Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.039
Filtrar
1.
Medicine (Baltimore) ; 99(35): e21488, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871870

RESUMO

BACKGROUND: Celiac disease is an autoimmune enteropathy characterized by an aberrant immune response to ingested gluten in genetically predisposed individuals. Studies have pointed to a rising prevalence of celiac disease in recent decades. Changes in diet and use of medication that may impact the gut microbiome have been suggested as potential contributors. Exposure to protein pump inhibitors (PPIs) was recently found to be associated with an increased risk for subsequent diagnosis of celiac disease. We aimed to investigate potential mechanisms for this link by examining the relationship between PPI use and gluten-related immune responses in the context of changes in gut microbiome. METHODS: We performed a post hoc analysis of blood and fecal samples from a recent randomized trial in order to assess the potential association between PPI use and development of celiac disease serology in conjunction with alterations in gastrointestinal microbial composition. The study included 12 healthy participants who were administered a PPI (Omeprazole; 40 mg twice daily) for 4 or 8 weeks. RESULTS: The analysis did not reveal an overall significant change in levels of serologic markers of celiac disease for the study cohort in response to PPI treatment. However, one individual developed a marked increase in the celiac disease-specific autoantibody response to transglutaminase 2 in conjunction with enhanced immune reactivity to gluten during the trial. Genotyping revealed positivity for the celiac disease-associated HLA-DQ2 and -DQ8 alleles. Furthermore, the observed elevation in antibody responses was closely associated with a sharp increase in fecal abundance of bacteria of the order Actinomycetales. CONCLUSIONS: The results of this exploratory analysis support further investigation of molecular mechanisms involved in the contribution of PPIs to celiac disease risk through the potential enhancement of gluten immunopathology and changes in gut microbial population.


Assuntos
Doença Celíaca/sangue , Doença Celíaca/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Omeprazol/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Actinomycetales/crescimento & desenvolvimento , Adulto , Alelos , Doença Celíaca/epidemiologia , Doença Celíaca/metabolismo , Fezes/microbiologia , Feminino , Proteínas de Ligação ao GTP/sangue , Proteínas de Ligação ao GTP/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/microbiologia , Genótipo , Glutens/efeitos adversos , Glutens/imunologia , Antígenos HLA-DQ/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Prevalência , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Transglutaminases/sangue , Transglutaminases/efeitos dos fármacos
2.
Clin Drug Investig ; 40(10): 897-899, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32779119

RESUMO

During the ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more attention should be paid to the balance of risks and benefits associated with proton pump inhibitors for the following reasons. One of the main functions of gastric juice is to inactivate swallowed microorganisms, thereby inhibiting infectious agents from reaching the intestine. Studies have documented that proton pump inhibitors are a risk factor for rotavirus, influenza virus, norovirus, and Middle East respiratory syndrome coronavirus infections, and are associated with an increased risk of acute gastroenteritis during periods of highest circulation of enteric viruses. In light of the evidence for gastrointestinal infection implying a fecal-oral transmission of SARS-CoV-2 and given the magnitude of the SARS-CoV-2/coronavirus disease 2019 pandemic, associated with the widespread misuse of proton pump inhibitors, this suggests that we should not rule out the hypothesis that patients treated with proton pump inhibitors may be more at risk of being infected by SARS-CoV-2.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Betacoronavirus/fisiologia , Infecções por Coronavirus/induzido quimicamente , Ácido Gástrico/fisiologia , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Pandemias , Pneumonia Viral/induzido quimicamente , Fatores de Risco
3.
Am J Gastroenterol ; 115(10): 1707-1715, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32852340

