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European Journal of Preventive... Apr 2024Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by markedly elevated circulating low-density lipoprotein cholesterol (LDL-C) from birth....
AIMS
Homozygous familial hypercholesterolemia (HoFH) is a rare disorder characterized by markedly elevated circulating low-density lipoprotein cholesterol (LDL-C) from birth. This review aimed to critically evaluate treatments for HoFH with respect to their efficacy, safety, accessibility, overall context and position within the treatment pathway.
METHODS
A mixed-methods review was undertaken to systematically identify and characterize primary interventional studies on HoFH, with a focus on LDL-C reduction as the primary outcome. Interventions assessed were ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), lomitapide, evinacumab, with or without LDL apheresis.
RESULTS
Twenty-six seminal studies reporting unique patient data were identified. Four studies were randomized controlled trials (RCTs) with the remainder being single-arm trials or observational registries. Data extracted were heterogeneous and not suitable for meta-analyses. Two RCTs, assessed at being low risk of bias, demonstrated PCSK9i were safe and moderately effective. An RCT demonstrated evinacumab was safe and effective in all HoFH subgroups. Lomitapide was reported to be efficacious in a single-arm trial, but issues with adverse events, tolerability, and adherence were identified. An RCT on ezetimibe showed it was moderately effective when combined with a statin. LDL apheresis was reported as effective, but its evidence base was at very high risk of bias. All interventions lowered LDL-C, but the magnitude of this, and certainty in the supporting evidence, varied.
CONCLUSION
In practice, multiple treatments are required to treat HoFH. The sequencing of these should be made on an individualized basis, with consideration made to the benefits of each intervention.
PubMed: 38640433
DOI: 10.1093/eurjpc/zwae144 -
Annals of Internal Medicine May 2024Newer diabetes medications may have beneficial effects on mortality, cardiovascular outcomes, and renal outcomes. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Newer diabetes medications may have beneficial effects on mortality, cardiovascular outcomes, and renal outcomes.
PURPOSE
To evaluate the effectiveness, comparative effectiveness, and harms of sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) agonists, dipeptidyl peptidase-4 (DPP4) inhibitors, and long-acting insulins as monotherapy or combination therapy in adults with type 2 diabetes mellitus (T2DM).
DATA SOURCES
MEDLINE and EMBASE for randomized controlled trials (RCTs) published from 2010 through January 2023.
STUDY SELECTION
RCTs lasting at least 52 weeks that included at least 500 adults with T2DM receiving eligible medications and reported any outcomes of interest.
DATA EXTRACTION
Data were abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE) were done.
DATA SYNTHESIS
A total of 130 publications from 84 RCTs were identified. CoE was appraised using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria for direct, indirect, and network meta-analysis (NMA); the highest CoE was reported. Compared with usual care, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (high CoE) and major adverse cardiovascular events (MACE) (moderate to high CoE), SGLT2 inhibitors reduce progression of chronic kidney disease (CKD) and heart failure hospitalizations and GLP1 agonists reduce stroke (high CoE), and SGLT2 inhibitors reduce serious adverse events and severe hypoglycemia (high CoE). The threshold for minimally important differences, which was predefined with the American College of Physicians Clinical Guidelines Committee, was not met for these outcomes. Compared with usual care, insulin, tirzepatide, and DPP4 inhibitors do not reduce all-cause mortality (low to high CoE). Compared with insulin, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (low to moderate CoE). Compared with DPP4 inhibitors, GLP1 agonists reduce all-cause mortality (moderate CoE). Compared with DPP4 inhibitors and sulfonylurea (SU), SGLT2 inhibitors reduce MACE (moderate to high CoE). Compared with SU and insulin, SGLT2 inhibitors and GLP1 agonists reduce severe hypoglycemia (low to high CoE).
LIMITATIONS
Infrequent direct comparisons between drugs of interest; sparse data for NMA on most outcomes; possible incoherence due to differences in baseline patient characteristics and usual care; insufficient data on predefined subgroups, including demographic subgroups, patients with prior cardiovascular disease, and treatment-naive persons.
