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Stroke Aug 2020Cilostazol, a phosphodiesterase 3' inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Cilostazol, a phosphodiesterase 3' inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease progression.
METHODS
A systematic review and meta-analysis of unconfounded randomized controlled trials of cilostazol to prevent stroke, cognitive decline, or radiological small vessel disease lesion progression. Two reviewers searched for papers (January 1, 2019 to July 16, 2019) and extracted data. We calculated Peto odds ratios (ORs) and 95% CIs for recurrent ischemic, hemorrhagic stroke, death, adverse symptoms, with sensitivity analyses. The review is registered (CRD42018084742).
RESULTS
We included 20 randomized controlled trials (n=10 505), 18 in ischemic stroke (total n=10 449) and 2 in cognitive impairment (n=56); most were performed in Asia-Pacific countries. Cilostazol decreased recurrent ischemic stroke (17 trials, n=10 225, OR=0.68 [95% CI, 0.57-0.81]; <0.0001), hemorrhagic stroke (16 trials, n=9736, OR=0.43 [95% CI, 0.29-0.64]; =0.0001), deaths (OR=0.64 [95% CI, 0.49-0.83], <0.0009), systemic bleeding (n=8387, OR=0.73 [95% CI, 0.54-0.99]; =0.04), but increased headache and palpitations, compared with placebo, aspirin, or clopidogrel. Cilostazol reduced recurrent ischemic stroke more when given long (>6 months) versus short term without increasing hemorrhage, and in trials with larger proportions (>40%) of lacunar stroke. Data were insufficient to assess effects on cognition, imaging, functional outcomes, or tolerance.
CONCLUSIONS
Cilostazol appears effective for long-term secondary stroke prevention without increasing hemorrhage risk. However, most trials related to Asia-Pacific patients and more trials in Western countries should assess its effects on cognitive decline, functional outcome, and tolerance, particularly in lacunar stroke and other presentations of small vessel disease.
Topics: Cilostazol; Cognitive Dysfunction; Fibrinolytic Agents; Humans; Phosphodiesterase 3 Inhibitors; Secondary Prevention; Stroke
PubMed: 32646330
DOI: 10.1161/STROKEAHA.120.029454 -
Medicina (Kaunas, Lithuania) Jun 2020: Lactation ketoacidosis is a rare cause of high anion gap metabolic acidosis affecting breastfeeding mothers. We aim to review and analyze all cases of lactation...
: Lactation ketoacidosis is a rare cause of high anion gap metabolic acidosis affecting breastfeeding mothers. We aim to review and analyze all cases of lactation ketoacidosis reported. : A systematic search of PubMed/MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL), identifying relevant case reports published from 1 January 1970 to 31 December 2019. We extracted the following data: the first author, country, year of publication, age of the mother, age of the child, weight/body mass index (BMI) of the mother, precipitating factors, presenting symptoms, biochemical results, treatment, breastfeeding, and time from presentation to the resolution of ketoacidosis. : Sixteen case reports and 1 case series reporting 18 cases of lactation ketoacidosis were found. Presenting symptoms were nausea (72%, 13/18), vomiting (67%, 12/18), malaise (56%, 10/18), abdominal pain (44%, 8/18), dyspnea (33%, 6/18), headache (22%, 4/18), and palpitation (11%, 2/18). Dieting and physical exercise to lose weight were reported in 76% (14/18). The treatments included IV dextrose, sodium bicarbonate, insulin, rehydration, monitoring and replacement of electrolytes, and resumption of a balanced diet. The prognoses were good, with no mortalities. lactation ketoacidosis should be suspected in unwell breastfeeding women with high anion gap metabolic acidosis, after excluding other causes.
Topics: Acidosis; Adult; Breast Feeding; Female; Humans; Hypoglycemic Agents; Insulin; Ketosis; Lactation; Mothers
PubMed: 32560535
DOI: 10.3390/medicina56060299 -
Frontiers in Genetics 2019Short QT syndrome (SQTS) is a rare syndrome and affects different types of genes. However, data on differences of clinical profile and outcome of different SQTS types...
BACKGROUND
Short QT syndrome (SQTS) is a rare syndrome and affects different types of genes. However, data on differences of clinical profile and outcome of different SQTS types are sparse.
