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The Cochrane Database of Systematic... Sep 2018People with thrombocytopenia often require a surgical procedure. A low platelet count is a relative contraindication to surgery due to the risk of bleeding. Platelet... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with thrombocytopenia often require a surgical procedure. A low platelet count is a relative contraindication to surgery due to the risk of bleeding. Platelet transfusions are used in clinical practice to prevent and treat bleeding in people with thrombocytopenia. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to surgery. Alternatives to platelet transfusion are also used prior surgery.
OBJECTIVES
To determine the clinical effectiveness and safety of prophylactic platelet transfusions prior to surgery for people with a low platelet count.
SEARCH METHODS
We searched the following major data bases: Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), PubMed (e-publications only), Ovid MEDLINE, Ovid Embase, the Transfusion Evidence Library and ongoing trial databases to 11 December 2017.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs), as well as non-RCTs and controlled before-and-after studies (CBAs), that met Cochrane EPOC (Effective Practice and Organisation of Care) criteria, that involved the transfusion of platelets prior to surgery (any dose, at any time, single or multiple) in people with low platelet counts. We excluded studies on people with a low platelet count who were actively bleeding.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane for data collection. We were only able to combine data for two outcomes and we presented the rest of the findings in a narrative form.
MAIN RESULTS
We identified five RCTs, all conducted in adults; there were no eligible non-randomised studies. Three completed trials enrolled 180 adults and two ongoing trials aim to include 627 participants. The completed trials were conducted between 2005 and 2009. The two ongoing trials are scheduled to complete recruitment by October 2019. One trial compared prophylactic platelet transfusions to no transfusion in people with thrombocytopenia in an intensive care unit (ICU). Two small trials, 108 participants, compared prophylactic platelet transfusions to other alternative treatments in people with liver disease. One trial compared desmopressin to fresh frozen plasma or one unit of platelet transfusion or both prior to surgery. The second trial compared platelet transfusion prior to surgery with two types of thrombopoietin mimetics: romiplostim and eltrombopag. None of the included trials were free from methodological bias. No included trials compared different platelet count thresholds for administering a prophylactic platelet transfusion prior to surgery. None of the included trials reported on all the review outcomes and the overall quality per reported outcome was very low.None of the three completed trials reported: all-cause mortality at 90 days post surgery; mortality secondary to bleeding, thromboembolism or infection; number of red cell or platelet transfusions per participant; length of hospital stay; or quality of life.None of the trials included children or people who needed major surgery or emergency surgical procedures.Platelet transfusion versus no platelet transfusion (1 trial, 72 participants)We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on all-cause mortality within 30 days (1 trial, 72 participants; risk ratio (RR) 0.78, 95% confidence interval (CI) 0.41 to 1.45; very-low quality evidence). We were very uncertain whether giving a platelet transfusion prior to surgery had any effect on the risk of major (1 trial, 64 participants; RR 1.60, 95% CI 0.29 to 8.92; very low-quality evidence), or minor bleeding (1 trial, 64 participants; RR 1.29, 95% CI 0.90 to 1.85; very-low quality evidence). No serious adverse events occurred in either study arm (1 trial, 72 participants, very low-quality evidence).Platelet transfusion versus alternative to platelet transfusion (2 trials, 108 participants)We were very uncertain whether giving a platelet transfusion prior to surgery compared to an alternative has any effect on the risk of major (2 trials, 108 participants; no events; very low-quality evidence), or minor bleeding (desmopressin: 1 trial, 36 participants; RR 0.89, 95% CI 0.06 to 13.23; very-low quality evidence: thrombopoietin mimetics: 1 trial, 65 participants; no events; very-low quality evidence). We were very uncertain whether there was a difference in transfusion-related adverse effects between the platelet transfused group and the alternative treatment group (desmopressin: 1 trial, 36 participants; RR 2.70, 95% CI 0.12 to 62.17; very-low quality evidence).
AUTHORS' CONCLUSIONS
Findings of this review were based on three small trials involving minor surgery in adults with thrombocytopenia. We found insufficient evidence to recommend the administration of preprocedure prophylactic platelet transfusions in this situation with a lack of evidence that transfusion resulted in a reduction in postoperative bleeding or all-cause mortality. The small number of trials meeting the inclusion criteria and the limitation in reported outcomes across the trials precluded meta-analysis for most outcomes. Further adequately powered trials, in people of all ages, of prophylactic platelet transfusions compared with no transfusion, other alternative treatments, and considering different platelet thresholds prior to planned and emergency surgical procedures are required. Future trials should include major surgery and report on bleeding, adverse effects, mortality (as a long-term outcome) after surgery, duration of hospital stay and quality of life measures.
