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.

Decalogue for the selection of oral antibiotics for lower respiratory tract infections.

Lower respiratory tract infections, including chronic obstructive pulmonary disease exacerbations (COPD-E) and community acquired pneumonia (CAP), are one of the most frequent reasons for consultation in primary care and hospital emergency departments, and are the cause of a high prescription of antimicrobial agents. The selection of the most appropriate oral antibiotic treatment is based on different aspects and includes to first consider a bacterial aetiology and not a viral infection, to know the bacterial pathogen that most frequently cause these infections and the frequency of their local antimicrobial resistance. Treatment should also be prescribed quickly and antibiotics should be selected among those with a quicker mode of action, achieving the greatest effect in the shortest time and with the fewest adverse effects (toxicity, interactions, resistance and/or ecological impact). Whenever possible, antimicrobials should be rotated and diversified and switched to the oral route as soon as possible. With these premises, the oral treatment guidelines for mild or moderate COPD-E and CAP in Spain include as first options beta-lactam antibiotics (amoxicillin and amoxicillin-clavulanate and cefditoren), in certain situations associated with a macrolide, and relegating fluoroquinolones as an alternative, except in cases where the presence of Pseudomonas aeruginosa is suspected.

Influence of glioblastoma contact with the subventricular zone on survival and recurrence patterns

Background There is growing evidence that the subventricular zone (SVZ) may be involved in both the initiation and progression of glioblastoma (GB). We aimed to assess tumor proximity to the SVZ as a potential prognostic factor in GB. Method Retrospective study of 133 patients diagnosed with primary GB who underwent surgery followed by temozolomide-based chemoradiation between 2010 and 2016. All lesions were classified according to their anatomic relation with the SVZ. We determined the effect of tumor contact with the SVZ on progression-free survival (PFS), overall survival (OS), type, and patterns of recurrence. Results At a median follow-up of 18.6 months (95% CI 15.9–21.2), PFS and OS were 7.5 (95% CI 6.7–8.3) and 13.9 (95% CI 10.9–16.9) months, respectively. On the univariate analyses, initial contact with the SVZ was a factor for poor prognosis for both PFS (6.1 vs. 8.7 months; p = 0.006) and OS (10.6 vs. 17.9 months; p = 0.037). On the multivariate analysis, tumor contact with the SVZ remained statistically significant for PFS, but not OS. Patients with SVZ-contacting tumors presented a higher rate of aggressive clinical progression (30.9% vs. 11.3%; p = 0.007) and contralateral relapse patterns (23.4% vs. 9.1%; p = 0.048). Conclusions Our results suggest that glioblastoma contact with the SVZ appears to be an independent prognostic factor for poor PFS. The presence of an SVZ-contacting tumor was associated with more aggressive recurrences and a higher rate of contralateral relapses. These findings suggest that this variable may be a new prognostic factor in glioblastoma (AU)

Influence of glioblastoma contact with the subventricular zone on survival and recurrence patterns.

BACKGROUND: There is growing evidence that the subventricular zone (SVZ) may be involved in both the initiation and progression of glioblastoma (GB). We aimed to assess tumor proximity to the SVZ as a potential prognostic factor in GB. METHOD: Retrospective study of 133 patients diagnosed with primary GB who underwent surgery followed by temozolomide-based chemoradiation between 2010 and 2016. All lesions were classified according to their anatomic relation with the SVZ. We determined the effect of tumor contact with the SVZ on progression-free survival (PFS), overall survival (OS), type, and patterns of recurrence. RESULTS: At a median follow-up of 18.6 months (95% CI 15.9-21.2), PFS and OS were 7.5 (95% CI 6.7-8.3) and 13.9 (95% CI 10.9-16.9) months, respectively. On the univariate analyses, initial contact with the SVZ was a factor for poor prognosis for both PFS (6.1 vs. 8.7 months; p = 0.006) and OS (10.6 vs. 17.9 months; p = 0.037). On the multivariate analysis, tumor contact with the SVZ remained statistically significant for PFS, but not OS. Patients with SVZ-contacting tumors presented a higher rate of aggressive clinical progression (30.9% vs. 11.3%; p = 0.007) and contralateral relapse patterns (23.4% vs. 9.1%; p = 0.048). CONCLUSIONS: Our results suggest that glioblastoma contact with the SVZ appears to be an independent prognostic factor for poor PFS. The presence of an SVZ-contacting tumor was associated with more aggressive recurrences and a higher rate of contralateral relapses. These findings suggest that this variable may be a new prognostic factor in glioblastoma.

