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  1. Ali Akbari Ghavimi S, Ebrahimzadeh MH, Solati-Hashjin M, Abu Osman NA
    J Biomed Mater Res A, 2015 Jul;103(7):2482-98.
    PMID: 25407786 DOI: 10.1002/jbm.a.35371
    Interests in the use of biodegradable polymers as biomaterials have grown. Among the different polymeric composites currently available, the blend of starch and polycaprolactone (PCL) has received the most attention since the 1980s. Novamont is the first company that manufactured a PCL/starch (SPCL) composite under the trademark Mater-Bi®. The properties of PCL (a synthetic, hydrophobic, flexible, expensive polymer with a low degradation rate) and starch (a natural, hydrophilic, stiff, abundant polymer with a high degradation rate) blends are interesting because of the composite components have completely different structures and characteristics. PCL can adjust humidity sensitivity of starch as a biomaterial; while starch can enhance the low biodegradation rate of PCL. Thus, by appropriate blending, SPCL can overcome important limitations of both PCL and starch components and promote controllable behavior in terms of mechanical properties and degradation which make it suitable for many biomedical applications. This article reviewed the different fabrication and modification methods of the SPCL composite; different properties such as structural, physical, and chemical as well as degradation behavior; and different applications as biomaterials.
    Matched MeSH terms: Polyesters/administration & dosage*; Starch/administration & dosage*
  2. Rathore C, Rathbone MJ, Chellappan DK, Tambuwala MM, Pinto TJA, Dureja H, et al.
    Expert Opin Drug Deliv, 2020 04;17(4):479-494.
    PMID: 32077770 DOI: 10.1080/17425247.2020.1730808
    Introduction: Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1, 4-quinone, the main active constituent of Nigella sativa (NS) plant, has been proven to be of great therapeutic aid in various in vitro and in vivo conditions. Despite the promising therapeutic activities of TQ, this molecule is not yet in the clinical trials, restricted by its poor biopharmaceutical properties including photo-instability.Area covered: This review compiles the different types of polymeric and lipidic nanocarriers (NCs), encapsulating TQ for their improved oral bioavailability, and augmented in vitro and in vivo efficacy, evidenced on various pathologies. Furthermore, we provide a comprehensive overview of TQ in relation to its encapsulation approaches advancing the delivery and improving the efficacy of TQ.Expert opinion: TQ was first identified in the essential oil of Nigella sativa L. black seed. TQ has not been used in formulations because it is a highly hydrophobic drug having poor aqueous solubility. To deal with the poor physicochemical problems associated with TQ, various NCs encapsulating TQ have been tried in the past. Nevertheless, these NCs could be impending in bringing forth this potential molecule to clinical reality. This will also be beneficial for a large research community including pharmaceutical & biological sciences and translational researchers.
    Matched MeSH terms: Drug Carriers/administration & dosage*; Benzoquinones/administration & dosage*; Nanoparticles/administration & dosage*
  3. Ling Tan JS, Roberts CJ, Billa N
    Pharm Dev Technol, 2019 Apr;24(4):504-512.
    PMID: 30132723 DOI: 10.1080/10837450.2018.1515225
    This study describes the properties of an amphotericin B-containing mucoadhesive nanostructured lipid carrier (NLC), with the intent to maximize uptake within the gastrointestinal tract. We have reported previously that lipid nanoparticles can significantly improve the oral bioavailability of amphotericin B (AmpB). On the other hand, the aggregation state of AmpB within the NLC has been ascribed to some of the side effects resulting from IV administration. In the undissolved state, AmpB (UAmpB) exhibited the safer monomeric conformation in contrast to AmpB in the dissolved state (DAmpB), which was aggregated. Chitosan-coated NLC (ChiAmpB NLC) presented a slightly slower AmpB release profile as compared to the uncoated formulation, achieving 26.1% release in 5 hours. Furthermore, the ChiAmpB NLC formulation appeared to prevent the expulsion of AmpB upon exposure to simulated gastrointestinal pH media, whereby up to 63.9% of AmpB was retained in the NLC compared to 56.1% in the uncoated formulation. The ChiAmpB NLC demonstrated mucoadhesive properties in pH 5.8 and 6.8. Thus, the ChiAmpB NLC formulation is well-primed for pharmacokinetic studies to investigate whether delayed gastrointestinal transit may be exploited to improve the systemic bioavailability of AmpB, whilst simultaneously addressing the side-effect concerns of AmpB.
