FGF23 as a Potential Pathophysiological Factor in Peripheral Arterial Disease Associated with Chronic Kidney Disease.

Fibroblast growth factor 23 (FGF23) levels are often elevated in chronic kidney disease (CKD). FGF23 and inflammation are common characteristics in CKD, and both are associated with worse disease progression and the occurrence of complications. The existence of an interaction between FGF23 and inflammation has been suggested, each of which influences the expression and activity of the other, leading to a vicious feedback loop with adverse outcomes, including cardiovascular disease and mortality. In this work, we determined circulating FGF23 levels in a group of patients with CKD stages 3 and 4 subjected to elective femoral endarterectomy due to established peripheral artery disease (PAD), a condition resulting from an athero-inflammatory process, and we studied its associations with different inflammatory markers and mediators. We evaluated its association with serum tumor necrosis factor (TNF)α, interleukin (IL) 6, and IL10, as well as with the gene expression levels of these parameters and A disintegrin and metalloproteinase domain-containing protein (ADAM) 17 in femoral vascular tissue and peripheral blood circulating cells (PBCCs). We also analyzed its association with serum concentrations of C-reactive protein (CRP), the systemic immune inflammation index (SII), and the neutrophil-to-lymphocyte ratio (NLR). Finally, we determined the vascular immunoreactivity of protein TNFα in a subgroup of patients. FGF23 concentrations were independently associated with circulating and PBCC mRNA levels of TNFα. Worst kidney function and diabetes were also found to be contributing to FGF23 levels. Patients with higher levels of FGF23 also had greater vascular immunoreactivity for TNFα.

Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease.

Cardiovascular disease is the leading cause of death worldwide. New therapeutic strategies are aimed to modulate the athero-inflammatory process that partially orchestrates underlying vascular damage. Peripheral blood circulating cells include different immune cells with a central role in the development of the atherogenic inflammatory response. The anti-aging protein α-Klotho has been related to protective effects against CVD. KL is expressed in monocytes, macrophages, and lymphocytes where it exerts anti-inflammatory effects. In this work, we analyse the relationships of the levels of inflammatory markers with the expression of the KL gene in PBCCs and with the serum levels of soluble KL in atherosclerotic vascular disease. For this, we conducted a cross-sectional single-center case-control study including a study group of 76 CVD patients and a control group of 16 cadaveric organ donors without medical antecedent or study indicating CVD. Vascular artery fragments and whole blood and serum samples were obtained during elective or organ retrieval surgery. Serum levels of sKL, TNFα and IL10, and gene expression levels of KL, TNF, IL10, NFKB1, DNMT1, and DNMT3A in PBCCs were measured. In these cells, we also determined KL promoter methylation percentage. Histological and immunohistochemical analyses were employed to visualize atherosclerotic lesions and to measure IL10 and TNFα levels in vascular fragments. Patients with CVD presented higher values of proinflammatory markers both at systemic and in the vasculature and in the PBCCs, compared to the control group. In PBCCs, CVD patients also presented lower gene expression levels of KL gene (56.4% difference, P < 0.001), higher gene expression levels of DNMT1 and DNMT3A (P < 0.0001, for both) and a higher methylation status of in the promoter region of KL (34.1 ± 4.1% vs. 14.6 ± 3.4%, P < 0.01). In PBCCs and vasculature, KL gene expression correlated inversely with pro-inflammatory markers and directly with anti-inflammatory markers. sKL serum levels presented similar associations with the expression levels of pro- and anti-inflammatory markers in PBCCs. The differences in KL expression levels in PBCCs and in serum sKL levels with respect to control group was even greater in those CVD patients with macroscopically observable atheromatous plaques. We conclude that promoter methylation-mediated downregulation of KL gene expression in PBCCs is associated with the pro-inflammatory status in atherosclerotic vascular disease.

Effectiveness and safety of PCSK9 inhibitors in real-world clinical practice. An observational multicentre study. The IRIS-PCSK9I study.