Recommendations for use of antigenic tests in the diagnosis of acute SARS-CoV-2 infection in the second pandemic wave: attitude in different clinical settings.

The high transmissibility of SARS-CoV-2 before and shortly after the onset of symptoms suggests that only diagnosing and isolating symptomatic patients may not be sufficient to interrupt the spread of infection; therefore, public health measures such as personal distancing are also necessary. Additionally, it will be important to detect the newly infected individuals who remain asymptomatic, which may account for 50% or more of the cases. Molecular techniques are the "gold standard" for the diagnosis of SARS-CoV-2 infection. However, the massive use of these techniques has generated some problems. On the one hand, the scarcity of resources (analyzers, fungibles and reagents), and on the other the delay in the notification of results. These two facts translate into a lag in the application of isolation measures among cases and contacts, which favors the spread of the infection. Antigen detection tests are also direct diagnostic methods, with the advantage of obtaining the result in a few minutes and at the very "pointof-care". Furthermore, the simplicity and low cost of these tests allow them to be repeated on successive days in certain clinical settings. The sensitivity of antigen tests is generally lower than that of nucleic acid tests, although their specificity is comparable. Antigenic tests have been shown to be more valid in the days around the onset of symptoms, when the viral load in the nasopharynx is higher. Having a rapid and real-time viral detection assay such as the antigen test has been shown to be more useful to control the spread of the infection than more sensitive tests, but with greater cost and response time, such as in case of molecular tests. The main health institutions such as the WHO, the CDC and the Ministry of Health of the Government of Spain propose the use of antigenic tests in a wide variety of strategies to respond to the pandemic. This document aims to support physicians involved in the care of patients with suspected SC2 infection, in the context of a growing incidence in Spain since September 2020, which already represents the second pandemic wave of COVID-19.

Improving quality of care and clinical outcomes for rectal cancer through clinical audits in a multicentre cancer care organisation.

INTRODUCTION: Colorectal cancer treatment requires a complex, multidisciplinary approach. Because of the potential variability, monitoring through clinical audits is advisable. This study assesses the effects of a quality improvement action plan in patients with locally advanced rectal cancer and treated with radiotherapy. METHODS: Comparative, multicentre study in two cohorts of 120 patients each, selected randomly from patients diagnosed with rectal cancer who had initiated radiotherapy with a curative intent. Based on the results from a baseline clinical audit in 2013, a quality improvement action plan was designed and implemented; a second audit in 2017 evaluated its impact. RESULTS: Standardised information was present on 77.5% of the magnetic resonance imaging (MRI) staging reports. Treatment strategies were similar in all three study centres. Of the patients whose treatment was interrupted, just 9.7% received a compensation dose. There was an increase in MRI re-staging from 32.5 to 61.5%, and a significant decrease in unreported circumferential resection margins following neoadjuvant therapy (ypCRM), from 34.5 to 5.6% (p <  0.001). CONCLUSIONS: The comparison between two clinical audits showed improvements in neoadjuvant radiotherapy in rectal cancer patients. Some indicators reveal areas in need of additional efforts, for example to reduce the overall treatment time.

[Utilisation of first-line antibiotics six years after a multifaceted intervention]. / Uso de antibióticos de primera línea 6 años después de una intervención multifacética.

