Ruboxistaurin for the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review of Randomized Clinical Trials

Dipika Bansal,Yogesh Badhan,Kapil Gudala,Fabrizio Schifano 대한당뇨병학회 2013 Diabetes and Metabolism Journal Vol.37 No.5

Background: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus. Protein kinase C (PKC) inhibitor’s has been thought to be a potential disease modifying drug’s in DPN as it slows or reverse neuropathy’s progression. To assesses the efficacy and safety of ruboxistaurin on the progression of symptoms, signs, or functional disability in DPN. Methods: A systematic review of the literature databases like PubMed, ProQuest, EBSCO, EMBASE, and Cochrane Central was performed up to August 2012. We included randomized controlled trials (RCTs) comparing PKC inhibitor ruboxistaurin (RBX)with control and lasting at least 6 months. Our primary outcome measure was change in neurological examination, measured by neurological total symptom score (NTSS) and vibration detection threshold (VDT). Secondary outcome measures were total quality of life (QoL), skin microvascular blood flow and others. Results: Six RCTs were included in review. Change in neurological function assessed by NTSS was reported in six studies, out of which significant difference between the RBX and placebo group seen in four studies favouring treatment group while remaining two studies reported no significant difference. VDT was assessed in only one study in which no significant difference seen between RBX and placebo group. Two studies reported significant improvement in QoL data. Safety data was reported in only two studies in which none of side effect was related to RBX. Conclusion: RBX had effects on DPN in some studies, but the evidence is not enough for meta-analysis and firm conclusion. Background: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus. Protein kinase C (PKC) inhibitor’s has been thought to be a potential disease modifying drug’s in DPN as it slows or reverse neuropathy’s progression. To assesses the efficacy and safety of ruboxistaurin on the progression of symptoms, signs, or functional disability in DPN. Methods: A systematic review of the literature databases like PubMed, ProQuest, EBSCO, EMBASE, and Cochrane Central was performed up to August 2012. We included randomized controlled trials (RCTs) comparing PKC inhibitor ruboxistaurin (RBX)with control and lasting at least 6 months. Our primary outcome measure was change in neurological examination, measured by neurological total symptom score (NTSS) and vibration detection threshold (VDT). Secondary outcome measures were total quality of life (QoL), skin microvascular blood flow and others. Results: Six RCTs were included in review. Change in neurological function assessed by NTSS was reported in six studies, out of which significant difference between the RBX and placebo group seen in four studies favouring treatment group while remaining two studies reported no significant difference. VDT was assessed in only one study in which no significant difference seen between RBX and placebo group. Two studies reported significant improvement in QoL data. Safety data was reported in only two studies in which none of side effect was related to RBX. Conclusion: RBX had effects on DPN in some studies, but the evidence is not enough for meta-analysis and firm conclusion.

Agreement between Framingham Risk Score and United Kingdom Prospective Diabetes Study Risk Engine in Identifying High Coronary Heart Disease Risk in North Indian Population

Dipika Bansal,Ramya S. R. Nayakallu1,Kapil Gudala,Rajavikram Vyamasuni,Anil Bhansali 대한당뇨병학회 2015 Diabetes and Metabolism Journal Vol.39 No.4

Background: The aim of the study is to evaluate the concurrence between Framingham Risk score (FRS) and United Kingdom Prospective Diabetes Study (UKPDS) risk engine in identifying coronary heart disease (CHD) risk in newly detected diabetes mellitus patients and to explore the characteristics associated with the discrepancy between them. Methods: A cross-sectional study involving 489 subjects newly diagnosed with type 2 diabetes mellitus was conducted. Agreement between FRS and UKPDS in classifying patients as high risk was calculated using kappa statistic. Subjects with discrepant scores between two algorithms were identified and associated variables were determined. Results: The FRS identified 20.9% subjects (range, 17.5 to 24.7) as high-risk while UKPDS identified 21.75% (range, 18.3 to 25.5) as high-risk. Discrepancy was observed in 17.9% (range, 14.7 to 21.7) subjects. About 9.4% had high risk by UKPDS but not FRS, and 8.6% had high risk by FRS but not UKPDS. The best agreement was observed at high-risk threshold of 20% for both (κ=0.463). Analysis showed that subjects having high risk on FRS but not UKPDS were elderly females having raised systolic and diastolic blood pressure. Patients with high risk on UKPDS but not FRS were males and have high glycosylated hemoglobin. Conclusion: The FRS and UKPDS (threshold 20%) identified different populations as being at high risk, though the agreement between them was fairly good. The concurrence of a number of factors (e.g., male sex, low high density lipoprotein cholesterol, and smoking) in both algorithms should be regarded as increasing the CHD risk. However, longitudinal follow-up is required to form firm conclusions.