RESUMO

INTRODUCTION: Proton pump inhibitors (PPIs) increase the risk for enteric infections that is likely related to PPI-induced hypochlorhydria. Although the impact of acid suppression on severe acute respiratory syndrome coronavirus 2 is unknown thus far, previous data revealed that pH ≤3 impairs the infectivity of the similar severe acute respiratory syndrome coronavirus 1. Thus, we aimed to determine whether use of PPIs increases the odds for acquiring coronavirus disease 2019 (COVID-19) among community-dwelling Americans. METHODS: From May 3 to June 24, 2020, we performed an online survey described to participating adults as a "national health survey." A multivariable logistic regression was performed on reporting a positive COVID-19 test to adjust for a wide range of confounding factors and to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Of 53,130 participants, 3,386 (6.4%) reported a positive COVID-19 test. In regression analysis, individuals using PPIs up to once daily (aOR 2.15; 95% CI, 1.90-2.44) or twice daily (aOR 3.67; 95% CI, 2.93-4.60) had significantly increased odds for reporting a positive COVID-19 test when compared with those not taking PPIs. Individuals taking histamine-2 receptor antagonists were not at elevated risk. DISCUSSION: We found evidence of an independent, dose-response relationship between the use of antisecretory medications and COVID-19 positivity; individuals taking PPIs twice daily have higher odds for reporting a positive test when compared with those using lower-dose PPIs up to once daily, and those taking the less potent histamine-2 receptor antagonists are not at increased risk. These findings emphasize good clinical practice that PPIs should only be used when indicated at the lowest effective dose, such as the approved once-daily label dosage of over-the-counter and prescription PPIs. Further studies examining the association between PPIs and COVID-19 are needed.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Ácido Gástrico/metabolismo , Inquéritos Epidemiológicos/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Adolescente , Adulto , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/estatística & dados numéricos , Fatores de Confusão Epidemiológicos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Refluxo Gastroesofágico/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Azia/tratamento farmacológico , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Adulto Jovem
4.
Arq Bras Cir Dig ; 33(2): e1506, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32844883

RESUMO

BACKGROUND: Acid inhibition from chronic proton pump inhibitor use and a possible increase in gastrin can lead to changes in the regulation of hydrochloric acid production. However, it has not known whether such chronic use changes the presence of gastrin, delta, and enterochromaffin-like cells in the stomach or the relationship between gastrin and delta cells. AIM: To analyze the number of gastrin-producing gastrin cells, somatostatin-producing cells, and histamine-producing cells in patients who were chronic users of proton pump inhibitor, with or without related Helicobacter pylori infection. METHODS: Biopsies from 105 patients, including 81 chronic proton pump inhibitor users (experimental group) and 24 controls, were processed immunohistochemically and subjected to counting of gastrin, delta, and enterochromaffin-like cells in high-magnification microscopic fields and in 10 glands. RESULTS: Gastrin cell, delta cell, and enterochromaffin-like cells counts were similar across the groups and appeared to be unaffected by Helicobacter pylori infection. The ratio between gastrin cells and delta cells was higher in the chronic users of proton pump inhibitor group than in controls. CONCLUSION: Chronic users of proton pump inhibitor does not affect gastrin cell, delta cell, and enterochromaffin-like cell counts significantly, but may alter the ratio between gastrin cells and delta cells.


Assuntos
Celulas Tipo Enterocromafim/metabolismo , Gastrinas/sangue , Infecções por Helicobacter/terapia , Helicobacter pylori/isolamento & purificação , Inibidores da Bomba de Prótons/uso terapêutico , Bombas de Próton/metabolismo , Gastropatias/induzido quimicamente , Estudos de Casos e Controles , Celulas Tipo Enterocromafim/efeitos dos fármacos , Gastrinas/fisiologia , Infecções por Helicobacter/diagnóstico , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Estômago , Gastropatias/sangue
5.
PLoS Med ; 17(6): e1003140, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32542023

RESUMO

BACKGROUND: Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs. METHODS AND FINDINGS: We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation. CONCLUSIONS: We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811835, NCT01331668.


Assuntos
Transplante de Rim/mortalidade , Inibidores da Bomba de Prótons/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de Risco
7.
Lancet Infect Dis ; 20(8): 964-975, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32275867