METHODS
We conducted a pooled analysis of 110 SQTS patients. Patients have been diagnosed between 2000 and 2017 at our institution (n = 12) and revealed using a literature review (n = 98). 29 studies were identified by analysing systematic data bases (PubMed, Web of Science, Cochrane Libary, Cinahl).
RESULTS
67 patients with genotype positive SQTS origin and 43 patients with genotype negative origin were found. A significant difference is documented between the sex with a higher predominance of male in genotype negative SQTS patients and predominance of females in genotype positive SQTS patients (male 52% versus 84%, female 45% versus 14%; p = 0.0016). No relevant difference of their median age (genotype positive 27 ± 19 versus genotype negative 29 ± 15; p = 0.48) was found. Asymptomatic patients and patients reporting symptoms such as syncope, sudden cardiac death, atrial flutter and ventricular fibrillation documented in both groups were similar except atrial fibrillation (genotype positive 19% versus genotype negative 0%; p = 0.0055). The QTc interval was not significantly different in both groups (genotype positive 315 ± 32 versus genotype negative 320 ± 19; p = 0.30). The treatments (medical treatment and ICD implantation) in both groups were comparable. Electrophysiology studies were not significantly higher documented in patients with genotype positive and negative origin (24% versus 9%; p = 0.075). Events at follow up such as VT, VF, and SCD were not higher presented in patients with genotype positive (13% versus 9%) (p = 0.25). 54% of genotype positive SQTS patients showed SQTS 1 followed by STQS 2 (21%) and SQTS 3 (10%).
CONCLUSIONS
The long-term risk of a malignant arrhythmic event is not higher in patients with genotype positive. However, patients with genotype positive present themselves more often with AF with a female predominance. Also, other events at follow up such as syncope, atrial flutter and palpitation were not significantly higher (9% versus 0%; p = 0.079).
PubMed: 32010184
DOI: 10.3389/fgene.2019.01312 -
Health Technology Assessment... Jan 2020Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with an increased risk of stroke and congestive heart failure. Lead-I...
BACKGROUND
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with an increased risk of stroke and congestive heart failure. Lead-I electrocardiogram (ECG) devices are handheld instruments that can be used to detect AF at a single time point in people who present with relevant signs or symptoms.
OBJECTIVE
To assess the diagnostic test accuracy, clinical impact and cost-effectiveness of using single time point lead-I ECG devices for the detection of AF in people presenting to primary care with relevant signs or symptoms, and who have an irregular pulse compared with using manual pulse palpation (MPP) followed by a 12-lead ECG in primary or secondary care.
DATA SOURCES
MEDLINE, MEDLINE Epub Ahead of Print and MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PubMed, Cochrane Databases of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects and the Health Technology Assessment Database.
METHODS
The systematic review methods followed published guidance. Two reviewers screened the search results (database inception to April 2018), extracted data and assessed the quality of the included studies. Summary estimates of diagnostic accuracy were calculated using bivariate models. An economic model consisting of a decision tree and two cohort Markov models was developed to evaluate the cost-effectiveness of lead-I ECG devices.
RESULTS
No studies were identified that evaluated the use of lead-I ECG devices for patients with signs or symptoms of AF. Therefore, the diagnostic accuracy and clinical impact results presented are derived from an asymptomatic population (used as a proxy for people with signs or symptoms of AF). The summary sensitivity of lead-I ECG devices was 93.9% [95% confidence interval (CI) 86.2% to 97.4%] and summary specificity was 96.5% (95% CI 90.4% to 98.8%). One study reported limited clinical outcome data. Acceptability of lead-I ECG devices was reported in four studies, with generally positive views. The de novo economic model yielded incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) gained. The results of the pairwise analysis show that all lead-I ECG devices generated ICERs per QALY gained below the £20,000-30,000 threshold. Kardia Mobile (AliveCor Ltd, Mountain View, CA, USA) is the most cost-effective option in a full incremental analysis.
LIMITATIONS
No published data evaluating the diagnostic accuracy, clinical impact or cost-effectiveness of lead-I ECG devices for the population of interest are available.
