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        "titulo" => "Uso de antiinflamatorios no esteroideos y monitorizaci&#243;n de la funci&#243;n renal&#46; Estudio piloto en un centro de salud de Atenci&#243;n Primaria"
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">Non-steroidal anti-inflammatory drugs &#40;NSAIDs&#41; constitute a heterogeneous group of medications that are widely used with varying levels of analgesic&#44; anti-pyretic&#44; anti-platelet&#44; and anti-inflammatory activities&#46; These drugs are the first step in providing analgesic treatment based on the recommendations of the World Health Organisation &#40;WHO&#41;&#46;</p><p class="elsevierStylePara">The consumption of NSAIDs in Spain has increased in recent years from 23&#46;67 daily doses per 1000 inhabitants per day &#40;DHD&#41; in the 1990s to 45&#46;8DHD in 2003&#46;<span class="elsevierStyleSup">1</span> In our country&#44; acetyl-salicylic acid is one of the top 10 most widely sold drugs &#40;source&#58; IMS EMF audit&#44; December 2010&#41;&#46; Given the characteristics of our population&#44; the use of these drugs will probably continue to increase&#46;</p><p class="elsevierStylePara">NSAIDs often produce alterations in renal function and various organ systems&#44; with gastrointestinal&#44; haematological&#44; and cardiological impacts&#44; particularly in elderly patients&#44; where the presence of other pathologies such as diabetes&#44; chronic kidney disease&#44; arteriosclerosis&#44; and simultaneous consumption of other drugs&#44; especially those that affect renal function and vascularisation &#40;angiotensin II receptor blockers &#91;ARB&#93;&#44; ACE inhibitors&#44; diuretics&#44; etc&#46;&#41;&#44; all magnify the deleterious effects of NSAIDs&#46; As such&#44; these drugs are not considered to be innocuous&#44; and must be prescribed with caution in high-risk patients&#46;<span class="elsevierStyleSup">2-7</span></p><p class="elsevierStylePara">Currently&#44; we have no information regarding whether the state of renal function or possible consequences of NSAIDs are taken into account prior to prescription&#44; especially in patients who might be considered to be particularly more vulnerable&#44; whether due to elevated comorbidity or concomitant prescriptions with potential toxicity implications&#46;</p><p class="elsevierStylePara">The objective of our study was to evaluate the current state of monitoring of renal function in patients treated with NSAIDs&#44; both at the moment of prescription and during treatment&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHOD</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">We designed an observational&#44; retrospective study that was approved by the clinical research ethics committee of the Hospital Universitario Ramon y Cajal&#44; and that was carried out in accordance with the standard regulations for this type of study&#46;</p><p class="elsevierStylePara">We chose to evaluate patients at a health institution that would be representative of the entire population in the health area of the Community of Madrid&#46; We received collaboration from the directors of the primary care department&#44; and using the data registered in the Digital Medical Office system&#44; we selected all patients who had received a prescription during the study period&#44; analysing cases in which NSAIDs were prescribed&#46; The study period was October-November 2006&#44; so as to avoid vacation periods in which the population might show substantial variations during the programmed follow-up&#46;</p><p class="elsevierStylePara">We examined whether or not renal function was measured and&#47;or controlled prior to and&#47;or after the prescription of NSAIDs&#46; For this analysis&#44; we included all patients older than 14 years of age who had been prescribed an NSAID during the study period&#44; as long as there was no other registry of a different NSAID being prescribed to the same patient for at least 8 weeks prior to the date of the prescription in question&#46; This &#8220;new prescription&#8221; also had to be maintained for at least 7 days&#46;</p><p class="elsevierStylePara">Once the study population was selected&#44; we identified which patients had been tested for renal function during the study period&#46; We considered renal function to have been evaluated if the clinical history included a registry of creatinine values during a six-month period prior