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Case Reports in Medicine 2019Gitelman syndrome is one of the few inherited causes of metabolic alkalosis due to salt losing tubulopathy. It is caused by tubular defects at the level of distal...
Gitelman syndrome is one of the few inherited causes of metabolic alkalosis due to salt losing tubulopathy. It is caused by tubular defects at the level of distal convoluted tubules, mimicking a thiazide-like tumor. It usually presents in late childhood or in teenage as nonspecific weakness, fatigability, polyuria, and polydipsia but very rarely with seizures. It is classically associated with hypokalemia, hypomagnesemia, hypocalciuria, hyperreninemia, and hyperaldosteronism. However, less frequently, it can present with normal magnesium levels. It is even rarer to find normomagnesemic patients of GS who develop seizures as the main complication since hypomagnesemia is considered the principal etiology of abnormal foci of seizure-related brain activity in GS cases. Interestingly, patients with GS are oftentimes diagnosed during pregnancy when the classic electrolyte pattern consistent with GS is noticed. Our case presents GS with normal serum magnesium in a patient, with seizures being the main clinical presentation. We also did a comprehensive literature review of 122 reported cases to show the prevalence of normal magnesium in GS cases and an overview of clinical and biochemical variability in GS. We suggest that further studies and in-depth analysis are required to understand the pathophysiology of seizures in GS patients with both normal and low magnesium levels.
PubMed: 30867665
DOI: 10.1155/2019/4204907 -
Arab Journal of Urology Dec 2018To evaluate the effect of oral desmopressin in patients with nocturia associated with benign prostatic hyperplasia (BPH). (Review)
Review
OBJECTIVE
To evaluate the effect of oral desmopressin in patients with nocturia associated with benign prostatic hyperplasia (BPH).
PATIENTS AND METHODS
With a rise of the use of oral desmopressin in the treatment of nocturia in patients with BPH, a systematic review was performed according to the Cochrane systematic reviews guidelines and in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.
RESULTS
The literature search yielded 18 studies. The studies were published between 1980 and 2017, and included 3072 patients. Eligible patients were men aged ≥50 years with lower urinary tract symptoms (LUTS) and persistent nocturia. There was a significant 43% reduction in nocturia after using desmopressin alone. Combined α-blockers and desmopressin lead to a decrease in the frequency of night voids by 64.3% compared to 44.6% when using α-blockers only. The first sleep period, significantly increased from 82.1 to 160.0 min and from 83.2 to 123.8 min when using desmopressin + α-blocker and α-blocker only, respectively. The desmopressin dose ranged from the lowest dose (0.05 mg) to the optimum dose (0.4 mg) at bed time. The incidence of hyponatraemia associated with desmopressin use was 4.4-5.7%.
CONCLUSION
Low-dose oral desmopressin therapy alone is an effective treatment for nocturia associated with LUTS in patients with BPH. Oral desmopressin combined with α-blockers is well tolerated and beneficial for improving the International Prostate Symptom Score and nocturnal symptoms. All patients should be educated about the mechanism of desmopressin action to avoid treatment discontinuation due to adverse events.
PubMed: 30534439
DOI: 10.1016/j.aju.2018.06.007 -
European Psychiatry : the Journal of... Oct 2018Many clinicians are reluctant to use traditional mood-stabilizing agents, especially lithium, in children and adolescents. This review examined the evidence for...
INTRODUCTION
Many clinicians are reluctant to use traditional mood-stabilizing agents, especially lithium, in children and adolescents. This review examined the evidence for lithium's safety and efficacy in this population.
METHODS
A systematic review was conducted on the use of lithium in children and adolescents with bipolar disorder (BD). Relevant papers published through June 30 2018 were identified searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library.
RESULTS
30 articles met inclusion criteria, including 12 randomized controlled trials (RCTs). Findings from RCTs demonstrate efficacy for acute mania in up to 50% of patients, and evidence of long-term maintenance efficacy. Lithium was generally safe, at least in the short term, with most common side effects being gastrointestinal, polyuria, or headache. Only a minority of patients experienced hypothyroidism. No cases of acute kidney injury or chronic kidney disease were reported.
CONCLUSIONS
Though the available literature is mostly short-term, there is evidence that lithium monotherapy is reasonably safe and effective in children and adolescents, specifically for acute mania and for prevention of mood episodes.
Topics: Adolescent; Antimanic Agents; Bipolar Disorder; Child; Gastrointestinal Diseases; Headache; Humans; Hypothyroidism; Lithium Compounds; Polyuria; Renal Insufficiency; Treatment Outcome
PubMed: 30130637
DOI: 10.1016/j.eurpsy.2018.07.012 -
The Cochrane Database of Systematic... Jun 2018Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer hospital stays. Many treatments, such as fluid restriction or vasopressin receptor antagonists can be used to improve the hyponatraemia, but whether that translates into improved patient-important outcomes is less certain.