Background and aims: The benefits of the PCSK9 inhibitors, alirocumab and evolocumab, in lowering LDL-cholesterol and preventing major adverse cardiac events (MACE) have been demonstrated in pivotal clinical trials. However, few studies of routine clinical practice have been conducted to analyse and compare the efficacy and safety of the two drugs. Methods: Retrospective observational study of patients treated with a PCSK9 inhibitor in five hospitals in Andalusia (southern Spain). Baseline demographic and clinical data, LDL-cholesterol levels and the occurrence of MACEs during the follow-up period were recorded. Results: A total of 141 patients were included in the study: 90 were treated with alirocumab and 51 with evolocumab. The patients' mean age (IQR) was 58 (11) years and 58 (41%) were women. The most frequent concomitant medications were statins, 94 (66.7%), followed by antiplatelet therapy (66%) and ezetimibe (65.2%). The median (IQR) follow-up period was 18 (18) months, with 18 (24) for alirocumab and 11 (18) for evolocumab. At the six-month follow-up visit, LDL-cholesterol values had decreased to pre-treatment levels and remained significantly decreased (p < 0.05) over time, for both drugs, and a greater reduction was achieved in patients with established cardiovascular disease and concomitant treatment with statins. With respect to adverse effects, there were nine MACEs (6.4%), of which seven were with alirocumab (7.8%) and two with evolocumab (3.9%) (p NS). Other adverse effects (9.2%) included local erythema (3.5%), muscle cramps (2.1%), respiratory symptoms (2.1%) and asthaenia (1.4%). Conclusions: The efficacy and safety of alirocumab and evolocumab in routine clinical practice are consistent with the findings of the pivotal clinical trials.

Association between serum levels of Klotho and inflammatory cytokines in cardiovascular disease: a case-control study.

Decrease in soluble anti-aging Klotho protein levels is associated to cardiovascular disease (CVD). Diverse studies have shown a bidirectional relationship between Klotho and inflammation, a risk factor for the development of CVD. In this work we aimed to evaluate the association between Klotho and inflammatory cytokines levels in the context of human CVD.The study included 110 patients with established CVD and preserved renal function, and a control group of 22 individuals without previous history of cardiovascular events. Serum Klotho and IL10 levels were significantly lower in the CVD group. Inflammatory status, marked by the TNFα/IL10 ratio and the C-reactive protein (CRP) levels, was significantly increased in the group of patients with established CVD. Soluble Klotho levels were directly correlated with eGFR (r=0.217) and IL10 (r=0.209) and inversely correlated with age (r=-0.261), CRP (r=-0.203), and TNFα/IL10 (r=-0.219). This association with TNFα/IL10 remained significant in age-matched subgroups. Multiple logistic regression analysis showed that age, smoking and the neutrophil-to-lymphocyte ratio (NLR) constituted risk factors for the presence of CVD, while Klotho was a protective factor.In conclusion, in patients with established CVD, the reduction in soluble Klotho is associated with a pro-inflammatory status marked by lower IL10 concentrations and higher TNFα/IL10 ratio and CRP levels.

Fibroblast growth factor 23 expression in human calcified vascular tissues.

Vascular calcification is a major risk for cardiovascular disease and implies the transformation of smooth muscle cells to an osteoblastic phenotype as a consequence of dysregulation of calcium and phosphate metabolism. Fibroblast growth factor (FGF) 23 is the most potent phosphate regulator. Observational studies suggest that high levels of FGF23 are related to cardiovascular morbidity and mortality. In this work, we determined the levels of both the intact and the carboxi-terminal fragments of circulating FGF23 in 133 patients with established cardiovascular disease, the expression of FGF23, its receptors 1 and 3, and its co-receptor Klotho in vascular fragments of aorta, carotid and femoral in 43 out of this group of patients, and in a control group of 20 organ donors. Patients with atherosclerosis and vascular calcification presented increased levels of FGF23 respect to the control group. Vascular immunoreactivity for FGF23 was also significantly increased in patients with vascular calcification as compared to patients without calcification and to controls. Finally, gene expression of FGF23 and RUNX2 were also higher and directly related in vascular samples with calcification. Conversely, expression of Klotho was reduced in patients with cardiovascular disease when comparing to controls. In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone.

Association Between Medication Adherence and Oxidative Stress in Patients With First-Episode Mania.

