Real-world effectiveness and factors associated with increased mortality in non-critically ill patients with COVID-19 pneumonia receiving remdesivir.

OBJECTIVES: Evidence on the effectiveness of remdesivir when used in real-life clinical practice is controversial. This study aims to analyse its effectiveness and the factors associated with increased mortality in non-critically ill patients with COVID-19 pneumonia who require supplemental low-flow oxygen and received remdesivir. METHODS: A retrospective cohort study was conducted at Ramón y Cajal University Hospital (Madrid, Spain) which included all patients treated with remdesivir in our institution during the second pandemic breakout in Spain, from August to November 2020. Treatment with remdesivir was limited to non-critically ill patients with COVID-19 pneumonia requiring low-flow supplemental oxygen, with a treatment duration of 5 days. RESULTS: A total of 1757 patients were admitted with COVID-19 pneumonia during the study period, of which 281 non-critically ill patients were treated with remdesivir and included in the analysis. Mortality at 28 days after initiation of treatment was 17.1%. The median (IQR) time to recovery was 9 days (6-15). 104 (37.0%) patients had complications during hospitalisation, with renal failure being the most frequent (31 patients; 36.5%). After adjustment for confounding factors, high-flow oxygen therapy was associated with increased 28-day mortality (HR 2.77; 95% CI 1.39 to 5.53; p=0.004) and decreased 28-day clinical improvement (HR 0.54; 95% CI 0.35 to 0.85; p=0.008). A significant difference in survival and clinical improvement was identified between patients treated with high and low-flow oxygen. CONCLUSION: The 28-day mortality rate in patients treated with remdesivir needing low-flow oxygen therapy was higher than that published in clinical trials. Age and increased oxygen therapy needed after the beginning of treatment were the main risk factors associated with mortality.

Postoperative Blood Pressure Deficit and Acute Kidney Injury After Liver Transplant.

OBJECTIVES: Acute kidney injury is a common cause of morbidity in liver transplant recipients. In critically ill patients who received an orthotopic liver transplant, we examined whether those with acute kidney injury had a greater deficit between pretransplant and posttransplant hemodynamic pressure-related parameters compared with those without acute kidney injury in the early postoperative period. MATERIALS AND METHODS: We included patients who underwent an orthotopic liver transplant during the study period. We obtained premorbid and intensive care unit time-weighted average values for hemodynamic pressure-related parameters (systolic, diastolic, and mean arterial pressure; central venous pressure; mean perfusion pressure; and diastolic perfusion pressure) and calculated deficits in those values. We defined acute kidney injury progression as an increase of ≥1 Kidney Disease: Improving Global Outcomes stage. RESULTS: We included 150 eligible transplantrecipients, with 88 (59%) having acute kidney injury progression. Acute kidney injury was associated with worse clinical outcomes. All achieved pressure-related values were similar between transplant recipients with or without acute kidney injury progression. However, those with acute kidney injury versus those without progression had greater diastolic perfusion pressure deficit at 12 hours (-8.33% vs 1.93%; P = .037) and 24 hours (-7.38% vs 5.11%; P = .002) and increased central venous pressure at 24 hours (46.13% vs 15%; P = .043) and 48 hours (40% vs 20.87%; P = .039). CONCLUSIONS: Patients with acute kidney injury progression had a greater diastolic perfusion pressure deficit and increased central venous pressure compared with patients without progression. Such deficits might be modifiable risk factors for the prevention of acute kidney injury progression.

Machine-learning-derived predictive score for early estimation of COVID-19 mortality risk in hospitalized patients.

The clinical course of COVID-19 is highly variable. It is therefore essential to predict as early and accurately as possible the severity level of the disease in a COVID-19 patient who is admitted to the hospital. This means identifying the contributing factors of mortality and developing an easy-to-use score that could enable a fast assessment of the mortality risk using only information recorded at the hospitalization. A large database of adult patients with a confirmed diagnosis of COVID-19 (n = 15,628; with 2,846 deceased) admitted to Spanish hospitals between December 2019 and July 2020 was analyzed. By means of multiple machine learning algorithms, we developed models that could accurately predict their mortality. We used the information about classifiers' performance metrics and about importance and coherence among the predictors to define a mortality score that can be easily calculated using a minimal number of mortality predictors and yielded accurate estimates of the patient severity status. The optimal predictive model encompassed five predictors (age, oxygen saturation, platelets, lactate dehydrogenase, and creatinine) and yielded a satisfactory classification of survived and deceased patients (area under the curve: 0.8454 with validation set). These five predictors were additionally used to define a mortality score for COVID-19 patients at their hospitalization. This score is not only easy to calculate but also to interpret since it ranges from zero to eight, along with a linear increase in the mortality risk from 0% to 80%. A simple risk score based on five commonly available clinical variables of adult COVID-19 patients admitted to hospital is able to accurately discriminate their mortality probability, and its interpretation is straightforward and useful.

