Search

This systematic review aimed to update the management of sleep bruxism (SB) in adults, as diagnosed using polysomnography (PSG) and/or electromyography (EMG). Management methods covered were oral appliance therapy (OAT) with stabilization splints, cognitive-behavioral therapy (CBT), biofeedback therapy (BFT), and pharmacological therapy. A comprehensive search was conducted on MEDLINE, Cochrane Library, and Web of Science up to October 1st, 2021. Reference list searches and hand searches were also performed by an external organization. Two reviewers for each therapy independently performed article selection, data extraction, and risk of bias assessment. The reviewers resolved any disagreements concerning the assortment of the articles by discussion. Finally, 11, 3, 14, and 22 articles were selected for each therapy. The results suggested that OAT tended to reduce the number of SB events, although there was no significant difference compared to other types of splints, that the potential benefits of CBT were not well supported, and that BFT, rabeprazole, clonazepam, clonidine, and botulinum toxin type A injection showed significant reductions in specific SB parameters, although several side effects were reported. It can be concluded that more methodologically rigorous randomized large-sample long-term follow-up clinical trials are needed to clarify the efficacy and safety of management for SB.

Context: Polycystic ovary syndrome (PCOS) is a complex endocrine disease that affects women of reproductive age and is characterised by biochemical and clinical androgen excess. Aim: To evaluate the efficacy of pharmacological interventions used to decrease androgen hormones in women with PCOS. Data source: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science from inception up to March 2021. Data synthesis Two reviewers selected eligible studies and extracted data, and the review is reported according to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Of the 814 randomised clinical trials (RCTs) located in the search, 92 met the eligibility criteria. There were significant reductions in total testosterone level with metformin versus (vs) placebo (SMD: - 0.33; 95% CI - 0.49 to - 0.17, p < 0.0001, moderate grade evidence) and dexamethasone vs placebo (MD:-0.86 nmol/L; 95% CI - 1.34 to - 0.39, p = 0.0004, very low-grade evidence). Significant reductions in the free testosterone with sitagliptin vs placebo (SMD: - 0.47; 95% CI - 0.97 to 0.04, p = 0.07, very low-grade evidence), in dehydroepiandrosterone sulphate (DHEAS) with flutamide vs finasteride (MD: - 0.37 mu g/dL; 95% CI - 0.05 to - 0.58, p = 0.02, very low-grade evidence), a significant reduction in androstenedione (A4) with rosiglitazone vs placebo (SMD: - 1.67; 95% CI - 2.27 to - 1.06; 59 participants, p < 0.00001, very low-grade evidence), and a significant increase in sex hormone-binding globulin (SHBG) with oral contraceptive pill (OCP) (35 mu g Ethinyl Estradiol (EE)/2 mg cyproterone acetate (CPA)) vs placebo (MD: 103.30 nmol/L; 95% CI 55.54-151.05, p < 0.0001, very low-grade evidence) were observed. Conclusion: Metformin, OCP, dexamethasone, flutamide, and rosiglitazone use were associated with a significant reduction in biochemical hyperandrogenemia in women with PCOS, though their individual use may be limited due to

Context: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age and is associated with increased body weight. Objective: To review the literature on the effect of different pharmacological interventions on the anthropometric indices in women with PCOS. Data sources: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library, and the Web of Science in April 2020 with an update in PubMed in March 2021. Study selection: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)2020. Data extraction: Reviewers extracted data and assessed the risk of bias using the Cochrane risk of bias tool. Results: 80 RCTs were included in the meta-analysis. Metformin vs placebo showed significant reduction in the mean body weight (MD: -3.13 kg; 95% confidence interval [CI]: -5.33 to -0.93, I-2 = 5%) and the mean body mass index (BMI) (MD: -0.75 kg/m(2); 95% CI: -1.15 to -0.36, I-2 = 0%). There was a significant reduction in the mean BMI with orlistat versus placebo (MD: -1.33 kg/m(2); 95% CI: -2.16 to -0.66, I-2 = 0.0%), acarbose versus metformin (MD: -1.26 kg/m(2); 95% CI: -2.13 to -0.38, I-2 = 0%), and metformin versus pioglitazone (MD: -0.91 kg/m(2); 95% CI: -1.62 to -0.19, I-2 = 0%). A significant increase in the mean BMI was also observed in pioglitazone versus placebo (MD: + 2.59 kg/m(2); 95% CI: 1.78-3.38, I-2 = 0%) and in rosiglitazone versus metformin (MD: + 0.80 kg/m(2); 95% CI: 0.32-1.27, I-2 = 3%). There was a significant reduction in the mean waist circumference (WC) with metformin versus placebo (MD: -1.21 cm; 95% CI: -3.71 to 1.29, I-2 = 0%) while a significant increase in the mean WC with pioglitazone versus placebo (MD: + 5.45 cm; 95% CI: 2.18-8.71, I-2 = 0%). Conclusion: Pharmacological interventions including metformin, sitagliptin, pioglitazone, rosiglitazone orlistat, and acarbose have significant effects on the anthropometric indices in women with PCOS.

Context: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD). Objective: To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS. Data Sources: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021. Study Selection: The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Data Extraction: Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection. Data Synthesis: In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I-2 = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I-2 = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I-2 = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I-2 = 75%, very low-grade evidence). Conclusion: There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.

Objective: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterized by insulin resistance and is a major risk factor for type 2 diabetes mellitus (T2DM). The objective was to review the literature on the effect of different pharmacological interventions on insulin resistance in women with PCOS. Design: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science in April 2020 and updated in March 2021. The study follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-ana. Reviwers extracted data and assessed the risk of bias using the Cochrane risk of bias tool. Results: In 58 randomized controlled trials there were significant reductions in the fasting blood glucose (FBG) with metformin versus placebo (standardized mean difference [SMD]: -0.23; 95% confidence interval [CI]: -0.40, -0.06; I-2 = 0%, low-grade evidence), and acarbose versus metformin (mean difference [MD]: -10.50 mg/dl; 95% CI: -15.76, -5.24; I-2 = 0%, low-grade evidence). Significant reductions in fasting insulin (FI) with pioglitazone versus placebo (SMD: -0.55; 95% CI: -1.03, -0.07; I-2 = 37%; p = .02, very-low-grade evidence). A significant reduction in homoeostatic model assessment of insulin resistance (HOMA-IR) was seen with exenatide versus metformin (MD: -0.34; 95% CI: -0.65, -0.03; I-2 = 0%, low-grade evidence). No effect on homoeostatic model assessment of beta cells (HOMA-B) was observed. Conclusions: Pharmacological interventions, including metformin, acarbose, pioglitazone and exenatide have significant effects on FBG, FI, HOMA-IR but not on HOMA-B.

Context: Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age, and metformin is a widely used medication in managing this condition. Aim: To review the available literature comprehensively on the therapeutic impact of metformin on the clinical and metabolic parameters of women with PCOS. Data source: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science and selected sources for grey literature from their inception to April 2020. An updated search in PubMed was performed in June 2022. Data synthesis: Two reviewers selected eligible studies and extracted data, and the review is reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: In 24 eligible randomised controlled trials (RCTs) involving 564 participants who received metformin therapy, metformin was associated with significant reduction in body weight by 3.13 kg (95% CI: -5.33, -0.93), body mass index (BMI) by 0.82 kg/m(2) (95% CI: -1.22, -0.41), fasting blood glucose [standardised mean difference (SMD): -0.23; 95% CI: -0.40, -0.06], low-density lipoprotein cholesterol (LDL-C) (SMD: -0.41; 95% CI: -0.85, 0.03), total testosterone (SMD: -0.33; 95% CI: -0.49, -0.17), androstenedione (SMD: -0.45; 95% CI: -0.70, -0.20), 17-hydroxyprogesterone (17-OHP) (SMD: -0.58; 95% CI: -1.16, 0.00) and increase the likelihood of clinical pregnancy rate [odds ratio (OR): 3.00; 95% CI: 1.95, 4.59] compared with placebo. Conclusion: In women with PCOS, metformin use has shown a positive impact in reducing body weight, BMI, total testosterone, androstenedione, 17-OHP, LDL-C, fasting blood glucose and increasing the likelihood of pregnancy in women with PCOS.

