Cost-Effectiveness of PHMB & betaine wound bed preparation compared with standard care in venous leg ulcers: A cost-utility analysis in the United Kingdom.

BACKGROUND: Wounds cost £8.3 billion per year in the United Kingdom (UK) annually. Venous leg ulcers (VLUs) account for 15% of wounds and can be complicated to heal, increasing nurse visits and resource costs. Recent wound bed preparation consensus recommends wound cleansing and biofilm disrupting agents. However, inert cleansers such as tap water or saline are inexpensive, an evaluation of evidence is required to justify the higher upfront costs of treatment with active cleansers. We undertook a cost-effectiveness analysis of the use of a biofilm disrupting and cleansing solution and gel, Prontosan® Solution and Gel X, (PSGX) (B Braun Medical), as compared to the standard practice of using saline solution, for treating VLUs. METHODS: A Markov model was parameterised to one-year costs and health-related quality of life consequences of treating chronic VLUs with PSGX versus saline solution. Costs are viewed from a UK healthcare payer perspective, include routine care and management of complications. A systematic literature search was performed to inform the clinical parameters of the economic model. Deterministic univariate sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) were undertaken. RESULTS: For PSGX an Incremental Net Monetary Benefit (INMB) of £1,129.65 to £1,042.39 per patient (with a Maximum Willingness to Pay of £30k and £20k per QALY respectively), of which cost savings are £867.87 and 0.0087 quality-adjusted life years (QALYs) gain per patient. PSA indicates a 99.3% probability of PSGX being cost-effective over saline. CONCLUSIONS: PSGX for the treatment of VLUs is dominant compared with saline solution in the UK with expected cost-savings within a year and improved patient outcomes.

Influence of basin-wide geomorphology on arsenic distribution in Nadia district.

The present study depicts the geospatial relation between basinal geomorphology and heterogeneous arsenic (As) distribution in the Bengal Delta Plain (BDP). The distribution pattern largely varies throughout the study area (higher: Karimpur-II AsT average 214.73 µgL-1; lower: Tehatta AsT average 27.84 µgL-1). Both safe (low As) and unsafe (high As) areas are identified within the single shallow aquifer (<50 m), where they are in close vicinity. Statistical analysis shows that Padma river basin is the most contaminated (AsT avg. 214.7 ± 160 µgL-1) and Churni-Ichhamati river basin (AsT avg. 108.54 ± 89.43 µgL-1) is the least contaminated with groundwater As. Moreover, the role of geomorphological features influencing the geospatial distribution of As has been studied and meandering features are found to correlate with high As wells (r2 = 0.52), whereas, natural levees are correlated with safer wells (r2 = 0.57). In the meandering features, the deposition of sedimentary organic matter (SOM) facilitates the reduction of As bearing Fe(III) oxy-hydroxides and subsequent higher As mobilization. In natural levees, surface derived labile organic matter (DOC and FOM, Fresh Organic Matter) from different land-use patterns (Habitation, degraded waterbodies, cattle dwelling, sanitation, etc.) is transported to shallow aquifers (notably protein rich leakage sewage). The fresh organic carbon transported to the shallow aquifers, thereby triggering As release by microbe-mediated reductive dissolution of hydrated Fe(III)-oxides (HFO). Iron reduction (mostly amorphous) is playing an important role in the release of As depending on basin-wise sedimentation pattern, local recharge, accumulation of silt/clay/micas at the top with corresponding reactive oxidation of organic carbon. These are important components and often helping the cyclic water-rock interaction of As causing such heterogeneous geospatial distribution. The delineation of aquifer with regard to safer and unsafe areas would immensely help to supply safe drinking water to the rural community.

Naringin and Sertraline Ameliorate Doxorubicin-Induced Behavioral Deficits Through Modulation of Serotonin Level and Mitochondrial Complexes Protection Pathway in Rat Hippocampus.

The present study was designed to investigate the neuroprotective effect of naringin (NR) alone as well as its combination with sertraline (SRT) against doxorubicin (DOX)-induced neurobehavioral and neurochemical anomalies. DOX (15 mg/kg; i.p.) administration caused behavioral alterations, oxidative stress, neuroinflammation, mitochondrial dysfunction and monoamines alteration in male Wistar rats. NR (50 and 100 mg/kg; i.p.) and SRT (5 mg/kg; i.p.) treatment significantly attenuated DOX-induced anxiety and depressive-like behavior as evident from elevated plus maze (EPM) and modified forced swimming test (mFST), respectively. NR treatment significantly attenuated DOX-induced raised plasma corticosterone (CORT), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) levels in the hippocampus (HC). Furthermore, we found that combination of NR and SRT regimen ameliorated DOX-induced behavioral anomalies through modulation of the 5-HT level and mitochondrial complexes protection pathway along with alleviation of oxidative stress in the HC region. Therefore, NR treatment alone or in combination with SRT could be beneficial against DOX-induced neurotoxicity.

