Biomechanisms of Comorbidity: Reviewing Integrative Analyses of Multi-omics Datasets and Electronic Health Records.

OBJECTIVES: Disease comorbidity is a pervasive phenomenon impacting patients' health outcomes, disease management, and clinical decisions. This review presents past, current and future research directions leveraging both phenotypic and molecular information to uncover disease similarity underpinning the biology and etiology of disease comorbidity. METHODS: We retrieved ~130 publications and retained 59, ranging from 2006 to 2015, that comprise a minimum number of five diseases and at least one type of biomolecule. We surveyed their methods, disease similarity metrics, and calculation of comorbidities in the electronic health records, if present. RESULTS: Among the surveyed studies, 44% generated or validated disease similarity metrics in context of comorbidity, with 60% being published in the last two years. As inputs, 87% of studies utilized intragenic loci and proteins while 13% employed RNA (mRNA, LncRNA or miRNA). Network modeling was predominantly used (35%) followed by statistics (28%) to impute similarity between these biomolecules and diseases. Studies with large numbers of biomolecules and diseases used network models or naïve overlap of disease-molecule associations, while machine learning, statistics, and information retrieval were utilized in smaller and moderate sized studies. Multiscale computations comprising shared function, network topology, and phenotypes were performed exclusively on proteins. CONCLUSION: This review highlighted the growing methods for identifying the molecular mechanisms underpinning comorbidities that leverage multiscale molecular information and patterns from electronic health records. The survey unveiled that intergenic polymorphisms have been overlooked for similarity imputation compared to their intragenic counterparts, offering new opportunities to bridge the mechanistic and similarity gaps of comorbidity.

Adverse reactions of prophylactic intravenous immunoglobulin; a 13-year experience with 3004 infusions in Iranian patients with primary immunodeficiency diseases.

Intravenous immunoglobulin (IVIG) replacement therapy improves health-related quality of life in patients with a primary immunodeficiency disease, although there have been reports of adverse reactions associated with its regular administration. The study population was composed of 99 patients with primary antibody deficiencies. All the patients were diagnosed with a primary immunodeficiency disease and received at least 4 infusions of IVIG at the Children's Medical Center Hospital, Tehran, Iran over a 13-year period (1995-2007). A total of 3004 infusions were recorded, and 216 (7.2%) of these were associated with adverse reactions in 66 patients. Adverse reactions were classified as mild (172 reactions), moderate (41 reactions), and severe (3 reactions). The rate of adverse reaction varied by diagnosis from 3.35% in patients with X-linked agammaglobulinemia to 17.4% in IgG subclass deficiency. There were no age-related differences in the rates of adverse reactions. Adverse reactions to IVIG infusions are occasionally encountered; therefore, physicians and nurses should be aware of these reactions in order to manage and prevent them.

ENT manifestations in Iranian patients with primary antibody deficiencies.

OBJECTIVE: One hundred and nine patients with primary antibody deficiencies were selected in order to determine the frequency of ENT complications. METHOD: Demographic information and ENT medical histories were collected for each patient. Duration of study for each patient was divided into two periods of before diagnosis and after diagnosis and the initiation of treatment. RESULTS: Eighty-two of 109 patients (75.2 per cent) experienced ENT infections during the course of the disease (63: otitis media, 75: sinusitis and nine: mastoiditis). At the time of diagnosis, 52 (47.7 per cent) out of 109 patients presented with an ENT symptom. The frequencies of episodes were 27 for sinusitis and 25 for otitis media (one complicated with mastoiditis). After immunoglobulin replacement therapy the incidence of otitis media was reduced from 1.75 before treatment to 0.39 after treatment per patient per year (p = 0.008). The incidence of sinusitis also significantly decreased from 2.38 to 0.78 (p value = 0.011). CONCLUSION: ENT infections are common medical problems in primary antibody deficiency patients. Persistent and recurrent ENT infections should be suspected as originating from a possible underlying immunodeficiency.