-
The Cochrane Database of Systematic... Oct 2020Electromechanical- and robot-assisted gait-training devices are used in rehabilitation and might help to improve walking after stroke. This is an update of a Cochrane... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Electromechanical- and robot-assisted gait-training devices are used in rehabilitation and might help to improve walking after stroke. This is an update of a Cochrane Review first published in 2007 and previously updated in 2017.
OBJECTIVES
Primary • To determine whether electromechanical- and robot-assisted gait training versus normal care improves walking after stroke Secondary • To determine whether electromechanical- and robot-assisted gait training versus normal care after stroke improves walking velocity, walking capacity, acceptability, and death from all causes until the end of the intervention phase SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 6 January 2020); the Cochrane Central Register of Controlled Trials (CENTRAL; 2020 Issue 1), in the Cochrane Library; MEDLINE in Ovid (1950 to 6 January 2020); Embase (1980 to 6 January 2020); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 20 November 2019); the Allied and Complementary Medicine Database (AMED; 1985 to 6 January 2020); Web of Science (1899 to 7 January 2020); SPORTDiscus (1949 to 6 January 2020); the Physiotherapy Evidence Database (PEDro; searched 7 January 2020); and the engineering databases COMPENDEX (1972 to 16 January 2020) and Inspec (1969 to 6 January 2020). We handsearched relevant conference proceedings, searched trials and research registers, checked reference lists, and contacted trial authors in an effort to identify further published, unpublished, and ongoing trials.
SELECTION CRITERIA
We included all randomised controlled trials and randomised controlled cross-over trials in people over the age of 18 years diagnosed with stroke of any severity, at any stage, in any setting, evaluating electromechanical- and robot-assisted gait training versus normal care.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, assessed methodological quality and risk of bias, and extracted data. We assessed the quality of evidence using the GRADE approach. The primary outcome was the proportion of participants walking independently at follow-up.
MAIN RESULTS
We included in this review update 62 trials involving 2440 participants. Electromechanical-assisted gait training in combination with physiotherapy increased the odds of participants becoming independent in walking (odds ratio (random effects) 2.01, 95% confidence interval (CI) 1.51 to 2.69; 38 studies, 1567 participants; P < 0.00001; I² = 0%; high-quality evidence) and increased mean walking velocity (mean difference (MD) 0.06 m/s, 95% CI 0.02 to 0.10; 42 studies, 1600 participants; P = 0.004; I² = 60%; low-quality evidence) but did not improve mean walking capacity (MD 10.9 metres walked in 6 minutes, 95% CI -5.7 to 27.4; 24 studies, 983 participants; P = 0.2; I² = 42%; moderate-quality evidence). Electromechanical-assisted gait training did not increase the risk of loss to the study during intervention nor the risk of death from all causes. Results must be interpreted with caution because (1) some trials investigated people who were independent in walking at the start of the study, (2) we found variation between trials with respect to devices used and duration and frequency of treatment, and (3) some trials included devices with functional electrical stimulation. Post hoc analysis showed that people who are non-ambulatory at the start of the intervention may benefit but ambulatory people may not benefit from this type of training. Post hoc analysis showed no differences between the types of devices used in studies regarding ability to walk but revealed differences between devices in terms of walking velocity and capacity.
AUTHORS' CONCLUSIONS
People who receive electromechanical-assisted gait training in combination with physiotherapy after stroke are more likely to achieve independent walking than people who receive gait training without these devices. We concluded that eight patients need to be treated to prevent one dependency in walking. Specifically, people in the first three months after stroke and those who are not able to walk seem to benefit most from this type of intervention. The role of the type of device is still not clear. Further research should consist of large definitive pragmatic phase 3 trials undertaken to address specific questions about the most effective frequency and duration of electromechanical-assisted gait training, as well as how long any benefit may last. Future trials should consider time post stroke in their trial design.