Ameliorative effect of naringin in acetaminophen-induced hepatic and renal toxicity in laboratory rats: role of FXR and KIM-1.

CONTEXT: Acetaminophen (APAP) is an analgesic and antipyretic agent commonly known agent to cause hepatic and renal toxicity at a higher dose. Naringin, a bioflavonoid possesses multiple pharmacological properties such as antioxidant, anti-inflammatory, analgesic and anti-hyperlipidemic activity. OBJECTIVE: To evaluate the effect of naringin against the APAP-induced hepatic and renal toxicity. MATERIALS AND METHODS: Male Wistar albino rats (180-220 g) were divided into various groups, and toxicity was induced by APAP (700 mg/kg, p.o., 14 days). Naringin (20, 40 and 80 mg/kg, p.o.) or Silymarin (25 mg/kg) was administered to rats 2 h before APAP oral administration. Various biochemical, molecular and histopathological parameter were accessed in hepatic and renal tissue. RESULTS: Naringin pretreatment significantly decreased (p < 0.05) serum creatinine, blood urea nitrogen, bilirubin, aspartate transaminase, alanine transaminase, lactate dehydrogenase, low-density lipoprotein, very low-density lipoprotein, cholesterol and triglycerides as compared with APAP control rats. Decreased level of serum albumin, uric acid, and high-density lipoprotein were also significantly restored (p < 0.05) by naringin pretreatment. It also significantly restores (p < 0.05) the altered level of superoxide dismutase, reduced glutathione, malondialdehyde and nitric oxide in hepatic and renal tissue. Moreover, altered mRNA expression of hepatic farnesoid X receptor and renal injury molecule-1 (KIM-1) were significantly restored (p < 0.05) by naringin treatment. Naringin treatment also reduced histological alteration induced by APAP in the liver and kidney. CONCLUSION: Naringin exerts its hepato- and nephroprotective effect via modulation of oxido-nitrosative stress, FXR and KIM-1 mRNA expression.

Ameliorative effect of berberine against gentamicin-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction.

BACKGROUND: Gentamicin (GM) is the commonly used antibiotics against Gram-negative infection, but the nephrotoxic potential of drug limit its clinical interest. The aim of this study was to investigate the protective effect of berberine (BER) against GM-induced nephrotoxicity and possible underlying mechanisms. MATERIAL AND METHODS: The rats were divided into various group, namely normal, GM-control, GM + BER (10, 20, and 40 mg/kg). Nephrotoxicity was induced by intraperitoneal administration of GM (120 mg/kg) for 7 consecutive days. BER (10, 20, and 40 mg/kg; p.o.) was also administered for the 7 days. Various biochemical, molecular, and histological parameters were assessed in serum and kidney. RESULTS: GM-administration significantly increased (p < 0.001) the serum creatinine and blood urea nitrogen (BUN) as well as renal malonaldehyde (MDA), nitric oxide (NO) along with Kidney Injury Molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), and nuclear factor-kappa B (NF-KB) renal mRNA expressions. In addition, GM also significantly decreased (p < 0.001) the renal superoxide dismutase (SOD), reduced glutathione (GSH), B-cell lymphoma 2 (Bcl-2) mRNA expression, and mitochondrial enzymes (NADH dehydrogenase and cytochrome c oxidase) activities. Rats treated with BER (20 and 40 mg/kg; p.o.) significantly and dose-dependently (p < 0.05 and p < 0.01) restore the altered levels of antioxidant, inflammatory, apoptosis, AKI markers as well as depleted mitochondrial enzymes. Histopathological abbreviations were also ameliorated by BER administration. CONCLUSION: Berberine exerts renoprotective effects through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.[Formula: see text].

Ameliorative effect of naringin against doxorubicin-induced acute cardiac toxicity in rats.