Herd Protection by a Bivalent Killed Whole-Cell Oral Cholera Vaccine in the Slums of Kolkata, India

Ali, Mohammad,Sur, Dipika,You, Young Ae,Kanungo, Suman,Sah, Binod,Manna, Byomkesh,Puri, Mahesh,Wierzba, Thomas F.,Donner, Allan,Nair, G. Balakrish,Bhattacharya, Sujit K.,Dhingra, Mandeep Singh,Deen, J Oxford University Press 2013 Clinical infectious diseases Vol.56 No.8

<P>We evaluated the herd protection conferred by the bivalent killed oral cholera vaccine. The vaccine conferred significant herd protection, suggesting that significant public health impact in cholera control may be achieved even with modest vaccination coverage.</P>

Usefulness of four commonly used neuropathic pain screening questionnaires in patients with chronic low back pain: a cross-sectional study

( Kapil Gudala ),( Babita Ghai ),( Dipika Bansal ) 대한통증학회 2017 The Korean Journal of Pain Vol.30 No.1

Background: Recently symptoms-based screening questionnaires have gained attention for screening for a neuropathic pain component (NePC) in various chronic pain conditions. The present study assessed the usefulness of four commonly used NePC screening questionnaires including the Self-completed douleur neuropathique 4 (S-DN4), the ID Pain, the painDETECT questionnaire (PDQ), and the Self-completed Leeds Assessment of neuropathic Symptoms and Signs (S-LANSS) questionnaire in patients with chronic low back pain (CLBP) to assess the presence of NePC. Methods: This is a single-center cross-sectional study where patients with CLBP, with or without leg pain, were included. Participants were initially screened for NePC presence by a physician according to the regular practice, and later assessed using screening questionnaires. The diagnostic accuracy of these questionnaires was compared assuming the physician-made diagnosis as the gold standard. Results: A total of 215 patients with CLBP of which 164 (76.3%, 95% CI, 70.2-81.5) had a NePC were included. S-DN4, ID Pain, and PDQ have an area under the curve (AUC) > 0.8 indicating excellent discrimination. However, S-LANSS has an AUC of 0.69 (0.62-0.75), indicating low discrimination. S-DN4 has a significantly higher AUC as compared to ID Pain (d(AUC) = 0.063, P < 0.01) and S-LANSS (d(AUC) = 0.197, P < 0.01). But the AUC of S-DN4 does not significantly differ from that of PDQ (d(AUC) = 0.013, P = 0.62). Conclusions: S-DN4, ID Pain, and PDQ, but not S-LANSS, have good discriminant validity to screen for NePCs in patients with CLBP. Despite using all the tests, 20-30% of patients with an NePC were missed. Thus, these questionnaires can only be used as an initial clue in screening for NePCs, but do not replace clinical judgment. (Korean J Pain 2017; 30: 51-8)

Hindi version of short form of douleur neuropathique 4 (S-DN4) questionnaire for assessment of neuropathic pain component: a cross-cultural validation study

( Kapil Gudala ),( Babita Ghai ),( Dipika Bansal ) 대한통증학회 2017 The Korean Journal of Pain Vol.30 No.3

Background: Pain with neuropathic characteristics is generally more severe and associated with a lower quality of life compared to nociceptive pain (NcP). Short form of the Douleur Neuropathique en 4 Questions (S-DN4) is one of the most used and reliable screening questionnaires and is reported to have good diagnostic properties. This study was aimed to cross-culturally validate the Hindi version of the S-DN4 in patients with various chronic pain conditions. Methods: The S-DN4 is already translated into the Hindi language by Mapi Research Trust. This study assessed the psychometric properties of the Hindi version of the S-DN4 including internal consistency and test-retest reliability after 3 days` post-baseline assessment. Diagnostic performance was also assessed. Results: One hundred sixty patients with chronic pain, 80 each in the neuropathic pain (NeP) present and NeP absent groups, were recruited. Patients with NeP present reported significantly higher S-DN4 scores in comparison to patients in the NeP absent group (mean (SD), 4.7 (1.7) vs. 1.8 (1.6), P < 0.01). The S-DN4 was found to have an AUC of 0.88 with adequate internal consistency (Cronbach`s α = 0.80) and a test-retest reliability (ICC = 0.92) with an optimal cut-off value of 3 (Youden`s index = 0.66, sensitivity and specificity of 88.7% and 77.5%). The diagnostic concordance rate between clinician diagnosis and the S-DN4 questionnaire was 83.1% (kappa = 0.66). Conclusions: Overall, the Hindi version of the S-DN4 has good internal consistency and test-retest reliability along with good diagnostic accuracy. (Korean J Pain 2017; 30: 197-206)

