Navigating the challenges of clinical trial professionals in the healthcare sector.

Clinical trials (CTs) are essential for medical advancements but face significant challenges, particularly in professional training and role clarity. Principal investigators, clinical research coordinators (CRCs), nurses, clinical trial pharmacists, and monitors are key players. Each faces unique challenges, such as maintaining protocol compliance, managing investigational products, and ensuring data integrity. Clinical trials' complexity and evolving nature demand specialized and ongoing training for these professionals. Addressing these challenges requires clear role delineation, continuous professional development, and supportive workplace environments to improve retention and trial outcomes. Enhanced training programs and a collaborative approach are essential for the successful conduct of clinical trials and the advancement of medical research.

The Cantabria Cohort, a protocol for a population-based cohort in northern Spain.

Cantabria Cohort stems from a research and action initiative lead by researchers from Valdecilla Research Institute (IDIVAL), Marqués de Valdecilla University Hospital and University of Cantabria, supported by the regional Goverment. Its aim is to identify and follow up a cohort that would provide information to improve the understanding of the etiology and prognosis of different acute and chronic diseases. The Cantabria Cohort will recruit between 40,000-50,000 residents aged 40-69 years at baseline, representing 10-20% of the target population. Currently, more than 30,000 volunteers have been enrolled. All participants will be invited for a re-assessment every three years, while the overall duration is planned for twenty years. The repeated collection of biomaterials combined with broad information from participant questionnaires, medical examinations, actual health system records and other secondary public data sources is a major strength of its design, which will make it possible to address biological pathways of disease development, identify new factors involved in health and disease, design new strategies for disease prevention, and advance precision medicine. It is conceived to allow access to a large number of researchers worldwide to boost collaboration and medical research.

Prioritizing Patient Safety: Analysis of the Procurement Process of Infusion Pumps in Spain.

To understand whether patient safety and human factors are considered in healthcare technology procurement, we analyzed the case of infusion pumps as their use critically affects patient safety. We reviewed infusion pump procurements in the Spanish Public Sector Procurement Database. Sixty-three batches in 29 tenders for supplying 12.224 volumetric and syringe infusion pumps and consumables for an overall budget of EUR 30.4 M were identified and reviewed. Concepts related to "ease of use" were identified in the selection requirements of 35 (55.6%) batches, as part of the criteria for the selection of pumps in 23 (36.5%) batches, related to "intuitiveness" in the selection requirements of 35 (55.6%) batches, and in the criteria in 10 (15.9%) batches. No method to evaluate the ease of use, intuitiveness, or usability was mentioned. A review of the procurement teams responsible for the evaluation of the tenders showed no reported human factors or patient safety expertise. We conclude that infusion pump procurement considers usability as a relevant criterion for selection. However, no human factor experts nor specific methods for evaluation of the technology in this field are usually defined. Potential room for refining the selection of healthcare technology to improve patient safety is detected.

Impact of empirical treatment in extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella spp. bacteremia. A multicentric cohort study.

BACKGROUND: The objective of this study is to analyze the factors that are associated with the adequacy of empirical antibiotic therapy and its impact in mortality in a large cohort of patients with extended-spectrum ß-lactamase (ESBL)--producing Escherichia coli and Klebsiella spp. bacteremia. METHODS: Cases of ESBL producing Enterobacteriaceae (ESBL-E) bacteremia collected from 2003 through 2008 in 19 hospitals in Spain. Statistical analysis was performed using multivariate logistic regression. RESULTS: We analyzed 387 cases ESBL-E bloodstream infections. The main sources of bacteremia were urinary tract (55.3%), biliary tract (12.7%), intra-abdominal (8.8%) and unknown origin (9.6%). Among all the 387 episodes, E. coli was isolated from blood cultures in 343 and in 45.71% the ESBL-E was multidrug resistant. Empirical antibiotic treatment was adequate in 48.8% of the cases and the in hospital mortality was 20.9%. In a multivariate analysis adequacy was a risk factor for death [adjusted OR (95% CI): 0.39 (0.31-0.97); P = 0.04], but not in patients without severe sepsis or shock. The class of antibiotic used empirically was not associated with prognosis in adequately treated patients. CONCLUSION: ESBL-E bacteremia has a relatively high mortality that is partly related with a low adequacy of empirical antibiotic treatment. In selected subgroups the relevance of the adequacy of empirical therapy is limited.