CONCLUSIONS
Single time point lead-I ECG devices for the detection of AF in people with signs or symptoms of AF and an irregular pulse appear to be a cost-effective use of NHS resources compared with MPP followed by a 12-lead ECG in primary or secondary care, given the assumptions used in the base-case model.
FUTURE WORK
Studies assessing how the use of lead-I ECG devices in this population affects the number of people diagnosed with AF when compared with current practice would be useful.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42018090375.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Atrial Fibrillation; Cost-Benefit Analysis; Electrocardiography; Heart Failure; Humans; Mass Screening; Models, Economic; Predictive Value of Tests; Primary Health Care; Pulse; Quality-Adjusted Life Years; Stroke; Technology Assessment, Biomedical
PubMed: 31933471
DOI: 10.3310/hta24030 -
The Cochrane Database of Systematic... Aug 2019Chronic venous insufficiency (CVI) is a progressive and common disease that affects the superficial and deep venous systems of the lower limbs. CVI is characterised by...
BACKGROUND
Chronic venous insufficiency (CVI) is a progressive and common disease that affects the superficial and deep venous systems of the lower limbs. CVI is characterised by valvular incompetence, reflux, venous obstruction, or a combination of these with consequent distal venous hypertension. Clinical manifestations of CVI include oedema, pain, skin changes, ulcerations and dilated skin veins in the lower limbs. It can result in a large financial burden on health systems. There is a wide variety of treatment options or therapies for CVI, ranging from surgery and medication to compression and physiotherapy. Balneotherapy (treatments involving water) is a relatively cheap option and potentially efficient way to deliver physical therapy for people with CVI.
OBJECTIVES
To assess the efficacy and safety of balneotherapy for the treatment of people with chronic venous insufficiency (CVI).
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and the Clinical Trials.gov trials register to August 2018. We searched the LILACS and IBECS databases. We also checked references, searched citations and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials comparing balneotherapy with no treatment or other types of treatment for CVI. We also included studies that used a combination of treatments.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed studies retrieved by the search strategies. Both review authors independently assessed selected studies for complete analysis. We resolved conflicts through discussion. We attempted to contact trial authors for missing data, obtaining additional information. For binary outcomes (leg ulcer incidence and adverse events), we presented the results using odds ratio (OR) with 95% confidence intervals (CI). For continuous outcomes (disease severity, health-related quality of life (HRQoL), pain, oedema, skin pigmentation), we presented the results as a mean difference (MD) with 95% CI.
MAIN RESULTS
We included seven randomised controlled trials with 891 participants (outpatients in secondary care). We found no quasi-randomised controlled trials. Six studies (836 participants) evaluated balneotherapy versus no treatment. One study evaluated balneotherapy versus a phlebotonic drug (melilotus officinalis) (55 participants). There was a lack of blinding of participants and investigators, imprecision and inconsistency, which downgraded the certainty of the evidence.For the balneotherapy versus no treatment comparison, there probably was no improvement in favour of balneotherapy in disease severity signs and symptom score as assessed using the Venous Clinical Severity Score (VCSS) (MD -1.66, 95% CI -4.14 to 0.83; 2 studies, 484 participants; moderate-certainty evidence). Balneotherapy probably resulted in a moderate improvement in HRQoL as assessed by the Chronic Venous Insufficiency Questionnaire 2 (CVIQ2) at three months (MD -9.38, 95% CI -18.18 to -0.57; 2 studies, 149 participants; moderate-certainty evidence), nine months (MD -10.46, 95% CI -11.81 to -9.11; 1 study; 55 participants; moderate-certainty evidence), and 12 months (MD -4.99, 95% CI -9.19 to -0.78; 2 studies, 455 participants; moderate-certainty evidence). There was no clear difference in HRQoL between balneotherapy and no treatment at six months (MD -1.64, 95% CI -9.18 to 5.89; 2 studies, 445 participants; moderate-certainty evidence). Balneotherapy probably slightly improved pain compared with no treatment (MD -1.23, 95% CI -1.33 to -1.13; 1 study; 390 participants; moderate-certainty evidence). There was no clear effect related to oedema between the two groups at 24 days (MD 43.28 mL, 95% CI -102.74 to 189.30; 2 studies, 153 participants; very-low certainty evidence). There probably was no improvement in favour of balneotherapy in the incidence of leg ulcers (OR 1.69, 95% CI 0.82 to 3.48; 2 studies, 449 participants; moderate-certainty evidence). There was probably a reduction in incidence of skin pigmentation changes in favour of balneotherapy at 12 months (pigmentation index: MD -3.59, 95% CI -4.02 to -3.16; 1 study; 59 participants; low-certainty evidence). The main complications reported included erysipelas (OR 2.58, 95% CI 0.65 to 10.22; 2 studies, 519 participants; moderate-certainty evidence), thromboembolic events (OR 0.35, 95% CI 0.09 to 1.42; 3 studies, 584 participants; moderate-certainty evidence) and palpitations (OR 0.33, 95% CI 0.01 to 8.52; 1 study; 59 participants; low-certainty evidence), with no clear evidence of an increase in reported adverse effects with balneotherapy. There were no serious adverse events reported in any of the studies.For the balneotherapy versus a phlebotonic drug (melilotus officinalis) comparison, we observed no clear difference in pain symptoms (OR 0.29, 95% CI 0.03 to 2.87; 1 study; 35 participants; very low-certainty evidence) and oedema (OR 0.21, 95% CI 0.02 to 2.27; 1 study; 35 participants; very low-certainty evidence). This single study did not report on the other outcomes of interest.
AUTHORS' CONCLUSIONS
We identified moderate- to low-certainty evidence that suggests that balneotherapy may result in a moderate improvement in pain, quality of life and skin pigmentation changes and has no clear effect on disease severity signs and symptoms score, adverse effects, leg ulcers and oedema when compared with no treatment. For future studies, measurements of outcomes such as disease severity sign and symptom score, quality of life, pain and oedema and choice of time points during follow-up must be standardised for adequate comparison between trials.
Topics: Balneology; Edema; Humans; Leg Ulcer; Pain Management; Quality of Life; Randomized Controlled Trials as Topic; Venous Insufficiency
PubMed: 31449319
DOI: 10.1002/14651858.CD013085.pub2 -
BMC Urology Jan 2019Paroxetine is one of the selective serotonin reuptake inhibitors (SSRIs) used in the treatment of premature ejaculation (PE). However, this use is not approved in many... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Paroxetine is one of the selective serotonin reuptake inhibitors (SSRIs) used in the treatment of premature ejaculation (PE). However, this use is not approved in many countries. The purpose of this systematic review and meta-analysis is to review the efficacy and safety of paroxetine for PE patients.
METHODS
We searched relevant randomized, controlled trials through May 2018, using PubMed, Embase and Cochrane Central Register. The main endpoint included intra-vaginal ejaculatory latency time (IELT) and side effects in the treatment of PE. Cochrane Collaboration's Revman software, version 5.3, was used for statistical analysis.
RESULTS
Out of 493 unique articles, a total of 19 randomized, controlled trials (RCTs) were reviewed. Quite a few RCTs were considered to have unclear risk of bias because of limited information. Pooled outcomes suggested that paroxetine was more effective than placebo, fluoxetine and escitalopram at increasing IELT (all p < 0.05). However, there existed a high level of heterogeneity in the paroxetine vs. fluoxetine groups and the paroxetine vs. placebo groups. Comparing paroxetine with tramadol, sertraline, phosphodiesterase 5 inhibitors (PDE5Is), local lidocaine gel, behaviour therapy or dapoxetine, we found that the increase in IELT was not statistically significant between groups. Paroxetine combined with tadalafil or behaviour therapy was more efficacious than paroxetine alone (all p < 0.05). Although the side effects in the combination group were more common than in the paroxetine alone group, the most common adverse events, such as nausea, muscle soreness, palpitation and flushing, were mild and tolerable. The main limitations of this systematic review and meta-analysis were the different definitions of PE and short follow-up times.
CONCLUSIONS
According to this systematic review and meta-analysis, paroxetine provided better efficacy than placebo, fluoxetine and escitalopram in the treatment of PE, with well-tolerated side effects. The combination group had better efficacy than the paroxetine alone group.
