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Clinical Infectious Diseases : An... Oct 2003Some studies have shown that currently available protease inhibitors (PIs) are associated with an increased risk of cardiovascular disease. We have systematically... (Review)
Review
Some studies have shown that currently available protease inhibitors (PIs) are associated with an increased risk of cardiovascular disease. We have systematically reviewed the published literature and conference abstracts for studies evaluating cardiovascular risk factors and events in patients receiving highly active antiretroviral therapy, with and without PIs. The majority of studies showed that the use of PIs was associated with increased levels of total cholesterol (36 [75%] of 48 studies), triglycerides (35 [73%] of 48 studies), and low-density lipoprotein (12 [100%] of 12 studies). PI use was often associated with morphological signs of cardiovascular disease, such as increased carotid intima thickness or atherosclerotic lesions (7 [88%] of 8 studies). Finally, 2 (67%) of 3 long-term observational studies that met our inclusion criteria demonstrated an association between use of PIs and subsequent myocardial infarction. The benefits of the currently available PIs should be balanced against the long-term risk of cardiovascular disease.
Topics: Antiretroviral Therapy, Highly Active; Cardiovascular Diseases; Clinical Trials as Topic; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Lipoproteins; Risk Factors
PubMed: 13130409
DOI: 10.1086/378064 -
Journal of Thrombosis and Haemostasis :... Oct 2011Although the association between intensive treatment and the formation of inhibiting antibodies towards factor VIII (FVIII) in hemophilia A has been demonstrated, the... (Review)
Review
BACKGROUND
Although the association between intensive treatment and the formation of inhibiting antibodies towards factor VIII (FVIII) in hemophilia A has been demonstrated, the contributing effect of surgery is presently unclear. The release of immunological danger signals resulting from tissue damage during surgery in the presence of a high FVIII antigen load may elicit the formation of FVIII antibodies. The aim of this systematic review was to investigate the role of surgery in the inhibitor risk associated with intensive treatment as compared with treatment for bleeding and prophylactic administration of FVIII.
METHODS
A comprehensive literature search was performed that identified four cohort studies and three case control studies, comprising 342 inhibitor patients among a total of 957 hemophilia A patients.
RESULTS
Intensive treatment increased the inhibitor risk, most pronounced with intensive treatment of ≥ 5 exposure days (EDs) compared with < 3 EDs (OR, 4.1; 95% confidence interval, 2.6-6.5). Pooled odds ratio for inhibitor development in severe hemophilia patients that received intensive treatment for surgery at first exposure was 4.1 (95% confidence interval, 2.0-8.4) compared with treatment for bleeding or prophylaxis. Information on continuous infusion, previously treated patients and non-severe hemophilia A was insufficient for valid meta-analyses.
CONCLUSIONS
Intensive FVIII treatment for surgery at first exposure leads to a higher inhibitor risk in hemophilia A patients compared with intensive treatment for bleeding.
Topics: Blood Loss, Surgical; Factor VIII; Hemophilia A; Humans; Risk Assessment; Serine Proteinase Inhibitors
PubMed: 21838755
DOI: 10.1111/j.1538-7836.2011.04467.x -
Journal of Clinical Medicine May 2023The use of integrase inhibitor-based antiretroviral therapy could be associated with worse weight and metabolic outcomes in patients with HIV infection. (Review)
Review
BACKGROUND
The use of integrase inhibitor-based antiretroviral therapy could be associated with worse weight and metabolic outcomes in patients with HIV infection.
METHODS
PubMed, EMBASE, and Scopus were searched from inception to March 2022. We selected randomized controlled trials (RCTs) comparing integrase inhibitors with other antiretroviral classes (efavirenz-based or protease inhibitor-based therapies) in naïve HIV patients. Random effects meta-analysis was used to assess the effects of integrase inhibitors vs. controls on weight and lipid outcomes. Effects were described as mean differences (MD) and their 95% confidence intervals (CI). Certain pieces of evidence (CoE) were evaluated using the GRADE methodology.