Factors associated with mortality in patients hospitalized for COVID-19 in Spain. Data from the RERFAR registry.

OBJECTIVE: To determine the baseline characteristics associated with higher  mortality at 42 days in patients hospitalized for COVID-19 in Spain. METHOD: The study analyzed a prospective cohort of hospitalized COVID-19  patients. The dependent variable was 42-day mortality. Data on the subjects'  demographic and clinical characteristics, comorbidities, usual therapy and  supportive interventions and treatments was collected within 48 hours from  admission. To determine the potential association of the data with mortality, a  multivariate analysis was performed using logistic regression. RESULTS: 15,628 patients were included, 18.2% of whom (n = 2,806) died  during the study period. According to the multivariate analysis, the variables  that were significantly associated (p < 0.05) with mortality upon admission  were: being referred from a nursing home (OR 1.9); having a high respiratory  rate (OR 1,5); having moderate (OR 1.7) or severe (OR 2.9) pneumonia  (CURB-65); aspartate aminotransferase transaminase ≥ 100 IU/l (OR 2.1);  lactate dehydrogenase ≥ 360 IU/L (OR 1.6); procalcitonin > 0.5 ng/mL (OR  1.8); creatine kinase ≥ 294 U/L (OR 1.5); D-dimer > 3,000 ng/mL (OR 1.5);  hemoglobin < 11.6 g/dL (OR 1.4) and C-reactive protein > 120 mg/L (OR 1.2;  requiring respiratory support within the first 48 hours (oxygen therapy [OR  2.0], non-invasive ventilation [OR 2.8], and mechanical ventilation [OR 3.5]);  and being treated with interferon-beta (OR 1.5). On the contrary, being under  80 years of age was associated with lower mortality. CONCLUSIONS: The analysis, based on the data in the RERFAR registry, showed that the factors associated with poorer prognosis were older age,  assessed using the CURB-65 scale, level of respiratory support required,  severe pneumonia (CURB-65), hypertransaminasemia, elevated creatine  kinase, lactate dehydrogenase, and D-dimer levels, anemia, and elevated  respiratory rate.

OBJETIVO: Determinar las características basales que se asocian a una mayor  mortalidad a los 42 días en aquellos pacientes hospitalizados por COVID-19 en  España.Método: Cohorte prospectiva de pacientes COVID-19 hospitalizados. La  variable dependiente fue la mortalidad a los 42 días. Además, se recogieron  características demográficas, clínicas, comorbilidades, tratamiento habitual,  intervenciones de soporte y tratamientos en las primeras 48 horas del ingreso.  Para determinar la asociación con la mortalidad, se realizó un análisis  multivariante mediante regresión logística. Resultados: Se incluyeron 15.628 pacientes, de ellos falleció el 18,2% (n =  2.806). El análisis multivariante mostró que las variables asociadas significativamente (p < 0,05) con la mortalidad al ingreso fueron:  proceder de un centro sociosanitario (odds ratio OR 1,9), frecuencia  respiratoria (odds ratio 1,5), gravedad de neumonía (CURB-65) moderada  (odds ratio 1,7) o alta (odds ratio 2,9), transaminasa aspartato  aminotransferasa ≥ 100 UI/l (odds ratio 2,1), lactato-deshidrogenasa ≥ 360  UI/l (odds ratio 1,6), procalcitonina > 0,5 ng/ml (odds ratio 1,8), creatina- quinasa ≥ 294 U/l (odds ratio 1,5), dímero D > 3.000 ng/ml (odds ratio 1,5),  hemoglobina < 11,6 g/dl (odds ratio 1,4) y proteína C reactiva > 120 mg/l  (odds ratio 1,2), necesidad de soporte respiratorio en las primeras 48 horas  (odds ratio 2,0 de oxigenoterapia; odds ratio 2,8 ventilación no invasiva y odds ratio 3,5 ventilación mecánica) y tratamiento con interferón-beta (odds ratio  1,5). Por el contrario, ser menor de 80 años se asoció a una menor mortalidad. Conclusiones: El análisis del Registro Español de Resultados de  farmacoterapia frente a COVID-19 muestra que los factores asociados a peor pronóstico son: mayor edad, valoración mediante la escala CURB­65, el nivel de requerimiento de soporte respiratorio, neumonía grave (CURB­65), hipertransaminasemia, elevación de creatina-quinasa, lactato- deshidrogenasa, y dímero-D, anemia y elevación de la frecuencia respiratoria.