    Matched MeSH terms: Adhesives/administration & dosage; Amphotericin B/administration & dosage; Anti-Bacterial Agents/administration & dosage; Drug Carriers/administration & dosage; Chitosan/administration & dosage; Nanostructures/administration & dosage
  4. Taha AM, Zainab T, Lau D, Yeo P
    Med J Malaysia, 1995 Dec;50(4):391-5.
    PMID: 8668062
    Three hundred and forty five salt samples were randomly taken from 106 sources where iodised salts were supplied or put for sale in all areas gazetted as endemic goitre areas in Sarawak. The samples were analysed for the presence of iodine. In areas in Sibu, Sarikei and Kapit Divisions, 53-70% of salt put for sale were iodised while in the other 6 Divisions, it was less than 27%. As iodisation of salt is an interventive measure in addressing the goitre problem in the State, regular monitoring of iodisation facilities and iodine content of iodised salt in the affected areas is important to ensure the effectiveness of the programme.
    Matched MeSH terms: Iodine/administration & dosage*; Sodium Chloride, Dietary/administration & dosage*
  5. O'Holohan DR, Dondero TJ, Ponnampalam JT
    Med J Malaysia, 1973 Jun;27(4):310.
    PMID: 4270792
    Matched MeSH terms: Antimalarials/administration & dosage*; Pyrimethamine/administration & dosage*
  6. Singh Y, Gupta G, Kazmi I, Al-Abbasi FA, Negi P, Chellappan DK, et al.
    Dermatol Ther, 2020 11;33(6):e13871.
    PMID: 32558055 DOI: 10.1111/dth.13871
    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the primary causative organism in corona virus disease-19 (COVID-19) infections, is a novel member of the human coronavirus family which was first identified in Wuhan, China, towards the end of 2019. This letter reveals new vital missing links in our current understanding of the mechanisms that lead to cell death triggered by ferroptotic stress in COVID-19 infection. It further reveal the importance of homocysteine mediated trans-sulfuration pathway in COVID-19 infection. Hence, Vitamin B6, folic acid, and Vitamin B12 should be incorporated in the treatment regimen for SARS CoV-2 infections to suppress complications, as the virus mediates altered host cell metabolism.
    Matched MeSH terms: Folic Acid/administration & dosage; Vitamin B 12/administration & dosage; Vitamin B 6/administration & dosage
  7. Kow CS, Aldeyab M, Hasan SS
    J Med Virol, 2021 04;93(4):1860-1861.
    PMID: 33118617 DOI: 10.1002/jmv.26638
    Matched MeSH terms: Adenosine Monophosphate/administration & dosage; Alanine/administration & dosage; Antiviral Agents/administration & dosage*
  8. Thong QX, Biabanikhankahdani R, Ho KL, Alitheen NB, Tan WS
    Sci Rep, 2019 03 08;9(1):3945.
    PMID: 30850643 DOI: 10.1038/s41598-019-40388-x
    Multifunctional nanocarriers displaying specific ligands and simultaneously response to stimuli offer great potentials for targeted and controlled drug delivery. Several synthetic thermally-responsive nanocarriers have been studied extensively for hyperthermia incorporated chemotherapy. However, no information is available on the application of virus-like particle (VLP) in thermally-controlled drug delivery systems. Here, we describe the development of a novel multifunctional nanovehicle based on the VLP of Macrobrachium rosenbergii nodavirus (MrNVLP). Folic acid (FA) was covalently conjugated to lysine residues located on the surface of MrNVLP, while doxorubicin (Dox) was loaded inside the VLP using an infusion method. This thermally-responsive nanovehicle, namely FA-MrNVLP-Dox, released Dox in a sustained manner and the rate of drug release increased in response to a hyperthermia temperature at 43 °C. The FA-MrNVLP-Dox enhanced the delivery of Dox to HT29 cancer cells expressing high level of folate receptor (FR) as compared to CCD841CoN normal cells and HepG2 cancer cells, which express low levels of FR. As a result, FA-MrNVLP-Dox increased the cytotoxicity of Dox on HT29 cells, and decreased the drug's cytotoxicity on CCD841CoN and HepG2 cells. This study demonstrated the potential of FA-MrNVLP-Dox as a thermally-responsive nanovehicle for targeted delivery of Dox to cancer cells rich in FR.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*; Doxorubicin/administration & dosage*; Nanostructures/administration & dosage*
  9. Choudhury H, Gorain B, Chatterjee B, Mandal UK, Sengupta P, Tekade RK
    Curr Pharm Des, 2017;23(17):2504-2531.
    PMID: 27908273 DOI: 10.2174/1381612822666161201143600
    BACKGROUND: Most of the active pharmaceutical ingredients discovered recently in pharmaceutical field exhibits poor aqueous solubility that pose major problem in their oral administration. The oral administration of these drugs gets further complicated due to their short bioavailability, inconsistent absorption and inter/intra subject variability.