to the prescription&#46; We examined whether or not renal function was monitored over time in the form of creatinine measurements during the 3 months following the prescription&#46; For this analysis&#44; we received the collaboration of the Clinical Biochemical Department of the Hospital Universitario Ramon y Cajal&#44; whose laboratory performs all such analyses for the health area that treats the patients from our study region&#46; By using digital medical information&#44; we had access to the diagnosis associated with each prescription and laboratory analysis request&#44; as well as information regarding comorbidity&#44; concomitant treatment&#44; and the cause for all hospitalisations&#46;</p><p class="elsevierStylePara">As secondary objectives&#44; we analysed the type of patients in which renal function was monitored&#44; as well as factors that may have influenced whether or not this parameter was measure in our patients&#58; type of NSAID prescribed&#44; reason for prescription based on age&#44; sex&#44; associated comorbidity &#40;diabetes&#44; hypertension&#44; chronic pulmonary obstructive disease&#44; cirrhosis&#44; heart failure&#44; gastropathy&#41;&#44; and concomitant treatment &#40;beta-blockers&#44; ACE inhibitors&#44; ARB&#44; diuretics&#44; calcium channel blockers&#44; digitalis&#44; gastric protectors etc&#46;&#41;&#46; We described all complications that appeared between the start of treatment and 6 months afterwards&#46; For this analysis&#44; we defined renal failure as a 50&#37; increase in creatinine values over the baseline measurement&#44; as long as these data were available&#44; or an absolute value of creatinine &#62;1&#46;3mg&#47;dl in females or &#62;1&#46;5mg&#47;dl in males&#46; Hospitalisation was categorised as Yes or No&#46; We considered hospitalisations to be all periods spent in the hospital of at least 24 hours within the department to which patients were sent from the emergency department&#46; We also examined the cause for the original decompensation and subsequent hospitalisation&#46;</p><p class="elsevierStylePara">Finally&#44; we analysed all summary of product characteristics for the NSAIDs approved for use in Spain and that were available on the website of the Spanish Agency of Medicines and Medical Devices &#40;<a href="http&#58;&#47;&#47;www&#46;aemps&#46;es" class="elsevierStyleCrossRefs">www&#46;aemps&#46;es</a>&#41;&#44; and evaluated whether these data contained contraindications&#44; special precautions&#44; or dosage modifications for use in patients with renal failure&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">During the months of October and November 2006&#44; a total of 42&#160;822 new prescriptions were registered in the study hospital&#46; A total of 8611 were classified as &#8220;new prescriptions&#8221; based on the study criteria&#44; and 482 of these &#40;5&#46;6&#37;&#41; were new NSAID prescriptions &#40;Figure 1&#41;&#46; These prescriptions were applied to a total of 450 patients&#44; 64&#37; of which were female and 36&#37; male&#46; We analysed the distribution of prescriptions based on patient age&#58; 51&#37; of new prescriptions were for patients aged 14-45 years&#44; 21&#37; were in patients older than 65 years&#44; and 14&#37; each were in patients aged 46-55 and 56-65 years&#46;&#160;</p><p class="elsevierStylePara">The most commonly prescribed NSAID was ibuprofen &#40;66&#46;0&#37;&#41;&#46; At the time of our analysis &#40;2008&#41;&#44; there were 58 pharmaceutical registries approved for use in our country with ibuprofen as the active ingredient&#46; This was followed in decreasing order by diclofenac &#40;10&#37;&#41;&#44; naproxen &#40;8&#37;&#41;&#44; dexketoprofen &#40;5&#37;&#41;&#44; and aceclofenac &#40;3&#37;&#41;&#46; Currently &#40;2011&#41;&#44; a total of 79 pharmaceutical compounds have been registered in Spain with ibuprofen as the active ingredient &#40;Medimecum 2011&#41;&#46;</p><p class="elsevierStylePara">In association with these prescriptions&#44; we registered approximately 200 different pathologies that we have classified into 4 general groups in order to simplify our analysis&#46; The most relevant group&#44; corresponding to 54&#46;6&#37; of all prescriptions&#44; was what we have called musculo-skeletal pain&#46; The second group corresponded to 25&#46;5&#37; of all prescriptions&#44; and constituted inflammatory processes of the upper respiratory tract&#46; This was followed by