Cholesterol-Lowering Treatment in Chronic Kidney Disease: Multistage Pairwise and Network Meta-Analyses.

Pairwise and network meta-analyses on the relationship between the efficacy of the use of statins with or without ezetimibe and reductions in low-density lipoprotein cholesterol (LDLc) and C-reactive protein (CRP) in patients with chronic kidney disease (CKD) are presented. In the pairwise meta-analysis, statins with or without ezetimibe were shown to be efficacious in reducing major adverse cardiovascular events (MACE) in patients with CKD and an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2, in the context of both primary prevention [odds ratio (OR)/95% confidence interval (95% CI)/I2/number of studies (n): 0.50/0.40-0.64/0%/6] and primary/secondary prevention (0.66/0.57-0.76/57%/18). However, in the Bayesian network meta-analysis, compared to the placebo, only atorvastatin 80 mg daily and atorvastatin and rosuvastatin at doses equivalent to simvastatin 20 mg daily reduced the odds of MACEs in this patient population. The network meta-analysis for LDLc and CRP treatment objectives also showed that, regardless of eGFR and excluding dialysis patients, the number of MACEs decreased in patients with CKD, with reductions in both LDLc and CRP of less than 50% (surface under the cumulative ranking (SUCRA)/heterogeneity (vague)/n: 0.77/0.14/3). The evaluation of the benefits of drugs may lead to individualized therapy for CKD patients: Cholesterol-lowering treatment for CKD patients with high levels of both LDLc and CRP is suggested.

Adherence to reporting guidelines increases the number of citations: the argument for including a methodologist in the editorial process and peer-review.

BACKGROUND: From 2005 to 2010, we conducted 2 randomized studies on a journal (Medicina Clínica), where we took manuscripts received for publication and randomly assigned them to either the standard editorial process or to additional processes. Both studies were based on the use of methodological reviewers and reporting guidelines (RG). Those interventions slightly improved the items reported on the Manuscript Quality Assessment Instrument (MQAI), which assesses the quality of the research report. However, masked evaluators were able to guess the allocated group in 62% (56/90) of the papers, thus presenting a risk of detection bias. In this post-hoc study, we analyse whether those interventions that were originally designed for improving the completeness of manuscript reporting may have had an effect on the number of citations, which is the measured outcome that we used. METHODS: Masked to the intervention group, one of us used the Web of Science (WoS) to quantify the number of citations that the participating manuscripts received up December 2016. We calculated the mean citation ratio between intervention arms and then quantified the uncertainty of it by means of the Jackknife method, which avoids assumptions about the distribution shape. RESULTS: Our study included 191 articles (99 and 92, respectively) from the two previous studies, which all together received 1336 citations. In both studies, the groups subjected to additional processes showed higher averages, standard deviations and annual rates. The intervention effect was similar in both studies, with a combined estimate of a 43% (95% CI: 3 to 98%) increase in the number of citations. CONCLUSIONS: We interpret that those effects are driven mainly by introducing into the editorial process a senior methodologist to find missing RG items. Those results are promising, but not definitive due to the exploratory nature of the study and some important caveats such as: the limitations of using the number of citations as a measure of scientific impact; and the fact that our study is based on a single journal. We invite journals to perform their own studies to ascertain whether or not scientific repercussion is increased by adhering to reporting guidelines and further involving statisticians in the editorial process.

The role of middle managers in tobacco control after a national smoke-free hospital campus ban.

BACKGROUND: Much of the recent health services research on tobacco control implementation has explored general views and perceptions of health professionals and has rarely taken into account middle management's perspectives. We state that middle managers may facilitate the implementation of smoke-free campus bans and thereby improve their effectiveness. The aim of this study was to assess middle managers' behaviors to enforce a new national smoke-free hospital campus ban, to evaluate their perceptions of the level of compliance of the new regulation, and to explore their attitudes towards how smoking affects the work environment. METHODS: We used a cross-sectional survey, conducted online to evaluate middle managers of a general hospital in Catalonia, Spain. Close-ended and open-ended questions were included. Results were analyzed by using quantitative and qualitative methods. The managers' open opinions to the proposed topics were assessed using UCINET, and a graph was generated in NetDraw. RESULTS: Sixty-three of the invited managers (78.7 %) participated in the survey. 87.2 % of them agreed that the hospital complied with the smoke-free campus ban and 79.0 % agreed that managers have an important role in enforcing the ban. They also perceived that smoking disturbs the dynamics of work, is a cause of conflict between smokers and non-smokers, and harms both the professional and the organization images. However, 96.8 % of respondents have never given out fines or similar measures and their active role in reminding others of the policy was limited; in addition, 68.2 % considered that hospitals should provide tobacco cessation treatments. Smoker middle managers were more likely than non-smokers to perceive that smoking has little impact on work. CONCLUSIONS: Middle managers play a limited role in controlling tobacco consumption; smokers are less prone to think that smoking disturbs work dynamics than non-smokers. Tailored training and clear proceedings for middle managers could encourage more active roles.

