Diagnostic odyssey of patients with mitochondrial disease: Results of a survey.

Neurol Genet. 2018 Apr;4(2):e230

Authors: Grier J, Hirano M, Karaa A, Shepard E, Thompson JLP

Abstract
Objective: To document the complex "diagnostic odyssey" of patients with mitochondrial disease.
Methods: We analyzed data from 210 Rare Diseases Clinical Research Network Contact Registry participants who were patients with a biochemical deficiency or self-reported diagnosis of mitochondrial disease, or their caregivers.
Results: Participants saw an average of 8.19 clinicians (SD 8.0, median 5). The first clinician consulted about symptoms was typically a primary care physician (56.7%), although 35.2% of participants initially sought a specialist. Of note, 55.2% of participants received their diagnosis from a neurologist, 18.2% from a clinical geneticist, and 11.8% from a metabolic disease specialist. A majority of the participants (54.6%) received 1 or more nonmitochondrial diagnoses before their final mitochondrial diagnosis. In their pursuit of a diagnosis, 84.8% of participants received blood tests, 71% a muscle biopsy, 60.5% MRI, and 38.6% urine organic acids. In addition, 39.5% of the participants underwent mitochondrial DNA sequencing, 19% sequencing of nuclear gene(s), and 11.4% whole-exome sequencing.
Conclusions: The diagnostic odyssey of patients with mitochondrial disease is complex and burdensome. It features multiple consultations and tests, and, often, conflicting diagnoses. These reflect disease variety, diagnostic uncertainty, and clinician unfamiliarity. The current survey provides an important benchmark. Its replication at appropriate intervals will assist in tracking changes that may accompany increased popularity of exome testing, more rigorous diagnostic criteria, increased patient reported outcome activity, and trials for promising therapies.

PMID: 29600276 [PubMed]

Myopathy With SQSTM1 and TIA1 Variants: Clinical and Pathological Features.

Front Neurol. 2018;9:147

Authors: Niu Z, Pontifex CS, Berini S, Hamilton LE, Naddaf E, Wieben E, Aleff RA, Martens K, Gruber A, Engel AG, Pfeffer G, Milone M

Abstract
Objective: The aim of this study is to identify the molecular defect of three unrelated individuals with late-onset predominant distal myopathy; to describe the spectrum of phenotype resulting from the contributing role of two variants in genes located on two different chromosomes; and to highlight the underappreciated complex forms of genetic myopathies.
Patients and methods: Clinical and laboratory data of three unrelated probands with predominantly distal weakness manifesting in the sixth-seventh decade of life, and available affected and unaffected family members were reviewed. Next-generation sequencing panel, whole exome sequencing, and targeted analyses of family members were performed to elucidate the genetic etiology of the myopathy.
Results: Genetic analyses detected two contributing variants located on different chromosomes in three unrelated probands: a heterozygous pathogenic mutation in SQSTM1 (c.1175C>T, p.Pro392Leu) and a heterozygous variant in TIA1 (c.1070A>G, p.Asn357Ser). The affected fraternal twin of one proband also carries both variants, while the unaffected family members harbor one or none. Two unrelated probands (family 1, II.3, and family 3, II.1) have a distal myopathy with rimmed vacuoles that manifested with index extensor weakness; the other proband (family 2, I.1) has myofibrillar myopathy manifesting with hypercapnic respiratory insufficiency and distal weakness.
Conclusion: The findings indicate that all the affected individuals have a myopathy associated with both variants in SQSTM1 and TIA1, respectively, suggesting that the two variants determine the phenotype and likely functionally interact. We speculate that the TIA1 variant is a modifier of the SQSTM1 mutation. We identify the combination of SQSTM1 and TIA1 variants as a novel genetic defect associated with myofibrillar myopathy and suggest to consider sequencing both genes in the molecular investigation of myopathy with rimmed vacuoles and myofibrillar myopathy although additional studies are needed to investigate the digenic nature of the disease.

PMID: 29599744 [PubMed]

Chitayat-Hall and Schaaf-Yang syndromes: a common aetiology: expanding the phenotype of MAGEL2-related disorders.

