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Antiviral Therapy 2019The purpose of this review is to critically analyse data regarding the prevalence and risk factors for developing a prolonged QTc interval and subsequent sudden cardiac... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The purpose of this review is to critically analyse data regarding the prevalence and risk factors for developing a prolonged QTc interval and subsequent sudden cardiac death (SCD) in persons living with HIV (PLWH).
METHODS
A systematic literature search using PubMed and Google Scholar databases was performed using the following search terms: 'HIV and prolonged QTc' and 'managing HIV-patients with prolonged QTc'. References within articles of interest were also evaluated.
RESULTS/DISCUSSION
PLWH are at an increased risk of having a prolonged QTc interval. Some risk factors for this include the virus itself, concomitant medications, comorbid conditions, addictions and electrolyte disturbances. PLWH who have an increased HIV RNA viral load or decreased CD4 T-cell count are at further risk for progressing to sudden cardiac death (SCD). Many medications commonly prescribed in the PLWH population, such as antiretrovirals and antimicrobials used in opportunistic infection prophylaxis, have also been shown to promote QTc prolongation through inhibition of human ether-a-go-go potassium channels or through drug metabolism inhibition of other QTc prolonging drugs.
CONCLUSIONS
Due to the high number of risk factors associated with QTc prolongation, clinicians should incorporate baseline and routine ECG monitoring for PLWH to potentially lower the increased risk of SCD in PLWH.
Topics: Anti-Infective Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; Death, Sudden, Cardiac; Disease Management; Female; HIV Infections; Humans; Long QT Syndrome; Male; Prevalence; Risk Assessment; Risk Factors; Viral Load
PubMed: 31570667
DOI: 10.3851/IMP3335 -
Italian Journal of Pediatrics Apr 2021The existing treatment options for neonatal seizures have expanded over the last few decades, but no consensus has been reached regarding the optimal therapeutic...
AIM
The existing treatment options for neonatal seizures have expanded over the last few decades, but no consensus has been reached regarding the optimal therapeutic protocols. We systematically reviewed the available literature examining neonatal seizure treatments to clarify which drugs are the most effective for the treatment of specific neurologic disorders in newborns.
METHOD
We reviewed all available, published, literature, identified using PubMed (published between August 1949 and November 2020), that focused on the pharmacological treatment of electroencephalogram (EEG)-confirmed neonatal seizures.
RESULTS
Our search identified 427 articles, of which 67 were included in this review. Current knowledge allowed us to highlight the good clinical and electrographic responses of genetic early-onset epilepsies to sodium channel blockers and the overall good response to levetiracetam, whose administration has also been demonstrated to be safe in both full-term and preterm newborns.
INTERPRETATION
Our work contributes by confirming the limited availability of evidence that can be used to guide the use of anticonvulsants to treat newborns in clinical practice and examining the efficacy and potentially harmful side effects of currently available drugs when used to treat the developing newborn brain; therefore, our work might also serve as a clinical reference for future studies.
Topics: Anticonvulsants; Channelopathies; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Seizures; Sodium Potassium Chloride Symporter Inhibitors; Stroke
PubMed: 33827647
DOI: 10.1186/s13052-021-01027-2 -
American Journal of Cardiovascular... Apr 2020Levosimendan, a calcium sensitizer and potassium channel opener, has been demonstrated to improve myocardial function without increasing oxygen consumption and to show... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Levosimendan, a calcium sensitizer and potassium channel opener, has been demonstrated to improve myocardial function without increasing oxygen consumption and to show protective effects in other organs. Recently, a prospective, randomized controlled trial (RCT) revealed an association between levosimendan use and a possible increased risk of bleeding postoperatively. Levosimendan's anti-platelet effects have been shown in in vitro studies. Current studies do not provide sufficient data to support a relation between perioperative levosimendan administration and increased bleeding risk.
PURPOSE
Our goal was to investigate the relation between perioperative levosimendan administration and increased bleeding risk using a meta-analysis study design.
METHODS
The PubMed, Ovid, EMBASE and Cochrane Library databases were searched for relevant RCTs before July 1, 2019. The outcome parameters included reoperation secondary to increased bleeding in the postoperative period, the amount of postoperative recorded blood loss, and the need for transfusion of packed red blood cells (RBCs) and other blood products.
RESULTS
A total of 1160 patients in nine RCTs (576 in the levosimendan group and 584 in the control group) were included according to our inclusion criteria. Analysis showed that perioperative levosimendan administration neither increased the rate of reoperation secondary to bleeding nor increased the amount of postoperative chest tube drainage when compared with the control group. In terms of blood product transfusion, levosimendan did not influence the requirement for RBC transfusion, platelet transfusion nor fresh frozen plasma (FFP) transfusion. Levosimendan also did not shorten or prolong the aortic cross-clamp time or the cardiopulmonary bypass time.