[Descriptive Study of sickness absence in the health care sector of Catalonia (2009-2012)]. / Estudio descriptivo de la incapacidad temporal en el sector sanitario de Cataluña (2009-2012).

OBJECTIVE: To describe the incidence and evolution of sickness absence (SA) for non-occupational and occupational illness/injury in the population of workers in Catalonian Health Centers based on the definition of a set of common indicators. METHODS: The study population consisted of 25,964 workers from 30 health centers in Catalonia, during 2009-2012. Information on SA episodes was obtained from records of the Directorate of Human Resources. SA indicators were defined, and SA incidence rates and temporal evolution were calculated, depending on the length and type of episode, and the size and activity of health centers. RESULTS: SA incidence rates for non-occupational illness and injury showed a decreasing trend during 2009-2012. Smaller centers had lower SA rates for non-occupational conditions than larger centers (p〈0.001). Social health centers had higher SA rates of non-occupational illness and injury, especially those with a very short duration (p〈0.001). Primary care centers had the lowest SA occupational illness and injury rates, with the highest rates occurring in the social health centers, especially long-term centers (p〈0.001). CONCLUSIONS: The differences in incidence rates of SA detected by type of activity of the health centers could be due to differences in working conditions.

OBJETIVO: Describir la incidencia y evolución de la incapacidad temporal (IT) por contingencias comunes y profesionales en la población trabajadora de los centros sanitarios de Cataluña. MÉTODOS: La población de estudio estuvo constituida por los 25.964 trabajadores de 30 centros sanitarios de Cataluña, durante el período 2009-2012. La información sobre los episodios de IT se obtuvo de los registros de las Direcciones de Recursos Humanos. Se definieron unos indicadores de IT, y se calcularon las tasas de incidencia de IT y la evolución temporal, según la duración y tipo de episodio, y el tamaño y actividad de los centros sanitarios. RESULTADOS: La evolución temporal de las tasas de incidencia de IT por contingencia común mostró una tendencia a la disminución en el período 2009-2012. Los centros de pequeño tamaño tuvieron tasa de IT por contingencia común inferior que los de mayor tamaño (p〈0,001). Los centros sociosanitarios son los que presentaron mayores tasas de IT por contingencia común, especialmente la de muy corta duración (p〈0,001). Los centros de atención primaria tuvieron las tasas más bajas de IT por contingencia profesional siendo la más elevada la de los centros sociosanitarios, especialmente la de larga duración (p〈0,001). CONCLUSIONES: Las diferencias observadas en las tasas de incidencia de IT según el tipo de actividad del centro sanitario podrían deberse a diferencias en las condiciones de trabajo.

Efficacy of cyclophospamide in the treatment of interstitial lung disease associated with systemic sclerosis.

BACKGROUND: Cyclophosphamide (CYC) stabilizes the parameters of lung function tests (LFT) of patients with (SSc) and interstitial lung disease (ILD) treated for 12 months. There is little information about long-term treatment (24 months). The aim of this study is to analyze the effect of intravenous CYC in LFT parameters in patients with SSc and ILD treated for 24 months. PATIENTS AND METHOD: Retrospective study of 37 patients with ILD associated with scleroderma treated with intravenous CYC for 24 months and regularly assessed by LFT (at baseline, 6, 12 and 24 months) including forced vital capacity (FVC) and transfer capacity of carbon monoxide (DL(CO)). To evaluate response to treatment the recommendations of the ATS and SEPAR were considered. RESULTS: The difference between FVC and DL(CO) values performed at baseline and those performed at 6, 12, and 24 months were less than 10%, which meant that CYC stabilized LFT. There were no differences in LFT when patients treated for 6 months were evaluated according to the type of skin involvement of the SSc (diffuse or limited) and the duration of the ILD. Although patients with severe restriction (FVC<70%) showed more improvement, it was less than 10% in all cases. CONCLUSION: In this series of patients with ILD associated with SSc intravenous CYC was effective in stabilizing LFT in long-term treatment.