Since the original description of Alzheimer¿s disease (AD), research into this condition has mainly focused on assessing the alterations to neurons associated with dementia, and those to the circuits in which they are involved. In most of the studies on human brains and in many models of AD, the glial cells accompanying these neurons undergo concomitant alterations that aggravate the course of neurodegeneration. As a result, these changes to neuroglial cells are now included in all the ¿pathogenic cascades¿ described in AD. Accordingly, astrogliosis and microgliosis, the main components of neuroinflammation, have been integrated into all the pathogenic theories of this disease, as discussed in this part of the two-part monograph that follows an accompanying article on gliopathogenesis and glioprotection. This initial reflection verified the implication of alterations to the neuroglia in AD, suggesting that these cells may also represent therapeutic targets to prevent neurodegeneration. In this second part of the monograph, we will analyze the possibilities of acting on glial cells to prevent or treat the neurodegeneration that is the hallmark of AD and other pathologies. Evidence of the potential of different pharmacological, non-pharmacological, cell and gene therapies (widely treated) to prevent or treat this disease is now forthcoming, in most cases as adjuncts to other therapies. A comprehensive AD multimodal therapy is proposed in which neuronal and neuroglial pharmacological treatments are jointly considered, as well as the use of new cell and gene therapies and nonpharmacological therapies that tend to slow down the progress of dem

This systematic review aimed to update the management of sleep bruxism (SB) in adults, as diagnosed using polysomnography (PSG) and/or electromyography (EMG). Management methods covered were oral appliance therapy (OAT) with stabilization splints, cognitive-behavioral therapy (CBT), biofeedback therapy (BFT), and pharmacological therapy. A comprehensive search was conducted on MEDLINE, Cochrane Library, and Web of Science up to October 1st, 2021. Reference list searches and hand searches were also performed by an external organization. Two reviewers for each therapy independently performed article selection, data extraction, and risk of bias assessment. The reviewers resolved any disagreements concerning the assortment of the articles by discussion. Finally, 11, 3, 14, and 22 articles were selected for each therapy. The results suggested that OAT tended to reduce the number of SB events, although there was no significant difference compared to other types of splints, that the potential benefits of CBT were not well supported, and that BFT, rabeprazole, clonazepam, clonidine, and botulinum toxin type A injection showed significant reductions in specific SB parameters, although several side effects were reported. It can be concluded that more methodologically rigorous randomized large-sample long-term follow-up clinical trials are needed to clarify the efficacy and safety of management for SB.

This systematic review aimed to update the management of sleep bruxism (SB) in adults, as diagnosed using polysomnography (PSG) and/or electromyography (EMG). Management methods covered were oral appliance therapy (OAT) with stabilization splints, cognitive-behavioral therapy (CBT), biofeedback therapy (BFT), and pharmacological therapy. A comprehensive search was conducted on MEDLINE, Cochrane Library, and Web of Science up to October 1st, 2021. Reference list searches and hand searches were also performed by an external organization. Two reviewers for each therapy independently performed article selection, data extraction, and risk of bias assessment. The reviewers resolved any disagreements concerning the assortment of the articles by discussion. Finally, 11, 3, 14, and 22 articles were selected for each therapy. The results suggested that OAT tended to reduce the number of SB events, although there was no significant difference compared to other types of splints, that the potential benefits of CBT were not well supported, and that BFT, rabeprazole, clonazepam, clonidine, and botulinum toxin type A injection showed significant reductions in specific SB parameters, although several side effects were reported. It can be concluded that more methodologically rigorous randomized large-sample long-term follow-up clinical trials are needed to clarify the efficacy and safety of management for SB.

Although pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), many patients have inoperable disease, and some have persistent or recurrent pulmonary hypertension (PH) after surgery. Alternative options (balloon pulmonary angioplasty (BPA) and PH-targeted medical therapy) are, therefore, required. Studies of medical therapies for CTEPH have evolved since Aerosolized Iloprost Randomized (AIR), the first randomized, controlled study of a PH-targeted therapy (inhaled iloprost) to include patients with CTEPH. Key learnings from these studies include the need to evaluate CTEPH separately from other types of PH, the importance of prospective operability adjudication as part of the protocol, and the need for sufficient duration to allow treatment benefits to become apparent. The 16-week Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Study 1 (CHEST-1) study was the first to operationalize these learnings, demonstrating a significant mean improvement in 6-minute walk distance (+46 m) and improvements in hemodynamic endpoints with riociguat versus placebo. Findings from previous studies will inform the design of future studies to address key issues related to combination medical therapy. Data on combinations of macitentan with phosphodiesterase type 5 inhibitors or oral prostanoids are available from MERIT, the first study to allow such regimens. No data on combinations including riociguat, the only licensed medical therapy for CTEPH, are available. Studies are also needed for multimodality treatment, including medical therapy plus BPA, and medical therapy as a bridge to PEA in selected operable patients. To address these issues and improve patient outcomes, it is vital that we learn from current studies to improve future trial design.