CONCLUSION
The analyzed parameters, including reoperations due to bleeding, postoperative chest drainage and the requirement for blood products, revealed that levosimendan did not increase postoperative bleeding risk. More studies with a larger sample size are needed to address a more reliable conclusion due to study limitations.
Topics: Blood Transfusion; Cardiac Surgical Procedures; Cardiotonic Agents; Humans; Perioperative Care; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Risk; Simendan
PubMed: 31523760
DOI: 10.1007/s40256-019-00372-2 -
Expert Opinion on Emerging Drugs Mar 2008This review summarizes several promising pharmacological approaches for the therapeutic management of traumatic spinal cord injury (SCI), which are either in early-phase... (Review)
Review
BACKGROUND
This review summarizes several promising pharmacological approaches for the therapeutic management of traumatic spinal cord injury (SCI), which are either in early-phase clinical trials or nearing clinical translation.
OBJECTIVE
This review provides the reader with an understanding of the key pathophysiological mechanisms that contribute to neurological deficits after SCI. Through discussion of the mechanism(s) of action of the selected therapeutic approaches potentially important targets to aid further drug discovery will be highlighted.
METHODS
Systematic literature review of the pre-clinical literature and clinical SCI trials related to neuroprotective, immunomodulatory and regenerative therapeutic approaches.
RESULTS/CONCLUSION
The next decade will witness an unprecedented number of clinical trials which will seek to translate key biomedical research discoveries. The promising drug-based therapeutic approaches include regenerative strategies to neutralize myelin-mediated neurite outgrowth inhibition, neuroprotective strategies to reduce apoptotic triggers, the targeting of cationic/glutamatergic toxicity, anti-inflammatory strategies and the use of approaches to stabilize disrupted cell membranes.
Topics: Animals; Clinical Trials as Topic; Drugs, Investigational; Humans; Nerve Regeneration; Neuroprotective Agents; Potassium Channel Blockers; Recovery of Function; Sodium Channel Blockers; Spinal Cord Injuries
PubMed: 18321149
DOI: 10.1517/14728214.13.1.63 -
Journal of Hypertension Dec 2019Reductions in albuminuria of more than 30% are considered a strong marker of delay of chronic kidney disease (CKD) progression. Single renin-angiotensin system (RAS)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Reductions in albuminuria of more than 30% are considered a strong marker of delay of chronic kidney disease (CKD) progression. Single renin-angiotensin system (RAS) blockade represents the cornerstone of CKD treatment. However, as CKD progression still occurs, other nephroprotective options were explored; mineralocorticoid receptor antagonists (MRA) were tested with generally positive results.
METHODS
We conducted a systematic review and meta-analysis on the effects of MRAs on albuminuria/proteinuria, and adverse events, such as change in renal function and hyperkalemia incidence. A detailed search in electronic databases, clinical trial registries and grey literature was performed to retrieve randomized controlled trials (RCTs) in which administration of an MRA alone or on-top of ACEi/ARB was compared with placebo or active treatment.
RESULTS
Of the 45 initially identified reports, 31, with 2767 participants, were included in analysis of the primary outcome. The use of MRAs (alone or on top of RAS blockade) compared with placebo decreased urine albumin-to-creatinine ratio (UACR) by -24.55% (95% CI -29.57 to -19.53%), urine protein-to-creatinine ratio (UPCR) by -53.93% (95% CI -79% to -28.86%) and 24 h albumin excretion by -32.47% (95% CI -41.1 to -23.85%). MRAs also reduced UACR by -22.48% (95% CI -24.51 to -20.44%) compared with calcium-channel-blockers (CCBs), whereas no differences were found compared with a second ACEi/ARB or nonpotassium-sparing diuretics. Addition of an MRA was associated with change in estimated glomerular filtration rate (eGFR) of -2.38 ml/min per 1.73 m (95% CI -3.51 to -1.25), rise in potassium by 0.22 mEq/l (95% CI 0.16-0.28 mEq/l) and a 2.6-fold increase in hyperkalemia risk (RR 2.63, 95% CI 1.69-4.08) compared with placebo/active control.
CONCLUSION
Use of MRAs alone or on top of RAS blockade confers important antiproteinuric effects in patients with CKD, with a slight increase in mean potassium levels.
Topics: Humans; Mineralocorticoid Receptor Antagonists; Proteinuria; Renal Insufficiency, Chronic
PubMed: 31688290
DOI: 10.1097/HJH.0000000000002187 -
International Urology and Nephrology Dec 2018The prevalence of hypertension and its associated complications are markedly growing. Most patients need more than one drug to achieve blood pressure (BP) target.... (Meta-Analysis)
Meta-Analysis
The benefits of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers combined with calcium channel blockers on metabolic, renal, and cardiovascular outcomes in hypertensive patients: a meta-analysis.
