Factors affecting compliance to intravitreal anti-vascular endothelial growth factor therapy in Indian patients with retinal vein occlusion,age-related macular degeneration,and diabetic macular edema

Purpose:To evaluate the rate of compliance and the reasons for loss to follow-up in Indian patients with diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) being treated with anti-vascular endothelial growth factor (VEGF) therapy.Methods:This was a retrospective single-center study. Patients with DME, AMD, or RVO were eligible if they initiated anti-VEGF therapy between January 2013 and December 2017. Patients'' data were obtained from hospital electronic records, including the number of injections received, visits, details of follow-up, missed appointments, and reasons for loss to follow-up (>365 days).Results:A total of 648 patients were eligible for the study, of which 334 (51.54%) patients were lost to follow-up. Overall, 343 (64.96%) were males and the overall mean (SD) age was 66.40 (7.44) years. A total of 376 (58.0%) patients had a history of diabetes and 364 (56.2%) patients had a history of hypertension. Further, 127 (38.0), 112 (33.5), and 95 (28.4) had DME, AMD, and RVO, respectively and were lost to follow-up. The most commonly reported reason for loss to follow-up was “non-affordability” (n = 120; 41.1%) followed by “no improvement in vision” (n = 83; 28.4%). “No improvement in vision” (42.2%) and “non-affordability” (37.5%) were higher among patients with DME. No association was found in gender- and treatment-wise distribution of reasons for loss to follow-up.Conclusion:The results showed that around half of the patients with DME, AMD, and RVO were lost to follow-up to intravitreal anti-VEGF therapy, and the most common factors were “non-affordability” and “no improvement in vision.”     

Effects of Exercise Intervention Program on Bone Mineral Accretion in Children and Adolescents with Cystic Fibrosis: A Randomized Controlled Trial

Indian Journal of Pediatrics - To evaluate effect of one year exercise intervention program on bone mineral accrual in children and adolescent with cystic fibrosis (CF). Fifty-two CF children (mean...     

The Constipation Severity Instrument: A Validated Measure

Purpose This study was designed to develop and test the validity and reliability of the Constipation Severity Instrument. Methods Scale development was conducted in two stages: 1) 74 items were generated through a literature review and focus groups of constipated patients and medical providers; and 2) a preliminary instrument was administered to 191 constipated patients and 103 healthy volunteers. Test-retest reliability of the constipated group was assessed (N = 90). Content, convergent, divergent, and discriminant validity were evaluated by using other validated measures by performing one-way analysis of variance and Pearson correlations. Results Exploratory and confirmatory factor analysis revealed three subscales: obstructive defecation, colonic inertia, and pain. Internal consistency (α = 0.88–0.91) and test-retest reliability (intraclass correlation coefficients = 0.84–0.91) were high for all subscales. Constipated patients were grouped by Rome II criteria: functional constipation (22 percent), pelvic floor dyssynergia (15 percent), constipation predominant irritable bowel syndrome (23 percent), and no specific criteria (40 percent). Those with constipation predominant irritable bowel syndrome or pelvic floor dyssynergia scored higher on the Obstructive Defecation and Colonic Inertia subscales than those with functional constipation or no specific criteria (P = 0.001–0.058). Subjects with functional constipation had much lower scores on the pain subscale than constipation predominant irritable bowel syndrome, functional constipation, or no specific criteria (P < 0.009).The Constipation Severity Instrument subscale and total score correlated very highly with the subscales and total score of the Patient Assessment of Constipation Symptom measure. The Constipation Severity Instrument subscales discriminated well between constipated patients and healthy volunteers (P < 0.001) and demonstrated excellent divergent validity. Higher Constipation Severity Instrument scores inversely correlated with general quality of life. Conclusions The Constipation Severity Instrument is a reliable and valid instrument for assessing constipated patients. Administration of the Constipation Severity Instrument to other constipated patients will further validate its use. Supported by the University of California San Francisco Hellman Family Award for Early Career Faculty. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007. Reprints are not available.     

