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1.
Nucleic Acids Res ; 51(17): 9214-9226, 2023 09 22.
Article in English | MEDLINE | ID: mdl-37572349

ABSTRACT

Bacteriophages and bacteria are engaged in a constant arms race, continually evolving new molecular tools to survive one another. To protect their genomic DNA from restriction enzymes, the most common bacterial defence systems, double-stranded DNA phages have evolved complex modifications that affect all four bases. This study focuses on modifications at position 7 of guanines. Eight derivatives of 7-deazaguanines were identified, including four previously unknown ones: 2'-deoxy-7-(methylamino)methyl-7-deazaguanine (mdPreQ1), 2'-deoxy-7-(formylamino)methyl-7-deazaguanine (fdPreQ1), 2'-deoxy-7-deazaguanine (dDG) and 2'-deoxy-7-carboxy-7-deazaguanine (dCDG). These modifications are inserted in DNA by a guanine transglycosylase named DpdA. Three subfamilies of DpdA had been previously characterized: bDpdA, DpdA1, and DpdA2. Two additional subfamilies were identified in this work: DpdA3, which allows for complete replacement of the guanines, and DpdA4, which is specific to archaeal viruses. Transglycosylases have now been identified in all phages and viruses carrying 7-deazaguanine modifications, indicating that the insertion of these modifications is a post-replication event. Three enzymes were predicted to be involved in the biosynthesis of these newly identified DNA modifications: 7-carboxy-7-deazaguanine decarboxylase (DpdL), dPreQ1 formyltransferase (DpdN) and dPreQ1 methyltransferase (DpdM), which was experimentally validated and harbors a unique fold not previously observed for nucleic acid methylases.


Subject(s)
Bacteriophages , Guanine , Bacteria/genetics , Bacteriophages/genetics , DNA/genetics , Guanine/analogs & derivatives
2.
Gastroenterol Hepatol ; 46 Suppl 1: S1-S56, 2023 Mar.
Article in English, Spanish | MEDLINE | ID: mdl-36731724

ABSTRACT

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory disease that compromises the colon, affecting the quality of life of individuals of any age. In practice, there is a wide spectrum of clinical situations. The advances made in the physio pathogenesis of UC have allowed the development of new, more effective and safer therapeutic agents. OBJECTIVES: To update and expand the evaluation of the efficacy and safety of relevant treatments for remission induction and maintenance after a mild, moderate or severe flare of UC. RECIPIENTS: Gastroenterologists, coloproctologists, general practitioners, family physicians and others health professionals, interested in the treatment of UC. METHODOLOGY: GADECCU authorities obtained authorization from GETECCU to adapt and update the GETECCU 2020 Guide for the treatment of UC. Prepared with GRADE methodology. A team was formed that included authors, a panel of experts, a nurse and a patient, methodological experts, and external reviewers. GRADE methodology was used with the new information. RESULTS: A 118-page document was prepared with the 44 GADECCU 2022 recommendations, for different clinical situations and therapeutic options, according to levels of evidence. A section was added with the new molecules that are about to be available. CONCLUSIONS: This guideline has been made in order to facilitate decision-making regarding the treatment of UC, adapting and updating the guide prepared by GETECCU in the year 2020.


Subject(s)
Colitis, Ulcerative , Humans , Colitis, Ulcerative/drug therapy , Quality of Life , Remission Induction
4.
J Crohns Colitis ; 18(3): 416-423, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37797293