Cryptococcosis is a mycosis caused by two encapsulated yeast fungi of the genus Cryptoccoccus, enters the body by inhalation with dissemination to the central nervous system, its prevalence is higher in immunosuppressed by HIV AIDS. It is a systemic mycosis that affects 80% of immunocompromised patients, being a public health problem in this group; Due to environmental conditions, the development of the microorganisms causing cryptococcosis is encouraged, which usually appears in patients with less than 30 cells / mL in their CD4 + lymphocyte count, deteriorating the quality of life and increasing mortality in these patients . By virtue of this, morbidity due to Criptococcus neoformans in HIV positive patients is described, through an observational, descriptive study of case series based on secondary sources and clinical cases of discharges from the Hospital of Infectology of the city of Guayaquil during the year 2017 and the first four-month period of the year 2018. From 1837 admissions to this health house, a prevalence of 4.25% (n: 78) was found, of which 1.0% (n: 20) of the cases developed meningeal cryptococcosis and 1.6% (n: 30) suffered complications. HIV / AIDS status is a frequent factor of cryptococcal infection, especially if TCD4 + cells are low, as observed in 99% of cases. The predominance of meningeal cryptococcosis in these immunocompromised patients, evidences the need to analyze the schemes divided in monotherapy and combined therapy of amphotericin B and the assessment of the decrease inmorbidity and mortality presented in these patients., A criptococose é uma micose causada por dois fungos encapsulados do gênero Cryptoccoccus, que entra no organismo por inalação com disseminação para o sistema nervoso central, sendo sua prevalência mais elevada em imunossuprimidos pelo HIV AIDS. É uma micose sistêmica que afeta 80% dos pacientes imunocomprometidos, sendo um problema de saúde públicanesse grupo; Devido às condições ambientais, o desenvolvimento dos microrganismos causadores da criptococose é encorajado, o que geralmente aparece em pacientes com menos de 30 células / mL em sua contagem de linfócitos CD4 +, deteriorando a qualidade de vida e aumentando a mortalidade nesses pacientes. . Em virtude disso, a morbidade por Criptococcus neoformans em pacientes HIV positivos é descrita, através de um estudo observacional, descritivo de séries de casos baseados em fontes secundárias e casos clínicos de alta hospitalar do Hospital de Infectologia da cidade de Guayaquil durante o ano de 2017 e o primeiro quadrimestre do ano de 2018. A partir de 1837 internações nesta casa de saúde, encontrou-se uma prevalência de 4,25% (n: 78), dos quais 1,0% (n:20) do casos desenvolveram criptococose meníngea e 1,6% (n: 30) sofreram complicações. O status de HIV / AIDS é um fator freqüente de infecção criptocócica, especialmente se as células TCD4 + são baixas, como observado em 99% dos casos. A predominância dacriptococose meníngea nesses pacientes imunocomprometidos evidencia a necessidade de análise dos esquemas divididos em monoterapia e terapia combinada de anfotericina B e a avaliação da diminuição da morbimortalidade apresentada nesses pacientes., La criptococosis es una micosis causada por dos hongos levaduriformes encapsulados del género Cryptoccoccus, ingresa al organismo por vía inhalatoria con diseminación al sistema nervioso central, su prevalencia es mayor en inmunodeprimidos por VIH SIDA. Es una micosis sistémica que afecta en 80% a pacientes inmunocomprometidos, siendo un problema de salud pública en este grupo; por causa de las condiciones ambientales, se propicia el desarrollo de los microorganismos causantes de la criptococosis, que suele aparecer en pacientes con menos de 30 cel/mL en su contaje de linfocitos CD4+, deteriorando la calidad de vida y aumentando la mortalidad en estos pacientes. En virtud de esto, se describe la morbilidad por Criptococcus neoformans en pacientes VIH positivo, a través de un estudio observacional, descriptivo de serie de casos en base a fuentes secundarias y casos clínicos de los egresos del Hospital de Infectología de la ciudad de Guayaquil durante el año 2017 y el primer cuatrimestre del año 2018. De 1837 ingresos a esta casa de salud, se encontró una prevalencia de 4,25% (n:78), de los cuales un 1,0% (n:20) de los casos desarrollaron criptococosis meníngea y el 1,6% (n:30) sufrieron complicaciones. El estado de VIH/SIDA es un factor frecuente de infección de criptococosis especialmente si las células TCD4+ son bajas, como se observó en el 99% de los casos. El predominio de criptococosis meníngea en estos pacientes inmunodeprimidos, evidencia la necesidad de analizar los esquemas divididos en monoterapia y terapia combinada de anfotericina B y la valoración de la disminución en la morbimortalidad presentada en estos pacientes.

Background: Attention deficit/hyperactivity disorder (ADHD) is a major public health problem with numerous negative outcomes for the affected individuals and with a high burden to families and society. Although a multimodal therapeutic approach (i.e., pharmacological treatment as well as non-pharmaceutical treatment options) is considered the gold standard, the observed increasing methylphenidate (MPH) treatment could correspond to a reduced use of other treatments options. This study therefore aims to providing insights into the actual practice of paediatricians as well as perceived challenges during the diagnosis and treatment. Methods: An online survey on diagnostic and therapy procedures, personal attitudes, and perceived challenges regarding ADHD was sent to the members of the Swiss Society for Paediatrics. With 151 questionnaires that were analyzed, response rate was low (9.3%). Results: Pediatricians reported the exchange with parents and children as well as the suffering of the children to be central when selecting a therapy. On average, they arrange three meetings with parents, of which two take place with the concerned child. They also report including information from several sources before arriving at a diagnosis. Pharmacological therapy was most frequent, followed by psychotherapy, and occupational therapy. Challenges mentioned were: the subjective character of the diagnosis and frequent co-morbidities, limited resources for case management, limited availability of child and youth psychiatry and psychotherapy, and unfavorable public attitudes toward medication. Conclusions: Pediatricians do consider a multimodal approach when treating ADHD and show a high involvement of family and child in the choice of therapy. However, they highlight the potential of improving the cooperation with other specialists, such as teachers and school social workers, and of improving the availability of psychotherapy and information on ADHD.

Cryptococcosis is a mycosis caused by two encapsulated yeast fungi of the genus Cryptoccoccus, enters the body by inhalation with dissemination to the central nervous system, its prevalence is higher in immunosuppressed by HIV AIDS. It is a systemic mycosis that affects 80% of immunocompromised patients, being a public health problem in this group; Due to environmental conditions, the development of the microorganisms causing cryptococcosis is encouraged, which usually appears in patients with less than 30 cells / mL in their CD4 + lymphocyte count, deteriorating the quality of life and increasing mortality in these patients . By virtue of this, morbidity due to Criptococcus neoformans in HIV positive patients is described, through an observational, descriptive study of case series based on secondary sources and clinical cases of discharges from the Hospital of Infectology of the city of Guayaquil during the year 2017 and the first four-month period of the year 2018. From 1837 admissions to this health house, a prevalence of 4.25% (n: 78) was found, of which 1.0% (n: 20) of the cases developed meningeal cryptococcosis and 1.6% (n: 30) suffered complications. HIV / AIDS status is a frequent factor of cryptococcal infection, especially if TCD4 + cells are low, as observed in 99% of cases. The predominance of meningeal cryptococcosis in these immunocompromised patients, evidences the need to analyze the schemes divided in monotherapy and combined therapy of amphotericin B and the assessment of the decrease inmorbidity and mortality presented in these patients., A criptococose é uma micose causada por dois fungos encapsulados do gênero Cryptoccoccus, que entra no organismo por inalação com disseminação para o sistema nervoso central, sendo sua prevalência mais elevada em imunossuprimidos pelo HIV AIDS. É uma micose sistêmica que afeta 80% dos pacientes imunocomprometidos, sendo um problema de saúde públicanesse grupo; Devido às condições ambientais, o desenvolvimento dos microrganismos causadores da criptococose é encorajado, o que geralmente aparece em pacientes com menos de 30 células / mL em sua contagem de linfócitos CD4 +, deteriorando a qualidade de vida e aumentando a mortalidade nesses pacientes. . Em virtude disso, a morbidade por Criptococcus neoformans em pacientes HIV positivos é descrita, através de um estudo observacional, descritivo de séries de casos baseados em fontes secundárias e casos clínicos de alta hospitalar do Hospital de Infectologia da cidade de Guayaquil durante o ano de 2017 e o primeiro quadrimestre do ano de 2018. A partir de 1837 internações nesta casa de saúde, encontrou-se uma prevalência de 4,25% (n: 78), dos quais 1,0% (n:20) do casos desenvolveram criptococose meníngea e 1,6% (n: 30) sofreram complicações. O status de HIV / AIDS é um fator freqüente de infecção criptocócica, especialmente se as células TCD4 + são baixas, como observado em 99% dos casos. A predominância dacriptococose meníngea nesses pacientes imunocomprometidos evidencia a necessidade de análise dos esquemas divididos em monoterapia e terapia combinada de anfotericina B e a avaliação da diminuição da morbimortalidade apresentada nesses pacientes., La criptococosis es una micosis causada por dos hongos levaduriformes encapsulados del género Cryptoccoccus, ingresa al organismo por vía inhalatoria con diseminación al sistema nervioso central, su prevalencia es mayor en inmunodeprimidos por VIH SIDA. Es una micosis sistémica que afecta en 80% a pacientes inmunocomprometidos, siendo un problema de salud pública en este grupo; por causa de las condiciones ambientales, se propicia el desarrollo de los microorganismos causantes de la criptococosis, que suele aparecer en pacientes con menos de 30 cel/mL en su contaje de linfocitos CD4+, deteriorando la calidad de vida y aumentando la mortalidad en estos pacientes. En virtud de esto, se describe la morbilidad por Criptococcus neoformans en pacientes VIH positivo, a través de un estudio observacional, descriptivo de serie de casos en base a fuentes secundarias y casos clínicos de los egresos del Hospital de Infectología de la ciudad de Guayaquil durante el año 2017 y el primer cuatrimestre del año 2018. De 1837 ingresos a esta casa de salud, se encontró una prevalencia de 4,25% (n:78), de los cuales un 1,0% (n:20) de los casos desarrollaron criptococosis meníngea y el 1,6% (n:30) sufrieron complicaciones. El estado de VIH/SIDA es un factor frecuente de infección de criptococosis especialmente si las células TCD4+ son bajas, como se observó en el 99% de los casos. El predominio de criptococosis meníngea en estos pacientes inmunodeprimidos, evidencia la necesidad de analizar los esquemas divididos en monoterapia y terapia combinada de anfotericina B y la valoración de la disminución en la morbimortalidad presentada en estos pacientes.