Poor adherence is a major problem in patients with manic episodes that impairs functionality and has unknown effects on oxidative stress. The objective of this study was to analyze the relationship between adherence to medication, severity of symptoms and oxidative stress in a sample of patients with a first episode of mania. A longitudinal, 6-month study was performed in 60 patients, who were classified as adherent and non-adherent to medication (mainly antipsychotics). Blood levels of oxidative stress parameters and expression of the antioxidant nuclear transcription factor NRF2 in mononuclear cells of peripheral blood were assessed at baseline and at the end of follow-up. In addition, clinical symptoms and functioning were evaluated. Linear multivariate regression was used to determine the relationship between adherence, oxidative stress, and clinical symptoms. Finally, 44 patients completed follow-up. The results of this study showed that at 6-month follow-up, adherence was significantly associated with better functioning and reduced clinical symptoms. Additionally, more severe symptoms were associated with increased levels of oxidative stress and antioxidant parameters. At study completion, non-adherents exhibited greater levels of antioxidants than adherent patients. In conclusion, poor adherence to medication is associated with a poorer prognosis in the medium term and causes increased antioxidant response.

FGF23 and Klotho Levels are Independently Associated with Diabetic Foot Syndrome in Type 2 Diabetes Mellitus.

BACKGROUND: Diabetic foot syndrome (DFS) is a prevalent complication in the diabetic population and a major cause of hospitalizations. Diverse clinical studies have related alterations in the system formed by fibroblast growth factor (FGF)-23 and Klotho (KL) with vascular damage. In this proof-of-concept study, we hypothesize that the levels of FGF23 and Klotho are altered in DFS patients. METHODS: Twenty patients with limb amputation due to DFS, 37 diabetic patients without DFS, and 12 non-diabetic cadaveric organ donors were included in the study. Serum FGF23/Klotho and inflammatory markers were measured by enzyme-linked immunosorbent assay (ELISA). Protein and gene expression levels in the vascular samples were determined by immunohistochemistry and quantitative real-time PCR, respectively. RESULTS: Serum Klotho is significantly reduced and FGF23 is significantly increased in patients with DFS (p < 0.01). Vascular immunoreactivity and gene expression levels for Klotho were decreased in patients with DFS (p < 0.01). Soluble Klotho was inversely related to serum C-reactive protein (r = -0.30, p < 0.05). Vascular immunoreactivities for Klotho and IL6 showed an inverse association (r = -0.29, p < 0.04). Similarly, vascular gene expression of KL and IL6 were inversely associated (r = -0.31, p < 0.05). Logistic regression analysis showed that higher Klotho serum concentrations and vascular gene expression levels were related to a lower risk of DFS, while higher serum FGF23 was associated with a higher risk for this complication. CONCLUSION: FGF23/Klotho system is associated with DFS, pointing to a new pathophysiological pathway involved in the development and progression of this complication.

Overdosing of benzodiazepines/Z-drugs and falls in older adults: Costs for the health system.

INTRODUCTION: Benzodiazepines and Z drugs (BZD/Z drugs) are commonly used for the treatment of insomnia and anxiety in older adults for long periods of time. Given the physiological and metabolic characteristics of this group of patients, they are more prone to the adverse effects of these drugs which include falls. The recommendations for use of BZD/Z drugs include the need to adjust the dose and select those with a short half-life, to avoid adverse events, which as well as potentially affecting patient outcome, increase healthcare costs. In this study, we have evaluated the hospital-related costs associated with falls in older adults who use BZD/Z drugs at doses higher than recommended for this age group. METHODS: We conducted a cross-sectional observational study assessing the BZD/Z drug prescriptions of older adults attending the emergency department after a fall. Cost analysis was performed for cases in which the prescriptions exceeded the maximum recommended dose for this age group. RESULTS: A total of 40.6% of the prescriptions recorded were higher than the defined daily dose in older adults (DDDolderadults). Of the 57 patients who used BZD/Z drugs at higher-than-recommended doses, 53 experienced trauma and 33 required hospitalisation. The costs associated with emergency department services, tests performed and hospitalisation amounted to €1850/patient. CONCLUSIONS: Appropriate dosage of BZD/Z drugs in older adults could reduce both patient suffering and costs for the health system.

