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"documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Med Clin. 2021;157:483-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "<span class="elsevierStyleItalic">PIK3CA</span>-related overgrowth spectrum (PROS): New insight in known diseases" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "483" "paginaFinal" => "488" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndromes de sobrecrecimiento relacionados con <span class="elsevierStyleItalic">PIK3CA</span> (PROS): Conocimiento nuevo de enfermedades conocidas" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1730 "Ancho" => 2175 "Tamanyo" => 178054 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Diagram of the canonical pathway of PI3K signaling activation and its intracellular signal transduction. 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Luisa Pedro-Botet, María Guadalupe Esteve, José Manuel Carrascosa" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Lourdes" "apellidos" => "Mateo" "email" => array:1 [ 0 => "mateolourdes@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M. Luisa" "apellidos" => "Pedro-Botet" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "María Guadalupe" "apellidos" => "Esteve" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "José Manuel" "apellidos" => "Carrascosa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:2 [ "colaborador" => "on behalf of the Committee of infections in patients treated with selective immunosuppressants of the Hospital Germans Trias i Pujol" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">◊</span>" "identificador" => "fn0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitari Germans Trias i Pujol, IGTP, Badalona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Enfermedades Infecciosas, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, IGTP, Investigador CIBERes, ISCIII, Badalona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Medicina Preventiva, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Aportaciones de un comité multidisciplinar para la prevención de infecciones en pacientes tratados con inmunosupresores selectivos" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1660 "Ancho" => 2917 "Tamanyo" => 667141 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Infection exposure according to geographical origin.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The development of selective immunosuppressants (SIS) has revolutionized the management of numerous inflammatory or neoplastic diseases that were difficult to treat until a few years ago, allowing in many cases an adequate control or even clinical remission. The term <span class="elsevierStyleItalic">biological therapy</span> encompasses, in a broad sense, any drug developed using molecular biology techniques and includes monoclonal antibodies, receptor analogues and chimeric molecules designed to bind to or mimic therapeutic targets. The main advantage of this therapeutic strategy lies in its specificity of action, which justifies a robust efficacy and an overall acceptable safety profile, and its main limitation is the potential risk of infection due to inhibition of certain immunological pathways.</p><p id="par0010" class="elsevierStylePara elsevierViewall">According to the ATC Classification (Classification based on Anatomical, Therapeutic and Chemical Structure Criteria) of drug substances issued by the Spanish Medicines Agency, biological medicines are included in group L, which includes antineoplastic and immunomodulatory agents.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The increasing use of biological therapy in a large number of different conditions makes it difficult to adequately manage infections which, although uncommon, can be serious in certain patients. The relative risk of infection is variable and depends on the different combinations of drug and host. Furthermore, it is difficult to establish the causal relationship between a biological agent and a certain infection, given the presence of a large number of confounding factors. In this context, the existence of consensual algorithms aimed at the prevention, diagnosis and treatment of possible adverse reactions can contribute to improving the management of these patients.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> To this end, the creation of a multidisciplinary committee to integrate knowledge on the target diseases of biological therapies, the peculiarities of infections in these patients, as well as some multidisciplinary aspects (pharmacy management, clinical pharmacology or vaccinations), seems essential in order to achieve a holistic view of infections in patients treated with SIS.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">On the other hand, targeted therapies represent not only a qualitative leap in the management of a large number of chronic diseases, mainly inflammatory, but also a growing financial impact on pharmaceutical spending.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> As an example, at the Germans Trias i Pujol University Hospital (HGTiP) the number of patients treated with SIS therapies - in particular with a higher prescription in rheumatological, dermatological and digestive system indications - almost doubled between 2015 and 2018. Although the cost per patient per year, based on reference prices, remained around 8500 euros in this period, the impact of this set of drugs on the pharmacy budget grew by 15%–20%, due to the increase in the number of patients treated.