J Med Genet. 2018 Mar 29;:

Authors: Jobling R, Stavropoulos DJ, Marshall CR, Cytrynbaum C, Axford MM, Londero V, Moalem S, Orr J, Rossignol F, Lopes FD, Gauthier J, Alos N, Rupps R, McKinnon M, Adam S, Nowaczyk MJM, Walker S, Scherer SW, Nassif C, Hamdan FF, Deal CL, Soucy JF, Weksberg R, Macleod P, Michaud JL, Chitayat D

Abstract
BACKGROUND: Chitayat-Hall syndrome, initially described in 1990, is a rare condition characterised by distal arthrogryposis, intellectual disability, dysmorphic features and hypopituitarism, in particular growth hormone deficiency. The genetic aetiology has not been identified.
METHODS AND RESULTS: We identified three unrelated families with a total of six affected patients with the clinical manifestations of Chitayat-Hall syndrome. Through whole exome or whole genome sequencing, pathogenic variants in the MAGEL2 gene were identified in all affected patients. All disease-causing sequence variants detected are predicted to result in a truncated protein, including one complex variant that comprised a deletion and inversion.
CONCLUSIONS: Chitayat-Hall syndrome is caused by pathogenic variants in MAGEL2 and shares a common aetiology with the recently described Schaaf-Yang syndrome. The phenotype of MAGEL2-related disorders is expanded to include growth hormone deficiency as an important and treatable complication.

PMID: 29599419 [PubMed - as supplied by publisher]

Effects of exercise on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: A systematic review.

Crit Rev Oncol Hematol. 2018 Jan;121:90-100

Authors: Duregon F, Vendramin B, Bullo V, Gobbo S, Cugusi L, Di Blasio A, Neunhaeuserer D, Zaccaria M, Bergamin M, Ermolao A

Abstract
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological and clinically relevant side effect of many commonly used chemotherapeutic agents. Moreover, little effort has been done to investigate the potentially beneficial effects of specific exercises to counteract the CIPN symptoms.
OBJECTIVE: This document aims to summarize and analyze systematically the current body of evidence about the effects of specific exercise protocols on CIPN symptoms, balance control, physical function and quality of life in patients with CIPN.
LITERATURE SURVEY: Specific terms were identified for the literature research in MEDLINE, Scopus, Bandolier, PEDro, and Web of Science.
METHODOLOGY: Five manuscripts were considered eligible for this review. Quality appraisal distinguished two studies as high quality investigations while three with low quality. Results were summarized in the following domains: "CIPN symptoms", "Static balance control", "Dynamic balance control", "Quality of life and Physical function".
SYNTHESIS: Significant improvements were detected on postural control. Additionally, patients' quality of life and independence were found ameliorated after exercise sessions. Combined exercise protocols including endurance, strength and sensorimotor training showed larger improvements.
CONCLUSIONS: This systematic review comes from a highly selected but small source of data. Nevertheless, specific exercise for cancer patients undergoing chemotherapy with CIPN symptoms should be recommended since these interventions appeared as feasible and have been demonstrated as useful tools to counteract some of the limitations due to chemotherapy.

PMID: 29198853 [PubMed - indexed for MEDLINE]

Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson's disease.

Mov Disord. 2017 Jun;32(6):893-903

Authors: Fox SH, Metman LV, Nutt JG, Brodsky M, Factor SA, Lang AE, Pope LE, Knowles N, Siffert J

