Technological readiness and implementation of genomic-driven precision medicine for complex diseases.

The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.

Hemoglobin-Based Oxygen Carrier Rescues Double-Transplant Patient From Life-Threatening Anemia.

This case describes a 46-year-old male recipient of a kidney-pancreas transplant who is Jehovah's Witness. Early in the postoperative period, he was found to have splenic vein thrombosis requiring heparin infusion. Two days later, he developed severe symptomatic anemia (hemoglobin <6 g/dL). Standard medical therapy for bloodless surgical patients with severe anemia was instituted. Nevertheless, the patient's hemoglobin concentration continued to decline to critical levels (2 g/dL). Because he was Jehovah's Witness, transfusion of allogeneic blood products was not an option, prompting use of a hemoglobin-based oxygen carrier (HBOC). After approval by the U.S. Food and Drug Administration and the local institutional review board, 12 U of HBOC-201 were transfused over a period of 8 days. Two weeks later, the patient's hemoglobin levels had increased to 6.8 g/dL. The patient's overall clinical condition improved, and he was discharged home. This case describes the first use of HBOC transfusion in a double solid organ transplant patient. HBOC may represent a viable option in patients with severe symptomatic anemia when allogeneic blood transfusion is not an option.

Genome-wide identification of copy number variations in Holstein cattle from Baja California, Mexico, using high-density SNP genotyping arrays.

Copy number variations (CNVs) are an important source of genomic structural variation, and can be used as markers to investigate phenotypic and economic traits. CNVs also have functional effects on gene expression and can contribute to disease susceptibility in mammals. Currently, single nucleotide polymorphism genotyping arrays (SNP chips) are the technology of choice for identifying CNV variations. Microarray technologies have recently been used to study the bovine genome. The objective of the present study was to develop CNVs in Holstein cows from the Northwest of Mexico using the Affymetrix Axiom Genome-Wide BOS 1 Array, which assays 648,315 SNPs and provides a wide coverage for genome-wide studies. We applied the two most widely used algorithms for the discovery of CNVs (PennCNV and QuantiSNP) and found 56 CNV regions (CNVRs) representing 0.33% of the bovine genome (8.46 Mb). These CNVRs ranged from 1.5 to 970.8 kb with an average length of 151 kb. They involved 103 genes and showed a 28% overlap with CNVRs already reported. Of the 56 CNVRs found, 20 were novel. In this study we present the first genomic analysis of CNVs in Mexican cattle using high-density SNP data. Our results provide a new reference basis for future genomic variation and association studies between CNVs and phenotypes, especially in Mexican cattle.

Influence of Feeding Enzymatically Hydrolyzed Yeast Cell Wall on Growth Performance and Digestive Function of Feedlot Cattle during Periods of Elevated Ambient Temperature.

In experiment 1, eighty crossbred steers (239±15 kg) were used in a 229-d experiment to evaluate the effects of increasing levels of enzymatically hydrolyzed yeast (EHY) cell wall in diets on growth performance feedlot cattle during periods of elevated ambient temperature. Treatments consisted of steam-flaked corn-based diets supplemented to provide 0, 1, 2, or 3 g EHY/hd/d. There were no effects on growth performance during the initial 139-d period. However, from d 139 to harvest, when 24-h temperature humidity index averaged 80, EHY increased dry matter intake (DMI) (linear effect, p<0.01) and average daily gain (ADG) (linear effect, p = 0.01). There were no treatment effects (p>0.10) on carcass characteristics. In experiment 2, four Holstein steers (292±5 kg) with cannulas in the rumen and proximal duodenum were used in a 4×4 Latin Square design experiment to evaluate treatments effects on characteristics of ruminal and total tract digestion in steers. There were no treatment effects (p>0.10) on ruminal pH, total volatile fatty acid, molar proportions of acetate, butyrate, or estimated methane production. Supplemental EHY decreased ruminal molar proportion of acetate (p = 0.08), increased molar proportion of propionate (p = 0.09), and decreased acetate:propionate molar ratio (p = 0.07) and estimated ruminal methane production (p = 0.09). It is concluded that supplemental EHY may enhance DMI and ADG of feedlot steers during periods of high ambient temperature. Supplemental EHY may also enhance ruminal fiber digestion and decrease ruminal acetate:propionate molar ratios in feedlot steers fed steam-flaked corn-based finishing diets.