Impact of Ceftazidime-Avibactam Treatment in the Emergence of Novel KPC Variants in the ST307-Klebsiella pneumoniae High-Risk Clone and Consequences for Their Routine Detection.

The emergence of Klebsiella pneumoniae isolates carrying novel blaKPC variants conferring ceftazidime-avibactam (CAZ/AVI) resistance is being increasingly reported. We evaluated the accuracy of phenotypic methods commonly used in routine clinical laboratories in the detection of novel K. pneumoniae carbapenemase (KPC) enzymes. Additionally, we characterized by whole-genome sequencing (WGS) the KPC-ST307-K. pneumoniae isolates recovered in our hospital before and after CAZ/AVI therapy. Rectal colonization or infection by carbapenem-resistant KPC-3 K. pneumoniae isolates (imipenem MIC, 16 mg/L; meropenem MIC, 8 to >16 mg/L) and CAZ/AVI-susceptible isolates (CAZ/AVI MIC, 1 to 2 mg/L) were first detected in three intensive care unit (ICU) patients admitted between March 2020 and July 2020. KPC K. pneumoniae isolates with increased CAZ/AVI MICs (8 to 32 mg/L) and carbapenem susceptibility (imipenem and meropenem MIC, <1 mg/L) were recovered within 6 to 24 days after CAZ/AVI treatment. WGS confirmed that all KPC K. pneumoniae isolates belonged to the sequence type 307 (ST307) high-risk clone and carried identical antimicrobial resistance genes and virulence factors. The presence of the novel blaKPC-46, blaKPC-66, and blaKPC-92 genes was confirmed in the K. pneumoniae isolates with increased CAZ/AVI MICs and restored carbapenem activity. KPC production was confirmed by immunochromatography, the eazyplex Superbug CRE system, and the Xpert Carba-R assay in all KPC K. pneumoniae isolates, but not in any isolate using chromogenic agar plates for carbapenemase producers (ChromID-CARBA), the KPC/MBL/OXA-48 Confirm kit, and the ß-CARBA test. Nevertheless, all grew in chromogenic agar plates for extended-spectrum ß-lactamase (ESBL) producers (ChromID-ESBL). We report the failure of the most common phenotypic methods used for the detection of novel KPC carbapenemases but not of rapid molecular or immunochromatography assays, thus highlighting their relevance in microbiology laboratories.

Combination of arterial lactate levels and Cv-aCO2/Da-vO2 ratio to predict early allograft dysfunction after liver transplantation.

PURPOSE: We examined the ability of the P(v-a)CO2/Da-vO2 ratio combined with elevated lactate levels to predict early allograft dysfunction (EAD). MATERIALS AND METHODS: Patients were classified into four groups according to lactate levels and P(v-a)CO2/Da-vO2 ratio: Group 1; lactate >2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio >1.0; Group 2; lactate >2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio <1.0; group 3; lactate<2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio >1.0; group 4; lactate<2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio <1.0. We defined EAD according to Olthoff criteria. RESULTS: One-hundred and fifty patients were included. EAD occurred in 41 patients (27.3%), and was associated with worse graft survival at 1 year (92% vs. 73%; P = ,003) as well as a higher re-transplantation rate (4,6% vs. 17,1%; P = ,019). The multivariate analysis revealed that P(v-a)CO2/Da-vO2 ratio at T6 [OR 7.05(CI95% 2.77-19.01, P<.001)] was an independent predictor for EAD. Belonging to group 1 at 6 h was associated with worse clinical outcomes but no association was found with 1-year graft survival or 1-year patient survival. CONCLUSIONS: In this single center, prospective, observational study in patients who received an OLT, we found that elevated lactate levels combined with a high Cv-aCO2/Da-vO2 after 6 h was associated with the development of EAD and worse clinical outcomes in the early postoperative period.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on nosocomial Clostridioides difficile infection.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has induced a reinforcement of infection control measures in the hospital setting. Here, we assess the impact of the COVID-19 pandemic on the incidence of nosocomial Clostridioides difficile infection (CDI). METHODS: We retrospectively compared the incidence density (cases per 10,000 patient days) of healthcare-facility-associated (HCFA) CDI in a tertiary-care hospital in Madrid, Spain, during the maximum incidence of COVID-19 (March 11 to May 11, 2020) with the same period of the previous year (control period). We also assessed the aggregate in-hospital antibiotic use (ie, defined daily doses [DDD] per 100 occupied bed days [BD]) and incidence density (ie, movements per 1,000 patient days) of patient mobility during both periods. RESULTS: In total, 2,337 patients with reverse transcription-polymerase chain reaction-confirmed COVID-19 were admitted to the hospital during the COVID-19 period. Also, 12 HCFA CDI cases were reported at this time (incidence density, 2.68 per 10,000 patient days), whereas 34 HCFA CDI cases were identified during the control period (incidence density, 8.54 per 10,000 patient days) (P = .000257). Antibiotic consumption was slightly higher during the COVID-19 period (89.73 DDD per 100 BD) than during the control period (79.16 DDD per 100 BD). The incidence density of patient movements was 587.61 per 1,000 patient days during the control period and was significantly lower during the COVID-19 period (300.86 per 1,000 patient days) (P < .0001). CONCLUSIONS: The observed reduction of ~70% in the incidence density of HCFA CDI in a context of no reduction in antibiotic use supports the importance of reducing nosocomial transmission by healthcare workers and asymptomatic colonized patients, reinforcing cleaning procedures and reducing patient mobility in the epidemiological control of CDI.