CONTEXT: Doxorubicin (Dox) is one of the most active chemotherapeutic agents used to treat various types of cancers. Its clinical utility is compromised due to fatal cardiac toxicity characterized by an irreversible cardiomyopathy. OBJECTIVE: This study evaluates the cardioprotective potential of naringin (NR) against Dox-induced acute cardiac toxicity in rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into five groups. NR (50 and 100 mg/kg) was administered intraperitoneally (i.p.) daily from 0 to 14 d. Doxorubicin (15 mg/kg, i.p.) was given as a single dose on the 10th day. On the 14th day, all animals were sacrificed and oxidative stress parameters that include malondialdehyde (MDA), glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) activities, and all mitochondrial complexes (I-IV) activities were evaluated along with histopathological studies of the heart. RESULTS: Doxorubicin-induced cardiotoxicity was confirmed by increased (p < 0.05) MDA, decreased (p < 0.05) GSH levels, SOD, and CAT activities, mitochondrial complexes (I-IV) activities in the heart tissue. NR (100 mg/kg) showed cardioprotection as evident from significant decreased MDA (p < 0.001) level, raised (p < 0.001) GSH level, SOD and CAT activities and increased mitochondrial complexes I (p < 0.01), II (p < 0.001), III (p < 0.001), and IV (p < 0.05) activities. Further, Dox-induced cardiotoxicity was confirmed by histopathological studies. These obtained results indicated the protective role of NR against Dox-induced cardiac toxicity in rats. CONCLUSION: NR can be used in combination with Dox due to its high cardioprotective effect against Dox-induced cardiomyopathy.

Hesperidin, a flavanoglycone attenuates experimental diabetic neuropathy via modulation of cellular and biochemical marker to improve nerve functions.

AIM: Diabetic neuropathy (DN) is one of the most common long-term complications of diabetes mellitus and clinically can be characterized by an elevated nociceptive response with electrophysiological conduction abnormalities. The present investigation was designed to evaluate the neuroprotective effect of hesperidin against STZ induced diabetic neuropathic pain in laboratory rats. MATERIALS AND METHODS: DN was induced in Sprague-Dawley rats (150-200 g) by intraperitoneal administration of streptozotocin (STZ) (55 mg/kg, p.o.). Rats were divided into various groups, namely, STZ control (vehicle), hesperidin (25, 50, and 100 mg/kg, p.o.), insulin (10 IU/kg, s.c.), and combination of hesperidin (100 mg/kg, p.o.) with insulin (10 IU/kg, s.c.) for 4 weeks. Various behavioral (allodynia and hyperalgesia), biochemical parameters [oxido-nitosative stress, Na-K-ATPase, aldose reductase (AR)], and molecular changes (TNF-α and IL-1ß) along with hemodynamic changes were determined. RESULTS: Rats treated with hesperidin (50 and 100 mg/kg, p.o., 4 weeks) significantly reduced (p < 0.05) hyperglycemia and its metabolic abnormalities induced by intraperitoneal administration of STZ. The decreased nociceptive threshold, motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV), serum insulin as well as Na-K-ATPase activity were significantly increase (p < 0.05) by hesperidin (50 and 100 mg/kg, p.o.) treatment. It significantly attenuated (p < 0.05) elevated glycated hemoglobin, AR activity, oxido-nitrosative stress, neural calcium, and pro-inflammatory cytokines (TNF-α and IL-1ß) levels. Histological aberration induced after STZ administration was restored by administration of hesperidin (50 and 100 mg/kg, p.o.) CONCLUSION: In combination with insulin, hesperidin not only attenuated the diabetic condition but also reversed neuropathic pain via control over hyperglycemia as well as hyperlipidemia to down-regulate generation of free radical, release of pro-inflammatory cytokines as well as elevation in membrane bound enzyme.

Environmental impact of e-waste management in Indian microscale informal sectors.

Inappropriate e-waste processing in the informal sector is a serious issue in developing countries. Field investigations in microscale informal recycling sites have been performed to study the impact of hazardous metal(loid)s (released from e-waste dismantling) on the environment (water and soil). Eight hazardous metal(loid)s (Pb, Cd, Cu, Zn, As, Hg, Ni, and Cr) were primarily found in the monitored water and soil samples (Sangrampur, West Bengal) because of widespread informal e-waste handling and primitive processing. Elevated concentrations of Cd, Pb, As, Cu, and Cr were observed in pond water samples (0.04, 1.62, 0.03, 1.40, 1.74 mg/L respectively). These ponds, which are regularly used for e-waste handling/dismantling, are usually flooded during the monsoon season mixing with further larger water resources - posing a serious threat to public health. Enriched levels of Pb, Cd, Cu, and Zn were detected in collected soil samples, both top surface soil (Pb up to 2042.27 ± 206.80, Cd up to 25.90 ± 9.53, Cu up to 6967.30 ± 711.70, and Zn up to 657.10 ± 67.05 mg/Kg) and deeper subsurface soil (Pb, 419.70 ± 44.70; Cd, 18.34 ± 3.81; Cu, 3928.60 ± 356.40; and Zn, 134.40 ± 33.40 mg/Kg), compared to the levels of As, Hg, Ni, and Cr. Seasonal variation of soil metal(loid) content indicated that higher levels of most of the metal(loids) were detected in the pre-monsoon (Nov-May) season, possibly due to the monsoonal dilution effect, except for Pb and Cd. The results highlighted that the composition and the handling of e-waste were important factors affecting the metal(loid) concentrations. E-waste policy and legislation have great influence on the handling and disposal procedures. An improved e-waste management practice has been proposed to encourage eco-friendly and safe e-waste disposal. It is recommended that regulatory agencies and manufacturers should create a road map to convince the informal sector to develop a systematic approach towards a more standardized formal e-waste management practices at the microscale field level.

