Preformed T cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with tacrolimus monotherapy in kidney transplantation: Results of the CELLIMIN trial.

Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogeneous regarding their immunological memory and primary alloimmune susceptibility. This biomarker-guided trial investigated whether in low immunological-risk kidney transplants without pretransplant DSA and donor-specific T cells assessed by a standardized IFN-γ ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non-inferior regarding 6-month BPAR than tacrolimus-based standard of care (SOC). Due to low recruitment rates, the trial was terminated when 167 patients were enrolled. ELISPOT negatives (E-) were randomized to LI (n = 48) or SOC (n = 53), E+ received the same SOC. Six- and 12-month BPAR rates were higher among LI than SOC/E- (4/35 [13%] vs. 1/43 [2%], p = .15 and 12/48 [25%] vs. 6/53 [11.3%], p = .073, respectively). E+ patients showed similarly high BPAR rates than LI at 6 and 12 months (12/55 [22%] and 13/66 [20%], respectively). These differences were stronger in per-protocol analyses. Post-hoc analysis revealed that poor class-II eplet matching, especially DQ, discriminated E- patients, notably E-/LI, developing BPAR (4/28 [14%] low risk vs. 8/20 [40%] high risk, p = .043). Eplet mismatch also predicted anti-class-I (p = .05) and anti-DQ (p < .001) de novo DSA. Adverse events were similar, but E-/LI developed fewer viral infections, particularly polyoma-virus-associated nephropathy (p = .021). Preformed T cell alloreactivity and HLA eplet mismatch assessment may refine current baseline immune-risk stratification and guide immunosuppression decision-making in kidney transplantation.

Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

Incidence and Outcomes of Staphylococcus aureus Bacteriuria: A Population-based Study.

BACKGROUND: Staphylococcus aureus bacteriuria (SABU) may represent multiple processes ranging from asymptomatic colonization to a marker of S. aureus bacteremia (SAB). Our objective was to describe SABU at a population-based level and determine patient characteristics associated with SAB. METHODS: A retrospective study was performed using electronic databases. All urine cultures positive for S. aureus between 2010 and 2013 within the Calgary Health Zone were included. Patient characteristics were compared among patients with and without SAB and risk factors identified using multiple logistic regression modeling. RESULTS: A total of 2540 urine cultures positive for S. aureus from 2054 patients were analyzed. The incidence of SABU was greatest among geriatric males with multiple comorbidities. SAB occurred in 175 (6.9%) of SABU patients. Those with SAB were more likely to be hospitalized, male, have a recent urinary procedure, have pure S. aureus culture in urine, and have laboratory findings suggesting systemic infection. Patients with isolated SABU were more likely to be ≥65 years, have dementia, and have abnormal urinalyses with pyuria and urine nitrites. In-hospital mortality in patients with SABU and SABU+SAB was 9.2% and 17.5%, respectively. Patients with SABU detected ≥48 hours before SAB had the highest risk of death. CONCLUSIONS: Less than 7% of patients with SABU have or will develop SAB. Characteristics associated with SABU were identified that established higher risk for systemic infection. Investigating SABU patients with these characteristics for systemic infection is warranted because a delay in diagnosis is associated with increased mortality.

A proliferation-inducing ligand increase precedes IgA nephropathy recurrence in kidney transplant recipients.