Topics: Aged; Bias; Cause of Death; Combined Modality Therapy; Confidence Intervals; Electric Stimulation Therapy; Equipment Design; Exercise Therapy; Gait; Humans; Middle Aged; Odds Ratio; Orthotic Devices; Randomized Controlled Trials as Topic; Robotics; Stroke Rehabilitation; Walking; Walking Speed
PubMed: 33091160
DOI: 10.1002/14651858.CD006185.pub5 -
Journal of Cardiovascular Pharmacology Feb 2022Sodium-glucose cotransporter 2 (SGLT2) inhibitors have well-documented effects on reducing hospitalization for heart failure and cardiovascular mortality, although the... (Meta-Analysis)
Meta-Analysis
Association of SGLT2 Inhibitors With Risk of Atrial Fibrillation and Stroke in Patients With and Without Type 2 Diabetes: A Systemic Review and Meta-Analysis of Randomized Controlled Trials.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have well-documented effects on reducing hospitalization for heart failure and cardiovascular mortality, although the effect on atrial fibrillation (AF) has not been comprehensively investigated. Therefore, we performed a meta-analysis to assess the association between SGLT2 inhibitors and AF risk by systematically searching PubMed, Embase, and ClinicalTrials.gov. Two investigators independently identified randomized controlled trials, which compared SGLT2 inhibitors with control in patients with type 2 diabetes, heart failure, or chronic kidney disease. Primary outcomes were incident AF and stroke. We included 20 randomized trials involving 63,604 patients. The SGLT2 inhibitors used were dapagliflozin (7 studies, 28,834 patients), canagliflozin (7 studies, 17,440 patients), empagliflozin (5 studies, 9082 patients), and ertugliflozin (1 study, 8246 patients). Follow-up ranged from 24 weeks to 202 weeks. SGLT2 inhibitors treatment was associated with a significant attenuation in the risk of incident AF (odds ratio = 0.82; 95% confidence interval, 0.72-0.93; P = 0.002) compared with control. No significant difference in stroke between SGLT2 inhibitors and control groups was found (odds ratio = 0.99; 95% confidence interval, 0.85-1.15; P = 0.908). This present meta-analysis indicates that SGLT2 inhibitors are associated with a lower risk of incident AF and do not significantly affect stroke risk for patients with and without type 2 diabetes.
Topics: Atrial Fibrillation; Diabetes Mellitus, Type 2; Heart Failure; Humans; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Stroke
PubMed: 34813574
DOI: 10.1097/FJC.0000000000001183 -
The Cochrane Database of Systematic... Sep 2022Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea... (Review)
Review
BACKGROUND
Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising foetal haemoglobin (HbF). This is an update of a previously published Cochrane Review.
OBJECTIVES
The aims of this review are to determine through a review of randomised or quasi-randomised studies whether the use of hydroxyurea in people with SCD alters the pattern of acute events, including pain; prevents, delays or reverses organ dysfunction; alters mortality and quality of life; or is associated with adverse effects. In addition, we hoped to assess whether the response to hydroxyurea in SCD varies with the type of SCD, age of the individual, duration and dose of treatment, and healthcare setting.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Haemoglobinopathies Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. The date of the most recent search was 17 February 2022.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials (RCTs and quasi-RCTs), of one month or longer, comparing hydroxyurea with placebo or standard therapy in people with SCD.
DATA COLLECTION AND ANALYSIS
Authors independently assessed studies for inclusion, carried out data extraction, assessed the risk of bias and assessed the quality of the evidence using GRADE.
MAIN RESULTS
We included nine RCTs recruiting 1104 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sβºthalassaemia (HbSβºthal) genotypes). Studies lasted from six to 30 months. We judged the quality of the evidence for the first two comparisons below as moderate to low as the studies contributing to these comparisons were mostly large and well-designed (and at low risk of bias); however, the evidence was limited and imprecise for some outcomes such as quality of life, deaths during the studies and adverse events, and the results are applicable only to individuals with HbSS and HbSβºthal genotypes. We judged the quality of the evidence for the third and fourth comparisons to be very low due to the limited number of participants, the lack of statistical power (both studies were terminated early with approximately only 20% of their target sample size recruited) and the lack of applicability to all age groups and genotypes. Hydroxyurea versus placebo Five studies (784 adults and children with HbSS or HbSβºthal) compared hydroxyurea to placebo; four recruited individuals with only severe disease and one recruited individuals with all disease severities. Hydroxyurea probably improves pain alteration (using measures such as pain crisis frequency, duration, intensity, hospital admissions and opoid use) and life-threatening illness, but we found no difference in death rates (10 deaths occurred during the studies, but the rates did not differ by treatment group) (all moderate-quality evidence). Hydroxyurea may improve measures of HbF (low-quality evidence) and probably decreases neutrophil counts (moderate-quality evidence). There were no consistent differences in terms of quality of life and adverse events (including serious or life-threatening events) (low-quality evidence). There were fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups. Hydroxyurea and phlebotomy versus transfusion and chelation Two studies (254 children with HbSS or HbSβºthal also with risk of primary or secondary stroke) contributed to this comparison. There were no consistent differences in terms of pain alteration, death or adverse events (low-quality evidence) or life-threatening illness (moderate-quality evidence). Hydroxyurea with phlebotomy probably increased HbF and decreased neutrophil counts (moderate-quality evidence), but there were more occurrences of acute chest syndrome and infections. Quality of life was not reported. In the primary prevention study, no strokes occurred in either treatment group but in the secondary prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group (none in the transfusion and chelation group) and the study was terminated early. Hydroxyurea versus observation One study (22 children with HbSS or HbSβºthal also at risk of stoke) compared hydroxyurea to observation. Pain alteration and quality of life were not reported. There were no differences in life-threatening illness, death (no deaths reported in either group) or adverse events (very low-quality evidence). We are uncertain if hydroxyurea improves HbF or decreases neutrophil counts (very low-quality evidence). Treatment regimens with and without hydroxyurea One study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea. Pain alteration, life-threatening illness and quality of life were not reported. There were no differences in death rates (no deaths reported in either group), adverse events or neutrophil levels (very low-quality evidence). We are uncertain if hydroxyurea improves HbF (very low-quality evidence).