OBJECTIVE: No study has evaluated the impact of a multifaceted intervention on the quality of the antibiotics prescribed more than 5 years later. METHODS: A total of 210 general practitioners (GP) from eight different regions of Spain were asked to participate in two registrations of respiratory tract infections (RTI) in 2008, before, and in 2009, just after a multifaceted intervention including prescriber feedback, clinical guidelines, training sessions focused on appropriate antibiotic prescribing, workshop on rapid tests and provision of these tests in the GP consultation. They were all again invited to participate in a similar registration in 2015. A new group of clinicians from the same areas who had never participated in antimicrobial stewardship courses were also invited to participate and acted as controls. RESULTS: The 121 GPs who continued the study (57.6%) and the 117 control GPs registered 22,407 RTIs. The antibiotic most commonly prescribed was amoxicillin and clavulanic acid, prescribed in 1,801 cases (8.1% of the total), followed by amoxicillin (1,372 prescriptions, 6.2%), being lower among GPs just after the intervention. The third leading antibiotic among GPs just after the intervention was penicillin V (127 cases, 3.3%) whereas macrolides ranked third in the other three groups of GPs. CONCLUSIONS: The use of first-line antibiotic for RTIs wanes over time after an intervention, but their utilisation is still significantly greater among intervened clinicians six years later compared to GPs who have never been exposed to any antimicrobial stewardship programmes.

Clinical Audit of the Radiotherapy Process in Rectal Cancer: Clinical Practice Guidelines and Quality Certification Do Not Avert Variability in Clinical Practice.

BACKGROUND: The therapeutic approach to cancer is complex and multidisciplinary. Radiotherapy is among the essential treatments, whether used alone or in conjunction with other therapies. This study reports a clinical audit of the radiotherapy process to assess the process of care, evaluate adherence to agreed protocols and measure the variability to improve therapeutic quality for rectal cancer. METHODS: Multicentre retrospective cohort study in a representative sample of patients diagnosed with rectal cancer in the Institut Català d'Oncologia, a comprehensive cancer centre with three different settings. We developed a set of indicators to assess the key areas of the radiotherapy process. The clinical audit consisted of a review of a random sample of 40 clinical histories for each centre. RESULTS: The demographic profile, histology and staging of patients were similar between centres. The MRI reports did not include the distance from tumour to mesorectal fascia (rCRM) in 38.3% of the cases. 96.7% of patients received the planned dose, and 57.4% received it at the planned time. Surgery followed neoadjuvant treatment in 96.7% of the patients. Among this group, postoperative CRM was recorded in 65.5% of the cases and was negative in 93.4% of these. With regard to the 34.5% (n = 40) of cases where no CRM value was stated, there were differences between the centres. Mean follow-up was 3.4 (SD 0.6) years, and overall survival at four years was 81.7%. CONCLUSIONS: The audit revealed a suboptimal degree of adherence to clinical practice guidelines. Significant variability between centres exists from a clinical perspective but especially with regard to organization and process.

The NRF2 transcription factor plays a dual role in colorectal cancer: A systematic review.

BACKGROUND: Colorectal cancer is one of the most common cancers worldwide, and is influenced by the interplay of various factors, including a very strong genetic component. For instance, incorrect mitochondrial biogenesis is correlated with increased risk of developing colorectal cancer. Thus, it is important to understand the consequences of changes in both the expression and the correct function of the transcription factors that regulate mitochondrial biogenesis, namely NRF2. OBJECTIVES: The main objective of this paper is to characterise the relationship between NRF2 and colorectal cancer by compiling data from an exhaustive literature search. METHODS: Information was obtained by defining specific search terms and searching in several databases. After a strict selection procedure, data were tabulated and the relationships between articles were assessed by measuring heterogeneity and by constructing conceptual maps. RESULTS AND DISCUSSION: We found a general consensus in the literature that the presence of oxidizing agents as well as the inhibition of the NRF2 repressor Keap1 maintain NRF2 expression at basal levels. This predominantly exerts a cytoprotective effect on cells and decreases risk of colorectal cancer. However, if NRF2 is inhibited, protection against external agents disappears and risk of colorectal cancer increases. Interestingly, colorectal cancer risk is also increased when NRF2 becomes overexpressed. In this case, the increased risk arises from NRF2-induced inflammation and resistance to chemotherapy. CONCLUSION: The proper basal function of NRF2 and Keap1 are essential for preventing oncogenic processes in the colon. Consequently, any disruption to the expression of these genes can promote the genesis and progression of colon cancer.