Altered blood glucose concentration is associated with risk of death among patients with community-acquired Gram-negative rod bacteremia.

BACKGROUND: Altered blood glucose concentration is commonly observed in patients with sepsis, even among those without hypoglycemic treatments or history of diabetes mellitus. These alterations in blood glucose are potentially detrimental, although the precise relationship with outcome in patients with bacteremia has not been yet determined. METHODS: A retrospective cohort study design for analyzing patients with Gram negative rod bacteremia was employed, with the main outcome measure being in-hospital mortality. Patients were stratified in quintiles accordingly deviation of the blood glucose concentration from a central value with lowest mortality. Cox proportional-hazards regression model was used for determining the relationship of same day of bacteremia blood glucose and death. RESULTS: Of 869 patients identified 63 (7.4%) died. Same day of bacteremia blood glucose concentration had a U-shaped relationship with in-hospital mortality. The lowest mortality (2%) was detected in the range of blood glucose concentration from 150 to 160 mg/dL. Greater deviation of blood glucose concentration from the central value of this range (155 mg/dL, reference value) was directly associated with higher risk of death (p = 0.002, chi for trend). The low-risk group (quintile 1) had a mortality of 3.3%, intermediate-risk group (quintiles 2, 3 and 4) a mortality of 7.1%, and the high-risk group (quintile 5) a mortality of 12.05%. In a multivariable Cox regression model, the hazard ratio for death among patients in the intermediate-risk group as compared with that in the low risk group was 2.88 (95% confidence interval, 1.01 to 8.18; P = 0.048), and for the high risk group it was 4.26 (95% confidence interval, 1.41 to 12.94; P = 0.01). CONCLUSIONS: Same day of bacteremia blood glucose concentration is related with outcome of patients with Gram-negative rod bacteremia. Lowest mortality is detected in patients with blood glucose concentration in an interval of 150-160 mg/dL. Deviations from these values are associated with an increased risk of death.

Diabetes does not affect outcome in patients with Enterobacteriaceae bacteremia.

BACKGROUND: There is limited information about the effect of diabetes on the prognosis of patients with bacterial infections. We performed a retrospective cohort study to investigate possible correlations between diabetes and prognosis in patients with Enterobacteriaceae bacteremia. METHODS: We reviewed the medical charts of 1112 patients who were treated at a community teaching hospital for Enterobacteriaceae bacteremia from January 1997 through June 2007. Factors associated with in-hospital mortality were analyzed by logistic regression analysis. RESULTS: Among the 1112 patients with Enterobacteriaceae bacteremia, 181 (16.3%) were diabetic patients; 90 patients (8.1%) died while in the hospital. Compared to non-diabetic patients, diabetic patients were older (75.4 +/- 11.9 years vs. 70 +/- 16.6 years, p < 0.001) and had more comorbidities. However, mortality among diabetic and non-diabetic patients was not different [7.2% vs. 8.2%, RR 1.13; 95% CI (0.67-1.9); p = 0.39]. In a multivariate analysis, the variables associated with in-hospital mortality were age, the origin of the bacteremia, and the presence of immunosuppression. Diabetes was not associated with outcome. CONCLUSION: In this cohort of patients with Enterobacteriaceae bacteremia, diabetes was not associated with a poorer prognosis.

Microbiology and outcome of iliopsoas abscess in 124 patients.