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Impact of infections in patients undergoing SIS treatment in real-world clinical practice</span><p id="par0025" class="elsevierStylePara elsevierViewall">Since the introduction of monoclonal antibody treatments two decades ago, special surveillance has been maintained regarding the occurrence of infectious complications. National and international registries monitoring adverse events for different autoimmune diseases have made it possible to correctly assess the risk of serious infections in patients treated with SIS.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The incidence of serious infections (those requiring hospital admission, parenteral antibiotic treatment or causing death) in rheumatic patients treated with anti-TNF has been around 4/100 patient-years, with an adjusted ratio of 1.2–1.4 with respect to patients treated with conventional disease-modifying drugs. The risk is higher during the first 6 months of treatment.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Although increasing age is an independent risk factor for serious infections, the relative risk of infection in the elderly population under biological treatment is not well established. Infections are recurrent in a small percentage of patients, so that after a first infection 14% have recurrent infections and up to 20% following sepsis.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> According to the BIOBADASER registry of rheumatic patients treated with SIS drugs, the incidence of infections in our country was 5.3 cases/100 patient-years in 2011.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> According to the PsoNeT network, including data from the BIOBADADERM, Psocare and <span class="elsevierStyleItalic">Clalit Health Services</span>, with 17,739 patients with psoriasis and 23,357.5 person-years of follow-up, an adjusted risk ratio of exposure to anti-TNF compared with non-biological drugs of 0.98 was determined for severe infections (confidence interval [95% CI]: 0.80–1.19), 1.00 (CI 95%: 0.62–1.61) for bacterial skin infections and 1.23 (CI 95%: 0.82–1.84) for granulomatous infections.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Besides the incidence of serious infections, one aspect to highlight is that mortality in patients with sepsis in the course of biological treatment not only does not seem to be increased but appears to be lower than in patients with sepsis without biological treatment, as shown by data from the German<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and British<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> registries.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In the Spanish BIOBADADERM registry, which includes patients with moderate and severe psoriasis under systemic and biological treatment in actual clinical practice, it was observed that infections were the most common adverse events, with a prevalence of upper respiratory tract infections, followed by skin and soft tissue infections.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The relative risk (RR) of serious infection according to meta-analyses in patients with rheumatoid arthritis on biological therapy was around 1.31–1.37.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Similarly, meta-analyses in inflammatory bowel disease estimate the RR to be between 1.2–1.4.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding the comparative risk of serious infections between the different biological drugs, it should be noted that in general it is similar with all anti-TNF agents, although several studies have shown a greater risk with infliximab and adalimumab. Some biologics have a better safety profile in terms of the risk of serious infections, such as abatacept and ustekinumab.</p><p id="par0050" class="elsevierStylePara elsevierViewall">When considering the risk of infection during these treatments, it is essential to take into account not only the effect of SIS, but also factors specific to the patient and the underlying disease, as well as the existence of previous infections. Pre-treatment frailty and advanced age have also been identified as risk factors for infection associated with biological treatment in patients with inflammatory bowel disease. The risk of infections in patients treated with anti-IL-17 drugs (secukinumab, ixekizumab) or with any anti-TNF〈 is higher in patients with psoriatic arthritis than in patients with skin psoriasis. In general, the risk of infection in patients receiving SIS treatment is higher in patients with inflammatory arthropathies, intermediate in patients with inflammatory bowel disease and clearly lower in patients with skin psoriasis.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Opportunistic infections are rare but serious in these patients. The incidence rates of opportunistic (nontuberculous) infection in real world registries range from 1.3 to 1.5/1000 patient-years.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The risk of these infections is clearly related to the joint use of glucocorticoids on a chronic basis. In patients treated with anti-TNF, herpes zoster, <span class="elsevierStyleItalic">Pneumocystis jerovecii</span> and <span class="elsevierStyleItalic">Legionella</span> infections are particularly prevalent. <span class="elsevierStyleItalic">P. jerovecii</span> infection has a higher risk in patients treated with rituximab compared to those treated with anti-TNFα drugs. The dietary recommendations established in 2006 regarding the consumption of dairy products, eggs and raw foods made it possible to reduce <span class="elsevierStyleItalic">Listeria</span> and <span class="elsevierStyleItalic">Salmonella</span> infections in 73% of cases.