AUTHORS' CONCLUSIONS
There is evidence to suggest that hydroxyurea may be effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia of HbSS or HbSβºthal genotypes and in preventing life-threatening neurological events in those with sickle cell anaemia at risk of primary stroke by maintaining transcranial Doppler velocities. However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly with regard to preventing chronic complications of SCD, or recommending a standard dose or dose escalation to maximum tolerated dose. There is also insufficient evidence about the long-term risks of hydroxyurea, including its effects on fertility and reproduction. Evidence is also limited on the effects of hydroxyurea on individuals with the HbSC genotype. Future studies should be designed to address such uncertainties.
Topics: Acute Chest Syndrome; Adult; Anemia, Sickle Cell; Antisickling Agents; Child; Hemoglobin, Sickle; Humans; Hydroxyurea; Pain; Stroke
PubMed: 36047926
DOI: 10.1002/14651858.CD002202.pub3 -
The Cochrane Database of Systematic... Jul 2023Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity... (Review)
Review
BACKGROUND
Different first-line drug classes for patients with hypertension are often assumed to have similar effectiveness with respect to reducing mortality and morbidity outcomes, and lowering blood pressure. First-line low-dose thiazide diuretics have been previously shown to have the best mortality and morbidity evidence when compared with placebo or no treatment. Head-to-head comparisons of thiazides with other blood pressure-lowering drug classes would demonstrate whether there are important differences.
OBJECTIVES
To compare the effects of first-line diuretic drugs with other individual first-line classes of antihypertensive drugs on mortality, morbidity, and withdrawals due to adverse effects in patients with hypertension. Secondary objectives included assessments of the need for added drugs, drug switching, and blood pressure-lowering.
SEARCH METHODS
Cochrane Hypertension's Information Specialist searched the Cochrane Hypertension Specialized Register, CENTRAL, MEDLINE, Embase, and trials registers to March 2021. We also checked references and contacted study authors to identify additional studies. A top-up search of the Specialized Register was carried out in June 2022.
SELECTION CRITERIA
Randomized active comparator trials of at least one year's duration were included. Trials had a clearly defined intervention arm of a first-line diuretic (thiazide, thiazide-like, or loop diuretic) compared to another first-line drug class: beta-blockers, calcium channel blockers, alpha adrenergic blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, direct renin inhibitors, or other antihypertensive drug classes. Studies had to include clearly defined mortality and morbidity outcomes (serious adverse events, total cardiovascular events, stroke, coronary heart disease (CHD), congestive heart failure, and withdrawals due to adverse effects).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
We included 20 trials with 26 comparator arms randomizing over 90,000 participants. The findings are relevant to first-line use of drug classes in older male and female hypertensive patients (aged 50 to 75) with multiple co-morbidities, including type 2 diabetes. First-line thiazide and thiazide-like diuretics were compared with beta-blockers (six trials), calcium channel blockers (eight trials), ACE inhibitors (five trials), and alpha-adrenergic blockers (three trials); other comparators included angiotensin II receptor blockers, aliskiren (a direct renin inhibitor), and clonidine (a centrally acting drug). Only three studies reported data for total serious adverse events: two studies compared diuretics with calcium channel blockers and one with a direct renin inhibitor. Compared to first-line beta-blockers, first-line thiazides probably result in little to no difference in total mortality (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.84 to 1.10; 5 trials, 