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Clinical Endocrinology Jun 2017International and national guidelines on the treatment of chronic nonhypovolaemic hypotonic hyponatraemia differ; therefore, we have undertaken this systematic review... (Meta-Analysis)
Meta-Analysis Review
International and national guidelines on the treatment of chronic nonhypovolaemic hypotonic hyponatraemia differ; therefore, we have undertaken this systematic review and meta-analysis to investigate the efficacy and safety of interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia. Following registration of the review protocol with PROSPERO, systematic literature searches were conducted to identify randomized and quasi-randomized controlled trials assessing any degree of fluid restriction or any drug treatment with the aim of increasing serum sodium concentration in patients with chronic nonhypovolaemic hypotonic hyponatraemia. Where appropriate, outcome data were synthesized in a meta-analysis. A total of 45 716 bibliographic records were identified from the searches and 18 trials (assessing conivaptan, lixivaptan, tolvaptan and satavaptan) met the eligibility criteria. Results suggest that all four vasopressin receptor agonists ("vaptans") significantly improve serum sodium concentration. Lixivaptan, satavaptan and tolvaptan were associated with greater rates of response versus placebo. There was no evidence of a difference between each of the vaptans compared with placebo for mortality, discontinuation and rates of hypernatraemia. No RCT evidence of treatments other than the vaptans for hyponatraemia such as oral urea, salt tablets, mannitol, loop diuretics demeclocycline or lithium was identified. Vaptans demonstrated superiority over placebo for outcomes relating to serum sodium correction. Few trials documented the potential benefit of vaptans on change in health-related quality of life as a result of treatment. There was also a lack of high-quality RCT evidence on the comparative efficacy of the vaptans and other treatment strategies for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia.
Topics: Antidiuretic Hormone Receptor Antagonists; Benzamides; Benzazepines; Humans; Hyponatremia; Morpholines; Osmotic Pressure; Pyrroles; Randomized Controlled Trials as Topic; Receptors, Vasopressin; Spiro Compounds; Tolvaptan
PubMed: 28214374
DOI: 10.1111/cen.13315 -
Oncotarget Dec 2016Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder characterized by early onset of extensive mineralization of the cardiovascular... (Comparative Study)
Comparative Study
Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder characterized by early onset of extensive mineralization of the cardiovascular system. The classical forms of GACI are caused by mutations in the ENPP1 gene, encoding a membrane-bound pyrophosphatase/phosphodiesterase that hydrolyzes ATP to AMP and inorganic pyrophosphate. The asj-2J mouse harboring a spontaneous mutation in the Enpp1 gene has been characterized as a model for GACI. These mutant mice develop ectopic mineralization in skin and vascular connective tissues as well as in cartilage and collagen-rich tendons and ligaments. This study examined in detail the temporal ectopic mineralization phenotype of connective tissues in this mouse model, utilizing a novel cryo-histological method that does not require decalcification of bones. The wild type, heterozygous, and homozygous mice were administered fluorescent mineralization labels at 4 weeks (calcein), 10 weeks (alizarin complexone), and 11 weeks of age (demeclocycline). Twenty-four hours later, outer ears, muzzle skin, trachea, aorta, shoulders, and vertebrae were collected from these mice and examined for progression of mineralization. The results revealed differential timeline for disease initiation and progression in various tissues of this mouse model. It also highlights the advantages of cryo-histological fluorescent imaging technique to study mineral deposition in mouse models of ectopic mineralization disorders.
Topics: Animals; Anthraquinones; Connective Tissue; Demeclocycline; Disease Progression; Fluoresceins; Fluorescent Dyes; Genetic Predisposition to Disease; Heterozygote; Homozygote; Mice, Inbred BALB C; Mice, Mutant Strains; Microscopy, Fluorescence; Mutation; Phenotype; Phosphoric Diester Hydrolases; Pyrophosphatases; Time Factors; Vascular Calcification
PubMed: 27863377
DOI: 10.18632/oncotarget.13335 -
Endocrine Feb 2017The syndrome of inappropriate antidiuresis is often undertreated with most patients discharged with persistent hyponatraemia. This study tested the hypothesis that an...