Prescripción de benzodiacepinas y caídas en mujeres y hombres ancianos / Benzodiazepine prescriptions and falls in older men and women

Objetivo. A pesar de las advertencias de numerosas asociaciones profesionales, las benzodiacepinas (BZD) y los hipnóticos Z (Z) son ampliamente prescritos a los ancianos ya que son especialmente susceptibles de padecer insomnio y ansiedad, pero a su vez resultan especialmente sensibles a la aparición de efectos secundarios a dichos medicamentos. En este estudio evaluamos la prescripción de BZD/Z en una muestra de ancianos (≥65) que se presentan en el servicio de urgencias de un hospital por haber sufrido una caída. Métodos. Recogimos información del tipo, número y dosis de los fármacos BZD/Z prescritos y exploramos la presencia de diferencias de género en dicha prescripción. Resultados. Las BZD/Z habían sido prescritas a un 43,6% de la muestra (n=654), más frecuentemente a las mujeres. El 78,4% de las prescripciones fueron de BZD/Z de vida media corta. La mayoría de los pacientes (83,5%) tomaban solamente un fármaco BZD/Z, pero un 16,5% consumían más de una BZD/Z, sin diferencias de género. Un 58% de los pacientes consumían dosis de BZD/Z más elevadas que las recomendadas para ancianos, siendo la proporción significativamente más elevada para los hombres (70% vs. 53,1%). Conclusiones. Alrededor de un 40% de los ancianos que acuden a un servicio de urgencias por haber sufrido una caída se encontraban tomando BZD/Z. Hemos hallado algunas diferencias de género en la prescripción de BZD/Z, especialmente en la prescripción por encima de la dosis recomendada para ancianos y de fármacos de vida media larga (AU)

Objective. Despite cautions by professional associations, benzodiazepines (BZD) and Z hypnotics (BZD/Z) are widely prescribed to older adults who are particularly susceptible to insomnia and anxiety, but who are also more sensitive to drugs adverse events. In this study, we assessed the prescription of BZD/Z drugs in a sample of older adults (≥65) who presented for emergency care after a fall. Methods. We collected the type, number and dose of BZD/Z drugs prescribed and explored gender differences in the prescription. Results. BZD/Z drugs were prescribed to 43.6% of the sample (n=654) and more frequently to women; 78.4% of prescriptions were for BZD/Z drugs with a short half-life. The majority of patients (83.5%) were prescribed only one type of BZD/Z, but 16.5% had been prescribed multiple BZD/Z drugs, with no gender difference. Doses higher than those recommended for older adults were prescribed to 58% of patients, being the doses significantly higher for men compared to women (70.0% vs 53.1%). Conclusions. Over 40% of older adults presenting for emergency care after a fall had previously been prescribed BZD/Z drugs. Some important gender differences in the prescription of BZD/Z drugs were seen, especially prescription above the recommended dose and of drugs with a long-half life (AU)

Benzodiazepine prescriptions and falls in older men and women. / Prescripción de benzodiacepinas y caídas en mujeres y hombres ancianos.

OBJECTIVE: Despite cautions by professional associations, benzodiazepines (BZD) and Z hypnotics (BZD/Z) are widely prescribed to older adults who are particularly susceptible to insomnia and anxiety, but who are also more sensitive to drugs adverse events. In this study, we assessed the prescription of BZD/Z drugs in a sample of older adults (≥65) who presented for emergency care after a fall. METHODS: We collected the type, number and dose of BZD/Z drugs prescribed and explored gender differences in the prescription. RESULTS: BZD/Z drugs were prescribed to 43.6% of the sample (n=654) and more frequently to women; 78.4% of prescriptions were for BZD/Z drugs with a short half-life. The majority of patients (83.5%) were prescribed only one type of BZD/Z, but 16.5% had been prescribed multiple BZD/Z drugs, with no gender difference. Doses higher than those recommended for older adults were prescribed to 58% of patients, being the doses significantly higher for men compared to women (70.0% vs 53.1%). CONCLUSIONS: Over 40% of older adults presenting for emergency care after a fall had previously been prescribed BZD/Z drugs. Some important gender differences in the prescription of BZD/Z drugs were seen, especially prescription above the recommended dose and of drugs with a long-half life.