RESUMO

BACKGROUND: (+)-SJ000557733 (SJ733) is a novel, orally bioavailable inhibitor of Plasmodium falciparum ATP4. In this first-in-human and induced blood-stage malaria phase 1a/b trial, we investigated the safety, tolerability, pharmacokinetics, and antimalarial activity of SJ733 in humans. METHODS: The phase 1a was a single-centre, dose-escalation, first-in-human study of SJ733 allowing modifications to dose increments and dose-cohort size on the basis of safety and pharmacokinetic results. The phase 1a took place at St Jude Children's Research Hospital and at the University of Tennessee Clinical Research Center (Memphis, TN, USA). Enrolment in more than one non-consecutive dose cohort was allowed with at least 14 days required between doses. Participants were fasted in seven dose cohorts and fed in one 600 mg dose cohort. Single ascending doses of SJ733 (75, 150, 300, 600, 900, or 1200 mg) were administered to participants, who were followed up for 14 days after SJ733 dosing. Phase 1a primary endpoints were safety, tolerability, and pharmacokinetics of SJ733, and identification of an SJ733 dose to test in the induced blood-stage malaria model. The phase 1b was a single-centre, open-label, volunteer infection study using the induced blood-stage malaria model in which fasted participants were intravenously infected with blood-stage P falciparum and subsequently treated with a single dose of SJ733. Phase 1b took place at Q-Pharm (Herston, QLD, Australia) and was initiated only after phase 1a showed that exposure exceeding the threshold minimum exposure could be safely achieved in humans. Participants were inoculated on day 0 with P falciparum-infected human erythrocytes (around 2800 parasites in the 150 mg dose cohort and around 2300 parasites in the 600 mg dose cohort), and parasitaemia was monitored before malaria inoculation, after inoculation, immediately before SJ733 dosing, and then post-dose. Participants were treated with SJ733 within 24 h of reaching 5000 parasites per mL or at a clinical score higher than 6. Phase 1b primary endpoints were calculation of a parasite reduction ratio (PRR48) and parasite clearance half-life, and safety and tolerability of SJ733 (incidence, severity, and drug-relatedness of adverse events). In both phases of the trial, SJ733 hydrochloride salt was formulated as a powder blend in capsules containing 75 mg or 300 mg for oral administration. Healthy men and women (of non-childbearing potential) aged 18-55 years were eligible for both studies. Both studies are registered with ClinicalTrials.gov (NCT02661373 for the phase 1a and NCT02867059 for the phase 1b). FINDINGS: In the phase 1a, 23 healthy participants were enrolled and received one to three non-consecutive doses of SJ733 between March 14 and Dec 7, 2016. SJ733 was safe and well tolerated at all doses and in fasted and fed conditions. 119 adverse events were recorded: 54 (45%) were unrelated, 63 (53%) unlikely to be related, and two (2%) possibly related to SJ733. In the phase 1b, 17 malaria-naive, healthy participants were enrolled. Seven participants in the 150 mg dose cohort were inoculated and dosed with SJ733. Eight participants in the 600 mg dose cohort were inoculated, but two participants could not be dosed with SJ733. Two additional participants were subsequently inoculated and dosed with SJ733. SJ733 exposure increased proportional to the dose through to the 600 mg dose, then was saturable at higher doses. Fasted participants receiving 600 mg exceeded the target area under the concentration curve extrapolated to infinity (AUC0-∞) of 13 000 µg × h/L (median AUC0-∞ 24 283 [IQR 16 135-31 311] µg × h/L, median terminal half-life 17·4 h [IQR 16·1-24·0], and median timepoint at which peak plasma concentration is reached 1·0 h [0·6-1·3]), and this dose was tested in the phase 1b. All 15 participants dosed with SJ733 had at least one adverse event. Of the 172 adverse events recorded, 128 (74%) were mild. The only adverse event attributed to SJ733 was mild bilateral foot paraesthesia that lasted 3·75 h and resolved spontaneously. The most common adverse events were related to malaria. Based on parasite clearance half-life, the derived log10PRR48 and corresponding parasite clearance half-lives were 2·2 (95% CI 2·0-2·5) and 6·47 h (95% CI 5·88-7·18) for 150 mg, and 4·1 (3·7-4·4) and 3·56 h (3·29-3·88) for 600 mg. INTERPRETATION: The favourable pharmacokinetic, tolerability, and safety profile of SJ733, and rapid antiparasitic effect support its development as a fast-acting component of combination antimalarial therapy. FUNDING: Global Health Innovative Technology Fund, Medicines for Malaria Venture, and the American Lebanese Syrian Associated Charities.