BACKGROUND: IgA nephropathy (IgAN) may recur in kidney transplant recipients. B-cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), and α-defensins are involved in the pathogenesis of native IgAN; however, their role on IgAN recurrence has not been previously analyzed. METHODS: Thirty-five patients with IgAN who received a kidney transplant in our center between January 1, 1993, and December 31, 2015, were included. Recurrence was diagnosed and ruled out in 14 and 11 patients, respectively, by indication biopsies. Pre-transplant, 6-month, 1-, 3-, and 5-year sera selected to measure BAFF, APRIL, and defensin by ELISA. RESULTS: Six months post-transplantation, APRIL levels (300.1 vs 1203.8 pg/mL, P = 0.033) and the mean APRIL values from 6 months to 3 years (409.8 vs 1258.0 pg/mL, P = 0.003) were higher in recurrent patients. Both 6-month APRIL levels (AUC-ROC 0.753, P = 0.033) and mean APRIL values (AUC-ROC 0.844, P = 0.004) discriminated patients with recurrence risk. By logistic regression, APRIL at 6 months (P = 0.044) and mean APRIL (P = 0.021) related to the risk of IgAN recurrence independently. Neither BAFF nor defensin related to recurrence. CONCLUSIONS: Serum APRIL increased at 6 months and mean APRIL remained higher the first 3 years in patients in whom IgAN was going to recur.

Treatment of chronic antibody mediated rejection with intravenous immunoglobulins and rituximab: A multicenter, prospective, randomized, double-blind clinical trial.

There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double-blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) <20 mL/min per 1.73m2 and/or severe interstitial fibrosis/tubular atrophy were excluded. Patients were randomized to receive IVIG (4 doses of 0.5 g/kg) and RTX (375 mg/m2 ) or a wrapped isovolumetric saline infusion. Primary efficacy variable was the decline of eGFR at one year. Secondary efficacy variables included evolution of proteinuria, renal lesions, and DSA at 1 year. The planned sample size was 25 patients per group. During 2012-2015, 25 patients were randomized (13 to the treatment and 12 to the placebo group). The planned patient enrollment was not achieved because of budgetary constraints and slow patient recruitment. There were no differences between the treatment and placebo groups in eGFR decline (-4.2 ± 14.4 vs. -6.6 ± 12.0 mL/min per 1.73 m2 , P-value = .475), increase of proteinuria (+0.9 ± 2.1 vs. +0.9 ± 2.1 g/day, P-value = .378), Banff scores at one year and MFI of the immunodominant DSA. Safety was similar between groups. These data suggest that the combination of IVIG and RTX is not useful in patients displaying transplant glomerulopathy and DSA.

Clinical evolution of post-transplant diabetes mellitus.

BACKGROUND: The long-term clinical evolution of prediabetes and post-transplant diabetes mellitus (PTDM) is unknown. METHODS: We analysed, in this cohort study, the reversibility, stability and progression of PTDM and prediabetes in 672 patients using repeated oral glucose tolerance tests (OGTTs) for ≤5 years. RESULTS: Most patients were on tacrolimus, steroids and mycophenolate. About half developed either PTDM or prediabetes. The incidence of PTDM was 32% and bimodal: early PTDM (≤3 months) and late PTDM. Early PTDM reverted in 31%; late PTDM developed in patients with post-transplant prediabetes. The use of OGTTs was necessary to detect around half of PTDM. Pretransplant obesity was a major risk factor for early PTDM, for its persistence and for late PTDM {odds ratio [OR] 1.18 [95% confidence interval (CI) 1.09-1.28]}. At 3 months, higher HbA1c promoted [OR 2.37 (95% CI 1.38-4.06)], while insulin sensitivity protected against [OR 0.64 (95% CI 0.48-0.86)] late PTDM. At 3 months, 28% had prediabetes; of these, 36% remained stable, 43% normalized and 21% developed late PTDM. Pretransplant obesity [OR 1.20 (95% CI 1.04-1.39)] and higher HbA1c [OR 3.80 (95% CI 1.45-9.94)] at 3 months promoted while insulin sensitivity protected against [OR 0.57 (95% CI 0.34-0.95)] evolution from prediabetes to late PTDM. Immunosuppressive levels or acute rejection did not influence PTDM. Most (84%) of the patients with normal tests at 3 months remained stable without evolving into PTDM; 14% developed prediabetes. CONCLUSIONS: PTDM and prediabetes are very common in renal transplantation. Classic metabolic factors like obesity, prediabetes and insulin resistance promote the evolution of PTDM and prediabetes. Patients with normal glucose metabolism rarely develop PTDM. OGTT is necessary to detect PTDM and prediabetes and thus should be included in clinical practice.

