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Annals of the Rheumatic Diseases Aug 2017The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new...
The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
Topics: Angiotensin-Converting Enzyme Inhibitors; Delphi Technique; Endothelin Receptor Antagonists; Europe; Fingers; Fluoxetine; Gastrointestinal Diseases; Glucocorticoids; Hematopoietic Stem Cell Transplantation; Humans; Hypertension, Pulmonary; Kidney Diseases; Lung Diseases; Phosphodiesterase 5 Inhibitors; Prostaglandins I; Pyrazoles; Pyrimidines; Raynaud Disease; Rheumatology; Scleroderma, Systemic; Selective Serotonin Reuptake Inhibitors; Ulcer
PubMed: 27941129
DOI: 10.1136/annrheumdis-2016-209909 -
JACC. Heart Failure Feb 2022This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction.
BACKGROUND
The estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized.
METHODS
We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor-neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]).
RESULTS
We identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses.
CONCLUSIONS
In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i.
Topics: Aged; Angiotensin Receptor Antagonists; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Network Meta-Analysis; Stroke Volume
PubMed: 34895860
DOI: 10.1016/j.jchf.2021.09.004 -
British Journal of Clinical Pharmacology Mar 2022Diverse genetic and/or external factors may induce psoriasis. Drug exposure is 1 such prominent external factor; antihypertensive drugs are reportedly associated with... (Meta-Analysis)
Meta-Analysis Review
AIMS
Diverse genetic and/or external factors may induce psoriasis. Drug exposure is 1 such prominent external factor; antihypertensive drugs are reportedly associated with psoriasis, but study results have been inconsistent. In this context, we investigated the associations between antihypertensive drugs and incidence if psoriasis via a systematic literature review and meta-analysis.
METHODS
Literature search in databases such as PubMed, Embase and Web of Science was conducted on 8 January 2021, and obtained data were pooled for meta- and network meta-analysis. Fixed- or random effect models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for evaluating the strength of the associations between antihypertensive drugs and psoriasis incidence. In addition to meta-analysis, Bayesian network meta-analysis was performed. ResultsThirteen eligible studies were included for meta-analysis with 6 378 116 individuals and 8 studies for network meta-analysis with 5 615 918 individuals. All antihypertensive drugs were significantly associated with psoriasis incidence. In a meta-analysis, the pooled ORs were 1.67 (95% CI: 1.31-2.13) for angiotensin-converting enzyme (ACE) inhibitors, 1.40 (95% CI: 1.20-1.63) for β-blockers, 1.53 (95% CI: 1.23-1.89) for calcium-channel blockers (CCBs), and 1.70 (95% CI: 1.40-2.06) for thiazide diuretics. For the comparative risks of psoriasis among antihypertensive drugs in the network meta-analysis, ORs were 2.09 (95% CI: 1.39-3.18) for ACE inhibitors, 1.35 (95% CI: 0.99-1.91) for BBs, 1.53 (95% CI: 1.07-2.24) for CCBs and 1.80 (95% CI: 1.23-2.66) for thiazide diuretics.
CONCLUSION
This study confirmed the associations between antihypertensive drugs and psoriasis; ACE inhibitors, BBs, CCBs and thiazide diuretics increased the risk of psoriasis. Therefore, antihypertensive drug users should be carefully monitored for psoriasis.
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Bayes Theorem; Calcium Channel Blockers; Humans; Hypertension; Network Meta-Analysis; Psoriasis; Sodium Chloride Symporter Inhibitors
PubMed: 34611920
DOI: 10.1111/bcp.15060 -
The Cochrane Database of Systematic... Apr 2018This is the first update of a review published in 2009. Sustained moderate to severe elevations in resting blood pressure leads to a critically important clinical... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is the first update of a review published in 2009. Sustained moderate to severe elevations in resting blood pressure leads to a critically important clinical question: What class of drug to use first-line? This review attempted to answer that question.