Eficacia y seguridad de la ketamina en depresión bipolar: una revisión sistemática / Efficacy and safety of ketamine in bipolar depression: a systematic review

El componente depresivo es el más prevalente del trastorno bipolar. La ketamina ha mostrado eficacia y rapidez como tratamiento de episodios depresivos. El objetivo del presente trabajo es realizar una revisión sistemática sobre la eficacia y seguridad de la ketamina como tratamiento de la depresión bipolar, y sus tipos de administración. Se obtuvieron 10 artículos relevantes que cumplían con los criterios del estudio: un ensayo clínico, 5 estudios de cohorte y 4 series de casos. La forma de administración utilizada en el 60% de los trabajos fue la infusión intravenosa. La ketamina parece ser un tratamiento seguro y eficaz para la depresión bipolar, aunque la duración de la acción es breve. Los efectos adversos que se observaron se produjeron generalmente en el momento de la infusión y tendieron a desaparecer completamente al cabo de 1-2h. Por tanto, es necesario realizar más estudios para explorar nuevas vías de administración, así como su seguridad y efectos adversos (AU)

The depression is the most prevalent state throughout the life of the bipolar patient. Ketamine has been shown to be an effective and rapid treatment for depression. The objective of the present work is to perform a systematic review on the efficacy and safety of ketamine as treatment of bipolar depression, as well as its different patterns of administration. The search found 10 relevant manuscripts that met the inclusion criteria: one clinical trial, 5 cohort studies, and 4 case reports. Intravenous infusion was used in 60% of the studies. According to data, ketamine seems to be an effective and safe treatment for bipolar depression, although the length of its effect is short. Adverse effects observed generally occurred at the time of infusion, and tended to completely disappear within 1-2h. Therefore, more studies are necessary to explore new patterns of administration, as well as on its safety and adverse effects (AU)

Efficacy and safety of ketamine in bipolar depression: A systematic review. / Eficacia y seguridad de la ketamina en depresión bipolar: una revisión sistemática.

The depression is the most prevalent state throughout the life of the bipolar patient. Ketamine has been shown to be an effective and rapid treatment for depression. The objective of the present work is to perform a systematic review on the efficacy and safety of ketamine as treatment of bipolar depression, as well as its different patterns of administration. The search found 10 relevant manuscripts that met the inclusion criteria: one clinical trial, 5 cohort studies, and 4 case reports. Intravenous infusion was used in 60% of the studies. According to data, ketamine seems to be an effective and safe treatment for bipolar depression, although the length of its effect is short. Adverse effects observed generally occurred at the time of infusion, and tended to completely disappear within 1-2h. Therefore, more studies are necessary to explore new patterns of administration, as well as on its safety and adverse effects.

Psychometric properties and validation of a four-item version of the Strauss-Carpenter scale in bipolar disorder.

BACKGROUND: Bipolar disorder is a chronic illness that impairs functioning and affects the quality of life of patients. The onset of this illness usually occurs at an early age, and the risk of relapse remains high for decades. Thus, due to the great clinical relevance of identifying long-term predictors of functioning in bipolar disorder, Strauss and Carpenter developed a scale composed of items known to have prognostic value. METHODS: To determine the clinical usefulness of the four-item Strauss-Carpenter scale in bipolar disorder, a 1-year prospective follow-up study was carried out. The internal consistency, convergent and discriminant validity, and test-retest reliability of the scale were assessed. We also compared the Strauss-Carpenter scale with the reference scales Global Assessment Functioning (GAF), Clinical Global Impression for Bipolar Disorder, the Modified Version (CGI-BIP-M) and the Sheehan Disability Scale (Sheehan). Additionally, a cut-off point for remission was established. RESULTS: The total sample was composed of 98 patients with a diagnosis of bipolar disorder. The four-item version of the Strauss-Carpenter scale showed to have appropriate psychometric properties, comparable to those of reference scales. The best cut-off point for remission was 14. CONCLUSIONS: The four-item version of the Strauss-Carpenter scale has suitable validity and reliability for the assessment of functioning in patients with bipolar disorder.