Maximizing protection from use of oral cholera vaccines in developing country settings: an immunological review of oral cholera vaccines.

Desai, Sachin N,Cravioto, Alejandro,Sur, Dipika,Kanungo, Suman Landes Bioscience 2014 Human Vaccines & Immunotherapeutics Vol.10 No.6

<P>When oral vaccines are administered to children in lower- and middle-income countries, they do not induce the same immune responses as they do in developed countries. Although not completely understood, reasons for this finding include maternal antibody interference, mucosal pathology secondary to infection, malnutrition, enteropathy, and previous exposure to the organism (or related organisms). Young children experience a high burden of cholera infection, which can lead to severe acute dehydrating diarrhea and substantial mortality and morbidity. Oral cholera vaccines show variations in their duration of protection and efficacy between children and adults. Evaluating innate and memory immune response is necessary to understand V. cholerae immunity and to improve current cholera vaccine candidates, especially in young children. Further research on the benefits of supplementary interventions and delivery schedules may also improve immunization strategies.</P>

Functional Roles of Ca _v 1.3(α _1D ) Calcium Channels in Atria : Insights Gained From Gene-Targeted Null Mutant Mice

Zhang, Zhao,He, Yuxia,Tuteja, Dipika,Xu, Danyan,Timofeyev, Valeriy,Zhang, Qian,Glatter, Kathryn A.,Xu, Yanfang,Shin, Hee-Sup,Low, Reginald,Chiamvimonvat, Nipavan Ovid Technologies Wolters Kluwer -American Heart A 2005 CIRCULATION - Vol.112 No.13

<P>Previous data suggest that L-type Ca2+ channels containing the Cav1.3(alpha(1D)) subunit are expressed mainly in neurons and neuroendocrine cells, whereas those containing the Cav1.2(alpha1C) subunit are found in the brain, vascular smooth muscle, and cardiac tissue. However, our previous report as well as others have shown that Cav1.3 Ca2+ channel-deficient mice (Cav1.3(-/-)) demonstrate sinus bradycardia with a prolonged PR interval. In the present study, we extended our study to examine the role of the Cav1.3(alpha1D) Ca2+ channel in the atria of Cav1.3(-/-) mice.</P>

Multiple Stakeholder Perspectives on Cancer Stigma in North India

Gupta, Adyya,Dhillon, Preet K,Govil, Jyotsna,Bumb, Dipika,Dey, Subhojit,Krishnan, Suneeta Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.14

Background: Cancer is a leading cause of death worldwide. A large proportion of cancer deaths are preventable through early detection but there are a range of social, emotional, cultural and financial dimensions that hinder the effectiveness of cancer prevention and treatment efforts. Cancer stigma is one such barrier and is increasingly recognized as an important factor influencing health awareness and promotion, and hence, disease prevention and control. The impact and extent of stigma on the cancer early detection and care continuum is poorly understood in India. Objectives: To evaluate cancer awareness and stigma from multiple stakeholder perspectives in North India, including men and women from the general population, health care professionals and educators, and cancer survivors. Materials and Methods: A qualitative study was conducted with in-depth interviews (IDIs) and focus group discussions (FGDs) among 39 individuals over a period of 3 months in 2014. Three groups of participants were chosen purposively - 1) men and women who attended cancer screening camps held by the Indian Cancer Society, Delhi; 2) health care providers and 3) cancer survivors. Results: Most participants were unaware of what cancers are in general, their causes and ways of prevention. Attitudes of families towards cancer patients were observed to be positive and caring. Nevertheless, stigma and its impact emerged as a cross cutting theme across all groups. Cost of treatment, lack of awarenes and beliefs in alternate medicines were identified as some of the major barriers to seeking care. Conclusions: This study suggests a need for spreading awareness, knowledge about cancers and assessing associated impact among the people. Also Future research is recommended to help eradicate stigma from the society and reduce cancer-related stigma in the Indian context.