Cryptococcosis is a mycosis caused by two encapsulated yeast fungi of the genus Cryptoccoccus, enters the body by inhalation with dissemination to the central nervous system, its prevalence is higher in immunosuppressed by HIV AIDS. It is a systemic mycosis that affects 80% of immunocompromised patients, being a public health problem in this group; Due to environmental conditions, the development of the microorganisms causing cryptococcosis is encouraged, which usually appears in patients with less than 30 cells / mL in their CD4 + lymphocyte count, deteriorating the quality of life and increasing mortality in these patients . By virtue of this, morbidity due to Criptococcus neoformans in HIV positive patients is described, through an observational, descriptive study of case series based on secondary sources and clinical cases of discharges from the Hospital of Infectology of the city of Guayaquil during the year 2017 and the first four-month period of the year 2018. From 1837 admissions to this health house, a prevalence of 4.25% (n: 78) was found, of which 1.0% (n: 20) of the cases developed meningeal cryptococcosis and 1.6% (n: 30) suffered complications. HIV / AIDS status is a frequent factor of cryptococcal infection, especially if TCD4 + cells are low, as observed in 99% of cases. The predominance of meningeal cryptococcosis in these immunocompromised patients, evidences the need to analyze the schemes divided in monotherapy and combined therapy of amphotericin B and the assessment of the decrease inmorbidity and mortality presented in these patients., A criptococose é uma micose causada por dois fungos encapsulados do gênero Cryptoccoccus, que entra no organismo por inalação com disseminação para o sistema nervoso central, sendo sua prevalência mais elevada em imunossuprimidos pelo HIV AIDS. É uma micose sistêmica que afeta 80% dos pacientes imunocomprometidos, sendo um problema de saúde públicanesse grupo; Devido às condições ambientais, o desenvolvimento dos microrganismos causadores da criptococose é encorajado, o que geralmente aparece em pacientes com menos de 30 células / mL em sua contagem de linfócitos CD4 +, deteriorando a qualidade de vida e aumentando a mortalidade nesses pacientes. . Em virtude disso, a morbidade por Criptococcus neoformans em pacientes HIV positivos é descrita, através de um estudo observacional, descritivo de séries de casos baseados em fontes secundárias e casos clínicos de alta hospitalar do Hospital de Infectologia da cidade de Guayaquil durante o ano de 2017 e o primeiro quadrimestre do ano de 2018. A partir de 1837 internações nesta casa de saúde, encontrou-se uma prevalência de 4,25% (n: 78), dos quais 1,0% (n:20) do casos desenvolveram criptococose meníngea e 1,6% (n: 30) sofreram complicações. O status de HIV / AIDS é um fator freqüente de infecção criptocócica, especialmente se as células TCD4 + são baixas, como observado em 99% dos casos. A predominância dacriptococose meníngea nesses pacientes imunocomprometidos evidencia a necessidade de análise dos esquemas divididos em monoterapia e terapia combinada de anfotericina B e a avaliação da diminuição da morbimortalidade apresentada nesses pacientes., La criptococosis es una micosis causada por dos hongos levaduriformes encapsulados del género Cryptoccoccus, ingresa al organismo por vía inhalatoria con diseminación al sistema nervioso central, su prevalencia es mayor en inmunodeprimidos por VIH SIDA. Es una micosis sistémica que afecta en 80% a pacientes inmunocomprometidos, siendo un problema de salud pública en este grupo; por causa de las condiciones ambientales, se propicia el desarrollo de los microorganismos causantes de la criptococosis, que suele aparecer en pacientes con menos de 30 cel/mL en su contaje de linfocitos CD4+, deteriorando la calidad de vida y aumentando la mortalidad en estos pacientes. En virtud de esto, se describe la morbilidad por Criptococcus neoformans en pacientes VIH positivo, a través de un estudio observacional, descriptivo de serie de casos en base a fuentes secundarias y casos clínicos de los egresos del Hospital de Infectología de la ciudad de Guayaquil durante el año 2017 y el primer cuatrimestre del año 2018. De 1837 ingresos a esta casa de salud, se encontró una prevalencia de 4,25% (n:78), de los cuales un 1,0% (n:20) de los casos desarrollaron criptococosis meníngea y el 1,6% (n:30) sufrieron complicaciones. El estado de VIH/SIDA es un factor frecuente de infección de criptococosis especialmente si las células TCD4+ son bajas, como se observó en el 99% de los casos. El predominio de criptococosis meníngea en estos pacientes inmunodeprimidos, evidencia la necesidad de analizar los esquemas divididos en monoterapia y terapia combinada de anfotericina B y la valoración de la disminución en la morbimortalidad presentada en estos pacientes.

Background: Attention deficit/hyperactivity disorder (ADHD) is a major public health problem with numerous negative outcomes for the affected individuals and with a high burden to families and society. Although a multimodal therapeutic approach (i.e., pharmacological treatment as well as non-pharmaceutical treatment options) is considered the gold standard, the observed increasing methylphenidate (MPH) treatment could correspond to a reduced use of other treatments options. This study therefore aims to providing insights into the actual practice of paediatricians as well as perceived challenges during the diagnosis and treatment. Methods: An online survey on diagnostic and therapy procedures, personal attitudes, and perceived challenges regarding ADHD was sent to the members of the Swiss Society for Paediatrics. With 151 questionnaires that were analyzed, response rate was low (9.3%). Results: Pediatricians reported the exchange with parents and children as well as the suffering of the children to be central when selecting a therapy. On average, they arrange three meetings with parents, of which two take place with the concerned child. They also report including information from several sources before arriving at a diagnosis. Pharmacological therapy was most frequent, followed by psychotherapy, and occupational therapy. Challenges mentioned were: the subjective character of the diagnosis and frequent co-morbidities, limited resources for case management, limited availability of child and youth psychiatry and psychotherapy, and unfavorable public attitudes toward medication. Conclusions: Pediatricians do consider a multimodal approach when treating ADHD and show a high involvement of family and child in the choice of therapy. However, they highlight the potential of improving the cooperation with other specialists, such as teachers and school social workers, and of improving the availability of psychotherapy and information on ADHD.