Abstract
BACKGROUND: Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia.
METHODS: PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout. After 14 days, a 2-hour intravenous levodopa-infusion was administered. Patient examinations were videotaped before infusion ("off" state) and every 30 minutes during and afterwards until patients returned to "off." The primary endpoint was dyskinesia-severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area-under-curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical-change, and adverse-events.
RESULTS: A total of 13 patients were randomized and completed the study (efficacy-evaluable population). Dyskinesia-severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area-under-curve 966.5 vs 1048.8; P = .191 [efficacy-evaluable patients]), and significantly lower in a post-hoc sensitivity analysis of the per-protocol-population (efficacy-evaluable patients with ≥ 80% study-drug-compliance, n = 12) when measured from infusion start to 4-hours post-infusion completion (area-under-curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion-start to return to "off" (13.3 vs 14.9; P = .018 [efficacy-evaluable patients]). A total of 9 patients rated dyskinesia "much/very much improved" on dextromethorphan/quinidine versus 1-patient on placebo. Dextromethorphan/quinidine did not worsen PD-motor scores, was generally well tolerated, and was associated with more frequent adverse events.
CONCLUSION: This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa-induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society.

PMID: 28370447 [PubMed - indexed for MEDLINE]

6 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Rare Diseases"[Mesh] OR "orphan disease"

These pubmed results were generated on 2018/03/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/03/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/03/30

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Prediction of Human Drug Targets and Their Interactions Using Machine Learning Methods: Current and Future Perspectives.

Methods Mol Biol. 2018;1762:21-30

Authors: Nath A, Kumari P, Chaube R

Abstract
Identification of drug targets and drug target interactions are important steps in the drug-discovery pipeline. Successful computational prediction methods can reduce the cost and time demanded by the experimental methods. Knowledge of putative drug targets and their interactions can be very useful for drug repurposing. Supervised machine learning methods have been very useful in drug target prediction and in prediction of drug target interactions. Here, we describe the details for developing prediction models using supervised learning techniques for human drug target prediction and their interactions.

PMID: 29594765 [PubMed - in process]

Identification of KX2-391 as an inhibitor of HBV transcription by a recombinant HBV-based screening assay.

Antiviral Res. 2017 Aug;144:138-146

Authors: Harada K, Nishitsuji H, Ujino S, Shimotohno K

Abstract
Antiviral therapies for chronic hepatitis B virus (HBV) infection that are currently applicable for clinical use are limited to nucleos(t)ide analogs targeting HBV polymerase activity and pegylated interferon alpha (PEG-IFN). Towards establishing an effective therapy for HBV related diseases, it is important to develop a new anti-HBV agent that suppresses and eradicates HBV. This study used recombinant HBV encoding NanoLuc to screen anti-HBV compounds from 1827 US Food and Drug Administration approved compounds and identified several compounds that suppressed HBV infection. Among them, KX2-391, a non-ATP-competitive inhibitor of SRC kinase and tubulin polymerization, was identified as a lead candidate for an anti-HBV drug. Treatment of sodium taurocholate cotransporting polypeptide (NTCP) transduced-HepG2 (HepG2-NTCP) or primary human hepatocytes with KX2-391 suppressed HBV replication in a dose-dependent manner. The anti-HBV activity of KX2-391 appeared not to depend on SRC kinase activity because siRNA for SRC mRNA did not impair the HBV infection/replication. The anti-HBV activity of KX2-391 depended on the inhibitory effect of tubulin polymerization similar to other tubulin polymerization inhibitors, some of which were shown to inhibit HBV replication. KX2-391 inhibited HBV transcription driven by a HBV precore promoter in an HBV X protein-independent manner but did not inhibit the activity of HBV-S1, -S2, -X or cytomegalovirus promoters. Treatment with KX2-391 reduced the expression of several various factors including hepatocyte nuclear factor-4a.

PMID: 28624460 [PubMed - indexed for MEDLINE]

Early Detection of Rapid Cystic Fibrosis Disease Progression Tailored to Point of Care: A Proof-of-Principle Study.

