Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences.

Paxlovid (nirmatrelvir plus ritonavir) is a new oral antiviral therapeutic for the treatment and post-exposure prophylaxis of COVID-19. Nirmatrelvir is an inhibitor of SARS-CoV-2 main protease, while ritonavir is used as a CYP3A inhibitor in low doses to slow the metabolism of nirmatrelvir, thus enhancing their therapeutic effect. The isoenzyme CYP3A4 is responsible for at least part of the oxidative metabolism of approximately 60% of available medications and ritonavir is therefore a significant source of drug interactions. We describe here the drugs that are contraindicated or should be used with or without precautions when Paxlovid (nirmaltrevir plus ritonavir) should be administered according to each fact sheet in force at the Spanish Agency for Medicines and Health Products.

Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn's disease: results from a large Italian cohort study.

OBJECTIVE: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn's Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics. PATIENTS AND METHODS: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients. RESULTS: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment. CONCLUSIONS: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

Impacto del Servicio de Farmacia en la disminución de errores en la medicación en pediatría / Impact of the pharmaceutical actions to decrease medication errors in pediatrics

Estudio descriptivo de errores de medicación en el Tecnológico de Monterrey, Hospital San José Tec Salud, Escuela de Medicina y Ciencias de la Salud.Objetivo: Describir las intervenciones farmacéuticas que contribuyen a tener una tasa de error de medicación por debajo de los estándares internacionales.Material y métodos: Se consideró como error de medicación cualquier fallo en el proceso de medicación. Se revisaron prescripciones por el método de reporte de incidentes en expedientes de pacientes de 0-17 añosA de los últimos 12 meses (2017-2018).Resultados: Se detectaron 776 errores de 6.119 prescripciones (2,47%). El error más común fue aquel relacionado con la dosificación (60,3%). No se reportaron errores que resultaran en daño letal al paciente. El grupo terapéutico con mayor incidencia de errores fue el de los antibióticos seguido de los analgésicos.Conclusión: La intervención multidisciplinaria con el farmacéutico en el proceso de medicación permite una detección oportuna de errores que impacta la seguridad del paciente. (AU)

Descriptive and retrospective study of medical errors at, San Jose Monterrey Hospital School of medicine and Health science.Objective: To describe pharmaceutical interventions in order to keep a low incidence of medical errors.Material and methods: Medical error was defined as any unintended error in medication. We present a 12 Month (2017-2018) retrospective study using incident reports.Results: We identified 776 medication errors over a total of 6,119 reviewed prescriptions. (2.4%) The most frequent errors in prescription were dosage associated (60.3%). No lethal outcomes were reported. The most common group of medication errors were antibiotics followed by analgesics.Conclusion: Involving pharmacists in checking drug prescriptions has been the main factor for detecting and improving pediatric dosages leading to an important improvement in patient safety. (AU)

Competition between Superconductor - Ferromagnetic stray magnetic fields in YBa2Cu3O7-x films pierced with Co nano-rods.

Superconductivity and ferromagnetism are two antagonistic phenomena that combined can lead to a rich phenomenology of interactions, resulting in novel physical properties and unique functionalities. Here we propose an original hybrid system formed by a high-temperature superconducting film, patterned with antidots, and with ferromagnetic nano-rods grown inside them. This particular structure exhibits the synergic influence of superconductor (SC) - ferromagnetic (FM) stray fields, in both the superconducting behaviour of the film and the three-dimensional (3D) magnetic structure of nano-rods. We show that FM stray fields directly influence the critical current density of the superconducting film. Additional functionalities appear due to the interaction of SC stray fields, associated to supercurrent loops, with the non-trivial 3D remanent magnetic structure of FM nano-rods. This work unravels the importance of addressing quantitatively the effect of stray magnetic fields from both, the superconductor and the ferromagnet in hybrid magnetic nano-devices based on high temperature superconductors.