18,241 participants; moderate-certainty), probably reduce total cardiovascular events (5.4% versus 4.8%; RR 0.88, 95% CI 0.78 to 1.00; 4 trials, 18,135 participants; absolute risk reduction (ARR) 0.6%, moderate-certainty), may result in little to no difference in stroke (RR 0.85, 95% CI 0.66 to 1.09; 4 trials, 18,135 participants; low-certainty), CHD (RR 0.91, 95% CI 0.78 to 1.07; 4 trials, 18,135 participants; low-certainty), or heart failure (RR 0.69, 95% CI 0.40 to 1.19; 1 trial, 6569 participants; low-certainty), and probably reduce withdrawals due to adverse effects (10.1% versus 7.9%; RR 0.78, 95% CI 0.71 to 0.85; 5 trials, 18,501 participants; ARR 2.2%; moderate-certainty). Compared to first-line calcium channel blockers, first-line thiazides probably result in little to no difference in total mortality (RR 1.02, 95% CI 0.96 to 1.08; 7 trials, 35,417 participants; moderate-certainty), may result in little to no difference in serious adverse events (RR 1.09, 95% CI 0.97 to 1.24; 2 trials, 7204 participants; low-certainty), probably reduce total cardiovascular events (14.3% versus 13.3%; RR 0.93, 95% CI 0.89 to 0.98; 6 trials, 35,217 participants; ARR 1.0%; moderate-certainty), probably result in little to no difference in stroke (RR 1.06, 95% CI 0.95 to 1.18; 6 trials, 35,217 participants; moderate-certainty) or CHD (RR 1.00, 95% CI 0.93 to 1.08; 6 trials, 35,217 participants; moderate-certainty), probably reduce heart failure (4.4% versus 3.2%; RR 0.74, 95% CI 0.66 to 0.82; 6 trials, 35,217 participants; ARR 1.2%; moderate-certainty), and may reduce withdrawals due to adverse effects (7.6% versus 6.2%; RR 0.81, 95% CI 0.75 to 0.88; 7 trials, 33,908 participants; ARR 1.4%; low-certainty). Compared to first-line ACE inhibitors, first-line thiazides probably result in little to no difference in total mortality (RR 1.00, 95% CI 0.95 to 1.07; 3 trials, 30,961 participants; moderate-certainty), may result in little to no difference in total cardiovascular events (RR 0.97, 95% CI 0.92 to 1.02; 3 trials, 30,900 participants; low-certainty), probably reduce stroke slightly (4.7% versus 4.1%; RR 0.89, 95% CI 0.80 to 0.99; 3 trials, 30,900 participants; ARR 0.6%; moderate-certainty), probably result in little to no difference in CHD (RR 1.03, 95% CI 0.96 to 1.12; 3 trials, 30,900 participants; moderate-certainty) or heart failure (RR 0.94, 95% CI 0.84 to 1.04; 2 trials, 30,392 participants; moderate-certainty), and probably reduce withdrawals due to adverse effects (3.9% versus 2.9%; RR 0.73, 95% CI 0.64 to 0.84; 3 trials, 25,254 participants; ARR 1.0%; moderate-certainty). Compared to first-line alpha-blockers, first-line thiazides probably result in little to no difference in total mortality (RR 0.98, 95% CI 0.88 to 1.09; 1 trial, 24,316 participants; moderate-certainty), probably reduce total cardiovascular events (12.1% versus 9.0%; RR 0.74, 95% CI 0.69 to 0.80; 2 trials, 24,396 participants; ARR 3.1%; moderate-certainty) and stroke (2.7% versus 2.3%; RR 0.86, 95% CI 0.73 to 1.01; 2 trials, 24,396 participants; ARR 0.4%; moderate-certainty), may result in little to no difference in CHD (RR 0.98, 95% CI 0.86 to 1.11; 2 trials, 24,396 participants; low-certainty), probably reduce heart failure (5.4% versus 2.8%; RR 0.51, 95% CI 0.45 to 0.58; 1 trial, 24,316 participants; ARR 2.6%; moderate-certainty), and may reduce withdrawals due to adverse effects (1.3% versus 0.9%; RR 0.70, 95% CI 0.54 to 0.89; 3 trials, 24,772 participants; ARR 0.4%; low-certainty). For the other drug classes, data were insufficient. No antihypertensive drug class demonstrated any clinically important advantages over first-line thiazides.
AUTHORS' CONCLUSIONS
When used as first-line agents for the treatment of hypertension, thiazides and thiazide-like drugs likely do not change total mortality and likely decrease some morbidity outcomes such as cardiovascular events and withdrawals due to adverse effects, when compared to beta-blockers, calcium channel blockers, ACE inhibitors, and alpha-blockers.