[Self-reported experience in patients treated with Hepatitis C direct acting antivirals]. / Experiencia autorreferida en pacientes tratados con antivirales directos frente al virus de la hepatitis C.

BACKGROUND AND OBJECTIVE: To learn about and analyze the self-reported treatment experience of HCV patients who started treatment with direct acting antivirals agents (DAA), at a real-time, proactive and integrated into the pharmaceutical care healthcare process, using a prospective questionnaire completed by patients as clinical tool. MATERIAL AND METHODS: Observational and cross-sectional study conducted between April (start of the National Strategic Plan) and December 2015 in the Outpatient Pharmacy Service. The questionnaire includes variables related to health related quality of life (HRQOL), adherence, adverse effects (AEs), satisfaction, and usefulness of the Pharmacy Service implemented training program. A descriptive analysis of all variables included in the study was conducted and the influence of different variables analyzed in the degree of adherence and HRQOL. The analysis of the differences was performed using chi-square test and simple logistic regression model for calculation of OR. We use SPSS version 20 program and statistical significance for values of p < 0.05 was considered. RESULTS: 155 of the 226 surveys returned, with a response rate of 68.6%. Referring to the HRQOL (evaluation of physical and emotional state), 38.7% of patients reports that their physical and emotional state is much better from the start of treatment. The presence of EA and worse global information of their disease was associated with worse physical and emotional state (p < 0.05). Reported adherence was 84.5% and the treatment was evaluated as very good or good by 87% of patients. 52.9% had no adverse effects related to the medication and the training process performed by the specialist pharmacist at the first visit 96.7% of patients assessed as very good or good. CONCLUSIONS: Self-reported experience acquired through direct and constant contact with patients provides information on important aspects of treatment. We believe that these tools should be incorporated into pharmaceutical care procedures as a way to maintain continuity in patients direct contact. They also induce patients to a self-assessment of various aspects of their own treatment, which can help achieve greater involvement in it and can contribute to achieve the maximum health outcome in pharmacotherapy.

