Uso inapropriado de inibidores da bomba de protões num serviço de medicina interna

ResumoIntroduçãoOs inibidores da bomba de protões são os agentes mais eficazes na redução da secreção ácida gástrica, sendo comum a sua utilização na profilaxia da doença ulcerosa.ObjetivosO estudo pretende avaliar a prescrição de inibidores da bomba de protões num serviço de medicina, determinar se o seu uso em profilaxia é apropriado e qual o impacto financeiro associado. Do mesmo modo, no caso do uso justificado, avaliar se a via de administração adotada foi a adequada. Definir posteriormente as orientações institucionais para a utilização destes medicamentos.MétodosFoi realizado um estudo transversal, prospetivo e observacional no serviço de medicina interna de um hospital distrital, num período de 2 meses em 2011. Foram analisados todos os doentes, com idade superior a 18 anos, que iniciaram este medicamento nas primeiras 72 horas de internamento. A subpopulação em que a prescrição foi efetuada de forma profilática foi identificada e o seu uso foi avaliado. As indicações adequadas foram definidas baseando-se em guidelines internacionais do American College of Gastroenterology e do American Journal of Health-System Pharmacy. Aplicou-se simultaneamente o índice de co-morbilidades de Charlson em todos os doentes.ResultadosDos 343 doentes internados no serviço no período em análise, 186 receberam este medicamento profilaticamente, sendo que 74 (39,8%) fizeram uso sem indicação e dos restantes 112, 25 fizeram uso endovenoso inapropriadamente. A maioria dos doentes em que tal medicação foi prescrita sem indicação tinha idade superior ou igual a 70 anos (p<0,001) e a aplicação do índice de Charlson demonstrou que estes doentes não apresentavam maior número de co-morbilidades (índice médio=1,68).O custo da utilização inapropriada deste medicamento no serviço de medicina foi de 483,28 euros neste período. Estima-se que, no ano de 2011, foram gastos inapropriadamente cerca de 3.000 euros, que correspondem a aproximadamente 9% do custo total do hospital com este fármaco.ConclusãoEste estudo mostra que o uso de inibidores da bomba de protões em doentes não críticos é muitas vezes desnecessário e resulta num aumento significativo dos custos. A implementação de normas de orientação clínica é essencial para o uso mais racional dos medicamentos.AbstractIntroductionProton pump inhibitors are the most effective medication for reducing gastric acid secretion, and are commonly utilized for the prophylaxis of ulcerative disease.ObjectiveThis study aims to evaluate the prescription of Proton Pump Inhibitors in an internal medicine department, to determine whether its use in prophylaxis is appropriate and what is the financial impact associated. Similarly, in the case of justified use, to assess whether the administration route adopted was appropriate. Define subsequently institutional guidelines for the use of these drugs.MethodsA cross-sectional, prospective and observational study was conducted in an internal medicine department of a District Hospital in a two-month period in 2011. We performed an analysis of all patients, aged 18 years and older, who started this medication in the first 72hours of admission. We identified the subgroup in which this agent was prescribed for prophylactic reasons and its use was evaluated. The appropriate indications were defined based on international guidelines of the American College of Gastroenterology and the American Journal of Health-System Pharmacy. Simultaneously, the Charlson's Comorbidity Index was applied in all patients.ResultsOf 343 patient admissions during this two-month period, 186 patients received this medication prophylactically, and from this group, 74 (39.8%) did not met the criteria for its use, while from the remaining 112, twenty-five received intravenous form inappropriately. Most patients who initiate this agent without indication aged more than 70 years (p < .001) and the application of Charlson's Comorbidity Index showed that these patients did not have a greater number of comorbidities (mean índex = 1.68).The cost of inappropriate use in this internal medicine department was € 483.28 in this 2-month period, and the estimated cost of unjustified use of Proton Pump Inhibitors in 2011 was approximately € 3000, which represents around 9% of the total cost of the Hospital with this medication.ConclusionThis study demonstrates that the use of Proton Pump Inhibitors in non-critical patients is often unnecessary and results in significant financial impact. Development of clinical guidelines is essential for the rational use of medicines

Novel and Recurrent Copy Number Variants in ABCA4-Associated Retinopathy

ABCA4 is the most frequently mutated gene leading to inherited retinal disease (IRD) with over 2200 pathogenic variants reported to date. Of these, ~1% are copy number variants (CNVs) involving the deletion or duplication of genomic regions, typically &gt;50 nucleotides in length. An in-depth assessment of the current literature based on the public database LOVD, regarding the presence of known CNVs and structural variants in ABCA4, and additional sequencing analysis of ABCA4 using single-molecule Molecular Inversion Probes (smMIPs) for 148 probands highlighted recurrent and novel CNVs associated with ABCA4-associated retinopathies. An analysis of the coverage depth in the sequencing data led to the identification of eleven deletions (six novel and five recurrent), three duplications (one novel and two recurrent) and one complex CNV. Of particular interest was the identification of a complex defect, i.e., a 15.3 kb duplicated segment encompassing exon 31 through intron 41 that was inserted at the junction of a downstream 2.7 kb deletion encompassing intron 44 through intron 47. In addition, we identified a 7.0 kb tandem duplication of intron 1 in three cases. The identification of CNVs in ABCA4 can provide patients and their families with a genetic diagnosis whilst expanding our understanding of the complexity of diseases caused by ABCA4 variants

Mutations in IMPG1 Cause Vitelliform Macular Dystrophies

Vitelliform macular dystrophies (VMD) are inherited retinal dystrophies characterized by yellow, round deposits visible upon fundus examination and encountered in individuals with juvenile Best macular dystrophy (BMD) or adult-onset vitelliform macular dystrophy (AVMD). Although many BMD and some AVMD cases harbor mutations in BEST1 or PRPH2, the underlying genetic cause remains unknown for many affected individuals. In a large family with autosomal-dominant VMD, gene mapping and whole-exome sequencing led to the identification of a c.713T>G (p.Leu238Arg) IMPG1 mutation, which was subsequently found in two other families with autosomal-dominant VMD and the same phenotype. IMPG1 encodes the SPACR protein, a component of the rod and cone photoreceptor extracellular matrix domains. Structural modeling indicates that the p.Leu238Arg substitution destabilizes the conserved SEA1 domain of SPACR. Screening of 144 probands who had various forms of macular dystrophy revealed three other IMPG1 mutations. Two individuals from one family affected by autosomal-recessive VMD were homozygous for the splice-site mutation c.807+1G>T, and two from another family were compound heterozygous for the mutations c.461T>C (p.Leu154Pro) and c.1519C>T (p.Arg507∗). Most cases had a normal or moderately decreased electrooculogram Arden ratio. We conclude that IMPG1 mutations cause both autosomal-dominant and -recessive forms of VMD, thus indicating that impairment of the interphotoreceptor matrix might be a general cause of VMD