TRIAL REGISTRATION
This review was reported in agreement with the PRISMA statement and was registered on PROSPERO 2018CRD42018097014 .
Topics: Humans; Male; Paroxetine; Premature Ejaculation; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 30606186
DOI: 10.1186/s12894-018-0431-7 -
The Egyptian Heart Journal : (EHJ) :... Dec 2018Idiopathic short-coupled ventricular tachyarrhythmias make up a considerable proportion of ventricular tachyarrhythmias in structurally normal hearts and are the cause... (Review)
Review
INTRODUCTION
Idiopathic short-coupled ventricular tachyarrhythmias make up a considerable proportion of ventricular tachyarrhythmias in structurally normal hearts and are the cause of 5-10% of unexpected sudden cardiac deaths. There is disparity in the literature regarding their description and a lack of formal diagnostic criteria to define them.
OBJECTIVE
To validate ECG indices for the diagnosis of these ventricular tachyarrythmias and to subsequently unify their differing descriptions in the literature under a new terminology: .
METHODS
We conducted a systematic review of all published studies describing short-coupled torsades de pointes, idiopathic ventricular fibrillation and polymorphic ventricular tachycardia. Published tracings were analysed using a standard set of criteria to define the different ECG intervals. Previously proposed diagnostic indices were validated using a control group of previously published long-coupled torsades de pointes cases.
RESULTS
Validation of the ECG indices revealed that a coupling interval < 400 ms was the most reliable measurement (sensitivity 100%, specificity 97%), followed by a coupling interval/QT < 1 (sensitivity 96%, specificity 100%).
CONCLUSION
Idiopathic short-coupled ventricular tachyarrhythmias encompass all previous descriptions of this tachyarrhythmia including idiopathic ventricular fibrillation, short-coupled torsades de pointes, Purkinje-related torsades de pointes and idiopathic polymorphic ventricular tachycardia. This arrhythmia can be diagnosed by newly proposed criteria with high sensitivity and specificity.
PubMed: 30591747
DOI: 10.1016/j.ehj.2018.06.003 -
British Journal of Clinical Pharmacology Sep 2018Several antihypertensive drugs are used in the treatment of severe hypertension in pregnancy. The present study is a network meta-analysis comparing the efficacy and... (Meta-Analysis)
Meta-Analysis Review
AIMS
Several antihypertensive drugs are used in the treatment of severe hypertension in pregnancy. The present study is a network meta-analysis comparing the efficacy and safety of these drugs.
METHODS
Electronic databases were searched for randomized clinical trials comparing drugs used in the treatment of severe hypertension in pregnancy. The number of women achieving the target blood pressure (BP) was the primary outcome. Doses required and time taken for achieving the target BP, failure rate, and incidences of maternal tachycardia, palpitation, hypotension, headache, and neonatal death and stillbirth were the secondary outcomes. Mixed treatment comparison pooled estimates were generated using a random-effects model. Odds ratios for the categorical and mean difference for the numerical outcomes were the effect estimates.
RESULTS
Fifty-one studies were included in the systematic review and 46 in the meta-analysis. No significant differences in the number of patients achieving target BP was observed between any of the drugs. Diazoxide [-15 (-20.6, -9.4)], nicardipine [-11.8 (-22.3, -1.2)], nifedipine/celastrol [-19.3 (-27.4, -11.1)], nifedipine/vitamin D [-17.1 (-25.7, -9.7)], nifedipine/resveratrol [-13.9 (-22.6, -5.2)] and glyceryl trinitrate [-33.8 (-36.7, -31)] were observed to achieve the target BP (in minutes) more rapidly than hydralazine. Nifedipine required fewer doses than hydralazine for achieving the target BP. Glyceryl trinitrate and labetalol were associated with fewer incidences of tachycardia and palpitation respectively than hydralazine. Trial sequential analysis concluded adequate evidence for hydralazine and nifedipine compared with labetalol. Moderate quality of evidence was observed for direct comparison estimate between labetalol and hydralazine but was either low or very low for other comparisons.
CONCLUSION
The present evidence suggests similar efficacy between nifedipine, hydralazine and labetalol in the treatment of severe hypertension in pregnancy. Subtle differences may exist in their safety profile. The evidence is inadequate for other drugs.