Evaluation of ameliorative effect of quercetin in experimental model of alcoholic neuropathy in rats.

OBJECTIVE: The objective of the present investigation was to study the neuroprotective effect of the quercetin in alcohol induced neuropathy in rats. MATERIALS AND METHODS: Male Wistar rats were administered alcohol (10 gm/kg, 35% v/v, p.o. b.i.d.) for 10 weeks. Alpha tocopherol (vitamin E) was used as a standard drug. Vitamin E (100 mg/kg) and quercetin (10, 20 and 40 mg/kg) were co-administered 1 h after ethanol administration for 10 weeks. Behavioral assessment parameters, such as motor incoordination, tactile allodynia, mechanical and thermal hyperalgesia were recorded in all groups of animals. Meanwhile, motor nerve conduction velocity was also recorded. Biochemical parameters, such as nitric oxide (NO), Na(+)-K(+)-ATPase, malondialdehyde (MDA) and myeloperoxidase (MPO) were estimated in sciatic nerve. Apoptosis index was determined with help of DNA fragmentation in sciatic nerve. RESULTS AND DISCUSSION: Chronic ethanol administration for 10 weeks resulted in significant (P < 0.001) development of neuropathic pain. Chronic treatment with quercetin (20 and 40 mg/kg) for 10 weeks significantly (P < 0.001) attenuated allodynia, hyperalgesia as well as motor coordination and impaired nerve conduction velocity along with decreased level of membrane-bound Na(+)-K(+)-ATPase. It also significantly (P < 0.001) decreased elevated levels of MDA, MPO as well as pro-inflammatory mediators, such as NO. It also decreased the extent of DNA fragmentation. This alteration was more significant in vitamin E treated rats (100 mg/kg). Quercetin is a proven antioxidant that might have decreased the oxidative stress produced by chronic alcoholism. CONCLUSION: The present investigation elucidates neuroprotective effect of quercetin in alcohol induced neuropathy through modulation of membrane-bound inorganic phosphate enzyme and inhibition of release of oxido-inflammatory mediators, such as MDA, MPO and NO.

Reduced ulcerogenic potential and antiarthritic effect of chitosan-naproxen sodium complexes.

The purpose of this research was to address the utility of naproxen sodium-chitosan spray-dried complexes for antiulcer and antiarthritic activities. The cold stress technique was used to examine the ulcerogenic potential of naproxen sodium (NPX) and spray-dried formulations in the different doses. The ulcerations reduced with the dose of spray-dried complexes of naproxen sodium and chitosan. The conspicuous hemorrhagic lesions were visible in the morphological features of the animal treated with naproxen 50 mg/kg (p.o.). Thus, the results suggest that the spray-dried naproxen sodium-chitosan complex (NPXF) was not corrosive to the gastric mucosa at high doses of 50, 100, and 200 mg/kg (p.o.) under stressful conditions. It is evident from the present investigation that NPXF does not possess any ulcerogenic potential in comparison to naproxen which, under stressful conditions, led to the hypersecretion of HCl, culminating to petichial hemorrhages in the gastric mucosa of the animals. The biphasic pattern was observed in the various arthritic parameters. The rise in paw volume, joint diameter, WBC count, arthritis score, and fall in body weight was significantly ameliorated in the animals treated with NPXF (5, 10, and 20 mg/kg, p.o). At the end of the study, slight erythema was visible in the naproxen-treated animals. However, no erythema, redness, or ulcers were visible in the animals treated with NPXF. Thus, the direct compression properties and reduced ulcerogenic activity, combined with the demonstrated solubilizing power and analgesic effect enhancer ability toward the drug, make naproxen sodium-chitosan spray-dried complexes particularly suitable for developing a reduced-dose, fast-release, solid oral dosage form of naproxen.

Risk factors and outcomes associated with diabetes mellitus in COVID-19 patients: a meta-analytic synthesis of observational studies.