A comparison of the nutritional status between adult celiac patients on a long-term, strictly gluten-free diet and healthy subjects.

BACKGROUND/OBJECTIVES: There are conflicting data on the effect of a gluten-free diet (GFD) on the nutritional status of celiac patients. In the present study, we evaluated, in adult celiac patients, the influence of a long-term, strictly GFD on their nutritional status and compared it with matched healthy volunteers. SUBJECTS/METHODS: Our study included 39 celiac patients and 39 healthy volunteers. The body mass index (BMI) of patients and controls was evaluated at enrollment, while the patients' BMI before the GFD was retrieved from clinical records. In addition, at enrollment, in both groups, we compared BMI, fat mass (FM), bone mineral density (BMD), as well as their dietary intake, recorded on a 7-day diary. RESULTS: At the time of diagnosis, the majority of celiac patients (82.0%) had a normal BMI or were overweight, while 10.3% were malnourished. After the GFD, patients with a normal BMI showed a significant weight increase (P=0.002), but none of them switched in the overweight or obese category. Two (50%) of the four malnourished patients achieved a normal BMI. Controls and patients on a GFD had a similar BMI, FM, BMD and total calorie intake, but the amount of lipids and fiber intake was significantly different in the two groups (P=0.003 and P<0.0001, respectively). CONCLUSIONS: Our study demonstrates that a GFD is able to improve the nutritional status of celiac patients without inducing overweight or obesity. Our findings are related to a celiac population adopting a GFD based on a Mediterranean-type diet.

THE INTAKE OF FIBER MESOCARP PASSIONFRUIT (PASSIFLORA EDULIS) LOWERS LEVELS OF TRIGLYCERIDE AND CHOLESTEROL DECREASING PRINCIPALLY INSULIN AND LEPTIN.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for coronary artery disease, renal failure, retinopathy, and neuropathy. Over the last years, there has been an increasing demand in folk medicine for natural sources that could help in the treatment of chronic diseases, including diabetes. The rind of passion fruit (Passiflora edulis f. Flavicarpa) is traditionally used as a functional food due to its high concentration of soluble and insoluble fiber. OBJECTIVE: The aim of this study was to determine the effect of high-fiber diet albedo of passion fruit on the metabolic and biochemical profile in diabetic rats induced by alloxan (2%). DESIGN: The passion fruit mesocarp fiber was dried in an oven with circulating air at 60°C and pulverized. We used 32 adult male rats, divided into 4 groups: Wistar group 1 control (GC), Wistar group 2, 15% fiber (GF15), Wistar group 3, 30% fiber (GF30), Wistar group 4, fiber disolved in water (GFH2O). The ratio of passion fruit was prepared according to the AIN 93M guidelines, varying only the source of dietary fiber. The corresponding diet for each group was offered to the animals for 60 days. RESULTS: There was a statically significant decrease in plasma glucose for GFH2O, GF15%, and GF30% groups with 27.0%, 37.4%, and 40.2%, respectively. CONCLUSION: The use of mesocarp fiber of passion fruit at concentrations of 15% and 30% are an important dietary supplement for the treatment of DM due to its potential hypoglycemic effect, and its ability to reduce triglycerides and VLDL-cholesterol levels with a principal reduction of insulin and leptin.

Assessment of activity of Crohn's disease of the ileum and large bowel: proposal for a new multiparameter MR enterography score.