Improving care and outcomes of inpatients with syndrome of inappropriate antidiuresis (SIAD): a prospective intervention study of intensive endocrine input vs. routine care.
PURPOSE
The syndrome of inappropriate antidiuresis is often undertreated with most patients discharged with persistent hyponatraemia. This study tested the hypothesis that an endocrine input is superior to routine care in correcting hyponatraemia and can improve patient outcomes.
METHODS
This single-centre prospective-controlled intervention study included inpatients admitted at a UK teaching hospital, with serum sodium ≤ 127 mmol/l, due to syndrome of inappropriate antidiuresis over a 6-month period. The prospective intervention group (18 subjects with mean serum sodium 120.7 mmol/l) received prompt endocrine input, while the historical control group (23 patients with mean serum sodium 124.1 mmol/l) received routine care. The time needed for serum sodium increase ≥ 5 mmol/l was the primary endpoint.
RESULTS
The intervention group achieved serum sodium rise by ≥5 mmol/l in 3.5 vs. 7.1 days in the control group (P = 0.005). In the intervention group, the mean total serum sodium increase was 12 mmol/l with only 5.8 % of patients discharged with serum sodium < 130 vs. 6.3 mmol/l increase (P < 0.001) and 42.1 % of the subjects discharged with serum sodium < 130 mmol/l in the control group (P = 0.012). The mean length of hospital stay in the intervention group (10.9 days) was significantly shorter than in the control group (14.5 days; P = 0.004).The inpatient mortality rate was 5.5 % in intervention arm vs. 17.4 % in control arm, but this difference was not statistically significant.
CONCLUSIONS
Since the endocrine input improved time for correction of hyponatraemia and shortened length of hospitalisation, widespread provision of endocrine input should be considered.
Topics: Aged; Aged, 80 and over; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Demeclocycline; Female; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Prospective Studies; Retrospective Studies; Saline Solution, Hypertonic; Sodium; Tolvaptan; Treatment Outcome
PubMed: 27837439
DOI: 10.1007/s12020-016-1161-9 -
Pharmaceuticals (Basel, Switzerland) Sep 2016An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired...
An intrinsic clindamycin-resistant Enterococcus faecalis, the most common single species present in teeth after failed root canal therapy, often possesses acquired tetracycline resistance. In these cases, root canal infections are commonly treated with Ledermix(®) paste, which contains demeclocycline, or the new alternative endodontic paste Odontopaste, which contains clindamycin; however, these treatments are often ineffective. We studied the killing activity of the cyclic antimicrobial peptide gramicidin S (GS) against planktonic and biofilm cells of tetracycline-resistant clinical isolates of E. faecalis. The high therapeutic potential of GS for the topical treatment of problematic teeth is based on the rapid bactericidal effect toward the biofilm-forming, tetracycline-resistant E. faecalis. GS reduces the cell number of planktonic cells within 20-40 min at a concentration of 40-80 μg/mL. It kills the cells of pre-grown biofilms at concentrations of 100-200 μg/mL, such that no re-growth is possible. The translocation of the peptide into the cell interior and its complexation with intracellular nucleotides, including the alarmon ppGpp, can explain its anti-biofilm effect. The successful treatment of persistently infected root canals of two volunteers confirms the high effectiveness of GS. The broad GS activity towards resistant, biofilm-forming E. faecalis suggests its applications for approval in root canal medication.
PubMed: 27618065
DOI: 10.3390/ph9030056 -
Swiss Dental Journal 2016The aim of this paper is to show aspects of dental treatment in pregnancy. The reader should gain security in the election of the proper drugs for antibiotic therapy and...