Health Innov Point Care Conf. 2017 Nov;2017:204-207

Authors: Szczesniak R, Brokamp C, Su W, McPhail GL, Pestian J, Clancy JP

Abstract
Slowing cystic fibrosis (CF) lung disease progression is crucial to survival, but point-of-care technologies aimed at early detection-and possibly prevention-of rapid lung function decline are limited. This proof-of-principle study leverages a rich national patient registry and follow-up data on a local CF cohort to build an algorithm and prototype prognostic tool aimed at early detection of rapid lung function decline. The algorithm was developed using a novel longitudinal analysis of lung function (measured as forced expiratory volume in 1 s of % predicted, FEV1). Covariates included clinical and demographic characteristics selected from the registry based on information criterion. Preliminary assessment of algorithm performance suggested excellent predictive accuracy and earlier detection of rapid decline than standard of care being applied at a local center. Graphical displays were presented and evaluated for clinical utility. Predictions from the algorithms and chosen graphical displays were translated into a prototype web application using RShiny and underwent iterative development based on clinician feedback. This paper suggests that the algorithm and its translation could offer a means for earlier detection and treatment of rapid decline, providing clinicians with a viable point-of-care technology to intervene prior to irreversible lung damage.

PMID: 29594261 [PubMed]

Joint hierarchical Gaussian process model with application to personalized prediction in medical monitoring.

Stat (Int Stat Inst). 2018;7(1):

Authors: Duan LL, Wang X, Clancy JP, Szczesniak RD

Abstract
A two-level Gaussian process (GP) joint model is proposed to improve personalized prediction of medical monitoring data. The proposed model is applied to jointly analyze multiple longitudinal biomedical outcomes, including continuous measurements and binary outcomes, to achieve better prediction in disease progression. At the population level of the hierarchy, two independent GPs are used to capture the nonlinear trends in both the continuous biomedical marker and the binary outcome, respectively; at the individual level, a third GP, which is shared by the longitudinal measurement model and the longitudinal binary model, induces the correlation between these two model components and strengthens information borrowing across individuals. The proposed model is particularly advantageous in personalized prediction. It is applied to the motivating clinical data on cystic fibrosis disease progression, for which lung function measurements and onset of acute respiratory events are monitored jointly throughout each patient's clinical course. The results from both the simulation studies and the cystic fibrosis data application suggest that the inclusion of the shared individual-level GPs under the joint model framework leads to important improvements in personalized disease progression prediction.

PMID: 29593867 [PubMed]

Hypertonic Saline Suppresses NADPH Oxidase-Dependent Neutrophil Extracellular Trap Formation and Promotes Apoptosis.

Front Immunol. 2018;9:359

Authors: Nadesalingam A, Chen JHK, Farahvash A, Khan MA

Abstract
Tonicity of saline (NaCl) is important in regulating cellular functions and homeostasis. Hypertonic saline is administered to treat many inflammatory diseases, including cystic fibrosis. Excess neutrophil extracellular trap (NET) formation, or NETosis, is associated with many pathological conditions including chronic inflammation. Despite the known therapeutic benefits of hypertonic saline, its underlying mechanisms are not clearly understood. Therefore, we aimed to elucidate the effects of hypertonic saline in modulating NETosis. For this purpose, we purified human neutrophils and induced NETosis using agonists such as diacylglycerol mimetic phorbol myristate acetate (PMA), Gram-negative bacterial cell wall component lipopolysaccharide (LPS), calcium ionophores (A23187 and ionomycin from Streptomyces conglobatus), and bacteria (Pseudomonas aeruginosa and Staphylococcus aureus). We then analyzed neutrophils and NETs using Sytox green assay, immunostaining of NET components and apoptosis markers, confocal microscopy, and pH sensing reagents. This study found that hypertonic NaCl suppresses nicotinamide adenine dinucleotide phosphate oxidase (NADPH2 or NOX2)-dependent NETosis induced by agonists PMA, Escherichia coli LPS (0111:B4 and O128:B12), and P. aeruginosa. Hypertonic saline also suppresses LPS- and PMA- induced reactive oxygen species production. It was determined that supplementing H2O2 reverses the suppressive effect of hypertonic saline on NOX2-dependent NETosis. Many of the aforementioned suppressive effects were observed in the presence of equimolar concentrations of choline chloride and osmolytes (d-mannitol and d-sorbitol). This suggests that the mechanism by which hypertonic saline suppresses NOX2-dependent NETosis is via neutrophil dehydration. Hypertonic NaCl does not significantly alter the intracellular pH of neutrophils. We found that hypertonic NaCl induces apoptosis while suppressing NOX2-dependent NETosis. In contrast, hypertonic solutions do not suppress NOX2-independent NETosis. Although hypertonic saline partially suppresses ionomycin-induced NETosis, it enhances A23187-induced NETosis, and it does not alter S. aureus-induced NETosis. Overall, this study determined that hypertonic saline suppresses NOX2-dependent NETosis induced by several agonists; in contrast, it has variable effects on neutrophil death induced by NOX2-independent NETosis agonists. These findings are important in understanding the regulation of NETosis and apoptosis in neutrophils.