BACKGROUND
The prevalence of hypertension and its associated complications are markedly growing. Most patients need more than one drug to achieve blood pressure (BP) target. However, most guidelines only focus on the first-line treatment. We conducted a meta-analysis to explore the benefits of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) combined with calcium channel blockers (CCBs) on metabolic, renal, and cardiovascular outcomes in hypertensive patients.
METHODS
A systematic literature search was conducted in MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov (until April 7, 2016) to identify randomized controlled trials (RCTs) comparing the benefits of ACEIs/ARBs combined with CCBs versus other dual or triple combinations on clinical outcomes in hypertensive patients. Random effects models were used to compute the weighted mean difference (WMD) for continuous variables.
RESULTS
Sixty RCTs (48,913 patients) were identified. When compared with other combinations, the combination of ACEIs/ARBs and CCBs had comparable WMD of systolic as well as diastolic BP (73 study arms) but provided better benefits on metabolic parameters, such as HDL, FBS, HbA1C, and serum uric acid; renal functions, including serum creatinine and estimated glomerular filtration rate; and cardiovascular diseases, including reduction of all cardiovascular events, myocardial infarction, and syncope/hypotension. A significant increase of serum potassium was observed.
CONCLUSION
The combination of ACEIs/ARBs with CCBs has superior benefits on metabolic, renal, and cardiovascular outcomes in hypertensive patients. Therefore, this combination should be considered whenever monotherapy does not achieve the guideline target.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Glucose; Blood Pressure; Calcium Channel Blockers; Cardiovascular Diseases; Creatinine; Drug Therapy, Combination; Fasting; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Hypertension; Incidence; Lipoproteins, HDL; Randomized Controlled Trials as Topic; Uric Acid
PubMed: 30324578
DOI: 10.1007/s11255-018-1991-x -
Molecular Medicine Reports Feb 2024Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in , or , which respectively encode the α, β and γ subunits of...
Liddle syndrome is an autosomal dominant form of monogenic hypertension that is caused by mutations in , or , which respectively encode the α, β and γ subunits of the epithelial sodium channel. In the present study, DNA was extracted from leukocytes in peripheral blood obtained from all members of a family with Liddle syndrome. Whole‑exome sequencing and Sanger sequencing were performed to assess the candidate variant and a co‑segregation analysis was conducted. A frameshift mutation in (NM_ 000336: c.1806dupG, p.Pro603Alafs*5) in the family was identified, characterized by early‑onset hypertension and hypokalemia. The mutation led to the truncation of the β subunit of the epithelial sodium channel and a lack of the conservative PY motif. Furthermore, a systematic review of follow‑up data from patients with Liddle syndrome with mutations was performed. The follow‑up data of 108 patients with pathogenic mutations from 47 families were summarized. Phenotypic heterogeneity was evident in patients with Liddle syndrome and early‑onset hypertension was the most frequent symptom. Patients responded well to targeted amiloride therapy with significant improvements in blood pressure and serum potassium concentration. The present study demonstrates that confirmatory genetic testing and targeted therapy can prevent premature onset of clinical endpoint events in patients with Liddle syndrome.
Topics: Humans; Liddle Syndrome; Epithelial Sodium Channels; Frameshift Mutation; Mutation; Hypertension; Potassium
PubMed: 38099339
DOI: 10.3892/mmr.2023.13142 -
Medical Gas Research Aug 2012This review evaluates the mechanism of volatile anesthetics as cardioprotective agents in both clinical and laboratory research and furthermore assesses possible cardiac...
This review evaluates the mechanism of volatile anesthetics as cardioprotective agents in both clinical and laboratory research and furthermore assesses possible cardiac side effects upon usage. Cardiac as well as non-cardiac surgery may evoke perioperative adverse events including: ischemia, diverse arrhythmias and reperfusion injury. As volatile anesthetics have cardiovascular effects that can lead to hypotension, clinicians may choose to administer alternative anesthetics to patients with coronary artery disease, particularly if the patient has severe preoperative ischemia or cardiovascular instability. Increasing preclinical evidence demonstrated that administration of inhaled anesthetics - before and during surgery - reduces the degree of ischemia and reperfusion injury to the heart. Recently, this preclinical data has been implemented clinically, and beneficial effects have been found in some studies of patients undergoing coronary artery bypass graft surgery. Administration of volatile anesthetic gases was protective for patients undergoing cardiac surgery through manipulation of the potassium ATP (KATP) channel, mitochondrial permeability transition pore (mPTP), reactive oxygen species (ROS) production, as well as through cytoprotective Akt and extracellular-signal kinases (ERK) pathways. However, as not all studies have demonstrated improved outcomes, the risks for undesirable hemodynamic effects must be weighed against the possible benefits of using volatile anesthetics as a means to provide cardiac protection in patients with coronary artery disease who are undergoing surgery.