CONCLUSION
In adults with T2DM, SGLT2 inhibitors and GLP1 agonists (but not DPP4 inhibitors, insulin, or tirzepatide) reduce all-cause mortality and MACE compared with usual care. SGLT2 inhibitors reduce CKD progression and heart failure hospitalization and GLP1 agonists reduce stroke compared with usual care. Serious adverse events and severe hypoglycemia are less frequent with SGLT2 inhibitors and GLP1 agonists than with insulin or SU.
PRIMARY FUNDING SOURCE
American College of Physicians. (PROSPERO: CRD42022322129).
Topics: Humans; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemic Agents; Network Meta-Analysis; Insulin; Adult; Cardiovascular Diseases; Glucagon-Like Peptide 1; Hypoglycemia; Drug Therapy, Combination
PubMed: 38639549
DOI: 10.7326/M23-1490 -
European Review For Medical and... Apr 2024This study aimed to assess the risks and benefits of reinitiating antiplatelet therapy after spontaneous intracerebral hemorrhage (ICH) through a systematic review and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to assess the risks and benefits of reinitiating antiplatelet therapy after spontaneous intracerebral hemorrhage (ICH) through a systematic review and meta-analysis. The reinitiation of antiplatelet therapy is commonly used to reduce major vascular events in patients with occlusive vascular diseases, but its use in ICH patients may increase the risk of bleeding.
MATERIALS AND METHODS
A comprehensive search was conducted on databases including MEDLINE, Embase, Cochrane Library, clinicaltrials.gov, and the International Standard Randomized Controlled Trial Number Register (ISRCTN). Randomized controlled trials and cohort studies that investigated the use of reinitiation of antiplatelet therapy after hemorrhagic stroke were included. Data on ICH recurrence, major bleeding events, major occlusive cerebrovascular events, ischemic stroke, and all-cause mortality were extracted and analyzed using R software.
RESULTS
The study included a total of 10 studies with 6,340 participants. The control group consisted of 2,964 patients who did not receive antiplatelet therapy, while the study group included 1,285 patients who received antiplatelet therapy without restrictions on the specific drug type. The meta-analysis showed that antiplatelet therapy significantly reduced the risk of ICH recurrence (RR=0.72, 95% CI: 0.59, 0.87), had no significant impact on the risk of severe bleeding events (RR=0.93, 95% CI: 0.80, 1.08), significantly lowered the risk of major occlusive cerebrovascular events (RR=0.59, 95% CI: 0.46, 0.77), had no significant effect on the risk of ischemic stroke (RR=0.77, 95% CI: 0.53, 1.12), and did not significantly influence the risk of all-cause mortality (RR=0.75, 95% CI: 0.45, 1.15).
CONCLUSIONS
Based on the findings, reinitiating antiplatelet therapy after spontaneous ICH appears to be generally safe. However, the benefits in terms of reducing the risk of all-cause mortality are not evident and require confirmation through large-scale, long-term, prospective, randomized controlled trials.
Topics: Humans; Cerebral Hemorrhage; Ischemic Stroke; Platelet Aggregation Inhibitors
PubMed: 38639508
DOI: 10.26355/eurrev_202404_35897 -
Therapeutic Innovation & Regulatory... Jul 2024Linagliptin is an oral dipeptidyl peptidase DPP-4 inhibitor, which is indicated for the treatment of Type 2 diabetes mellitus (T2DM) as monotherapy or add-on to therapy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Linagliptin is an oral dipeptidyl peptidase DPP-4 inhibitor, which is indicated for the treatment of Type 2 diabetes mellitus (T2DM) as monotherapy or add-on to therapy with other hypoglycemic drugs.
OBJECTIVES
We aimed to summarize the evidence from randomized controlled trials (RCTs) to assess the safety of linagliptin focusing on cardiovascular risks among subjects with type 2 diabetes mellitus.