Association of HLA class II genes with systemic sclerosis in Spanish patients.

OBJECTIVE: To examine the role of HLA-DRB1 and HLA-DQB1 alleles in the susceptibility to systemic sclerosis (SSc) and its clinical expression in a Spanish population. METHODS: One hundred Spanish Caucasian patients with SSc and 130 controls were studied. Molecular HLA-DRB1 and HLA-DQB1 typing was performed by polymerase chain reaction (PCR) sequence-based typing and PCR sequence-specific oligonucleotide. RESULTS: HLA-DRB1*11 was associated with genetic susceptibility to SSc, whereas HLA-DRB1*07 (HLA-DRB1*0701) showed a protective effect. A significant increase in the frequency of the DRB1*1104 allele was observed in patients with anti-topoisomerase I autoantibodies (anti-Topo I) while HLA-DRB1*01 and HLA-DQB1*05 alleles were significantly increased in patients with anti-centromere antibodies (ACA). The HLA-DRB1*11 allele was more frequent in patients with pulmonary fibrosis; however, no significant association with any HLA-DRB1 or DQB1 alleles was identified in patients with pulmonary arterial hypertension. CONCLUSION: HLA alleles play a role in genetic susceptibility to SSc in Spanish patients. Some alleles are more prevalent in patients with pulmonary fibrosis and in patients with certain SSc-specific autoantibodies (anti-Topo I and ACA).

Protein Z levels and anti-protein Z antibodies in patients with arterial and venous thrombosis.

INTRODUCTION: The thrombotic risk associated with protein Z (PZ) deficiency is unclear. Anti-protein Z (anti-PZ) has been described as a risk factor in unexplained embryo demise. The aim of our study was to evaluate a possible PZ deficiency and presence of anti-PZ antibodies on thrombotic diseases. MATERIAL AND METHODS: We performed a case-control study on 114 patients with preexisting arterial or venous thrombosis (50 and 64, respectively). Thrombosis was studied based on etiology (creating factor risk subgroups) and on specific thrombotic disease. RESULTS: PZ levels of patients were significantly lower compared to controls (1709+-761.3 ng/mL vs. 2437+-964.7 ng/mL P=0.001). The high arterial risk factor subgroup showed the lowest PZ level (1267.5+-609 ng/mL) whereas the rest of arterial and venous etiological subgroups presented similar PZ levels. Patients with peripheral artery disease had the lowest PZ level (1022+-966 ng/mL). The rest of arterial and venous thrombotic diseases presented similar PZ levels. A significant increased risk for arterial and venous thrombosis for the lowest (<1685 ng/mL) quartile of PZ has been founded (OR:52, P=0.001 and OR:18, P=0.007, respectively). Anti-PZ antibodies were negative in the majority of patients, although mean anti-PZ IgG antibody levels in the arterial thrombosis group were significantly higher compared to venous thrombosis and control groups (P=0.05 and P=0.005, respectively). CONCLUSIONS: The results suggest that both arterial and venous thrombotic events are related to low PZ levels and that low PZ concentrations are associated with thrombosis in our study. In arterial thrombosis our findings strengthen previous studies that related low PZ levels to atherosclerotic disease. Anti-PZ antibodies do not seem to play a potent role in thrombosis.

Statistical reviewers improve reporting in biomedical articles: a randomized trial.