OBJECTIVES
This review aimed to 1) look at the benefits and harms of interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared with placebo, no treatment or head-to-head; and 2) determine if benefits and harms vary in absolute or relative terms dependent on the specific compound within a drug class, on the dosage used, or the underlying disorder causing the hyponatraemia.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 1 December 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also screened the reference lists of potentially relevant studies, contacted authors, and screened the websites of regulatory agencies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of any intervention with placebo, no treatment, standard care, or any other intervention in patients with chronic non-hypovolaemic hypotonic hyponatraemia. We also included subgroups with hyponatraemia from studies with broader inclusion criteria (e.g. people with chronic heart failure or people with cirrhosis with or without hyponatraemia), provided we could obtain outcomes for participants with hyponatraemia from the report or the study authors.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias. We expressed treatment effects as mean difference (MD) for continuous outcomes (health-related quality of life, length of hospital stay, change from baseline in serum sodium concentration, cognitive function), and risk ratio (RR) for dichotomous outcomes (death, response and rapid increase in serum sodium concentration, hypernatraemia, polyuria, hypotension, acute kidney injury, liver function abnormalities) together with 95% confidence intervals (CI).
MAIN RESULTS
We identified 35 studies, enrolling 3429 participants. Twenty-eight studies (3189 participants) compared a vasopressin receptor antagonist versus placebo, usual care, no treatment, or fluid restriction. In adults with chronic, non-hypovolaemic hypotonic hyponatraemia, vasopressin receptor antagonists have uncertain effects on death at six months (15 studies, 2330 participants: RR 1.11, 95% CI 0.92 to 1.33) due to risk of selective reporting and serious imprecision; and on health-related quality of life because results are at serious risk of performance, selective reporting and attrition bias, and suffer from indirectness related to the validity of the Short Form Health Survey (SF-12) in the setting of hyponatraemia. Vasopressin receptor antagonists may reduce hospital stay (low certainty evidence due to risk of performance bias and imprecision) (3 studies, 610 participants: MD -1.63 days, 95% CI -2.96 to -0.30), and may make little or no difference to cognitive function (low certainty evidence due to indirectness and imprecision). Vasopressin receptor antagonists probably increase the intermediate outcome of serum sodium concentration (21 studies, 2641 participants: MD 4.17 mmol/L, 95% CI 3.18 to 5.16), corresponding to two and a half as many people having a 5 to 6 mmol/L increase in sodium concentration compared with placebo at 4 to 180 days (moderate certainty evidence due to risk of attrition bias) (18 studies, 2014 participants: RR 2.49, 95% CI 1.95 to 3.18). But they probably also increase the risk of rapid serum sodium correction - most commonly defined as > 12 mmol/L/d (moderate certainty evidence due to indirectness) (14 studies, 2058 participants: RR 1.67, 95% CI 1.16 to 2.40) and commonly cause side-effects such as thirst (13 studies, 1666 participants: OR 2.77, 95% CI 1.80 to 4.27) and polyuria (6 studies, 1272 participants): RR 4.69, 95% CI 1.59 to 13.85) (high certainty evidence). The potential for liver toxicity remains uncertain due to large imprecision. Effects were generally consistent across the different agents, suggesting class effect.Data for other interventions such as fluid restriction, urea, mannitol, loop diuretics, corticosteroids, demeclocycline, lithium and phenytoin were largely absent.
AUTHORS' CONCLUSIONS
In people with chronic hyponatraemia, vasopressin receptor antagonists modestly raise serum sodium concentration at the cost of a 3% increased risk of it being rapid. To date there is very low certainty evidence for patient-important outcomes; the effects on mortality and health-related quality of life are unclear and do not rule out appreciable benefit or harm; there does not appear to be an important effect on cognitive function, but hospital stay may be slightly shorter, although available data are limited. Treatment decisions must weigh the value of an increase in serum sodium concentration against its short-term risks and unknown effects on patient-important outcomes. Evidence for other treatments is largely absent.Further studies assessing standard treatments such as fluid restriction or urea against placebo and one-another would inform practice and are warranted. Given the limited available evidence for patient-important outcomes, any study should include these outcomes in a standardised manner.
Topics: Antidiuretic Hormone Receptor Antagonists; Chronic Disease; Humans; Hyponatremia; Length of Stay; Quality of Life; Randomized Controlled Trials as Topic; Sodium
PubMed: 29953167
DOI: 10.1002/14651858.CD010965.pub2 -
The Cochrane Database of Systematic... Oct 2017Nocturia is the bothersome symptom of awakening one or more times per night to void. Desmopressin is a commonly used medication for treating nocturia. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nocturia is the bothersome symptom of awakening one or more times per night to void. Desmopressin is a commonly used medication for treating nocturia.
OBJECTIVES
To assess the effects of desmopressin as compared to other interventions in the treatment of nocturia in men.
SEARCH METHODS
We performed a comprehensive search of medical literature with no restrictions on the language of publication or publication status. The date of the latest search of all databases was August 2017.
SELECTION CRITERIA
We included randomized or quasi-randomized trials. Inclusion criteria were men with nocturia defined as one or more voids per night. Trials of children, adults with primary or secondary enuresis or underlying distinct disorders were excluded.