RESULTS
Six RCTs (n = 3521) were included, with patients followed up between 48 and 96 weeks. The use of integrase inhibitors in comparison with other antiretroviral classes was associated with an increase in weight (MD 2.15 kg, 95%CI 1.40 to 2.90, I = 0%, moderate CoE), and decreases in total cholesterol (MD -13.44 mg/dL, 95%CI -23.49 to -3.39, I = 96%, low CoE), LDL cholesterol (MD -1.37 mg/dL, 95%CI -19.24 to -3.50, I = 83%, low CoE), HDL cholesterol (MD -5.03 mg/dL, 95%CI -10.61 to 0.54, I = 95%, low CoE), and triglycerides (MD -20.70 mg/dL, 95%CI -37.25 to -4.15, I = 92%, low CoE). There was a high risk of bias in two RCTs and some concerns about bias in two RCTs.
CONCLUSIONS
In HIV patients, the use of integrase inhibitor-based therapy in comparison with protease inhibitor- or NNRTI-based therapy was associated with a small increase in weight and small decreases in lipid serum levels.
PubMed: 37297839
DOI: 10.3390/jcm12113644 -
PloS One 2023Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic kidney disease (DKD) is a health burden of rising importance. Slowing progression to end stage kidney disease is the main goal of drug treatment. The aim of this analysis is to compare drug treatments of DKD by means of a systemic review and a network meta-analysis.
METHODS
We searched Medline, CENTRAL and clinicaltrials.gov for randomized, controlled studies including adults with DKD treated with the following drugs of interest: single angiotensin-converting-enzyme-inhibitor or angiotensin-receptor-blocker (single ACEi/ARB), angiotensin-converting-enzyme-inhibitor and angiotensin-receptor-blocker combination (ACEi+ARB combination), aldosterone antagonists, direct renin inhibitors, non-steroidal mineralocorticoid-receptor-antagonists (nsMRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i). As primary endpoints, we defined: overall mortality and end-stage kidney disease, as secondary endpoints: renal composite outcome and albuminuria and as safety endpoints: acute kidney injury, hyperkalemia and hypotension. Under the use of a random effects model, we computed the overall effect estimates using the statistic program R4.1 and the corresponding package "netmeta". Risk of bias was assessed using the RoB 2 tool and the quality of evidence of each pairwise comparison was rated according to GRADE (Grading of Recommendations Assessment, Development and Evaluation).
RESULTS
Of initial 3489 publications, 38 clinical trials were found eligible, in total including 42346 patients. Concerning the primary endpoints overall mortality and end stage kidney disease, SGLT2i on top of single ACEi/ARB compared to single ACEi/ARB was the only intervention significantly reducing the odds of mortality (OR 0.81, 95%CI 0.70-0.95) and end-stage kidney disease (OR 0.69, 95%CI 0.54-0.88). The indirect comparison of nsMRA vs SGLT2i in our composite endpoint suggests a superiority of SGLT2i (OR 0.60, 95%CI 0.47-0.76). Concerning safety endpoints, nsMRA and SGLT2i showed benefits compared to the others.
CONCLUSIONS
As the only drug class, SGLT2i showed in our analysis beneficial effects on top of ACEi/ARB treatment regarding mortality and end stage kidney disease and by that reconfirmed its position as treatment option for diabetic kidney disease. nsMRA reduced the odds for a combined renal endpoint and did not raise any safety concerns, justifying its application.