BACKGROUND: Although peer review is widely considered to be the most credible way of selecting manuscripts and improving the quality of accepted papers in scientific journals, there is little evidence to support its use. Our aim was to estimate the effects on manuscript quality of either adding a statistical peer reviewer or suggesting the use of checklists such as CONSORT or STARD to clinical reviewers or both. METHODOLOGY AND PRINCIPAL FINDINGS: Interventions were defined as 1) the addition of a statistical reviewer to the clinical peer review process, and 2) suggesting reporting guidelines to reviewers; with "no statistical expert" and "no checklist" as controls. The two interventions were crossed in a 2x2 balanced factorial design including original research articles consecutively selected, between May 2004 and March 2005, by the Medicina Clinica (Barc) editorial committee. We randomized manuscripts to minimize differences in terms of baseline quality and type of study (intervention, longitudinal, cross-sectional, others). Sample-size calculations indicated that 100 papers provide an 80% power to test a 55% standardized difference. We specified the main outcome as the increment in quality of papers as measured on the Goodman Scale. Two blinded evaluators rated the quality of manuscripts at initial submission and final post peer review version. Of the 327 manuscripts submitted to the journal, 131 were accepted for further review, and 129 were randomized. Of those, 14 that were lost to follow-up showed no differences in initial quality to the followed-up papers. Hence, 115 were included in the main analysis, with 16 rejected for publication after peer review. 21 (18.3%) of the 115 included papers were interventions, 46 (40.0%) were longitudinal designs, 28 (24.3%) cross-sectional and 20 (17.4%) others. The 16 (13.9%) rejected papers had a significantly lower initial score on the overall Goodman scale than accepted papers (difference 15.0, 95% CI: 4.6-24.4). The effect of suggesting a guideline to the reviewers had no effect on change in overall quality as measured by the Goodman scale (0.9, 95% CI: -0.3-+2.1). The estimated effect of adding a statistical reviewer was 5.5 (95% CI: 4.3-6.7), showing a significant improvement in quality. CONCLUSIONS AND SIGNIFICANCE: This prospective randomized study shows the positive effect of adding a statistical reviewer to the field-expert peers in improving manuscript quality. We did not find a statistically significant positive effect by suggesting reviewers use reporting guidelines.

[Usefulness of oral pilocarpin therapy in the treatment of xerostomia and xerophthalmia in patients with primary Sjögren's syndrome]. / Pilocarpina oral en el tratamientode la xerostomía y xeroftalmía en pacientes con síndrome de Sjögren primario.

BACKGROUND AND OBJECTIVE: We aimed to asses the efficacy of pilocarpine tablets as a symptomatic treatment for dry mouth and dry eyes in patients with primary Sjögren's syndrome (SS). PATIENTS AND METHOD: We included 40 patients with SS (38 women and 2 men), mean age 49.2 years (range, 35-68), with severe xerostomia and xerophthalmia. Objective tests (salivary scintigraphy, Schirmer's test, break-up time, Rose Bengal staining) and subjective tests (symptoms' questionnaire) were carried out before starting treatment and 6 months later to evaluate any glandular function improvement. RESULTS: All patients initially received 15 mg daily of pilocarpine. Twelve (30%) patients received 20 mg daily. Dry mouth-related symptoms improved in 57.5% of patients and dry eyes-related ones improved in 35%. Scintigraphic studies demonstrated an objective improvement of the glandular function in 35% patients. Ocular tests showed an improvement in 30% cases. CONCLUSIONS: Pilocarpine therapy is useful to improve xerostomia and xerophthalmia in SS patients with moderate and severe glandular involvement. However, we have not observed a good correlation between subjective improvement of symptoms and the objective test results.

[Prospective multicenter study of adverse drug reactions in hospitalized elderly patients]. / Estudio multicéntrico prospectivo de reacciones adversas a medicamentos en pacientes ancianos hospitalizados.

BACKGROUND AND OBJECTIVE: The incidence of adverse drug reactions (ADRs) in hospitalized elderly patients is an important clinical problem. The purpose of this study was to determine the incidence of ADRs in elderly in-patients, to analyze the factors involved in their presentation and to evaluate the reactions detected. PATIENTS AND METHOD: Prospective multicenter study in patients older than 65 years during their stay in hospital or nursing home. The assessment consisted of a complete geriatric evaluation and a protocol for collecting information on suspected ADRs during hospitalization or nursing home stay. A multivariate analysis by multiple logistic regression was performed. RESULTS: The study included 865 patients: 185 (21%) from 5 hospital units; 325 (38%) from 8 convalescent centers; and 355 (41%) from 8 long-term centers. The incidence of ADRs was 9%. In acute units the incidence was 15%; in post-acute units, 5%; and in long-term centers, 10% (p < 0.004). In the global multivariate analysis, the risk of experiencing an ADR was associated with a greater use of medications (OR = 1.15; 1.07 1.23 for each additional drug), the presentation of delirium (OR = 3.6; 1.95-6.85) and the type of unit (acute OR = 2.6; 1.16-6.01; long-term OR = 3.3; 1.62-7.05). Fifty type A ADRs were detected (65%). With regard to severity, 36 (47%) were moderate, 27 (35%) were mild, and 14 (18%) were severe. Causality: 58 (76%) probable and 17 (20%) possible. Potential avoidability: 39 (51%) were unavoidable and 38 (49%) were totally or partially avoidable; of these, 15 (39%) were the result of an interaction with another drug. CONCLUSIONS: The incidence of ADRs in our study was close to 10%. ADRs were associated with the frequency of use, presence of delirium and type of unit, and occurred most frequently in acute and long-term units. ADRs were principally type A, moderate severity, probable causality and partially avoidable.