ABSTRACT

BACKGROUND AND AIMS: Durable clinical remission, endoscopic healing, and biomarker normalization are key treatment goals for Crohn's disease. The selective anti-interleukin-23 p19 inhibitor risankizumab has demonstrated efficacy and safety in moderately to severely active Crohn's disease. This post-hoc analysis of data from the pivotal risankizumab maintenance study assessed whether risankizumab maintenance therapy sustained the clinical and endoscopic outcomes achieved with risankizumab induction therapy. METHODS: We evaluated 462 patients who achieved a clinical response to risankizumab intravenous induction treatment and were re-randomized to receive subcutaneous risankizumab 360 mg, subcutaneous risankizumab 180 mg, or placebo [withdrawal] every 8 weeks for 52 weeks in the randomized, controlled FORTIFY maintenance study. Maintenance of clinical, endoscopic, and biomarker endpoints at week 52 among patients who achieved these endpoints after 12 weeks of induction treatment was evaluated. RESULTS: A significantly higher proportion of patients receiving maintenance treatment with risankizumab 360 or 180 mg compared with placebo [withdrawal] maintained Crohn's Disease Activity Index remission [68.6%, 70.8%, vs 56.3%; p < 0.05], stool frequency/abdominal pain remission [69.2%, 64.1%, vs 50.5%; p < 0.01], endoscopic response [70.2%, 68.2%, vs 38.4%; p < 0.001], endoscopic remission [74.4%, 45.5%, vs 23.9%; p < 0.05], and Simple Endoscopic Score for Crohn's Disease of 0-2 [65.5%, 36.7%, vs 21.9%]. Most patients [56.8-83.3%] who achieved normalized faecal calprotectin or C-reactive protein during induction sustained them with maintenance risankizumab. CONCLUSIONS: Subcutaneous risankizumab maintenance therapy results in durable improvement in clinical and endoscopic outcomes over 1 year in patients with moderately to severely active Crohn's disease. CLINICAL TRIAL REGISTRATION NUMBER: NCT03105102.


Subject(s)
Antibodies, Monoclonal , Crohn Disease , Humans , Crohn Disease/drug therapy , Abdominal Pain , Administration, Intravenous , Biomarkers
5.
Article in English | MEDLINE | ID: mdl-39367753

ABSTRACT

BACKGROUND: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD. RESULTS: One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint. CONCLUSIONS: A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment.

6.
Medicina (B Aires) ; 83(6): 1003-1006, 2023.
Article in Spanish | MEDLINE | ID: mdl-38117723

ABSTRACT

Plasminogen deficiency is a very rare multisystem entity that affects different tissues of the economy through the deposition of fibrin-rich pseudomembrane and determines a heterogeneous and diverse clinical presentation. It is transmitted in an autosomal recessive manner by mutations of the PLG gene on chromosome 6 and can be divided into hypoplasminogenemia or type I and dysplasminogenemia or type II, the latter not related to clinical pathology. Severe plasminogen deficiency has a prevalence of 1.6 individuals per million inhabitants and although it can be diagnosed in adulthood, the most severe symptoms are observed in infants and children. The most common form of onset is the so-called woody conjunctivitis, characterized by fibrin membranes that are deposited on the eyelids since childhood, causing exophytic lesions that affect vision. It can also affect other mucous membranes such as the gingival, respiratory, oropharyngeal, digestive and genital mucosa, among others. We present a rare case of severe plasminogen deficiency with conjunctivitis and woody cervicitis who was admitted with clinical acute abdominal symptoms, associated with a tumor mass due to pseudomembranous deposition in the ascending colon that simulated inflammatory bowel disease and resolved spontaneously.


La deficiencia de plasminógeno es una entidad multisistémica, muy infrecuente, que afecta diferentes tejidos de la economía mediante el depósito de pseudo membranas ricas en fibrina y que determina una presentación clínica heterogénea y diversa. Se transmite en forma autosómica recesiva por mutaciones del gen PLG del cromosoma 6 y se puede dividir en hipoplasminogenemia o tipo I y displasminogenemia o tipo II, esta última no relacionada con patología clínica. El déficit grave de plasminógeno tiene una prevalencia de 1.6 individuos por millón de habitantes y si bien puede diagnosticarse en edad adulta, los síntomas más graves se observan en lactantes y niños. La forma de inicio más común es la denominada conjuntivitis leñosa, caracterizada por membranas de fibrina que se depositan en los parpados desde la infancia, provocando lesiones exofíticas que afectan la visión. También puede afectar otras mucosas como la gingival, respiratoria, orofaríngea, digestiva y genital entre otros. Presentamos un raro caso de deficiencia grave de plasminógeno con conjuntivitis y cervicitis leñosa que ingresó con un cuadro de abdomen agudo clínico, asociado a una masa tumoral por depósito de pseudomembranas en el colon ascendente que simuló una enfermedad inflamatoria intestinal y que se resolvió espontáneamente.