Purpose: We carried out a meta-analytic synthesis to evaluate the association between diabetes mellitus (DM) and related clinical outcomes, co-morbidities, their risk factors and resource utilization in patients with COVID-19. Methods: The MEDLINE and Web of Science databases were reviewed for identification of eligible studies. Meta-analysis was carried out using Review Manager 5.3. The random- effects model was used to compute the pooled estimates of odds ratio (OR)/mean difference and 95% confidence interval (CI). Results: A total of 14 studies including 3,644 individuals without DM and 1,428 with DM were included in the meta-analysis. Cardiovascular diseases (CVDs) [OR 2.91, 95% CI 2.34, 3.63], hypertension [OR 2.19, 95% CI 1.39, 3.46], acute kidney injury (AKI) [OR 3.59, 95% CI 1.46, 8.84], cerebrovascular disease [OR 2.09, 95% CI 1.22, 3.61], and acute respiratory distress syndrome (ARDS) [OR 3.40, 95% CI 2.09, 5.55] were significantly associated with DM in COVID-19 patients compared with non-DM patients (p < 0.05 for all instances). Mortality was significantly higher among COVID-19 patients with DM [OR 2.46, 95% CI 1.68, 3.58]. Intensive Care Unit (ICU) admission and use of mechanical ventilation were significantly associated with COVID-19 patients with DM [OR 2.79, 95% CI 1.79, 4.34], and [OR 3.33, 95% CI 2.05, 5.42], respectively. No significant difference was observed in the length of stay (LOS) and hospitalization. Conclusions: This meta-analysis shows that CVDs, hypertension, AKI, cerebrovascular disease, and ARDS are significantly higher among DM patients with COVID-19 compared with non-DM patients. Mortality, ICU admission and the use of mechanical ventilation were significantly associated with COVID-19 patients with DM. Further long-term, multinational and large sample size clinical studies are warranted to justify the current findings.

Efficacy and safety of neural stem cell therapy for spinal cord injury: A systematic literature review.

AIMS: To summarize the evidence on the efficacy and safety of neural stem cell therapy (NSCT) for the treatment of spinal cord injury (SCI). METHODS: A systematic literature review of Medline®, EMBASE® and Cochrane library was performed to identify studies reporting efficacy and safety of NSCT in SCI. Articles were included if they reported efficacy and safety data of SCI patients who received NSCT. RESULTS: Overall, four studies of the 277 records met all the study eligibility criteria. Over the 1-year follow-up period, motor scores were significantly higher among patients who received NSCT compared with those who did not (American Spinal Injury Association [ASIA] motor scores (mean±standard deviation [SD]): 7.9±1.2 versus 3.9±0.6; upper extremity motor score: 7.8±2.1 versus 3.9±0.6, both P<0.05). Sensory scores (pinprick score: 4.8±1.3 versus 2.9±0.6; P=0.5; light touch score: 6.9±3.1 versus 2.3±0.5, P=0.3), ASIA impairment scale (26% versus 7%) or pain score (baseline: 2.4±0.6; 1-year: 3.4±0.4) were comparable in both NSCT and non-NSCT cohorts. Over the 1-year follow-up period, the graded redefined assessment of strength, sensibility, and prehension and international standards for neurological classification of SCI scores showed a mean improvement of 14.8 and 17.8 points respectively. Overall, treatment with NSCT showed favorable safety and tolerability profile. CONCLUSIONS: Due to the limited and poor-quality evidence, it is too early to make robust conclusions on the efficacy of NSCT in the treatment of SCI. However, based on the included studies, NSCT seems to be a potential option worth exploring among patients with SCI. Nonetheless, prospective, randomized trials in larger cohorts are needed to validate the efficacy and safety of NSCT in the treatment of SCI.

Health-related quality of life and sleep quality among North Indian type 2 diabetes mellitus patients: evidence from a cross-sectional study.