Topics: Aged; Female; Humans; Male; Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Coronary Disease; Diabetes Mellitus, Type 2; Diuretics; Heart Failure; Hypertension; Stroke; Thiazides; Middle Aged
PubMed: 37439548
DOI: 10.1002/14651858.CD008161.pub3 -
Human Reproduction Update Nov 2020Polycystic ovary syndrome (PCOS) is associated with cardiometabolic disease, but recent systematic reviews and meta-analyses of longitudinal studies that quantify these... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polycystic ovary syndrome (PCOS) is associated with cardiometabolic disease, but recent systematic reviews and meta-analyses of longitudinal studies that quantify these associations are lacking.
OBJECTIVE AND RATIONALE
Is PCOS a risk factor for cardiometabolic disease?
SEARCH METHODS
We searched from inception to September 2019 in MEDLINE and EMBASE using controlled terms (e.g. MESH) and text words for PCOS and cardiometabolic outcomes, including cardiovascular disease (CVD), stroke, myocardial infarction, hypertension (HT), type 2 diabetes (T2D), metabolic syndrome and dyslipidaemia. Cohort studies and case-control studies comparing the prevalence of T2D, HT, fatal or non-fatal CVD and/or lipid concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) between women with and without PCOS of ≥18 years of age were eligible for this systematic review and meta-analysis. Studies were eligible regardless of the degree to which they adjusted for confounders including obesity. Articles had to be written in English, German or Dutch. Intervention studies, animal studies, conference abstracts, studies with a follow-up duration less than 3 years and studies with less than 10 PCOS cases were excluded. Study selection, quality assessment (Newcastle-Ottawa Scale) and data extraction were performed by two independent researchers.
OUTCOMES
Of the 5971 identified records, 23 cohort studies were included in the current systematic review. Women with PCOS had increased risks of HT (risk ratio (RR): 1.75, 95% CI 1.42 to 2.15), T2D (RR: 3.00, 95% CI 2.56 to 3.51), a higher serum concentration of TC (mean difference (MD): 7.14 95% CI 1.58 to 12.70 mg/dl), a lower serum concentration of HDL-C (MD: -2.45 95% CI -4.51 to -0.38 mg/dl) and increased risks of non-fatal cerebrovascular disease events (RR: 1.41, 95% CI 1.02 to 1.94) compared to women without PCOS. No differences were found for LDL-C (MD: 3.32 95% CI -4.11 to 10.75 mg/dl), TG (MD 18.53 95% CI -0.58 to 37.64 mg/dl) or coronary disease events (RR: 1.78, 95% CI 0.99 to 3.23). No meta-analyses could be performed for fatal CVD events due to the paucity of mortality data.
WIDER IMPLICATIONS
Women with PCOS are at increased risk of cardiometabolic disease. This review quantifies this risk, which is important for clinicians to inform patients and to take into account in the cardiovascular risk assessment of women with PCOS. Future clinical trials are needed to assess the ability of cardiometabolic screening and management in women with PCOS to reduce future CVD morbidity.
Topics: Adult; Cardiometabolic Risk Factors; Cardiovascular Diseases; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Female; Humans; Obesity; Polycystic Ovary Syndrome; Risk Factors; Stroke; Triglycerides; Young Adult
PubMed: 32995872
DOI: 10.1093/humupd/dmaa029 -
Neuroscience and Biobehavioral Reviews Sep 2023In recent decades, new virtual reality (VR)-based protocols have been proposed for the rehabilitation of Unilateral Spatial Neglect (USN), a debilitating disorder of... (Review)
Review
INTRODUCTION
In recent decades, new virtual reality (VR)-based protocols have been proposed for the rehabilitation of Unilateral Spatial Neglect (USN), a debilitating disorder of spatial awareness. However, it remains unclear which type of VR protocol and level of VR immersion can maximize the clinical benefits. To answer these questions, we conducted a systematic review of the use of VR for the rehabilitation of USN.
METHOD
Studies between 2000 and 2022 that met the inclusion criteria were classified according to their research design and degree of immersion (non-immersive, NIVR; semi-immersive, SIVR; immersive, IVR).
RESULTS
A total of 375 studies were identified, of which 26 met the inclusion criteria. Improvements were found in 84.6% of the reviewed studies: 85.7% used NIVR, 100% used SIVR and 55.6% used IVR. However, only 42.3% of them included a control group and only 19.2% were randomized control trials (RCT).