Pathways of Acetyl-CoA Metabolism Involved in the Reversal of Palmitate-Induced Glucose Production by Metformin and Salicylate.

The pathways through which fatty acids induce insulin resistance have been the subject of much research. We hypothesise that by focussing on the reversal of insulin resistance, novel insights can be made regarding the mechanisms by which insulin resistance can be overcome. Using global gene and lipid expression profiling, we aimed to identify biological pathways altered during the prevention of palmitate-induced glucose production in hepatocytes using metformin and sodium salicylate. FAO hepatoma cells were treated with palmitate (0.075 mM, 48 h) with or without metformin (0.25 mM) and sodium salicylate (2 mM) in the final 24 h of palmitate treatment, and effects on glucose production were determined. RNA microarray measurements followed by gene set enrichment analysis were performed to investigate pathway regulation. Lipidomic analysis and measurement of secreted bile acids and cholesterol were also performed. Reversal of palmitate-induced glucose production by metformin and sodium salicylate was characterised by co-ordinated down-regulated expression of pathways regulating acetyl-CoA to cholesterol and bile acid biosynthesis. All 20 enzymes that regulate the conversion of acetyl-CoA to cholesterol were reduced following metformin and sodium salicylate. Selected findings were confirmed using primary mouse hepatocytes. Although total intracellular levels of diacylglycerol, triacylglycerol and cholesterol esters increased with palmitate, these were not, however, further altered by metformin and sodium salicylate. 6 individual diacylglycerol, triacylglycerol and cholesterol ester species containing 18:0 and 18:1 side-chains were reduced by metformin and sodium salicylate. These results implicate acetyl-CoA metabolism and C18 lipid species as modulators of hepatic glucose production that could be targeted to improve glucose homeostasis.

Selected ginsenosides of the protopanaxdiol series are novel positive allosteric modulators of P2X7 receptors.

BACKGROUND AND PURPOSE: The P2X7 receptor is an ATP-gated ion channel predominantly expressed in immune cells and plays a key role in inflammatory processes. Ginseng is a well-known Chinese herb with both pro- and anti-inflammatory properties and many of its actions have been ascribed to constituent ginsenosides. We screened a number of ginsenoside compounds for pharmacological activity at P2X7 receptors, that might contribute to the reported immunomodulatory actions of ginseng. EXPERIMENTAL APPROACH: We used several assays to measure responses of P2X7 receptors, ATP-mediated dye uptake, intracellular calcium measurement and whole-cell patch-clamp recordings. HEK-293 cells stably expressing human P2X7 receptors were used in addition to mouse macrophages endogenously expressing P2X7 receptors. KEY RESULTS: Four ginsenosides of the protopanaxdiol series, Rb1, Rh2, Rd and the metabolite compound K (CK) potentiated the dye uptake responses of P2X7 receptors, whereas other ginsenosides tested were ineffective (1-10 µM). The potentiation was rapid in onset, required a threshold concentration of ATP (>50 µM) and had an EC50 of 1.08 µM. CK markedly enhanced ATP-activated P2X7 currents, probably via an extracellular site of action. One of the consequences of this potentiation effect is a sustained rise in intracellular Ca(2+) that could account for the decrease in cell viability in mouse macrophages after a combination of 500 µM ATP and 10 µM CK that are non-toxic when applied alone. CONCLUSIONS AND IMPLICATIONS: This study identifies selected ginsenosides as novel potent allosteric modulators of P2X7 channels that may account for some of the reported immune modulatory actions of protopanaxdiol ginsenosides in vivo.

[Clinical management of patient with benign prostatic hyperplasia in Spain]. / Manejo asistencial del paciente con hiperplasia benigna de próstata en España.