generalised pain &#40;dysmenorrhea&#44; etc&#46;&#41; at 10&#37; and other processes not included in the other sections at 9&#46;9&#37;&#46;</p><p class="elsevierStylePara">In 168 patients&#44; we observed registries of serum creatinine measurements during the study period&#44; and only 42 patients &#40;9&#37;&#41; had more than one measurement available&#46; The majority of patients in which creatinine values were measured were female &#40;68&#37;&#41;&#46; Renal function was more commonly measured in patients older than 65 years of age &#40;39&#37;&#41; and in the youngest group &#40;31&#37;&#41;&#46; Only 14&#37; of patients had creatinine values measured during the 6 months prior to NSAID prescription &#40;63 patients&#41;&#44; and 129 patients &#40;28&#46;6&#37;&#41; had creatinine values measured at least once following NSAID prescription &#40;Figure 2&#41;&#46; Two patients were prescribed NSAIDs despite creatinine values of 1&#46;8mg&#47;dl and 2&#46;46mg&#47;dl&#44; respectively&#46;</p><p class="elsevierStylePara">In terms of monitoring renal function parameters&#44; 123 patients were tested for creatinine values at least 7 days after the prescription of NSAIDs&#58; on one occasion in 105 patients&#44; on two occasions in 15 patients&#44; and on 3 occasions in 3 patients&#46; We did not observe a relationship between underlying pathology &#40;renal failure or diabetes mellitus&#41; and the frequency of renal function assessments&#46;</p><p class="elsevierStylePara">We did not observe creatinine values indicative of renal failure as defined in our study design in any of the patients with creatinine values measured before or after NSAID prescription&#46; Nor did we observe any female patients with creatinine &#62;1&#46;3mg&#47;dl or males with creatinine &#62;1&#46;5mg&#47;dl following the prescription of NSAIDs&#44; except for the two aforementioned patients&#44; and in both cases&#44; the creatinine values indicative of renal failure were measured prior to NSAID prescription&#46;</p><p class="elsevierStylePara">Twenty-six patients were hospitalised during the 6 months following NSAID prescription&#46; None of the final diagnoses that caused hospitalisation involved pathologies related to NSAID use&#46;</p><p class="elsevierStylePara">We reviewed 19 summary of product characteristics corresponding to NSAIDs approved for use in Spain &#40;those available on the website of the Spanish Agency of Medicines and Medical Devices&#41;&#44; evaluating whether information was provided in terms of warnings or precautions&#44; contraindications&#44; and recommendations for modification of dosage in patients with altered renal function&#46; In section 4&#46;2 of the medication technical data sheets regarding dosage and mode of administration&#44; 68&#37; of the drugs evaluated recommended reducing dosage in patients with renal failure&#44; although no specifications were provided regarding the exact amount of decrease&#59; in section 4&#46;3 &#40;contraindications&#41;&#44; 47&#37; of drugs reported contraindications in patients with severe renal failure&#44; 15&#46;5&#37; in patients with moderate&#47;severe renal failure&#44; 10&#46;5&#37; in patients with creatinine clearance &#60;30&#44; and 5&#46;5&#37; in patients with severe renal failure in which dialysis is not an option&#59; in section 4&#46;4 &#40;warnings and special precautions&#41;&#44; 79&#37; of drugs mentioned warnings for use in patients with renal failure&#44; although severity was not specified&#46;</p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">In our study&#44; which took place at a hospital representative of the population in the health area of the Community of Madrid&#44; the prescription of NSAIDs constituted a substantial percentage of all new prescriptions made during the study period &#40;5&#46;6&#37;&#41;&#46; Ibuprofen was the most commonly prescribed active ingredient&#44; with 58 different pharmaceutical compounds on the market at the time of the study &#40;2008&#41;&#46; These results coincide with those published in 2007 in a report from the Spanish Agency of Medicines and Medical Devices regarding the use of NSAIDs in Spain&#44; which showed that the global use of NSAIDs in extra-hospital patients in Spain increased significantly from 26&#46;3DHD in 1992 to 45&#46;8DHD in 2006&#46; This report also demonstrated that this increase was primarily due to the prescription of ibuprofen&#44; which &#8220;came to