METHODS
We conducted a systematic search across the following databases: Medline, Embase, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov from inception to November 2021. Randomized controlled trials (RCTs) of linagliptin compared to placebo in patients with Type 2 diabetes were included. The primary safety points were cardiovascular (CV) adverse events including non-fatal stroke, non-fatal myocardial infarction (MI), CV death, MI, stroke, and hospitalization for unstable angina. While, secondary safety points included 17 reported adverse events such as infections, hypoglycemia and abdominal pain. Three reviewers independently screened and reviewed each study to extract relevant information. Any discrepancies were resolved by consensus. We conducted a meta-analysis using the random effects model. Pooled risk ratios (RRs) of targeted adverse events with linagliptin compared to placebo were estimated using the Mantel-Haenszel test.
RESULTS
A total of 24 studies with 19,981 adult patients were included. There was no difference in the incidence of all CV adverse events or individual CV adverse events between linagliptin and the placebo arms. The pooled estimate of the risk of upper respiratory tract infection was reported in twelve trials with a 38% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR = 0.62, 95% CI: 0.45-0.85, and I = 0%), while no difference was found in other infections. For gastrointestinal disorders, the risk of abdominal pain showed a 65% risk reduction among patients treated with the linagliptin group compared to the placebo group (RR = 0.35, 95% CI: 0.16-0.77, and I = 0%).
CONCLUSION
Our study showed an overall acceptable safety profile of linagliptin in patients with T2DM. Moreover, our study showed a risk reduction of upper respiratory tract infection and abdominal pain when using linagliptin compared to placebo.
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Hypoglycemic Agents; Linagliptin; Randomized Controlled Trials as Topic
PubMed: 38634983
DOI: 10.1007/s43441-024-00637-2 -
Journal of Clinical Medicine Mar 2024Exercise has shown beneficial effects on neuronal neuroplasticity; therefore, we want to analyze the influence of high-intensity interval training (HIIT) on... (Review)
Review
Exercise has shown beneficial effects on neuronal neuroplasticity; therefore, we want to analyze the influence of high-intensity interval training (HIIT) on neuroplasticity markers in post-stroke patients. A systematic review of RCTs including studies with stroke participants was conducted using the following databases (PubMed, LILACS, ProQuest, PEDro, Web of Science). Searches lasted till (20/11/2023). Studies that used a HIIT protocol as the main treatment or as a coadjutant treatment whose outcomes were neural plasticity markers were used and compared with other exercise protocols, controls or other kinds of treatment. Studies that included other neurological illnesses, comorbidities that interfere with stroke or patients unable to complete a HIIT protocol were excluded. HIIT protocol, methods to assess intensity, neuroplasticity markers (plasmatic and neurophysiological) and other types of assessments such as cognitive scales were extracted to make a narrative synthesis. Jadad and PEDro scales were used to assess bias. Eight articles were included, one included lacunar stroke (less than 3 weeks) and the rest had chronic stroke. The results found here indicate that HIIT facilitates neuronal recovery in response to an ischemic injury. This type of training increases the plasma concentrations of lactate, BDNF and VEGF, which are neurotrophic and growth factors involved in neuroplasticity. HIIT also positively regulates other neurophysiological measurements that are directly associated with a better outcome in motor learning tasks. We conclude that HIIT improves post-stroke recovery by increasing neuroplasticity markers. However, a limited number of studies have been found indicating that future studies are needed that assess this effect and include the analysis of the number of intervals and their duration in order to maximize this effect.