PURPOSE: We evaluated the diagnostic accuracy of magnetic resonance enterography (MR-E) in assessing Crohn's disease (CD) activity by differentiating acute, chronic and remission stages of disease through a quantitative MR-E assessment. MATERIALS AND METHODS: One hundred patients with a histological diagnosis of CD were studied with MR-E. Intestinal distension was obtained by oral administration of approximately 2 L of a polyethylene glycol solution (PEG). In all cases, the ileum and large bowel were imaged with morphological sequences (heavily T2-weighted single-shot, dual fast-field echo, balanced fast-field echo) and a postcontrast dynamic sequence (T1-weighted high-resolution isotropic volume excitation). Disease activity was assessed according to a multiparameter score (0-8) based on lesion morphology, signal intensity and contrast enhancement. MR-E findings were compared with clinical-laboratory data and disease activity indices [Crohn's Disease Activity Index (CDAI); Inflammatory Bowel Disease Questionnaire (IBDQ)]. Multiple regression analysis was performed by correlating MR-E score, CDAI and IBDQ. Frequencies were then compared using the χ (2) test. RESULTS: MR-E identified inactive disease in 9% of cases, chronic disease in 57% and active disease in the remaining 34%. The most frequently involved bowel segment was the terminal ileum (52%). A statistically significant correlation was found between MR-E score and CDAI (R=0.86; p<0.001) and between MR-E score and IBDQ (R=-0.83; p<0.001). The most suggestive parameter for disease activity was layered bowel-wall enhancement, a finding predominantly present in patients with increased CDAI (≥ 150) and/or local complications (χ (2)=7.13; p<0.01). CONCLUSIONS: MR-E is a noninvasive and diagnostic imaging modality for CD study and follow-up. The MR-E score proposed in this study proved to be useful in assessing disease severity and monitoring response to treatment.

Segmental colitis associated with diverticula: a rare clinical entity and a new challenge for the gastroenterologist.

BACKGROUND AND AIM: Segmental colitis associated with diverticula (SCAD) has recently drawn a particular attention in the field of rare forms of colitis because of some peculiarities suggesting both its autonomy as a clinical entity and a resemblance with the most relevant forms of inflammatory bowel diseases (IBD). Aim of this review was to report the state of art on this topic. METHODS: Epidemiological, clinical, endoscopic/histological and diagnostic features are described. Moreover, from both the pathogenetic and therapeutic point of view, new relevant information is highlighted regarding the possible role of tumour necrosis factor alpha (TNF-alpha) in mucosal inflammation. RESULTS: SCAD would appear as a rare autonomous clinical entity distinctive of old age, although it is still not well defined. It is likely that prevalence of SCAD could have been underestimated in the past since its main clinical presentation (namely bleeding without pain) is often found in elderly patients with diverticula. Endoscopy and histology could be helpful to discriminate it from infectious diverticulitis. Increasing evidence encourages the concept that SCAD includes pathogenetic and therapeutic aspects peculiar of IBD. This could be relevant for clinical management of SCAD. Indeed, the resolution of a severe, refractory case of SCAD has been recently reported with biological drugs used for IBD therapy. This observation could encourage, in the near future, the use of biological therapy in severe forms of SCAD as an alternative to surgery.

DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3.

Aberrant activation of the Wnt/beta-catenin signaling pathway is a hallmark of colon cancer. We show that the Wnt antagonist DICKKOPF-4 (DKK-4) gene is repressed by 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) in human colon cancer cells. This effect correlated with the inhibition of the DKK-4 promoter. Chromatin immunoprecipitation assays revealed that 1,25(OH)2D3 induces early and transient binding of the vitamin D receptor (VDR) and the SMRT corepressor to the region adjacent to the transcription start site of DKK-4. Additionally, we demonstrate that the DKK-4 gene is a new downstream target of TCF/beta-catenin. Remarkably, expression of DKK-4 messenger RNA (mRNA) was not detected in a series of 29 human normal (N) colon biopsies but expression was upregulated in all the matched tumour (T) tissues. An inverse correlation existed between the expression of DKK-4 and VDR RNA in the Ts. Ectopic DKK-4 expression increased the migration and invasion properties of colon cancer cells and conditioned media (CM) from DKK-4-expressing cells enhanced the capacity to migrate and form capillary-like tubules of human primary microvascular endothelial cells. In conclusion, DKK-4 is upregulated in colon cancer and is associated with the acquisition of malignant properties by neoplastic cells. DKK-4 downregulation is a novel effect of 1,25(OH)2D3 that may contribute to its anticancer action.