Short form of Spanish version of the WISC-IV for intelligence assessment in elementary school children.

In educational settings, quick assessments of intelligence are often required to screen children with potential special needs. The WISC-IV is administered individually and takes between one and two hours to complete. Given its widespread use in Spain, a short-form of the Spanish version is likely to be of use to professionals. The goal of this research was to develop a short form of the WISC-IV that can be performed in approximately half an hour. Data obtained in 100 elementary school children were analyzed following the criteria of Resnick and Entin (1971) . The results showed that the most accurate estimation of intelligence was achieved with a combination of the Vocabulary, Block Design, Letter-Number Sequencing, and Coding subtests.

Long-term prognostic significance of response in multiple myeloma after stem cell transplantation.

For establishing the true effect of different response categories in patients with multiple myeloma (MM) treated with autologous stem cell transplantation, we evaluated, after a median follow-up of 153 months, 344 patients with MM who received a transplant between 1989 and 1998. Overall survival (OS) at 12 years was 35% in complete response (CR) patients, 22% in near complete response (nCR), 16% in very good partial response (VGPR), and 16% in partial response (PR) groups. Significant differences in OS and progression-free survival were found between CR and nCR groups (P = .01 and P = .002, respectively), between CR and VGPR groups (P = .0001 and P = .003), or between CR and PR groups (P = .003 and P = < 10(-5)); no differences were observed between the nCR and VGPR groups (P = .2 and P = .9) or between these groups and the PR group (P = .1 and P = .8). A landmark study found a plateau phase in OS after 11 years; 35% patients in the CR group and 11% in the nCR+VGPR+PR group are alive at 17 years; 2 cases had relapsed in the nCR+VGPR+PR group. In conclusion, MM achieving CR after autologous stem cell transplantation is a central prognostic factor. The relapse rate is low in patients with > 11 years of follow-up, possibly signifying a cure for patients in CR.

Reproducibility of the World Health Organization 2008 criteria for myelodysplastic syndromes.

The reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is uncertain and its assessment was the major aim of this study. The different peripheral blood and bone marrow variables required for an adequate morphological classification were blindly evaluated by four cytomorphologists in samples from 50 patients with myelodysplastic syndromes. The degree of agreement among observers was calculated using intraclass correlation coefficient and the generalized kappa statistic for multiple raters. The degree of agreement for the percentages of blasts in bone marrow and peripheral blood, ring sideroblasts in bone marrow, and erythroid, granulocytic and megakaryocytic dysplastic cells was strong (P<0.001 in all instances). After stratifying the percentages according to the categories required for the assignment of World Health Organization subtypes, the degree of agreement was not statistically significant for cases with 5-9% blasts in bone marrow (P=0.07), 0.1-1% blasts in peripheral blood (P=0.47), or percentage of erythroid dysplastic cells (P=0.49). Finally, the interobserver concordance for World Health Organization-defined subtypes showed a moderate overall agreement (P<0.001), the reproducibility being lower for cases with refractory anemia with excess of blasts type 1 (P=0.05) and refractory anemia with ring sideroblasts (P=0.09). In conclusion, the reproducibility of the World Health Organization 2008 classification for myelodysplastic syndromes is acceptable but the defining criteria for blast cells and features of erythroid dysplasia need to be refined.

Aggressive lung donor management increases graft procurement without increasing renal graft loss after transplantation.