PMID: 29593709 [PubMed]

Novel Nonsense Mutation in SLC39A13 Initially Presenting as Myopathy: Case Report and Review of the Literature.

Mol Syndromol. 2018 Feb;9(2):100-109

Authors: Dusanic M, Dekomien G, Lücke T, Vorgerd M, Weis J, Epplen JT, Köhler C, Hoffjan S

Abstract
Myopathies comprise a heterogeneous group of disorders characterized by variable phenotypes. The increasing use of next-generation sequencing allows identification of the causative genes in a much higher percentage of patients with hereditary muscle disorders and also illustrates a considerable degree of overlap with other clinical entities, including connective tissue disorders. Here, we present a 14-year-old German patient who was initially suspected to suffer from myopathy based on his clinical, radiological, and muscle biopsy findings. Exome sequencing revealed a novel homozygous nonsense mutation in the SLC39A13 gene, causative for spondylocheiro dysplastic Ehlers Danlos syndrome (SCD-EDS), suggesting a connective tissue disorder. Including our patient, only 9 affected individuals from 4 families have been described for SCD-EDS so far. The previously reported patients did not show obvious evidence of myopathy, suggesting a broader clinical presentation than originally suspected. We summarize herein the current knowledge on clinical features as well as pathophysiological pathways for this rare connective tissue disease and discuss the high degree of clinical overlap between myopathic and connective tissue disorders.

PMID: 29593477 [PubMed]

Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity.

Cancer Discov. 2017 07;7(7):750-765

Authors: Patnaik A, Swanson KD, Csizmadia E, Solanki A, Landon-Brace N, Gehring MP, Helenius K, Olson BM, Pyzer AR, Wang LC, Elemento O, Novak J, Thornley TB, Asara JM, Montaser L, Timmons JJ, Morgan TM, Wang Y, Levantini E, Clohessy JG, Kelly K, Pandolfi PP, Rosenblatt JM, Avigan DE, Ye H, Karp JM, Signoretti S, Balk SP, Cantley LC

Abstract
Several kinase inhibitors that target aberrant signaling pathways in tumor cells have been deployed in cancer therapy. However, their impact on the tumor immune microenvironment remains poorly understood. The tyrosine kinase inhibitor cabozantinib showed striking responses in cancer clinical trial patients across several malignancies. Here, we show that cabozantinib rapidly eradicates invasive, poorly differentiated PTEN/p53-deficient murine prostate cancer. This was associated with enhanced release of neutrophil chemotactic factors from tumor cells, including CXCL12 and HMGB1, resulting in robust infiltration of neutrophils into the tumor. Critically, cabozantinib-induced tumor clearance in mice was abolished by antibody-mediated granulocyte depletion or HMGB1 neutralization or blockade of neutrophil chemotaxis with the CXCR4 inhibitor plerixafor. Collectively, these data demonstrate that cabozantinib triggers a neutrophil-mediated anticancer innate immune response, resulting in tumor clearance.Significance: This study is the first to demonstrate that a tyrosine kinase inhibitor can activate neutrophil-mediated antitumor innate immunity, resulting in invasive cancer clearance. Cancer Discov; 7(7); 750-65. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 653.

PMID: 28274958 [PubMed - indexed for MEDLINE]

Treatment of familial Mediterranean fever with anakinra in patients unresponsive to colchicine.

Scand J Rheumatol. 2017 09;46(5):407-409

Authors: Pecher AC, Igney-Oertel A, Kanz L, Henes J

PMID: 28097903 [PubMed - indexed for MEDLINE]

Did Frédéric Chopin Die From Heart Failure?