OBJECTIVES: To identify clinical management of benign prostatic hyperplasia (BPH) in Spain and its associated health care resources. MATERIAL AND METHODS: A qualitative cross-sectional study was conducted through telephone interviews to general practitioners (GP) and urologists. Information about diagnosis, pharmacologic treatment and follow-up was collected. Results were clustered according to the key variables considered as drivers of clinical practice patterns: BPH diagnosis, severity classification, treatment initiation and follow up of patients. RESULTS: 153 GP and 154 urologists participated in the study. 7 different clinical patterns were identified in primary care (PC). Resource use during diagnosis is relatively homogeneous, reporting a range of 2.0 to 2.6 visits employed and being the most frequent test performed PSA and urine test. Follow-up is heterogeneous; frequency of follow-up visits oscillates from 3.2 to 7.0 visits/patient/year and type of tests performed is different among patterns and within the same pattern. In Urology, 3 clinical patterns were identified. Resource use is homogeneous in the diagnosis and in the follow-up; urologists employed 2 visits in diagnosis and a range of 2.1 to 3.2 visits/patient/year in the follow-up. The most frequent tests both in diagnosis and follow-up are PSA and digital test. CONCLUSIONS: BPH management shows variability in PC, identifying 7 different clinical practice patterns with different resource use during the follow-up among patterns and within the same pattern. The implementation of clinical guidelines could be justified to reduce heterogeneity.

Coste-efectividad de la combinación dutasterida y tamsulosina en el tratamiento de la hiperplasia benigna de próstata en España / Cost-Effectiveness of the Combination Therapy of Dutasteride and Tamsulosin in the Treatment of Benign Prostatic Hyperlasia in Spain

Objetivos: evaluar el coste-efectividad incremental (CEI) de la combinación dutasterida y tamsulosina (DUT+TAM) de inicio frente al tratamiento más utilizado, tamsulosina (TAM), en pacientes con hiperplasia benigna de próstata (HBP) moderada-grave con riesgo de progresión. Material y métodos: se diseñó un modelo semi-Markov con un horizonte temporal a 4 y a 35 años desde la perspectiva del Sistema Nacional de Salud español a partir del estudio CombAT. La efectividad de los tratamientos se midió en años de vida ajustados por calidad (AVAC). El uso de recursos sanitarios se obtuvo de un panel de expertos. Los costes unitarios proceden de tarifas publicadas por las Comunidades Autónomas. El coste del tratamiento farmacológico se expresa en PVP-IVA; en el caso de TAM se utilizó el precio del genérico y en el de DUT+TAM el de la combinación a dosis fija. Todos los costes se expresan en euros de 2010. Resultados: DUT+TAM produce una mejoría incremental respecto a TAM de 0,06 AVAC a los 4 años y de 0,4 AVAC a los 35 años. El coste incremental de DUT+TAM es de 810,53 € a los 4 años y 3.443,62 € a los 35 años. Por tanto, El CEI de TAM+DUT respecto a TAM es 14.023,32 €/ AVAC y 8.750,15 €/ AVAC a los 4 y 35 años respectivamente. Conclusiones: el tratamiento de inicio con la combinación DUT+TAM es un tratamiento coste-efectivo frente TAM, el tratamiento más habitual en la práctica clínica española, al encontrase el ratio CEI por debajo del umbral que usualmente se considera para clasificar las tecnologías como coste-efectivas (AU)

Objectives: to evaluate the incremental cost-effectiveness ratio (ICER) of the combination therapy with dutasteride and tamsulosin (DUT+TAM) as initiation treatment versus the most used drug in Spain, tamsulosin (TAM), in the treatment of moderate to severe benign prostatic hyperplasia (BPH) with risk of progression. Methods: a semi-Markov model was developed using 4-year and 35-year time horizons and from the Spanish National Healthcare Service perspective. Data were obtained from the CombAT trial. Effectiveness was measured in terms of quality adjusted life years (QALYs). Health care resources were defined by an experts’ panel, and unitary costs were obtained from published Spanish sources. Pharmacologic cost is expressed in PTPWAT; in the case of TAM, the generic price is used, in the case of DUT+TAM the price of a fixed dose combination is used. Costs are expressed in 2010 Euros. Results: combination therapy with DUT+TAM produces an incremental effectiveness of 0.06QALY at year 4 and 0.4QALY at year 35. DUT+TAM represents an incremental cost of € 810.53 at 4 years and € 3,443.62 at 35 years. Therefore, the ICER for DUT+TAM versus TAM is € 14,023.32/QALY at year 4 and € 8,750.15/QALY at year 35. Conclusions: initiation treatment with DUT+TAM represents a cost-effective treatment versus TAM, the most used treatment in Spain, due to the fact the ICER is below the threshold that usually allows a technology to be considered as cost-effective (AU)