OBJECTIVES
To quantify the mortality and morbidity effects from different first-line antihypertensive drug classes: thiazides (low-dose and high-dose), beta-blockers, calcium channel blockers, ACE inhibitors, angiotensin II receptor blockers (ARB), and alpha-blockers, compared to placebo or no treatment.Secondary objectives: when different antihypertensive drug classes are used as the first-line drug, to quantify the blood pressure lowering effect and the rate of withdrawal due to adverse drug effects, compared to placebo or no treatment.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to November 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work.
SELECTION CRITERIA
Randomized trials (RCT) of at least one year duration, comparing one of six major drug classes with a placebo or no treatment, in adult patients with blood pressure over 140/90 mmHg at baseline. The majority (over 70%) of the patients in the treatment group were taking the drug class of interest after one year. We included trials with both hypertensive and normotensive patients in this review if the majority (over 70%) of patients had elevated blood pressure, or the trial separately reported outcome data on patients with elevated blood pressure.
DATA COLLECTION AND ANALYSIS
The outcomes assessed were mortality, stroke, coronary heart disease (CHD), total cardiovascular events (CVS), decrease in systolic and diastolic blood pressure, and withdrawals due to adverse drug effects. We used a fixed-effect model to to combine dichotomous outcomes across trials and calculate risk ratio (RR) with 95% confidence interval (CI). We presented blood pressure data as mean difference (MD) with 99% CI.
MAIN RESULTS
The 2017 updated search failed to identify any new trials. The original review identified 24 trials with 28 active treatment arms, including 58,040 patients. We found no RCTs for ARBs or alpha-blockers. These results are mostly applicable to adult patients with moderate to severe primary hypertension. The mean age of participants was 56 years, and mean duration of follow-up was three to five years.High-quality evidence showed that first-line low-dose thiazides reduced mortality (11.0% with control versus 9.8% with treatment; RR 0.89, 95% CI 0.82 to 0.97); total CVS (12.9% with control versus 9.0% with treatment; RR 0.70, 95% CI 0.64 to 0.76), stroke (6.2% with control versus 4.2% with treatment; RR 0.68, 95% CI 0.60 to 0.77), and coronary heart disease (3.9% with control versus 2.8% with treatment; RR 0.72, 95% CI 0.61 to 0.84).Low- to moderate-quality evidence showed that first-line high-dose thiazides reduced stroke (1.9% with control versus 0.9% with treatment; RR 0.47, 95% CI 0.37 to 0.61) and total CVS (5.1% with control versus 3.7% with treatment; RR 0.72, 95% CI 0.63 to 0.82), but did not reduce mortality (3.1% with control versus 2.8% with treatment; RR 0.90, 95% CI 0.76 to 1.05), or coronary heart disease (2.7% with control versus 2.7% with treatment; RR 1.01, 95% CI 0.85 to 1.20).Low- to moderate-quality evidence showed that first-line beta-blockers did not reduce mortality (6.2% with control versus 6.0% with treatment; RR 0.96, 95% CI 0.86 to 1.07) or coronary heart disease (4.4% with control versus 3.9% with treatment; RR 0.90, 95% CI 0.78 to 1.03), but reduced stroke (3.4% with control versus 2.8% with treatment; RR 0.83, 95% CI 0.72 to 0.97) and total CVS (7.6% with control versus 6.8% with treatment; RR 0.89, 95% CI 0.81 to 0.98).Low- to moderate-quality evidence showed that first-line ACE inhibitors reduced mortality (13.6% with control versus 11.3% with treatment; RR 0.83, 95% CI 0.72 to 0.95), stroke (6.0% with control versus 3.9% with treatment; RR 0.65, 95% CI 0.52 to 0.82), coronary heart disease (13.5% with control versus 11.0% with treatment; RR 0.81, 95% CI 0.70 to 0.94), and total CVS (20.1% with control versus 15.3% with treatment; RR 0.76, 95% CI 0.67 to 0.85).Low-quality evidence showed that first-line calcium channel blockers reduced stroke (3.4% with control versus 1.9% with treatment; RR 0.58, 95% CI 0.41 to 0.84) and total CVS (8.0% with control versus 5.7% with treatment; RR 0.71, 95% CI 0.57 to 0.87), but not coronary heart disease (3.1% with control versus 2.4% with treatment; RR 0.77, 95% CI 0.55 to 1.09), or mortality (6.0% with control versus 5.1% with treatment; RR 0.86, 95% CI 0.68 to 1.09).There was low-quality evidence that withdrawals due to adverse effects were increased with first-line low-dose thiazides (5.0% with control versus 11.3% with treatment; RR 2.38, 95% CI 2.06 to 2.75), high-dose thiazides (2.2% with control versus 9.8% with treatment; RR 4.48, 95% CI 3.83 to 5.24), and beta-blockers (3.1% with control versus 14.4% with treatment; RR 4.59, 95% CI 4.11 to 5.13). No data for these outcomes were available for first-line ACE inhibitors or calcium channel blockers. The blood pressure data were not used to assess the effect of the different classes of drugs as the data were heterogeneous, and the number of drugs used in the trials differed.