Hemorrhagic cytitis after bone marrow transplantation.

OBJECTIVES: Hemorrhagic cystitis (HC) presenting with gross hematuria, bladder pain and urinary frequency develops in 13-38% of patients following bone marrow transplantation (BMT). The objective of the study was to study the characteristics of patients suffering hemorrhagic cystitis after hematopoietic stem cell transplantation in our center. METHODS: We conducted a retrospective chart review of all patients who underwent BMT at our institution between January 1996 and August 2012. We recorded the age, sex, diagnosis, conditioning regimen, interval between BMT and development of symptoms of cystitis and treatment instituted. RESULTS: Five hundred patients underwent BMT in the period of time studied. 52 of them developed hemorrhagic cystitis. The mean age of the affected patients was 39 years; there were 34 males and 18 females. The diagnoses include AML (n=11), ALL (n=8), CML (n=6), MDS (n=11), CLL (n=5), NHL (n=1), HD (n=5), MM (n=2), Medular aplasia((n=3). HC appeared 59.48 days after BMT. There were no differences between sexes. Mortality among the 52 patients was 51.14% but HC was not the cause of death in any patient. Polyomaviruses were detected in the urine of 78.94 % of survivors. CONCLUSIONS: Polyomavirus infection with BK and JC types is usually acquired in infancy and the virus remains latent in renal tissue. Immunosuppression facilitates reactivation of the renal infection and replication of the virus responsible for the clinical manifestations of HC. The differential diagnoses include other urinary infections, lithiasis, thrombocytopenia and adverse effects of pharmacological agents. The urologist plays a limited role in the management of this disease.

Quality of information about urologic pathology in English and Spanish from ChatGPT, BARD, and Copilot.

INTRODUCTION AND OBJECTIVE: Generative artificial intelligence makes it possible to ask about medical pathologies in dialog boxes. Our objective was to analyze the quality of information about the most common urological pathologies provided by ChatGPT (OpenIA), BARD (Google), and Copilot (Microsoft). METHODS: We analyzed information on the following pathologies and their treatments as provided by AI: prostate cancer, kidney cancer, bladder cancer, urinary lithiasis, and benign prostatic hypertrophy (BPH). Questions in English and Spanish were posed in dialog boxes; the answers were collected and analyzed with DISCERN questionnaires and the overall appropriateness of the response. Surgical procedures were performed with an informed consent questionnaire. RESULTS: The responses from the three chatbots explained the pathology, detailed risk factors, and described treatments. The difference is that BARD and Copilot provide external information citations, which ChatGPT does not. The highest DISCERN scores, in absolute numbers, were obtained in Copilot; however, on the appropriacy scale it was noted that their responses were not the most appropriate. The best surgical treatment scores were obtained by BARD, followed by ChatGPT, and finally Copilot. CONCLUSIONS: The answers obtained from generative AI on urological diseases depended on the formulation of the question. The information provided had significant biases, depending on pathology, language, and above all, the dialog box consulted.

Evaluation of a therapeutic vaccine for the prevention of recurrent urinary tract infections versus prophylactic treatment with antibiotics.

INTRODUCTION AND HYPOTHESIS: Urinary tract infections (UTIs) are considered the most common bacterial infections, especially in women. The objective of this study was to evaluate the use of the sublingual bacterial vaccine Uromune® in order to prevent recurrent UTIs (RUTIs). METHODS: This study was conceived as a multicenter observational study. The clinical history of 319 women who presented at least 2 episodes of UTI in the last 6 months or 3 in 12 months was reviewed. Data related to treatment and clinical evolution were recorded and analyzed. A total of 159 patients received prophylactic treatment with Uromune® for a period of 3 months (group A) and 160 with sulfamethoxazole/trimethoprim 200/40 mg/day for a period of 6 months (group B). Uromune® contained an inactivated bacterial cell suspension of selected strains of Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis. RESULTS: Patients in group A experienced a highly significant reduction in the number of infections compared to patients in group B. In the first 3 months, the mean number of infections was 0.36 versus 1.60 (P < 0.0001), respectively. A significant reduction was also observed after 9 and 15 months (P < 0.0001). The numbers of patients who did not have any UTI at 3, 9, and 15 months were 101, 90, and 55 in group A versus 9, 4, and 0 in group B (P < 0.0001). CONCLUSIONS: The results obtained in this study favor the use of this bacterial-based therapeutic vaccine as an effective strategy to reduce frequency, duration, severity, and costs of RUTIs.