[Cost-effectiveness of the combination therapy of dutasteride and tamsulosin in the treatment of benign prostatic hyperlasia in Spain]. / Coste-efectividad de la combinación dutasterida y tamsulosina en el tratamiento de la hiperplasia benigna de próstata en España.

OBJECTIVES: to evaluate the incremental cost-effectiveness ratio (ICER) of the combination therapy with dutasteride and tamsulosin (DUT+TAM) as initiation treatment versus the most used drug in Spain, tamsulosin (TAM), in the treatment of moderate to severe benign prostatic hyperplasia (BPH) with risk of progression. METHODS: a semi-Markov model was developed using 4-year and 35-year time horizons and from the Spanish National Healthcare Service perspective. Data were obtained from the CombAT trial. Effectiveness was measured in terms of quality adjusted life years (QALYs). Health care resources were defined by an experts' panel, and unitary costs were obtained from published Spanish sources. Pharmacologic cost is expressed in PTP(WAT); in the case of TAM, the generic price is used, in the case of DUT+TAM the price of a fixed dose combination is used. Costs are expressed in 2010 Euros. RESULTS: combination therapy with DUT+TAM produces an incremental effectiveness of 0.06QALY at year 4 and 0.4QALY at year 35. DUT+TAM represents an incremental cost of € 810.53 at 4 years and € 3,443.62 at 35 years. Therefore, the ICER for DUT+TAM versus TAM is € 14,023.32/QALY at year 4 and € 8,750.15/QALY at year 35. CONCLUSIONS: initiation treatment with DUT+TAM represents a cost-effective treatment versus TAM, the most used treatment in Spain, due to the fact the ICER is below the threshold that usually allows a technology to be considered as cost-effective.

El control estadístico de proceso puede ayudar a prevenir los errores de tratamiento sin aumentar los costes en radioterapia / Statistical Process Control (SPC) can help prevent treatment errors without increasing costs in radiotherapy

Objetivo. El control estadístico de proceso (SPC) fue aplicado para monitorizar la estabilidad del proceso de colocación de pacientes en un tratamiento de radioterapia. Una vez medidos los errores de colocación, si estos indicaban una pérdida de estabilidad se identificaba la causa principal y se procedía a eliminarla para prevenir dichos errores. Material y métodos. Se midieron los errores de colocación en las dimensiones medial-laterales, craneal-caudal y anterior-posterior y se calcularon los límites de control superiores. Una vez conocidos los límites de control y el rango de variabilidad era aceptable, se procedió a observar los errores de colocación utilizando subgrupos de tres pacientes tres veces cada turno y se representaron en una gráfica de control a tiempo real. Resultados. Los valores de límite de control mostraron que la variabilidad existente era aceptable. Los errores de colocación, medidos y representados en un gráfico de promedio del proceso, ayudaron a controlar la estabilidad del proceso de colocación, ya que si la estabilidad se perdía, el tratamiento se interrumpía, se identificaba la causa específica responsable del patrón no aleatorio y se llevaba a cabo una acción correctora antes de proceder con el tratamiento. Conclusiones. El protocolo del SPC se centra en el control de la variabilidad debido a una causa asignable en lugar de centrarse en la variabilidad paciente a paciente, la cual no existe normalmente. Conclusiones A diferencia del método actual, que consiste en un único control semanal de colocación por paciente y, por tanto, solo asegura la correcta colocación del paciente en dicha sesión, el SPC permite prevenir el error de colocación de todos los pacientes en todas las sesiones al mismo tiempo que se reducen los costes de control(AU)