Adherence to Antipsychotic Medication in Bipolar Disorder and Schizophrenic Patients: A Systematic Review.

Antipsychotics are the drugs prescribed to treat psychotic disorders; however, patients often fail to adhere to their treatment, and this has a severe negative effect on prognosis in these kinds of illnesses. Among the wide range of risk factors for treatment nonadherence, this systematic review covers those that are most important from the point of view of clinicians and patients and proposes guidelines for addressing them. Analyzing 38 studies conducted in a total of 51,796 patients, including patients with schizophrenia spectrum disorders and bipolar disorder, we found that younger age, substance abuse, poor insight, cognitive impairments, low level of education, minority ethnicity, poor therapeutic alliance, experience of barriers to care, high intensity of delusional symptoms and suspiciousness, and low socioeconomic status are the main risk factors for medication nonadherence in both types of disorder. In the future, prospective studies should be conducted on the use of personalized patient-tailored treatments, taking into account risk factors that may affect each individual, to assess the ability of such approaches to improve adherence and hence prognosis in these patients.

Evaluación de la influencia de los factores de riesgo en la incidencia y dinámica de aparición de las flebitis de via periférica: Estudio de cohortes observacional / Assessing the influence of risk factors on rates and dynamics of peripheral vein phlebitis: An observational cohort study

Fundamento y objetivo: Valorar la influencia de los factores de riesgo en la incidencia y cinética de flebitis.Material y métodos: Todos los catéteres cortos de inserción periférica insertados durante un mes (1201 catéteres y 967 pacientes) en un hospital médico-quirúrgico general. Los factores de riesgo de flebitis se analizaron mediante regresión de Cox. Se calcularon la probabilidad acumulada, el riesgo condicional de flebitis y el beneficio teórico del recambio en diferentes periodos. Resultados: Fueron predictores independientes de desarrollo de flebitis el sexo femenino, la inserción de un catéter en el servicio de urgencias o en las unidades medico-quirúrgicas, la localización en el antebrazo y la administración de amoxicilina-clavulánico y aminoglucósidos con hazard ratios (intervalo de confianza al 95%) respectivas de: 1.46 (1.09-2.15), 1.94 (1.01-3.73), 2.51(1.29-4.88), 1.93(1.10-3.01), 2.15 (1.45-3.20) y 2.10 (1.01-4.63). La máxima incidencia se alcanzó de forma más precoz en los catéteres con ≥2 factores de riesgo (dias 3 y 4) que en los de <2 (dias 4 y 5). El riesgo condicional aumentó de 0.08 flebitis/1 cat-día para los catéteres de ≤1 factor de riesgo hasta 0.26 para aquellos con ≥3. El mayor beneficio del recambio del catéter se obtuvo a las 60 horas, variando en función de los factores de riesgo: 24.8% reducción con ≥3, 13.1% con 2 y 9.2% con ≤1. Conclusiones: La dinámica de aparición de flebitis se halla muy influenciada por la interacción de los factores de riesgo. El recambio sistemático cada 72 horas solo parece ser estrictamente necesario en los catéteres de alto riesgo (AU)

Background and objectives: To assess the influence of risk factors on the rates and kinetics of peripheral vein phlebitis (PVP) development and its theoretical influence in absolute PVP reduction after catheter replacement. Methods:All peripheral short intravenous catheters inserted during one month were included (1201 catheters and 967 patients). PVP risk factors were assessed by a Cox proportional hazard model. Cumulative probability, conditional failure of PVP and theoretical estimation of the benefit from replacement at different intervals were performed. Results: Female gender, catheter insertion at the emergency or medical-surgical wards, forearm site, amoxicillin-clavulamate or aminoglycosides were independent predictors of PVP with hazard ratios (95 confidence interval) of 1.46 (1.09-2.15), 1.94 (1.01-3.73), 2.51 (1.29-4.88), 1.93 (1.20-3.01), 2.15 (1.45-3.20) and 2.10 (1.01-4.63), respectively. Maximum phlebitis incidence was reached sooner in patients with ≥2 risk factors (days 3-4) than in those with <2 (days 4-5). Conditional failure increased from 0.08 phlebitis/one catheter-day for devices with ≤1 risk factors to 0.26 for those with ≥3. The greatest benefit of routine catheter exchange was obtained by replacement every 60h. However, this benefit differed according to the number of risk factors: 24.8% reduction with ≥3, 13.1% with 2, and 9.2% with ≤1. Conclusions: PVP dynamics is highly influenced by identifiable risk factors which may be used to refine the strategy of catheter management. Routine replacement every 72h seems to be strictly necessary only in high-risk catheters (AU)

Assessing the influence of risk factors on rates and dynamics of peripheral vein phlebitis: an observational cohort study.