Clinical profile and epidemiological changes of clear cell renal carcinoma during 12 years in our health area.

OBJECTIVES: To investigate changes in the epidemiology and clinical profile of patients diagnosed with renal clear cell carcinoma in a community health area over 12 years. METHODS: Retrospective analysis of epidemiological characteristics and clinical profile of patients diagnosed with renal clear cell carcinoma in a health area composed of a population of 353.619 inhabitants from January 1999 to December 2010. Descriptive statistical and multivariate analysis, Fisher exact test and Chi-Square were utilized. p<0.05 was accepted as significant. RESULTS: 349 diagnoses of renal mass were reported; 165 of them were clear renal cell carcinoma. Median age was 70.41 years, and the Female/Male rate was 28% and 72%, respectively. 4% women and 30% men smoked ≥20 cigarettes/day, more frequently during the period 1999-2001. 52% women and 30% men had hypertension. Hematuria was the most frequent symptom (23%), more frequent in the period 2007-2010, followed by abdominal pain (16%) and renal colic(13%). Weight loss (12%) was more frequent between 1999-2000. Asthenia appeared as the first symptom in 8% of cases. The tumor was incidentally diagnosed in 20% of cases, more frequently in the period between 2007-2010. Diagnosis was established in the Urology Department in 36% of the cases. Stages T1-2 N0 were more frequent between 2007-2010, and M1 between 1999-2000. G3 was more frequent in the entire series. The relative cancer specific mortality of patients who were surgically treated was less in the last 2 years of the period. CONCLUSIONS: Clear renal cell carcinoma is the most frequent renal cancer and its incidence is increasing in our environment. It affects more frequently males than females, and at an earlier age. The last few years are showing a decrease in the habitual smoker males and an increase in HTN in females. A tendency has been detected to the early stage clinical diagnosis but with a higher histopathological grade. It is most frequent diagnosed by a non-Urology speciality.

[Impact of pharmaceutical care in polymedicated patients admitted to a geriatric ward].

BACKGROUND: The aim of the study was estimate the prevalence of potentially inappropriate prescribing (PIP) and drug related problems (DRP) in an acute geriatric ward, and to evaluate the impact of pharmaceutical intervention on their prevalence. METHODS: Quasi-experimental, interventional study in polymedicated patients (= 6 drugs) who were admitted to a Geriatric ward in 2018-2019. PIP were analyzed according to STOPP/START 2014 criteria and DRP on the Third Consensus of Granada. The PIP and DRP detected, and the possible actions to correct them, were sent to the physician in charge. The effect of the intervention was analyzed at hospital discharge; if the change of prevalence of PIP and DRP was =75%, the pharmaceutical intervention was considered to be accepted. RESULTS: Pharmaceutical intervention was performed on 218 patients, analyzing 1,837 prescriptions. On admission, PIP (90.8%) and DRP (99.5%) were observed. We carried out 1,227 interventions, 57.6% on DRP. More than half (53.6%) of the pharmaceutical interventions were accepted; the PIP according to the STOPP and START criteria was reduced by 49.7 and 22.1%, respectively; DRP decreased by 60.1%. The frequencies and medians of PRM and PPI according to the START and STOPP criteria decreased significantly at discharge. The variables most frequently associated with acceptance of the pharmaceutical intervention were the geriatrician at charge, the number of PPI START and the number of PPI STOPP. CONCLUSION: The detection of PIP and DRP of chronic treatment during hospital admission by the pharmacist, and in collaboration with the patient's doctor, helps to reduce the prevalence of PIP and DRP.

The impact of psychiatric pathology on the prognosis and survival of men with prostate cancer undergoing radical prostatectomy.