To describe the microbiology and outcome of iliopsoas abscess (IPA) in a large case series, we analyzed 124 cases of IPA collected from 1990 through 2004 in 11 hospitals in Spain. Twenty-seven (21.8%) patients had primary and 97 (78.2%) had secondary IPA. The main sources of infection were bone (50.5%), gastrointestinal tract (24.7%), and urinary tract (17.5%). A definitive microbial diagnosis was achieved in 93 (75%) cases. Abscess culture was the most frequent procedure leading to microbial diagnosis, followed by blood cultures. Staphylococcus aureus, Escherichia coli, and Bacteroides species were the most frequent microbial causes: S. aureus was the most common organism in patients with primary abscesses (42.9%) and with abscesses of skeletal origin (35.2%), whereas E. coli was the leading organism in those with abscesses of urinary (61.5%) and gastrointestinal (42.1%) tracts. Mycobacterium tuberculosis was found in 15 patients, 4 of them associated with human immunodeficiency virus (HIV) infection. Twenty (21.5%) cases had polymicrobial infections; these were more common among patients with abscesses of gastrointestinal origin. Information on clinical outcome was available for 120 patients; 19 (15.8%) had a relapse and 6 (5%) died due to complications related to the IPA. Patients who died were older and more likely to have bacteremia and E. coli isolated from cultures. In conclusion, secondary IPA is more prevalent than primary IPA. Among those with secondary IPA, most abscesses are secondary to a skeletal source. A bacterial etiology can be identified in most cases. The overall prognosis of patients with this condition is good.

Characteristics and outcome of AIDS-related Hodgkin lymphoma before and after the introduction of highly active antiretroviral therapy.

OBJECTIVES: We analyzed survival, therapeutic response, and prognostic factors in patients with HIV-related Hodgkin lymphoma (HL) treated or not with highly active antiretroviral therapy (HAART). METHODS: This study included 104 patients with HL, treated (n = 83) or not (n = 21) with HAART. Outcomes and prognostic factors of complete remission (CR), overall survival (OS), and disease-free survival (DFS) were assessed by an intention-to-treat analysis of all patients who received at least 1 chemotherapy course. RESULTS: No differences were found between groups at baseline in the specific characteristics of HIV and HL. The proportion of patients receiving appropriate-for-stage therapy for HL was similar for both groups. The CR rates in the HAART (-) and HAART (+) groups were 14 (70%) of 20 versus 71 (91%) of 78 (P = 0.023). The median OS in the HAART (-) group was 39 months (95% confidence interval [CI]: 0 to 89) and was not reached in the HAART (+) group (P = 0.0089). The median DFS in the HAART (-) group was 85 months (95% CI: 73 to 97) and was not reached in the HAART (+) group (P = 0.129). Factors independently associated with CR by logistic regression analysis were appropriate-for-stage therapy of HL, HAART, and baseline CD4 count > or =100 cells/microL. CR was the only factor independently associated with OS by Cox regression analysis. CONCLUSIONS: The achievement of CR was independently associated with appropriate-for-stage therapy for HL, with HAART, and with a baseline CD4 count > or =100 cells/microL. The only variable independently associated with OS was the achievement of CR.

[P-glycoprotein and human immunodeficiency virus infection]. / Glucoproteína P e infección por el virus de la inmunodeficiencia humana.

P-glycoprotein (PGP) is a membrane protein and product of the MDR-1 gene, which acts as an efflux pump for several drugs, such as protease inhibitors (PI) used in HIV. Numerous studies in vitro, in experimental animals, and in patients have analyzed the relationships between PGP and the pharmacokinetic and pharmacodynamic properties of antiretroviral agents, with differing conclusions. In addition, studies focusing on the impact of single nucleotide polymorphisms in the MDR-1 gene, mainly C3435T in exon 26 and G2677A/G2677T in exon 21, on antiretroviral plasma concentrations, efficacy and adverse effects, have reported varying results, which have been attributed to the influence of other polymorphisms, such as cytochrome P450.