    METHODS: Pharmaceutical emulsion holds a significant place as a primary choice of oral drug delivery system for lipophilic drugs used in pediatric and geriatric patients. Pharmacokinetic studies on nanoemulsion mediated drugs delivery approach indicates practical feasibility in regards to their clinical translation and commercialization.

    RESULTS: This review article is to provide an updated understanding on pharmacokinetic and pharmacodynamic features of nanoemulsion delivered via oral, intravenous, topical and nasal route.

    CONCLUSION: The article is of huge interest to formulation scientists working on range of lipophilic drug molecules intended to be administered through oral, intravenous, topical and nasal routes for vivid medical benefits.

    Matched MeSH terms: Pharmaceutical Preparations/administration & dosage*; Emulsions/administration & dosage*; Nanostructures/administration & dosage*
  10. Shimbo S, Zhang ZW, Miyake K, Watanabe T, Nakatsuka H, Matsuda-Inoguchi N, et al.
    Eur J Clin Nutr, 1999 Mar;53(3):233-8.
    PMID: 10201806
    To examine the accuracy of food composition table (FCT)-based estimation of dietary nutrient element intake in reference to the instrumental measurement by inductively-coupled plasma mass spectrometry (ICP-MS), as an extension of the first part of this study.
    Matched MeSH terms: Copper/administration & dosage*; Magnesium/administration & dosage*; Potassium/administration & dosage*; Sodium/administration & dosage*; Zinc/administration & dosage*
  11. Haque ST, Chowdhury EH
    Curr Drug Deliv, 2018;15(4):485-496.
    PMID: 29165073 DOI: 10.2174/1567201814666171120114034
    BACKGROUND: Delivery of conventional small molecule drugs and currently evolving nucleic acid-based therapeutics, such as small interfering RNAs (siRNAs) and genes, and contrast agents for high resolution imaging, to the target site of action is highly demanding to increase the therapeutic and imaging efficacy while minimizing the off-target effects of the delivered molecules, as well as develop novel therapeutic and imaging approaches.

    METHODS: We have undertaken a structured search for peer-reviewed research and review articles predominantly indexed in PubMed focusing on the organic-inorganic hybrid nanoparticles with evidence of their potent roles in intracellular delivery of therapeutic and imaging agents in different animal models.

    RESULTS: Organic-inorganic hybrid nanoparticles offer a number of advantages by combining the unique properties of the organic and inorganic counterparts, thus improving the pharmacokinetic behavior and targetability of drugs and contrast agents, and conferring the exclusive optical and magnetic properties for both therapeutic and imaging purposes. Different polymers, lipids, dendrimers, peptides, cell membranes, and small organic molecules are attached via covalent or non-covalent interactions with diverse inorganic nanoparticles of gold, mesoporous silica, magnetic iron oxide, carbon nanotubes and quantum dots for efficient drug delivery and imaging purposes.

    CONCLUSION: We have thus highlighted here the progress made so far in utilizing different organicinorganic hybrid nanoparticles for in vivo delivery of anti-cancer drugs, siRNA, genes and imaging agents.