Subject(s)
Coagulation Protein Disorders , Conjunctivitis , Child , Infant , Female , Humans , Plasminogen/genetics , Conjunctivitis/etiology , Coagulation Protein Disorders/complications , Fibrin
7.
Medicina (B Aires) ; 81(1): 91-95, 2021.
Article in Spanish | MEDLINE | ID: mdl-33611249

ABSTRACT

Whipple's disease is a chronic mutisystem disease caused by the bacteria Tropherima whipplei. Approximately 1200 cases have been described in the literature. The worldwide incidence is estimated at 9.8 cases per million people. Data from South America and Europe show that it affects middle-aged males. It is believed that host immunological factors rather than agent genotypic traits influence the course of the infection. Since the clinical characteristics are usually nonspecific and the wide spectrum of manifestations in individual organs may be underestimated, the diagnosis remains challenging. We present a case with multisystem compromise confirmed by histopathology. We consider its publication important given the few cases documented in South America and the relevance of bearing in mind the importance of an early diagnosis for a prompt treatment that improves the prognosis of this rare disease.


La enfermedad de Whipple es una enfermedad multisistémica crónica, causada por la bacteria Tropherima whipplei. Se han descripto aproximadamente 1200 casos en la literatura. La incidencia mundial se estima en 9.8 casos por millón de personas. Los datos provenientes de Sudamérica y Europa muestran que afecta a varones de mediana edad. Se cree que los factores inmunológicos del huésped son los que influyen en el curso de la infección y no el genotipo del agente. Dado que las características clínicas no suelen ser específicas y el espectro de manifestaciones en órganos individuales puede ser subestimado, el diagnóstico sigue siendo muy difícil. Presentamos un caso confirmado por histopatología con compromiso multisistémico. Consideramos importante su difusión dados los escasos casos documentados en Sudamérica y la relevancia de tener presente la sospecha diagnóstica para el abordaje terapéutico precoz que mejora el pronóstico de esta rara enfermedad.


Subject(s)
Hypertension, Pulmonary , Whipple Disease , Aged , Anti-Bacterial Agents/therapeutic use , Europe , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/etiology , Male , Middle Aged , Tropheryma , Whipple Disease/complications , Whipple Disease/diagnosis , Whipple Disease/drug therapy
8.
Arq Gastroenterol ; 57(1): 87-90, 2020.
Article in English | MEDLINE | ID: mdl-32294741

ABSTRACT

Inflammatory bowel disease comprises two distinct conditions - Crohn's disease and ulcerative colitis - which can be treated with immunomodulators. A non-neglectable proportion of these patients will need biologic therapy, and many patients under biologic treatment will experience either primary or secondary failure. As a consequence, clinical trials evaluating new therapeutic alternatives are being developed. These trials share common features, such as being controlled with placebo. Placebo use in clinical trials is a matter of intense debate. Those who support placebo use highlight the methodologic advantages placebo-controlled trials have. Those against placebo use argue that it would be against ethical principles in clinical research to expose a patient to placebo when a valid therapeutic alternative exists. In this review, we summarize the existing arguments for and against the use of placebo in the context of inflammatory bowel disease research. We finally suggest that it is very likely that in the near future inflammatory bowel disease trials will no longer be controlled with a placebo arm, but instead they will be non-inferiority trials with an active comparator.


Subject(s)
Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Clinical Trials as Topic , Humans , Placebos
9.
Gastroenterol Res Pract ; 2020: 4060648, 2020.
Article in English | MEDLINE | ID: mdl-32411197

ABSTRACT

METHODS: A multicenter cross-sectional study involving seven referral centers from three cities of Argentina was undertaken. Patients with a diagnosis of ulcerative colitis (UC), Crohn's disease (CD), or indeterminate colitis (IBDU/IC) were invited to answer an anonymous survey, which included a 5-point Likert scale to evaluate adherence to therapies. Independent variables associated with inadequate adherence were evaluated. RESULTS: Overall, 447 UC/IBDU and 135 CD patients were enrolled. Median age was 37 years (range 21-72); 39.8% were male; median time from diagnosis was 6 years (0.5-35). 91.4% were under treatment with at least one oral medication; 50.3% of patients reported inadequate adherence to oral medications. Patients with UC/IBDU had a lower risk of inadequate adherence when compared to patients with CD (OR 0.57 (0.37-0.87)). 21.8% reported inadequate adherence to biologics; subcutaneous administration was significantly associated with inadequate adherence to biologics (OR 4.8 (1.57-14.66)). CONCLUSION: Inadequate treatment adherence is common among patients with IBD, and potentially modifiable factors were identified.