Introducción y objetivo: Conocer y analizar la experiencia autorreferida del tratamiento de los pacientes VHC que iniciaron tratamiento con agentes antivirales directos (AAD), a tiempo real, de forma proactiva e integrada en el proceso asistencial de atención farmacéutica. Material y métodos: Estudio observacional y transversal desarrollado entre abril (inicio del Plan Estratégico Nacional) y diciembre de 2015 en la Consulta Externa del Servicio de Farmacia. Se utilizó como herramienta un cuestionario prospectivo cumplimentado por los pacientes donde se recogieron variables relacionadas con la calidad de vida vinculadas con la salud (CVRS), adherencia, efectos adversos (EA), satisfacción con el tratamiento, y valoración y utilidad del programa formativo implementado por el Servicio de Farmacia. Se realizó un análisis descriptivo de todas las variables incluidas en el estudio y se analizó la influencia de las diferentes variables en el grado de adherencia y CVRS. El análisis de las diferencias entre los dos grupos se realizó mediante el test de chi cuadrado y el cálculo de las OR con un modelo de regresión logística simple. Se utilizó el programa SPSS® versión 20, y se estableció una significación estadística para valores de p < 0,05. Resultados: Se recogieron155 encuestas de las 226 enviadas, tasa de respuesta del 68,6%.En referencia a la CVRS (valoración del estado físico y emocional), un 38,7% de los pacientes refieren que su estado físico y emocional es mucho mejor desde el inicio del tratamiento. La presencia de EA y una peor información global de su enfermedad se asoció con un peor estado físico y emocional (p < 0,05). La adherencia reportada fue del 84,5% y el tratamiento fue valorado como muy bueno o bueno por el 87% de los pacientes. Un 52,9% de los pacientes no tuvieron efectos adversos relacionados con la medicación y el proceso formativo realizado por el farmacéutico especialista en la primera consulta fue valorado por el 96,7% de los pacientes como muy bueno o bueno. Conclusiones: La experiencia autorreferida obtenida a través de un contacto directo y permanente con los pacientes permite obtener información sobre aspectos importantes del tratamiento. Creemos que estas herramientas deben incorporarse a los procedimientos de atención farmacéutica como una forma de mantener la continuidad. Además, inducen al paciente a una autoevaluación de diversos aspectos de su propio tratamiento, que pueden ayudar a conseguir una mayor implicación en el mismo y contribuir a conseguir el máximo resultado en salud posible de la farmacoterapia.

Cross-cultural Adaptation and Validation of the Medication Regimen Complexity Index Adapted to Spanish.

BACKGROUND: The most widely used validated instrument to assess the complexity of medication regimens is the Medication Regimen Complexity Index (MRCI). OBJECTIVE: This study aimed to translate, adapt, and validate a reliable version of the MRCI adapted to Spanish (MRCI-E). METHODS: The cross-cultural adaptation process consisted of an independent translation by 3 clinical pharmacists and a backtranslation by 2 native English speakers. A reliability analysis was conducted on 20 elderly randomly selected patients. Two clinical pharmacists calculated the MRCI-E from discharge treatments and 2 months later. For the validity analysis, the sample was augmented to 60 patients. Convergent validity was assessed by analyzing the correlation between the number of medications; discriminant validity was stratified by gender; and predictive validity was determined by analyzing the ability to predict readmission and mortality at 3 and 6 months. RESULTS: The MRCI-E retained the original structure of 3 sections. The reliability analysis demonstrated an excellent internal consistency (Cronbach's α=0.83), and the intraclass correlation coefficient exceeded 0.9 in all cases. The correlation coefficient with the number of medications was 0.883 ( P<0.001). No significant differences were found when stratified by gender (3.6; 95%CI=-2.9 to 10.2; P=0.27). Patients who were readmitted at 3 months had a higher MRCI-E score (10.7; 95%CI=4.4 to 17.2; P=0.001). The differences remained significant in patients readmitted at 6 months, but differences in mortality were not detected. CONCLUSIONS: The MRCI-E retains the reliability and validity of the original index and provides a suitable tool to assess the complexity of medication regimens in Spanish.

Enteral Nutrition in Patients Receiving Mechanical Ventilation in a Prone Position.

BACKGROUND: Patients treated with mechanical ventilation in the prone position (PP) could have an increased risk for feeding intolerance. However, the available evidence supporting this hypothesis is limited and contradictory. OBJECTIVE: To examine the feasibility and efficacy of enteral nutrition (EN) support and its associated complications in patients receiving mechanical ventilation in PP. METHODS: Prospective observational study including 34 mechanically ventilated intensive care patients who were turned to the prone position over a 3-year period. End points related to efficacy and safety of EN support were studied. RESULTS: In total, more than 1200 patients were admitted to the intensive care unit over a period of 3 years. Of these, 34 received mechanical ventilation in PP. The mean days under EN were 24.7 ± 12.3. Mean days under EN in the supine position were significantly higher than in PP (21.1 vs 3.6; P < .001), but there were no significant differences in gastric residual volume adjusted per day of EN (126.6 vs 189.2; P = .054) as well as diet volume ratio (94.1% vs 92.8%; P = .21). No significant differences in high gastric residual events per day of EN (0.06 vs 0.09; P = .39), vomiting per day of EN (0.016 vs 0.03; P = .53), or diet regurgitation per day of EN (0 vs 0.04; P = .051) were found. CONCLUSIONS: EN in critically ill patients with severe hypoxemia receiving mechanical ventilation in PP is feasible, safe, and not associated with an increased risk of gastrointestinal complications. Larger studies are needed to confirm these findings.