OBJECTIVE: The objective of this study is to measure the relationship between sleep quality and health-related quality of life (HRQOL), in Indian population with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study, included a total of 300 patients with T2DM. All participants were responding to the Pittsburgh Sleep Quality Index (PSQI) and European Quality of Life-5 Dimensions Questionnaire (EQ-5D). A PSQI global score ≥5 was defined as poor sleep quality. EQ-5D visual analogue scale (VAS), determining the overall health status. Logistic regression analysis was used to examine the association between PSQI and EQ-5D. All the study data were analysed using the SPSS software version 20.0. Values of p < 0.05 were considered statistically significant. RESULTS: The mean age of included participants were 55.29. Majority of the participants (55.3%) were identified as "poor sleepers" and female (31.3%) contributing higher proportion. Poor sleepers had significantly lower the HRQoL (p < 0.001). After adjustment, poor sleep quality was significantly associated with a lower HRQoL; EQ-5D index (OR = 1.080, 95%, CI: 1.015-1.148, p < 0.05), and EQ-5D VAS (OR = 1.092, 95%, CI: 1.021-1.176, p < 0.01). Overall, the EQ-5D index and EQ-5D VAS were found to be an independent predictors of sleep quality. CONCLUSIONS: Poor sleep quality is prevalent in Indian T2DM population, and it imparts negative impact on several dimensions of EQ-5D that characterising the daily activities performance. Therefore, further real-world studies are needed to determine the causal relationship between T2DM patients and measure of objective sleep and their impact on health.

Systematic evidence of health economic evaluation of drugs for postmenopausal osteoporosis: A quality appraisal.

This paper systematically and critically reviewed all published economic evaluations of drugs for the treatment of postmenopausal osteoporosis. A systematic search was conducted using relevant databases for economic evaluations to include all relevant English articles published between January 2008 to January 2020. After extracting the key study characteristics, methods and outcomes, we evaluated each article using the Quality of Health Economic Studies (QHES) and the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) instruments. A total of 49 studies met the inclusion criteria. Majority of studies were funded by the industry and reported favorable cost-effectiveness. Based on the QHES total scores, studies (n = 35) were found to be industry-funded with higher QHES mean 82.44 ± 8.69 as compared with nonindustry funding studies (n = 11) with mean 72.22 ± 17.67. The overall mean QHES scores were found to be higher 79.06 ± 11.84, representing high quality (75-100) compared to CHEERS scores (%) 75.03 ± 11.21. The statistical pairwise comparison between CHEERS mean (75.03 ± 11.21) and QHES mean (79.06 ± 11.84) were not statistically significant (P = 0.10) whereas, QHES score showed higher means as compared to CHEERS. This study suggests the overall quality of the published literatures was relatively few high-quality health economic evaluation demonstrating the cost-effectiveness of drugs for postmenopausal osteoporosis, and the majority of the literature highlights that methodological shortcoming.

Periostin as a novel biomarker of cardiovascular disease: A systematic evidence landscape of preclinical and clinical studies.

BACKGROUND: Periostin is a matricellular protein, expressed in various normal adult and fetal tissues. Recently, elevated periostin levels have been reported in heart failure, coronary artery disease, and stroke. However, there is lack of clinical studies to clarify the prognostic significance of systemic periostin levels in cardiovascular diseases (CVDs). The aim of the study was to perform a systematic review of published evidence on periostin and CVDs, and to clarify the diagnostic and prognostic significance of systemic periostin levels in CVDs. METHODS: A systematic search on PubMed was performed to identify relevant articles from inception to December 2018. The eligible studies evaluating the periostin expression and periostin levels in animal and human studies. RESULTS: A total of 24 relevant studies, including both animal and human data, were included. Periostin is significantly observed in myocardium tissue of failing hearts compared with control, and is also expressed in atherosclerotic plaques. Systemic periostin levels were significantly correlated with cardiac function and severity of CVD in several studies. A clinical study also observed positive correlation between periostin and N-terminal pro b-type natriuretic peptide (NT-proBNP), highly sensitive troponin (hsTnT), and ST2 cardiac biomarker. Studies reported limited adjustment for potential confounders. CONCLUSIONS: The evidence of current review support potential role of periostin in the pathophysiology of CVD. However, scarcity of data regarding the clinical use of periostin levels in the current management of CVDs further creates room for the future investigation. Therefore, further studies warrant to clarify its potential role, if any, as a novel cardiac biomarker.

Sodium-glucose cotransporter 2 inhibitors and fracture risk in patients with type 2 diabetes mellitus: A systematic literature review and Bayesian network meta-analysis of randomized controlled trials.