INTRODUCTION AND OBJECTIVE: Cancer-specific anxiety is the most frequently reported psychological response after radical prostatectomy (RP). We evaluated the prevalence of pretreatment psychiatric pathology in patients with prostate cancer undergoing RP and identified the effects of psychiatric diagnoses on their survival and prognosis. MATERIAL AND METHODS: Retrospective multicenter observational study including 1078 men treated with RP for organ-confined prostate cancer. Groups: GP: patients with psychiatric pathology prior to RP; GNP: patients without psychiatric pathology prior to RP. Urological, oncological and psychiatric variables, descriptive statistics and multivariate analysis were included. RESULTS: 37.94% of patients presented a psychiatric diagnosis. Adjuvant radiotherapy was required in 27.83% and hormone therapy in 23.38%; being more frequent in GP. Cancer-specific survival was higher in GNP. Anxiety, depression, insomnia, smoking, psychosis and alcoholism were the most frequent. Low TNM and low presence of LUTS and SUI increased the probability of absence of psychiatric pathology. Fatigue, erectile dysfunction and cognitive impairment after RP with RT and/or HT were higher in GP. Older age and higher PSA at diagnosis increased the relative risk of psychiatric pathology and worse outcome. The most frequently related factors were RP, PSA, age and survival time. CONCLUSIONS: Psychiatric pathology is present in patients undergoing radical prostatectomy for prostate cancer, with a high impact on survival and prognostic outcomes.

Improvements in the Effectiveness of Early Detection in Colorectal Cancer with Open-Label Randomised Study.

INTRODUCTION: The general objective of this research is to improve the quality of colorectal cancer screening (CRC) by assessing, as an indicator of effectiveness, the ability of colonoscopy to detect more advanced adenomas in the exposed group than in the control group. MATERIAL AND METHODS: The present work is designed as an open-label randomized study on cancer screening, using two groups based on their exposure to the protocol: an exposed to intervention group (EIG, 167), and a control group (CG, 167), without the intervention of the protocol and by 1:1 matching. RESULTS: In 167 patients in the GEI, 449 polyps are visualized and 274 are adenomas (80.58%), of which 100 (36.49%) are advanced adenomas. In the CG (n = 174), there are 321 polyps and 152 adenomas (82.60%). The variables significantly associated by logistic regression to the detection of adenomas are the male sex with an OR of 2.52. The variable time to withdrawal, ≥9 min, is significant at 99% confidence (p = 0.002/OR 34.67) and the fractional dose is significant at 99% (p = 0.009, OR 7.81). CONCLUSION: Based on the observations made, our study suggests that the intervention in collaboration between primary care and hospital care is effective from a preventive point of view and achieves the objective of effectiveness and quality of the PCCR.

Complications of transrectal prostate biopsy in our context. International multicenter study of 3350 patients. / Complicaciones de la biopsia transrectal de próstata en nuestro medio. Estudio multicéntrico internacional de 3.350 pacientes.

INTRODUCTION: Prostate cancer is the most common visceral neoplasm in men and the second one in the United States with the highest mortality behind lung cancer and ahead of colorectal cancer. While prostate cancer mortality rates have been reduced in the United States, Austria, United Kingdom and France, 5-year survival rates have been incremented in Sweden, probably due to a higher diagnostic activity and non-lethal tumor detection. TRPB usually has low rates of serious complications, with a not negligible number of minor complications. Mortality directly associated with this procedure is low and usually related to septic shock. The main complications derived from prostate biopsy can be infectious (mild or severe) and non-infectious (hematuria consistent with hemorrhage, urethral bleeding, rectal bleeding or hemospermia, acute urinary retention, pain or vasovagal reactions). MATERIAL AND METHOD: The objective of the study is to compare three usual TRPB protocols and their relationship with the incidence of complications. Retrospective multicenter observational study conducted in three countries (Spain, Italy and Portugal). We have reviewed the medical records of 3350 men who underwent TRPB to evaluate the existence of prostate cancer, with a minimum evolutionary control of 6months. RESULTS: The mean age was 65,50years, median 66, range 43-79. The subgroup analysis showed that younger patients had higher rates of acute urine retention (AUR) (P=.0000001). Likewise, our results revealed that younger patients presented more procedural pain (P=.0000001) than older patients. Regarding PSA, the mean value was 10.44, SD 7.73, median 8.15, range 0.98-68.09. A higher body mass index (BMI) was not associated with further infection (P=.000004). When performing the multivariate analysis, it was found that the significant variables in the general group were: age (P=.0013), PSA (P=.0402), local infiltration anesthesia (P=.0001) and prophylaxis with metronidazole +tobramycin +amoxicillin/clavulanic acid +gentamicin (P=.0001), presenting a normal distribution with high confidence interval (95%) and significant correlation. Prophylaxis is the most significant variable for no complications and pain (P=.0001), age (P=.0013) and prophylaxis (P=.0001) are for bleeding, age (P=.0013), prophylaxis and PSA (P=.0001) are for infection, and finally, age (P=.0013), anesthesia with local infiltration and prophylaxis (P=.0001) and PSA (P=.0402) are for AUR. CONCLUSIONS: Sedation has fewer side effects and complications related to the transrectal prostate biopsy procedure with respect to transrectal local anesthesia. The choice of the antibiotic prophylaxis scheme is decisive in the onset of complications arising from the performance of a transrectal prostate biopsy.