BACKGROUND AND OBJECTIVES: To assess the influence of risk factors on the rates and kinetics of peripheral vein phlebitis (PVP) development and its theoretical influence in absolute PVP reduction after catheter replacement. METHODS: All peripheral short intravenous catheters inserted during one month were included (1201 catheters and 967 patients). PVP risk factors were assessed by a Cox proportional hazard model. Cumulative probability, conditional failure of PVP and theoretical estimation of the benefit from replacement at different intervals were performed. RESULTS: Female gender, catheter insertion at the emergency or medical-surgical wards, forearm site, amoxicillin-clavulamate or aminoglycosides were independent predictors of PVP with hazard ratios (95 confidence interval) of 1.46 (1.09-2.15), 1.94 (1.01-3.73), 2.51 (1.29-4.88), 1.93 (1.20-3.01), 2.15 (1.45-3.20) and 2.10 (1.01-4.63), respectively. Maximum phlebitis incidence was reached sooner in patients with ≥2 risk factors (days 3-4) than in those with <2 (days 4-5). Conditional failure increased from 0.08 phlebitis/one catheter-day for devices with ≤1 risk factors to 0.26 for those with ≥3. The greatest benefit of routine catheter exchange was obtained by replacement every 60h. However, this benefit differed according to the number of risk factors: 24.8% reduction with ≥3, 13.1% with 2, and 9.2% with ≤1. CONCLUSIONS: PVP dynamics is highly influenced by identifiable risk factors which may be used to refine the strategy of catheter management. Routine replacement every 72h seems to be strictly necessary only in high-risk catheters.

Poor long-term prognosis in mixed bipolar patients: 10-year outcomes in the Vitoria prospective naturalistic study in Spain.

OBJECTIVE: There have been few prospective long-term naturalistic studies of patients with mixed episodes of bipolar disorder. The aim of this study was to examine 10-year outcomes in patients with at least 1 mixed episode. METHOD: A naturalistic sample of bipolar I disorder patients (n = 120), representative of bipolar patients treated in a catchment area of Spain, was followed prospectively for up to 10 years. Outcomes including number (primary study outcome) and severity of episodes, hospitalizations, and suicide attempts were recorded at bimonthly visits. Bivariate and logistic regression models identified factors significantly associated with mixed episodes. The study was conducted from 1994 through 2004. RESULTS: 37% of patients had mixed episodes. Mixed-episode patients had younger mean age at onset compared with the nonmixed group (25.3 vs 30.8 years; P = .025). After adjusting for age at onset, mixed-episode patients had an increased risk of hospitalization compared with the nonmixed group (OR = 2.86; 95% CI, 1.09-7.52; P = .033) and more episodes (OR = 1.21; 95% CI, 1.10-1.31; P < .001). Other differences between mixed and nonmixed patients, such as alcohol abuse, psychotic symptoms, and suicidality, were partially mediated by age at onset and were not significantly different after controlling for this variable. Mixed-episode patients with previous suicide attempts had a significantly shorter time to first suicide attempt during follow-up than those without history of suicide attempts (P = .014). CONCLUSIONS: Although some factors associated with mixed episodes are mediated by a younger age at onset, the long-term prognosis of mixed-episode patients is worse than patients with nonmixed episodes.

Different profile of substance abuse in relation to predominant polarity in bipolar disorder: The Vitoria long-term follow-up study.