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III-IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multi-disciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group AD classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) -0.79 (-1.39 to -0.19), p = 0.010). Conclusion: Most stage III-IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III-IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multi-disciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group AD classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) -0.79 (-1.39 to -0.19), p = 0.010). Conclusion: Most stage III-IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III–IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multidisciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group A–D classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) −0.79 (−1.39 to −0.19), p = 0.010). Conclusion: Most stage III–IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III–IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multidisciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group A–D classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) −0.79 (−1.39 to −0.19), p = 0.010). Conclusion: Most stage III–IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III–IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multidisciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group A–D classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) −0.79 (−1.39 to −0.19), p = 0.010). Conclusion: Most stage III–IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III-IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multi-disciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group AD classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) -0.79 (-1.39 to -0.19), p = 0.010). Conclusion: Most stage III-IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III-IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multi-disciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group AD classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) -0.79 (-1.39 to -0.19), p = 0.010). Conclusion: Most stage III-IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation, Funding Agency:Region Örebro County through ALF

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III-IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multi-disciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group AD classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) -0.79 (-1.39 to -0.19), p = 0.010). Conclusion: Most stage III-IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III–IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multidisciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group A–D classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) −0.79 (−1.39 to −0.19), p = 0.010). Conclusion: Most stage III–IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III-IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multi-disciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group AD classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) -0.79 (-1.39 to -0.19), p = 0.010). Conclusion: Most stage III-IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation

Introduction: Only a selected proportion of chronic obstructive pulmonary disease (COPD) patients are managed in secondary care. The aim of this study was to characterize disease severity, treatment and structure of secondary care for COPD in Sweden. Methods: Information was collected from 29 of 33 existing secondary care units of respiratory medicine in Sweden, using both individual data from 373 consecutively enrolled COPD patients with Global initiative on Obstructive Lung Disease (GOLD) stage III–IV and a structural questionnaire about available resources at the units. Patient data included exacerbations, health status assessed by COPD Assessment Test (CAT), lung function, comorbid conditions, pharmacological treatment and vaccinations. Structural data included available smoking cessation support, multidisciplinary rehabilitation, physical training, patient education and routine follow-up after exacerbations at the respective unit. All patients were reclassified according to the GOLD 2014 group A–D classification. Multiple linear regression investigated associations of available resources with number of exacerbations and CAT score. Results: According to GOLD 2014, 87% of the population were GOLD D and 13% were GOLD C. Triple inhaled therapy were prescribed in 88% of the patients. Over 75% of the units had resources for smoking cessation, multidisciplinary rehabilitation, physical training and patient education. Routine follow-up after exacerbations was available in 35% of the units. Being managed at units with access to structured patient education was associated with statistically significantly fewer exacerbations (adjusted regression coefficient (95% confidence interval) −0.79 (−1.39 to −0.19), p = 0.010). Conclusion: Most stage III–IV COPD patients managed at secondary care respiratory units in Sweden have maximized inhaled therapy and high risk disease even when reclassified according to GOLD 2014. Most units have access to smoking cessation, rehabilitation

Worldwide, each year more than 7 million people experience myocardial infarction, in which one-year mortality rates are now in the range of 10%, but vary with patient characteristics. The consequences are even more dramatic: among patients who survive, 20% suffer a second cardiovascular event in the first year and approximately 50% of major coronary events occur in those with a previous hospital discharge diagnosis of ischaemic heart disease. The people behind these numbers spur this call for action. Prevention after myocardial infarction is crucial to reduce risk and suffering. Evidence-based interventions include optimal medical treatment with anti-platelets and statins, achievement of blood pressure, lipid and blood glucose targets, and appropriate lifestyle changes. The European Society of Cardiology and its constituent bodies are determined to embrace this challenge by developing a consensus document in which the existing gaps for secondary prevention strategies are reviewed. Effective interventions in relation to the patients, healthcare providers and healthcare systems are proposed and discussed. Finally, innovative strategies in hospital as well as in outpatient and long-term settings are endorsed.

In the structure of inflammatory di­seases postpartum endometritis (PE) retains its leading position. The likelihood of postpartum endometritis deve­lopment after cesarean section increases by 5-10 times compared with spontaneous labor and its frequency has no tendency to decrease. The urgency of PE problem is determined not only by its high prevalence, economic losses, but its possible complications (uterine suture failure and generalization of infection as well). Clinical picture of PE currently is characterized by late manifastation, presence of atypical and asymptomatic forms with mismatched general reaction of the organism and severity of the local pathological process. The leading role in the etiology of PE belongs to conditionaly pathogenic microflora, in the most cases (90%) presence of strict anaerobic nonsporeforming mic­roorganisms, composing part of the normal flora of the genital tract in women. The aim of the study was the development of the principles of active prevention of postpartum endometritis in women with severe vaginal anaerobic dysbiosis while planning cesarean section.

Background Rheumatoid arthritis (RA) is a systemic progressive destructive joint disease with an increased risk for co-morbidity and premature death if untreated. Cardiovascular disease (CVD) is the main cause of death but also other co-morbid conditions contribute to the patient’s shorter life expectancy. Inflammation is important for the development of CVD, but knowledge of its relationship with other co-morbidities is sparse. Early disease modifying anti rheumatic drugs (DMARDs) can suppress disease activity and improve the long-term outcome. The aim of this thesis was to evaluate prospectively aspects of disease activity and severity in a large cohort of patients with early RA. Predictive and prognostic markers, e.g., antibodies against citrullinated proteins/peptides (ACPAs), occurring in early disease and with implications for disease outcome and co-morbidity were evaluated. Methods Patients with early RA (i.e., symptomatic for ≤12 months) have, since December 1995, been consecutively included in a large survey of prospective and observational studies on the progression of RA and the development of co-omorbidity. Autoantibodies, inflammatory, genetic markers and radiographs have been analyzed. In paper I, 210 RA patients and 102 controls were followed regularly for two years. The predictive value of four different ACPAs in relation to disease activity and radiological progression was evaluated. In Paper II (n = 700) and in Papers III-IV (n =950), patients with early RA from the four northern-most counties of Sweden were followed regularly for 5 years. Data on risk factors and co-morbidity was collected, according to the study protocol, from clinical records and self-reported questionnaires from patients at inclusion into the study cohort and after five years. The predictive value of traditional and potential disease related risk factors for new cardiovascular events (CVE) was evaluated (II). In Paper III, the impact of age at the onset RA, stratified as being

Background Rheumatoid arthritis (RA) is a systemic progressive destructive joint disease with an increased risk for co-morbidity and premature death if untreated. Cardiovascular disease (CVD) is the main cause of death but also other co-morbid conditions contribute to the patient’s shorter life expectancy. Inflammation is important for the development of CVD, but knowledge of its relationship with other co-morbidities is sparse. Early disease modifying anti rheumatic drugs (DMARDs) can suppress disease activity and improve the long-term outcome. The aim of this thesis was to evaluate prospectively aspects of disease activity and severity in a large cohort of patients with early RA. Predictive and prognostic markers, e.g., antibodies against citrullinated proteins/peptides (ACPAs), occurring in early disease and with implications for disease outcome and co-morbidity were evaluated. Methods Patients with early RA (i.e., symptomatic for ≤12 months) have, since December 1995, been consecutively included in a large survey of prospective and observational studies on the progression of RA and the development of co-omorbidity. Autoantibodies, inflammatory, genetic markers and radiographs have been analyzed. In paper I, 210 RA patients and 102 controls were followed regularly for two years. The predictive value of four different ACPAs in relation to disease activity and radiological progression was evaluated. In Paper II (n = 700) and in Papers III-IV (n =950), patients with early RA from the four northern-most counties of Sweden were followed regularly for 5 years. Data on risk factors and co-morbidity was collected, according to the study protocol, from clinical records and self-reported questionnaires from patients at inclusion into the study cohort and after five years. The predictive value of traditional and potential disease related risk factors for new cardiovascular events (CVE) was evaluated (II). In Paper III, the impact of age at the onset RA, stratified as being