Atorvastatin versus Bezafibrate in Mixed Hyperlipidaemia : Randomised Clinical Trial of Efficacy and Safety (the ATOMIX Study).

OBJECTIVE: Combined hyperlipidaemia is a common and highly atherogenic lipid phenotype with multiple lipoprotein abnormalities that are difficult to normalise with single-drug therapy. The ATOMIX multicentre, controlled clinical trial compared the efficacy and safety of atorvastatin and bezafibrate in patients with diet-resistant combined hyperlipidaemia. PATIENTS AND STUDY DESIGN: Following a 6-week placebo run-in period, 138 patients received atorvastatin 10mg or bezafibrate 400mg once daily in a randomised, double-blind, placebo-controlled trial. To meet predefined low-density lipoprotein-cholesterol (LDL-C) target levels, atorvastatin dosages were increased to 20mg or 40mg once daily after 8 and 16 weeks, respectively. RESULTS: After 52 weeks, atorvastatin achieved greater reductions in LDL-C than bezafibrate (percentage decrease 35 vs 5; p < 0.0001), while bezafibrate achieved greater reductions in triglyceride than atorvastatin (percentage decrease 33 vs 21; p < 0.05) and greater increases in high-density lipoprotein-cholesterol (HDL-C) [percentage increase 28 vs 17; p < 0.01 ]. Target LDL-C levels (according to global risk) were attained in 62% of atorvastatin recipients and 6% of bezafibrate recipients, and triglyceride levels <200 mg/dL were achieved in 52% and 60% of patients, respectively. In patients with normal baseline HDL-C, bezafibrate was superior to atorvastatin for raising HDL-C, while in those with baseline HDL-C <35 mg/dL, the two drugs raised HDL-C to a similar extent after adjustment for baseline values. Both drugs were well tolerated. CONCLUSION: The results show that atorvastatin has an overall better efficacy than bezafibrate in concomitantly reaching LDL-C and triglyceride target levels in combined hyperlipidaemia, thus supporting its use as monotherapy in patients with this lipid phenotype.

Panniculitis: a cutaneous manifestation of dermatomyositis.

Specific and nonspecific panniculitis sometimes occurs during the course of connective tissue diseases. However, the association of panniculitis and dermatomyositis (DM) has only rarely been described. Previous reports have suggested that panniculitis may be an inherent part of DM but, because the cases reported are few, it is difficult to know the significance of this unusual association. We describe 2 patients with DM in whom panniculitis developed during the course of the disease, and discuss its clinical and diagnostic significance.

Effect of atorvastatin and bezafibrate on plasma levels of C-reactive protein in combined (mixed) hyperlipidemia.

C-reactive protein (CRP) is a non-specific but sensitive marker of underlying systemic inflammation. High CRP plasma levels correlate with risk for future cardiovascular events. The present study evaluated the effects of atorvastatin (10-40 mg) and bezafibrate (400 mg) on CRP concentrations after 6 and 12 months of treatment in 103 patients with combined (mixed) hyperlipidemia. The number of cardiovascular risk factors present in a given patient was associated with baseline CRP levels. After 6 months and 1 year, atorvastatin treatment was associated with significant (P<0.001) decreases from baseline of CRP concentrations by 29 and 43%, respectively, while bezafibrate-treated patients showed non-significant reductions of 2.3 and 14.6%, respectively (P=0.056 and 0.005 for the respective differences between the two treatment arms at 6 months and 1 year). The magnitude of change in CRP after 1 year was directly related to baseline CRP levels. Covariance analysis showed that CRP decreases in the atorvastatin group were unrelated to total cholesterol and LDL cholesterol reductions; however, they were directly related to triglyceride changes (r=0.28, P=0.047) and inversely related to HDL cholesterol changes (r=-0.28, P=0.045). A model including baseline CRP values and treatment effect showed that atorvastatin use was a significant predictor of change in CRP levels over time (beta=0.82, P=0.023). These results suggest a potential anti-atherosclerotic additional benefit of atorvastatin in patients at a risk of cardiovascular disease.