Topics: Adult; Benzoates; Deamino Arginine Vasopressin; Hemostatics; Humans; Hydrazines; Plasma; Platelet Transfusion; Postoperative Care; Postoperative Hemorrhage; Pyrazoles; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Thrombocytopenia; Thrombopoietin
PubMed: 30221749
DOI: 10.1002/14651858.CD012779.pub2 -
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 -
JAMA May 2018Vasopressin is an alternative to catecholamine vasopressors for patients with distributive shock-a condition due to excessive vasodilation, most frequently from severe... (Comparative Study)
Comparative Study Meta-Analysis Review
Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock: A Systematic Review and Meta-analysis.
IMPORTANCE
Vasopressin is an alternative to catecholamine vasopressors for patients with distributive shock-a condition due to excessive vasodilation, most frequently from severe infection. Blood pressure support with a noncatecholamine vasopressor may reduce stimulation of adrenergic receptors and decrease myocardial oxygen demand. Atrial fibrillation is common with catecholamines and is associated with adverse events, including mortality and increased length of stay (LOS).
OBJECTIVES
To determine whether treatment with vasopressin + catecholamine vasopressors compared with catecholamine vasopressors alone was associated with reductions in the risk of adverse events.
DATA SOURCES
MEDLINE, EMBASE, and CENTRAL were searched from inception to February 2018. Experts were asked and meta-registries searched to identify ongoing trials.
STUDY SELECTION
Pairs of reviewers identified randomized clinical trials comparing vasopressin in combination with catecholamine vasopressors to catecholamines alone for patients with distributive shock.
DATA EXTRACTION AND SYNTHESIS
Two reviewers abstracted data independently. A random-effects model was used to combine data.
MAIN OUTCOMES AND MEASURES
The primary outcome was atrial fibrillation. Other outcomes included mortality, requirement for renal replacement therapy (RRT), myocardial injury, ventricular arrhythmia, stroke, and LOS in the intensive care unit and hospital. Measures of association are reported as risk ratios (RRs) for clinical outcomes and mean differences for LOS.
RESULTS
Twenty-three randomized clinical trials were identified (3088 patients; mean age, 61.1 years [14.2]; women, 45.3%). High-quality evidence supported a lower risk of atrial fibrillation associated with vasopressin treatment (RR, 0.77 [95% CI, 0.67 to 0.88]; risk difference [RD], -0.06 [95% CI, -0.13 to 0.01]). For mortality, the overall RR estimate was 0.89 (95% CI, 0.82 to 0.97; RD, -0.04 [95% CI, -0.07 to 0.00]); however, when limited to trials at low risk of bias, the RR estimate was 0.96 (95% CI, 0.84 to 1.11). The overall RR estimate for RRT was 0.74 (95% CI, 0.51 to 1.08; RD, -0.07 [95% CI, -0.12 to -0.01]). However, in an analysis limited to trials at low risk of bias, RR was 0.70 (95% CI, 0.53 to 0.92, P for interaction = .77). There were no significant differences in the pooled risks for other outcomes.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, the addition of vasopressin to catecholamine vasopressors compared with catecholamines alone was associated with a lower risk of atrial fibrillation. Findings for secondary outcomes varied.
Topics: Atrial Fibrillation; Catecholamines; Drug Therapy, Combination; Female; Humans; Length of Stay; Male; Publication Bias; Shock; Vasoconstrictor Agents; Vasopressins
PubMed: 29801010
DOI: 10.1001/jama.2018.4528 -
Frontiers in Neuroscience 2018Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are...
Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these. This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment. A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug, antipsychotic, schizophrenia, schizophren, psychos, psychotic, mental ill, mental disorder, neuroleptic, cardiovascular, cardiovascular diseases, clozapine, clozaril, autonomic, sympathetic, catecholamine, norepinephrine, noradrenaline, epinephrine, adrenaline. The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports. The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage cardiovascular side effects associated with clozapine. As there is often no alternative treatment for refractory schizophrenia, the current review highlights the need for better designed studies, use of autonomic tests for prevention of cardiovascular disease and development of novel interventions for clozapine-induced side effects.
PubMed: 29670504
DOI: 10.3389/fnins.2018.00203 -
The Cochrane Database of Systematic... Oct 2016People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents... (Meta-Analysis)
Meta-Analysis Review
Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review.
BACKGROUND
People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents that could replace, or reduce platelet transfusion, and are effective at reducing bleeding are needed.
OBJECTIVES
To compare the relative efficacy of different interventions for patients with thrombocytopenia due to chronic bone marrow failure and to derive a hierarchy of potential alternative treatments to platelet transfusions.
SEARCH METHODS
We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (the Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 27 April 2016.