10.
Arq Gastroenterol ; 55(3): 216-220, 2018.
Article in English | MEDLINE | ID: mdl-30540081

ABSTRACT

BACKGROUND: An association has been established between low serum values of vitamin D and inflammatory bowel disease. There is a lack of evidence on whether this association is still observed in regions where sun exposure throughout the year is higher. OBJECTIVE: To compare the prevalence of vitamin D deficiency between inflammatory bowel disease patients and healthy controls. METHODS: Inflammatory bowel disease patients were consecutively enrolled as cases. Age and gender-matched healthy subjects who agreed to undertake a determination of serum vitamin D were enrolled as controls. Demographic features, medical treatment, need for hospital admission at diagnosis, steroid treatment, smoking, need for surgical treatment were evaluated as factors associated with vitamin D deficiency. RESULTS: Overall, 59 patients with a diagnosis of either Crohn's disease or ulcerative colitis were enrolled, as well as 56 controls. Median age was 41 years (19-79) and 56% were male. Vitamin D deficiency was observed in 66.1% of inflammatory bowel disease patients versus 21.42% of healthy controls (OR 7.15 (3.1-16.48), P=0.001). Among inflammatory bowel disease patients, male gender, disease duration, moderate-to-severe disease and hospital admission at the moment of diagnosis were found to be associated with vitamin D deficiency. On multivariate analysis, only longer disease duration [(OR 1.01 (1-1.06)] and hospital admission at diagnosis [(OR 5.63 (1.01-31.61)] were found to be significantly associated with the latter. CONCLUSION: Vitamin D deficiency was more frequent among inflammatory bowel disease patients. Longer disease duration and need for hospital admission at diagnosis were associated to vitamin D deficiency among these patients.


Subject(s)
Colitis, Ulcerative/epidemiology , Crohn Disease/epidemiology , Vitamin D Deficiency/epidemiology , Adult , Aged , Argentina/epidemiology , Case-Control Studies , Cholecalciferol/blood , Colitis, Ulcerative/blood , Colitis, Ulcerative/complications , Crohn Disease/blood , Crohn Disease/complications , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Multivariate Analysis , Prevalence , Risk Factors , Severity of Illness Index , Statistics, Nonparametric , Vitamin D Deficiency/blood , Vitamin D Deficiency/complications , Young Adult
11.
J Vasc Interv Neurol ; 10(2): 62-64, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30746014

ABSTRACT

The TNF-α antagonists are the drugs used for the treatment of ulcerative colitis (UC). Nontraumatic convexity subarachnoid hemorrhage is an infrequent nonaneurysmal subtype of subarachnoid bleeding caused mainly by reversible cerebral vasoconstriction syndrome (RCVS), cerebral amyloid angiopathy, and posterior reversible encephalopathy syndrome (PRES). We present a 26-year-old female patient with a diagnosis of UC taking Adalimumab. She received her last doses the same day she was admitted to our hospital for an acute severe UC exacerbation. Steroids were added to the treatment. Five days after admission she presented a thunderclap headache with photophobia, nausea, and vomiting. An MRI was performed showing left frontal convexity subarachnoid hemorrhage and hyperintense lesions on T2-weighted and FLAIR sequences located in both occipital lobes, left cerebellar hemisphere, and brainstem. Digital angiography was unremarkable. Adalimumab was discontinued but persisted on treatment with steroids. The patient evolved with complete resolution of her symptoms and was discharged with a normal neurological exam. Two months later, she was asymptomatic and her MRI revealed superficial siderosis secondary to cSAH with resolution of white matter hyperintensities. Convexity subarachnoid hemorrhage in our patient could be secondary to PRES or to RCVS. Analogous MRI findings can be observed in both syndromes, along with similar clinical and angiographic findings. This suggests that both conditions may reflect different manifestations of the same pathology, in which vascular tone and endothelial dysfunction play a major role. To our knowledge, this is the first report of a patient with severe UC and convexity subarachnoid hemorrhage associated with Adalimumab.