Purpose. Statistical Process Control (SPC) was applied to monitor patient set-up in radiotherapy and, when the measured set-up error values indicated a loss of process stability, its root cause was identified and eliminated to prevent set-up errors. Materials and methods. Set up errors were measured for medial-lateral (ml), cranial-caudal (cc) and anterior-posterior (ap) dimensions and then the upper control limits were calculated. Materials and methods. Once the control limits were known and the range variability was acceptable, treatment set-up errors were monitored using sub-groups of 3 patients, three times each shift. These values were plotted on a control chart in real time. Results. Control limit values showed that the existing variation was acceptable. Set-up errors, measured and plotted on a X¯ chart, helped monitor the set-up process stability and, if and when the stability was lost, treatment was interrupted, the particular cause responsible for the non-random pattern was identified and corrective action was taken before proceeding with the treatment. Conclusion. SPC protocol focuses on controlling the variability due to assignable cause instead of focusing on patient-to-patient variability which normally does not exist. Compared to weekly sampling of set-up error in each and every patient, which may only ensure that just those sampled sessions were set-up correctly, the SPC method enables set-up error prevention in all treatment sessions for all patients and, at the same time, reduces the control costs(AU)

[Statistical Process Control (SPC) can help prevent treatment errors without increasing costs in radiotherapy]. / El control estadístico de proceso puede ayudar a prevenir los errores de tratamiento sin aumentar los costes en radioterapia.

PURPOSE: Statistical Process Control (SPC) was applied to monitor patient set-up in radiotherapy and, when the measured set-up error values indicated a loss of process stability, its root cause was identified and eliminated to prevent set-up errors. MATERIALS AND METHODS: Set up errors were measured for medial-lateral (ml), cranial-caudal (cc) and anterior-posterior (ap) dimensions and then the upper control limits were calculated. Once the control limits were known and the range variability was acceptable, treatment set-up errors were monitored using sub-groups of 3 patients, three times each shift. These values were plotted on a control chart in real time. RESULTS: Control limit values showed that the existing variation was acceptable. Set-up errors, measured and plotted on a X chart, helped monitor the set-up process stability and, if and when the stability was lost, treatment was interrupted, the particular cause responsible for the non-random pattern was identified and corrective action was taken before proceeding with the treatment. CONCLUSION: SPC protocol focuses on controlling the variability due to assignable cause instead of focusing on patient-to-patient variability which normally does not exist. Compared to weekly sampling of set-up error in each and every patient, which may only ensure that just those sampled sessions were set-up correctly, the SPC method enables set-up error prevention in all treatment sessions for all patients and, at the same time, reduces the control costs.

[Referral criteria for benign prostatic hyperplasia in primary care.Sociedad Española de Médicos de Atención Primaria, Sociedad Española de Medicina General, Sociedad Española de Medicina de Familia y Comunitaria, Asociación Española de Urología]. / Criterios de derivación en hiperplasia benigna de próstata para atención primaria. Sociedad Española de Médicos de Atención Primaria, Sociedad Española de Medicina General, Sociedad Española de Medicina de Familia y Comunitaria, y la Asociación Española de Urología.

Benign prostatic hyperplasia (BPH) is a high prevalence condition in men over 50 years that requires continued assistance between primary care and urology. Therefore, consensus around common referral criteria was needed to guide and support both levels. Medical history, symptom assessment with International Prostate Symptom Score (IPSS) questionnaire, digital rectal examination and prostate-specific antigen (PSA) measurement are diagnostic tests available for general practitioners that allow setting a correct BPH diagnose. Patients with an IPSS<8 should be monitored by evaluating them annually. Treatment with alpha-blockers and an evaluation at the first and third month is recommended in patients with an IPSS 8-20 and if the prostate is small, if the prostate size is large treatment with alpha-blockers or 5alpha-reductase inhibitors and evaluation at the third and six month is recommended, and in patients with a large prostate and a PSA >1.5 ng/ ml combined treatment and evaluation at the first and sixth month is recommended. Some clear criteria for referral to urology are established in this document, which help in the management of these patients. Those patients with BPH who do not show any improvement at the third month of treatment with alpha-blockers, or the sixth month with 5alpha-reductase inhibitors, will be referred to urology. Patients will also be referred to urology if they have lower urinary tract symptoms, a pathological finding during rectal examination, IPSS>20, PSA>10 ng/ml or PSA>4 ng/ml and free PSA<20% or if they are <50 years with suspected BHP, or if they have any urological complication.