SELECTION CRITERIA
We included randomised controlled trials in people with thrombocytopenia due to chronic bone marrow failure who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII (rFVIIa), desmopressin (DDAVP), recombinant factor XIII (rFXIII), recombinant interleukin (rIL)6 or rIL11, or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard of care or platelet transfusion). We excluded people undergoing intensive chemotherapy or stem cell transfusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results, extracted data and assessed trial quality. We estimated summary risk ratios (RR) for dichotomous outcomes. We planned to use summary mean differences (MD) for continuous outcomes. All summary measures are presented with 95% confidence intervals (CI).We could not perform a network meta-analysis because the included studies had important differences in the baseline severity of disease for the participants and in the number of participants undergoing chemotherapy. This raised important concerns about the plausibility of the transitivity assumption in the final dataset and we could not evaluate transitivity statistically because of the small number of trials per comparison. Therefore, we could only perform direct pairwise meta-analyses of included interventions.We employed a random-effects model for all analyses. We assessed statistical heterogeneity using the I statistic and its 95% CI. The risk of bias of each study included was assessed using the Cochrane 'Risk of bias' tool. The quality of the evidence was assessed using GRADE methods.
MAIN RESULTS
We identified seven completed trials (472 participants), and four ongoing trials (recruiting 837 participants) which are due to be completed by December 2020. Of the seven completed trials, five trials (456 participants) compared a TPO mimetic versus placebo (four romiplostim trials, and one eltrombopag trial), one trial (eight participants) compared DDAVP with placebo and one trial (eight participants) compared tranexamic acid with placebo. In the DDAVP trial, the only outcome reported was the bleeding time. In the tranexamic acid trial there were methodological flaws and bleeding definitions were subject to significant bias. Consequently, these trials could not be incorporated into the quantitative synthesis. No randomised trial of artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII, rIL6 or rIL11 was identified.We assessed all five trials of TPO mimetics included in this review to be at high risk of bias because the trials were funded by the manufacturers of the TPO mimetics and the authors had financial stakes in the sponsoring companies.The GRADE quality of the evidence was very low to moderate across the different outcomes.There was insufficient evidence to detect a difference in the number of participants with at least one bleeding episode between TPO mimetics and placebo (RR 0.86, 95% CI 0.56 to 1.31, four trials, 206 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of a life-threatening bleed between those treated with a TPO mimetic and placebo (RR 0.31, 95% CI 0.04 to 2.26, one trial, 39 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of all-cause mortality between those treated with a TPO mimetic and placebo (RR 0.74, 95%CI 0.52 to 1.05, five trials, 456 participants, very low-quality evidence).There was a significant reduction in the number of participants receiving any platelet transfusion between those treated with TPO mimetics and placebo (RR 0.76, 95% CI 0.61 to 0.95, four trials, 206 participants, moderate-quality evidence).There was no evidence for a difference in the incidence of transfusion reactions between those treated with TPO mimetics and placebo (pOR 0.06, 95% CI 0.00 to 3.44, one trial, 98 participants, very low-quality evidence).There was no evidence for a difference in thromboembolic events between TPO mimetics and placebo (RR 1.41, 95%CI 0.39 to 5.01, five trials, 456 participants, very-low quality evidence).There was no evidence for a difference in drug reactions between TPO mimetics and placebo (RR 1.12, 95% CI 0.83 to 1.51, five trials, 455 participants, low-quality evidence).No trial reported the number of days of bleeding per participant, platelet transfusion episodes, mean red cell transfusions per participant, red cell transfusion episodes, transfusion-transmitted infections, formation of antiplatelet antibodies or platelet refractoriness.In order to demonstrate a reduction in bleeding events from 26 in 100 to 16 in 100 participants, a study would need to recruit 514 participants (80% power, 5% significance).
AUTHORS' CONCLUSIONS
There is insufficient evidence at present for thrombopoietin (TPO) mimetics for the prevention of bleeding for people with thrombocytopenia due to chronic bone marrow failure. There is no randomised controlled trial evidence for artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII or rIL6 or rIL11, antifibrinolytics or DDAVP in this setting.
Topics: Benzoates; Bone Marrow Diseases; Chronic Disease; Deamino Arginine Vasopressin; Hemorrhage; Hemostatics; Humans; Hydrazines; Platelet Transfusion; Pyrazoles; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Thrombocytopenia; Thrombopoietin; Tranexamic Acid
PubMed: 27797129
DOI: 10.1002/14651858.CD012055.pub2 -
World Journal of Hepatology Feb 2016To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review.
AIM
To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review.
METHODS
Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG.
RESULTS
PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension.
CONCLUSION
PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.