GNAS1 T393C polymorphism is associated with migraine.

Migraineurs have an interictal sympathetic nervous system (SNS) hypofunctionality and hypersensitivity to adrenergic amines. The GNAS1 T393C polymorphism has been associated with a distinct SNS sensitivity in healthy subjects. We tested GNAS1 T393C variant in two independent sets of subjects. In the case-control subset, 365 migraine patients [194 with aura (MA)] vs. 347 healthy controls were studied. A significant excess of the CC genotype was found in migraneurs (31.2%) as opposed to controls (20.2%; P=0.003). Using a logistic regression model corrected for sex, the CC genotype conferred a general risk for migraine twice [odds ratio (OR) 1.79, 95% confidence interval (CI) 1.27-2.53; P=0.001] higher than CT/TT genotypes. Using parents from 117 migraine families, a marginally significant trend for association could be observed (P=0.025), but the transmission disequilibrium test for alleles maternally transmitted failed to demonstrate familial association. In this subgroup, CC genotype conferred a risk for migraine over twice (OR 2.20; 95% CI 1.14-4.40; P=0.019) higher than TT/TC genotypes. In conclusion, the GNAS1 T393C variant is associated with migraine, which suggests a genetic basis for its higher SNS sensitivity.

Arritmia más frecuente en Pediatría. Taquicardia Paroxística Supraventricular

La taquicardia supraventricular es la arritmia más frecuente en Pediatría, siendo conocida por Taquicardia Paroxística Supraventricular (TPSV) por su comienzo y final brusco. Por la importancia de actualizar dicha temática, se realiza el presente estudio dada la incidencia que ha tenido en la Unidad de Cuidados Intensivos Pediátricos de Sancti Spíritus con el objetivo de lograr elevar los conocimientos de nuestros profesionales. Por definición se produce en cualquier localización por encima del haz de His. El mecanismo de producción más frecuente es por reentrada que puede ser en el propio nodo AV o por una vía accesoria como en el síndrome de Wolf Parkinson-White. El 50 % de los casos no se encuentra la causa desencadenante presentándose asintomática o con pocos síntomas a excepción del menor de un año en el que se presenta como insuficiencia cardíaca congestiva. En el momento de la crisis debe realizarse el EKG de 12 derivaciones el cual se repetirá al ceder el episodio. Para el manejo terapéutico es necesario comprobar el estado hemodinámico del niño y cuando se presenta fallo cardíaco es eficaz la cardioversión eléctrica sincronizada. La adenosina es el fármaco de elección, aunque en el mayor de dos años se puede valorar el uso del verapamilo. Así mismo otros medicamentos pueden ser utilizados como procainamida, beta-bloqueadores y propafenona. Generalmente para su manejo terapéutico continuo se necesitará amiodarona. Se impone para el seguimiento un trabajo de equipo constituido por cardiólogos, intensivistas y pediatras

Primary clarithromycin resistance in Italy assessed on Helicobacter pylori DNA sequences by TaqMan real-time polymerase chain reaction.

BACKGROUND: Helicobacter pylori clarithromycin resistance is increasing worldwide and different mutations are involved in its mechanisms. Recently, molecular methods have been proposed to assess these mutations. AIM: To assess prevalence of primary clarithromycin resistance in two Italian areas, and the distribution of involved mutations, by using a novel method for real-time polymerase chain reaction. METHODS: Two hundred and thirty-two H. pylori-positive patients undergoing oesophagogastroduodenoscopy in two Italian towns (Rome, centre Italy; Foggia, south Italy) were enrolled. Helicobacter pylori infection was detected by histology, rapid urease and urea breath tests. Clarithromycin resistance was assessed by TaqMan real-time polymerase chain reaction on paraffin-embedded antral biopsies. Results Primary clarithromycin resistance was detected in 62 (26.7%) patients. Its prevalence did not differ between the two areas (31.5%, centre vs. 23.3%, south; P=0.17) and between non-ulcer dyspepsia and peptic ulcer patients (28.4% vs. 20.7%, P=0.2). The A2143G point mutation was detected in 35 (56.4%) patients, A2142G in 14 (22.6%), A2142C in eight (12.9%), whilst a double mutation (A2143G plus A2142C or A2142G) was present in the remaining five (8.1%) cases. CONCLUSIONS: Our study found that primary clarithromycin resistance is highly prevalent in both central and southern Italy, and that A2143G is the most frequent point mutation involved in these areas.