Criterios de derivación en hiperplasia benigna de próstata para atención primaria / Referral criteria for benign prostatic hyperplasia in primary care

La hiperplasia benigna de próstata (HPB) es una enfermedad con alta prevalencia entre los varones de más de 50 años que requiere una continuidad asistencial entre los 2 niveles existentes en nuestro país, el de atención primaria (AP) y el de atención especializada; motivo por el que era necesario consensuar unos criterios de derivación o de continuidad que sirvan de orientación a ambos colectivos. La historia clínica del paciente, el Índice Internacional de Síntomas Prostáticos (IPSS, International Prostate Symptom Score), el tacto rectal y el antígeno prostático específico (PSA, prostate-specific antigen) son herramientas accesibles en el ámbito de la AP que permiten un diagnóstico adecuado de la HBP. Conscientes de tal necesidad, las sociedades científicas de atención primaria (Sociedad Española de Médicos de Atención Primaria [SEMERGEN], Sociedad Española de Medicina General [SEMG], Sociedad Española de Medicina de Familia y Comunitaria [semFYC]) y la Asociación Española de Urología (AEU) elaboraron este documento de consenso. A los pacientes con IPSS<8 se los deberá mantener en vigilancia y evaluar anualmente; en los pacientes con IPSS 8-20, si el tamaño de la próstata es pequeño, se recomienda el tratamiento con bloqueadores alfa y evaluación al primer y tercer mes, si el tamaño de la próstata es grande se recomienda el tratamiento con bloqueadores alfa o inhibidores 5-alfa-reductasa y evaluación al tercer y sexto mes, y en el caso de pacientes con próstata grande y PSA 41,5 ng/ml se recomienda el tratamiento combinado y la evaluación al primer y sexto mes. En este documento se establecen unos criterios de derivación al urólogo claros, que facilitan el tratamiento de este tipo de pacientes. Se derivarán al urólogo aquellos pacientes con HBP que no presenten mejoría al tercer mes de tratamiento con bloqueadores alfa, o al sexto mes de tratamiento con inhibidores 5-alfa-reductasa. Se derivarán también los pacientes con síntomas del tracto urinario inferior en los que se observe algún hallazgo patológico durante el tacto rectal, IPSS >20, PSA >10 ng/ml o PSA >4 ng/ml y PSA libre <20% o pacientes con edades <50 años y sospecha de HBP, así como aquellos pacientes con alguna complicación urológica(AU)

Benign prostatic hyperplasia (BPH) is a high prevalence condition in men over 50 years that requires continued assistance between primary care and urology. Therefore, consensus around common referral criteria was needed to guide and support both levels. Medical history, symptom assessment with International Prostate Symptom Score (IPSS) questionnaire, digital rectal examination and prostate-specific antigen (PSA) measurement are diagnostic tests available for general practitioners that allow setting a correct BPH diagnose. Patients with an IPSS<8 should be monitored by evaluating them annually. Treatment with alpha-blockers and an evaluation at the first and third month is recommended in patients with an IPSS 8-20 and if the prostate is small, if the prostate size is large treatment with alpha-blockers or 5alpha-reductase inhibitors and evaluation at the third and six month is recommended, and in patients with a large prostate and a PSA >1.5 ng/ ml combined treatment and evaluation at the first and sixth month is recommended. Some clear criteria for referral to urology are established in this document, which help in the management of these patients. Those patients with BPH who do not show any improvement at the third month of treatment with alpha-blockers, or the sixth month with 5á-reductase inhibitors, will be referred to urology. Patients will also be referred to urology if they have lower urinary tract symptoms, a pathological finding during rectal examination, IPSS>20, PSA>10 ng/ml or PSA>4 ng/ml and free PSA<20% or if they are <50 years with suspected BHP, or if they have any urological complication(AU)