AIM: To perform a systematic literature review and network meta-analysis (NMA) of randomized controlled trials (RCTs) to estimate effect of SGLT2 inhibitors on fracture risk in patients with T2DM. METHODS: A systematic search was performed on PubMed/Medline and ClinicalTrials.gov from inception to May 2018 to identify RCTs reporting fracture events with the use of SGLT2 inhibitors compared to control group in patients with T2DM. NMA within a Bayesian framework was performed to calculate the odds ratio (OR) and 95% credible intervals (CrI) using random effect model. Node splitting method was applied to evaluate the presence of inconsistency for NMA. RESULTS: A total of 40 RCTs including 32,343 T2DM patients with 466 fracture cases. Pairwise meta-analysis showed no association between risk of fracture and SGLT2 inhibitors use (OR = 1.01, 95%CI 0.83-1.23; p = 0.91; I2 = 27%) compared with the control group. The NMA has shown a non-significant association with fracture risk and canagliflozin (OR = 0.57, 95%CrI 0.12-1.90), dapagliflozin (OR = 0.58, 95%CrI 0.13-2.00), and empagliflozin (OR = 0.78, 95%CrI 0.23-2.80) use when compared to placebo. No association was also found among SGLT-2 inhibitors (canagliflozin OR = 2.6, 95%CrI 0.69-16.00; dapagliflozin OR = 2.6, 95%CrI 0.52-22.00; and empagliflozin OR = 3.7, 95% CrI 1.0-27.00), when compared to active treatment. Node-splitting analysis shows non-significant inconsistency between direct and indirect comparisons. CONCLUSION: The current NMA result suggests no detrimental effect of SGLT2 inhibitors on fracture risk in patients with T2DM. Further RCTs and real-world studies with long-term follow up are required to confirm the present findings.

Effect of anti-diabetic drugs on bone metabolism: Evidence from preclinical and clinical studies.

Diabetes mellitus is associated with abnormal bone health and an increased risk of fracture even though patients have normal or higher BMD. The mechanisms behind diabetes mellitus- induced various skeletal disorders remain unclear. Anti-diabetic drugs may have negative or positive impact on bone metabolism. For instance, thiazolidinediones increases the bone loss and risk of fracture possibly through PPARγ activation in bone marrow cells and hamper osteoblastogenesis via decreasing Runx2 transcription factor, IGF-1 and Wnt signalling pathways. In contrast, metformin and sulfonylureas have a neutral or positive effect on bone health and reduced risk of fracture. Results from the preclinical and clinical studies convey conflicting findings over insulin safety profile on bone health. Incretin-based therapy (GLP-1 receptor agonist and DPP-4 inhibitors) and SGLT2 inhibitors are currently marketed anti- diabetic drugs. While evidence from animal studies suggest that incretin-based therapy have anabolic effect on bone, limited clinical data of DPP-4 inhibitors and GLP-1 receptor agonist indicated a neutral effect on the bone health and risk of fracture. SGLT2 inhibitors may cause bone loss or increase fracture risk due to altered calcium, phosphate and sodium concentration. Therefore, safety concerns of anti-diabetic drugs are crucial for the management of diabetes mellitus. In this review, analysis of the available evidence for effect of anti-diabetic drugs on the bone metabolism and fracture risk in diabetes mellitus is described.

Sodium arsenite-induced myocardial bruise in rats: Ameliorative effect of naringin via TGF-ß/Smad and Nrf/HO pathways.

BACKGROUND: Arsenic poisoning is a serious medical condition caused by consumption of contaminated food and water. Cardiovascular toxicity is one of the important risk factors associated with arsenic toxicity. AIM: To elucidate efficacy and possible mechanism of action of naringin in arsenic-induced cardiac toxicity in laboratory rats. MATERIALS AND METHODS: Arsenic toxicity was induced in Sprague-Dawley rats by sodium arsenite (5 mg/kg, p.o., 28 days). Rats were either concomitantly treated with vehicle (5 mL/kg, p.o.) or naringin (20, 40 and 80 mg/kg, p.o.) for 28 days. Chronic administration of sodium arsenite caused significant alterations in electrocardiographic, hemodynamic and left ventricle contractile functions. RESULTS: Treatment with naringin (40 and 80 mg/kg, p.o.) significantly restored (p < 0.05) these altered myocardial functions. Administration of naringin (40 and 80 mg/kg, p.o.) significantly inhibited (p < 0.05) arsenite-induced increased cardiac markers (LDH, CK-MB, AST, ALT, and ALP) and altered lipid metabolism (total cholesterol, triglyceride, LDL, HDL, and VLDL). The elevated level of heart oxido-nitrosative stress and decreased cardiac Na-K-ATPase level after arsenite administration was significantly attenuated (p < 0.05) by naringin (40 and 80 mg/kg, p.o.) treatment. Naringin also significantly increased (p < 0.05) myocardial mitochondrial enzymes (I-IV) activity. Arsenite-induced alteration in heart Nrf-2, HO-1, Smad-3, and TGF-ß mRNA expression were significantly restored (p < 0.05) by naringin (40 and 80 mg/kg) treatment. Treatment with naringin (40 and 80 mg/kg) significantly inhibited (p < 0.05) arsenite-induce apoptosis revealed by flow cytometric analysis. Naringin administration reduced histopathological aberrations (measured using transmission electron microscopy) induced by sodium arsenite. CONCLUSION: The results of present investigation suggest that naringin ameliorates arsenite-induced cardiotoxicity via modulation of TGF-ß/Smad-3 and Nrf-2/HO-1 pathways along with a reduction in myocardial apoptosis.