12.
Gastroenterol Res Pract ; 2018: 6150145, 2018.
Article in English | MEDLINE | ID: mdl-29849594

ABSTRACT

BACKGROUND: The association between celiac disease and colorectal neoplasia has been previously studied, but the question whether recently diagnosed celiac patients show an increased colorectal adenoma prevalence remains unanswered. AIMS: To compare the prevalence of colorectal adenomas between adult patients with a recent diagnosis of celiac disease versus healthy controls. MATERIALS AND METHODS: A retrospective case-control study was undertaken. Patients with a diagnosis of celiac disease at an age of 45 years or more who undertook colonoscopy six months before or six months after the initiation of a gluten-free diet were enrolled as cases. Asymptomatic subjects undertaking screening colonoscopy were recruited as controls in a 2 : 1 fashion. The prevalence of colorectal adenomas and the prevalence of advanced adenomas were compared between groups. RESULTS: 57 celiac disease patients and 118 controls were enrolled. There was a greater prevalence of female patients among the celiac group, with no significant differences in terms of age. There were more obese patients among controls and a higher proportion of tabaquism among celiac patients. Adenoma prevalence was significantly higher among celiac patients (47.37% versus 27.97%, p = 0.01). Advanced adenoma detection was not different between groups. CONCLUSION: Adult patients with a recent diagnosis of celiac disease have an increased prevalence of colorectal adenomas.

13.
Medicina (B.Aires) ; Medicina (B.Aires);83(6): 1003-1006, dic. 2023. graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1558428

ABSTRACT

Resumen La deficiencia de plasminógeno es una entidad multisistémica, muy infrecuente, que afecta diferentes tejidos de la economía mediante el depósito de pseu do membranas ricas en fibrina y que determina una presentación clínica heterogénea y diversa. Se trans mite en forma autosómica recesiva por mutaciones del gen PLG del cromosoma 6 y se puede dividir en hipoplasminogenemia o tipo I y displasminogenemia o tipo II, esta última no relacionada con patología clínica. El déficit grave de plasminógeno tiene una prevalencia de 1.6 individuos por millón de habitan tes y si bien puede diagnosticarse en edad adulta, los síntomas más graves se observan en lactantes y ni ños. La forma de inicio más común es la denominada conjuntivitis leñosa, caracterizada por membranas de fibrina que se depositan en los parpados desde la infancia, provocando lesiones exofíticas que afectan la visión. También puede afectar otras mucosas como la gingival, respiratoria, orofaríngea, digestiva y genital entre otros. Presentamos un raro caso de deficiencia grave de plasminógeno con conjuntivitis y cervicitis leñosa que ingresó con un cuadro de abdomen agudo clínico, asociado a una masa tumoral por depósito de pseudomembranas en el colon ascendente que simu ló una enfermedad inflamatoria intestinal y que se resolvió espontáneamente.


Abstract Plasminogen deficiency is a very rare multisystem entity that affects different tissues of the economy through the de position of fibrin-rich pseudomembrane and determines a heterogeneous and diverse clinical presentation. It is trans mitted in an autosomal recessive manner by mutations of the PLG gene on chromosome 6 and can be divided into hypoplasminogenemia or type I and dysplasminogenemia or type II, the latter not related to clinical pathology. Severe plasminogen deficiency has a prevalence of 1.6 individuals per million inhabitants and although it can be diagnosed in adulthood, the most severe symptoms are observed in infants and children. The most common form of onset is the so-called woody conjunctivitis, characterized by fibrin membranes that are deposited on the eyelids since child hood, causing exophytic lesions that affect vision. It can also affect other mucous membranes such as the gingival, respiratory, oropharyngeal, digestive and genital mucosa, among others. We present a rare case of severe plasminogen deficiency with conjunctivitis and woody cervicitis who was admitted with clinical acute abdominal symptoms, associated with a tumor mass due to pseudomembranous deposition in the ascending colon that simulated inflam matory bowel disease and resolved spontaneously.