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Multidisciplinary committee objectives</span><p id="par0060" class="elsevierStylePara elsevierViewall">In order to implement and optimise both epidemiological surveillance and the correct diagnosis, management and prevention of infections in these patients, the creation of a multidisciplinary committee comprising professionals from various specialties was considered. The committee should serve in an advisory capacity, be in coordination with the medical and hospital management, have an annual action plan and be endorsed by the centre's quality of care management.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The initial objectives contemplated were:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0070" class="elsevierStylePara elsevierViewall">Commit to optimising the identification and management of infections in patients receiving SSI treatment on behalf of the institution and the patients themselves.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0075" class="elsevierStylePara elsevierViewall">Periodically record the initiation of new treatments according to drug and specialty.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0080" class="elsevierStylePara elsevierViewall">Optimize the vaccination of these patients.</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0085" class="elsevierStylePara elsevierViewall">Agree on how to detect the underlying latent infection, as well as infection that could be exacerbated or emerge in this therapeutic setting.</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">•</span><p id="par0090" class="elsevierStylePara elsevierViewall">Agree on how to evaluate the baseline immunological condition of the patient.</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">•</span><p id="par0095" class="elsevierStylePara elsevierViewall">Agree on microbiological and immunological monitoring.</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">•</span><p id="par0100" class="elsevierStylePara elsevierViewall">Prepare documents with hygienic-dietary recommendations and aspects related to daily life, such as caring for pets.</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">•</span><p id="par0105" class="elsevierStylePara elsevierViewall">Identify and understand the differential aspects in the case of immigrant patients, tourists or people who have to travel for work reasons.</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">•</span><p id="par0110" class="elsevierStylePara elsevierViewall">Enhance reporting and recording of serious infections as adverse drug reactions by hospital specialists.</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">•</span><p id="par0115" class="elsevierStylePara elsevierViewall">Periodically review the infection registry for infections potentially preventable through vaccination or lifestyle.</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">•</span><p id="par0120" class="elsevierStylePara elsevierViewall">Promote and ensure the training of hospital physicians.</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">•</span><p id="par0125" class="elsevierStylePara elsevierViewall">Establish a communication channel with patients to inform and recommend in the event of a pandemic/epidemic or other unforeseeable situations that may particularly affect patients under treatment with SIS.</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">•</span><p id="par0130" class="elsevierStylePara elsevierViewall">Promote research in the field of SIS.</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Committee structure and operation</span><p id="par0135" class="elsevierStylePara elsevierViewall">In order to meet the above-mentioned objectives, it was considered essential to involve the different SIS prescribing specialties (rheumatology, dermatology, gastroenterology, neurology, paediatrics, nephrology, oncology, haematology) and members of certain services with a more multidisciplinary care (preventive medicine, pharmacology, hospital pharmacy, infectious diseases or internal medicine, microbiology and immunology) in the committee.</p><p id="par0140" class="elsevierStylePara elsevierViewall">In terms of functioning, it was considered advisable for the committee to have a rotating chair with the aim of leading the group, setting the guidelines of the action plan annually by consensus and making an annual report on it, as well as someone in charge of the formal dynamics of the meetings. The frequency of meetings may vary depending on the characteristics of the centre, but it is considered that they should be held at least every three months. The actions and decisions agreed by the committee should be communicated to the rest of the centre's physicians through close contact with the quality department and the hospital's communication office in order to facilitate the dissemination of documents and care protocols among physicians, as well as recommendations for patients. Finally, the committee must take on a training responsibility for the staff of the hospital and of the centre's territorial reference area.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Committee functions</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Necessary screening of patients who are candidates for SIS therapy</span><p id="par0145" class="elsevierStylePara elsevierViewall">Infections are the most common adverse manifestations in patients receiving SIS. Some of these infections may be reactivations of opportunistic and/or latent infections. On the other hand, it is also necessary to know the immune status of these patients against some immuno-preventable infections.