BACKGROUND: To determine the impact of an aggressive protocol on the rate of lung grafts available for transplant. We analyzed the impact of this management on kidney graft survival after kidney transplantation. METHODS: A cohort study. Lung donors and kidney recipients from 2009 and 2010 were considered the prospective cohort with 2003-2008 as the historical control period. The number of lungs available for transplantation was the main outcome measures. For recipients, kidney graft survival was the main outcome measure. RESULTS: We quadrupled the number of lung donors in the period 2009-2010 compared with the historical control. Management in the prospective cohort included higher use of positive end-expiratory pressure (PEEP) (p < 0.0001), increased use of hormonal resuscitation therapy (HRT) (p < 0.0001), and lower level of central venous pressure (p < 0.05) than historical control. The probability of renal graft survival at one yr after transplant was 88.6% (CI 95%: 74.8-95.1) in historical control and 94.7% (CI 95%: 81-98.7%) in the prospective cohort (p = 0.226). CONCLUSIONS: Aggressive management strategy in potential lung donors, which includes ventilator recruitment maneuvers, PEEP ≥ 8 cm H(2)O, the use of HRT, and restrictive fluid balance increases the rate of lung grafts available for transplantation without adverse effect on kidney graft survival.

Cystatin C and albuminuria as predictors of long-term allograft outcomes in kidney transplant recipients.

Although cystatin C (Cys) and albuminuria (Alb) are predictors of end-stage renal disease in the general population, there are limited data about the performance of these markers alone or combined with respect to the prediction of the kidney transplant outcome. We assessed the ability of one-yr creatinine (Cr), MDRD equation, Cys, Hoek equation, Alb, the logarithm of albuminuria (LogAlb), and two products of these variables for predicting death-censored graft loss (DCGL) in 127 kidney transplant recipients. Mean follow-up time was 5.6 ± 1.7 yr. During this time, 18 patients developed DCGL. The area under the receiver operating characteristic curve for DCGL ranged from 71.1% to 85.4%, with Cys*LogAlb being the best predictor. Cys-based variables and variables combining LogAlb and renal function estimates have better discrimination ability than Cr-based variables alone. After multivariate analysis, quartiles of all one-yr variables (except of Cr and MDRD) were independent predictors for DCGL. Predictors combining Alb and a Cr- or Cys-based estimate of renal function performed better than those markers alone to predict DCGL. Cys-based predictors performed better than Cr-based predictors. Using a double-marker in kidney transplantation, it is possible to identify the highest risk group in which to prioritize specialty care.

Canadian multidisciplinary expert consensus on the use of biologics in upper airways: a Delphi study.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases. Knowledge gaps nevertheless exist in how best to approach patient care as a whole. There have been sixteen randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL- 5R, IL-33, and immunoglobulin (Ig)E. This white paper considers the perspectives of experts in various disciplines such as rhinology, allergy, and respirology across Canada, all of whom have unique and valuable insights to contribute on how to best approach patients with upper airway disease from a multidisciplinary perspective. METHODS: A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. A national multidisciplinary expert panel of 34 certified specialists was created, composed of 16 rhinologists, 7 allergists, and 11 respirologists who evaluated the 20 original statements on a scale of 1-9 and provided comments. All ratings were quantitively reviewed by mean, median, mode, range, standard deviation and inter-rater reliability. Consensus was defined by relative interrater reliability measures-kappa coefficient ([Formula: see text]) value > 0.61. RESULTS: After three rounds, a total of 22 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with upper airway disease. CONCLUSION: This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of upper airway disease from a multidisciplinary perspective, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years.

[Analysis of the rational use of anti-hypertensives in the Murcia (Spain) region]. / Análisis del uso racional de antihipertensivos en la región de Murcia.