Glucoproteína P e infección por el virus de la inmunodeficiencia humana / P-glycoprotein and human immunodeficiency virus infection

La glucoproteína P (PGP) es una proteína de membrana, producto del gen MDR-1, que actúa como bomba expulsora de diversos fármacos, entre ellos los inhibidores de proteasa (IP) del virus de la inmunodeficiencia humana (VIH). Numerosos estudios in vitro, en animales y en pacientes, han analizado las relaciones de esta proteína con la farmacocinética y farmacodinamia de los antirretrovirales, con conclusiones dispares. Por otra parte, las publicaciones que analizan la influencia de los polimorfismos de nucleótido único del gen MDR-1, principalmente el C3435T en el exón 26, y el G2677A/G2677T en el exón 21, con las concentraciones plasmáticas de los antirretrovirales, su eficacia y efectos secundarios también demuestran resultados variables que se han tratado de explicar mediante la influencia de otros polimorfismos como el del citocromo p-450 (AU)

P-glycoprotein (PGP) is a membrane protein and product of the MDR-1 gene, which acts as an efflux pump for several drugs, such as protease inhibitors (PI) used in HIV. Numerous studies in vitro, in experimental animals, and in patients have analyzed the relationships between PGP and the pharmacokinetic and pharmacodynamic properties of antiretroviral agents, with differing conclusions. In addition, studies focusing on the impact of single nucleotide polymorphisms in the MDR-1 gene, mainly C3435T in exon 26 and G2677A/G2677T in exon 21, on antiretroviral plasma concentrations, efficacy and adverse effects, have reported varying results, which have been attributed to the influence of other polymorphisms, such as cytochrome P450 (AU)

Effectiveness and safety of simplification therapy with once-daily tenofovir, lamivudine, and efavirenz in HIV-1-infected patients with undetectable plasma viral load on HAART.

OBJECTIVE: To evaluate the effectiveness and tolerability of a simplification regimen with tenofovir DF (TDF), lamivudine (3TC), and efavirenz (EFV) in HAART-experienced HIV-1-infected subjects with sustained viral suppression. METHOD: Patients with HIV-1 RNA <200 copies/mL during the previous 6 months and who switched their current twice-daily or three-times-daily HAART to a simplified once-daily regimen of TDF (300 mg), 3TC (300 mg), and EFV (600 mg) were included. RESULTS: 154 patients (70% males, mean age 42 years) were included. Previous HAART included a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in 55% of the patients and a thymidine analog in 87%. The percentage of patients with viral load <200 copies/mL in the intent-to-treat (ITT) data set was 83% at 6 months and 75% at 12 months (98% and 96%, respectively, in the on-treatment [OT] analysis). Five patients (3%) were identified as virologic failures according to the study protocol. The mean CD4 T-cell count increased significantly 12 months after simplification (from 570 to 632 cells/mm3; p < .01). At 12 months, mean triglyceride levels decreased from 233 to 170 mg/dL (p < .01) and mean cholesterol levels decreased from 205 to 189 mg/dL (p < .01). Thirty-three patients (21%) discontinued the study treatment prior to completing the 12-month follow-up. CONCLUSION: Simplification to a once-daily regimen containing TDF, 3TC, and EFV is virologically and immunologically effective, well-tolerated, and safe with benefits in the lipid profile in the majority of patients.

Impact of antibiotic resistance and of adequate empirical antibiotic treatment in the prognosis of patients with Escherichia coli bacteraemia.

