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author:("S, raji")
1.  Rate, delay and predictors of hepatitis C treatment in British Columbia 
The increased rate of hepatitis C-related morbidity and mortality in the late 1990s and early 2000s, coupled with low treatment uptake rates, prompted the search for and development of newer, more efficacious treatments and management strategies. The emergence of direct-acting antiviral agents has resulted in impressive sustained virological response rates in treatment-naive patients. Despite the success of protease inhibitors, such as boceprevir and teleprevir, treatment rates remain suboptimal. This retrospective analysis examined uptake, barriers and wait times concerning current hepatitis C treatment in British Columbia.
The current treatment rate for chronic hepatitis C virus (HCV) infection is suboptimal despite the availability of efficacious antiviral therapy.
To determine the rate, delay and predictors of treatment in patients with chronic HCV infection.
A retrospective chart review of chronic HCV patients who were being evaluated at a tertiary hepatology centre in Vancouver, British Columbia, was performed.
One hundred sixty-four patients with chronic HCV infection who were assessed for treatment between February 2008 and January 2013 were reviewed. Treatment was initiated in 25.6% (42 of 164). In multivariate analyses, male sex (OR 7.90 [95% CI 1.35 to 46.15]) and elevated alanine aminotransferase (ALT) level (>1.5 times the upper limit of normal) (OR 3.10 [95% CI 1.32 to 7.27]) were positive predictors of treatment, whereas active smoking (OR 0.09 [95% CI 0.02 to 0.53]) and Charlson comorbidity index (per point increase) (OR 0.47 [95% CI 0.27 to 0.83]) were negative predictors of treatment. The most common reasons for treatment deferral were no or minimal liver fibrosis in 57.7% (n=30), persistently normal ALT levels in 57.7% (n=30) and patient unreadiness in 28.8% (n=15). The most common reasons for treatment noninitiation were patient refusal in 59.1% (n=26), medical comorbidities in 36.4% (n=16), psychiatric comorbidities in 9.1% (n=4) and decompensated cirrhosis in 9.1% (n=4). There was a statistically significant difference in the median time delay from HCV diagnosis to general practitioner referral between the treated and untreated patients (66.3 versus 119.5 months, respectively [P=0.033]). The median wait time from general practitioner referral to hepatologist consult was similar between the treated and untreated patients (1.7 months versus 1.5 months, respectively [P=0.768]). Among the treated patients, the median time delay was 6.8 months from hepatologist consult to treatment initiation.
The current treatment rate for chronic HCV infection remains suboptimal. Medical and psychiatric comorbidities represent a major obstacle to HCV treatment. Minimal hepatic fibrosis may no longer be a major reason for treatment deferral as more efficacious and tolerable antiviral therapies become available in the future. Greater educational initiatives for primary care physicians would promote early referral of patients. More nursing support would alleviate the backlog of patients awaiting treatment.
PMCID: PMC4578455  PMID: 25874651
Boceprevir; Direct-acting antiviral agent; Hepatitis C; Telaprevir; Treatment
2.  Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets 
Cytokine & Growth Factor Reviews  2015;26(6):673-685.
Atherosclerosis, a chronic inflammatory disorder of the arteries, is responsible for most deaths in westernized societies with numbers increasing at a marked rate in developing countries. The disease is initiated by the activation of the endothelium by various risk factors leading to chemokine-mediated recruitment of immune cells. The uptake of modified lipoproteins by macrophages along with defective cholesterol efflux gives rise to foam cells associated with the fatty streak in the early phase of the disease. As the disease progresses, complex fibrotic plaques are produced as a result of lysis of foam cells, migration and proliferation of vascular smooth muscle cells and continued inflammatory response. Such plaques are stabilized by the extracellular matrix produced by smooth muscle cells and destabilized by matrix metalloproteinase from macrophages. Rupture of unstable plaques and subsequent thrombosis leads to clinical complications such as myocardial infarction. Cytokines are involved in all stages of atherosclerosis and have a profound influence on the pathogenesis of this disease. This review will describe our current understanding of the roles of different cytokines in atherosclerosis together with therapeutic approaches aimed at manipulating their actions.
PMCID: PMC4671520  PMID: 26005197
Atherosclerosis; Cytokines; Chemokines; Inflammation; Therapeutic avenues; ABC, ATP-binding cassette; ACAT-1, acyl-CoA acyl transferase-1; ADRP, adipocyte differentiation related protein; Apo, apolipoprotein; BMT, bone marrow transplantation; CANTOS, Canakinumab Anti-inflammatory Thrombosis Outcomes Study; CIRT, Cardiovascular Inflammation Reduction Trial; CCR2, CC-chemokine receptor-2; CR, chemokine receptor; CVD, cardiovascular disease; CSF, colony-stimulating factor; DCs, dendritic cells; ECs, endothelial cells; ECM, extracellular matrix; eNOS, endothelial nitric oxide synthase; ER, endoplasmic reticulum; ERK, extracellular signal-regulated kinase; Fn14, fibroblast growth factor-inducible 14; G-CSF, granulocyte colony-stimulating factor; GDF-15, growth differentiation factor-15; GM-CSF, granulocyte macrophage colony-stimulating factor; ICAM-1, intercellular adhesion molecule-1; IFN, interferon; IL, interleukin; IL-18BP, IL-18 binding protein; IL-1RA, IL-1 receptor antagonist; LDL, low-density lipoprotein; LDLr, low-density lipoprotein receptor; LFA1, lymphocyte function-associated antigen 1; LIGHT, homologous to lymphotoxin, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes; M-CSF, macrophage-colony stimulating factor; MHC, major histocompatibility complex; MIF, macrophage migration inhibitory factor; miRNA, micro RNA; mmLDL, minimally modified LDL; MMP, matrix metalloproteinase; LXR, liver X receptors; NK, natural killer; NOD, nucleotide-binding oligomerization domain; NLR, NOD-like receptor; NLRP3, NLR family, pyrin domain containing 3; NPC, Niemann-Pick disease, type C; OxLDL, oxidized LDL; PAI, plasminogen activator inhibitor; PECAM-1, platelet endothelial cell adhesion molecule-1; PRR, pattern recognition receptor; RCT, reverse cholesterol transport; ROS, reactive oxygen species; SMCs, smooth muscle cells; SOCS, suppressor of cytokine signaling; SR, scavenger receptor; SREBP, sterol response element binding protein; SR-PSOX, SR that binds phosphatidyl serine and oxidized lipoprotein; STAT1, signal transducer and activator of transcription-1; TF, tissue factor; TGF, transforming growth factor; Th, T-helper; TIMP, tissue inhibitor of metalloproteinases; TNF, tumor necrosis factor; TL1A, TNF-like protein 1A; TNFSF12, TNF superfamily member 12; TLR, Toll-like receptor; TRAIL, TNF-related apoptosis-inducing ligand; Tregs, regulatory T cells; TWEAK, TNF-related weak inducer of apoptosis; VCAM-1, vascular cell adhesion molecule-1; VLA4, very late antigen 4; wt, wild type
3.  Determinants of waterpipe use amongst adolescents in Northern Sweden: a survey of use pattern, risk perception, and environmental factors 
BMC Research Notes  2015;8:441.
Determinants of waterpipe use in adolescents are believed to differ from those for other tobacco products, but there is a lack of studies of possible social, cultural, or psychological aspects of waterpipe use in this population. This study applied a socioecological model to explore waterpipe use, and its relationship to other tobacco use in Swedish adolescents.
A total of 106 adolescents who attended an urban high-school in northern Sweden responded to an anonymous questionnaire. Prevalence rates for waterpipe use were examined in relation to socio-demographics, peer pressure, sensation seeking behavior, harm perception, environmental factors, and depression.
Thirty-three percent reported ever having smoked waterpipe (ever use), with 30 % having done so during the last 30 days (current use). Among waterpipe ever users, 60 % had ever smoked cigarettes in comparison to 32 % of non-waterpipe smokers (95 % confidence interval 1.4–7.9). The odds of having ever smoked waterpipe were three times higher among male high school seniors as well as students with lower grades. Waterpipe ever users had three times higher odds of having higher levels of sensation-seeking (95 % confidence interval 1.2–9.5) and scored high on the depression scales (95 % confidence interval 1.6–6.8) than non-users. The odds of waterpipe ever use were four times higher for those who perceived waterpipe products to have pleasant smell compared to cigarettes (95 % confidence interval 1.7–9.8). Waterpipe ever users were twice as likely to have seen waterpipe use on television compared to non-users (95 % confidence interval 1.1–5.7). The odds of having friends who smoked regularly was eight times higher for waterpipe ever users than non-users (95 % confidence interval 2.1–31.2).
The current study reports a high use of waterpipe in a select group of students in northern Sweden. The study adds the importance of looking at socioecological determinants of use, including peer pressure and exposure to media marketing, as well as mental health among users.
PMCID: PMC4570251  PMID: 26374502
Hookah; Argile; Depression; Socioecological model
4.  Significantly reduced lymphadenopathy, salivary gland infiltrates and proteinuria in MRL-lpr/lpr mice treated with ultrasoluble curcumin/turmeric: increased survival with curcumin treatment 
Lupus Science & Medicine  2015;2(1):e000114.
Commercial curcumin (CU), derived from food spice turmeric (TU), has been widely studied as a potential therapeutic for a variety of oncological and inflammatory conditions. Lack of solubility/bioavailability has hindered curcumin's therapeutic efficacy in human diseases. We have solubilised curcumin in water applying heat/pressure, obtaining up to 35-fold increase in solubility (ultrasoluble curcumin (UsC)). We hypothesised that UsC or ultrasoluble turmeric (UsT) will ameliorate systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS)-like disease in MRL-lpr/lpr mice.
Eighteen female MRL-lpr/lpr (6 weeks old) and 18 female MRL-MpJ mice (6 weeks old) were used. Female MRL-lpr/lpr mice develop lupus-like disease at the 10th week and die at an average age of 17 weeks. MRL-MpJ mice develop lupus-like disease around 47 weeks and typically die at 73 weeks. Six mice of each strain received autoclaved water only (lpr-water or MpJ-water group), UsC (lpr-CU or MpJ-CU group) or UsT (lpr-TU or MpJ-TU group) in the water bottle.
UsC or UsT ameliorates SLE in the MRL-lpr/lpr mice by significantly reducing lymphoproliferation, proteinuria, lesions (tail) and autoantibodies. lpr-CU group had a 20% survival advantage over lpr-water group. However, lpr-TU group lived an average of 16 days shorter than lpr-water group due to complications unrelated to lupus-like illness. CU/TU treatment inhibited lymphadenopathy significantly compared with lpr-water group (p=0.03 and p=0.02, respectively) by induction of apoptosis. Average lymph node weights were 2606±1147, 742±331 and 385±68 mg, respectively, for lpr-water, lpr-CU and lpr-TU mice. Transferase dUTP nick end labelling assay showed that lymphocytes in lymph nodes of lpr-CU and lpr-TU mice underwent apoptosis. Significantly reduced cellular infiltration of the salivary glands in the lpr-TU group compared with the lpr-water group, and a trend towards reduced kidney damage was observed in the lpr-CU and lpr-TU groups.
These studies show that UsC/UsT could prove useful as a therapeutic intervention in SLE/SS.
PMCID: PMC4567741  PMID: 26380101
Autoantibodies; Autoimmunity; Sjøgren's Syndrome; Systemic Lupus Erythematosus; Treatment
5.  Interferon-γ: Promising therapeutic target in atherosclerosis 
Atherosclerosis is a chronic inflammatory disorder of the vasculature and is the primary cause of cardiovascular disease (CVD). CVD is currently the world’s leading cause of death and the numbers are predicted to rise further because of a global increase in risk factors such as diabetes and obesity. Current therapies such as statins have had a major impact in reducing mortality from CVD. However, there is a marked residual CVD risk in patients on statin therapy. It is therefore important to understand the molecular basis of this disease in detail and to develop alternative novel therapeutics. Interferon-γ (IFN-γ) is a pro-inflammatory cytokine that is often regarded as a master regulator of atherosclerosis development. IFN-γ is able to influence several key steps during atherosclerosis development, including pro-inflammatory gene expression, the recruitment of monocytes from the blood to the activated arterial endothelium and plaque stability. This central role of IFN-γ makes it a promising therapeutic target. The purpose of this editorial is to describe the key role IFN-γ plays during atherosclerosis development, as well as discuss potential strategies to target it therapeutically.
PMCID: PMC4543809  PMID: 26309816
Atherosclerosis; Interferon-γ; Inflammation; Neutralization; MicroRNA
6.  Prolonged Remission of Psoriasis with Azathioprine Pulse Therapy 
Indian Journal of Dermatology  2015;60(4):360-363.
Although various therapies used for the treatment of psoriasis are able to produce remission, yet relapses, a common problem, remains frequent. It was observed that treatment with intermittent high dose (IHD) and continuous low dose (CLD) azathioprine can produce prolonged and durable remission in psoriasis.
To see the long term effect of azathioprine pulse therapy (APT) in psoriasis.
Ten patients with psoriasis who has completed more than 5 years in remission with azathioprine pulse therapy are being taken in the study. They were given IHD azathioprine (500 mg on 3 consecutive days which is repeated every month) with CLD azathioprine (100 mg orally) daily in between IHD. The entire treatment schedule was divided into four phases. During phase I, treatment with IHD and CLD azathioprine was started and continued till complete clearance of lesions after which, patients proceeded to Phase II. In phase II, they continued to get treatment with IHD and CLD. After continued remission for a period of nine months, they entered into phase III, when the treatment with IHD was stopped, but CLD continued. If there was no recurrence after nine months of phase III treatment, CLD was also withdrawn, and patients were followed-up without any treatment (Phase IV).
All 10 patients completed treatment and are in remission for more than five years without any treatment.
Out of 60 patients in phase IV, 10 patients were in continuous remission for more than five years, after all treatment had been stopped. Thus, azathioprine pulse therapy regimen produces prolonged remission in psoriasis.
PMCID: PMC4533533  PMID: 26288403
Azathioprine pulse therapy; continuous low dose azathioprine; intermittent high dose azathioprine; methotrexate; prolong remission; psoriasis
7.  Epidermal Growth Factor Receptor Expression in Triple Negative and Nontriple Negative Breast Carcinomas 
The panel of markers used for molecular classification include estrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor (HER)-2/neu, p53, Bcl-2 and basal markers like cytokeratin 5/6 or epidermal growth factor receptor (EGFR). Among these, EGFR plays an important role and is associated with bad prognosis.
Aims and Objectives:
To study EGFR expression in triple negative breast carcinoma (TNBC) and non-TNBCs (NTNBCs).
Materials and Methods:
Fifty cases of breast carcinomas were classified and graded according to World Health Organization and Nottingham modification of Scarff-Bloom-Richardson (SBR) system, respectively. The age of the patients ranged from 28 to 69 years. Histological features such as necrosis, pushing borders, lymphocytic infiltrate and periductal elastosis were noted. The panel of markers used in our study included ER, PR, HER-2/neu and EGFR. EGFR expression was assessed based on membrane staining. Chi-square test was applied for statistical analysis to compare EGFR expression with hormonal status and prognostic factors. P < 0.05 was considered significant.
The mean age was 49.8 ± 7.2 years. There were 44 (88%) infiltrating ductal carcinoma, 3 (6%) medullary carcinoma and 3 (6%) mucinous carcinoma. EGFR expression was common in young patients and was predominant in TNBC (89.47%), was also expressed in few cases of NTNBC. There was a positive correlation of EGFR expression (P = 0.03491) with a high grade. Medullary carcinomas were triple negative and strongly expressed EGFR. EGFR expression was inversely associated with ER status and showed strong association with necrosis and lymphocytic infiltrate, but not with pushing border and periductal elastosis.
EGFR is an important marker to stratify patients with breast cancer according to molecular classification. Its expression correlated positively with young age, higher SBR grade, necrosis, lymphocytic infiltrate and inversely with hormonal receptor expression.
PMCID: PMC4559633  PMID: 26417156
Epidermal growth factor receptor; hormonal status; nontriple negative breast carcinoma; triple negative breast carcinoma
8.  Underweight Full-Term Indian Neonates Show Differences in Umbilical Cord Blood Leukocyte Phenotype: A Cross-Sectional Study 
PLoS ONE  2015;10(4):e0123589.
While infections are a major cause of neonatal mortality in India even in full-term neonates, this is an especial problem in the large proportion (~20%) of neonates born underweight (or small-for-gestational-age; SGA). One potential contributory factor for this susceptibility is the possibility that immune system maturation may be affected along with intrauterine growth retardation.
In order to examine the possibility that differences in immune status may underlie the susceptibility of SGA neonates to infections, we enumerated the frequencies and concentrations of 22 leukocyte subset populations as well as IgM and IgA levels in umbilical cord blood from full-term SGA neonates and compared them with values from normal-weight (or appropriate-for-gestational-age; AGA) full-term neonates. We eliminated most SGA-associated risk factors in the exclusion criteria so as to ensure that AGA-SGA differences, if any, would be more likely to be associated with the underweight status itself.
An analysis of 502 such samples, including 50 from SGA neonates, showed that SGA neonates have significantly fewer plasmacytoid dendritic cells (pDCs), a higher myeloid DC (mDC) to pDC ratio, more natural killer (NK) cells, and higher IgM levels in cord blood in comparison with AGA neonates. Other differences were also observed such as tendencies to lower CD4:CD8 ratios and greater prominence of inflammatory monocytes, mDCs and neutrophils, but while some of them had substantial differences, they did not quite reach the standard level of statistical significance.
These differences in cellular lineages of the immune system possibly reflect stress responses in utero associated with growth restriction. Increased susceptibility to infections may thus be linked to complex immune system dysregulation rather than simply retarded immune system maturation.
PMCID: PMC4405369  PMID: 25898362
9.  The Bracka two-stage repair for severe proximal hypospadias: A single center experience 
Surgical correction of severe proximal hypospadias represents a significant surgical challenge and single-stage corrections are often associated with complications and reoperations. Bracka two-stage repair is an attractive alternative surgical procedure with superior, reliable, and reproducible results.
To study the feasibility and applicability of Bracka two-stage repair for the severe proximal hypospadias and to analyze the outcomes and complications of this surgical technique.
Materials and Methods:
This prospective study was conducted from January 2011 to December 2013. Bracka two-stage repair was performed using inner preputial skin as a free graft in subjects with proximal hypospadias in whom severe degree of chordee and/or poor urethral plate was present. Only primary cases were included in this study. All subjects received three doses of intra-muscular testosterone 3 weeks apart before first stage. Second stage was performed 6 months after the first stage. Follow-up ranged from 6 months to 24 months.
A total of 43 patients operated for Bracka repair, out of which 30 patients completed two-stage repair. Mean age of the patients was 4 years and 8 months. We achieved 100% graft uptake and no revision was required. Three patients developed fistula, while two had metal stenosis. Glans dehiscence, urethral stricture and the residual chordee were not found during follow-up and satisfactory cosmetic results with good urinary stream were achieved in all cases.
The Bracka two-stage repair is a safe and reliable approach in select patients in whom it is impractical to maintain the axial integrity of the urethral plate, and, therefore, a full circumference urethral reconstruction become necessary. This gives good results both in terms of restoration of normal function with minimal complication.
PMCID: PMC4360458  PMID: 25829670
Bracka repair; proximal hypospadias; two-stage repair
10.  Transgenerational effects from early developmental exposures to bisphenol A or 17α-ethinylestradiol in medaka, Oryzias latipes 
Scientific Reports  2015;5:9303.
The transgenerational consequences of environmental contaminant exposures of aquatic vertebrates have the potential for broad ecological impacts, yet are largely uninvestigated. Bisphenol A (BPA) and 17α-ethinylestradiol (EE2) are two ubiquitous estrogenic chemicals present in aquatic environments throughout the United States and many other countries. Aquatic organisms, including fish, are exposed to varying concentrations of these chemicals at various stages of their life history. Here, we tested the ability of embryonic exposure to BPA or EE2 to cause adverse health outcomes at later life stages and transgenerational abnormalities in medaka fish. Exposures of F0 medaka to either BPA (100 μg/L) or EE2 (0.05 μg/L) during the first 7 days of embryonic development, when germ cells are differentiating, did not cause any apparent phenotypic abnormalities in F0 or F1 generations, but led to a significant reduction in the fertilization rate in offspring two generations later (F2) as well as a reduction of embryo survival in offspring three generations later (F3). Our present observations suggest that BPA or EE2 exposure during development induces transgenerational phenotypes of reproductive impairment and compromised embryonic survival in fish of subsequent generations. These adverse outcomes may have negative impacts on populations of fish inhabiting contaminated aquatic environments.
PMCID: PMC4366817  PMID: 25790734
11.  The Phosphoinositide 3-Kinase Signaling Pathway is Involved in the Control of Modified Low-Density Lipoprotein Uptake by Human Macrophages 
Lipids  2015;50(3):253-260.
The transformation of macrophages into lipid-loaded foam cells is a critical early event in the pathogenesis of atherosclerosis. Both receptor-mediated uptake of modified LDL, mediated primarily by scavenger receptors-A (SR-A) and CD36 along with other proteins such as lipoprotein lipase (LPL), and macropinocytosis contribute to macrophage foam cell formation. The signaling pathways that are involved in the control of foam cell formation are not fully understood. In this study, we have investigated the role of phosphoinositide 3-kinase (PI3K) in relation to foam cell formation in human macrophages. The pan PI3K inhibitor LY294002 attenuated the uptake of modified LDL and macropinocytosis, as measured by Lucifer Yellow uptake, by human macrophages. In addition, the expression of SR-A, CD36 and LPL was attenuated by LY294002. The use of isoform-selective PI3K inhibitors showed that PI3K-β, -γ and -δ were all required for the expression of SR-A and CD36 whereas only PI3K-γ was necessary in the case of LPL. These studies reveal a pivotal role of PI3K in the control of macrophage foam cell formation and provide further evidence for their potential as therapeutic target against atherosclerosis.
Electronic supplementary material
The online version of this article (doi:10.1007/s11745-015-3993-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4339697  PMID: 25663263
Atherosclerosis; Foam cell; Cholesterol; Macrophage; Phosphoinositide 3-kinase
12.  Topical Adapalene in the Treatment of Plantar Warts; Randomized Comparative Open Trial in Comparison with Cryo-Therapy 
Various therapeutic modalities, which are available for treating plantar wart, have not been successful every time.
To evaluate topical adapalene under occlusion in the treatment of plantar warts and compare it with cryo-therapy.
Materials and Methods:
50 patients with 424 plantar warts were included in this single center, two arm, prospective, randomized, control, open study. Patients were allocated randomly into two groups consisting of 25 patients each. Group A patients having 299 plantar warts were treated using adapalene gel 0.1% under occlusion while Group B patients having 125 warts were treated using cryo-therapy. All the patients were evaluated weekly till the clearance of all the warts and the results compared.
All the warts of 25 patients of Group A that were treated using adapalene gel 0.1% cleared in 36.71 ± 19.24 (55.95-17.47) days except those in one patient. In Group B, warts in all except one treated by cryo-therapy cleared in 52.17 ± 30.06 (82.23-22.11) days. There were no side effects like scar formation, irritation, erythema, or infections with adapalene group while in the cryo group scar was seen in 2 patients, pain in 24, erythema in 10, and infection in 3 patients.
Adapalene gel 0.1% under occlusion is an effective, safe and easy to use treatment for plantar warts and may help clear lesions faster than cryo-therapy.
PMCID: PMC4318023  PMID: 25657417
Adapalene; cryo-therapy; occlusion; plantar wart
13.  Burden of disease and cost of chronic hepatitis C virus infection in Canada 
Although the exact prevalence of hepatitis C virus (HCV) infection in Canada is unknown, previous studies and anecdotal evidence suggest that the burden of HCV disease, including cirrhosis and hepatocellular carcinoma, is increasing. Recent modelling studies investigating disease burden, however, have reported results that are discordant with actual outcomes. Although likely due to varying methodology, these discrepancies prompted the authors of this study to develop a more refined disease progression model that could describe the future burden of disease and cost of HCV infection. The results may facilitate disease forecasting, resource planning and the development of new management strategies.
Chronic infection with hepatitis C virus (HCV) is a major cause of cirrhosis, hepatocellular carcinoma and liver transplantation.
To estimate the burden of HCV-related disease and costs from a Canadian perspective.
Using a system dynamic framework, the authors quantified the HCV-infected population, disease progression and costs in Canada between 1950 and 2035. Specifically, 36 hypothetical, ageand sex-defined cohorts were tracked to define HCV prevalence, complications and direct medical costs (excluding the cost of antivirals). Model assumptions and costs were extracted from the literature with an emphasis on Canadian data. No incremental increase in antiviral treatment over current levels was assumed, despite the future availability of potent antivirals.
The estimated prevalence of viremic hepatitis C cases peaked in 2003 at 260,000 individuals (uncertainty interval 192,460 to 319,880), reached 251,990 (uncertainty interval 177,890 to 314,800) by 2013 and is expected to decline to 188,190 (uncertainty interval 124,330 to 247,200) in 2035. However, the prevalence of advanced liver disease is increasing. The peak annual number of patients with compensated cirrhosis (n=36,210), decompensated cirrhosis (n=3380), hepatocellular carcinoma (n=2220) and liver-related deaths (n=1880) are expected to occur between 2031 and 2035. During this interval, an estimated 32,460 HCV-infected individuals will die of liver-related causes. Total health care costs associated with HCV (excluding treatment) are expected to increase by 60% from 2013 until the peak in 2032, with the majority attributable to cirrhosis and its complications (81% in 2032 versus 56% in 2013). The lifetime cost for an individual with HCV infection in 2013 was estimated to be $64,694.
Although the prevalence of HCV in Canada is decreasing, cases of advanced liver disease and health care costs continue to rise. These results will facilitate disease forecasting, resource planning and the development of rational management strategies for HCV in Canada.
PMCID: PMC4049256  PMID: 24839620
Cirrhosis; Hepatitis C; Hepatocellular carcinoma; Mortality; Outcomes; Treatment
14.  Fixed Drug Eruption Due to Ornidazole 
A 56-year-old male developed an ulcer on his glans penis and mucosae of upper and lower lips 3 days after taking ofloxacin, cephalexin, and ornidazole. Clinically, a provisional diagnosis of fixed drug eruption was made. The causative drug was confirmed by an oral provocation test which triggered a reactivation of all lesions only with ornidazole.
PMCID: PMC4248543  PMID: 25484435
Fixed drug eruption; ornidazole; provocation test
15.  Can Preterm Labour Be Predicted in Low Risk Pregnancies? Role of Clinical, Sonographic, and Biochemical Markers 
Journal of Pregnancy  2014;2014:623269.
Background and Objectives. This is a prospective nested cohort study conducted over a period of 3 years. 2644 women were recruited, out of which final analysis was done for 1884 women. Methods. Cervicovaginal and blood samples were collected for all recruited women. Out of these, 137 women who delivered before 35 weeks were treated as cases and equal number of matched controls were chosen. Analysis of samples for serum G-CSF, AFP, ferritin, and cervicovaginal interleukin-6 and IGFBP-1 was done. Results. Poor orodental hygiene, which can be a social marker, was significantly more common in women who delivered preterm (P = 0.008). Serum alkaline phosphatase and serum ferritin were found to be significantly associated with preterm deliveries. The 90th percentile value of these parameters was considered as cut-off as there is no specific cut-off. Conclusions. Our study did not prove usefulness of any predictive marker. Serum ferritin and alkaline phosphatase were found to have correlation but their values are affected in many conditions and need to be elucidated with caution. Larger studies are needed for predicting preterm labour in asymptomatic women.
PMCID: PMC4227377  PMID: 25405034
16.  Magnitude of peripheral neuropathy in cirrhosis of liver patients from central rural India 
Cirrhosis of liver is an important cause of morbidity and mortality and if associated with peripheral neuropathy (PN) it also poses a huge financial, psychological burden for the patients and their families.
The aim of the present study was to study the magnitude of PN among subjects with cirrhosis of liver presenting to tertiary care teaching hospital in central rural India.
Settings and Design:
A cross-sectional study was performed in a tertiary care teaching hospital.
Materials and Methods:
In all patients of cirrhosis of liver irrespective of etiology, aged 15 and above, undergone clinical assessment for peripheral nervous systems damage and confirmed by nerve conduction studies.
Statistical Analysis Used:
We used chi square test to study associations. P value ≤0.05 was considered as significant. Crude odds ratios were computed to assess the strength of association between independent variables and dependent variables along with their 95% confidence intervals.
We included 207 of cirrhosis of liver patients admitted in medicine department from November 2010 through November 2013. Nearly 83% patients were male and 63.2% patients were under the age of 45 years. Common features in these patients were ascites (71%) splenomegaly (63.3%) pedal edema (61.4%) icterus (46.4%) tingling (44.9%) gastrointestinal bleeding(39.1%), ataxia (26.6%), numbness(26.6%), distal motor weakness (21.7%) and paresthesia(20.8%). Among the manifestation of peripheral nerve involvement, loss of ankle reflex was the most common feature in 51.7%, followed by loss of temperature sense 29.5%, loss of vibration sense 20.8%, loss of touch 16.4%, loss of position sense 14.5% and loss of pain in 6.3% of the patients. Peripheral neuropathy was found in 53.6% [95% CI: 46.58- 60.56] study subjects on electrophysiological study.
Analysis of electrophysiological study shows that the PN is very common in study subjects with cirrhosis of liver, especially in male subjects, during the middle age group.
PMCID: PMC4251014  PMID: 25506162
Chronic liver disease; cirrhosis of liver; nerve conduction studies; peripheral neuropathy
17.  Influence of visual angle on pattern reversal visual evoked potentials 
Oman Journal of Ophthalmology  2014;7(3):120-125.
The aim of this study was to find whether the visual evoked potential (VEP) latencies and amplitude are altered with different visual angles in healthy adult volunteers or not and to determine the visual angle which is the optimum and most appropriate among a wide range of check sizes for the reliable interpretation of pattern reversal VEPs (PRVEPs).
Materials and Methods:
The present study was conducted on 40 healthy volunteers. The subjects were divided into two groups. One group consisted of 20 individuals (nine males and 11 females) in the age range of 25-57 years and they were exposed to checks subtending a visual angle of 90, 120, and 180 minutes of arc. Another group comprised of 20 individuals (10 males and 10 females) in the age range of 36-60 years and they were subjected to checks subtending a visual angle of 15, 30, and 120 minutes of arc. The stimulus configuration comprised of the transient pattern reversal method in which a black and white checker board is generated (full field) on a VEP Monitor by an Evoked Potential Recorder (RMS EMG. EPMARK II). The statistical analysis was done by One Way Analysis of Variance (ANOVA) using EPI INFO 6.
In Group I, the maximum (max.) P100 latency of 98.8 ± 4.7 and the max. P100 amplitude of 10.05 ± 3.1 μV was obtained with checks of 90 minutes. In Group II, the max. P100 latency of 105.19 ± 4.75 msec as well as the max. P100 amplitude of 8.23 ± 3.30 μV was obtained with 15 minutes. The min. P100 latency in both the groups was obtained with checks of 120 minutes while the min. P100 amplitude was obtained with 180 minutes. A statistically significant difference was derived between means of P100 latency for 15 and 30 minutes with reference to its value for 120 minutes and between the mean value of P100 amplitude for 120 minutes and that of 90 and 180 minutes.
Altering the size of stimulus (visual angle) has an effect on the PRVEP parameters. Our study found that the 120 is the appropriate (and optimal) check size that can be used for accurate interpretation of PRVEPs. This will help in better assessment of the optic nerve function and integrity of anterior visual pathways.
PMCID: PMC4220397  PMID: 25378875
Pattern reversal; P100 latency; P100 amplitude; VEP; visual angle
19.  Brainstem Auditory Evoked Potentials (BAEP)- A Pilot Study Conducted on Young Healthy Adults from Central India 
Objective: To Evaluate I, II, III, IV, V wave latencies and I-III, III-V, I-V inter-peak latencies and V/I wave amplitude ratio in Normal subjects in Central India.
Methods: We recorded BAEP from 50 healthy normal subjects from the community of same sex and geographical setup. The absolute, interpeak and wave V/I amplitude ratio were measurement and recording was done using RMS EMG EP MARK II machine manufactured by RMS recorders and Medicare system, Chandigarh.
Result: Absolute, interpeak and wave V/I amplitude ratio were measured in normal subjects and compared with other previous studies.
Conclusion: This study was conducted as exploratory pilot study only on male healthy controls. Since, the study conducted in different regions, there are some differences in the latencies and interpeak latencies and amplitude ratio but they are within range, so reference range of this study can be used for future studies in this Wardha region of Central India.
PMCID: PMC4129266  PMID: 25120971
Conductive deafness; Inter-peak latency; Peak latency; Sensory-neural hearing loss
20.  Hereditary Multiple Gastrointestinal Atresia associated with Choledochal Cyst: A Rare Entity with Management Dilemma  
Multiple intestinal atresias are rare and its treatment is challenging. Here, we present a case of multiple gastro-intestinal atresia associated with choledochal cyst posing us a surgical challenge.
PMCID: PMC4420447  PMID: 26023510
Multiple intestinal atresia; Choledochal cyst; Polyhydramnios
21.  Chronic hepatitis C in Western Canada: A survey of practice patterns among gastroenterologists in Alberta and British Columbia 
To survey gastroenterologists in British Columbia and Alberta with regard to awareness of chronic hepatitis C virus (HCV) management and practice patterns among physicians who treat and do not treat HCV-infected patients.
An anonymous two-page mail survey was distributed to actively practicing adult gastroenterologists in British Columbia and Alberta. Among physicians who treated HCV patients, respondents answered assessment of fibrosis pretreatment, measurement of rapid virological response, prescription of protease inhibitors (PIs), barriers to using these agents and referral patterns. For those who did not treat HCV, referral of patients for treatment and to whom was assessed.
Seventy-seven of 166 individuals completed the survey (46% response rate). Most (49%) practiced in academic or large community (42%) settings. Chronic liver disease comprised <25% of individual practice in 71%. Forty-eight (62%) treated HCV and two-thirds prescribed a PI. Barriers to prescription included unfamiliarity (six of 16), lack of allied health (five of 16) and few suitable patients (seven of 16). Pretreatment liver biopsy was performed by 33% (16 of 48) and 69% (33 of 48) used noninvasive measures. Rapid virological response was measured in 83% (40 of 48). Referral patterns changed in 46% (22 of 48) of physicians who treated HCV. All respondents who did not treat HCV referred patients for consideration, with 90% (26 of 29) made to hepatologists.
Chronic liver disease comprised <25% of practice in the majority of surveyed respondents. Among those who treated HCV, one-third have not prescribed a PI. Barriers to prescription and referral pattern changes are noted by those currently treating patients with HCV infection.
PMCID: PMC4071898  PMID: 24212914
Barriers; Guidelines; HCV; Practice; Rapid virological response; Referral; Survey
22.  LDL-cholesterol: Friedewald calculated versus direct measurement-study from a large Indian laboratory database 
Validity of Friedewald formula (FF) in patients with serum triglycerides (TGs) <400 mg/dl is unclear.
Materials and Methods:
We compared low-density lipoprotein (LDL)-cholesterol calculated by FF to directly measured LDL in a laboratory database of 14,620 lipid profile samples from south India.
LDL by FF correlated with directly measured LDL with correlation coefficient of 0.89 with the best correlation seen in TG levels 100-150. Higher level of TG (>200) underestimates the LDL calculated by FF particularly at LDL values <70 mg/dl. On the other hand, LDL is overestimated by FF in more than 70% of cases at LDL levels >130 mg/dl.
We suggest repeating the LDL by direct assay techniques particularly in patients with TG >200 and when LDL <70 or >130. This helps in correctly stratifying the coronary artery diseases’ (CADs’) risk and goals of treatment.
PMCID: PMC4138905  PMID: 25143906
Friedewald formula; LDL cholesterol; triglyceride
23.  Validation of pharyngeal findings on sleep nasopharyngoscopy in children with snoring/sleep disordered breathing 
To validate the pharyngeal findings in sleep nasopharyngoscopy (SNP) of children with snoring - sleep disordered breathing (S-SDB).
Prospective agreement diagnostic study on retrospective data.
We conducted an inter-and intra-rater agreement study on video documentations of SNP performed on children (non-syndromic, complex, or operated upon) who presented with S-SDB. The videos featured various pharyngeal findings (normal, collapse, mixed or obstruction). Three ‘non-expert’ raters at various stages in their otolaryngological careers rated the videos independently, and on two separate occasions following an instructional session. We calculated both weighted and non-weighted linear kappa.
Each independent observer rated sixty-one videos (2 weeks apart). Intra-observer agreement was 0.64 ± 0.08 (95% CI 0.48-0.81), 0.74 ± 0.07 (95% CI 0.60-0.88), 0.59 ± 0.08 (95% CI 0.43-0.74), for raters 1, two and three. Weighted kappa was 0.6 ± 0.1 (95% CI 0.41-0.79), 0.8 ± 0.06 (95% CI 0.7-0.92), 0.7 ± 0.07 (95% CI 0.57-0.83), respectively. Inter-rater agreements between raters one and two, two and three, three and four were 0.83 ± 0.06 (95% CI 0.71-0.95), 0.52 ± 0.08 (95% CI 0.36-0.70), and 0.53 ± 0.08 (95% CI 0.37-0.69), respectively. Weighted kappa was 0.83 ± 0.073 (95% CI 0.69-0.98), 0.68 ± 0.06 (95% CI 0.56-0.79), and 0.64 ± 0.07 (95% CI 0.49-0.78), respectively.
This is the first validation of pharyngeal findings on SNP in children. It is based on a four types’ classification. Overall reproducibility amongst the three raters and their agreement was moderate to good. Further work should be phase four trials investigating the impact on outcome.
PMCID: PMC4092353  PMID: 24919758
Sleep apnea; Children; Endoscopy; Propofol; Agreement; Diagnosis; Adenotonsillectomy
24.  A comparison of performance of plant miRNA target prediction tools and the characterization of features for genome-wide target prediction 
BMC Genomics  2014;15(1):348.
Deep-sequencing has enabled the identification of large numbers of miRNAs and siRNAs, making the high-throughput target identification a main limiting factor in defining their function. In plants, several tools have been developed to predict targets, majority of them being trained on Arabidopsis datasets. An extensive and systematic evaluation has not been made for their suitability for predicting targets in species other than Arabidopsis. Nor, these have not been evaluated for their suitability for high-throughput target prediction at genome level.
We evaluated the performance of 11 computational tools in identifying genome-wide targets in Arabidopsis and other plants with procedures that optimized score-cutoffs for estimating targets. Targetfinder was most efficient [89% ‘precision’ (accuracy of prediction), 97% ‘recall’ (sensitivity)] in predicting ‘true-positive’ targets in Arabidopsis miRNA-mRNA interactions. In contrast, only 46% of true positive interactions from non-Arabidopsis species were detected, indicating low ‘recall’ values. Score optimizations increased the ‘recall’ to only 70% (corresponding ‘precision’: 65%) for datasets of true miRNA-mRNA interactions in species other than Arabidopsis. Combining the results of Targetfinder and psRNATarget delivers high true positive coverage, whereas the intersection of psRNATarget and Tapirhybrid outputs deliver highly ‘precise’ predictions. The large number of ‘false negative’ predictions delivered from non-Arabidopsis datasets by all the available tools indicate the diversity in miRNAs-mRNA interaction features between Arabidopsis and other species. A subset of miRNA-mRNA interactions differed significantly for features in seed regions as well as the total number of matches/mismatches.
Although, many plant miRNA target prediction tools may be optimized to predict targets with high specificity in Arabidopsis, such optimized thresholds may not be suitable for many targets in non-Arabidopsis species. More importantly, non-conventional features of miRNA-mRNA interaction may exist in plants indicating alternate mode of miRNA target recognition. Incorporation of these divergent features would enable next-generation of algorithms to better identify target interactions.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-348) contains supplementary material, which is available to authorized users.
PMCID: PMC4035075  PMID: 24885295
miRNA; Target prediction; Plants; Deep-sequencing; Non-model plants
25.  Genetic Risk of Azoospermia Factor (AZF) Microdeletions in Idiopathic Cases of Azoospermia and Oligozoospermia in Central Indian Population 
Background: Genetic factors cause about 15% of male infertility. Azoospermia factors (AZFa, AZFb, and AZFc) present on Yq are most important for spermatogenesis. We have made an attempt to evaluate the frequencies of microdeletions of AZFa, AZFb, AZFc in idiopathic cases of azoospermia and oligozoospermia from central Indian population.
Materials and Methods: We have analyzed a total of 156 subjects (95 oligozoospermia and 61 azoospermia) & 50 control subjects. DNA samples were analyzed for microdeletions of Y chromosome by PCR-screening of 18 sequences-tagged-site (STS) markers from different region of the AZF on Yq and SRY on Yp.
Results: Out of 156 cases analyzed, 13 (8.33%) subjects (8 azoospermia and 5 oligozoospermia) showed partial deletion of AZF regions, of which deletion in AZFc region was the most common (84.6%) followed by AZFb (15.4%) and AZFa (15.4%). The sites and sizes of deletions varied among patients. Histological study of the testicular tissue of the available subjects, who showed microdeletions of Y chromosome, showed spermatogenic arrest at different stages. The frequency of Y chromosome microdeletion in our subjects was 8.33%.
Conclusion: Some Indian studies reported low frequencies of microdeletions than that of our result. We suggest that the frequency of deletions may be affected by the involvement of different genetic factors, ethnic population and different geographical regions. PCR based Y chromosome screening for microdeletions will be useful and great help to infertility clinics for genetic counselling and assisted reproduction.
PMCID: PMC4003696  PMID: 24783090
Male Infertility; Y microdeletions; AZF factor

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