Assuntos
Antimaláricos/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Isoquinolinas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Antimaláricos/farmacocinética , Estudos de Casos e Controles , Eritrócitos/efeitos dos fármacos , Eritrócitos/parasitologia , Feminino , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética , Humanos , Isoquinolinas/administração & dosagem , Isoquinolinas/efeitos adversos , Isoquinolinas/farmacocinética , Estágios do Ciclo de Vida/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/metabolismo , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/farmacocinética , Resultado do Tratamento , Adulto Jovem
8.
Pediatr. aten. prim ; 22(85): 81-84, ene.-mar. 2020.
Artigo em Espanhol | IBECS | ID: ibc-193452

RESUMO

CONCLUSIONES DE LOS AUTORES DEL ESTUDIO: el uso de tratamiento antisecretor en el primer año de vida, inhibidores de bomba de protones solos o en combinación con antagonistas de receptores H2, está asociado con un incremento del riesgo de fracturas en niños. Este riesgo puede ser mayor si el tratamiento se inicia en los primeros meses de vida y es de mayor duración. COMENTARIO DE LOS REVISORES: el aumento del riesgo de fracturas asociado al tratamiento antisecretor durante el primer año es un argumento más para valorar cuidadosamente la indicación de estos fármacos, especialmente los inhibidores de la bomba de protones, sobre todo en tratamientos precoces o prolongados


AUTHORS' CONCLUSIONS: infant proton pump inhibitors alone or together with H2 receptor antagonists is associated with an increased childhood fracture risk. This risk appears amplified by duration or early initiation of the therapy. REVIEWERS' COMMENTARY: the increased risk of fractures associated with antisecretory treatment during the first year of life another argument to carefully assess the indication of these drugs, especially proton pump inhibitors, particularly in treatments at an early age or long-term treatments


Assuntos
Humanos , Masculino , Feminino , Lactente , Inibidores da Bomba de Prótons/efeitos adversos , Fraturas Ósseas/induzido quimicamente , Antagonistas dos Receptores Histamínicos H2/efeitos adversos , Azia/tratamento farmacológico , Antiulcerosos/efeitos adversos , Antiácidos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
10.
Bull Cancer ; 107(4): 458-464, 2020 Apr.
Artigo em Francês | MEDLINE | ID: mdl-32057465

RESUMO

Proton pump inhibitors, a major progress in gastro-enterology, are globally among the most widely prescribed drugs. But, due to their strong gastric acid inhibition, they can be responsible for side effects, particularly in cancer patients. They are involved in renal function impairment, bone fractures, digestive bacterial overgrowth, particularlyclostridium difficile infections, anemia and hypomagnesemia. Long term use can increase the risks of gastric, pancreatic and liver cancers. They decrease absorption of weak bases drugs, particularly tyrosine kinase inhibitors and capecitabine and are responsible for a poorer prognosis if taken concomitantly with erlotinib, gefitinib and pazopanib. Modification of cyclin dependent kinases is also possible as well as decrease of efficacy of immune check point inhibitors (microbiome modifications). Absoption and efficacy of capecitabine seem also poorer with negative prognosis effect on treatment of gastric and colon cancer. Their long term use, particularly in cancer patients, should probably be avoided.


Assuntos
Neoplasias/complicações , Inibidores da Bomba de Prótons/efeitos adversos , Antineoplásicos/farmacocinética , Infecções Bacterianas/induzido quimicamente , Capecitabina/farmacocinética , Contraindicações de Medicamentos , Interações Medicamentosas , Disbiose/induzido quimicamente , Cloridrato de Erlotinib/administração & dosagem , Fraturas Ósseas/induzido quimicamente , Absorção Gastrointestinal/efeitos dos fármacos , Neoplasias Gastrointestinais/induzido quimicamente , Gefitinibe/administração & dosagem , Humanos , Rim/efeitos dos fármacos , Prognóstico , Proteínas Tirosina Quinases/antagonistas & inibidores , Inibidores da Bomba de Prótons/farmacologia , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem
11.
Medicine (Baltimore) ; 99(3): e18610, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011441