BACKGROUND: Escherichia coli is the most frequent Gram-negative organism causing bacteraemia. There are few data about prognostic factors of bloodstream infections due to E. coli. In particular, the consequences of antibiotic resistance and of adequate empirical antibiotic treatment on outcome remain broadly unknown. METHODS: We conducted a retrospective cohort study of patients with E. coli bacteraemia between January 1997 and June 2005 to identify any association between antibiotic resistance, adequacy of empirical antibiotic therapy and mortality. RESULTS: Of 663 patients with E. coli bacteraemia, 36 (5.4%) died. Patients with multidrug-resistant (MDR) E. coli bacteraemia had a significantly lower frequency of correct empirical antibiotic treatment than patients with non-MDR E. coli bacteraemia [relative risk (RR) 0.53; 95% confidence interval (CI) 0.48-0.67], and also had a significantly higher mortality (RR 3.31; 95% CI 1.72-6.36). An association between the number of antibiotics to which E. coli was resistant with adequacy of empirical antibiotic (P < 0.001) and with mortality (P < 0.001) was detected. After adjustment for other significant risk factors and confounders, the inadequacy of empirical antibiotic treatment was associated with an increased mortality (adjusted OR 2.98; 95% CI 1.25-7.11). When the adequacy of empirical treatment was excluded from the model, the presence of MDR E. coli in blood cultures was also associated with the prognosis (adjusted OR 3.11; 95% CI 1.3-7.44). In multivariate analysis, other variables associated with the outcome were age, the presence of severe sepsis or shock, Charlson index score and a non-urinary origin of the bacteraemia. CONCLUSIONS: Adequacy of empirical antibiotic treatment is an independent risk factor for mortality in patients with E. coli bacteraemia. MDR E. coli bacteraemia had a worse prognosis due, at least in part, to a lower frequency of correct empirical treatment.

Time to positivity in blood cultures of adults with Streptococcus pneumoniae bacteremia.

BACKGROUND: previous studies have established that bacterial blood concentration is related with clinical outcome. Time to positivity of blood cultures (TTP) has relationship with bacterial blood concentration and could be related with prognosis. As there is scarce information about the usefulness of TTP, we study the relationship of TTP with clinical parameters in patients with Streptococcus pneumoniae bacteremia. METHODS: TTP of all cases of Streptococcus pneumoniae bacteremia, detected between January 1995 and December 2004 using the BacT/Alert automated blood culture system in a teaching community hospital was analyzed. When multiple cultures were positive only the shortest TTP was selected for the analysis. RESULTS: in the study period 105 patients with Streptococcus pneumoniae bacteremia were detected. Median TTP was 14.1 hours (range 1.2 h to 127 h). Immunosuppressed patients (n = 5), patients with confusion (n = 19), severe sepsis or shock at the time of blood culture extraction (n = 12), those with a diagnosis of meningitis (n = 7) and those admitted to the ICU (n = 14) had lower TTP. Patients with TTP in the first quartile were more frequently hospitalized, admitted to the ICU, had meningitis, a non-pneumonic origin of the bacteremia, and a higher number of positive blood cultures than patients with TTP in the fourth quartile. None of the patients with TTP in the 90th decile had any of these factors associated with shorter TTP, and eight out of ten patients with TTP in the 10th decile had at least one of these factors. The number of positive blood cultures had an inverse correlation with TTP, suggesting a relationship of TTP with bacterial blood concentration. CONCLUSION: Our data support the relationship of TTP with several clinical parameters in patients with Streptococcus pneumoniae bacteremia, and its potential usefulness as a surrogate marker of outcome.

Neutropenia secundaria a betalactámicos. Una vieja compañera olvidada / Beta-lactam-induced neutropenia. An old forgotten companion

La neutropenia provocada por los betalactámicos es un problema conocido desde que se utiliza la penicilina. Aparece por lo general tras tratamientos con más de 10 días con betalactámicos a dosis altas, aumentando su incidencia al incrementarse la dosis acumulativa del antibiótico. Con frecuencia está precedida de fiebre o exantema que sirven de señales de alarma. A diferencia de la neutropenia provocada por otros fármacos no quimioterápicos, la neutropenia por betalactámicos no suele durar más de 10 días, y excepcionalmente conlleva complicaciones infecciosas o muerte. Aunque cualquier betalactámico puede provocar neutropenia, las publicaciones en los últimos años se han centrado en la neutropenia causada por piperacilina-tazobactam o por cefepima, demostrando que la incidencia de neutropenia durante tratamientos prolongados con ellos es elevada. La aparente contradicción con los resultados de los ensayos clínicos con estos antibióticos, que no habían detectado esta complicación, se debe a que en estos ensayos los tratamientos eran menores de 2 semanas. En el desarrollo de nuevos betalactámicos se debe tener presente la posible aparición de neutropenia durante tratamientos intravenosos prolongados (AU)