DNA sequences and proteic antigens of H. pylori in cholecystic bile and tissue of patients with gallstones.

BACKGROUND: Although Helicobacter pylori DNA sequences have been detected in cholecystic bile and tissue of patients with gallstones, controversial results are reported from different geographic areas. AIM: To detect H. pylori in cholecystic bile and tissue of patients with gallstones from a previously uninvestigated geographic area, southern Italy. Detection included both the bacterial DNA and the specific antigen (H. pylori stool antigen) identified in the stools of infected patients for diagnostic purposes. PATIENTS AND METHODS: The study enclosed 33 consecutive patients undergoing laparoscopic cholecystectomy for gallstones. DNA sequences of H. pylori were detected by polymerase chain reaction in both cholecystic bile and tissue homogenate. Moreover, we assayed H.pylori stool antigen on gall-bladder cytosolic and biliary proteins after their extraction. Bacterial presence in the stomach was assessed by urea breath test in all patients and Deltadelta13CPDB value assumed as marker of intragastric load. Fisher's exact probability and Student's t-tests were used for statistical analysis. RESULTS: DNA sequences of H. pylori in bile were found in 51.5% and significantly correlated with its presence in cholecystic tissue homogenate (P<0.005), H. pylori stool antigen in gall-bladder (P=0.0013) and bile (P=0.04) proteins, gastric infection (P<0.01) and intragastric bacterial load (P<0.001). No correlation was found, however, with sex and age of the patients. CONCLUSIONS: Our prevalence value of bacterial DNA in bile and gall-bladder of patients with gallstones agreed with that of the only other Italian study. The simultaneous presence of both bacterial DNA and proteic antigen suggests that the same prototype of bacterium could be located at both intestinal and cholecystic level and, therefore, the intestine represents the source of biliary contagion.

Differential expression of multiple transglutaminases in human colon: impaired keratinocyte transglutaminase expression in ulcerative colitis.

BACKGROUND AND AIMS: Ulcerative colitis (UC) is characterised by refractory inflammatory ulceration and damage to the colon. The mechanisms underlying impaired healing have yet to be defined. As transglutaminase expression resulting in matrix protein cross linking is associated with increased wound healing in a rat model of colitis, we hypothesised that different types of transglutaminase might also play a role in UC. PATIENTS AND METHODS: Endoscopic and histological indices were studied in 26 patients with UC (10 active and 16 inactive) and in 20 normal controls undergoing colonoscopy. Transglutaminase activity was evaluated in plasma (factor XIIIa) by a radioenzymatic method. Factor XIIIa, tissue and keratinocyte transglutaminase protein content, and mRNA expression in the colon were evaluated by western blot analysis and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively. Colonic location of transglutaminases and their reaction products, the epsilon-(gamma-glutamyl)lysine bonds, was evaluated by immunohistochemistry using specific monoclonal antibodies. RESULTS: Transglutaminase activity was significantly lower in the plasma of patients with active UC (4.2 (2.4) mU/ml; p<0.05 v controls) than in those with inactive UC and controls (10.6 (2.2) and 12.1 (1.7) mU/ml). As shown by western blot, protein levels of tissue transglutaminase and factor XIIIa were unchanged in active UC compared with inactive disease and controls, while the keratinocyte form was reduced in active UC. Tissue transglutaminase and factor XIIIa immunostaining was strongly present in damaged areas colocalising with isopeptide bonds. In contrast, the keratinocyte form was almost absent in active UC and localised in the upper part of the crypts in normal subjects. RT-PCR showed upregulation of tissue transglutaminase mRNA in active UC (320% compared with controls) while keratinocyte transglutaminase gene expression was downregulated in active UC. CONCLUSIONS: The results of the present study support the concept that, in the damaged colon, transglutaminases are needed in response to chronic injury and underline the key role of these enzymes in mucosal healing.