AUTHORS' CONCLUSIONS
First-line low-dose thiazides reduced all morbidity and mortality outcomes in adult patients with moderate to severe primary hypertension. First-line ACE inhibitors and calcium channel blockers may be similarly effective, but the evidence was of lower quality. First-line high-dose thiazides and first-line beta-blockers were inferior to first-line low-dose thiazides.
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Coronary Disease; Humans; Hypertension; Middle Aged; Randomized Controlled Trials as Topic; Sodium Chloride Symporter Inhibitors; Stroke; Thiazides
PubMed: 29667175
DOI: 10.1002/14651858.CD001841.pub3 -
The Cochrane Database of Systematic... Jan 2022This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the... (Review)
Review
BACKGROUND
This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated.
OBJECTIVES
To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events.
SEARCH METHODS
For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to 1 September 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted the authors of relevant papers regarding further published and unpublished work and checked the references of published studies to identify additional trials. The searches had no language restrictions.
SELECTION CRITERIA
Randomised controlled trials comparing first-line CCBs with other antihypertensive classes, with at least 100 randomised hypertensive participants and a follow-up of at least two years.
DATA COLLECTION AND ANALYSIS
Three review authors independently selected the included trials, evaluated the risk of bias, and entered the data for analysis. Any disagreements were resolved through discussion. We contacted study authors for additional information.
MAIN RESULTS
This update contains five new trials. We included a total of 23 RCTs (18 dihydropyridines, 4 non-dihydropyridines, 1 not specified) with 153,849 participants with hypertension. All-cause mortality was not different between first-line CCBs and any other antihypertensive classes. As compared to diuretics, CCBs probably increased major cardiovascular events (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.09, P = 0.03) and increased congestive heart failure events (RR 1.37, 95% CI 1.25 to 1.51, moderate-certainty evidence). As compared to beta-blockers, CCBs reduced the following outcomes: major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92), stroke (RR 0.77, 95% CI 0.67 to 0.88, moderate-certainty evidence), and cardiovascular mortality (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence). As compared to angiotensin-converting enzyme (ACE) inhibitors, CCBs reduced stroke (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence) and increased congestive heart failure (RR 1.16, 95% CI 1.06 to 1.28, low-certainty evidence). As compared to angiotensin receptor blockers (ARBs), CCBs reduced myocardial infarction (RR 0.82, 95% CI 0.72 to 0.94, moderate-certainty evidence) and increased congestive heart failure (RR 1.20, 95% CI 1.06 to 1.36, low-certainty evidence).
AUTHORS' CONCLUSIONS
For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Humans; Hypertension; Pharmaceutical Preparations
PubMed: 35000192
DOI: 10.1002/14651858.CD003654.pub6 -
The Cochrane Database of Systematic... Aug 2014Angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) are widely prescribed for primary hypertension (systolic blood... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) are widely prescribed for primary hypertension (systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg). However, while ACE inhibitors have been shown to reduce mortality and morbidity in placebo-controlled trials, ARBs have not. Therefore, a comparison of the efficacies of these two drug classes in primary hypertension for preventing total mortality and cardiovascular events is important.
OBJECTIVES
To compare the effects of ACE inhibitors and ARBs on total mortality and cardiovascular events, and their rates of withdrawals due to adverse effects (WDAEs), in people with primary hypertension.