Topics: Adult; Humans; Angiotensin-Converting Enzyme Inhibitors; Diabetic Nephropathies; Angiotensin Receptor Antagonists; Network Meta-Analysis; Sodium-Glucose Transporter 2 Inhibitors; Kidney Failure, Chronic; Angiotensins; Diabetes Mellitus
PubMed: 37917640
DOI: 10.1371/journal.pone.0293183 -
International Journal of STD & AIDS Apr 2018This systematic review and meta-analysis tries to determine whether there is an association between the use of protease inhibitors (PIs) and the incidence of diabetes... (Meta-Analysis)
Meta-Analysis Review
Association between the use of protease inhibitors in highly active antiretroviral therapy and incidence of diabetes mellitus and/or metabolic syndrome in HIV-infected patients: A systematic review and meta-analysis.
This systematic review and meta-analysis tries to determine whether there is an association between the use of protease inhibitors (PIs) and the incidence of diabetes mellitus (DM) and/or metabolic syndrome (MS) in HIV-infected patients. A systematic literature search was performed using MEDLINE/PubMed, CENTRAL, LILACS, and EMBASE. Included articles were observational studies published on or prior to November 2015 that met specific inclusion criteria. Pooled relative risks (RRs) and hazard ratios (HRs) were calculated. Nine articles met the inclusion criteria, describing 13,742 HIV patients. Use of PIs was associated with the development of MS (RR: 2.11; 95% CI 1.28-3.48; p-value 0.003). No association between the use of PIs and development of DM was found: the HR for the incidence of DM among patients using PIs was 1.23 (95% CI 0.66-2.30; p-value: 0.51) and the RR was 1.25 (95% CI 0.99-1.58; p-value 0.06). Use of PIs in HIV-infected patients is associated with an increased risk of MS. No evidence of an increased risk of DM was found. However, because MS is a precursor to DM, it is possible that studies with a longer follow-up duration are needed in order to detect an association between PI use and onset of DM.
Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Diabetes Mellitus; Female; HIV Infections; Humans; Incidence; Metabolic Syndrome; Protease Inhibitors; United Kingdom
PubMed: 28956700
DOI: 10.1177/0956462417732226 -
British Journal of Clinical Pharmacology Oct 2022Dabigatran etexilate is an oral direct thrombin inhibitor used in preventing thromboembolism in patients with atrial fibrillation and several other conditions. Routine... (Meta-Analysis)
Meta-Analysis Review
Dabigatran etexilate is an oral direct thrombin inhibitor used in preventing thromboembolism in patients with atrial fibrillation and several other conditions. Routine dabigatran concentration monitoring is not recommended in clinical practice; however, measurement of dabigatran concentration may be required in several conditions. This study aims to pool the peak and trough dabigatran concentration from real-world studies. A systematic review was performed to identify studies that measured the peak and trough dabigatran concentrations. Observational studies reporting dabigatran peak or trough concentrations and patients' clinical characteristics of either sex, age or weight were included. Random-effect meta-analyses and metaregression were conducted to pool dabigatran concentrations and to identify the correlation between factors affecting dabigatran concentrations. Fifteen studies with a total of 1226 patients were included. The pooled peak dabigatran concentration was 133 ng/mL (95% CI: 113-154, I = 86%, n = 655), while the pooled dabigatran trough concentration was 80 ng/mL (95% CI: 69-91, I = 93%, n = 1010). Metaregression analyses suggested that age is significantly correlated to trough concentration, while body weight and creatinine clearance significantly correlated to peak concentration. Subgroup results revealed that dabigatran concentration when measured with liquid chromatography-tandem mass spectrometry was higher than haemoclot thrombin inhibitor assay. Several guidelines have proposed dabigatran concentrations target range and the pooled dabigatran concentrations were in line with the suggested range. Further studies to correlate dabigatran concentrations and clinical outcomes is warranted to improve the safety and efficacy monitoring of dabigatran therapy.