RESUMO

To compare the Stretta procedure with proton pump inhibitors for the treatment of nonerosive reflux disease (NERD).From July 2018 to April 2019, patients diagnosed with NERD and referred for treatment were enrolled. They were treated with either Stretta procedure or proton pump inhibitor (PPI) medication and followed-up for 6 months. The symptom control, quality of life, lower esophageal sphincter (LES) pressure, 24-hour pH parameters, PPI usage and satisfaction rate were evaluated. The complications were assessed. The outcomes of the 2 groups were analyzed and compared.Twenty-eight patients in the Stretta group and 21 patients in the PPI group completed the 6-month follow-up. No severe adverse events occurred in both groups. Both interventions were effective in improvement of symptom and quality of life. The symptom score improvement was significantly superior in the Stretta group compared to the PPI group (6.3 ±â€Š3.4 vs 8.5 ±â€Š4.1, P = .03). LES pressure increased significantly in the Stretta group compared to the PPI group (14.2 ±â€Š4.4 mm Hg vs 10.0 ±â€Š4.0 mm Hg, P < .01). Although both interventions improved 24-hour pH parameters, including number of acid episodes (P = .27), acid exposure time (P = .39), and DeMeester score (P = .28), no difference was found between the 2 groups. Complete PPI cessation rate (82% vs 52%, P = .03) as well as satisfaction rate (89% vs 57%, P = .02) was much higher in Stretta group than those in the PPI groupThe Stretta procedure was safe and effective in the short term for the management of NERD. The Stretta procedure resulted in higher LES pressure and achieved better improvement of symptom control and PPI cessation than did PPI in the short term.


Assuntos
Ablação por Cateter/métodos , Refluxo Gastroesofágico/terapia , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Ablação por Cateter/efeitos adversos , Esfíncter Esofágico Inferior/fisiopatologia , Feminino , Seguimentos , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Inibidores da Bomba de Prótons/efeitos adversos , Qualidade de Vida
12.
Int J Mol Sci ; 21(2)2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31963924

RESUMO

Neuroendocrine tumors (NETs) throughout the body are the focus of much current interest. Most occur in the gastrointestinal tract and have shown a major increase in incidence over the past 30 years, roughly paralleling the world-wide increase in the use of proton pump inhibitor (PPI) drugs. The greatest rise has occurred in gastric carcinoids (g-NETs) arising from enterochromaffin-like (ECL) cells. These tumors are long known to occur in auto-immune chronic atrophic gastritis (CAG) and Zollinger-Ellison syndrome (ZES), with or without multiple endocrine neoplasia type-1 (MEN-1), but the incidences of these conditions do not appear to have increased over the same time period. Common to these disease states is persistent hypergastrinemia, generally accepted as causing g-NETs in CAG and ZES, and postulated as having similar tumorigenic effects in PPI users. In efforts to study the increase in their occurrence, g-NETs have been classified in a number of discussed ways into different grades that differ in their incidence and apparent pathogenesis. Based on a large amount of experimental data, tumorigenesis is mediated by gastrin's effects on the CCK2R-receptor on ECL-cells that in turn leads to hyperplasia, dysplasia, and finally neoplasia. However, in all three conditions, the extent of response of ECL-cells to gastrin is modified by a number of genetic influences and other underlying risk factors, and by the duration of exposure to the hormonal influence. Data relating to trophic effects of hypergastrinemia due to PPI use in humans are reviewed and, in an attached Appendix A, all 11 reports of g-NETs that occurred in long-term PPI users in the absence of CAG or ZES are summarized. Mention of additional suspected cases reported elsewhere are also listed. Furthermore, the risk in humans may be affected by the presence of underlying conditions or genetic factors, including their PPI-metabolizer phenotype, with slow metabolizers likely at increased risk. Other problems in estimating the true incidence of g-NETs are discussed, relating to non-reporting of small tumors and failure of the Surveillance, Epidemiology, and End Results Program (SEER) and other databases, to capture small tumors or those not accorded a T1 rating. Overall, it appears likely that the true incidence of g-NETs may be seriously underestimated: the possibility that hypergastrinemia also affects tumorigenesis in additional gastrointestinal sites or in tumors in other organ systems is briefly examined. Overall, the risk of developing a g-NET appears greatest in patients who are more than 10 years on drug and on higher doses: those affected by chronic H. pylori gastritis and/or consequent gastric atrophy may also be at increased risk. While the overall risk of g-NETs induced by PPI therapy is undoubtedly low, it is real: this necessitates caution in using PPI therapy for long periods of time, particularly when initiated in young subjects.