Efficacy of antioxidant in idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

Idiopathic pulmonary fibrosis (IPF) is a chronic oxido-inflammatory disorder of the lung. Oxidative stress is widely recognized as a central feature of IPF. Antioxidant therapy has been proposed as an effective treatment for IPF. An array of clinical trials describing the therapeutic impact of these drugs have been reporting albeit with conflicting evidence points. We performed a meta-analysis of trials in which efficacy of antioxidant therapy was compared with control in IPF. Systematic literature search was conducted in PubMed, EMBASE, the Cochrane Library, CPCI-S (Conference Proceedings Citation Index-Science), ICTRP (International Clinical Trials Registry Platform), and Google Scholar till June 2016 by two independent researchers. Various outcomes such as changes in pulmonary function tests (change in vital capacity [ΔVC], change in forced vital capacity [ΔFVC], change in percentage of predicted vital capacity [Δ%VC], and change in percentage of predicted carbon monoxide diffusing capacity [Δ%DLco]), changes in 6 minutes walking test distance (Δ6MWT), rates of adverse events, and rates of death, were included. All statistical analyses were performed using RevMan V.5.3. Twelve studies (n = 1062) were identified that used antioxidants (N-acetylcysteine and lecithinized superoxide dismutase) as a treatment for IPF. Overall, there was no association of antioxidant therapy with ΔFVC (SMD = 0.27, 95% CI:-0.07 to 0.61; P = 0.12), ΔFVC (%) (SMD = -0.10, 95% CI:-0.56 to 0.36; P = 0.66) and 6MWT (SMD = -0.04, 95% CI:-0.11 to 0.20; P = 0.59) in IPF patients. However, combined antioxidant therapy was found to be associated with %VC (SMD = 0.37, 95% CI: 0.09 to 0.64; P = 0.008) and Δ%DLco (SMD = 0.15, 95% CI: 0.00 to 0.29; P = 0.05) in IPF patients. Strong evidence was obtained that the antioxidants increased adverse effects adverse events (OR = 1.56, 95% CI: 0.75 to 3.24; P = 0.23) but it did not associate mortality (OR = 0.96, 95% CI: 0.44 to 2.11; P = 0.92). The use of significant clinical heterogeneity, low statistical power, high dropout rates, duration of follow-ups, and dosing regimens of antioxidant agents. Combined antioxidant therapy seems to be a safe and effective therapy for IPF patients which provides a more beneficial effect in terms of VC, and DLco rather than monotherapy. Further randomized controlled trials with homogeneous outcome measures are needed.

Naringin, a flavanone glycoside, promotes angiogenesis and inhibits endothelial apoptosis through modulation of inflammatory and growth factor expression in diabetic foot ulcer in rats.

Chronic, unhealed diabetic foot ulcer (DFU) is one of the most severe complications of diabetes mellitus (DM). Naringin, a flavanone glycoside antioxidant, was reported to have antidiabetic and anti-apoptotic properties. In the present study DM was induced experimentally by streptozotocin (STZ, 55 mg/kg, i.p.). In surgically introduced wounds on the dorsal surface of the hind paw of rats, the healing potential of naringin was investigated. Rats were treated with naringin (20, 40 and 80 mg/kg, p.o.), insulin (10 IU/kg, s.c.) and tetrachlorodecaoxide (TCDO) (1 drop, twice a day, topically) for 16 days. The wound area was measured every second day, and on day 17 various biochemical parameters were determined in serum, wound tissue, and histopathological examination of the wound was performed. Naringin (40 and 80 mg/kg) significantly (P<0.05) improved wound area, serum glucose level, glycated Hb and serum insulin. Naringin treatment at 40 and 80 mg/kg resulted in significant (P<0.05) up-regulation of mRNA expression of growth factor (IFG-1, TGF-ß and VEGF-c), Ang-1 and collagen-1 whereas mRNA expression of inflammatory mediators (TNF-α, IL-1ß and IL-6) was down-regulated. Furthermore, naringin significantly (P<0.05) attenuated STZ-induced apoptosis and stimulated angiogenesis in the wound tissue. Further results suggest that angiogenesis was improved via naringin-mediated inhibition of hyperglycemia, oxidative stress, down-regulation of inflammatory mediator expression and up-regulation of growth factor expression, leading to improved wound healing of DFU.