Topics: Antihypertensive Agents; Dose-Response Relationship, Drug; Female; Headache; Humans; Hydralazine; Hypertension; Hypotension; Incidence; Labetalol; Network Meta-Analysis; Nifedipine; Perinatal Death; Pregnancy; Pregnancy Complications, Cardiovascular; Randomized Controlled Trials as Topic; Stillbirth; Tachycardia; Treatment Outcome
PubMed: 29974489
DOI: 10.1111/bcp.13649 -
The Lancet. Infectious Diseases Aug 2018Dihydroartemisinin-piperaquine is an effective and well tolerated artemisinin-based combination therapy that has been assessed extensively for the prevention and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dihydroartemisinin-piperaquine is an effective and well tolerated artemisinin-based combination therapy that has been assessed extensively for the prevention and treatment of malaria. Piperaquine, similar to several structurally related antimalarials currently used, can prolong cardiac ventricular repolarisation duration and the electrocardiographic QT interval, leading to concerns about its proarrhythmic potential. We aimed to assess the risk of potentially lethal iatrogenic ventricular arrhythmias in individuals receiving dihydroartemisinin-piperaquine.
METHODS
We did a systematic review and Bayesian meta-analysis. We searched clinical bibliographic databases (last on May 24, 2017) for studies of dihydroartemisinin-piperaquine in human beings. Further unpublished studies were identified with the WHO Evidence Review Group on the Cardiotoxicity of Antimalarials. We searched for articles containing "dihydroartemisinin-piperaquine" as title, abstract, or subject heading keywords, with synonyms and variant spellings as additional search terms. We excluded animal studies, but did not apply limits on language or publication date. Eligible studies were prospective, randomised, controlled trials or cohort studies in which individuals received at least one 3-day treatment course of dihydroartemisinin-piperaquine for mass drug administration, preventive therapy, or case management of uncomplicated malaria, with follow-up over at least 3 days. At least two independent reviewers screened titles, abstracts, and full texts, agreed study eligibility, and extracted information about study and participant characteristics, adverse event surveillance methodology, dihydroartemisinin-piperaquine exposures, loss-to-follow up, and any deaths after dihydroartemisinin-piperaquine treatment into a standardised database. The risk of sudden unexplained death after dihydroartemisinin-piperaquine with 95% credible intervals (CI) generated by Bayesian meta-analysis was compared with the baseline rate of sudden cardiac death.
FINDINGS
Our search identified 94 eligible primary studies including data for 197 867 individuals who had received dihydroartemisinin-piperaquine: 154 505 in mass drug administration programmes; 15 188 in 14 studies of repeated courses in preventive therapies and case management of uncomplicated malaria; and 28 174 as single-course treatments of uncomplicated malaria in 76 case-management studies. There was one potentially drug-related sudden unexplained death: a healthy woman aged 16 in Mozambique who developed heart palpitations several hours after the second dose of dihydroartemisinin-piperaquine and collapsed and died on the way to hospital (no autopsy or ECG was done). The median pooled risk estimate of sudden unexplained death after dihydroartemisinin-piperaquine was 1 in 757 950 (95% CI 1 in 2 854 490 to 1 in 209 114). This risk estimate was not higher than the baseline rate of sudden cardiac death (0·7-11·9 per 100 000 person-years or 1 in 1 714 280 to 1 in 100 835 over a 30-day risk period). The risk of bias was low in most studies and unclear in a few.
INTERPRETATION
Dihydroartemisinin-piperaquine was associated with a low risk of sudden unexplained death that was not higher than the baseline rate of sudden cardiac death. Concerns about repolarisation-related cardiotoxicity need not limit its current use for the prevention and treatment of malaria.
FUNDING
Wellcome Trust, UK Medical Research Council, WHO, Bill & Melinda Gates Foundation, and University of Oxford.
Topics: Adolescent; Animals; Antimalarials; Artemisinins; Bayes Theorem; Cause of Death; Cohort Studies; Drug Therapy, Combination; Female; Humans; Malaria; Mozambique; Prospective Studies; Quinolines
PubMed: 29887371
DOI: 10.1016/S1473-3099(18)30297-4 -
The Cochrane Database of Systematic... May 2018Nicotine replacement therapy (NRT) aims to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nicotine replacement therapy (NRT) aims to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence.