SEARCH METHODS
We searched the Cochrane Hypertension Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the World Health Organization (WHO) International Clinical Trials Registry Platform, and the ISI Web of Science up to July 2014. We contacted study authors for missing and unpublished information, and also searched the reference lists of relevant reviews for eligible studies.
SELECTION CRITERIA
We included randomized controlled trials enrolling people with uncontrolled or controlled primary hypertension with or without other risk factors. Included trials must have compared an ACE inhibitor and an ARB in a head-to-head manner, and lasted for a duration of at least one year. If background blood pressure lowering agents were continued or added during the study, the protocol to do so must have been the same in both study arms.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
Nine studies with 11,007 participants were included. Of the included studies, five reported data on total mortality, three reported data on total cardiovascular events, and four reported data on cardiovascular mortality. No study separately reported cardiovascular morbidity. In contrast, eight studies contributed data on WDAE. Included studies were of good to moderate quality. There was no evidence of a difference between ACE inhibitors and ARBs for total mortality (risk ratio (RR) 0.98; 95% confidence interval (CI) 0.88 to 1.10), total cardiovascular events (RR 1.07; 95% CI 0.96 to 1.19), or cardiovascular mortality (RR 0.98; 95% CI 0.85 to 1.13). Conversely, a high level of evidence indicated a slightly lower incidence of WDAE for ARBs as compared with ACE inhibitors (RR 0.83; 95% CI 0.74 to 0.93; absolute risk reduction (ARR) 1.8%, number needed to treat for an additional beneficial outcome (NNTB) 55 over 4.1 years), mainly attributable to a higher incidence of dry cough with ACE inhibitors. The quality of the evidence for mortality and cardiovascular outcomes was limited by possible publication bias, in that several studies were initially eligible for inclusion in this review, but had no extractable data available for the hypertension subgroup. To this end, the evidence for total mortality was judged to be moderate, while the evidence for total cardiovascular events was judged to be low by the GRADE approach.
AUTHORS' CONCLUSIONS
Our analyses found no evidence of a difference in total mortality or cardiovascular outcomes for ARBs as compared with ACE inhibitors, while ARBs caused slightly fewer WDAEs than ACE inhibitors. Although ACE inhibitors have shown efficacy in these outcomes over placebo, our results cannot be used to extrapolate the same conclusion for ARBs directly, which have not been studied in placebo-controlled trials for hypertension. Thus, the substitution of an ARB for an ACE inhibitor, while supported by evidence on grounds of tolerability, must be made in consideration of the weaker evidence for the efficacy of ARBs regarding mortality and morbidity outcomes compared with ACE inhibitors. Additionally, our data mostly derives from participants with existing clinical sequelae of hypertension, and it would be useful to have data from asymptomatic people to increase the generalizability of this review. Unpublished subgroup data of hypertensive participants in existing trials comparing ACE inhibitors and ARBs needs to be made available for this purpose.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Essential Hypertension; Heart Diseases; Humans; Hypertension; Hypotension; Randomized Controlled Trials as Topic; Stroke
PubMed: 25148386
DOI: 10.1002/14651858.CD009096.pub2 -
The Cochrane Database of Systematic... Oct 2018Dysphagia (swallowing problems), which is common after stroke, is associated with increased risk of death or dependency, occurrence of pneumonia, poor quality of life,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dysphagia (swallowing problems), which is common after stroke, is associated with increased risk of death or dependency, occurrence of pneumonia, poor quality of life, and longer hospital stay. Treatments provided to improve dysphagia are aimed at accelerating recovery of swallowing function and reducing these risks. This is an update of the review first published in 1999 and updated in 2012.
OBJECTIVES
To assess the effects of swallowing therapy on death or dependency among stroke survivors with dysphagia within six months of stroke onset.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (26 June 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library (searched 26 June 2018), MEDLINE (26 June 2018), Embase (26 June 2018), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (26 June 2018), Web of Science Core Collection (26 June 2018), SpeechBITE (28 June 2016), ClinicalTrials.Gov (26 June 2018), and the World Health Organization International Clinical Trials Registry Platform (26 June 2018). We also searched Google Scholar (7 June 2018) and the reference lists of relevant trials and review articles.