[Risk prevention evaluation in the incorporation of new drugs for healthcare practices: a methodological proposal]. / Evaluación preventiva de riesgos en la incorporación de nuevos medicamentos a la práctica asistencial: una propuesta metodológica.

OBJECTIVE: Submit a preventive assessment methodology for the risk of medication errors when incorporating new drugs in clinical practice as well as a description of the types of actions arising from such action. MATERIALS AND METHODS: A Standard Operating Procedure was established which defines and plans the process of assessing the risks of new drugs purchased by the Pharmacy Services before being incorporated into the distribution and dispensation channels. The pharmacist responsible for each area fills the Risk Assessment Form, a questionnaire that facilitates the analysis of the product characteristics and provides guidance on safety measures to be taken depending on the results of that assessment. If it is confirmed that the drug requires some additional security measures to be taken, all professionals and technical staff of the Pharmacy Services shall be informed of measures to be taken. RESULTS: Between 2011 and 2013, 64 drugs were assessed. 35 of them (54.6%) required some additional security measure to be applied before being incorporated into clinical practice. CONCLUSIONS: The implementation of the method of preventive risk assessment for new drugs purchased by the Pharmacy Services can be a very useful tool when taking the measures deemed necessary to minimize the likelihood of a medication error occurring before they are incorporated into the distribution/dispensing channels put in place by the Pharmacy Services.

Drug prescribing in patients with renal impairment optimized by a computer-based, semi-automated system.

BACKGROUND: According to several studies, despite of the existence of several published guidelines for dosing adjustments based on renal function, inappropriate prescribing is a common drug-related problem in inpatient care. OBJECTIVE: We developed and implemented a system for drug dosage adjustment integrated into the Hospital computer provider order entry system. This system allows pharmacists to identify patients with reduced renal function, identify medication orders that may require dosage modifications based on renal function, and generate an alert with a recommendation of specific dosage adjustment. Using the Summary of Product Characteristics and two drug databases (Micromedex 2.0® and Lexicomp®), specific dosage guidelines for drugs used in patients with renal impairment were established. SETTING: A 264-bed tertiary teaching hospital. METHODS: We performed a quasi-experimental, one-group, pretest-posttest study to assess the efficacy of this intervention program. We compared the differences between the frequency of appropriate orders pre- and post-test using the McNemar test. MAIN OUTCOME MEASURES: the frequency of appropriate orders before the recommendation (pre-test) and after the recommendation (post-test). RESULTS: Before the intervention, the frequency of appropriate prescribing based on renal function was 65 %. After the intervention, this frequency was 86 % (p < 0.001). The interventions were more frequent in the emergency department (45 %). The program required 30-45 min of pharmacist time per day. The average number of patients reviewed daily was 28. This study found that a computer-based, semi-automated drug-dosage program for renal failure patients was able to reduce the number of inappropriate orders due to renal insufficiency.

Study of the gastrointestinal tolerance of a new tablet formulation of the lopinavir/ritonavir antiretroviral in HIV-infected patients.

BACKGROUND: Preliminary studies suggest that the new film-coated tablet formulation of lopinavir/ritonavir (LPV/r-fct) could cut down the rate of adverse gastrointestinal symptoms of the conventional lopinavir/ritonavir soft gelatine capsules (LPV/r-sgc). OBJECTIVE: To ascertain the difference in the rate of adverse gastrointestinal symptoms in patients who switch from LPV/r-sgc to LPV/r-fct. METHODS: An uncontrolled, open, prospective study including a pre/post comparison using the Gastrointestinal Symptom Rating Scale (GSRS) modified to the characteristics of the protease inhibitors. RESULTS: Seventy patients were included, with a mean time of treatment, with the new formulation of 77 days [confidence interval (CI) 95%: 70 to 84]. The total GSRS score was 26.96 (CI 95%: 25.02 to 28.89) in the prechange survey and 26.27 (CI 95%: 24.08 to 28.47) in the postchange survey, with a mean difference of 0.69 points (CI 95%: -1.18 to 2.55, P = 0.47). None of the questions obtained the objective of a difference of at least 2 points, previously set as a clinically significant difference. Only 1 patient dropped the study due to gastrointestinal toxicity. CONCLUSIONS: Our study has unearthed no clinically significant differences in the gastrointestinal tolerance profile of (LPV/r-sgc) and (LPV/r-fct), measuring this tolerance level by application of the GSRS scale.