The prolongation of triple therapy for Helicobacter pylori does not allow reaching therapeutic outcome of sequential scheme: a prospective, randomised study.

BACKGROUND AND AIM: One-week triple therapy for Helicobacter pylori revealed, during these last few years, a decrease in the eradication rate, so that the prolongation of its duration has been proposed. A sequential scheme recently showed very satisfactory results. We performed a prospective randomised study with the aim of either evaluating whether the triple therapy prolongation may improve its effectiveness and comparing its outcome with that of sequential regimen. PATIENTS AND METHODS: Three hundred and forty-two H. pylori positive patients completed the study. They were randomised to receive one of the following treatments: (i) a 7-day triple therapy comprising of rabeprazole (20 mg, b.i.d.) plus clarithromycin (500 mg, b.i.d.) and amoxycillin (1 g, b.i.d.); (ii) a 10-day triple therapy comprising the same scheme; (iii) a 10-day sequential regimen comprising of rabeprazole (20 mg, b.i.d.) plus amoxycillin (1 g, b.i.d.) for 5 days followed by rabeprazole (20 mg, b.i.d.) plus clarithromycin (500 mg, b.i.d.) and tinidazole (500 mg, b.i.d.) for the next 5 days. Therapeutic results were expressed using both intention-to-treat and per protocol analyses with 95% confidence intervals. A model of multivariate logistic regression analysis was performed using therapeutic outcome as a dependent variable and including endoscopic finding, smoking habit, age and sex as candidates for the model. RESULTS: Sequential regimen showed a significant gain in the eradication rate as compared to the 7-day (P < 0.0001) and the 10-day (P < 0.01) triple therapies, respectively. Overall eradication was lower in smokers than in non-smokers, but the difference remained significant only in the 7-day triple therapy (P < 0.01). Additionally, the overall eradication was higher in peptic ulcer than dyspepsia (P < 0.01), even if this difference was significant only for both triple therapies. CONCLUSIONS: Seven-day triple therapy achieves disappointing eradication rates in dyspeptics and smokers. Prolonging triple therapy to 10 days does not significantly improve the eradication rate. The novel 10-day sequential regimen is more effective and equally tolerated than the 10-day triple therapy.

MTHFR T677 homozygosis influences the presence of aura in migraineurs.

It has been suggested that folate metabolism could be involved in migraine pathogenesis. We analysed the 5',10'-methylenetetrahydrofolate reductase (MTHFR) genotypic distribution in a large migraine sample. We genotyped 230 migraine patients (152 migraine without aura (MO) and 78 migraine with aura (MA)) and 204 nonheadache controls. The incidence of TT homozygosis for migraine in general (12%), MO (9%) and MA (18%) did not significantly differ from that found in healthy controls (13%). Differences were significant when the frequency of TT homozygosis between MA and MO (P = 0.03, OR = 2.34, 95% CI = 1.04-5.26) was compared. There was a tendency for a higher frequency of the MTHFR T allele in the MA group (42%) as compared to MO (29%) and controls (36%). These differences were significant only in the case of MA vs. MO (P = 0.006, OR = 1.75, 95% CI = 1.15-2.65). These results could indicate that the MTHFR C677T polymorphism, causing mild hyperhomocystinaemia, might be a genetic risk factor for experiencing aura among migraineurs. Overall, however, there was no association between migraine and the C677T MTHFR polymorphism.