaction conditions are mild, and in all cases the yields were very high (>90%). The (E) and (Z) dienes were separable by preparative TLC and could be fully characterized. This isomerization proceeded readily in the case of a butynyl chain, but didn''t take place with a pentynyl chain. A mechanism was proposed for this reaction, based on previous studies on the isomerization of alkynes in basic media, and a key intermediate that supports the proposed mechanism could be isolated and fully characterized. A theoretical study of the proposed mechanism was performed by computational methods and the results validated the proposal. The reactivity of the synthesized dienes was studied in Diels–Alder reactions with p-benzoquinone, to obtain a small library of new 5-(N-indolyl)-1,4-naphthoquinones.The lack of reactivity in the case of the (Z) isomers was explained by calculation of the rotational curves of the central bond of the (Z) and (E) dienes. Finally, the cytotoxicity of the new 5-(N-indolyl)-1,4-naphthoquinones was tested against a panel of three cell lines.

A series of novel 1-(N-indolyl)-1,3-butadienes, was easily prepared in one step and used for the synthesis of 5-(N-indolyl) naphthoquinones.     

Cocaine use in Europe - a multi-centre study. Methodology and prevalence estimates

An increase in the use of cocaine and crack in several parts of Europe has raised the question whether this trend is similar to that of the USA in the 1980s. However, research in the field of cocaine use in Europe has been only sporadic. Therefore, a European multi-centre and multi-modal project was designed to study specific aspects of cocaine and crack use in Europe, in order to develop guidelines for public health strategies. Data on prevalence rates were analysed for the general population and for specific subgroups. Despite large differences between countries in the prevalence of cocaine use in the general population, most countries show an increase in the last few years. The highest rate with a lifetime prevalence of 5.2% was found for the United Kingdom, although with a plateau effect around the year 2000. With regard to specific subgroups, three groups seem to show a higher prevalence than the general population: (1) youth, especially in the party scene; (2) socially marginalized groups, such as homeless and prostitutes or those found in open drug scenes; (3) opiate-dependent patients in maintenance treatment who additionally use cocaine. Specific strategies need to be developed to address problematic cocaine use in these subgroups.