14.
Medicina (B.Aires) ; Medicina (B.Aires);81(1): 91-95, mar. 2021. graf
Article in Spanish | LILACS | ID: biblio-1287245

ABSTRACT

Resumen La enfermedad de Whipple es una enfermedad multisistémica crónica, causada por la bacteria Tropherima whipplei. Se han descripto aproximadamente 1200 casos en la literatura. La incidencia mundial se estima en 9.8 casos por millón de personas. Los datos provenientes de Sudamérica y Europa muestran que afecta a varones de mediana edad. Se cree que los factores inmunológicos del huésped son los que influyen en el curso de la infección y no el genotipo del agente. Dado que las características clínicas no suelen ser específicas y el espectro de manifestaciones en órganos individuales puede ser subestimado, el diagnóstico sigue siendo muy difícil. Presentamos un caso confirmado por histopatología con compromiso multisistémico. Consideramos importante su difusión dados los escasos casos documentados en Sudamérica y la relevancia de tener presente la sospecha diagnóstica para el abordaje terapéutico precoz que mejora el pronóstico de esta rara enfermedad.


Abstract Whipple's disease is a chronic mutisystem disease caused by the bacteria Tropherima whipplei. Approximately 1200 cases have been described in the literature. The worldwide incidence is estimated at 9.8 cases per million people. Data from South America and Europe show that it affects middle-aged males. It is believed that host immunological factors rather than agent genotypic traits influence the course of the infection. Since the clinical characteristics are usually nonspecific and the wide spectrum of manifestations in individual organs may be underestimated, the diagnosis remains challenging. We present a case with multisystem compromise confirmed by histopathology. We consider its publication important given the few cases documented in South America and the relevance of bearing in mind the importance of an early diagnosis for a prompt treatment that improves the prognosis of this rare disease.


Subject(s)
Humans , Male , Middle Aged , Aged , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/etiology , Whipple Disease/complications , Whipple Disease/diagnosis , Whipple Disease/drug therapy , Europe , Tropheryma , Anti-Bacterial Agents/therapeutic use
15.
Arq. gastroenterol ; Arq. gastroenterol;57(1): 87-90, Jan.-Feb. 2020.
Article in English | LILACS | ID: biblio-1098055

ABSTRACT

ABSTRACT Inflammatory bowel disease comprises two distinct conditions - Crohn's disease and ulcerative colitis - which can be treated with immunomodulators. A non-neglectable proportion of these patients will need biologic therapy, and many patients under biologic treatment will experience either primary or secondary failure. As a consequence, clinical trials evaluating new therapeutic alternatives are being developed. These trials share common features, such as being controlled with placebo. Placebo use in clinical trials is a matter of intense debate. Those who support placebo use highlight the methodologic advantages placebo-controlled trials have. Those against placebo use argue that it would be against ethical principles in clinical research to expose a patient to placebo when a valid therapeutic alternative exists. In this review, we summarize the existing arguments for and against the use of placebo in the context of inflammatory bowel disease research. We finally suggest that it is very likely that in the near future inflammatory bowel disease trials will no longer be controlled with a placebo arm, but instead they will be non-inferiority trials with an active comparator.


RESUMO A doença inflamatória intestinal compreende duas condições distintas: a doença de Crohn e a retocolite ulcerativa, que podem ser tratadas com imunomoduladores. Uma proporção não negligenciável desses pacientes necessitará de terapia biológica e, muitos destes em tratamento biológico, experimentarão falha primária ou secundária. Como consequência, ensaios clínicos avaliando novas alternativas terapêuticas estão sendo desenvolvidos. Estes ensaios partilham características comuns, tais como ser controlado com placebo. O uso de placebo em ensaios clínicos é uma questão de intenso debate. Aqueles que apoiam o uso do placebo destacam as vantagens metodológicas que os ensaios controlados com placebo têm. Aqueles contra o uso de placebo argumentam que seria contra os princípios éticos na investigação clínica expor um paciente ao placebo quando uma alternativa terapêutica válida existe. Nesta revisão, resumimos os argumentos existentes a favor e contra o uso de placebo no contexto da pesquisa de doença inflamatória intestinal. Finalmente, sugerimos que é muito provável que em um futuro próximo os ensaios de doença inflamatória intestinal não serão mais controlados com um braço placebo; em vez disso, serão feitos ensaios de não-inferioridade com um comparador ativo.