SELECTION CRITERIA
We sought to include randomised controlled trials (RCTs) of interventions for people with dysphagia and recent stroke (within six months).
DATA COLLECTION AND ANALYSIS
Two review authors independently applied the inclusion criteria, extracted data, assessed risk of bias, used the GRADE approach to assess the quality of evidence, and resolved disagreements through discussion with the third review author (PB). We used random-effects models to calculate odds ratios (ORs), mean differences (MDs), and standardised mean differences (SMDs), and provided 95% confidence intervals (CIs) for each.The primary outcome was functional outcome, defined as death or dependency (or death or disability), at the end of the trial. Secondary outcomes were case fatality at the end of the trial, length of inpatient stay, proportion of participants with dysphagia at the end of the trial, swallowing ability, penetration aspiration score, or pneumonia, pharyngeal transit time, institutionalisation, and nutrition.
MAIN RESULTS
We added 27 new studies (1777 participants) to this update to include a total of 41 trials (2660 participants).We assessed the efficacy of swallowing therapy overall and in subgroups by type of intervention: acupuncture (11 studies), behavioural interventions (nine studies), drug therapy (three studies), neuromuscular electrical stimulation (NMES; six studies), pharyngeal electrical stimulation (PES; four studies), physical stimulation (three studies), transcranial direct current stimulation (tDCS; two studies), and transcranial magnetic stimulation (TMS; nine studies).Swallowing therapy had no effect on the primary outcome (death or dependency/disability at the end of the trial) based on data from one trial (two data sets) (OR 1.05, 95% CI 0.63 to 1.75; 306 participants; 2 studies; I² = 0%; P = 0.86; moderate-quality evidence). Swallowing therapy had no effect on case fatality at the end of the trial (OR 1.00, 95% CI 0.66 to 1.52; 766 participants; 14 studies; I² = 6%; P = 0.99; moderate-quality evidence). Swallowing therapy probably reduced length of inpatient stay (MD -2.9, 95% CI -5.65 to -0.15; 577 participants; 8 studies; I² = 11%; P = 0.04; moderate-quality evidence). Researchers found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.54). Swallowing therapy may have reduced the proportion of participants with dysphagia at the end of the trial (OR 0.42, 95% CI 0.32 to 0.55; 1487 participants; 23 studies; I² = 0%; P = 0.00001; low-quality evidence). Trial results show no evidence of a subgroup effect based on testing for subgroup differences (P = 0.91). Swallowing therapy may improve swallowing ability (SMD -0.66, 95% CI -1.01 to -0.32; 1173 participants; 26 studies; I² = 86%; P = 0.0002; very low-quality evidence). We found no evidence of a subgroup effect based on testing for subgroup differences (P = 0.09). We noted moderate to substantial heterogeneity between trials for these interventions. Swallowing therapy did not reduce the penetration aspiration score (i.e. it did not reduce radiological aspiration) (SMD -0.37, 95% CI -0.74 to -0.00; 303 participants; 11 studies; I² = 46%; P = 0.05; low-quality evidence). Swallowing therapy may reduce the incidence of chest infection or pneumonia (OR 0.36, 95% CI 0.16 to 0.78; 618 participants; 9 studies; I² = 59%; P = 0.009; very low-quality evidence).
AUTHORS' CONCLUSIONS
Moderate- and low-quality evidence suggests that swallowing therapy did not have a significant effect on the outcomes of death or dependency/disability, case fatality at the end of the trial, or penetration aspiration score. However, swallowing therapy may have reduced length of hospital stay, dysphagia, and chest infections, and may have improved swallowing ability. However, these results are based on evidence of variable quality, involving a variety of interventions. Further high-quality trials are needed to test whether specific interventions are effective.