    Matched MeSH terms: Contrast Media/administration & dosage*; Pharmaceutical Preparations/administration & dosage*; Inorganic Chemicals/administration & dosage; Organic Chemicals/administration & dosage; Nanoparticles/administration & dosage*
  12. Citartan M, Kaur H, Presela R, Tang TH
    Int J Pharm, 2019 Aug 15;567:118483.
    PMID: 31260780 DOI: 10.1016/j.ijpharm.2019.118483
    Aptamers, nucleic acid ligands that are specific against their corresponding targets are increasingly employed in a variety of applications including diagnostics and therapeutics. The specificity of the aptamers against their targets is also used as the basis for the formulation of the aptamer-based drug delivery system. In this review, we aim to provide an overview on the chaperoning roles of aptamers in acting as the cargo or load carriers, delivering contents to the targeted sites via cell surface receptors. Internalization of the aptamer-biomolecule conjugates via receptor-mediated endocytosis and the strategies to augment the rate of endocytosis are underscored. The cargos chaperoned by aptamers, ranging from siRNAs to DNA origami are illuminated. Possible impediments to the aptamer-based drug deliveries such as susceptibility to nuclease resistance, potentiality for immunogenicity activation, tumor heterogeneity are speculated and the corresponding amendment strategies to address these shortcomings are discussed. We prophesy that the future of the aptamer-based drug delivery will take a trajectory towards DNA nanorobot-based assay.
    Matched MeSH terms: DNA/administration & dosage; RNA, Small Interfering/administration & dosage; MicroRNAs/administration & dosage; Nanostructures/administration & dosage; Aptamers, Nucleotide/administration & dosage*
  13. Tan YZ, Chong YQ, Khong E, Liew YK, Chieng N
    Int J Pharm, 2019 Jul 20;566:400-409.
    PMID: 31136777 DOI: 10.1016/j.ijpharm.2019.05.063
    Live attenuated Mycobacterium bovis (M. bovis), marketed as Bacille Calmette-Guérin is the only FDA-approved vaccine against tuberculosis. The prerequisite of cold chain storage between 2 and 8 °C hinders the global vaccination effort. The study aims to investigate the effect of trehalose, sucrose and glycerol combinations in enhancing the stability of M. bovis. The bacilli were formulated in various ratios of trehalose-glycerol, sucrose-glycerol, trehalose-sucrose-glycerol systems (test samples) and sodium glutamate (control), freeze-dried and stored for 28 days at 4 °C, 25 °C and 37 °C. Bacteria viability at pre-, post-freeze-drying and after storage were quantified by its density in colony-forming unit per milliliter (CFU/mL) as obtained through the pour plate method. Formulations were characterized using differential scanning calorimetry. Structural collapsed cakes were found on all freeze-dried formulations because of the low Tg'. Comparing between binary and ternary formulations, trehalose-sucrose-glycerol was found to be a superior lyoprotectant. Upon storage, the viability of bacteria in disaccharide-polyol formulations was highest when stored at 4 °C followed by 25 °C. The lowest viability was found after storage at 37 °C. While the ternary disaccharide-polyol system may be used as a thermoprotectant up to 25 °C, sodium glutamate has a superior thermoprotective effect at temperature above 25 °C.
    Matched MeSH terms: Excipients/administration & dosage*; Glycerol/administration & dosage*; Polymers/administration & dosage*; Sucrose/administration & dosage*; Trehalose/administration & dosage*
  14. Sohail M, Mudassir, Minhas MU, Khan S, Hussain Z, de Matas M, et al.
    Drug Deliv Transl Res, 2019 04;9(2):595-614.
    PMID: 29611113 DOI: 10.1007/s13346-018-0512-x
    Ulcerative colitis (UC) is an inflammatory disease of the colon that severely affects the quality of life of patients and usually responds well to anti-inflammatory agents for symptomatic relief; however, many patients need colectomy, a surgical procedure to remove whole or part of the colon. Though various types of pharmacological agents have been employed for the management of UC, the lack of effectiveness is usually predisposed to various reasons including lack of target-specific delivery of drugs and insufficient drug accumulation at the target site. To overcome these glitches, many researchers have designed and characterized various types of versatile polymeric biomaterials to achieve target-specific delivery of drugs via oral route to optimize their targeting efficiency to the colon, to improve drug accumulation at the target site, as well as to ameliorate off-target effects of chemotherapy. Therefore, the aim of this review was to summarize and critically discuss the pharmaceutical significance and therapeutic feasibility of a wide range of natural and synthetic biomaterials for efficient drug targeting to colon and rationalized treatment of UC. Among various types of biomaterials, natural and synthetic polymer-based hydrogels have shown promising targeting potential due to their innate pH responsiveness, sustained and controlled release characteristics, and microbial degradation in the colon to release the encapsulated drug moieties. These characteristic features make natural and synthetic polymer-based hydrogels superior to conventional pharmacological strategies for the management of UC.
    Matched MeSH terms: Biocompatible Materials/administration & dosage*; Polymers/administration & dosage*; Polysaccharides/administration & dosage; Hydrogels/administration & dosage; Nanoparticles/administration & dosage
  15. Fong CY, Lim WK, Li L, Lai NM
    Cochrane Database Syst Rev, 2021 08 16;8:CD011786.
    PMID: 34397100 DOI: 10.1002/14651858.CD011786.pub3
    BACKGROUND: This is an updated version of a Cochrane Review published in 2017. Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure.

    OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children.

    SEARCH METHODS: We searched the following databases on 14 May 2020, with no language restrictions: the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 12 May 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy.

    SELECTION CRITERIA: Randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo.

    DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated studies identified by the search for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals (CIs).

    MAIN RESULTS: We included 16 studies with a total of 2922 children. The methodological quality of the included studies was mixed. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 16 studies were at high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in small studies. Fewer children who received oral chloral hydrate had sedation failure compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study; moderate-certainty evidence). More children who received oral chloral hydrate had sedation failure after one dose compared to intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study; low-certainty evidence), but there was no clear difference after two doses (RR 3.00, 95% CI 0.33 to 27.46; 1 study; very low-certainty evidence). Children with oral chloral hydrate had more sedation failure compared with rectal sodium thiopental (RR 1.33, 95% CI 0.60 to 2.96; 1 study; moderate-certainty evidence) and music therapy (RR 17.00, 95% CI 2.37 to 122.14; 1 study; very low-certainty evidence). Sedation failure rates were similar between groups for comparisons with oral dexmedetomidine, oral hydroxyzine hydrochloride, oral midazolam and oral clonidine. Children who received oral chloral hydrate had a shorter time to adequate sedation compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study) (moderate-certainty evidence for three aforementioned outcomes), rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study), and oral clonidine (MD -37.48, 95% CI -55.97 to -18.99; 1 study) (low-certainty evidence for two aforementioned outcomes). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study; low-certainty evidence), intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study; moderate-certainty evidence), and intranasal dexmedetomidine (MD 2.80, 95% CI 0.77 to 4.83; 1 study, moderate-certainty evidence). Children who received oral chloral hydrate appeared significantly less likely to complete neurodiagnostic procedure with child awakening when compared with rectal sodium thiopental (RR 0.95, 95% CI 0.83 to 1.09; 1 study; moderate-certainty evidence). Chloral hydrate was associated with a higher risk of the following adverse events: desaturation versus rectal sodium thiopental (RR 5.00, 95% 0.24 to 102.30; 1 study), unsteadiness versus intranasal dexmedetomidine (MD 10.21, 95% CI 0.58 to 178.52; 1 study), vomiting versus intranasal dexmedetomidine (MD 10.59, 95% CI 0.61 to 185.45; 1 study) (low-certainty evidence for aforementioned three outcomes), and crying during administration of sedation versus intranasal dexmedetomidine (MD 1.39, 95% CI 1.08 to 1.80; 1 study, moderate-certainty evidence). Chloral hydrate was associated with a lower risk of the following: diarrhoea compared with rectal sodium thiopental (RR 0.04, 95% CI 0.00 to 0.72; 1 study), lower mean diastolic blood pressure compared with sodium thiopental (MD 7.40, 95% CI 5.11 to 9.69; 1 study), drowsiness compared with oral clonidine (RR 0.44, 95% CI 0.30 to 0.64; 1 study), vertigo compared with oral clonidine (RR 0.15, 95% CI 0.01 to 2.79; 1 study) (moderate-certainty evidence for aforementioned four outcomes), and bradycardia compared with intranasal dexmedetomidine (MD 0.17, 95% CI 0.05 to 0.59; 1 study; high-certainty evidence). No other adverse events were significantly associated with chloral hydrate, although there was an increased risk of combined adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study; low-certainty evidence).

    AUTHORS' CONCLUSIONS: The certainty of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine. Sedation failure was similar between groups for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. Oral chloral hydrate had a higher sedation failure rate when compared with intravenous pentobarbital, rectal sodium thiopental, and music therapy. Chloral hydrate appeared to be associated with higher rates of adverse events than intranasal dexmedetomidine. However, the evidence for the outcomes for oral chloral hydrate versus intravenous pentobarbital, rectal sodium thiopental, intranasal dexmedetomidine, and music therapy was mostly of low certainty, therefore the findings should be interpreted with caution. Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for an additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially for major adverse effects such as oxygen desaturation.