J Card Fail. 2018 Mar 26;:

Authors: Perciaccante A, Charlier P, Negri C, Coralli A, Appenzeller O, Bianucci R

Abstract
On October 17, 1849, Poland's greatest composer, Frédéric Chopin (1810-1849) died aged 39. His cause of death remains unknown. An investigation of the documental sources was performed to reconstrcuct the medical history of the artist. Since his earliest years, his life had been dominated by poor health. Recurrent episodes of cough, fever, headaches, lymphadenopathy- a series of symptoms that may be attributed to viral respiratory infections- manifested in his teens. Later in life, he had chest pain, hemoptysis, hematemesis, neuralgia, and arthralgia. Exhaustion and breathlessness characterized all his adult life. Coughing, choking, and edema of the legs and ankles manifested four months before his death. Several hypotheses ranging from cystic fibrosis to alpha-1 anti-trypsin deficiency and pulmonary tuberculosis have been proposed to explain Chopin's lifelong illness. We suggest that Chopin had dilated cardiomyopathy with consequent heart failure and cirrhosis that caused his death.

PMID: 29597050 [PubMed - as supplied by publisher]

Influenza virus: 16 years' experience of clinical epidemiologic patterns and associated infection factors in hospitalized children in Argentina.

PLoS One. 2018;13(3):e0195135

Authors: Gentile A, Lucion MF, Del Valle Juarez M, Martinez AC, Romanin V, Bakir J, Viegas M, Mistchenko A

Abstract
BACKGROUND: Influenza is an important cause of acute lower respiratory tract infection (aLRTI), hospitalization, and mortality in children. This study aimed to describe the clinical and epidemiologic patterns and infection factors associated with influenza, and compare case features of influenza A and B.
METHODS: In a prospective, cross-sectional study, patients admitted for aLRTI, between 2000 and 2015, were tested for respiratory syncytial virus, adenovirus, influenza, or parainfluenza, and confirmed by fluorescent antibody (FA) or real-time polymerase chain reaction (RT-PCR) assay of nasopharyngeal aspirates.
RESULTS: Of 14,044 patients, 37.7% (5290) had FA- or RT-PCR-confirmed samples that identified influenza in 2.8% (394/14,044; 91.4% [360] influenza A, 8.6% [34] influenza B) of cases. Influenza frequency followed a seasonal epidemic pattern (May-July, the lowest average temperature months). The median age of cases was 12 months (interquartile range: 6-21 months); 56.1% (221/394) of cases were male. Consolidated pneumonia was the most frequent clinical presentation (56.9%; 224/394). Roughly half (49.7%; 196/394) of all cases had previous respiratory admissions; 9.4% (37/394) were re-admissions; 61.5% (241/392) had comorbidities; 26.2% (102/389) had complications; 7.8% (30/384) had nosocomial infections. The average case fatality rate was 2.1% (8/389). Chronic neurologic disease was significantly higher in influenza B cases compared to influenza A cases (p = 0.030). The independent predictors for influenza were: age ≥6 months, odds ratio (OR): 1.88 (95% confidence interval [CI]: 1.44-2.45); p<0.001; presence of chronic neurologic disease, OR: 1.48 (95% CI: 1.01-2.17); p = 0.041; previous respiratory admissions, OR: 1.71 (95% CI: 1.36-2.14); p<0.001; re-admissions, OR: 1.71 (95% CI: 1.17-2.51); p = 0.006; clinical pneumonia, OR: 1.50 (95% CI: 1.21-1.87); p<0.001; immunodeficiency, OR: 1.87 (95% CI: 1.15-3.05); p = 0.011; cystic fibrosis, OR: 4.42 (95% CI: 1.29-15.14); p = 0.018.
CONCLUSION: Influenza showed an epidemic seasonal pattern (May-July), with higher risk in children ≥6 months, or with pneumonia, previous respiratory admissions, or certain comorbidities.

PMID: 29596527 [PubMed - in process]