represent 46&#37; of all NSAID consumption in Spain in 2006 &#40;the most heavily consumed NSAID in this year&#41;&#8221;&#46;<span class="elsevierStyleSup">8</span></p><p class="elsevierStylePara">In this study&#44; NSAIDs were more frequently used by females and patients aged 14-45 years&#46; Musculo-skeletal pain was the most common indication for NSAID prescriptions&#46;</p><p class="elsevierStylePara">Although it might seem surprising that the population comprising the lower age range &#40;14-45 years&#41; constituted more than 50&#37; of all prescriptions&#44; a review of the common pathologies that warranted these prescriptions shows that these are typical of this age range&#58; dysmenorrhea and injury caused by physical exercise&#46;</p><p class="elsevierStylePara">In our study&#44; it was uncommon for the renal function of these patients to be monitored either prior to or after NSAID prescription&#46; In fact&#44; only 14&#37; of patients who received these drugs had undergone an analysis of serum creatinine values prior to prescription&#46; Two patients were even prescribed NSAIDs despite elevated serum creatinine levels &#40;1&#46;8mg&#47;dl and 2&#46;4mg&#47;dl&#41;&#46; We believe that the summary of product characteristics for these medications should be modified to reflect current clinical recommendations&#46;</p><p class="elsevierStylePara">Our study did involve certain limitations&#44; such as its retrospective design and the difficulties inherent in collecting information regarding patient comorbidity and concomitant treatments&#44; primarily since the information was provided by a database organised by syndrome in the majority of cases&#46; Due to the retrospective nature of the study&#44; we were unable to conclude whether patients with altered creatinine levels who were not prescribed NSAIDs did not receive prescriptions precisely for this reason&#46; We must also add that&#44; although we initially intended to evaluate renal function based on estimated glomerular filtration rates&#44; we were forced to modify this criterion and use creatinine values instead due to insufficient data in the digital database for this type of analysis&#46; Although proteinuria could be affected by the use of NSAIDs&#44; we did not take this into account for our study&#46;</p><p class="elsevierStylePara">A prospective study would have allowed us to analyse whether a more strict control of renal function could have identified a higher rate of renal failure in patients who received NSAIDs&#46; Although pathologies related to the use of NSAIDs were not present in the final diagnoses registered for our study patients&#44; we cannot conclusively rule out this phenomenon&#44; since we did not perform an exhaustive review of all clinical histories&#46; Ours was a pilot study&#44; and its conclusions must be assessed with this in mind&#46; However&#44; it would certainly be desirable to observe a greater degree of control of renal function parameters prior to and following the prescription of NSAIDs&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">&#160;</span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Conflicts of interest</span></p><p class="elsevierStylePara">&#160;</p><p class="elsevierStylePara">The authors declare that they have no conflicts of interest related to the contents of this article&#46;</p><p class="elsevierStylePara"><a href="grande&#47;11483&#95;16025&#95;38431&#95;en&#95;f111483&#46;jpg" class="elsevierStyleCrossRefs"><img src="11483_16025_38431_en_f111483.jpg" alt="Relationship between new prescriptions and all prescriptions&#46; Percentage of non-steroidal anti-inflammatory drug &#40;NSAID&#41; prescriptions out of the total of all prescriptions"></img></a></p><p class="elsevierStylePara">Figure 1&#46; Relationship between new prescriptions and all prescriptions&#46; Percentage of non-steroidal anti-inflammatory drug &#40;NSAID&#41; prescriptions out of the total of all prescriptions</p><p class="elsevierStylePara"><a href="grande&#47;11483&#95;16025&#95;38432&#95;en&#95;f211483&#46;jpg" class="elsevierStyleCrossRefs"><img src="11483_16025_38432_en_f211483.jpg" alt="Serum creatinine &#40;Cr&#41; measurements in 450 patients who received non-steroidal anti-inflammatory drugs &#40;NSAID&#41; for the first time"></img></a></p><p class="elsevierStylePara">Figure 2&#46; Serum creatinine &#40;Cr&#41; measurements in 450 patients who received non-steroidal anti-inflammatory drugs &#40;NSAID&#41; for the first time</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Objetivos&#58;</span> Conocer el estado actual del seguimiento de la funci&#243;n renal realizada a los pacientes tratados con antiinflamatorios no esteroideos &#40;AINE&#41;&#46; <span class="elsevierStyleBold">Material y m&#233;todos&#58; </span>Se seleccionaron los pacientes adultos atendidos en un centro de Atenci&#243;n Primaria de la Comunidad de Madrid que recibieron alg&#250;n AINE por primera vez&#46; Se analiz&#243; si durante los 2 meses previos y los 6 posteriores a la prescripci&#243;n del AINE se conoc&#237;a la funci&#243;n renal&#46; <span class="elsevierStyleBold">Resultados&#58;</span> Durante el per&#237;odo de estudio se registraron 42&#46;822 prescripciones&#46; Un total de 8611 figuran como nuevas prescripciones&#44; 482 de las cuales &#40;5&#44;6 &#37;&#41; fueron prescripci&#243;n de AINE y se realizaron en pacientes mayores de 14 a&#241;os&#46; Recibieron alg&#250;n AINE 450 pacientes &#40;64 &#37; mujeres&#41;&#46; Ibuprofeno &#40;66&#44;0 &#37;&#41; fue el m&#225;s frecuentemente prescrito&#46; El grupo de edad con m&#225;s prescripciones de AINE fue el de 14-45 a&#241;os&#46; Solo 168 &#40;37&#44;1 &#37;&#41; cuentan con alguna anal&#237;tica solicitada durante el estudio &#40;68 &#37; mujeres&#41;&#46; Antes de recibir AINE&#44; solo en el 14 &#37; &#40;63 pacientes&#41; se conoc&#237;a el valor de creatinina s&#233;rica&#46; Dos pacientes recibieron AINE pese a tener cifras elevadas de creatinina&#46; Tras la prescripci&#243;n se solicit&#243; creatinina s&#233;rica en 129 pacientes &#40;28&#44;7 &#37;&#41;&#46; <span class="elsevierStyleBold">Conclusiones&#58; </span>Se prescribe un n&#250;mero importante de AINE&#46; El m&#225;s utilizado es el ibuprofeno&#46; Las prescripciones son m&#225;s frecuentes en mujeres y en personas de entre 14-45 a&#241;os de edad&#46; El dolor musculoesquel&#233;tico es la causa principal de esta indicaci&#243;n&#46; Solo en el 14 &#37; de los pacientes a los que se les trat&#243; con AINE se conoc&#237;a el valor de creatinina&#44; que no siempre se tuvo en cuenta a la hora de la prescripci&#243;n&#46; El control de la funci&#243;n renal tras prescribir AINE fue porcentualmente bajo&#46;</p>"
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        "resumen" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">Objectives&#58;</span> To determine the current state of renal function monitoring carried out on patients treated with NSAIDs&#46; Material and <span class="elsevierStyleBold">Method&#58;</span> We selected patients from a Primary Care Centre who had received NSAIDs for the first time&#46; We checked if renal function was measured and&#47;or controlled 2 months pre&#47;6 months post-NSAID administration in order to assess if patient renal function was known at the time of prescription and afterwards&#46; <span class="elsevierStyleBold">Results&#58;</span> During the study period&#44; there were 42&#160;822 prescriptions made&#46; Of these&#44; 8611 were new drug prescriptions&#44; of which 482 &#40;5&#46;6&#37;&#41; were NSAIDs in patients older than 14 years of age&#46; A total of 450 patients &#40;64&#37; female&#41; were treated with NSAIDs&#46; Ibuprofen &#40;66&#46;0&#37;&#41; was the most commonly prescribed&#46; NSAIDs were more frequently used in patients between 14-45 years of age&#46; Only 168 &#40;37&#46;1&#37;&#41; patients underwent any analytical tests over the course of the study &#40;68&#37; female&#41;&#46; Before prescription&#44; renal function was measured in only 14&#37; of cases &#40;63 patients&#41;&#46; Two patients received NSAIDs despite having high serum creatinine levels&#46; During the follow-up&#44; serum creatinine was measured in 129 patients &#40;28&#46;7&#37;&#41;&#46; <span class="elsevierStyleBold">Conclusions&#58;</span> In primary care&#44; NSAIDs represent a substantial percentage of the drugs prescribed &#40;5&#46;6&#37;&#41;&#46; Ibuprofen is the most commonly prescribed&#46; NSAIDs are more frequently used in women between 14-45 years&#46; Musculo-skeletal pain is the main indication for prescription&#46; Only 14&#37; of patients receiving these drugs had previously measured levels of serum creatinine&#46; These values are rarely taken into account when prescribing NSAIDs&#46; Control of renal function after NSAID prescription was unusual&#46;</p>"
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