Gab1, SHP2, and protein kinase A are crucial for the activation of the endothelial NO synthase by fluid shear stress

Fluid shear stress enhances NO production in endothelial cells by a mechanism involving the activation of the phosphatidylinositol 3-kinase and the phosphorylation of the endothelial NO synthase (eNOS). We investigated the role of the scaffolding protein Gab1 and the tyrosine phosphatase SHP2 in this signal transduction cascade in cultured and native endothelial cells. Fluid shear stress elicited the phosphorylation and activation of Akt and eNOS as well as the tyrosine phosphorylation of Gab1 and its association with the p85 subunit of phosphatidylinositol 3-kinase and SHP2. Overexpression of a Gab1 mutant lacking the pleckstrin homology domain abrogated the shear stress-induced phosphorylation of Akt but failed to affect the phosphorylation or activity of eNOS. The latter response, however, was sensitive to a protein kinase A (PKA) inhibitor. Mutation of Gab1 Tyr627 to phenylalanine (YF-Gab1) to prevent the binding of SHP2 completely prevented the shear stress-induced phosphorylation of eNOS, leaving the Akt response intact. A dominant-negative SHP2 mutant prevented the activation of PKA and phosphorylation of eNOS without affecting that of Akt. Moreover, shear stress elicited the formation of a signalosome complex including eNOS, Gab1, SHP2 and the catalytic subunit of PKA. In isolated murine carotid arteries, flow-induced vasodilatation was prevented by a PKA inhibitor as well as by overexpression of either the YF-Gab1 or the dominant-negative SHP2 mutant. Thus, the shear stress-induced activation of eNOS depends on Gab1 and SHP2, which, in turn, regulate the phosphorylation and activity of eNOS by a PKA-dependent but Akt-independent mechanism.     

Malnutrition after pancreatic enzyme replacement therapy in chronic pancreatitis: Risk factors in real world practice

BackgroundRCTs that have shown improvement in coefficient of fat absorption with pancreatic enzyme replacement therapy (PERT) have seldom evaluated the impact on overall nutritional status.ObjectiveIn this study we evaluated factors responsible for persistence of malnutrition after PERT.MethodsIn this cross-sectional observational study, patients were enrolled based on predefined enrolment criteria. Patients were divided into those taking PERT regularly (Group A), irregularly (Group B) and not taking (Group C) for at least 3 months. Comprehensive evaluation of anthropometric measurements, nutritional assessment and dietary intake was performed. Malnutrition was measured using the Subjective Global Assessment (SGA) tool. Relationship between PERT status, dietary intake and nutritional status were evaluated using standard statistical methods. Logistic regression was performed to identify factors associated with persistence of malnutrition after PERT.Results377 patients with CP and 50 controls were included. 95 (25.2%) patients with CP were in Group A, 106 (28.1%) in Group B and 176 (46.7%) in Group C. 130 (34.5%) patients were malnourished, of which 76 (58.5%) were continuing PERT. There were no differences in clinical and biochemical nutritional markers between Groups A, B, and C. Calorie deficit and daily intake of calorie, protein, carbohydrates and fats were not different between those with and without PERT, but was significantly less in those with malnutrition. Logistic regression demonstrated inadequate dietary intake as independent risk factor for persistence of malnutrition.ConclusionEven though PERT is effective in PEI, comprehensive nutritional assessment, personalized nutritional counselling and therapy along with PERT is mandatory.     

Imatinib-Induced Hypogammaglobulinemia in Children and Adolescents with Chronic Myeloid Leukemia

Abstract

Imatinib-induced tyrosine kinase inhibition extends beyond the BCR-ABL mutation, resulting in adverse effects. We evaluated hypogammaglobulinemia as a potential ‘off-target’ action of imatinib in children with CML. A cross-sectional, observational study was performed. Patients with CML in chronic phase, age <18-years at diagnosis, receiving imatinib for a duration exceeding 6-months were enrolled. Serum immunoglobulin G, A, and M were measured by end-point nephelometry. Thirty patients were enrolled. The mean age at diagnosis was 10.4?±?3.1?years (range: 5-18). The mean age at enrollment was 16.4?±?4.1?years (range: 9-23). The median dose of imatinib was 287.5?mg/m² (IQR: 267.3, 345.0). The median duration of imatinib-therapy was 6-years (IQR: 3.0, 10.3). The median (IQR) normalized levels of IgG, IgA, and IgM were 33.0% (IQR: ?12.8, 58.7), 28.1% (IQR: ?17.0, 90.1) and 15.9% (IQR: ?9.3, 40.5), respectively. The IgG, IgA, and IgM levels were reduced in 9 (30%), 8 (27%), and 10 (33%) patients, respectively. Five (17%) patients had pan-hypogammaglobulinemia. We suggest checking immunoglobulin levels in patients with CML receiving imatinib with recurrent/unusual infections.