Subject(s)
Humans , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Placebos , Clinical Trials as Topic
16.
Arq. gastroenterol ; Arq. gastroenterol;55(3): 216-220, July-Sept. 2018. tab, graf
Article in English | LILACS | ID: biblio-973900

ABSTRACT

ABSTRACT BACKGROUND: An association has been established between low serum values of vitamin D and inflammatory bowel disease. There is a lack of evidence on whether this association is still observed in regions where sun exposure throughout the year is higher. OBJECTIVE: To compare the prevalence of vitamin D deficiency between inflammatory bowel disease patients and healthy controls. METHODS: Inflammatory bowel disease patients were consecutively enrolled as cases. Age and gender-matched healthy subjects who agreed to undertake a determination of serum vitamin D were enrolled as controls. Demographic features, medical treatment, need for hospital admission at diagnosis, steroid treatment, smoking, need for surgical treatment were evaluated as factors associated with vitamin D deficiency. RESULTS: Overall, 59 patients with a diagnosis of either Crohn's disease or ulcerative colitis were enrolled, as well as 56 controls. Median age was 41 years (19-79) and 56% were male. Vitamin D deficiency was observed in 66.1% of inflammatory bowel disease patients versus 21.42% of healthy controls (OR 7.15 (3.1-16.48), P=0.001). Among inflammatory bowel disease patients, male gender, disease duration, moderate-to-severe disease and hospital admission at the moment of diagnosis were found to be associated with vitamin D deficiency. On multivariate analysis, only longer disease duration [(OR 1.01 (1-1.06)] and hospital admission at diagnosis [(OR 5.63 (1.01-31.61)] were found to be significantly associated with the latter. CONCLUSION: Vitamin D deficiency was more frequent among inflammatory bowel disease patients. Longer disease duration and need for hospital admission at diagnosis were associated to vitamin D deficiency among these patients.


RESUMO CONTEXTO: Uma associação foi estabelecida entre os baixos valores séricos de vitamina D e doença inflamatória intestinal. Falta evidência se esta associação ainda é observada em regiões onde a exposição ao sol durante todo o ano é maior. OBJETIVO: Comparar a prevalência de deficiência de vitamina D entre pacientes com doença inflamatória intestinal e indivíduos controles saudáveis. MÉTODOS: Pacientes com doença inflamatória intestinal foram consecutivamente selecionados. Indivíduos saudáveis combinados da mesma idade e gênero que concordaram em fornecer uma determinação da vitamina D do soro foram considerados como controles. Características demográficas, tratamento médico, necessidade de admissão hospitalar no diagnóstico, tratamento de esteroides, tabagismo, necessidade de tratamento cirúrgico foram avaliados como fatores associados à deficiência de vitamina D. RESULTADOS: No geral, 59 pacientes com diagnóstico de doença de Crohn ou colite ulcerosa foram observados, bem como 56 controles. A idade mediana era de 41 anos (19-79) e 56% eram do sexo masculino. A deficiência de vitamina D foi observada em 66,1% dos pacientes com doença inflamatória intestinal versus 21,42% dos controles saudáveis (OR 7,15 (3.1-16.48), P=0,001). Entre os pacientes com doença inflamatória intestinal, sexo masculino, duração da doença, doença de moderada a severa e admissão hospitalar no momento do diagnóstico foram associados com a deficiência de vitamina D. Na análise multivariada, apenas a duração da doença [(OR 1; 1 (1-1,06)] e a admissão hospitalar no diagnóstico [(OR 5,63 (1,01-31,61)] foram encontradas significativamente associadas ao último. CONCLUSÃO: A deficiência de vitamina D foi mais frequente entre os pacientes com doença inflamatória intestinal. Maior duração da doença e necessidade de admissão hospitalar no diagnóstico foram associadas à deficiência de vitamina D entre esses pacientes.


Subject(s)
Humans , Male , Female , Adult , Aged , Young Adult , Vitamin D Deficiency/epidemiology , Colitis, Ulcerative/epidemiology , Crohn Disease/epidemiology , Argentina/epidemiology , Vitamin D Deficiency/complications , Vitamin D Deficiency/blood , Severity of Illness Index , Colitis, Ulcerative/complications , Colitis, Ulcerative/blood , Crohn Disease/complications , Crohn Disease/blood , Case-Control Studies , Prevalence , Cross-Sectional Studies , Multivariate Analysis , Risk Factors , Cholecalciferol/blood , Statistics, Nonparametric , Middle Aged
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