PubMed: 38610750
DOI: 10.3390/jcm13071985 -
Sensors (Basel, Switzerland) Mar 2024The global aging population faces significant health challenges, including an increasing vulnerability to disability due to natural aging processes. Wearable lower limb... (Review)
Review
The global aging population faces significant health challenges, including an increasing vulnerability to disability due to natural aging processes. Wearable lower limb exoskeletons (LLEs) have emerged as a promising solution to enhance physical function in older individuals. This systematic review synthesizes the use of LLEs in alignment with the WHO's healthy aging vision, examining their impact on intrinsic capacities and functional abilities. We conducted a comprehensive literature search in six databases, yielding 36 relevant articles covering older adults (65+) with various health conditions, including sarcopenia, stroke, Parkinson's Disease, osteoarthritis, and more. The interventions, spanning one to forty sessions, utilized a range of LLE technologies such as Ekso, HAL, Stride Management Assist, Honda Walking Assist, Lokomat, Walkbot, Healbot, Keeogo Rehab, EX1, overground wearable exoskeletons, Eksoband, powered ankle-foot orthoses, HAL lumbar type, Human Body Posturizer, Gait Enhancing and Motivation System, soft robotic suits, and active pelvis orthoses. The findings revealed substantial positive outcomes across diverse health conditions. LLE training led to improvements in key performance indicators, such as the 10 Meter Walk Test, Five Times Sit-to-Stand test, Timed Up and Go test, and more. Additionally, enhancements were observed in gait quality, joint mobility, muscle strength, and balance. These improvements were accompanied by reductions in sedentary behavior, pain perception, muscle exertion, and metabolic cost while walking. While longer intervention durations can aid in the rehabilitation of intrinsic capacities, even the instantaneous augmentation of functional abilities can be observed in a single session. In summary, this review demonstrates consistent and significant enhancements in critical parameters across a broad spectrum of health conditions following LLE interventions in older adults. These findings underscore the potential of LLE in promoting healthy aging and enhancing the well-being of older adults.
Topics: Humans; Aged; Exoskeleton Device; Healthy Aging; Postural Balance; Time and Motion Studies; World Health Organization
PubMed: 38610440
DOI: 10.3390/s24072230 -
Journal of Stroke and Cerebrovascular... Jun 2024Stroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Stroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes mellitus (T2DM) is not only widespread but also a known risk factor for stroke. Our meta-analysis aims to assess the influence of pre-stroke metformin use on the clinical outcomes in AIS patients with T2DM.
MATERIALS AND METHODS
We conducted this study following PRISMA guidelines, searching the following databases: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials up to February 29, 2024. All studies providing separate data on AIS patients using metformin were included, and statistical analysis was conducted using R software to pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI).
RESULTS
Out of 1051 studies, 7 met the inclusion criteria for our meta-analysis with a total of 11589 diabetic patients, including 5445 patients taking metformin and 6144 diabetic patients in the non-metformin group. Compared to the non-metformin group, the metformin group had a significantly higher rate of mRS 0-2 score at discharge (OR 1.56; 95% CI 1.25:1.95; p=< 0.01) and a lower rate of 90-day mortality (OR 0.51; 95% CI 0.42:0.61; p=< 0.01), with no significant difference in sICH (OR 0.88; 95% CI 0.47:1.64; p= 0.68) between the two groups.
CONCLUSIONS
Our meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Ischemic Stroke; Hypoglycemic Agents; Treatment Outcome; Risk Factors; Male; Aged; Female; Middle Aged; Risk Assessment; Time Factors; Recovery of Function; Disability Evaluation; Aged, 80 and over; Functional Status
PubMed: 38604350
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107716 -
Journal of Clinical Medicine Feb 2024Indication to perform surgical explantation of TAVR is becoming increasingly more frequent, due to the higher number of transcatheter procedures performed in patients... (Review)
Review
Indication to perform surgical explantation of TAVR is becoming increasingly more frequent, due to the higher number of transcatheter procedures performed in patients with longer life expectancy. We proposed to perform a systematic review and meta-analysis with metaregression to identify potential factors that can determine an increase in the high mortality and morbidity that characterize these surgical procedures. MEDLINE and Embase were searched for relevant studies. Twelve studies were eligible according to our inclusion criteria. TAVR explantation was confirmed as a procedure with high 30-day mortality (0.17; 95% CI, 0.14-0.21) and morbidity (stroke incidence 5%; 95% CI, 0.04-0.07; kidney injury incidence 16%; 95% CI, 0.11-0.24). The type of transcatheter valve implanted during the index procedure did not influence the outcomes after surgical explantation. The role of these high-risk operations is growing, and it will likely expand in the coming years. Specific tools for risk stratification are required.