Assuntos
Tumor Carcinoide/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Neoplasias Gástricas/epidemiologia , Tumor Carcinoide/induzido quimicamente , Relação Dose-Resposta a Droga , Gastrite Atrófica/tratamento farmacológico , Humanos , Incidência , Tumores Neuroendócrinos/induzido quimicamente , Tumores Neuroendócrinos/epidemiologia , Inibidores da Bomba de Prótons/uso terapêutico , Neoplasias Gástricas/induzido quimicamente , Síndrome de Zollinger-Ellison/tratamento farmacológico
13.
Libyan J Med ; 15(1): 1708639, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31905110

RESUMO

Introduction: Clostridioides difficile (C. difficile) infection (CDI) is one of the most common healthcare-associated (HA) infections in contemporary medicine. The risk factors (RFs) for HA CDI in medical and surgical patients are poorly investigated in countries with a limited resource healthcare system. Therefore, the aim of the study was to investigate differences in patients' characteristics, factors related to healthcare and outcomes associated with HA CDI in surgical and medical patients in tertiary healthcare centre in Serbia.Materials and Methods: A prospective cohort study was conducted including adult patients diagnosed with initial episode of HA CDI, first recurrence of disease, readmission to hospital, while deaths within 30 days of CDI diagnosis and in-hospital mortality were also recorded. Patients hospitalized for any non-surgical illness, who developed initial HA CDI were assigned to medical group, whereas those who developed initial HA CDI after surgical procedures were in surgical group. The data on patients' characteristics and factors related to healthcare were collected, too.Results: During 7-year period, from 553 patients undergoing in-hospital treatment and diagnosed with CDI, 268 (48.5%) and 285 (51.5%) were surgical and medical patients, respectively. Age ≥ 65 years, use of proton pump inhibitors, chemotherapy and fluoroquinolones were positively associated with being in medical group, whereas admission to intensive care unit and use of second- and third-generation cephalosporins were positively associated with being in surgical group.Conclusions: Based on obtained results, including significant differences in 30-day mortality and in-hospital mortality, it can be concluded that medical patient were more endangered with HA CDI than surgical ones.


Assuntos
Infecções por Clostridium/microbiologia , Clostridium difficile/isolamento & purificação , Infecção Hospitalar/diagnóstico , Hospitalização/tendências , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Cefalosporinas/efeitos adversos , Cefalosporinas/uso terapêutico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Clostridium difficile/efeitos dos fármacos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/mortalidade , Assistência à Saúde/economia , Tratamento Farmacológico/métodos , Tratamento Farmacológico/estatística & dados numéricos , Feminino , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de Risco , Sérvia/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos
14.
Int J Mol Sci ; 21(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947724

RESUMO

Long-term use of proton pump inhibitors (PPIs) is common in patients with muscle wasting-related chronic diseases. We explored the hypothesis that the use of PPIs may contribute to a reduction in muscle mass and function in these patients. Literature indicates that a PPI-induced reduction in acidity of the gastrointestinal tract can decrease the absorption of, amongst others, magnesium. Low levels of magnesium are associated with impaired muscle function. This unwanted side-effect of PPIs on muscle function has been described in different disease backgrounds. Furthermore, magnesium is necessary for activation of vitamin D. Low vitamin D and magnesium levels together can lead to increased inflammation involved in muscle wasting. In addition, PPI use has been described to alter the microbiota's composition in the gut, which might lead to increased inflammation. However, PPIs are often provided together with nonsteroidal anti-inflammatory drugs (NSAIDs), which are anti-inflammatory. In the presence of obesity, additional mechanisms could further contribute to muscle alterations. In conclusion, use of PPIs has been reported to contribute to muscle function loss. Whether this will add to the risk factor for development of muscle function loss in patients with chronic disease needs further investigation.