</p><p id="par0150" class="elsevierStylePara elsevierViewall">In order to prevent these infections, the Working Group agreed on the tests and determinations to be implemented early in all patients who are candidates to receive these treatments, in order to avoid some infections through prophylaxis and/or treatment of the latent infection and/or vaccination (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Vaccines in patients who are candidates for selective immunosuppressant therapy</span><p id="par0155" class="elsevierStylePara elsevierViewall">The degree of immunosuppression in these patients will depend on the type of drug used, the dose and duration of treatment and, ultimately, individual variability. For practical purposes, from the point of view of vaccination, patients undergoing treatment with biological therapies and/or high doses of corticosteroids are considered to have a high level of immunosuppression. In the immunisation of these patients, the safety and immune response induced by these vaccines must be carefully assessed.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">If possible, vaccination should be carried out before starting immunosuppressive treatment, although it is not justified to delay the start of treatment for this reason. Attenuated vaccines are contraindicated in patients receiving treatments involving severe immunosuppression. These vaccines should not be administered during the 4 weeks prior to the start of treatment and a minimum interval of 3 months between the end of treatment and the administration of attenuated vaccines (up to 12 months in the case of rituximab)<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> should be observed.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Inactivated vaccines do not require special precautions for administration, but it is recommended that vaccination be performed 2 weeks prior to the start of immunosuppressive therapy in order to obtain an optimal response. In case of vaccination during the period of immunosuppressive therapy, revaccination is recommended 3 months after completion, if the patient is still at risk.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Despite the wide variety of immunosuppressive drugs available and their different mechanisms of action, vaccination recommendations are relatively homogeneous for different groups of patients.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,18</span></a> The vaccines indicated in patients receiving SIS are:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">1</span><p id="par0175" class="elsevierStylePara elsevierViewall">Annual influenza vaccination, since they are at higher risk of serious flu complications. Quadrivalent or adjuvanted influenza vaccines are recommended.</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">2</span><p id="par0180" class="elsevierStylePara elsevierViewall">Pneumococcal vaccines in a sequential regimen starting with the 13 valent pneumococcal vaccine and then the 23 valent pneumococcal vaccine, with a booster dose of the latter at 5 years of age.</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">3</span><p id="par0185" class="elsevierStylePara elsevierViewall">In patients with HBV infection and biological therapies, reactivation of infection has been reported even with fulminant liver failure, so serological screening (HBsAg, HBcAc and HBsAc) and vaccination of those who are susceptible is advised.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Adjuvanted or dual-antigen-loaded hepatitis B vaccines may be necessary.</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">4</span><p id="par0190" class="elsevierStylePara elsevierViewall">Meningococcal vaccines (ACYW Meningococcal Conjugate Vaccine and Meningococcal B Vaccine) will be administered in case there is a risk factor that justifies it: anatomic or functional asplenia, treatment with eculizumab, history of invasive meningococcal disease and others.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">5</span><p id="par0195" class="elsevierStylePara elsevierViewall">Attenuated virus vaccines: if the initiation of immunosuppressive treatment is not urgent, it is advisable to ensure the immunity of these patients against measles, mumps and rubella (MMR vaccine) and chickenpox (chickenpox vaccine). Post-vaccination serologies in these patients are not routinely recommended.</p></li></ul></p><p id="par0200" class="elsevierStylePara elsevierViewall">It is advised that both healthcare personnel caring for these patients and those living with them should be vaccinated against influenza every year. Cohabitants over 12 years of age should be properly immunized against measles, rubella, mumps (MMR vaccine) and chickenpox. No special precautions are necessary with these vaccines (only if the cohabitant vaccinated with chickenpox vaccine develops a rash after vaccination, direct contact with the susceptible patient should be avoided until the rash is resolved). It must be remembered that attenuated virus vaccines are contraindicated in pregnant and immunosuppressed patients. Vaccines administered should be recorded in the medical record and patients should be provided with a vaccination card with a record of doses and dates of vaccine administration.</p><p id="par0205" class="elsevierStylePara elsevierViewall">As an example, the implementation of this vaccination programme in our hospital has grown significantly in recent years: from 55 patients included in 2015 to 364 patients in 2019. However, the number of patients who start SIS treatment without having undergone preventive medicine consultation is still considerable.</p><p id="par0210" class="elsevierStylePara elsevierViewall">In relation to COVID-19 vaccination, most of the clinical trials assessed did not authorise use in people with diseases at high risk of COVID-19 complications, such as severe immunosuppression. In any case and given that none of these vaccines are attenuated virus vaccines, there is no contraindication for their administration. On the contrary, vaccination against COVID-19 is especially indicated in patients treated with SIS, even though the immune response to the vaccine may be lower in these patients.