The influence of smoking on bacterial resistance after vaccine or antibiotic prophylaxis against recurrent urinary tract infections. / Influencia del tabaquismo en la resistencia bacteriana después de la profilaxis frente a infecciones urinarias recurrentes con antibiótico o con vacuna.

INTRODUCTION: The influence of tobacco on the microbiological spectrum, resistance-sensitivity pattern and evolution in patients with recurrent urinary tract infections (RUTI) is analyzed. Evaluation of the effect of polyvalent bacterial vaccine on the prevention of RUTI and smoking status. MATERIAL AND METHODS: Retrospective multicenter study of 855 women with RUTI receiving suppressive antibiotic treatment or bacterial vaccine between 2009 and 2013. Group A (GA): Antibiotic (n=495); Subgroups: GA1 non-smoker (n=417), GA2 smoker (n=78). Group B (GB): Vaccine (n=360); Subgroups: GB1 non-smoker (n=263), GB2 smoker (n=97). VARIABLES: Age, pre-treatment UTI, disease-free time (DFT), microbial species, sensitivity and resistance. Follow-up at 3, 6 and 12 months with culture and SF-36 questionnaire. RESULTS: Mean age 56.51 years (18-75), similar between groups (P=.2257). No difference in the number of pretreatment UTIs (P=.1329) or in the distribution of the bacterial spectrum (P=.7471). DFT was higher in subgroups B compared with A. Urine cultures in GA1: E. coli 62.71% with 8.10% resistance (33% quinolones; 33% cotrimoxazole; 33% quinolones + cotrimoxazole); in GA2 E. coli 61.53% with 75% resistance (16.66% quinolones; 33.33% quinolones + cotrimoxazole; 16.66% amoxicillin-clavulanate; 16.66% erythromycin + phosphomycin + clindamycin) (P=.0133). There were no differences between patients of GA treated with cotrimoxazole and nitrofurantoin (P=.8724). Urine cultures in GB1: E. coli 47.36% with 22.22% resistance (5.55% ciprofloxacin; 5.55% cotrimoxazole; 5.55% ciprofloxacin + cotrimoxazole; 5.55% amoxicillin/clavulanic acid). In GB2 E. coli 70.02% with 61.90% resistances (30.76% quinolones; 30.76% cotrimoxazole; 30.76% quinolones + cotrimoxazole; 17.69% amoxicillin-clavulanic acid) (P=.0144). CONCLUSIONS: The development of bacterial resistance is more frequent among women with smoking habits and recurrent urinary infections. This could influence a worse response to preventive treatments, either with antibiotics or vaccines.

Impact of organ confined prostate cancer treatment on quality of life. / Impacto en la calidad de vida del tratamiento del cáncer de próstata organoconfinado.

INTRODUCTION: Prostate cancer (PCa) is the second most common male cancer in the world. Its incidence is estimated to grow to 1.7 million new cases and 499,000 new deaths by 2030. Treatment of OCPC can affect patients physically and mentally, as well as their close relationships and their job or career, which conditions health-related quality of life (QoL). OBJECTIVE: Evaluate the impact on QoL attributable to the treatment for Organ Confined Prostate Cancer (OCPC). MATERIALS AND METHODS: Prospective multicenter observational study of 406 patients with OCPC treated from January 2015 to June 2018. The sample was divided into four study groups, according to the type of treatment: radical prostatectomy (RP) (GA), external radiotherapy (ERT) (GB), brachytherapy (BT) (GC) and other treatments different from monotherapy with RP, ERT or BT (GD). RESULTS: The age in GC was lower, the mean Prostate Specific Antigen (PSA) of all patients was 8.13 ng/ml, the group with the highest mean PSA was GB with a mean of 10.43 ng/dL, the mean Tumor Stage (TNM) was 3.82, and GD had the lowest post treatment quality of life. CONCLUSION: OCPC treatment affects QoL. Curative monotherapies, specifically RP and BT, have less effect on QoL than external radiotherapy or other therapeutic alternatives. Urinary incontinence and fistulas secondary to OCPC have the highest impact on QOL impairment. The internationally validated SF 36 questionnaire is a useful cross-sectional measure of QOL to compare the impact of OCPC treatment modalities.