Use of oral cholera vaccine as a vaccine probe to define the geographical dimensions of person-to-person transmission of cholera

Ali, Mohammad,Kim, Deok Ryun,Kanungo, Suman,Sur, Dipika,Manna, Byomkesh,Digilio, Laura,Dutta, Shanta,Marks, Florian,Bhattacharya, Sujit K.,Clemens, John Elsevier 2018 INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES Vol.66 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Cholera is known to be transmitted from person to person, and inactivated oral cholera vaccines (OCVs) have been shown to confer herd protection via interruption of this transmission. However, the geographic dimensions of chains of person-to-person transmission of cholera are uncertain. The ability of OCVs to confer herd protection was used to define these dimensions in two cholera-endemic settings, one in rural Bangladesh and the other in urban India.</P> <P><B>Methods</B></P> <P>Two large randomized, placebo-controlled trials of inactivated OCVs, one in rural Matlab, Bangladesh and the other in urban Kolkata, India, were reanalyzed. Vaccine herd protection was evaluated by relating the risk of cholera in placebo recipients to vaccine coverage of surrounding residents residing within concentric rings. In Matlab, concentric rings in 100-m increments up to 700m were evaluated; in Kolkata, 50-m increments up to 350m were evaluated.</P> <P><B>Results</B></P> <P>One hundred and eight cholera cases among 24667 placebo recipients were detected during 1year of post-vaccination follow-up at Matlab; 128 cholera cases among 34968 placebo recipients were detected during 3 years of follow-up in Kolkata. Consistent inverse relationships were observed between vaccine coverage of the ring and the risk of cholera in the central placebo recipient for rings with radii up to 500m in Matlab and up to 150m in Kolkata.</P> <P><B>Conclusions</B></P> <P>These results suggest that the dimensions of chains of person-to-person transmission in endemic settings can be quite large and may differ substantially from setting to setting. Using OCVs as ‘probes’ to define these dimensions can inform geographical targeting strategies for the deployment of these vaccines in endemic settings.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cholera, a waterborne disease, is known to be transmitted from person to person. </LI> <LI> However, the geographical dimensions of this transmission are uncertain. </LI> <LI> Oral cholera vaccines were used as probes to define these dimensions. </LI> <LI> Dimensions were 500m in rural Bangladesh and 150m in Kolkata, India. </LI> <LI> Person-to-person transmission of cholera can be sustained over long distances. </LI> </UL> </P>

Cancer Detection Rates in a Population-Based, Opportunistic Screening Model, New Delhi, India

Shridhar, Krithiga,Dey, Subhojit,Bhan, Chandra Mohan,Bumb, Dipika,Govil, Jyostna,Dhillon, Preet K Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.5

Background: In India, cancer accounts for 7.3% of DALY's, 14.3% of mortality with an age-standardized incident rate of 92.4/100,000 in men and 97.4/100,000 in women and yet there are no nationwide screening programs. Materials and Methods: We calculated age-standardized and age-truncated (30-69 years) detection rates for men and women who attended the Indian Cancer Society detection centre, New Delhi from 2011-12. All participants were registered with socio-demographic, medical, family and risk factors history questionnaires, administered clinical examinations to screen for breast, oral, gynecological and other cancers through a comprehensive physical examination and complete blood count. Patients with an abnormal clinical exam or blood result were referred to collaborating institutes for further investigations and follow-up. Results: A total of n=3503 were screened during 2011-12 (47.8% men, 51.6% women and 0.6% children <15 years) with a mean age of 47.8 yrs (${\pm}15.1yrs$); 80.5% were aged 30-69 years and 77.1% had at least a secondary education. Tobacco use was reported by 15.8%, alcohol consumption by 11.9% and family history of cancer by 9.9% of participants. Follow-up of suspicious cases yielded 45 incident cancers (51.1% in men, 48.9% in women), consisting of 55.5% head and neck (72.0% oral), 28.9% breast, 6.7% gynecological and 8.9% other cancer sites. The age-standardized detection rate for all cancer sites was 340.8/100,000 men and 329.8/100,000 women. Conclusions: Cancer screening centres are an effective means of attracting high-risk persons in low-resource settings. Opportunistic screening is one feasible pathway to address the rising cancer burden in urban India through early detection.