CONCLUSION
VR protocols may offer new opportunities for USN rehabilitation, although further RCTs are needed to validate their clinical efficacy.
Topics: Humans; Stroke; Stroke Rehabilitation; Perceptual Disorders; Treatment Outcome; Virtual Reality
PubMed: 37247829
DOI: 10.1016/j.neubiorev.2023.105248 -
Academic Emergency Medicine : Official... May 2023History and physical examination are key features to narrow the differential diagnosis of central versus peripheral causes in patients presenting with acute vertigo. We... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
History and physical examination are key features to narrow the differential diagnosis of central versus peripheral causes in patients presenting with acute vertigo. We conducted a systematic review and meta-analysis of the diagnostic test accuracy of physical examination findings.
METHODS
This study involved a patient-intervention-control-outcome (PICO) question: (P) adult ED patients with vertigo/dizziness; (I) presence/absence of specific physical examination findings; and (O) central (ischemic stroke, hemorrhage, others) versus peripheral etiology. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was assessed.
RESULTS
From 6309 titles, 460 articles were retrieved, and 43 met the inclusion criteria: general neurologic examination-five studies, 869 patients, pooled sensitivity 46.8% (95% confidence interval [CI] 32.3%-61.9%, moderate certainty) and specificity 92.8% (95% CI 75.7%-98.1%, low certainty); limb weakness/hemiparesis-four studies, 893 patients, sensitivity 11.4% (95% CI 5.1%-23.6%, high) and specificity 98.5% (95% CI 97.1%-99.2%, high); truncal/gait ataxia-10 studies, 1810 patients (increasing severity of truncal ataxia had an increasing sensitivity for central etiology, sensitivity 69.7% [43.3%-87.9%, low] and specificity 83.7% [95% CI 52.1%-96.0%, low]); dysmetria signs-four studies, 1135 patients, sensitivity 24.6% (95% CI 15.6%-36.5%, high) and specificity 97.8% (94.4%-99.2%, high); head impulse test (HIT)-17 studies, 1366 patients, sensitivity 76.8% (64.4%-85.8%, low) and specificity 89.1% (95% CI 75.8%-95.6%, moderate); spontaneous nystagmus-six studies, 621 patients, sensitivity 52.3% (29.8%-74.0%, moderate) and specificity 42.0% (95% CI 15.5%-74.1%, moderate); nystagmus type-16 studies, 1366 patients (bidirectional, vertical, direction changing, or pure torsional nystagmus are consistent with a central cause of vertigo, sensitivity 50.7% [95% CI 41.1%-60.2%, moderate] and specificity 98.5% [95% CI 91.7%-99.7%, moderate]); test of skew-15 studies, 1150 patients (skew deviation is abnormal and consistent with central etiology, sensitivity was 23.7% [95% CI 15%-35.4%, moderate] and specificity 97.6% [95% CI 96%-98.6%, moderate]); HINTS (head impulse, nystagmus, test of skew)-14 studies, 1781 patients, sensitivity 92.9% (95% CI 79.1%-97.9%, high) and specificity 83.4% (95% CI 69.6%-91.7%, moderate); and HINTS+ (HINTS with hearing component)-five studies, 342 patients, sensitivity 99.0% (95% CI 73.6%-100%, high) and specificity 84.8% (95% CI 70.1%-93.0%, high).
CONCLUSIONS
Most neurologic examination findings have low sensitivity and high specificity for a central cause in patients with acute vertigo or dizziness. In acute vestibular syndrome (monophasic, continuous, persistent dizziness), HINTS and HINTS+ have high sensitivity when performed by trained clinicians.
Topics: Adult; Humans; Dizziness; Stroke; Vertigo; Emergency Service, Hospital; Nystagmus, Pathologic; Physical Examination
PubMed: 36453134
DOI: 10.1111/acem.14630 -
Annals of Internal Medicine Nov 2019This article has been corrected. The original version (PDF) is appended to this article as a Supplement. (Meta-Analysis)
Meta-Analysis
UNLABELLED
This article has been corrected. The original version (PDF) is appended to this article as a Supplement.
BACKGROUND
Dietary guidelines generally recommend limiting intake of red and processed meat. However, the quality of evidence implicating red and processed meat in adverse health outcomes remains unclear.
PURPOSE
To evaluate the association between red and processed meat consumption and all-cause mortality, cardiometabolic outcomes, quality of life, and satisfaction with diet among adults.
DATA SOURCES
EMBASE (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), Web of Science (Clarivate Analytics), CINAHL (EBSCO), and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019, without language restrictions, as well as bibliographies of relevant articles.