[The influence of alternative medicine in highly active antiretroviral treatment]. / Influencia de la medicina alternativa en el tratamiento antirretroviral de gran actividad.

OBJECTIVE: Over the last few years, there has been a notable increase in the use of alternative medicine by the general population. The aim of this study is two-fold. Firstly we will analyse the incidence of the use of medicinal plants in patients with HIV undergoing Highly Active Anti-Retroviral Therapy (HAART). Secondly, with the help of existing bibliographic information, we want to study the existence of possible interactions. MATERIAL AND METHODS: We carried out a prospective study with a targeted interview (October to December 2007) on consenting patients with HIV undergoing HAART treatment. RESULTS: Of the 193 patients that agreed to take part in the survey, 16.6 % confirmed they used alternative medicinal therapies. In 46 % of the cases there was a potential interaction with the effectiveness of HAART. 46 % of the potential interactions were in the case of the patients who used grapefruit as an alternative medicine, 21 % in the case of patients using thistle and Echinacea respectively, 4 % for those using omega-3, Chinese herbs and ginseng. CONCLUSION: There is a significant use of natural products by these groups of patients, of which a significant percentage interact with HAART. A better understanding of the possible interactions with HAART and improved information offered to patients with HIV is needed.

Research of the impact of urinary infection teaching methods on the learning process. / Investigación de la repercusión en el proceso de aprendizaje según la metodología docente en la infección urinaria.

INTRODUCTION: The classical teaching methodology was based on passive transmission-based learning. The model has changed towards an orientation based on student-centred learning. OBJECTIVE: The objective of the study has been to evaluate the students' perception when learning about urinary tract infections, and their perspective about the teaching imparted on this pathology in the various subjects that include ITU in their syllabus. METHODS: A cross-sectional analytical study of the responses to an anonymous survey entitled: "Methodology on urine infections. Teaching aspects "issued by 228 students at their fifth year of Medical School, from two promotions. They referred to the following subjects: Pharmacy, Pathophisiology, Gynecology and Obstetrics, Infectious diseases, Microbiology, Nephrology, Pediatrics and Urology. RESULTS: The following variables have been analysed: teaching content, teaching basic aspects of the disease, consideration of teaching methodology and improvement suggestions. Descriptive and inferential statistics were used. CONCLUSION: The study has concluded that teaching urinary tract infection is perceived in specific subjects related to microorganism (Microbiology), the target organ (Infectious diseases, Urology), affected patients (Pediatrics, Gynecology and Obstetrics) rather than transversal subjects such as Pathophysiology or Pharmacy. The teaching methodology has been considered appropriate by more than 50% of the students in five from the 8 subjects that teach the concept of urinary tract infection. The students suggest convenient changes in current teaching methodology in several subjects that impart the urinary tract infection concept.

Upregulated TRPC1 channel in vascular injury in vivo and its role in human neointimal hyperplasia.

Occlusive vascular disease is a widespread abnormality leading to lethal or debilitating outcomes such as myocardial infarction and stroke. It is part of atherosclerosis and is evoked by clinical procedures including angioplasty and grafting of saphenous vein in bypass surgery. A causative factor is the switch in smooth muscle cells to an invasive and proliferative mode, leading to neointimal hyperplasia. Here we reveal the importance to this process of TRPC1, a homolog of Drosophila transient receptor potential. Using 2 different in vivo models of vascular injury in rodents we show hyperplasic smooth muscle cells have upregulated TRPC1 associated with enhanced calcium entry and cell cycle activity. Neointimal smooth muscle cells after balloon angioplasty of pig coronary artery also express TRPC1. Furthermore, human vein samples obtained during coronary artery bypass graft surgery commonly exhibit an intimal structure containing smooth muscle cells that expressed more TRPC1 than the medial layer cells. Veins were organ cultured to allow growth of neointimal smooth muscle cells over a 2-week period. To explore the functional relevance of TRPC1, we used a specific E3-targeted antibody to TRPC1 and chemical blocker 2-aminoethoxydiphenyl borate. Both agents significantly reduced neointimal growth in human vein, as well as calcium entry and proliferation of smooth muscle cells in culture. The data suggest upregulated TRPC1 is a general feature of smooth muscle cells in occlusive vascular disease and that TRPC1 inhibitors have potential as protective agents against human vascular failure.