Background Rheumatoid arthritis (RA) is a systemic progressive destructive joint disease with an increased risk for co-morbidity and premature death if untreated. Cardiovascular disease (CVD) is the main cause of death but also other co-morbid conditions contribute to the patient’s shorter life expectancy. Inflammation is important for the development of CVD, but knowledge of its relationship with other co-morbidities is sparse. Early disease modifying anti rheumatic drugs (DMARDs) can suppress disease activity and improve the long-term outcome. The aim of this thesis was to evaluate prospectively aspects of disease activity and severity in a large cohort of patients with early RA. Predictive and prognostic markers, e.g., antibodies against citrullinated proteins/peptides (ACPAs), occurring in early disease and with implications for disease outcome and co-morbidity were evaluated. Methods Patients with early RA (i.e., symptomatic for ≤12 months) have, since December 1995, been consecutively included in a large survey of prospective and observational studies on the progression of RA and the development of co-omorbidity. Autoantibodies, inflammatory, genetic markers and radiographs have been analyzed. In paper I, 210 RA patients and 102 controls were followed regularly for two years. The predictive value of four different ACPAs in relation to disease activity and radiological progression was evaluated. In Paper II (n = 700) and in Papers III-IV (n =950), patients with early RA from the four northern-most counties of Sweden were followed regularly for 5 years. Data on risk factors and co-morbidity was collected, according to the study protocol, from clinical records and self-reported questionnaires from patients at inclusion into the study cohort and after five years. The predictive value of traditional and potential disease related risk factors for new cardiovascular events (CVE) was evaluated (II). In Paper III, the impact of age at the onset RA, stratified as being

Background Rheumatoid arthritis (RA) is a systemic progressive destructive joint disease with an increased risk for co-morbidity and premature death if untreated. Cardiovascular disease (CVD) is the main cause of death but also other co-morbid conditions contribute to the patient’s shorter life expectancy. Inflammation is important for the development of CVD, but knowledge of its relationship with other co-morbidities is sparse. Early disease modifying anti rheumatic drugs (DMARDs) can suppress disease activity and improve the long-term outcome. The aim of this thesis was to evaluate prospectively aspects of disease activity and severity in a large cohort of patients with early RA. Predictive and prognostic markers, e.g., antibodies against citrullinated proteins/peptides (ACPAs), occurring in early disease and with implications for disease outcome and co-morbidity were evaluated. Methods Patients with early RA (i.e., symptomatic for ≤12 months) have, since December 1995, been consecutively included in a large survey of prospective and observational studies on the progression of RA and the development of co-omorbidity. Autoantibodies, inflammatory, genetic markers and radiographs have been analyzed. In paper I, 210 RA patients and 102 controls were followed regularly for two years. The predictive value of four different ACPAs in relation to disease activity and radiological progression was evaluated. In Paper II (n = 700) and in Papers III-IV (n =950), patients with early RA from the four northern-most counties of Sweden were followed regularly for 5 years. Data on risk factors and co-morbidity was collected, according to the study protocol, from clinical records and self-reported questionnaires from patients at inclusion into the study cohort and after five years. The predictive value of traditional and potential disease related risk factors for new cardiovascular events (CVE) was evaluated (II). In Paper III, the impact of age at the onset RA, stratified as being

Background Rheumatoid arthritis (RA) is a systemic progressive destructive joint disease with an increased risk for co-morbidity and premature death if untreated. Cardiovascular disease (CVD) is the main cause of death but also other co-morbid conditions contribute to the patient’s shorter life expectancy. Inflammation is important for the development of CVD, but knowledge of its relationship with other co-morbidities is sparse. Early disease modifying anti rheumatic drugs (DMARDs) can suppress disease activity and improve the long-term outcome. The aim of this thesis was to evaluate prospectively aspects of disease activity and severity in a large cohort of patients with early RA. Predictive and prognostic markers, e.g., antibodies against citrullinated proteins/peptides (ACPAs), occurring in early disease and with implications for disease outcome and co-morbidity were evaluated. Methods Patients with early RA (i.e., symptomatic for ≤12 months) have, since December 1995, been consecutively included in a large survey of prospective and observational studies on the progression of RA and the development of co-omorbidity. Autoantibodies, inflammatory, genetic markers and radiographs have been analyzed. In paper I, 210 RA patients and 102 controls were followed regularly for two years. The predictive value of four different ACPAs in relation to disease activity and radiological progression was evaluated. In Paper II (n = 700) and in Papers III-IV (n =950), patients with early RA from the four northern-most counties of Sweden were followed regularly for 5 years. Data on risk factors and co-morbidity was collected, according to the study protocol, from clinical records and self-reported questionnaires from patients at inclusion into the study cohort and after five years. The predictive value of traditional and potential disease related risk factors for new cardiovascular events (CVE) was evaluated (II). In Paper III, the impact of age at the onset RA, stratified as being

Health technology assessment (HTA) is a potential multidisciplinary tool for decision-making in healthcare policy. Scientific evidences for HTA processes usually come from randomized clinical trials (RCTs), which are the gold standard, but observational studies can be used to overcome study design limitations of RCTs. Nowadays, the use of healthcare administrative databases (HADs) in HTA is not widespread, despite their apparent utility. The objective of this work was to use HADs to conduct a cost-effectiveness evaluation of a pharmacological therapy under real world adherence to treatment. We analyzed the case of statin therapy in the secondary prevention of acute myocardial infarction (AMI). Data were derived from HADs of the healthcare authority of Lombardy, a region in Northern Italy. Patients hospitalized for a first event of AMI in the year 2003 were followed until the 31st December 2008, collecting data on healthcare services and vital status. We used regression methods to estimate the incremental net benefit of treatment or of adherence levels to treatment. HADs provide a rich source of information but the analysis must account for the correlation between repeated measures of the same subject, possible selection bias and endogeneity of the data. In this situation classical regression methods are not appropriate, so we applied marginal structural models (MSMs) to the health economics framework. The cost-effectiveness analysis of statin treatment in the secondary prevention of AMI confirms that statins are cost-effective while the analysis of adherence to treatment needs further assessments. The implementation of MSMs could be a future tool in economic healthcare evaluations, because MSMs make possible to account for time-varying confounding and selection bias typical of longitudinal observational studies. In this way the use of data from HADs or from observational studies could become more reliable., 1863, open, open, Fornari, Fornari, C

Epidermolysis bullosa simplex (EBS) and epidermolytic ichthyosis (EI) are rare skin fragility diseases characterized by intra-epidermal blistering due to autosomal dominant-negative mutations in basal (KRT5 or KRT14) and suprabasal (KRT1 or KRT10) keratin genes, respectively. Despite vast knowledge in the disease pathogenesis, the pathomechanisms are not fully understood, and no effective remedies exist. The purpose of this work was to search for keratin gene mutations in EBS patients, to develop in vitro models for studying EBS and EI, and to investigate novel pharmacological approaches for both diseases. We identified both novel and recurrent KRT5 mutations in all studied EBS patients but one which did not show any pathogenic keratin mutations. Using cultured primary keratinocytes from EBS patients, we reproduced a correlation between clinical severity and cytoskeletal instability in vitro. Immortalized keratinocyte cell lines were established from three EBS and three EI patients with different phenotypes using HPV16-E6E7. Only cell lines derived from severely affected patients exhibited spontaneous keratin aggregates under normal culture conditions. However, heat stress significantly induced keratin aggregates in all patient cell lines. This effect was more dramatic in cells from patients with a severe phenotype. In organotypic cultures, the immortalized cells were able to differentiate and form a multilayered epidermis reminiscent of those observed in vivo. Addition of two molecular chaperones, trimethylamine N-oxide dihydrate (TMAO) and sodium 4-phenylbutyrate (4-PBA), reduced the keratin aggregates in both stressed and unstressed EBS and EI keratinocytes, respectively. The mechanism of action of TMAO and 4-PBA was shown to involve the endogenous chaperone system (Heat shock proteins e.g. Hsp70). Besides, MAPK signaling pathways also seemed to be incriminated in the pathogenesis of EBS. Furthermore, depending on which type of keratin is mutated, 4-PBA up-regul