PubMed: 26855694
DOI: 10.4254/wjh.v8.i4.231 -
The Cochrane Database of Systematic... Jul 2015Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disorder causing kidney disease. Current clinical management of ADPKD focuses primarily... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disorder causing kidney disease. Current clinical management of ADPKD focuses primarily on symptom control and reducing associated complications, particularly hypertension. In recent years, improved understanding of molecular and cellular mechanisms involved in kidney cyst growth and disease progression has resulted in new pharmaceutical agents to target disease pathogenesis to prevent progressive disease.
OBJECTIVES
We aimed to evaluate the effects of interventions for preventing ADPKD progression on kidney function, kidney endpoints, kidney structure, patient-centred endpoints (such as cardiovascular events, sudden death, all-cause mortality, hospitalisations, BP control, quality of life, and kidney pain), as well as the general and specific adverse effects related to their use.
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register to 6 June 2015 using relevant search terms.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing any interventions for preventing the progression of ADPKD with other interventions or placebo were considered for inclusion without language restriction.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study risks of bias and extracted data. We summarised treatment effects on clinical outcomes, kidney function and structure and adverse events using random effects meta-analysis. We assessed heterogeneity in estimated treatment effects using the Cochran Q test and I(2) statistic. Summary treatment estimates were calculated as a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes and a risk ratio (RR) for dichotomous outcomes together with their 95% confidence intervals.
MAIN RESULTS
We included 30 studies (2039 participants) that investigated 11 pharmacological interventions (angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), calcium channel blockers, beta blockers, vasopressin receptor 2 (V2R) antagonists, mammalian target of rapamycin (mTOR) inhibitors, somatostatin analogues, antiplatelet agents, eicosapentaenoic acids, statins and vitamin D compounds) in this review.ACEi significantly reduced diastolic blood pressure (9 studies, 278 participants: MD -4.96 mm Hg, 95% CI -8.88 to -1.04), but had uncertain effects on kidney volumes (MD -42.50 mL, 95% CI -115.68 to 30.67), GFR (MD -3.41 mL/min/1.73 m(2), 95% CI -15.83 to 9.01), and SCr (MD -0.02 mg/dL, 95% CI -0.14 to 0.09), in data largely restricted to children. ACEi did not show different effects on GFR (MD -8.19 mL/min/1.73 m(2), 95% CI -29.46 to 13.07) and albuminuria (SMD -0.19, 95% CI -1.77 to 1.39) when compared with beta-blockers, or SCr (MD 0.00 mg/dL, 95% CI -0.09 to 0.10) when compared with ARBs.Data for effects of V2R antagonists on kidney function and volumes compared to placebo were limited to narrative information within a single study while these agents increased thirst (1444 participants: RR 2.70, 95% CI 2.24 to 3.24) and dry mouth (1455 participants: RR 1.33, 95% CI 1.01 to 1.76).Compared with no treatment, mTOR inhibitors had uncertain effects on kidney function (2 studies, 115 participants: MD 4.45 mL/min/1.73 m(2), 95% CI -3.20 to 12.11) and kidney volume (MD -0.08 L, 95% CI -0.75 to 0.59) but in three studies (560 participants) caused angioedema (RR 13.39, 95% CI 2.56 to 70.00), oral ulceration (RR 6.77, 95% CI 4.42 to 10.38), infections (RR 1.14, 95% CI 1.04 to 1.25) and diarrhoea (RR 1.70, 95% CI 1.26 to 2.29).Somatostatin analogues (6 studies, 138 participants) slightly improved SCr (MD -0.43 mg/dL, 95% CI -0.86 to -0.01) and total kidney volume (MD -0.62 L, 95% CI -1.22 to -0.01) but had no definite effects on GFR (MD 9.50 mL/min, 95% CI -4.45 to 23.44) and caused diarrhoea (RR 3.72, 95% CI 1.43 to 9.68).Data for calcium channel blockers, eicosapentaenoic acids, statins, vitamin D compounds and antiplatelet agents were sparse and inconclusive.Random sequence generation was adequate in eight studies, and in almost half of the studies, blinding was not present or not specified. Most studies did not adequately report outcomes, which adversely affected our ability to assess this bias. The overall drop-out rate was over 10% in nine studies, and few were conducted using intention-to-treat analyses.
AUTHORS' CONCLUSIONS
Although several interventions are available for patients with ADPKD, at present there is little or no evidence that treatment improves patient outcomes in this population and is associated with frequent adverse effects. Additional large randomised studies focused on patient-centred outcomes are needed.
Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antidiuretic Hormone Receptor Antagonists; Child; Disease Progression; Eicosapentaenoic Acid; Humans; Platelet Aggregation Inhibitors; Polycystic Kidney, Autosomal Dominant; Randomized Controlled Trials as Topic; TOR Serine-Threonine Kinases
PubMed: 26171904
DOI: 10.1002/14651858.CD010294.pub2