Assuntos
Caquexia/etiologia , Músculos/efeitos dos fármacos , Inibidores da Bomba de Prótons/efeitos adversos , Sarcopenia/etiologia , Animais , Caquexia/fisiopatologia , Doença Crônica , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Magnésio/metabolismo , Músculos/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Sarcopenia/fisiopatologia
15.
Aliment Pharmacol Ther ; 51(4): 410-420, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31909512

RESUMO

BACKGROUND: There have been safety concerns considering long-term proton pump inhibitor (PPI) use, also during pregnancy. AIMS: To assess the risk of adverse neonatal outcomes associated with maternal intake of PPIs by means of systematic review and meta-analysis. METHODS: The systematic search included PubMed, Web of Science, Cochrane Database and Embase (inception until June 2019). All studies reporting ≥1 adverse pregnancy outcome comparing PPI users to non-users. Histamine-2 receptor antagonists (H2RA) were also compared to both non-users and PPI users. Outcomes included congenital malformations, abortion, stillbirth, neonatal death, preterm birth, small for gestational age and low birth weight. Pooled odds ratios (OR) and 95% confidence intervals (CI) were obtained by random-effects modelling. PROSPERO study-protocol: CRD42018103320. RESULTS: In total, 26 observational studies (20 cohort, 6 case-control studies) were identified, of which 19 assessed PPIs and 12 H2RA. PPI use was associated with an increased risk of congenital malformations (OR 1.28, 95% CI 1.09-1.52), especially in case-control studies (OR 2.04, 1.46-2.86). No associations were found between H2RA and congenital malformations. No significant associations were found between PPI use and abortions, stillbirth, neonatal death, preterm birth and low-birth weight, although H2RA use may be associated with an increased risk of preterm birth (OR 1.25, 95% CI 1.02-1.56). Although statistical heterogeneity and the risk of bias were overall low, clinical heterogeneity, information and selection bias may be present in the individual studies. CONCLUSIONS: This meta-analysis suggests an association between maternal PPI use and congenital malformations in humans, yet power was insufficient to assess specific malformations and drugs.


Assuntos
Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Anormalidades Induzidas por Medicamentos/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Anormalidades Congênitas/epidemiologia , Feminino , Azia/tratamento farmacológico , Azia/epidemiologia , Antagonistas dos Receptores Histamínicos H2/efeitos adversos , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Masculino , Gravidez , Nascimento Prematuro/epidemiologia , Fatores de Risco , Natimorto/epidemiologia
16.
Aliment Pharmacol Ther ; 51(5): 534-543, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31990424

RESUMO

BACKGROUND: Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses. AIMS: To evaluate the acid-inhibitory effect of V 10/20 mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20 mg twice-daily (BID; R20/R40) in healthy Japanese volunteers. METHODS: This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7 days and, following a washout period ≥7 days, the other treatment for 7 days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH ≥ 3, ≥4 and ≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24 hours were evaluated as primary pharmacodynamic endpoints. RESULTS: Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P = .0049) and R40 (98.5% vs 85.9%; P = .0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P = .0319) and 5 HTRs (78.8% vs 62.2%; P = .0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related. CONCLUSIONS: Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm).


Assuntos
Antiácidos/administração & dosagem , Ácido Gástrico/metabolismo , Suco Gástrico/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Pirróis/administração & dosagem , Rabeprazol/administração & dosagem , Sulfonamidas/administração & dosagem , Adolescente , Adulto , Antiácidos/efeitos adversos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Suco Gástrico/metabolismo , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Japão , Masculino , Polimorfismo Genético , Inibidores da Bomba de Prótons/efeitos adversos , Pirróis/efeitos adversos , Rabeprazol/efeitos adversos , Sulfonamidas/efeitos adversos , Adulto Jovem
17.
Gut ; 69(2): 224-230, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31409606

RESUMO

OBJECTIVE: To establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO). DESIGN: In this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs). RESULTS: In the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI -3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI -1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI -4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI -5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI -8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI -9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively. CONCLUSION: Our findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms. TRIAL REGISTRATION NUMBER: NCT02388724.


Assuntos
Esofagite Péptica/tratamento farmacológico , Lansoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Lansoprazol/administração & dosagem , Lansoprazol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Índice de Gravidade de Doença , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Cicatrização
18.
Expert Opin Drug Saf ; 19(1): 59-67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31795777