[Treatment of stress urinary incontinence with perineal biofeedback by using superficial electrodes]. / Tratamiento de la incontinencia urinaria de esfuerzo con biofeedback perineal con electrodos de superficie.

PURPOSE: We analyze the pelvic floor muscles treatment outcomes by using biofeedback (BFB) with electromyography with superficial electrodes in women diagnosed as having stress urinary incontinence (SUI). Besides, we compare this treatment with pelvic floor muscle exercises (PFME) plus vaginal electrostimulation. METHODS: 85 women with stress urinary incontinence, aged 42 - 74 years. We divided the patients in two groups: Group 1 (N = 50): This patients carry out a perineal biofeedback with superficial electrodes without electrostimulation, and Group 2 (N = 35): This patients were treated with pelvis floor muscle exercices and vaginal electrostimulation. All patients carry out two session per week (of 30 minutes each one) during ten weeks. We assess the outcomes through international urinary incontinence questionnaires (IU-5 and ICIQ-SF) and urinary incontinence related quality of life test (King's questionnaire). Student t-test and Fisher Exact test were used, p < 0.05 was considered statistically significant. RESULTS: No difference was found in the age average of both groups. 84% of patients of group 1 and 80% of patients of group 2 were cured with the treatment. We assumed they were cured when incontinence episodes not happened or they do not need to use absorbent materials. In the Group 1, 50% of patients in the fourth week and 84% in the tenth week were cured. In the Group 2, 71.42% of patients in the fourth week and 80% in the tenth week were cured. In the Group 2, eight patients (22.85%) complained side effects. Both groups improved the quality of life similarly. CONCLUSION: Grade 1 and grade 2 stress urinary incontinence treatment by using perineal biofeedback with superficial electrodes electromyography is better or similar to more invasive treatments. Also pelvic floor muscle exercices plus vaginal electrostimulation have good outcomes although some patients complain side effects. Both conservative treatments are effective and feasible.

Estudio del switch de adalimumab por su biosimilar en un hospital de tercer nivel / Study of adalimumab switch for its biosimilar in a tertiary hospital

Objetivos: Debido al aumento en el consumo de los medicamentos biológicos y al impacto que esto supone en el gasto hospitalario, los objetivos de este estudio son: calcular el ahorro económico anual generado por el switch a adalimumab biosimilar y analizar el porcentaje de pacientes que mantienen dicho tratamiento en un hospital de tercer nivel. Material y métodos: Estudio descriptivo, observacional, longitudinal, retrospectivo en el que se incluyeron un grupo de pacientes a los que se les realizó switch de adalimumab por su biosimilar cuando en la Comisión Asesora Técnica de medicamentos de la comunidad se autorizó dicho cambio. Resultados: De los 218 pacientes, nueve tuvieron que volver al medicamento original (4,13%). La motivación fue: pérdida de eficacia en cinco, reacción alérgica en tres y otro, un paciente pediátrico con dolor tras la inyección del medicamento biosimilar. El coste de adquisición en nuestro hospital de una unidad del medicamento original es de 195,6 €, mientras que del biosimilar es de 75 €. Si consideramos una posología cada dos semanas, ya que es la más frecuente en nuestros pacientes, el coste anual por paciente con el original sería de 5.085 € y con el biosimilar de 1.950 €. Por lo tanto, el ahorro anual que supone el cambio del medicamento original al biosimilar es de 683.560 €. Conclusiones: El switch de adalimumab original al biosimilar supone un importante ahorro económico sin que se reduzca la efectividad en el proceso de su enfermedad. Lo que contribuye a la eficiencia y sostenibilidad del sistema sanitario. En nuestra población, el 4,13% tuvo que volver al medicamento original. Sería conveniente realizar estudios en un número superior de pacientes y continuar su seguimiento a largo plazo para obtener conclusiones más firmes. (AU)