BACKGROUND: There is a need for comparisons of long-term outcomes in bipolar disorder patients with predominantly manic symptoms vs. predominantly depressive symptoms, especially the course of comorbid alcohol/substance abuse. METHOD: A naturalistic sample of bipolar I patients (n=120) was followed prospectively for up to 10years. At baseline, number and polarity of past episodes were used to classify patients as predominantly manic or predominantly depressive if there were more manic or more depressive episodes, respectively. 25 patients were excluded from the analyses. Outcomes including episodes, hospitalisations and suicide attempts were recorded at bimonthly visits. Mixed effects models compared the course of alcohol and other substance abuse in predominantly manic vs. depressive patients. RESULTS: Of the 95 patients analyzed, 44 (46.3%) had predominantly manic episodes and 51 (53.7%) had predominantly depressive episodes. At baseline, the predominantly depressive group had more history of suicide attempts (45.1% vs. 20.5%; p=0.021) and more family history of affective disorders (64.7% vs. 38.6%; p=0.020), but they had fewer previous hospitalisations than the manic group (mean 0.38 vs. 0.50; p=0.025). During the 10-year follow-up, the predominantly depressive group was associated with more episodes (p=0.001), more hospitalisations (p=0.004) and more suicide attempts (p=0.002). At baseline, there were no differences between the manic and depressive groups in the frequency of alcohol abuse (43.2% and 35.3%, p=0.565) or other substance abuse (13.6% and 9.8%, p=0.794). During the 10-year follow-up, the frequency of alcohol and other substance abuse decreased significantly in the manic group only, after controlling by age at onset and civil (marital) status. CONCLUSION: Long-term clinical outcomes differ between predominantly manic vs. depressive bipolar patients, with the predominantly depressive group having a worse prognosis and maintained alcohol and other substance abuse. These differences should be considered when designing treatment approaches for bipolar patients with comorbid alcohol/substance abuse.

Age at onset in bipolar I disorder: two may be better than three subgroups.

INTRODUCTION AND OBJECTIVE: Age at onset in bipolar disorder is related to prognosis and to treatment response. However, it is not clear if there are three or two subgroups in relation to age at onset. The objective of this study is to analyze the number of subgroups in relation to age at the beginning of the disease in a representative sample of bipolar I patients and to compare the subgroups in relation to clinical variables. METHOD: We included 169 patients diagnosed with bipolar I disorder. Normal mixture analysis was performed. The subgroups of patients formed above were compared regarding clinical characteristics. Patients were followed-up during six years. RESULTS: We found three ages at onset subgroups. The early onset group (18.2±2 years) included 34% of the patients. The second group (26.1±5.5 years) included 44% of the patients. The third group (50.9±9.1 years) included 22% of the patients. Early and intermediate onset groups were not significantly different, and had more family history of affective disorders, more psychotic symptoms, more history of suicide attempts and more history of drug abuse history than the late onset group. CONCLUSIONS: Our results suggest that there are three groups of age at onset but early and intermediate groups are similar in relation to clinical variables. The late onset group includes almost a quartile of patients and has different clinical profile.

Suicidal risk in bipolar I disorder patients and adherence to long-term lithium treatment.

OBJECTIVES: Among the well-established treatments for bipolar disorder (BPD), lithium continues to offer an unusually broad spectrum of benefits that may include reduction of suicidal risk. METHODS: We examined the association of suicidal acts with adherence to long-term lithium maintenance treatment and other potential risk factors in 72 BP I patients followed prospectively for up to 10 years at a Mood Disorders Research Center in Spain. RESULTS: The observed rates of suicide were 0.143, and of attempts, 2.01%/year, with a 5.2-fold (95% CI: 1.5-18.6) greater risk among patients consistently rated poorly versus highly adherent to lithium prophylaxis (11.4/2.2 acts/100 person-years). Treatment non-adherence was associated with substance abuse, being unmarried, being male, and having more hypomanic-manic illness and hospitalizations. Suicidal risk was higher with prior attempts, more depression and hospitalization, familial mood disorders, and being single and younger, as well as treatment non-adherence, but with neither sex nor substance abuse. In multivariate analysis, suicidal risk was associated with previous suicidality > poor treatment adherence > more depressive episodes > younger age. CONCLUSIONS: The findings support growing evidence of lower risk of suicidal acts during closely monitored and highly adherent, long-term treatment with lithium and indicate that treatment adherence is a potentially modifiable factor contributing to antisuicidal benefits.