    Matched MeSH terms: Chloral Hydrate/administration & dosage*; Hydroxyzine/administration & dosage; Hypnotics and Sedatives/administration & dosage*; Midazolam/administration & dosage; Pentobarbital/administration & dosage
  16. Lambert P, Cyna AM, Knight N, Middleton P
    Cochrane Database Syst Rev, 2014 Jan 28;2014(1):CD009633.
    PMID: 24470114 DOI: 10.1002/14651858.CD009633.pub2
    BACKGROUND: Postoperative pain remains a significant problem following paediatric surgery. Premedication with a suitable agent may improve its management. Clonidine is an alpha-2 adrenergic agonist which has sedative, anxiolytic and analgesic properties. It may therefore be a useful premedication for reducing postoperative pain in children.

    OBJECTIVES: To evaluate the evidence for the effectiveness of clonidine, when given as a premedication, in reducing postoperative pain in children less than 18 years of age. We also sought evidence of any clinically significant side effects.

    SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 12, 2012), Ovid MEDLINE (1966 to 21 December 2012) and Ovid EMBASE (1982 to 21 December 2012), as well as reference lists of other relevant articles and online trial registers.

    SELECTION CRITERIA: We included all randomized (or quasi-randomized), controlled trials comparing clonidine premedication to placebo, a higher dose of clonidine, or another agent when used for surgical or other invasive procedures in children under the age of 18 years and where pain or a surrogate (principally the need for supplementary analgesia) was reported.

    DATA COLLECTION AND ANALYSIS: Two authors independently performed the database search, decided on the inclusion eligibility of publications, ascertained study quality and extracted data. They then resolved any differences between their results by discussion. The data were entered into RevMan 5 for analyses and presentation. Sensitivity analyses were performed, as appropriate, to exclude studies with a high risk of bias.

    MAIN RESULTS: We identified 11 trials investigating a total of 742 children in treatment arms relevant to our study question. Risks of bias in the studies were mainly low or unclear, but two studies had aspects of their methodology that had a high risk of bias. Overall, the quality of the evidence from pooled studies was low or had unclear risk of bias. Four trials compared clonidine with a placebo or no treatment, six trials compared clonidine with midazolam, and one trial compared clonidine with fentanyl. There was substantial methodological heterogeneity between trials; the dose and route of clonidine administration varied as did the patient populations, the types of surgery and the outcomes measured. It was therefore difficult to combine the outcomes of some trials for meta-analysis.When clonidine was compared to placebo, pooling studies of low or unclear risk of bias, the need for additional analgesia was reduced when clonidine premedication was given orally at 4 µg/kg (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.11 to 0.51). Only one small trial (15 patients per arm) compared clonidine to midazolam for the same outcome; this also found a reduction in the need for additional postoperative analgesia (RR 0.25, 95% CI 0.09 to 0.71) when clonidine premedication was given orally at 2 or 4 µg/kg compared to oral midazolam at 0.5 mg/kg. A trial comparing oral clonidine at 4 µg/kg with intravenous fentanyl at 3 µg/kg found no statistically significant difference in the need for rescue analgesia (RR 0.89, 95% CI 0.56 to 1.42). When clonidine 4 µg/kg was compared to clonidine 2 µg/kg, there was a statistically significant difference in the number of patients requiring additional analgesia, in favour of the higher dose, as reported by a single, higher-quality trial (RR 0.38, 95% CI 0.23 to 0.65).The effect of clonidine on pain scores was hard to interpret due to differences in study methodology, the doses and route of drug administration, and the pain scale used. However, when given at a dose of 4 µg/kg, clonidine may have reduced analgesia requirements after surgery. There were no significant side effects of clonidine that were reported such as severe hypotension, bradycardia, or excessive sedation requiring intervention. However, several studies used atropine prophylactically with the aim of preventing such adverse effects.

    AUTHORS' CONCLUSIONS: There were only 11 relevant trials studying 742 children having surgery where premedication with clonidine was compared to placebo or other drug treatment. Despite heterogeneity between trials, clonidine premedication in an adequate dosage (4 µg/kg) was likely to have a beneficial effect on postoperative pain in children. Side effects were minimal, but some of the studies used atropine prophylactically with the intention of preventing bradycardia and hypotension. Further research is required to determine under what conditions clonidine premedication is most effective in providing postoperative pain relief in children.