Objectives: Due to the increase in the consumption of biologic drugs and the impact this has on hospital spending, the objectives of this study are: to calculate the economic savings generated by switching to biosimilar adalimumab and to analyze the percentage of patients who maintain this treatment in a tertiary level hospital. Material and methods: Descriptive, observational, longitudinal, retrospective study that included a group of patients who were switched from adalimumab to its biosimilar, when the Technical Advisory Committee for Medicines of the community authorized the change. Results: Of the 218 patients, nine had to return to the original drug (4.13%). The motivation was: loss of efficacy in five, allergic reaction in three and the other was a pediatric patient with pain after injection of the biosimilar drug. The acquisition cost in our hospital of an unit of the original drug is €195.6, while that of the biosimilar is €75. If we consider a dosage every two weeks, since this is the most frequent in our patients, the annual cost per patient with the original drug would be €5,085 and with the biosimilar €1,950. Therefore, the annual savings from switching from the original drug to the biosimilar is €683,560. Conclusions: Switching from the original adalimumab to the biosimilar means significant economic savings without reducing the effectiveness of the disease process. This contributes to the efficiency and sustainability of the halthcare system. In our population, 4.13% had to return to the original drug. It would be advisable to carry out the study in a larger number of patients and to continue its long-term follow-up to obtain firmer conclusions. (AU)

[Design and validation of a classification system for assessing the degree of disability of patients with amyotrophic lateral sclerosis]. / Diseño y validacion de un sistema de clasificacion para evaluar el grado de discapacidad de los pacientes con esclerosis lateral amiotrofica.

INTRODUCTION: Currently there is no system of classification validated and commonly used to allow staging the severity of amyotrophic lateral sclerosis. PATIENTS AND METHODS: Based on the ALSFRS-R, four domains were established (bulbar, manual skills, gross motor function and respiratory function). Each item had a 0 score if the rate was >= 3 (independence) or 1 if the rate was < 3 (dependence). The functional classification scale was defined as follows: stage 1, without a loss of independence on any domain, until stage 5, with loss of independence in all four domains. This classification is correlated with the need of external support, quality of life with the application of the ALSAQ-40 scale, muscle strength and survival. RESULTS: From a total of 244 patients, 14.3% were in stage 1, 23.8% in stage 2, 21.3% in stage 3, 19.3% in stage 4 and 21.3% in stage 5. Muscle strength and quality of life were inversely proportional to the stage of the disease, while the need for external aids is directly related to the increase in disease stages 1 to 5 (p < 0.012). Increased survival of patients was found in stages 1 and 2 with respect to those in stages 3, 4 and 5 (p = 0.004). CONCLUSION: The proposed classification system is easy to apply and correlates well with the patient's clinical, quality of life, resource requirements and survival.

TITLE: Diseño y validacion de un sistema de clasificacion para evaluar el grado de discapacidad de los pacientes con esclerosis lateral amiotrofica.Introduccion. Actualmente no existe un sistema de clasificacion validado y de uso comun para estadificar la gravedad de la esclerosis lateral amiotrofica. Pacientes y metodos. Basados en la escala de valoracion funcional para la esclerosis lateral amiotrofica revisada, se establecieron cuatro dominios (bulbar, destrezas manuales, funcion motora gruesa y funcion respiratoria). A cada item se le asigno una puntuacion de 0 si su calificacion era igual o mayor de 3 (independencia), o 1 si su calificacion era menor de 3 (dependencia). La escala de clasificacion funcional se definio desde el estadio 1 (sin perdida de independencia en ningun dominio) hasta el estadio 5 (perdida de independencia en los cuatro dominios). Esta clasificacion se correlaciono con la necesidad de ayudas externas, la calidad de vida aplicando la escala del cuestionario de evaluacion de la esclerosis lateral amiotrofica-40, la fuerza muscular y la sobrevida. Resultados. De un total de 244 pacientes, el 14,3% se encontraba en estadio 1; el 23,8%, en estadio 2; el 21,3%, en estadio 3; el 19,3%, en estadio 4; y el 21,3%, en estadio 5. Fuerza muscular y calidad de vida fueron inversamente proporcionales a la etapa de la enfermedad. La necesidad de ayudas externas se relaciona directamente con el aumento de los estadios de la enfermedad de 1 a 5 (p < 0,012). Se encontro una mayor sobrevida de los pacientes en los estadios 1 y 2 con respecto a los estadios 3, 4 y 5 (p = 0,004). Conclusion. El sistema de clasificacion propuesto es de facil aplicacion y se correlaciona bien con la clinica del paciente, su calidad de vida, el requerimiento de recursos y la sobrevida.