Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice.

PURPOSE: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice. MATERIALS AND METHODS: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression. RESULTS: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001). CONCLUSION: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.

Oral Methods of Urinary Alkalinization for High-dose Methotrexate Administration: Alternatives to Intravenous Sodium Bicarbonate During a Critical Drug Shortage.

A nationwide shortage of intravenous (IV) sodium bicarbonate required institutions to explore alternative options for urinary alkalinization for high-dose methotrexate (HDMTX). Children's Hospital Colorado implemented a protocol utilizing oral alkalinizing agents as alternatives to intravenous sodium bicarbonate during the shortage. The purpose of this study was to determine the safety and efficacy of oral alkalinization strategies for HDMTX administration. This retrospective study was conducted at a pediatric institution and evaluated cycles of HDMTX administered with at least one dose of oral sodium bicarbonate tablets or sodium citrate-citric acid oral solution. The time to achieve urine pH of ≥7 was 3.48 hours from the start of alkalinization. A median dose of 66.4 mEq/m/day of oral sodium bicarbonate was administered to maintain a urine pH of ≥7 until methotrexate was cleared. Gastrointestinal side effects occurred with 43% of HDMTX cycles and patients switched to IV sodium acetate in 25.5% of HDMTX cycles, primarily due to inadequate alkalinization or intolerance. During a shortage of IV sodium bicarbonate, oral alkalinization is an effective strategy for most patients to allow for administration of HDMTX.

Association of Clostridium difficile infections with acid suppression medications in children.

OBJECTIVE: Multiple studies have confirmed associations between acid suppression medication and Clostridium difficile infections (CDIs) in adults. Therefore, we sought to evaluate an association between acid suppression medications and CDI in children. STUDY DESIGN: A retrospective self-controlled case series was performed utilizing billing records from the TRICARE Management Activity military health system database. Children ages 2-18 years from October 1, 2001 to July 31, 2013, who had an outpatient or inpatient record of CDI diagnosis were included. The relative incidences (RIs) of CDI or recurrent CDI were calculated comparing time periods prescribed and not prescribed proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs). RESULTS: There were 2531 cases of CDI among 2437 patients, and 1190 (48.8%) were prescribed acid suppression medications. CDI were more likely to occur during periods when patients were prescribed a PPI (RI 2.36; 95% CI 2.22-2.52), H2RA (RI 1.95; 95% CI 1.63-2.34), or during periods while prescribed both simultaneously (RI 2.40; 95% CI 1.90-3.04). There were 265 (10.4%) cases that were classified as recurrent among 217 (8.9%) patients. Recurrent CDI also was found to be more likely during prescription periods of PPI (RI 1.74; 95% CI 1.51-2.00) and H2RA (RI 2.63; 95% CI 1.89-3.66). CONCLUSIONS: Acid suppression medications are associated with an increased risk of CDI and recurrent CDI. Judicious use of acid suppression medication should be considered, especially among those at highest risk for CDI.

Dispepsia funcional / Functional dyspepsia

As micoses superficisis säo as infecçöes mais comuns do tegumento cutâneo, envolvendo as partes queratinizadas, semiqueratinizadas, mucosas e os anexos pêlos e unhas.(au)

Calcium acetate versus calcium carbonate in the control of hyperphosphatemia in hemodialysis patients.