OBJECTIVES
To determine the effectiveness and safety of nicotine replacement therapy (NRT), including gum, transdermal patch, intranasal spray and inhaled and oral preparations, for achieving long-term smoking cessation, compared to placebo or 'no NRT' interventions.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group trials register for papers mentioning 'NRT' or any type of nicotine replacement therapy in the title, abstract or keywords. Date of most recent search is July 2017.
SELECTION CRITERIA
Randomized trials in people motivated to quit which compared NRT to placebo or to no treatment. We excluded trials that did not report cessation rates, and those with follow-up of less than six months, except for those in pregnancy (where less than six months, these were excluded from the main analysis). We recorded adverse events from included and excluded studies that compared NRT with placebo. Studies comparing different types, durations, and doses of NRT, and studies comparing NRT to other pharmacotherapies, are covered in separate reviews.
DATA COLLECTION AND ANALYSIS
Screening, data extraction and 'Risk of bias' assessment followed standard Cochrane methods. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model.
MAIN RESULTS
We identified 136 studies; 133 with 64,640 participants contributed to the primary comparison between any type of NRT and a placebo or non-NRT control group. The majority of studies were conducted in adults and had similar numbers of men and women. People enrolled in the studies typically smoked at least 15 cigarettes a day at the start of the studies. We judged the evidence to be of high quality; we judged most studies to be at high or unclear risk of bias but restricting the analysis to only those studies at low risk of bias did not significantly alter the result. The RR of abstinence for any form of NRT relative to control was 1.55 (95% confidence interval (CI) 1.49 to 1.61). The pooled RRs for each type were 1.49 (95% CI 1.40 to 1.60, 56 trials, 22,581 participants) for nicotine gum; 1.64 (95% CI 1.53 to 1.75, 51 trials, 25,754 participants) for nicotine patch; 1.52 (95% CI 1.32 to 1.74, 8 trials, 4439 participants) for oral tablets/lozenges; 1.90 (95% CI 1.36 to 2.67, 4 trials, 976 participants) for nicotine inhalator; and 2.02 (95% CI 1.49 to 2.73, 4 trials, 887 participants) for nicotine nasal spray. The effects were largely independent of the definition of abstinence, the intensity of additional support provided or the setting in which the NRT was offered. A subset of six trials conducted in pregnant women found a statistically significant benefit of NRT on abstinence close to the time of delivery (RR 1.32, 95% CI 1.04 to 1.69; 2129 participants); in the four trials that followed up participants post-partum the result was no longer statistically significant (RR 1.29, 95% CI 0.90 to 1.86; 1675 participants). Adverse events from using NRT were related to the type of product, and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets. Attempts to quantitatively synthesize the incidence of various adverse effects were hindered by extensive variation in reporting the nature, timing and duration of symptoms. The odds ratio (OR) of chest pains or palpitations for any form of NRT relative to control was 1.88 (95% CI 1.37 to 2.57, 15 included and excluded trials, 11,074 participants). However, chest pains and palpitations were rare in both groups and serious adverse events were extremely rare.
AUTHORS' CONCLUSIONS
There is high-quality evidence that all of the licensed forms of NRT (gum, transdermal patch, nasal spray, inhalator and sublingual tablets/lozenges) can help people who make a quit attempt to increase their chances of successfully stopping smoking. NRTs increase the rate of quitting by 50% to 60%, regardless of setting, and further research is very unlikely to change our confidence in the estimate of the effect. The relative effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the individual. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT. NRT often causes minor irritation of the site through which it is administered, and in rare cases can cause non-ischaemic chest pain and palpitations.
Topics: Administration, Cutaneous; Administration, Inhalation; Chewing Gum; Female; Humans; Male; Nicotine; Nicotinic Agonists; Randomized Controlled Trials as Topic; Smoking Cessation; Smoking Prevention; Tablets; Time Factors; Tobacco Use Cessation Devices
PubMed: 29852054
DOI: 10.1002/14651858.CD000146.pub5