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Immigrant and traveller patient department assessment in at-risk populations</span><p id="par0215" class="elsevierStylePara elsevierViewall">If the patient is an immigrant, assessment at the International Health Clinic is recommended to screen for imported infections specific to the patient's country of origin.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,23</span></a> In low-income countries, infections are the leading cause of morbidity and mortality. The vast majority of infections that will manifest and be diagnosed in a country other than the area in which they were acquired are generally of a time-limited course in the absence of reinfection. However, some may persist asymptomatic for more than 40 years, such as strongyloidiasis, <span class="elsevierStyleItalic">Trypanosoma cruzi</span> infection (Chagas disease), schistosomiasis or malaria, while other infections may have a higher incidence during the first years of reception in host countries, such as tuberculosis. In addition, attention should be paid to international travel to the country of origin because of the risk of re-infection. In this context, it deserves special attention to prevent serious conditions with high mortality such as miliary tuberculosis, hyperinfection syndrome caused by <span class="elsevierStyleItalic">Strongyloides</span> spp. or disseminated histoplasmosis before immunity is severely compromised. For this purpose, the immunological status of the patient as well as the geographical area (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) from which he/she comes from must be considered in order to individualise prophylaxis, treatment and follow-up in each case.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24–26</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0220" class="elsevierStylePara elsevierViewall">In general, screening of immigrant patients who are candidates for SIS includes these tests in addition to those performed in all other cases:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">•</span><p id="par0225" class="elsevierStylePara elsevierViewall">Determination of <span class="elsevierStyleItalic">Plasmodium</span> spp. and filariae in peripheral blood and/or thick blood film.</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">•</span><p id="par0230" class="elsevierStylePara elsevierViewall">Determination of <span class="elsevierStyleItalic">Strongyloides</span>, <span class="elsevierStyleItalic">Squistosomes</span> spp., amoebae, and other parasites in three separate stool samples.</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">•</span><p id="par0235" class="elsevierStylePara elsevierViewall">Determination of <span class="elsevierStyleItalic">Strongyloides</span> in larval culture.</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">•</span><p id="par0240" class="elsevierStylePara elsevierViewall">Serologies for Chagas, <span class="elsevierStyleItalic">Strongyloides</span>, HBV and HCV, <span class="elsevierStyleItalic">Leishmania</span> spp. and toxoplasmosis.</p></li><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">•</span><p id="par0245" class="elsevierStylePara elsevierViewall">Plain chest X-ray to evaluate lesions suggestive of infection caused by <span class="elsevierStyleItalic">Mycobacterium tuberculosis complex</span>, <span class="elsevierStyleItalic">Histoplasma</span> spp. or <span class="elsevierStyleItalic">Coccidioides</span> spp.</p></li></ul></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Development of guidelines with recommendations for patients receiving biological therapies (SIS)</span><p id="par0250" class="elsevierStylePara elsevierViewall">From the outset the Working Group raised the need to develop general recommendations for these patients, emphasising the recommendation of annual influenza vaccination and the need for other vaccinations, the need to advise their doctor in case of international travel and to always consult their doctor in the presence of high fever.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Food recommendations include advice on hand hygiene before and after eating, washing fruit and vegetables properly, making sure food is well cooked, keeping food in the refrigerator, checking expiry dates, keeping open containers in suitable conditions, avoiding eating raw meat and fish <span class="elsevierStyleItalic">(carpaccio, sushi, tartar, sashimi, tataki)</span> and avoiding unpasteurised dairy products or homemade mayonnaise.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">As for domestic animals, it is recommended to avoid aggressive or exotic breeds (due to the risk of scratches and transmission of infections), maintain good veterinary control with updated vaccinations, deworm animals when necessary, avoid giving them raw meat to eat, handle aquariums with gloves, clean cages with a mask and consult a veterinarian if animals show digestive, respiratory and/or skin symptoms.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29,30</span></a> These recommendations are available on the hospital's intranet and are given to all patients from the pharmacy office when they collect their treatment.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Protocols</span><p id="par0260" class="elsevierStylePara elsevierViewall">One of the objectives of multidisciplinary working groups is to promote standardised clinical practice in the different specialties and to reduce variability in patient management.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The protocols agreed within the committee (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>) provide practical support and are available on the hospital intranet.