Topics: Acupuncture Therapy; Acute Disease; Deglutition; Deglutition Disorders; Electric Stimulation Therapy; Gastrostomy; Humans; Intubation, Gastrointestinal; Length of Stay; Lisinopril; Metoclopramide; Nifedipine; Physical Stimulation; Pneumonia; Randomized Controlled Trials as Topic; Stroke; Stroke Rehabilitation; Time Factors; Transcranial Direct Current Stimulation
PubMed: 30376602
DOI: 10.1002/14651858.CD000323.pub3 -
Muscle & Nerve Oct 2022Prognostic factors in Duchenne muscular dystrophy (DMD) predict the disease course and may help individualize patient care. The aim was to summarize the evidence on... (Meta-Analysis)
Meta-Analysis
INTRODUCTION/AIMS
Prognostic factors in Duchenne muscular dystrophy (DMD) predict the disease course and may help individualize patient care. The aim was to summarize the evidence on prognostic factors that may support treatment decisions.
METHODS
We searched six databases for prospective studies that each included ≥50 DMD patients with a minimum follow-up of 1 y. Primary outcomes were age at loss of ambulation (LoA), pulmonary function (forced vital capacity percent of predicted, FVC%p), and heart failure.
RESULTS
Out of 5074 references, 59 studies were analyzed. Corticosteroid use was associated with a delayed LoA (pooled effect hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.23-0.75, I2 94%), better pulmonary function tests (higher peak FVC%, prolonged time with FVC%p > 50%, and reduced need for assisted ventilation) and delayed cardiomyopathy. Longer corticosteroid treatment was associated with later LoA (>1 y compared to <1 y; pooled HR: 0.50, 95% CI 0.27-0.90) and early treatment start (aged <5 y) may be associated with early cardiomyopathy and higher fracture risk. Genotype appeared to be an independent driver of LoA in some studies. Higher baseline physical function tests (e.g., 6-minute walk test) were associated with delayed LoA. Left ventricular dysfunction and FVC <1 L increased and the use of angiotensin-converting enzyme (ACE) inhibitors reduced the risk of heart failure and death. Fusion surgery in scoliosis may potentially preserve pulmonary function.
DISCUSSION
Prognostic factors that may inform clinical decisions include age at corticosteroid treatment initiation and treatment duration, ACE-inhibitor use, baseline physical function tests, pulmonary function, and cardiac dysfunction.
Topics: Adrenal Cortex Hormones; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Cardiomyopathies; Disease Progression; Heart Failure; Humans; Muscular Dystrophy, Duchenne; Prognosis; Prospective Studies; Treatment Outcome
PubMed: 35860996
DOI: 10.1002/mus.27682 -
JAMA Network Open Feb 2021Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes.
OBJECTIVE
To assess whether different ED combination therapies were associated with improved outcomes compared with first-line ED monotherapy in various subgroups of patients with ED.
DATA SOURCES
Studies were identified through a systematic search in MEDLINE, Cochrane Library, and Scopus from inception of these databases to October 10, 2020.
STUDY SELECTION
Randomized clinical trials or prospective interventional studies of the outcomes of combination therapy vs recommended monotherapy in men with ED were identified. Only comparative human studies, which evaluated the change from baseline of self-reported erectile function using validated questionnaires, that were published in any language were included.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
MAIN OUTCOMES AND MEASURES
A meta-analysis was conducted that included randomized clinical trials that compared outcomes of combination therapy with phosphodiesterase type 5 (PDE5) inhibitors plus another agent vs PDE5 inhibitor monotherapy. Separate analyses were performed for the mean International Index of Erectile Function (IIEF) score change from baseline and the number of adverse events (AEs) by different treatment modalities and subgroups of patients.