Beta-lactam-induced neutropenia has been a well-recognized problem since the initiation of penicillin use. It generally develops following high-dose beta-lactam treatment lasting longer than 10 days, and its frequency rises with increases in the cumulative antibiotic dose. Beta-lactam-induced neutropenia is frequently preceded by fever or rash, which can be considered alarm signs. Unlike neutropenia induced by other nonchemotherapy drugs, beta-lactam-induced neutropenia usually lasts less than 10 days and infrequently causes infectious complications or death. Although any beta-lactam agent can cause neutropenia, recent studies have focused on cases of piperacillin-tazobactam- or cefepime-induced neutropenia; a high incidence of neutropenia has been demonstrated during prolonged treatment with these antibiotics. The apparent contradiction with the results of clinical trials that did not detect this complication is due to the fact that they involved treatments shorter than two weeks. The potential for the development of neutropenia during lengthy intravenous treatment should be borne in mind in the development of new beta-lactams (AU)

[Beta-lactam-induced neutropenia. An old forgotten companion]. / Neutropenia secundaria a betalactámicos. Una vieja compañera olvidada.

Beta-lactam-induced neutropenia has been a well-recognized problem since the initiation of penicillin use. It generally develops following high-dose beta-lactam treatment lasting longer than 10 days, and its frequency rises with increases in the cumulative antibiotic dose. Beta-lactam-induced neutropenia is frequently preceded by fever or rash, which can be considered alarm signs. Unlike neutropenia induced by other nonchemotherapy drugs, beta-lactam-induced neutropenia usually lasts less than 10 days and infrequently causes infectious complications or death. Although any beta-lactam agent can cause neutropenia, recent studies have focused on cases of piperacillin-tazobactam- or cefepime-induced neutropenia; a high incidence of neutropenia has been demonstrated during prolonged treatment with these antibiotics. The apparent contradiction with the results of clinical trials that did not detect this complication is due to the fact that they involved treatments shorter than two weeks. The potential for the development of neutropenia during lengthy intravenous treatment should be borne in mind in the development of new beta-lactams.

[Necrotizing soft tissue infections: nomenclature and classification]. / Infecciones necrosantes de partes blandas: nomenclatura y clasificación.

Terminology used to refer to necrotizing infections is extensive because of the absence of clear definitions and the use of classification systems based on a variety of criteria, including etiologic, microbiologic, anatomic, and clinical aspects. This situation has led to some confusion. In the attempt to unify terminology, it might be more appropriate to use only the terms necrotizing fasciitis and myonecrosis, in which differentiation is mainly anatomical. Another option would be to use only the expression necrotizing soft tissue infections, a non-specific term, since these constitute a group of clinical processes having similar pathophysiologic characteristics and therapeutic principles.

Infecciones necrosantes de partes blandas:nomenclatura y clasificación / Necrotizing soft tissue infections: nomenclature and classification

La terminología utilizada para referirse a las infecciones necrosantes de partes blandas (INPB) es abundante debido a la ausencia de definiciones claras y a la utilización de diversas clasificaciones que han considerado aspectos etiológicos, microbiológicos, anatómicos y/o clínicos. Esto ha llevado a un cierto grado de confusión. A efectos de unificar la terminología sería más adecuado emplear exclusivamente los términos fascitis necrosante y mionecrosis, cuya diferenciación es básicamente anatómica, o incluso emplear únicamente la expresión INPB, sin especificar, por cuanto constituye un conjunto de condiciones clínicas con importantes semejanzas fisiopatológicas y principios terapéuticos similares. (AU)