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0265" class="elsevierStylePara elsevierViewall">The rate of infections as a cause of hospital admission in these patients has decreased since the implementation of the protocols in the site: from 22.5% of the causes of admission in 2017, to 12.9% in 2018 and to 8, 9% in 2019.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Dissemination of the committee's actions and continuing medical training</span><p id="par0270" class="elsevierStylePara elsevierViewall">The proposals, programmes, actions and recommendations of the committee, made up of a limited number of professionals who are aware of the diagnosis and management of infections in these patients, would have little impact if they were not accompanied by a programme of dissemination and continuous medical training aimed at the various levels of care: primary care, emergency, outpatients, hospitalisation…</p><p id="par0275" class="elsevierStylePara elsevierViewall">Strategies should be varied and complementary, including the dissemination of content via the web and hospital protocols, the development of recommendation leaflets for patients, and providing educational and content dissemination sessions for hospital and primary care practitioners. Planning of continuing medical education workshops or strategies - courses, webinars - not only helps to consolidate the committee's track record, dissemination and experience, but also makes it possible to identify aspects that have not been covered. The recent SARS-CoV-2 pandemic has encouraged the development of telematic strategies that can assist in the dissemination of content and its storage for delayed viewing.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Future actions: involvement of specialized nursing and medical specialists in the reference health area</span><p id="par0280" class="elsevierStylePara elsevierViewall">The integration of specialised nursing in many of the departments caring for patients with immune-mediated diseases has been one of the great achievements in the management of chronic patients in the last decade. The knowledge that this group has acquired in terms of recognising adverse events has made it a key player, often as the first contact for patients with an infection. The health education they provide to the patient at the start of treatment and the direct access of patients to report any adverse events makes them an additional reference specialist. Both nursing specialised in outpatient care and nursing involved in treatments administered in the day hospital are key players that can and should be integrated in these multidisciplinary and multiprofessional committees.</p><p id="par0285" class="elsevierStylePara elsevierViewall">Finally, it is also essential that these committees include the participation of specialists from the reference health area involved in immuno-mediated diseases: not only in the training sessions organised by the committee, but also in the committee's own working meetings, in access to protocols and in the development of research projects.</p><p id="par0290" class="elsevierStylePara elsevierViewall">The recent SARS-CoV-2 pandemic has tested the usefulness and versatility of the committee's real-time operation. Communication between committee members has not only enabled the sharing of documents and useful information from the different specialties involved, providing a holistic view of infections in this group, but has also been useful for the rapid detection of cases, the development of proposals from the committee to the hospital's executive bodies and the implementation of multi-centre research projects.</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusions</span><p id="par0295" class="elsevierStylePara elsevierViewall">The creation of a multidisciplinary committee for patients undergoing treatment with SIS has meant a qualitative improvement in the strategy for the diagnosis and management of patients with these complications. From an initial phase of diagnosis of the situation, the establishment of a communication network between the professionals involved and the search for basic objectives, other more ambitious, proactive objectives have been derived, both in terms of care and education, useful for professionals and patients beyond the local setting. The consolidation of the working group, from a personal and professional perspective, has also led to the creation of an agile collaborative network and the implementation of clinical and basic multicentre collaborative projects.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Funding and conflict of interest</span><p id="par0300" class="elsevierStylePara elsevierViewall">The authors declare that they have no financial relationship that could give rise to a conflict of interest in relation to this paper.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Impact of infections in patients undergoing SIS treatment in real-world clinical practice" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Multidisciplinary committee objectives" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Committee structure and operation" ] 4 => array:3 [ "identificador" => "sec0025" "titulo" => "Committee functions" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Necessary screening of patients who are candidates for SIS therapy" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Vaccines in patients who are candidates for selective immunosuppressant therapy" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Immigrant and traveller patient department assessment in at-risk populations" ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Development of guidelines with recommendations for patients receiving biological therapies (SIS)" ] 4 => array:2 [ "identificador" => "sec0050" "titulo" => "Protocols" ] 5 => array:2 [ "identificador" => "sec0055" "titulo" => "Dissemination of the committee's actions and continuing medical training" ] 6 => array:2 [ "identificador" => "sec0060" "titulo" => "Future actions: involvement of specialized nursing and medical specialists in the reference health area" ] ] ] 5 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusions" ] 6 => array:2 [ "identificador" => "sec0070" "titulo" => "Funding and conflict of interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-12-23" "fechaAceptado" => "2021-03-21" "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Mateo L, Pedro-Botet ML, Esteve MG, Carrascosa JM. Aportaciones de un comité multidisciplinar para la prevención de infecciones en pacientes tratados con inmunosupresores selectivos. Med Clin (Barc). 