PubMed: 38592075
DOI: 10.3390/jcm13051262 -
Nutrition Research and Practice Apr 2024Mushroom consumption, rich in diverse nutrients and bioactive compounds, is suggested as a potential significant contributor to preventing cardiometabolic diseases... (Review)
Review
BACKGROUND/OBJECTIVES
Mushroom consumption, rich in diverse nutrients and bioactive compounds, is suggested as a potential significant contributor to preventing cardiometabolic diseases (CMDs). This systematic review aimed to explore the association between mushrooms and cardiometabolic health outcomes, utilizing data from prospective cohort studies and clinical trials focusing on the general population, with mushrooms themselves as a major exposure.
SUBJECTS/METHODS
All original articles, published in English until July 2023, were identified through searches on PubMed, Ovid-Embase, and google scholar. Of 1,328 studies, we finally selected 5 prospective cohort studies and 4 clinical trials.
RESULTS
Existing research is limited, typically consisting of 1 to 2 studies for each CMD and cardiometabolic condition. Examination of articles revealed suggestive associations in some cardiometabolic conditions including blood glucose (both fasting and postprandial), high-density lipoprotein cholesterol related indices, high-sensitivity C-reactive protein, and obesity indices (body weight, body mass index, and waist circumference). However, mushroom consumption showed no association with the mortality and morbidity of cardiovascular diseases, stroke, and type 2 diabetes, although there was a potentially beneficial connection with all cause-mortality, hyperuricemia, and metabolic syndrome.
CONCLUSION
Due to the scarcity of available studies, drawing definitive conclusions is premature. Further comprehensive investigations are needed to clarify the precise nature and extent of this relationship before making conclusive recommendations for the general population.
PubMed: 38584813
DOI: 10.4162/nrp.2024.18.2.165 -
PloS One 2024Health state utility values (HSUV) for Type 2 diabetes mellitus (T2DM) complications are useful in economic evaluations to determine cost effectiveness of an...
INTRODUCTION
Health state utility values (HSUV) for Type 2 diabetes mellitus (T2DM) complications are useful in economic evaluations to determine cost effectiveness of an intervention. However, there is a lack of reference ranges for different severity and stages of individual complications. This study aimed to provide an overview of HSUV decrement ranges for common T2DM complications focusing on different severity and stages of complications.
METHOD
A systematic search was conducted in MEDLINE, SCOPUS, WEB OF SCIENCE. (Jan 2000 to April 2022). Included studies for HSUV estimates were from outpatient setting, regardless of treatment types, complication stages, regions and HRQoL instruments. Health Related Quality of Life (HRQoL) outcomes was to be presented as HSUV decrement values, adjusted according to social demographics and comorbidities. Adjusted HSUV decrements were extracted and compiled according to individual complications. After which, subsequently grouped into mild or severe category for comparison.
RESULTS
Searches identified 35 studies. The size of the study population ranged from 160 to 14,826. The HSUV decrement range was widest for cerebrovascular disease (stroke): -0.0060 to -0.0780 for mild stroke and -0.035 to -0.266 for severe stroke; retinopathy: mild (-0.005 to -0.0862), moderate (-0.0030 to -0.1845) and severe retinopathy (-0.023 to -0.2434); amputation: (-0.1050 to -0.2880). Different nature of complication severity defined in studies could be categorized into: those with acute nature, chronic with lasting effects, those with symptoms at early stage or those with repetitive frequency or episodes.
DISCUSSION
Overview of HSUV decrement ranges across different stages of each T2DM diabetes-related complications shows that chronic complications with lasting impact such as amputation, severe stroke with sequelae and severe retinopathy with blindness were generally associated with larger HSUV decrement range. Considerable heterogeneities exist across the studies. Promoting standardized complication definitions and identifying the most influential health state stages on HSUV decrements may assist researchers for future cost-effectiveness studies.
Topics: Humans; Diabetes Mellitus, Type 2; Quality of Life; Diabetes Complications; Stroke; Retinal Diseases
PubMed: 38574169
DOI: 10.1371/journal.pone.0297589