The aim of this paper is to show aspects of dental treatment in pregnancy. The reader should gain security in the election of the proper drugs for antibiotic therapy and rinsing solutions. Antibiotics as penicillins are the first choice in case of dental infections in pregnancy. In allergic patients, macrolides may be an alternative. Wound and mouth rinsing solutions containing chlorhexidine should be preferred in pregnancy. Ledermix(®) in endodontic treatment should be avoided in the pregnant woman. Solcoseryl(®) can be used for wound healing. Elective dental procedures should be postponed after delivery and after lactation period.
Topics: Actihaemyl; Anti-Bacterial Agents; Demeclocycline; Dental Care; Drug Combinations; Female; Humans; Infant, Newborn; Lactation; Mouthwashes; Pregnancy; Prenatal Exposure Delayed Effects; Triamcinolone Acetonide
PubMed: 27377565
DOI: 10.61872/sdj-2016-06-04 -
Swiss Dental Journal 2016The aim of this paper is to show aspects of dental treatment in pregnancy. The reader should gain security in the election of the proper drugs for antibiotic therapy and...
The aim of this paper is to show aspects of dental treatment in pregnancy. The reader should gain security in the election of the proper drugs for antibiotic therapy and rinsing solutions. Antibiotics as penicillins are the first choice in case of dental infections in pregnancy. In allergic patients, macrolides may be an alternative. Wound and mouth rinsing solutions containing chlorhexidine should be preferred in pregnancy. Ledermix(®) in endodontic treatment should be avoided in the pregnant woman. Solcoseryl(®) can be used for wound healing. Elective dental procedures should be postponed after delivery and after lactation period.
Topics: Actihaemyl; Anti-Bacterial Agents; Chlorhexidine; Demeclocycline; Drug Combinations; Female; Humans; Mouth Diseases; Mouthwashes; Pregnancy; Pregnancy Complications, Infectious; Tooth Diseases; Triamcinolone Acetonide
PubMed: 27277144
DOI: 10.61872/sdj-2016-05-05 -
Endocrinology, Diabetes & Metabolism... 2015The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur following traumatic brain injury (TBI), but is usually transient. There are very few case...
UNLABELLED
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur following traumatic brain injury (TBI), but is usually transient. There are very few case reports describing chronic SIADH and all resolved within 12 months, except for one case complicated by meningo-encephalitis. Persistent symptomatic hyponatremia due to chronic SIADH was present for 4 years following a TBI in a previously well 32-year-old man. Hyponatremia consistent with SIADH initially occurred in the immediate period following a high-speed motorbike accident in 2010. There were associated complications of post-traumatic amnesia and mild cognitive deficits. Normalization of serum sodium was achieved initially with fluid restriction. However, this was not sustained and he subsequently required a permanent 1.2 l restriction to maintain near normal sodium levels. Multiple episodes of acute symptomatic hyponatremia requiring hospitalization occurred over the following years when he repeatedly stopped the fluid restriction. Given the ongoing nature of his hyponatremia and difficulties complying with strict fluid restriction, demeclocycline was commenced in 2014. Normal sodium levels without fluid restriction have been maintained for 6 months since starting demeclocycline. This case illustrates an important long-term effect of TBI, the challenges of complying with permanent fluid restrictions and the potential role of demeclocycline in patients with chronic hyponatremia due to SIADH.
LEARNING POINTS
Hyponatraemia due to SIADH commonly occurs after TBI, but is usually mild and transient.Chronic hyponatraemia due to SIADH following TBI is a rare but important complication.It likely results from damage to the pituitary stalk or posterior pituitary causing inappropriate non-osmotic hypersecretion of ADH.First line management of SIADH is generally fluid restriction, but hypertonic saline may be required in severe cases. Adherence to long-term fluid restriction is challenging. Other options include oral urea, vasopressin receptor antagonists and demeclocycline.While effective, oral urea is poorly tolerated and vasopressin receptor antagonists are currently not licensed for use in Australia or the USA beyond 30 days due to insufficient long-term safety data and specific concerns of hepatotoxicity.Demeclocycline is an effective, well-tolerated and safe option for management of chronic hyponatraemia due to SIADH.