Epidermolysis bullosa simplex (EBS) and epidermolytic ichthyosis (EI) are rare skin fragility diseases characterized by intra-epidermal blistering due to autosomal dominant-negative mutations in basal (KRT5 or KRT14) and suprabasal (KRT1 or KRT10) keratin genes, respectively. Despite vast knowledge in the disease pathogenesis, the pathomechanisms are not fully understood, and no effective remedies exist. The purpose of this work was to search for keratin gene mutations in EBS patients, to develop in vitro models for studying EBS and EI, and to investigate novel pharmacological approaches for both diseases. We identified both novel and recurrent KRT5 mutations in all studied EBS patients but one which did not show any pathogenic keratin mutations. Using cultured primary keratinocytes from EBS patients, we reproduced a correlation between clinical severity and cytoskeletal instability in vitro. Immortalized keratinocyte cell lines were established from three EBS and three EI patients with different phenotypes using HPV16-E6E7. Only cell lines derived from severely affected patients exhibited spontaneous keratin aggregates under normal culture conditions. However, heat stress significantly induced keratin aggregates in all patient cell lines. This effect was more dramatic in cells from patients with a severe phenotype. In organotypic cultures, the immortalized cells were able to differentiate and form a multilayered epidermis reminiscent of those observed in vivo. Addition of two molecular chaperones, trimethylamine N-oxide dihydrate (TMAO) and sodium 4-phenylbutyrate (4-PBA), reduced the keratin aggregates in both stressed and unstressed EBS and EI keratinocytes, respectively. The mechanism of action of TMAO and 4-PBA was shown to involve the endogenous chaperone system (Heat shock proteins e.g. Hsp70). Besides, MAPK signaling pathways also seemed to be incriminated in the pathogenesis of EBS. Furthermore, depending on which type of keratin is mutated, 4-PBA up-regul

Epidermolysis bullosa simplex (EBS) and epidermolytic ichthyosis (EI) are rare skin fragility diseases characterized by intra-epidermal blistering due to autosomal dominant-negative mutations in basal (KRT5 or KRT14) and suprabasal (KRT1 or KRT10) keratin genes, respectively. Despite vast knowledge in the disease pathogenesis, the pathomechanisms are not fully understood, and no effective remedies exist. The purpose of this work was to search for keratin gene mutations in EBS patients, to develop in vitro models for studying EBS and EI, and to investigate novel pharmacological approaches for both diseases. We identified both novel and recurrent KRT5 mutations in all studied EBS patients but one which did not show any pathogenic keratin mutations. Using cultured primary keratinocytes from EBS patients, we reproduced a correlation between clinical severity and cytoskeletal instability in vitro. Immortalized keratinocyte cell lines were established from three EBS and three EI patients with different phenotypes using HPV16-E6E7. Only cell lines derived from severely affected patients exhibited spontaneous keratin aggregates under normal culture conditions. However, heat stress significantly induced keratin aggregates in all patient cell lines. This effect was more dramatic in cells from patients with a severe phenotype. In organotypic cultures, the immortalized cells were able to differentiate and form a multilayered epidermis reminiscent of those observed in vivo. Addition of two molecular chaperones, trimethylamine N-oxide dihydrate (TMAO) and sodium 4-phenylbutyrate (4-PBA), reduced the keratin aggregates in both stressed and unstressed EBS and EI keratinocytes, respectively. The mechanism of action of TMAO and 4-PBA was shown to involve the endogenous chaperone system (Heat shock proteins e.g. Hsp70). Besides, MAPK signaling pathways also seemed to be incriminated in the pathogenesis of EBS. Furthermore, depending on which type of keratin is mutated, 4-PBA up-regul

Epidermolysis bullosa simplex (EBS) and epidermolytic ichthyosis (EI) are rare skin fragility diseases characterized by intra-epidermal blistering due to autosomal dominant-negative mutations in basal (KRT5 or KRT14) and suprabasal (KRT1 or KRT10) keratin genes, respectively. Despite vast knowledge in the disease pathogenesis, the pathomechanisms are not fully understood, and no effective remedies exist. The purpose of this work was to search for keratin gene mutations in EBS patients, to develop in vitro models for studying EBS and EI, and to investigate novel pharmacological approaches for both diseases. We identified both novel and recurrent KRT5 mutations in all studied EBS patients but one which did not show any pathogenic keratin mutations. Using cultured primary keratinocytes from EBS patients, we reproduced a correlation between clinical severity and cytoskeletal instability in vitro. Immortalized keratinocyte cell lines were established from three EBS and three EI patients with different phenotypes using HPV16-E6E7. Only cell lines derived from severely affected patients exhibited spontaneous keratin aggregates under normal culture conditions. However, heat stress significantly induced keratin aggregates in all patient cell lines. This effect was more dramatic in cells from patients with a severe phenotype. In organotypic cultures, the immortalized cells were able to differentiate and form a multilayered epidermis reminiscent of those observed in vivo. Addition of two molecular chaperones, trimethylamine N-oxide dihydrate (TMAO) and sodium 4-phenylbutyrate (4-PBA), reduced the keratin aggregates in both stressed and unstressed EBS and EI keratinocytes, respectively. The mechanism of action of TMAO and 4-PBA was shown to involve the endogenous chaperone system (Heat shock proteins e.g. Hsp70). Besides, MAPK signaling pathways also seemed to be incriminated in the pathogenesis of EBS. Furthermore, depending on which type of keratin is mutated, 4-PBA up-regul

Some studies have raised the question of the need for chronic controller therapy in mild persistent asthma as suggested by international guidelines. Although the Improving Asthma Control (IMPACT) and Beclomethasone plus Salbutamol (BEST) studies suggest that on-demand therapy in some patients with mild persistent asthma achieves a similar degree of asthma control based on symptoms and functional outcomes, the IMPACT study indicates that regular and on-demand therapy is not equivalent for controlling airway inflammation. Persistent airway inflammation might lead to airway remodelling with onset or worsening of symptoms, deterioration in lung function, and reduced response to pharmacological therapy. However, the relationships between chronic airway inflammation and airway remodelling need to be clarified. Choosing the ‘right’ pharmacological strategy (regular versus on-demand treatment) for asthma control is currently difficult due to the fact that (1) inflammatory outcome measures were not generally incorporated into asthma clinical trials; (2) the relationships between chronic airway inflammation and airway remodelling are largely unknown; (3) current clinical asthma trials that are generally based on symptomatic and functional outcome measures are too short to assess the impact of regular anti-inflammatory therapy on natural history of asthma; (4) asthma is an heterogeneous disease and different phenotypes of asthma patients likely requiring a different therapeutic approach can be identified, even in the same class of asthma severity. Guidelines for asthma management are valuable tools, although they are necessarily based on a strategy directed to the best outcome in a group of patients. Asthma phenotyping is becoming central for asthma management. The issue of regular versus on-demand treatment of intermittent and mild persistent asthma would be better addressed if considered within an individualized approach to asthma management and assessment. Identification of