RESUMO

Introduction: The objective of this study was to review the current status of drug-induced hypomagnesemia and its adverse effects on cardiovascular disease (CVD) and hypertension. Since magnesium is a potent vasodilator, which modulates vasomotor tone, peripheral blood flow, and hypertension, its deficiency could have significant cardiovascular and blood pressure (BP) effects.Areas covered: Studies have shown that several factors can contribute to magnesium deficiency including age, diet, disease, and certain drugs such as diuretics and proton-pump inhibitors (PPIs). For an updated perspective of drug-induced hypomagnesemia, a Medline search of the English language literature was conducted between 2010 and 2019 using the terms diuretics, proton-pump inhibitors, hypomagnesemia, cardiovascular disease, hypertension, and 35 pertinent papers were retrieved.Expert opinion: The data showed that magnesium deficiency is difficult to occur since it is plentiful in green leafy vegetables, cereals, nuts, and the drinking water. However, magnesium deficiency can occur with the use of diuretics for the treatment of hypertension and heart failure, or the use of PPIs for the treatment of gastroesophageal reflux disease. Therefore, magnesium deficiency should be detected and treated to prevent the aggravation of hypertension and the onset of CVD and serious cardiac arrhythmias including torsades de points.


Assuntos
Diuréticos/efeitos adversos , Deficiência de Magnésio/induzido quimicamente , Inibidores da Bomba de Prótons/efeitos adversos , Animais , Arritmias Cardíacas/induzido quimicamente , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Diuréticos/administração & dosagem , Humanos , Hipertensão/etiologia , Deficiência de Magnésio/complicações , Deficiência de Magnésio/diagnóstico , Inibidores da Bomba de Prótons/administração & dosagem
19.
Z Rheumatol ; 79(1): 78-82, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-31776649

RESUMO

A 61-year-old male patient had suffered from inflammatory arthralgia since 2014 and had been taking a proton pump inhibitor (PPI) for many years. Additionally, the patient was prescribed apixaban for atrial fibrillation. The blood tests on admission showed a marked hypomagnesemia with secondary hypocalcemia and hypokalemia. After discontinuation of the PPI and through substitution of magnesium, the blood results normalized completely and the patient was finally symptom-free. This case report underlines the important role of magnesium in rheumatology and presents the various mechanisms of action of magnesium.


Assuntos
Artralgia , Fibrilação Atrial , Deficiência de Magnésio , Parestesia , Fibrilação Atrial/tratamento farmacológico , Humanos , Magnésio , Deficiência de Magnésio/complicações , Deficiência de Magnésio/diagnóstico , Deficiência de Magnésio/etiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/efeitos adversos
20.
Drugs Aging ; 37(1): 67-74, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31560115

RESUMO

BACKGROUND: In accordance with current guidelines, proton pump inhibitors (PPIs) are now generally prescribed as a protective co-medication in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose acetylsalicylic acid (LDASA). However, less attention is paid to the corresponding discontinuation of a PPI after cessation of NSAID or LDASA treatment. OBJECTIVE: The aim of this study was to assess the extent of inappropriate PPI use, as the proportion of patients who started a PPI as a protective co-medication but continued using these drugs after cessation of NSAID and LDASA treatment. We also sought to estimate the potential cost savings and effect gains of discontinuing inappropriate PPI use and the resulting decrease in adverse effects and their detrimental consequences. METHODS: Pharmacy dispensing data were used to map inappropriate PPI use in 2014 for community-dwelling patients. Strategies with or without PPI continuation were compared in the cost-utility analysis for a time horizon of 5 years from a healthcare perspective. Subsequently, incremental costs and effects (quality-adjusted life-years) were estimated with a Markov model. RESULTS: Related to NSAID and LDASA treatment, 11.0% and 5%, respectively, of the PPI users were found to inappropriately continue PPI co-treatment. Discontinuation in 71- to 80-year-old patients suggested cost savings of €170.46 (95% confidence interval 75-282) at a 0.003 (95% confidence interval 0.001-0.005) quality-adjusted life-year increase. The total budget impact of stopping inappropriate PPI use related to NSAID/LDASA treatment in the Netherlands would amount to almost €1,050,000 after 1 year. Correspondingly, successful interventions to stop a patient's inappropriate use would cost up to €29 and probably would pay for themselves in the following years. CONCLUSIONS: A substantial number of patients inappropriately continue to use a PPI after cessation of NSAID or LDASA treatment. Because adverse effects and their detrimental consequences are avoided, interventions to stop inappropriate PPI use, particularly in older patients, are likely to pay for themselves.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Humanos , Prescrição Inadequada , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/economia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA