Assessment of needs and gaps in public health cadre in India - a situational analysis.

BACKGROUND: A structured and organized public health set up with systematically trained personnel to manage and deliver public health services from grassroot levels to higher administrative levels with separate public health directorate is the need of the hour. The objective of this study was to conduct a situational analysis of public health cadre in select states in India to gain an in-depth understanding of the progress and explore the gaps and challenges in its implementation. METHODS: Four states from the country were selected based on stages of implementation of the cadre. The WHO health systems framework was the basis of assessment. In-depth interviews of 78 stakeholders from public health system across various categories and levels were conducted. RESULTS: Every state has a dedicated cadre for public health in the form of a separate hierarchical structure and Directorate. There are deficits in human resources skilled enough to manage and implement public health across all levels. Its penetration below districts level is limited. There are limited opportunities available for contractual staffs in terms of remuneration and job progression. The respondents strongly emphasized on having personnel with training in public health, especially at leadership positions. Funding was not reported to be a problem although some challenges in the timeliness of release of funds were reported. Under the existing Health Management Information System, duplication of data exists and there is underutilization of data for policy making. CONCLUSION: A dedicated public health cadre is under evolution in India. The main challenge is inadequate workforce skilled in public health management. States are committed to finding solutions to overcome these barriers.

Extraintestinal Manifestations of Inflammatory Bowel Disease: Current Concepts, Treatment, and Implications for Disease Management.

Inflammatory bowel diseases (IBDs) are systemic diseases that manifest not only in the gut and gastrointestinal tract, but also in the extraintestinal organs in many patients. The quality of life for patients with IBD can be substantially affected by these extraintestinal manifestations (EIMs). It is important to have knowledge of the prevalence, pathophysiology, and clinical presentation of EIMs in order to adapt therapeutic options to cover all aspects of IBD. EIMs can occur in up to 24% of patients with IBD before the onset of intestinal symptoms, and need to be recognized to initiate appropriate diagnostic procedures. EIMs most frequently affect joints, skin, or eyes, but can also affect other organs, such as the liver, lung, and pancreas. It is a frequent misconception that a successful therapy of the intestinal inflammation will be sufficient to treat EIMs satisfactorily in most patients with IBD. In general, peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum can be associated with active intestinal inflammation and can improve on standard treatment of the intestinal inflammation. However, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis usually occur independent of disease flares. This review provides a comprehensive overview of epidemiology, pathophysiology, clinical presentation, and treatment of EIMs in IBD.

Paternal Exposure to Immunosuppressive and/or Biologic Agents and Birth Outcomes in Patients With Immune-Mediated Inflammatory Diseases.

BACKGROUND & AIMS: We conducted a retrospective cohort study to inform the safety of exposure to immunosuppressive and/or biologic agents around conception in expectant fathers with immune-mediated inflammatory diseases (IMIDs) on birth outcomes. METHODS: Using a deidentified administrative claims database (OptumLabs Data Warehouse), we identified 7453 expectant fathers with IMIDs (inflammatory bowel diseases, rheumatoid arthritis, psoriasis/psoriatic arthritis, and ankylosing spondylitis) linked to newborns with periconception medication exposure between 38 and 60 weeks before the newborn birth date (34-58 weeks prior for preterm newborns) and neonatal follow-up for 3 months after the birth date. Through logistic regression adjusting for paternal age and race (and, in a subset, for maternal age, race, presence of IMIDs, and nonsingleton births), we compared the risk of major congenital malformations (primary outcome) and preterm birth and low birth weight in fathers exposed to thiopurines (n = 461), methotrexate (n = 171), tumor necrosis factor (TNF) α antagonists (n = 1082), or non-TNF-targeting biologic agents (n = 132) vs fathers not exposed to any of these medications (n = 5607). RESULTS: As compared to unexposed fathers (3.4% prevalence of major congenital malformations), exposure to thiopurines (relative risk [RR], 1.12; 95% confidence interval [CI], 0.66-1.76), methotrexate (RR, 0.67; 95% CI, 0.21-1.55), TNF-α antagonists (RR, 1.14; 95% CI, 0.81-1.57), and non-TNF-targeting biologic agents (RR, 1.75; 95% CI, 0.80-3.24) was not associated with increased risk of major congenital malformations. No association was observed between paternal medication exposure and risk of preterm birth or low birth weight. Results were stable on subanalyses of linked father-mother-newborn triads. CONCLUSIONS: In a large cohort study of 7453 expectant fathers with IMIDs, exposure to immunosuppressive or biologic agents around conception was not associated with increased risk of adverse birth outcomes.

Rate, risk factors and causes of mortality in patients with Sjögren's syndrome: a systematic review and meta-analysis of cohort studies.

OBJECTIVES: There is conflicting evidence regarding prognosis in patients with primary SS (pSS). The aim of this study was to estimate the rate, risk factors and causes of mortality in patients with pSS through a systematic review and meta-analysis. METHODS: Through a systematic review of multiple databases through October 2014, we identified cohort studies reporting relative risk (compared with standardized population), risk factors and causes of mortality in patients with pSS. We estimated summary risk ratios (RRs) with 95% CIs using random effects model. RESULTS: We identified 10 studies with 7888 patients (91% females) with pSS, of whom 682 patients died over a median average follow-up of 9 years. The pooled standardized mortality ratio in patients with pSS was 1.38 (95% CI 0.94, 2.01). Leading causes of mortality were cardiovascular diseases, solid-organ and lymphoid malignancies and infections; however, it is unclear whether these observed causes were overrepresented in patients with pSS as compared with the general population. Risk factors associated with increased mortality were advanced age at diagnosis [RR 1.09 (95% CI 1.07, 1.12)], male sex [RR 2.18 (95% CI 1.45, 3.27)], parotid enlargement [RR 1.81 (95% CI 1.02, 3.21)], abnormal parotid scintigraphy [RR 2.96 (95% CI 1.36, 6.45)], extraglandular involvement [RR 1.77 (95% CI 1.06, 2.95)], vasculitis [RR 7.27 (95% CI 2.70, 19.57)], anti-SSB positivity [RR 1.45 (95% CI 1.03, 2.04)], low C3 [RR 2.14 (95% CI 1.38, 3.32)] and C4 [RR 3.08 (95% CI 2.14, 4.42)] and cryoglobulinaemia [RR 2.62 (95% CI 1.77, 3.90)]. CONCLUSION: pSS is not associated with an increase in all-cause mortality as compared with the general population. However, a subset of patients with extraglandular involvement, vasculitis, hypocomplementaemia and cryoglobulinaemia may be at increased risk of mortality and require close follow-up.

Cancer risk in cutaneous lupus erythematosus: a population-based cohort study.

OBJECTIVE: Immune dysregulation associated with chronic autoimmune diseases, such as SLE, has been associated with increased cancer risk. It is unclear whether isolated cutaneous lupus erythematosus (CLE) modifies cancer risk. We estimated the cumulative incidence of cancer in a population-based CLE cohort and compared the risk with a matched non-CLE cohort. METHODS: All incident cases of CLE in Olmsted County, MN, USA between 1965 and 2005 were identified and followed to December 2013. Estimates for the cumulative incidence of any cancer and skin cancer in patients with CLE were derived and compared with an age-, sex- and calendar-year-matched non-CLE cohort using Cox models. RESULTS: There were a total of 155 patients with CLE [age at diagnosis, 48 (sd 16) years; 65% females; BMI, 26.3 (sd 7.1) kg/m2; 40% smokers, 9% with diabetes]. During a median follow-up of 14.6 years, we observed 35 cases of incident cancer (including 10 cases of skin cancer). The cumulative 1-, 5- and 10-year incidence of any cancer after diagnosis of CLE was 1.4, 7.5 and 11.6%, respectively. Compared with matched non-CLE controls, the overall risk of malignancies was not increased in patients with CLE (smoking-adjusted hazard ratio = 1.29; 95% CI: 0.78, 2.13; P = 0.31). There was also no significant increase in risk of any skin cancer in patients with CLE (hazard ratio = 2.51; 95% CI: 0.91, 6.96; P = 0.16). CONCLUSION: CLE is not associated with an increased risk of any cancers, including skin cancers, compared with the general population. However, the number of events was small, limiting the power of the study.

Effect of l-Arginine on Nitric Oxide Levels in Intrauterine Growth Restriction and its Correlation with Fetal Outcome.

The current management of intrauterine growth restriction (IUGR) being empirical and aimed at selecting a safe time for delivery. Acknowledging the beneficial effects of l-arginine on endothelial vasculature the present study was designed to evaluate efficacy of l-arginine on bioavailability of nitric oxide (NO) with respect to fetal outcome. With l-arginine supplementation, mean NO levels were significantly increased and a significant mild reduction in systolic/end-diastolic velocity ratio (S/D ratio) was observed on doppler blood flow study, also neonatal outcome improved and incidences of complications were lowered. A deficiency in NO may play an important role in the causation of asymmetric fetal growth restriction. l-Arginine can be used to increase maternal NO levels, enhancing birth weight and decreasing neonatal morbidity. The ideal candidate for arginine therapy according to our study would be IUGR cases with S/D ratio less than 4.96 ± 0.49 and NO levels below 33 µmol/L with minimum of 3 weeks duration of arginine supplementation.

Statins are associated with a reduced risk of hepatocellular cancer: a systematic review and meta-analysis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Several studies have shown that statins could have chemopreventive effects on HCC. We performed a systematic review and meta-analysis of studies that evaluated the effects of statins on the risk of HCC. METHODS: We conducted a systematic search of MEDLINE, Embase, and Web of Science through May 2012 and manually reviewed the literature. Studies were included if they evaluated and clearly defined exposure to statins, reported the incidence of HCC, and reported relative risks or odds ratios (ORs) or provided data for their estimation. Ten studies reporting 4298 cases of HCC in 1,459,417 patients were analyzed. Summary OR estimates with 95% confidence intervals (CIs) were calculated using the random effects model. Statistical heterogeneity was assessed with the Cochran's Q statistic and I(2) statistic. RESULTS: Statin users were less likely to develop HCC than statin nonusers (adjusted OR, 0.63; 95% CI, 0.52-0.76), although the results were heterogeneous (P = .01, I(2) = 59%). This heterogeneity could be accounted for by study location (Asian population [n = 4]: adjusted OR, 0.52; 95% CI, 0.42-0.64; Western population [n = 6]: adjusted OR, 0.67; 95% CI, 0.53-0.85) and design (observational studies [n = 7]: adjusted OR, 0.60; 95% CI, 0.49-0.73; clinical trials [n = 3]: adjusted OR, 0.95; 95% CI, 0.62-1.45). CONCLUSIONS: Based on meta-analysis, statin use is associated with a reduced risk of HCC, most strongly in Asian but also in Western populations. Randomized clinical trials in populations at high risk for HCC (especially in Asian populations with hepatitis B) are warranted.

Accuracy of Dare's formula in estimating fetal birth weight in pregnant women.

OBJECTIVE: To evaluate the accuracy of Dare's formula in estimating fetal birth weight in pregnant women. METHODS: A prospective study was conducted at a tertiary care hospital in New Delhi after institutional ethical committee clearance. In all, 175 pregnant women with singleton pregnancies of 37 weeks or more were included. The aim was to assess fetal birth weight by Dare's formula and ultrasonography. This estimated fetal weight (EFW) was compared with actual birth weight (ABW) of newborn. RESULTS: Estimated fetal birth weight by Dare's formula was within 10% of ABW in 77 (44.00%) cases. Meanwhile in the majority (98; 56.00%), EFW by Dare's formula was not within 10% of ABW. The proportion of EFW by ultrasonography within 10% and not within 10% of ABW were comparable (50.29% [88] and 49.71% [87], respectively). CONCLUSION: Dare's formula can be used by medical personnel as a clinical method in routine prenatal care to estimate fetal weight, for better management of women in labor to decrease the maternal and neonatal mortality and morbidity.

Finite element analysis of cross fluid model over a vertical disk suspended to a tetra hybrid nanoparticles mixture.

Nanoparticles have numerous applications and are used frequently in different cooling, heating, treatment of cancer cells and manufacturing processes. The current investigation covers the utilization of tetra hybrid nanofluid (aluminum oxide, iron dioxide, titanium dioxide and copper) for Crossflow model over a vertical disk by considering the shape effects (bricks, cylindrical and platelet) of nanoparticles, electro-magneto-hydrodynamic effect and quadratic thermal radiation. In the current inspection model is first derived given PD-equations and then altered into a system of OD-equations by including similarity variables. The converted ordinary differential equations are solved by using the finite element procedure and the impact of the solution against numerous involved parameters is displayed through tables and graphs. It is observed that tetra-hybrid nanoparticles are recommended better in industrial applications where the highest production of thermal energy. Moreover, an enhancement of thermal production can be achieved utilizing different values of the magnetic parameter, time relaxation number, variable thermal radiation number and magnetic induction number but the opposite trend has been noticed with the effects of radiation number.

Electrochemical and DFT Studies of the Pistacia Integerrima Gall Extract: An Eco-friendly Approach towards the Corrosion of Steel in Acidic Medium.

A novel application of the Pistacia integerrima gall extract as an environmentally friendly corrosion inhibitor is reported in this study. The major phytochemicals present in the gall extract, namely pistagremic acid, ß-sitosterol, pistiphloroglucinyl ether, pistaciaphenyl ester, naringenin, and 5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one, play key roles in its anticorrosive behavior on steel in aggressive media. Several approaches were used to study the corrosion prevention activity of steel in 1 M H2SO4, including weight loss analysis, scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), and density functional theory (DFT). At 2000 mg L-1, the highest efficiency of 92.19% was observed in 1 M H2SO4. An SEM study was conducted to validate the surface coverage of the metal surface. DFT studies revealed several nucleophilic regions present in the phytochemicals of the inhibitor, which supported the favorable nucleophilicity. Corrosion studies have not been performed on this sample. Phytochemicals make it an effective corrosion inhibitor, and its extraction process utilizes distilled water, making it better than other inhibitors. It has been proven that the obtained values of ΔEInhDFT for pistiphloroglucinyl, pistaciaphenyl ether, and naringenin organic compounds were very low, confirming the high reactivity of these corrosion inhibitors. The order of the values of ΔEInhDFT is as follows: pistaciaphenyl ether > pistiphloroglucinyl ether > naringenin organic compound; this suggests that pistaciaphenyl ether is more reactive than the other compounds. In this study, P. integerrima gall extract emerges as a novel and highly effective corrosion resistance agent in 1 M H2SO4, chosen for its relevance to acid pickling and cleaning processes.

Maternal Mortality and COVID-19 Pandemic: Looking Beyond SARS CoV-2 Infection.

Objective: To study the impact of COVID-19 pandemic on maternal mortality ratio, aetiological and modifiable factors for maternal mortality and key interventions performed. Method: Retrospective exploratory study evaluating maternal mortality between April to November 2020 (study group) and 2019 (control group). Results: Demographic variations existed in the two groups. Increased maternal age and illiteracy were significantly more in the study group. Maternal mortality ratio (MMR) was significantly high in the study group (792 vs. 296 p value = 0.0). Hemorrhage accounted for 20% and COVID-19-related maternal deaths accounted for 15% deaths in the study group. Level 3 delay (delay in receiving care/inadequate care) was observed in 35% in the study group and 28% in control group (p value = 0.349). 17.5% of mothers in the study group as compared to 8% of control group were dead on arrival to hospital though not statistically significant (p value = 0.28). Significantly more women in study group died within 24 h of admission (45% vs. 20%, p value 0.04). Among the key interventions, the use of supplemental oxygen was significantly high in study group (p value = 0.02). Conclusion: Maternal mortality ratio was high in the pandemic year because of a significant decline in hospital delivery rate. The lesson learnt from this pandemic needs to be documented to guide better planning in the future to face similar situations.

Appraisal of reservoir quality for hydrocarbon-bearing deep-water Miocene sandstones incised valley, south-east Asian offshore Indus: An application of seismic attributes and instantaneous spectral porosity quantitative reservoir simulations.

Incised marine valleys (IVS) are hot topics in exploring the stratigraphic oil and gas-bearing plays. Multiple channelized sandstone lenses at varying depths [m], thicknesses [m], and porosities [%] constrain seismic impedance. The presence of hydrocarbon-bearing resources affects the seismic impedance (density (g/cc) and velocity (m/s)). Therefore, a quantitative prediction has been carried out for determining the thickness [m], porosity [%], and depths [m] of laterally distributed channelized sandstone lenses (SLS) for IVS, Indus offshore Basin (IOB), Pakistan, using 2-D instantaneous spectral porosity quantitative modelling (2DSSM), continuous wavelet transforms-based (CWT) 2-D instantaneous spectral density modelling (2DSSDM), and spectral decomposition tools. The 2DSSM remained limited in predicting the number of channelized sandstone lenses and their quantitative stratigraphic attributes. The 45-Hz-based processing of conventional 2DSSM has resolved the two channelized sandstone lenses of the stratigraphic trap. The deepest channelized sandstone lens has attained 1-6 m thickness with a lateral extent of 3 km, within the porosity range of 18-33 %. The highest confidence level for predicted petrophysical attributes such as 13 m-thick pay zones, -0.08, -0.067, and -0.07 acoustic impedances [g/c.c.*m/s], and 28 % porosities with R2 > 0.85 have validated interpretations. The response of 45-Hz CWT waveform-based inverted density and thickness simulations has predicted the highest thicknesses and lowest densities of reservoir sandstones within the meandering channel belt of the deepwater depositional system. The predicted densities and thicknesses for the coarse-grained sandstone lenses of point bars were 1.8-1.9 g/cc and 15 m, respectively. In the same way, the quantitative estimates of predicted density and simulated thickness have shown a strong coefficient correlation (R2 > 0.80), which confirms the presence of gas-bearing prospects within the IVS. The facies-controlled migration is thought to be the movement of the reservoir facies of the point bars and channelled sandstone-filled lenses to the side.

Synovial 5-Lipoxygenase-Derived Oxylipins Define a Lympho-Myeloid-Enriched Synovium.

OBJECTIVE: Oxylipins are bioactive lipids derived from polyunsaturated fatty acids (PUFAs) that modulate inflammation and may remain overexpressed in refractory synovitis. In plasma, they could also be biomarkers of synovial pathology. The aim of this study is to determine if synovial oxylipins in inflamed joints correlate with plasma oxylipins and with synovial histologic patterns. METHODS: Patients with established rheumatoid or psoriatic arthritis with active disease despite treatment were recruited, and paired synovial tissue (ST) and plasma were collected. Oxylipins were determined by liquid chromatography with tandem mass spectrometry and were classified into groups according to their PUFA precursor and enzyme. The expression of CD20, CD68, CD3, and CD138 was obtained to describe synovial histology. Cell-specific expression of oxylipin-related genes was identified by examining available synovial single-cell RNA sequencing data. RESULTS: We included a total of 32 ST and 26 paired-plasma samples. A total of 71 oxylipins were identified in ST, but only 24 were identified in plasma. Only levels of 9,10-dihydroxyoctadecenoic acid and tetranor-Prostaglandin FM had a significant positive correlation between plasma and ST. Several oxylipins and oxylipin-related genes were differentially expressed among synovial phenotypes. Specifically, several 5-lipoxygenase (LOX)-derived oxylipins were statistically elevated in the lympho-myeloid phenotype and associated with B cell expression in rheumatoid arthritis samples. CONCLUSION: The lack of correlation between ST and plasma oxylipins suggests that ST lipid profiling better characterizes active pathways in treated joints. Synovial 5-LOX-derived oxylipins were highly expressed in lympho-myeloid-enriched synovium. Combination therapy with 5-LOX inhibitors to improve refractory inflammation may be needed in patients with this histologic group.

Seismic attributes and spectral decomposition-based inverted porosity-constrained simulations for appraisal of shallow-marine lower-Cretaceous sequences of Miano gas field, Southern Pakistan.

Seismic attributes can play an important role in the exploration of hydrocarbon-bearing stratigraphic systems. Incised valley systems are developed during the falling sea, which causes the deposition of coarse-grained sandstone facies inside the low-standing tracts (LST). These regional phenomena constrain the quantitative attributes of ultra-thin-bedded stratigraphic petroleum traps, e.g., vertical and lateral variations in the thickness, accommodation space, lithology, and porosity. This study deals with the application of the continuous wavelet transform (CWT) of a spectral decomposition (SD) tool on a 3D post-stack seismic volume of the Miano gas Field, Lower Indus basin, Pakistan. The results show that the CWT accurately detected the regionally faulted/fractured system and distinguished the frequency-dependent amplitude anomalies. The wedge model resolved a 24-meter-thick gas-bearing resource. Quality control analysis was carried out using CWT-based broadband processing between the designed amplitude spectrum of 17 Hz and 70 Hz. The reservoirs with over 25% porosity that were located within the shale-dominated facies with less than 8% porosity were imaged through the processing of the instantaneous spectral porosity model at the 48-Hz tuning block. Moreover, 190 to 165-m-thick thin-bedded sandstone reservoirs at a 25% porosity zone were resolved using 22-Hz and 28-Hz, which implicates the sea standstill and medium-to-coarse-grained depositional reservoir facies. The ultra-thin-bedded traps inside the laterally continuous stratigraphic lens of 121 m and the prograding clinoform lens of 101-m within the incised valley petroleum system were resolved using 48-Hz, which implicates the falling sea and fine-scaled transgressed erosional facies. These implications suggest that the identified regional stratigraphic traps have development potential for this gas field. The treatment of the inverted model at the highest frequencies can be utilized to investigate the porous stratigraphically trapped facies of LST and can serve as an important analogue for the leading gas field of the Indus Basin and similar basins.

Bisphosphonates are associated with reduced risk of colorectal cancer: a systematic review and meta-analysis.

BACKGROUND & AIMS: Colorectal cancer (CRC) is the third most common cancer worldwide. Several preclinical and observational studies have shown that bisphosphonates may have chemopreventive effects against CRC. We performed a systematic review and meta-analysis of all studies evaluating the effect of bisphosphonates on the risk of CRC. METHODS: We conducted a systematic search of Medline, Embase, and Web of Science through August 2012 and manually reviewed the literature. Studies were included if they met the following criteria: (1) evaluated and clearly defined exposure to bisphosphonates, (2) reported CRC outcomes, and (3) reported relative risks or odds ratio (OR) or provided sufficient data for their estimation. Summary OR estimates with 95% confidence intervals (CIs) were estimated using the random-effects model. Statistical heterogeneity was assessed with the Cochran's Q and I(2) statistic. RESULTS: We analyzed data from 6 population-based observational studies reporting 20,001 cases of CRC in 392,106 patients. A meta-analysis of these studies showed a statistically significant 17% reduction in CRC incidence with bisphosphonate use (unadjusted OR, 0.83; 95% CI, 0.76-0.90), with borderline heterogeneity across studies (Cochran's Q, P = .16; I(2) = 37%). This effect persisted after correcting for multiple covariates in individual studies (adjusted OR, 0.85; 95% CI, 0.74-0.98). When the analysis was restricted to women only, use of bisphosphonates was associated with a 16% reduction in CRC incidence, which bordered on statistical significance (n = 5 studies; adjusted OR, 0.84; 95% CI, 0.70-1.01). This chemopreventive effect of bisphosphonates was observed for proximal and distal colon cancers, as well as rectal cancer, independently. CONCLUSIONS: Based on meta-analysis, bisphosphonate use is associated with a modest, but statistically significant, reduction in CRC risk.

Statins are associated with reduced risk of esophageal cancer, particularly in patients with Barrett's esophagus: a systematic review and meta-analysis.