Heart Failure (HF) is a prevalent syndrome in the elderly due to the aging of the population and the improvement in the life expectancy in people with cardiovascular diseases. Aim: To assess the clinical characteristics and the quality of care in elderly patients admitted for heart failure to the Hospital Clínico de la Pontificia Universidad Católica de Chile, from 2002 to 2006. Results: 71% (n=130) of the patients has over 65 y.o. The mean age 76±7.3 y.o. 60% are men. Ethiology for HF: 30% ischemic; hypertension: 27%. A 71.5% (n=93) of the elderly patients has HTN as a concomitant disease. The FC NHYA at admission, is 50% FC III and 36.9% FC IV. Echocardiogram: EF 33.2±13 % vs 27.7±11.6% in the younger patients (p=0.093), DD=60.3±10 mm; DS=47.2±11 mm vs DD=67.3±11.4 mm, DS=55±13 mm (p=0.001). Among elderly patients, the leading contribuiting cause for readmission was infection (29.2%), followed by the progression of the disease (19.2%). No compliance to treatment caused 13.8% of readmissions. Conclusions: In our centre, the patients with heart failure are predominantly elderly, being the infections the main cause of decompesation. The elderly patients had smaller ventricular diameters and has a long-term mortality similar to younger patients., La insuficiencia cardiaca (IC) es una entidad clínica de elevada prevalencia e incidencia entre los adultos mayores (AM) resultante del proceso de envejecimiento de la población y la simultanea mejoría en la expectativa de vida en personas con enfermedades cardíacas. Objetivo: Identificar las características clínicas y de la calidad del cuidado en la población de insuficientes cardiacos AM ingresados al Hospital Clínico de la Pontificia Universidad Católica de Chile durante los años 2002-2006. Resultados: Un 71% (n=130) de la población con IC evaluados, corresponde a mayores de 65 años. La edad promedio es de 76±7.3 años. 60% son hombres. La etiología para IC es en un 30% isquémica; e hipertensiva en un 27%. El 71.5% (n=93) de los pacientes AM presenta HTA como enfermedad concomitante. La CF NHYA al ingreso, en un 50% de los casos es III y en un 36.9% es IV. Ecocardiograma: FE promedio de 33.2±13 % vs 27.7±11.6% en la población más joven (p=0.093), DD=60.3±10 mm; DS=47.2±11 mm vs DD=67.3±11.4 mm, DS=55±13 mm (p=0.001). Entre los AM la causa predominante para rehospitalización es infecciosa en un 29.2%, seguido por la progresión de la enfermedad de base (19.2%).La no adherencia a tratamiento contribuye en un 13.8% a la descompensación. Conclusiones: En nuestro centro la población de pacientes con IC es predominantemente adulta mayor, siendo las infecciones respiratorias la principal causa de descompensación en este grupo. Presentaron diámetros ventriculares menores. Existe una mortalidad alejada similar a la de los pacientes más jóvenes.

Heart Failure (HF) is a prevalent syndrome in the elderly due to the aging of the population and the improvement in the life expectancy in people with cardiovascular diseases. Aim: To assess the clinical characteristics and the quality of care in elderly patients admitted for heart failure to the Hospital Clínico de la Pontificia Universidad Católica de Chile, from 2002 to 2006. Results: 71% (n=130) of the patients has over 65 y.o. The mean age 76±7.3 y.o. 60% are men. Ethiology for HF: 30% ischemic; hypertension: 27%. A 71.5% (n=93) of the elderly patients has HTN as a concomitant disease. The FC NHYA at admission, is 50% FC III and 36.9% FC IV. Echocardiogram: EF 33.2±13 % vs 27.7±11.6% in the younger patients (p=0.093), DD=60.3±10 mm; DS=47.2±11 mm vs DD=67.3±11.4 mm, DS=55±13 mm (p=0.001). Among elderly patients, the leading contribuiting cause for readmission was infection (29.2%), followed by the progression of the disease (19.2%). No compliance to treatment caused 13.8% of readmissions. Conclusions: In our centre, the patients with heart failure are predominantly elderly, being the infections the main cause of decompesation. The elderly patients had smaller ventricular diameters and has a long-term mortality similar to younger patients., La insuficiencia cardiaca (IC) es una entidad clínica de elevada prevalencia e incidencia entre los adultos mayores (AM) resultante del proceso de envejecimiento de la población y la simultanea mejoría en la expectativa de vida en personas con enfermedades cardíacas. Objetivo: Identificar las características clínicas y de la calidad del cuidado en la población de insuficientes cardiacos AM ingresados al Hospital Clínico de la Pontificia Universidad Católica de Chile durante los años 2002-2006. Resultados: Un 71% (n=130) de la población con IC evaluados, corresponde a mayores de 65 años. La edad promedio es de 76±7.3 años. 60% son hombres. La etiología para IC es en un 30% isquémica; e hipertensiva en un 27%. El 71.5% (n=93) de los pacientes AM presenta HTA como enfermedad concomitante. La CF NHYA al ingreso, en un 50% de los casos es III y en un 36.9% es IV. Ecocardiograma: FE promedio de 33.2±13 % vs 27.7±11.6% en la población más joven (p=0.093), DD=60.3±10 mm; DS=47.2±11 mm vs DD=67.3±11.4 mm, DS=55±13 mm (p=0.001). Entre los AM la causa predominante para rehospitalización es infecciosa en un 29.2%, seguido por la progresión de la enfermedad de base (19.2%).La no adherencia a tratamiento contribuye en un 13.8% a la descompensación. Conclusiones: En nuestro centro la población de pacientes con IC es predominantemente adulta mayor, siendo las infecciones respiratorias la principal causa de descompensación en este grupo. Presentaron diámetros ventriculares menores. Existe una mortalidad alejada similar a la de los pacientes más jóvenes.

Excessive cellular proliferation contributes to the pathobiology of vascular obstructive diseases (e.g., atherosclerosis, in-stent restenosis, transplant vasculopathy, and vessel bypass graft failure). Therefore, anti-proliferative therapies may be a suitable approach in the treatment of these disorders. Candidate targets for such strategies include the cyclin-dependent kinase / cyclin holoenzymes, members of the cyclin-dependent kinase family of inhibitory proteins, tumor suppressors, growth factors and transcription factors that control cell cycle progression. In this review, we will discuss the use of pharmacological agents and gene therapy approaches targeting cellular proliferation in animal models and clinical trials of cardiovascular disease.

Excessive cell proliferation is thought to contribute to the development of neointimal lesions during the pathogenesis of atherosclerosis, restenosis and vessel bypass graft failure. Since cell cycle progression requires the sequential activation of cyclin-dependent kinases (CDKs), through their association with regulatory subunits dubbed cyclins, therapeutic strategies via CDK inhibition may reduce the burden of vascular proliferative disease. Some of these approaches may rely on the use of pharmacological CDK inhibitors that target the ATP-binding pocket of the catalytic site of CDK. Others are based on the overexpression of members of the family of CDK inhibitory proteins (CKIs), which associate with and inhibit the activity of CDK/cyclin holoenzymes. In this review, animal studies that document the efficacy of pharmacological agents and gene therapy approaches directly targeting CDK/cyclins for the treatment of vascular proliferative disease are discussed. Recent patent applications in this field are also analysed.