    Matched MeSH terms: Analgesics/administration & dosage*; Clonidine/administration & dosage*; Fentanyl/administration & dosage; Midazolam/administration & dosage; Adrenergic alpha-2 Receptor Agonists/administration & dosage*
  17. Nájera F, Hearn AJ, Ross J, Ramírez Saldivar DA, Evans MN, Guerrero-Sánchez S, et al.
    J Vet Med Sci, 2017 Nov 17;79(11):1892-1898.
    PMID: 28904261 DOI: 10.1292/jvms.17-0259
    There is currently no available information regarding the veterinary management of Sunda clouded leopards (Neofelis diardi), either in captivity or in the wild. In this study, 12 Sunda clouded leopards were anesthetized between January 2008 and February 2014 for medical exams, and/or GPS-collaring. Seven wild-caught individuals were kept in captivity and 5 free-ranging animals were captured by cage traps. Two anesthesia combinations were used: medetomidine-ketamine (M-K) or tiletamine-zolazepam (T-Z). Atipamezole (0.2 mg/kg im) was used as an antagonist for medetomidine. Medetomidine (range: 0.039-0.054 mg/kg) and ketamine (range: 3-4.39 mg/kg) were administered during 5 immobilizations, resulting in median induction times of 7 min. After a median anesthesia time of 56 min, atipamezole was injected, observing effects of antagonism at a median time of 12 min. T-Z (range: 6.8-10.8 mg/kg) was administered on 7 occasions. Median induction times observed with this combination were shorter than with M-K (4 min vs 7 min; P=0.04), and anesthesia and recovery times were significantly longer (244 and 35 min vs 56 and 16 min, respectively; P=0.02). Lower heart rates were measured in the M-K group, while lower rectal temperatures were found in the T-Z group. Both combinations resulted in safe and reliable immobilizations, although given the favorable anesthesia and recovery times of M-K, we recommend this approach over T-Z for the veterinary handling of Sunda clouded leopards.
    Matched MeSH terms: Imidazoles/administration & dosage; Ketamine/administration & dosage*; Tiletamine/administration & dosage*; Zolazepam/administration & dosage*; Anesthetics, Combined/administration & dosage; Medetomidine/administration & dosage*
  18. Mahachai V, Vilaichone RK, Pittayanon R, Rojborwonwitaya J, Leelakusolvong S, Maneerattanaporn M, et al.
    J Gastroenterol Hepatol, 2018 Jan;33(1):37-56.
    PMID: 28762251 DOI: 10.1111/jgh.13911
    Helicobacter pylori (H. pylori) infection remains to be the major cause of important upper gastrointestinal diseases such as chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. H. pylori management in ASEAN: the Bangkok consensus report gathered key opinion leaders for the region to review and evaluate clinical aspects of H. pylori infection and to develop consensus statements, rationales, and grades of recommendation for the management of H. pylori infection in clinical practice in ASEAN countries. This ASEAN Consensus consisted of 34 international experts from 10 ASEAN countries, Japan, Taiwan, and the United States. The meeting mainly focused on four issues: (i) epidemiology and disease association; (ii) diagnostic tests; (iii) management; and (iv) follow-up after eradication. The final results of each workshop were presented for consensus voting by all participants. Statements, rationale, and recommendations were developed from the available current evidence to help clinicians in the diagnosis and treatment of H. pylori and its clinical diseases.
    Matched MeSH terms: Amoxicillin/administration & dosage; Anti-Bacterial Agents/administration & dosage; Bismuth/administration & dosage; Metronidazole/administration & dosage; Tetracycline/administration & dosage; Clarithromycin/administration & dosage; Fluoroquinolones/administration & dosage; Proton Pump Inhibitors/administration & dosage
  19. Fong CY, Tay CG, Ong LC, Lai NM
    Cochrane Database Syst Rev, 2017 Nov 03;11(11):CD011786.
    PMID: 29099542 DOI: 10.1002/14651858.CD011786.pub2
    BACKGROUND: Paediatric neurodiagnostic investigations, including brain neuroimaging and electroencephalography (EEG), play an important role in the assessment of neurodevelopmental disorders. The use of an appropriate sedative agent is important to ensure the successful completion of the neurodiagnostic procedures, particularly in children, who are usually unable to remain still throughout the procedure.

    OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children.

    SEARCH METHODS: We used the standard search strategy of the Cochrane Epilepsy Group. We searched MEDLINE (OVID SP) (1950 to July 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 7, 2017), Embase (1980 to July 2017), and the Cochrane Epilepsy Group Specialized Register (via CENTRAL) using a combination of keywords and MeSH headings.

    SELECTION CRITERIA: We included randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo for children undergoing non-invasive neurodiagnostic procedures.

    DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data, mean difference (MD) for continuous data, with 95% confidence intervals (CIs).

    MAIN RESULTS: We included 13 studies with a total of 2390 children. The studies were all conducted in hospitals that provided neurodiagnostic services. Most studies assessed the proportion of sedation failure during the neurodiagnostic procedure, time for adequate sedation, and potential adverse effects associated with the sedative agent.The methodological quality of the included studies was mixed, as reflected by a wide variation in their 'Risk of bias' profiles. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 13 studies had high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in single small studies.Children who received oral chloral hydrate had lower sedation failure when compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study, moderate-quality evidence). Children who received oral chloral hydrate had a higher risk of sedation failure after one dose compared to those who received intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study, low-quality evidence), but after two doses there was no evidence of a significant difference between the two groups (RR 3.00, 95% CI 0.33 to 27.46; 1 study, very low-quality evidence). Children who received oral chloral hydrate appeared to have more sedation failure when compared with music therapy, but the quality of evidence was very low for this outcome (RR 17.00, 95% CI 2.37 to 122.14; 1 study). Sedation failure rates were similar between oral chloral hydrate, oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam.Children who received oral chloral hydrate had a shorter time to achieve adequate sedation when compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study, moderate-quality evidence), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study, moderate-quality evidence), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study, moderate-quality evidence), and rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study, low-quality evidence) and intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study, moderate-quality evidence).No data were available to assess the proportion of children with successful completion of neurodiagnostic procedure without interruption by the child awakening. Most trials did not assess adequate sedation as measured by specific validated scales, except in the comparison of chloral hydrate versus intranasal midazolam and oral promethazine.Compared to dexmedetomidine, chloral hydrate was associated with a higher risk of nausea and vomiting (RR 12.04 95% CI 1.58 to 91.96). No other adverse events were significantly associated with chloral hydrate (including behavioural change, oxygen desaturation) although there was an increased risk of adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study, low-quality evidence).

    AUTHORS' CONCLUSIONS: The quality of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was very variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine for children undergoing paediatric neurodiagnostic procedures. The sedation failure was similar for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. When compared with intravenous pentobarbital and music therapy, oral chloral hydrate had a higher sedation failure rate. However, it must be noted that the evidence for the outcomes for the comparisons of oral chloral hydrate against intravenous pentobarbital and music therapy was of very low to low quality, therefore the corresponding findings should be interpreted with caution.Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially the risk of major adverse effects such as bradycardia, hypotension, and oxygen desaturation.

    Matched MeSH terms: Chloral Hydrate/administration & dosage*; Hydroxyzine/administration & dosage; Hypnotics and Sedatives/administration & dosage*; Melatonin/administration & dosage; Midazolam/administration & dosage; Pentobarbital/administration & dosage; Promethazine/administration & dosage; Dexmedetomidine/administration & dosage
  20. Freisling H, Pisa PT, Ferrari P, Byrnes G, Moskal A, Dahm CC, et al.
    Eur J Nutr, 2016 Sep;55(6):2093-104.
    PMID: 26303194 DOI: 10.1007/s00394-015-1023-x
    PURPOSE: Various food patterns have been associated with weight change in adults, but it is unknown which combinations of nutrients may account for such observations. We investigated associations between main nutrient patterns and prospective weight change in adults.

    METHODS: This study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders.

    RESULTS: Mean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year; 95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant.

    CONCLUSIONS: We identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults.

    Matched MeSH terms: Ascorbic Acid/administration & dosage; Calcium, Dietary/administration & dosage; Dietary Fiber/administration & dosage; Dietary Proteins/administration & dosage; Folic Acid/administration & dosage; Riboflavin/administration & dosage; Phosphorus, Dietary/administration & dosage; beta Carotene/administration & dosage
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