2021;157:489–494.</p>" ] 1 => array:3 [ "etiqueta" => "◊" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">The members of said Committee are presented in <a class="elsevierStyleCrossRef" href="#sec0075">Appendix A</a>.</p>" "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0305" class="elsevierStylePara elsevierViewall">Maria Luisa Pedro-Botet, Lourdes Mateo, María Esteve, José Manuel Carrascosa, Silvia Roure, Glòria Cardona, María Méndez, Eva Montane, María Cristina Ramo, Montserrat Batlle, Eva Martínez Cáceres, Helena Guardiola, Miriam Mañosa, Adrià Antuori, David López, Rosa Serrano, Marina López.</p>" "etiqueta" => "Appendix A" "titulo" => "Members of the Committee of infections in patients treated with selective immunosuppressants of the Hospital Germans Trias i Pujol" "identificador" => "sec0075" ] ] ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1660 "Ancho" => 2917 "Tamanyo" => 667141 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Infection exposure according to geographical origin.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Analytical determinations and recommended consultations at the beginning of selective immunosuppressive therapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Complete blood count, biochemistry and immunological profile. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Serologies of infections susceptible to immunization or that must be monitored for eventual reactivation: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Serological markers for HBV infection: HBsAg, HBcAb, HBsAb (in the event that any of the first two were positive, a determination of HBV DNA should be performed to individualize the need for antiviral prophylaxis to avoid virus reactivation) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Hepatitis C virus and human immunodeficiency virus serology \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Varicella virus IgG determination \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Measles virus IgG determination \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. Detection of <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>-specific interferon-gamma (IGRAs) for latent tuberculosis infection screening \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4. Request consultation with the Preventive Medicine Department for early administration of the necessary vaccinations \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5. Consultation with the International Health department (in the case of an immigrant patient) for the screening of imported infections \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2794092.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Screening prior to the start of biological treatment.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Screening for infections in patients who are candidates for SIS drugs \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tuberculous infection protocol in patients under SIS treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prevention of hepatitis B virus reactivation with SIS treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Progressive multifocal leukoencephalopathy and biologics \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vaccination protocol in patients who are candidates for SIS drugs \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recording protocol of serious infections in patients under SIS treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2794093.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Protocols for the prevention of infections in patients treated with SIS.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Infections associated with immunotherapeutic and molecular targeted agents in hematology and oncology. 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Journal Information
Vol. 157. Issue 10.
Pages 489-494 (November 2021)
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Vol. 157. Issue 10.
Pages 489-494 (November 2021)
Special article
Contributions from a multidisciplinary committee for the prevention of infections in patients with targeted immunosuppressive therapy
Aportaciones de un comité multidisciplinar para la prevención de infecciones en pacientes tratados con inmunosupresores selectivos
Visits
2
Lourdes Mateoa,
, M. Luisa Pedro-Botetb, María Guadalupe Estevec, José Manuel Carrascosad, on behalf of the Committee of infections in patients treated with selective immunosuppressants of the Hospital Germans Trias i Pujol ◊
Corresponding author
a Servicio de Reumatología, Hospital Universitari Germans Trias i Pujol, IGTP, Badalona, Barcelona, Spain
b Servicio de Enfermedades Infecciosas, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, IGTP, Investigador CIBERes, ISCIII, Badalona, Barcelona, Spain
c Servicio de Medicina Preventiva, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain
d Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain
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