PubMed: 22929111
DOI: 10.1186/2045-9912-2-22 -
Topics in Spinal Cord Injury... 2018Spasticity is a common secondary complication of spinal cord injury (SCI), which can severely impact functional independence and quality of life. 4-Aminopyridine (4-AP)...
Spasticity is a common secondary complication of spinal cord injury (SCI), which can severely impact functional independence and quality of life. 4-Aminopyridine (4-AP) is a potassium channel blocker that has been studied as an intervention for spasticity in individuals with SCI. To conduct a systematic review of the available evidence regarding the effectiveness of 4-AP for the management of spasticity in individuals with SCI. A comprehensive literature search was conducted on five electronic databases for articles published in English up to January 2017. Studies were included if (1) the sample size was three or more subjects, (2) the population was ≥50% SCI, (3) the subjects were ≥18 years old, (4) the treatment was 4-AP via any route, and (5) spasticity was assessed before and after the intervention. Subject characteristics, study design, intervention protocol, assessment methods, side effects, adverse events, and outcomes were extracted from selected studies. Randomized controlled trials (RCTs) were evaluated for methodological quality using the Physiotherapy Evidence Database (PEDro) tool. Levels of evidence were assigned using a modified Sackett scale. Nine studies met inclusion criteria with a pooled sample size of 591 subjects. Six studies were RCTs (PEDro = 6-10, Level 1 evidence) and three studies were pre-post tests (Level 4 evidence). There was a wide range in duration, severity, and level of SCI across subjects. Oral 4-AP was investigated in five studies; one study reported significant improvements on the Ashworth Scale (AS), while the remaining four studies found no improvement. Three studies found no significant improvements on the Spasm Frequency Scale. Intravenous 4-AP was investigated in three studies; no significant improvements were found on the AS or in the Reflex Score. Intrathecal 4-AP was investigated in one study, which did not find significant improvements on the AS. There is weak evidence supporting the effectiveness of 4-AP in reducing spasticity post SCI. Future research should utilize contemporary measures of spasticity and address methodological limitations such as small sample sizes.
Topics: 4-Aminopyridine; Humans; Muscle Relaxants, Central; Muscle Spasticity; Potassium Channel Blockers; Spinal Cord Injuries; Treatment Outcome
PubMed: 30459498
DOI: 10.1310/sci17-00048 -
BMC Endocrine Disorders Nov 2021Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant type of diabetes. Pathogenic variants in fourteen genes are reported as causes of MODY. Its symptoms...
BACKGROUND
Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant type of diabetes. Pathogenic variants in fourteen genes are reported as causes of MODY. Its symptoms overlap with type 1 and type 2 diabetes. Reviews for clinical characteristics, diagnosis and treatments are available but a comprehensive list of genetic variants, is lacking. Therefore this study was designed to collect all the causal variants involved in MODY, reported to date.
METHODS
We searched PubMed from its date of inception to December 2019. The search terms we used included disease names and name of all the known genes involved. The ClinVar database was also searched for causal variants in the known 14 MODY genes.
RESULTS
The record revealed 1647 studies and among them, 326 studies were accessed for full-text. Finally, 239 studies were included, as per our inclusion criteria. A total of 1017 variants were identified through literature review and 74 unpublished variants from Clinvar database. The gene most commonly affected was GCK, followed by HNF1a. The traditional Sanger sequencing was used in 76 % of the cases and 65 % of the studies were conducted in last 10 years. Variants from countries like Jordan, Oman and Tunisia reported that the MODY types prevalent worldwide were not common in their countries.
CONCLUSIONS
We expect that this paper will help clinicians interpret MODY genetics results with greater confidence. Discrepancies in certain middle-eastern countries need to be investigated as other genes or factors, like consanguinity may be involved in developing diabetes.
Topics: Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins; Basic Helix-Loop-Helix Transcription Factors; Diabetes Mellitus, Type 2; Glucokinase; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 1-beta; Hepatocyte Nuclear Factor 4; High-Throughput Nucleotide Sequencing; Homeodomain Proteins; Humans; Insulin; Lipase; Paired Box Transcription Factors; Potassium Channels, Inwardly Rectifying; Repressor Proteins; Sequence Analysis, DNA; Sulfonylurea Receptors; Trans-Activators; src-Family Kinases
PubMed: 34763692
DOI: 10.1186/s12902-021-00891-7