BACKGROUND & AIMS: The incidence of esophageal cancer is increasing in the United States, especially among patients with Barrett's esophagus (BE). Statins might prevent this cancer. We performed a systematic review with a meta-analysis of studies that evaluated the effect of statins on the risk of esophageal cancer. METHODS: We conducted a systematic search of Medline, Embase, and Web of Science through August 2012. Studies were included if they evaluated exposure to statins, reported the development of esophageal cancer, and reported relative risks or odds ratios (OR), or provided data for their estimation. Summary OR estimates with 95% confidence intervals (CI) were calculated using the random-effects model. The analysis included 13 studies (including a post hoc analysis of 22 randomized controlled trials) reporting 9285 cases of esophageal cancer among 1,132,969 patients. RESULTS: A meta-analysis of the studies showed a significant (28%) reduction in the risk of esophageal cancer among patients who took statins (adjusted OR, 0.72; 95% CI, 0.60-0.86), although there was considerable heterogeneity among studies. In analyzing a subset of patients known to have BE (5 studies, 312 esophageal adenocarcinomas [EAC] developed in 2125 patients), statins were associated with a significant (41%) decrease in the risk of EAC, after adjusting for potential confounders (adjusted OR, 0.59; 95% CI, 0.45-0.78) with consistent results among all studies. The number needed to treat with statins to prevent 1 case of EAC in patients with BE was 389. CONCLUSIONS: Based on meta-analysis of observational studies, statin use may be associated with lower risk of esophageal cancer, particularly risk of EAC in patients with BE.

Anti-diabetic medications and the risk of hepatocellular cancer: a systematic review and meta-analysis.

Several preclinical and observational studies have shown that anti-diabetic medications (ADMs) can modify the risk of hepatocellular cancer (HCC) in patients with diabetes mellitus (DM). We performed a systematic review and meta-analyses of studies evaluating the effect of metformin, thiazolidinediones (TZDs), sulfonylureas, and/or insulin on the risk of HCC. We conducted a systematic search of Medline, EMBASE, and Web of Science up to August 2012. Studies were included if they (1) evaluated and clearly defined exposure to metformin, TZDs, sulfonylureas, and/or insulin, (2) reported HCC outcomes in patients with DM, and (3) reported relative risks or odds ratio (OR) or provided data for their estimation. Summary OR estimates with 95% confidence intervals (CIs) were estimated using the random-effects model. Ten studies reporting 22,650 cases of HCC in 334,307 patients with type 2 DM were included in the analysis. Meta-analysis of observational studies showed a 50% reduction in HCC incidence with metformin use (n=8 studies; OR 0.50, 95% CI 0.34-0.73), 62% and 161% increase in HCC incidence with sulfonylurea (n=8 studies; OR 1.62, 95% CI 1.16-2.24) or insulin use (n=7; OR 2.61, 95% CI 1.46-4.65), respectively. TZDs did not modify the risk of HCC (n=4; OR 0.54, 95% CI 0.28-1.02). There was considerable heterogeneity across studies, which was partly explained by study setting, location, and whether the studies adjusted for the concomitant use of other ADMs. Post-hoc analysis of randomized controlled trials did not reveal any significant association between ADM use and risk of HCC. ADMs may modify the risk of HCC in patients with DM, especially in the Western population. However, the effect of each individual agent should be interpreted with caution owing to inherent cancer-modifying effect of the comparator group.