PubMed: 26527077
DOI: 10.1530/EDM-15-0070 -
Water Science and Technology : a... 2015Phosphorus (P) recovery was carried out through struvite precipitation from urines. Human urine, however, contains not only high nutrients for plants, such as P and...
Phosphorus (P) recovery was carried out through struvite precipitation from urines. Human urine, however, contains not only high nutrients for plants, such as P and nitrogen, but also pharmaceuticals and hormones. In this work, effects of magnesium (Mg) dose (in terms of Mg:P ratio) on P recovery efficiency and pharmaceutical amounts contained in struvite were investigated. Batch-scale experiments of synthetic and human urines revealed that struvite precipitation formed more X-shaped crystals with an increased molar ratio of Mg:P, while the amount of pharmaceuticals (tetracycline, demeclocycline, and oxytetracycline) in struvite decreased with an increased molar ratio of Mg:P. The lowest pharmaceutical amounts in struvite were found at the Mg:P ratio of 2:1 from both samples. Moreover, the maximum P recovery efficiency, quantity and purity of struvite were found in the range of 1.21 to 2:1. It indicated that the molar ratio of Mg:P has a significant impact on struvite precipitation in terms of pharmaceutical amounts in struvite; morphology, quantity and purity of struvite; and P recovery.
Topics: Humans; Magnesium Compounds; Microscopy, Electron, Scanning; Models, Theoretical; Nitrogen; Pharmaceutical Preparations; Phosphates; Phosphorus; Struvite; Surface Properties
PubMed: 26398025
DOI: 10.2166/wst.2015.313 -
European Journal of Clinical... Nov 2015
Topics: Algorithms; Anti-Bacterial Agents; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Demeclocycline; Fluid Therapy; Humans; Hyponatremia; Inappropriate ADH Syndrome
PubMed: 26343423
DOI: 10.1111/eci.12515 -
International Journal of Clinical... Dec 2015Hyponatraemia (HN) is the most common electrolyte balance disorder in clinical practice. Since the 1970s, demeclocycline has been used in some countries to treat chronic... (Review)
Review
AIMS
Hyponatraemia (HN) is the most common electrolyte balance disorder in clinical practice. Since the 1970s, demeclocycline has been used in some countries to treat chronic HN secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH). The precise mechanism of action of demeclocycline is unclear, but has been linked to the induction of nephrogenic diabetes insipidus. Furthermore, the safety profile of demeclocycline is variable with an inconsistent time to onset, and a potential for complications. There has been no systematic evaluation of the use of demeclocycline for the treatment of HN secondary to SIADH to date. A systematic literature review was performed to obtain an insight into the clinical safety and efficacy of demeclocycline for this condition.
METHODS
Embase(™) , MEDLINE(®) , MEDLINE(®) In-Process, and The Cochrane Library were searched on two occasions using MeSH terms combined with free-text terms. References were screened by two independent reviewers. Relevant publications were then extracted by two independent reviewers, with a third reviewer collating and finalising extractions.
RESULTS
The searches returned a total of 705 hits. 632 abstracts were screened after the removal of duplicates. Following screening, 35 full-length publications were reviewed. Of these, 17 were excluded, resulting in 18 studies deemed relevant for data extraction. Two were randomised controlled trials (RCTs), 16 were non-RCTs, and 10 were case reports.
DISCUSSION
Although most reports suggest that demeclocycline can address serum sodium levels in specific patients with HN, efficacy is variable, and may depend upon the underlying aetiology. Demeclocycline dose adjustments can be complex, and as its use in clinical practice is not well defined, it can differ between healthcare professionals.
CONCLUSION
There is a lack of clinical and economic evidence supporting the use of demeclocycline for HN secondary to SIADH. Patients receiving demeclocycline for HN secondary to SIADH must be closely monitored.
Topics: Demeclocycline; Humans; Hyponatremia; Inappropriate ADH Syndrome
PubMed: 26289137
DOI: 10.1111/ijcp.12713