OBJECTIVE: The objective of this study was to determine the pattern of use of antihypertensive drugs in the Murcia Region, comparing the results with the national data, and detecting problems in order to make improvements, or establish hypotheses and to plan new studies. DESIGN: Pharmacoepidemiological study (from 2004 to 2008) in accordance with the recommendations from World Heath Organization. SETTING: : Murcia Region. PARTICIPANTS: Annual census of each year. MAIN MEASUREMENTS: The use of antihypertensive drugs was measured by the daily doses per 1000 inhabitans-day (DHD). RESULTS: The use of antihypertensive drugs has significantly increased from 196.6 DHD to 235.8 DHD. The antihypertensives more used at the end of 2008 were: angiotensin II receptor blockers-ARB- (38.6%) and angiotensin converting enzyme inhibitors-ACEI- (21.8%). There has been a tendency to change the use of rennin-angiotensin system blockers-RASB-, with an increase in ARB of 77.5% and and a decrease in ACEI 9.5%. The comparison with the national data shows qualitative and quantitative differences in the pattern of antihypertensive drugs used during the studied period. CONCLUSIONS: The use of antihypertensive drugs in Murcia is less than in the rest of Spain. Therefore, this may be due to a problem of under treatment of this illness or other cardiovascular illnesses in the region. A greater use of ARB in Murcia and a lower use of ACEI was observed in Murcia. The differences found suggest that further studies are required to clarify their origins and causes, with the objective of achieving a more rational and efficient use of these drugs.

The physiology of hemostasis.

The breakdown of vascular integrity triggers a series of reactions, initially involving a vasoconstriction phenomenon that reduces blood loss and leads to platelet plug formation under changing flow conditions. Once the platelet plug has formed, the coagulation system is activated in order to allow the formation of fibrin, which anchors the platelet plug to the vessel breach. Finally, once the damage has resolved, the fibrin is eliminated through fibrinolysis. This article explains all these regulatory mechanisms.

Public stigma profile toward mental disorders across different university degrees in the University of Valencia (Spain).

Background: A large proportion of studies carried out in recent years in different populations have shown that stigma toward mental disorders is highly prevalent. In the present study we conducted a comprehensive assessment of stigma to describe and compare stigma toward mental disorders in students enrolled in five different university degrees. Methods: Three hundred and twenty-five students from the University of Valencia (Spain), attending the second term of their first-degree courses in the faculties of medicine, psychology, teaching, economics, and data science participated in this cross-sectional study. Stigma was measured using: the Reported and Intended Behavior Scale (RIBS), the Scale of Community Attitudes toward Mental Illness (CAMI), the Attribution Questionnaire (AQ-27), and the Knowledge about Mental Illness test (KMI). Results: We found different patterns of stigma according to gender, the fact of knowing or living with a person with mental disorders and the university degree studied. Overall, women show fewer stigmatizing attitudes than men but similar stereotypes and prejudice toward people with mental disorders. However, the pattern of results across degrees is more complex. Overall, students of medicine, psychology and teaching showed fewer stigmatizing attitudes than students of economics and data science but differences between degrees were more subtle in stereotypes and prejudice toward people with mental disorders. Conclusion: Our study suggests the existence of different profiles of stigma in relation to mental disorders in university students. These profiles varied in relation with the degree being studied, gender and already knowing or living with a person with mental disorders.

Cannabinoid receptor type 2 agonist JWH-133 decreases cathepsin B secretion and neurotoxicity from HIV-infected macrophages.

HIV-associated neurocognitive disorders (HAND) are prevalent despite combined antiretroviral therapy (cART), affecting 52% of people living with HIV. Our laboratory has demonstrated increased expression of cathepsin B (CATB) in postmortem brain tissue with HAND. Increased secretion of CATB from in vitro HIV-infected monocyte-derived macrophages (MDM) induces neurotoxicity. Activation of cannabinoid receptor type 2 (CB2R) inhibits HIV-1 replication in macrophages and the neurotoxicity induced by viral proteins. However, it is unknown if CB2R agonists affect CATB secretion and neurotoxicity in HIV-infected MDM. We hypothesized that HIV-infected MDM exposed to CB2R agonists decrease CATB secretion and neurotoxicity. Primary MDM were inoculated with HIV-1ADA and treated with selective CB2R agonists JWH-133 and HU-308. HIV-1 p24 and CATB levels were determined from supernatants using ELISA. MDM were pre-treated with a selective CB2R antagonist SR144528 before JWH-133 treatment to determine if CB2R activation is responsible for the effects. Neuronal apoptosis was assessed using a TUNEL assay. Results show that both agonists reduce HIV-1 replication and CATB secretion from MDM in a time and dose-dependent manner and that CB2R activation is responsible for these effects. Finally, JWH-133 decreased HIV/MDM-CATB induced neuronal apoptosis. Our results suggest that agonists of CB2R represent a potential therapeutic strategy against HIV/MDM-induced neurotoxicity.