STUDY SELECTION
Cohort studies with at least 1000 participants that reported an association between unprocessed red or processed meat intake and outcomes of interest.
DATA EXTRACTION
Teams of 2 reviewers independently extracted data and assessed risk of bias. One investigator assessed certainty of evidence, and the senior investigator confirmed the assessments.
DATA SYNTHESIS
Of 61 articles reporting on 55 cohorts with more than 4 million participants, none addressed quality of life or satisfaction with diet. Low-certainty evidence was found that a reduction in unprocessed red meat intake of 3 servings per week is associated with a very small reduction in risk for cardiovascular mortality, stroke, myocardial infarction (MI), and type 2 diabetes. Likewise, low-certainty evidence was found that a reduction in processed meat intake of 3 servings per week is associated with a very small decrease in risk for all-cause mortality, cardiovascular mortality, stroke, MI, and type 2 diabetes.
LIMITATION
Inadequate adjustment for known confounders, residual confounding due to observational design, and recall bias associated with dietary measurement.
CONCLUSION
The magnitude of association between red and processed meat consumption and all-cause mortality and adverse cardiometabolic outcomes is very small, and the evidence is of low certainty.
PRIMARY FUNDING SOURCE
None. (PROSPERO: CRD42017074074).
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet; Humans; Meat Products; Myocardial Infarction; Red Meat; Stroke
PubMed: 31569213
DOI: 10.7326/M19-0655 -
Cardiovascular Diabetology Mar 2022We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients with diabetic kidney disease (DKD).
METHODS
We searched electronic databases for major randomized placebo-controlled clinical trials published up to September 30, 2021 and reporting on cardiovascular and kidney outcomes of SGLT2i in patients with DKD. DKD was defined as chronic kidney disease in individuals with type 2 diabetes. Random-effects meta-analysis models were used to estimate pooled hazard ratios (HR) and 95% confidence intervals (CI) for clinical outcomes including major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, and cardiovascular death), kidney composite outcomes (a combination of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes), hospitalizations for heart failure (HHF), deaths and safety events (mycotic infections, diabetic ketoacidosis [DKA], volume depletion, amputations, fractures, urinary tract infections [UTI], acute kidney injury [AKI], and hyperkalemia).
RESULTS
A total of 26,106 participants with DKD from 8 large-scale trials were included (median age: 65.2 years, 29.7-41.8% women, 53.2-93.2% White, median follow-up: 2.5 years). SGLT2i were associated with reduced risks of MACE (HR 0.83, 95% CI 0.75-0.93), kidney composite outcomes (HR 0.66, 95% CI 0.58-0.75), HHF (HR 0.62, 95% CI 0.55-0.71), cardiovascular death (HR 0.84, 95% CI 0.74-0.96), MI (HR 0.78, 95% CI 0.67-0.92), stroke (HR 0.76, 95% CI 0.59-0.97), and all-cause death (HR 0.86, 95% CI 0.77-0.96), with no significant heterogeneity detected. Similar results were observed among participants with reduced estimated glomerular filtration rate (eGFR: < 60 mL/min/1.73m). The relative risks (95% CI) for adverse events were 3.89 (1.42-10.62) and 2.50 (1.32-4.72) for mycotic infections in men and women respectively, 3.54 (0.82-15.39) for DKA, and 1.29 (1.13-1.48) for volume depletion.
CONCLUSIONS
Among adults with DKD, SGLT2i were associated with reduced risks of MACE, kidney outcomes, HHF, and death. With a few exceptions of more clear safety signals, we found overall limited data on the associations between SGLT2i and safety outcomes. More research is needed on the safety profile of SGLT2i in this population.
Topics: Adult; Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diabetic Nephropathies; Female; Heart Failure; Humans; Kidney; Male; Myocardial Infarction; Sodium-Glucose Transporter 2 Inhibitors; Stroke
PubMed: 35321742
DOI: 10.1186/s12933-022-01476-x -
The Cochrane Database of Systematic... Oct 2020Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for people who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) reduce LDL-C and CVD risk.
OBJECTIVES
Primary To quantify the effects of PCSK9 inhibitors on CVD, all-cause mortality, myocardial infarction, and stroke, compared to placebo or active treatment(s) for primary and secondary prevention. Secondary To quantify the safety of PCSK9 inhibitors, with specific focus on the incidence of influenza, hypertension, type 2 diabetes, and cancer, compared to placebo or active treatment(s) for primary and secondary prevention.