Anti-diabetic medications and risk of pancreatic cancer in patients with diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVES: Several preclinical and observational studies have shown that anti-diabetic medications (ADMs) may modify the risk of pancreatic cancer (PaC). We performed a systematic review and meta-analysis evaluating the effect of metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), and insulin on the risk of PaC in patients with diabetes mellitus (DM). METHODS: We conducted a systematic search of Medline, EMBASE, and Web of Science, up to June 2012, and published abstracts from major gastroenterology and oncology meetings from 2003 to 2012. Studies were included if they (1) evaluated and clearly defined exposure to metformin, SU, TZDs, and/or insulin, (2) reported PaC outcomes in patients with DM and (3) reported relative risks or odds ratio (OR) or provided data for their estimation. Summary OR estimates with 95% confidence intervals (CIs) were estimated using the random-effects model. RESULTS: Eleven studies (6 cohort, 3 case-control, and 2 randomized controlled trials (RCTs)) reported 1770 cases of PaC in 730,664 patients with DM. Meta-analysis of observational studies showed no significant association between metformin (n=9 studies; adjusted OR 0.76, 95% CI 0.57-1.03, P=0.073), insulin (n=7 studies; adjusted OR 1.59, 95% CI 0.85-2.96, P=0.144), or TZD (n=4 studies; adjusted OR 1.02, 95% CI 0.81-1.30, P=0.844) use and risk of developing PaC. Use of SU was associated with a 70% increase in the odds of PaC (n=8 studies; adjusted OR 1.70, 95% CI 1.27-2.28, P<0.001). There was considerable inherent heterogeneity between studies not explained by study design, setting, or comparator drug and is likely related to confounding by indication and reverse causality. The pooled analyses of the two RCTs were underpowered and provided non-significant results with wide, non-informative 95% CIs. CONCLUSIONS: Although SU seems to be associated with increased risk of PaC, meta-analysis of existing studies does not support a protective or harmful association between ADM use and risk of PaC in patients with DM. There was considerable heterogeneity across studies, and future, well-designed, prospective studies would be required to understand this association better.

Postnatal outcome of congenital anomalies in low resource setting.

OBJECTIVE: This study aimed to determine the postnatal outcome of congenital malformations in a tertiary care hospital of India. MATERIAL AND METHODS: This was a prospective study of all women with prenatally detected major congenital malformations. Postnatal follow-up of live born babies was carried out for 1 year. RESULTS: There were 574 cases with major congenital anomalies, 523 of which were fully followed. Only 69 women (13.6%) had the initial scan before 20 weeks of gestation. Craniospinal defects were the most common (42.7%), followed by genitourinary anomalies (28%). There was no live birth in cases such as anencephaly, iniencephaly, bilateral renal agenesis, gastroschisis, and cystic hygroma. Survival at 1 year was less than 25% in spina bifida, bilateral cystic kidneys, complex cardiac disease, and non-immune hydrops fetalis. In cases with mild hydrocephalus or unilateral and mild renal disease, the survival was over 75%. CONCLUSION: In India, the majority of congenital anomalies present late in gestation. Although fetal outcome is invariably poor for severe defects, existing legislation in the country leaves pregnancy continuation as the only option.

Zeta-associated protein 70 expression in chronic lymphocytic leukemia: Relevance in Indian context.

Background: Chronic lymphocytic leukemia (CLL) is prognosticated using the Rai and the Binet's staging. In the past few years, new parameters have been considered for prognostication. One such marker that has been a subject of speculation and found useful by some western studies is zeta-associated protein 70 (ZAP-70). Aim: To investigate the prevalence of ZAP-70 and find out its association with other prognostic markers like Rai and Binet's stage and CD38 in Indian CLL patients. Materials and Methods: Twenty-nine newly diagnosed cases of CLL were selected over 1 year. Immunophenotyping was done and expression of CD38 and ZAP-70 was evaluated on gated CLL cells. Statistical Analysis: Qualitative data were expressed as frequency and percentage. Differences between groups were evaluated using Student's t-test for quantitative data and Chi-square test/Fisher's exact t-test for qualitative variables. A P value less than 0.05 was considered significant. Results and Conclusion: We found a lower prevalence rate of ZAP-70 (2/29, 6.89%) with no association with any of the conventional poor prognostic factors. A large number of our CLL patients fall into the good prognostic group (22/29, ZAP 70-/CD38-) with a least number in the poor prognostic group (2/29, ZAP-70 + CD38+). Also, no association was found between ZAP-70 and CD38. The findings of the present study suggest that the majority of CLL patients in India have a good prognosis, may not require treatment, and have good overall survival. Geographical variations, genetic makeup, and natural history of the CLL could be the cause of such differences from western literature.