RESULTS
A total of 44 studies included 3853 men with a mean (SD) age of 55.8 (11.9) years. Combination therapy compared with monotherapy was associated with a mean IIEF score improvement of 1.76 points (95% CI, 1.27-2.24; I2 = 77%; 95% PI, -0.56 to 4.08). Adding daily tadalafil, low-intensity shockwave therapy, vacuum erectile device, folic acid, metformin hydrochloride, or angiotensin-converting enzyme inhibitors was associated with a significant IIEF score improvement, but each measure was based on only 1 study. Specifically, the weighted mean difference (WMD) in IIEF score was 1.70 (95% CI, 0.79-2.61) for the addition of daily tadalafil, 3.50 (95% CI, 0.22-6.78) for the addition of low-intensity shockwave therapy, 8.40 (95% CI, 4.90-11.90) for the addition of a vacuum erectile device, 3.46 (95% CI, 2.16-4.76) for the addition of folic acid, 4.90 (95% CI, 2.82-6.98) for the addition of metformin hydrochloride and 2.07 (95% CI, 1.37-2.77) for the addition of angiotensin-converting enzyme inhibitors. The addition of α-blockers to PDE5 inhibitors was not associated with improvement in IIEF score (WMD, 0.80; 95% CI, -0.06 to 1.65; I2 = 72%). Compared with monotherapy, combination therapy was associated with improved IIEF score in patients with hypogonadism (WMD, 1.61; 95% CI, 0.99-2.23; I2 = 0%), monotherapy-resistant ED (WMD, 4.38; 95% CI, 2.37-6.40; I2 = 52%), or prostatectomy-induced ED (WMD, 5.47; 95% CI, 3.11-7.83; I2 = 53%). The treatment-related AEs did not differ between combination therapy and monotherapy (odds ratio, 1.10; 95% CI, 0.66-1.85; I2 = 78%). Despite multiple subgroup and sensitivity analyses, the levels of heterogeneity remained high.
CONCLUSIONS AND RELEVANCE
This study found that combination therapy of PDE5 inhibitors and antioxidants was associated with improved ED without increasing the AEs. Treatment with PDE5 inhibitors and daily tadalafil, shockwaves, or a vacuum device was associated with additional improvement, but this result was based on limited data. These findings suggest that combination therapy is safe, associated with improved outcomes, and should be considered as a first-line therapy for refractory, complex, or difficult-to-treat cases of ED.
Topics: Adrenergic alpha-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Combined Modality Therapy; Drug Therapy, Combination; Equipment and Supplies; Erectile Dysfunction; Extracorporeal Shockwave Therapy; Folic Acid; Humans; Hypoglycemic Agents; Male; Metformin; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Treatment Outcome; Vitamin B Complex
PubMed: 33599772
DOI: 10.1001/jamanetworkopen.2020.36337 -
Journal of Clinical Hypertension... May 2022Dihydropyridine calcium channel blockers (DHPCCBs) are widely used to treat hypertension and chronic coronary artery disease. One common adverse effect of DHPCCBs is... (Meta-Analysis)
Meta-Analysis
Dihydropyridine calcium channel blockers (DHPCCBs) are widely used to treat hypertension and chronic coronary artery disease. One common adverse effect of DHPCCBs is peripheral edema, particularly of the lower limbs. The side effect could lead to dose reduction or discontinuation of the medication. The combination of DHPCCBs and renin-angiotensin system blockers has shown to reduce the risk of DHPCCBs-associated peripheral edema compared with DHPCCBs monotherapy. We performed the current systematic review and network meta-analysis of randomized controlled trials (RCTs) to estimate the rate of peripheral edema with DHPCCBs as a class and with individual DHPCCBs and the ranking of the reduction of peripheral edema. The effects of renin-angiotensin system blockers on DHPCCBs network meta-analysis were created to analyze the ranking of the reduction of peripheral edema. A total of 3312 publications were identified and 71 studies with 56,283 patients were included. Nifedipine ranked highest in inducing peripheral edema (SUCRA 81.8%) and lacidipine (SUCRA 12.8%) ranked the least. All DHPCCBs except lacidipine resulted in higher relative risk (RR) of peripheral edema compared with placebo. Nifedipine plus angiotensin receptor blocker (SUCRA: 92.3%) did not mitigate peripheral edema and amlodipine plus angiotensin-converting enzyme inhibitors (SUCRA: 16%) reduced peripheral edema the most. Nifedipine ranked the highest and lacidipine ranked the lowest amongst DHPCCBs for developing peripheral edema when used for cardiovascular indications. The second or higher generation of DHPCCBs combination with ACEIs or ARBs or diuretics lowered the chance of peripheral edema development compared to single DHPCCB treatment.
Topics: Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Edema; Humans; Hypertension; Network Meta-Analysis; Nifedipine
PubMed: 35234349
DOI: 10.1111/jch.14436