DATA COLLECTION AND ANALYSIS
Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model and interpreted data according to the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We included 14 studies with 2966 randomized men across five comparisons. Desmopressin versus placebo: based on short-term follow-up (up to three months), desmopressin may have a similar effect on the number of nocturnal voids (mean difference (MD) -0.46, 95% confidence interval (CI) -0.94 to 0.01; low-quality evidence). We are uncertain about the effect of desmopressin on major adverse events at short-term follow-up (risk ratio (RR) 0.97, 95% CI 0.10 to 9.03; very low-quality evidence). For intermediate-term follow-up (three to 12 months), desmopressin may reduce the number of nocturnal voids in an appreciable number of participants (MD -0.85, 95% CI -1.17 to -0.53; low-quality evidence). Desmopressin may result in little or no difference in major adverse events at intermediate-term follow-up (RR 3.05, 95% CI 0.13 to 73.39; low-quality evidence). We found no evidence on quality of life. Subgroup analyses suggest a larger effect with oral, higher-dose formulations of desmopressin and in men with documented nocturnal polyuria. Desmopressin versus behavior modification: there were no data regarding the effect on the number of nocturnal voids, quality of life, or major adverse events. Desmopressin versus alpha-blocker: based on short-term follow-up, desmopressin likely has a similar effect on the number of nocturnal voids (MD 0.30, 95% CI -0.20 to 0.80; moderate-quality evidence) and quality of life (MD 0.00, 95% CI -0.35 to 0.35; moderate-quality evidence). There were no major adverse events in either study group. Desmopressin plus alpha-blocker versus alpha-blocker alone: based on short-term follow-up, combination therapy likely results in a small, unimportant reduction in the number of nocturnal voids (MD -0.47, 95% CI -0.73 to -0.21; moderate-quality evidence) and quality of life (MD -0.29, 95% CI -0.51 to -0.07; moderate-quality evidence). The risk of major adverse events may be similar (RR 0.30, 95% CI 0.01 to 7.32; low-quality evidence). Desmopressin plus alpha-blocker versus alpha-blocker plus an anticholinergic: based on short-term follow-up, combination therapy likely results in little or no difference in the number of nocturnal voids (MD -0.43, 95% CI -0.97 to 0.11; moderate-quality evidence). We found no evidence on quality of life. There were no major adverse events in either study group.
AUTHORS' CONCLUSIONS
Desmopressin may reduce the number of nocturnal voids in an appreciable number of participants compared to placebo in intermediate-term (three to 12 months) follow-up without increase in major adverse events. We found no evidence to compare its effects to behavior modification. The effect on the number of nocturnal voids is likely similar to that of alpha-blockers short-term with very infrequent major adverse events. There appears to be no added benefit in the combined use of desmopressin with an alpha-blocker or an anticholinergic. The findings of this review were limited by short-term follow-up, study limitations, and imprecision.
Topics: Adrenergic alpha-Antagonists; Aged; Antidiuretic Agents; Cholinergic Antagonists; Deamino Arginine Vasopressin; Drug Therapy, Combination; Humans; Male; Middle Aged; Nocturia; Quality of Life; Randomized Controlled Trials as Topic; Withholding Treatment
PubMed: 29055129
DOI: 10.1002/14651858.CD012059.pub2 -
Indian Journal of Endocrinology and... 2015To evaluate the efficacy and safety of canagliflozin in combination therapy among patients with type 2 diabetes mellitus with inadequate glycemic control. (Review)
Review
OBJECTIVE
To evaluate the efficacy and safety of canagliflozin in combination therapy among patients with type 2 diabetes mellitus with inadequate glycemic control.
METHODS
Two review authors independently searched for the relevant randomized controlled clinical trials from the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, IndMed, LILACS, and clinical trials registry www.clinicaltrials.gov. Primary outcomes for this review included: change in hemoglobin A1c (HbA1c) levels, fasting plasma glucose (FPG) levels and risk of occurrence of genital mycotic infections at 26 weeks. We combined results using mean difference (MD) for continuous data, and risk ratio (RR) for dichotomous data.
RESULTS
Of the 124 identified reports, five RCTs with 3565 participants were eligible for the meta-analysis. All included studies had compared canagliflozin 100 mg and 300 mg once daily with placebo or sitagliptin 100 mg once daily. We judged that most of the studies had low risk of bias or unclear risk of bias in five major domains. Canagliflozin 300 mg once daily led to a significant decrease in HbA1c levels (IV Fixed -0.77, 95% CI [-0.90, -0.64] P < 0.00001) and FPG levels (IV Fixed -2.08; 95% CI [-2.32, -1.84], P <0.00001), body weight, systolic blood pressure and triglyceride levels after 26 weeks as compared to placebo. There was a also a significant difference in the efficacy of canagliflozin 300 mg and sitagliptin 100 mg once daily in favour of canagliflozin. Both doses of canagliflozin led to genital mycotic infections among males and females, urinary tract infections, pollakiuria, polyuria and postural dizziness.
CONCLUSIONS
Canagliflozin significantly decreases HbA1c and FPG levels and body weight as compared to placebo among patients with inadequate glycemic control with an earlier regime of glucose lowering agents. Long term safety studies are required to evaluate the incidence of adverse events.
PubMed: 26693420
DOI: 10.4103/2230-8210.167562