SEARCH METHODS
We identified studies by systematically searching CENTRAL, MEDLINE, Embase, and Web of Science in December 2019. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform in August 2020 and screened the reference lists of included studies. This is an update of the review first published in 2017.
SELECTION CRITERIA
All parallel-group and factorial randomised controlled trials (RCTs) with a follow-up of at least 24 weeks were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed and extracted data. Where data were available, we calculated pooled effect estimates. We used GRADE to assess certainty of evidence and in 'Summary of findings' tables.
MAIN RESULTS
We included 24 studies with data on 60,997 participants. Eighteen trials randomised participants to alirocumab and six to evolocumab. All participants received background lipid-lowering treatment or lifestyle counselling. Six alirocumab studies used an active treatment comparison group (the remaining used placebo), compared to three evolocumab active comparison trials. Alirocumab compared with placebo decreased the risk of CVD events, with an absolute risk difference (RD) of -2% (odds ratio (OR) 0.87, 95% confidence interval (CI) 0.80 to 0.94; 10 studies, 23,868 participants; high-certainty evidence), decreased the risk of mortality (RD -1%; OR 0.83, 95% CI 0.72 to 0.96; 12 studies, 24,797 participants; high-certainty evidence), and MI (RD -2%; OR 0.86, 95% CI 0.79 to 0.94; 9 studies, 23,352 participants; high-certainty evidence) and for any stroke (RD 0%; OR 0.73, 95% CI 0.58 to 0.91; 8 studies, 22,835 participants; high-certainty evidence). Compared to active treatment the alirocumab effects, for CVD, the RD was 1% (OR 1.37, 95% CI 0.65 to 2.87; 3 studies, 1379 participants; low-certainty evidence); for mortality, RD was -1% (OR 0.51, 95% CI 0.18 to 1.40; 5 studies, 1333 participants; low-certainty evidence); for MI, RD was 1% (OR 1.45, 95% CI 0.64 to 3.28, 5 studies, 1734 participants; low-certainty evidence); and for any stroke, RD was less than 1% (OR 0.85, 95% CI 0.13 to 5.61; 5 studies, 1734 participants; low-certainty evidence). Compared to placebo the evolocumab, for CVD, the RD was -2% (OR 0.84, 95% CI 0.78 to 0.91; 3 studies, 29,432 participants; high-certainty evidence); for mortality, RD was less than 1% (OR 1.04, 95% CI 0.91 to 1.19; 3 studies, 29,432 participants; high-certainty evidence); for MI, RD was -1% (OR 0.72, 95% CI 0.64 to 0.82; 3 studies, 29,432 participants; high-certainty evidence); and for any stroke RD was less than -1% (OR 0.79, 95% CI 0.65 to 0.94; 2 studies, 28,531 participants; high-certainty evidence). Compared to active treatment, the evolocumab effects, for any CVD event RD was less than -1% (OR 0.66, 95% CI 0.14 to 3.04; 1 study, 218 participants; very low-certainty evidence); for all-cause mortality, the RD was less than 1% (OR 0.43, 95% CI 0.14 to 1.30; 3 studies, 5223 participants; very low-certainty evidence); and for MI, RD was less than 1% (OR 0.66, 95% CI 0.23 to 1.85; 3 studies, 5003 participants; very low-certainty evidence). There were insufficient data on any stroke. AUTHORS' CONCLUSIONS: The evidence for the clinical endpoint effects of evolocumab and alirocumab were graded as high. There is a strong evidence base to prescribe PCSK9 monoclonal antibodies to people who might not be eligible for other lipid-lowering drugs, or to people who cannot meet their lipid goals on more traditional therapies, which was the main patient population of the available trials. The evidence base of PCSK9 inhibitors compared with active treatment is much weaker (low very- to low-certainty evidence) and it is unclear whether evolocumab or alirocumab might be effectively used as replacement therapies. Related, most of the available studies preferentially enrolled people with either established CVD or at a high risk already, and evidence in low- to medium-risk settings is minimal. Finally, there is very limited evidence on any potential safety issues of both evolocumab and alirocumab. While the current evidence synthesis does not reveal any adverse signals, neither does it provide evidence against such signals. This suggests careful consideration of alternative lipid lowering treatments before prescribing PCSK9 inhibitors.
Topics: Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cardiovascular Diseases; Cause of Death; Cholesterol, LDL; Cholinergic Antagonists; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Middle Aged; Myocardial Infarction; PCSK9 Inhibitors; Primary Prevention; Proprotein Convertase 9; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke; Time Factors
PubMed: 33078867
DOI: 10.1002/14651858.CD011748.pub3