In vivo expansion of a CD9+ decidual-like NK cell subset following autologous hematopoietic stem cell transplantation.

Autologous hematopoietic stem cell transplantation (autoHSCT) is a treatment option for hematological disorders and pediatric solid tumors. After an autoHSCT, natural killer (NK) cells are the first lymphocyte subset returning to normal levels. To uncover global changes during NK cell reconstitution after autoHSCT, we performed RNA-sequencing on NK cells before and after autoHSCT. Results showed profound changes in the gene expression profile of NK cells immediately after autoHSCT. Several biological processes including cell cycle, DNA replication and the mevalonate pathway were enriched. Significantly, we observed that following autoHSCT, NK cells acquired a decidual-like gene expression profile, including the expression of CD9. By using multiparametric flow cytometry, we confirmed the expansion of NK cells expressing CD9 immediately after autoHSCT, which exhibited higher granzyme B and perforin expression levels than CD9- NK cells. These results provide insights into the physiopathology of NK cells during their reconstitution after autoHSCT.

Effectiveness of the cognitive differentiation program of the integrated psychological therapy: group versus individual treatment.

The aim of the current pilot study was to compare two strategies in the application of the cognitive differentiation program of Integrated Psychological Therapy for people with schizophrenia. Twenty-six outpatients were randomly assigned to the application of the program in group sessions (CDg), or to its application in individualized sessions (CDi). The program provides cognitive exercises to promote better performance in cognition, and both groups of participants completed the same number of exercises following the same number of sessions per week. Outcomes were assessed on neuropsychological measures of attention, executive functioning and everyday memory, and everyday functioning. Effect sizes showed the absence of effects in everyday memory and social functioning, higher improvements in the CDi group in attention, and a higher improvement in the CDg condition in executive functioning. The results suggest that the program application model could be individualized, depending on patient-specific cognitive deficits.

[A hazard scale for severe interactions: a tool for establishing prioritising strategies to improve the safety of the prescription in family medicine]. / Escala de peligro para interacción grave: una herramienta para la priorización de estrategias de mejora en la seguridad de la prescripción en medicina de familia.

OBJECTIVE: To effectively locate the drugs most implicated in severe interactions as a basis of designing actions to improve patient safety in Primary Care. DESIGN: Cross-sectional study of prescriptions using the Primary Care computerised medical records database (OMI-PC). SETTING: Murcia (Spain) Health Areas I, VI, VII and IX (723,664 inhabitants). PARTICIPANTS: There are 362,271 patients over 14 years-old available in the OMI-PC and are assigned to a doctor who uses the OMI-PC regularly. MAIN MEASUREMENTS: We analysed the drugs that each patient could be taking, looking for severe interactions. We constructed a severe interaction hazard scale (e-PIG) calculating [1] the probability that a non-selected patient may be taking a particular drug and [2] the probability that a drug may produce a severe interaction. With this, we estimated the risk of producing a severe interaction for each drug, which was converted into a 5 point logarithmic scale. RESULTS: We found 83,138 patients (22.9%) at risk (they took 2 or more drugs). We identified 466,940 prescriptions providing 939 drugs and 5,597 severe interactions (prevalence 5.8%). In these, 167 drugs were involved, of which e-PIG identified 5 (3%) with an extreme value: omeprazole, diazepam, acenocoumarol, ibuprofen and calcium. CONCLUSIONS: e-PIG is a logarithmic expression of the risk that prescribing a particular drug may produce a severe interaction in a determined setting and time. Its monitoring could become a prioritisation element that may assist the design of strategies for improving the safety of the use of drugs.