CONTEXT: Hyperphosphatemia has an important role in the development of bone and mineral abnormalities in end-stage renal disease (ESRD). OBJECTIVE: To compare the phosphorus binding power and the hypercalcemic effect of calcium acetate and calcium carbonate in hemodialysis patients. TYPE OF STUDY: Crossover, randomized, double-blind study. PLACE: A private hospital dialysis center. PARTICIPANTS: Fifty-two patients who were undergoing regular hemodialysis three times a week ([Ca++] dialysate = 3.5 mEq/L). PROCEDURES: Half of the patients were started on 5.6 g/day of calcium acetate and, after a 2 week washout period, received 6.2 g/day of calcium carbonate. The other half followed an inverse protocol. MAIN MEASUREMENTS: Clinical interviews were conducted 3 times a week to monitor for side effects. Determinations of serum urea, calcium, phosphorus, hematocrit, Kt/V and blood gas analysis were obtained before and after each treatment. RESULTS: Twenty-three patients completed the study. A significant increase in calcium plasma levels was only observed after treatment with calcium carbonate [9.34 mg/dl (SD 0.91) vs. 9.91 mg/dl (SD 0.79), P < 0.01]. The drop in phosphorus levels was substantial and significant for both salts [5.64 mg/dl (SD 1.54) vs. 4.60 mg/dl (SD 1.32), P < 0.01 and 5.89 mg/dl (SD 1.71) vs. 4.56 mg/dl (SD 1.57), P < 0.01, for calcium acetate and calcium carbonate respectively]. The percentage reduction in serum phosphorus (at the end of the study) per milliequivalent of salt administered per day tended to be higher with calcium acetate but statistical significance was not found. CONCLUSION: Calcium acetate can be a good alternative to calcium carbonate in the handling of hyperphosphatemia in ESRD patients. When calcium acetate is used, control of hyperphosphatemia can be achieved with a lower administration of calcium, perhaps with a lower risk of hypercalcemia.

Principales interacciones medicamentosas en una emergencia hospitalaria: análisis de 100 casos / Main drug interactions at hospital: emergency department analysis of 100 cases

Revisamos prospectivamente las historias clínicas de 100 pacientes consecutivos que ingresaron por emergencia de un hospital general el primer tremestre de 1991, para determinar fármacos más frecuentemente usados y sus interacciones utilizando un programa computarizado (Drug Interaction Program) haciendo énfasis en medicamentos antiulcerosos. El número de drogas indicada por pacientes fue 4.29 ñ 1.39. Los antiácidos (39%) y la cimetidina (35%) ocuparon el tercero y cuarto lugar. Hubo interaciones en 79 pacientes y en 66 (84%) fueron importantes, promediandose 2.44 ñ 2.13 interacciones por paciente. Los antiácidos y la cimetidina fueron igualmente indicados, de 35 pacientes que recibieron cimetidina 3 (8.5%) tenían indicación primaria de su uso (Hemorragia Digestiva). La interacción clínica de la cimetidina con otros medicamentos es analizada. Nuestros resultados indican que las interacciones medicamentosas son un riesgo permanente en nuestros hospitales. Sugerimos la utilización de un programa computarizado de interacciones medicamentosas o una tabla actualizada de medicamentos en las emergencias de nuestros hospitales

[Main drug interactions at a hospital emergency department. Analysis of 100 cases]. / Principales interacciones medicamentosas en una emergencia hospitalaria. Analysis de 100 casos.

We prospectively reviewed clinical charts of 100 consecutive patients that were admitted during the first trimester 1991 to the Emergency Department of a general hospital in order to determine the more frequent prescribed drugs and their interactions using a computer program (Drug Interaction Program), emphasizing in those drugs used to treat peptic ulcers. Number of drugs prescribed to each patient was 4.20 +/- 1.39. Antacids (39%) and cimetidine (35%) occupied the third and fourth place. There were interactions in 79 patients and in 66 of them (84%) they were important. Antacid and cimetidine were similarly prescribed, but of 35 patients who received cimetidine only 3 (8.5%) had a primary indication for its use (Gastrointestinal bleeding). Significant clinical interactions of cimetidine with other medications are analyzed. Our results indicate that drug interactions are a permanent risk in our hospitals. We suggest to use a computer program on drug interactions or an updated chart of medications in the emergency rooms of our hospitals.

Tratamiento de la enfermedad acidopeptica / Treatment of the acidpeptic disease

Se hace una revision del tratamiento de la enfermedad acidopeptica, definiendo para el efecto, las drogas existentes y su utilidad. Se clasifican en aquellas que modfician el factor acido (antiacidos, anticolinergicos, antogonistas de los receptores H2 y los Benzimidazoles sustitiudos), las que aumentan la resistencia (sucralfate, bismutos y carbenoxolona), y otras (tranquilizantes y neurolepticos y las prostaglandinas). Se discuten los esquemas terapeuticos utilizados. Finalmente se hacen algunas anotaciones sobre la importancia que tiene la cirugia en el tratamiento de la enfermedad acidopeptica