Topics: Adult; Antithrombins; Atrial Fibrillation; Blood Coagulation Tests; Chromatography, Liquid; Dabigatran; Humans
PubMed: 35665523
DOI: 10.1111/bcp.15431 -
The Cochrane Database of Systematic... Nov 2018Elevated blood pressure (hypertension) affects about one billion people worldwide. It is important as it is a major risk factor for stroke and myocardial infarction.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Elevated blood pressure (hypertension) affects about one billion people worldwide. It is important as it is a major risk factor for stroke and myocardial infarction. However, it remains a challenge for the medical profession as many people with hypertension have blood pressure (BP) that is not well controlled. According to Traditional Chinese Medicine theory, acupuncture has the potential to lower BP.
OBJECTIVES
To assess the effectiveness and safety of acupuncture for lowering blood pressure in adults with primary hypertension.
SEARCH METHODS
We searched the Hypertension Group Specialised Register (February 2017); the Cochrane Central Register of Controlled Trials (CENTRAL) 2017, Issue 2; MEDLINE (February 2017); Embase (February 2017), China National Knowledge Infrastructure (CNKI) (January 2015), VIP Database (January 2015), the World Health Organisation Clinical Trials Registry Platform (February 2017)and ClinicalTrials.gov (February 2017). There were no language restrictions.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) that compared the clinical effects of an acupuncture intervention (acupuncture used alone or add-on) with no treatment, a sham acupuncture or an antihypertensive drug in adults with primary hypertension.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies according to inclusion and exclusion criteria. They extracted data and assessed the risk of bias of each trial, and telephoned or emailed the authors of the studies to ask for missing information. A third review author resolved disagreements. Outcomes included change in systolic blood pressure (SBP), change in diastolic blood pressure (DBP), withdrawal due to adverse effects, and any adverse events. We calculated pooled mean differences (MD) with 95% confidence intervals (CI) for continuous outcomes using a fixed-effect or random-effects model where appropriate.
MAIN RESULTS
Twenty-two RCTs (1744 people) met our inclusion criteria. The RCTs were of variable methodological quality (most at high risk of bias because of lack of blinding). There was no evidence for a sustained BP lowering effect of acupuncture; only one trial investigated a sustained effect and found no BP lowering effect at three and six months after acupuncture. Four sham acupuncture controlled trials provided very low quality evidence that acupuncture had a short-term (one to 24 hours) effect on SBP (change) -3.4 mmHg (-6.0 to -0.9) and DBP -1.9 mmHg (95% CI -3.6 to -0.3). Pooled analysis of eight trials comparing acupuncture with angiotensin-converting enzyme inhibitors and seven trials comparing acupuncture to calcium antagonists suggested that acupuncture lowered short-term BP better than the antihypertensive drugs. However, because of the very high risk of bias in these trials, we think that this is most likely a reflection of bias and not a true effect. As a result, we did not report these results in the 'Summary of findings' table. Safety of acupuncture could not be assessed as only eight trials reported adverse events.
AUTHORS' CONCLUSIONS
At present, there is no evidence for the sustained BP lowering effect of acupuncture that is required for the management of chronically elevated BP. The short-term effects of acupuncture are uncertain due to the very low quality of evidence. The larger effect shown in non-sham acupuncture controlled trials most likely reflects bias and is not a true effect. Future RCTs must use sham acupuncture controls and assess whether there is a BP lowering effect of acupuncture that lasts at least seven days.
Topics: Acupuncture Therapy; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Humans; Hypertension; Publication Bias; Randomized Controlled Trials as Topic
PubMed: 30480757
DOI: 10.1002/14651858.CD008821.pub2 -
Clinical Infectious Diseases : An... Jun 2018In sub-Saharan Africa, 25.5 million people are living with human immunodeficiency virus (HIV), representing 70% of the global total. The need for second-line... (Meta-Analysis)
Meta-Analysis
Effectiveness of Protease Inhibitor/Nucleos(t)ide Reverse Transcriptase Inhibitor-Based Second-line Antiretroviral Therapy for the Treatment of Human Immunodeficiency Virus Type 1 Infection in Sub-Saharan Africa: A Systematic Review and Meta-analysis.
BACKGROUND
In sub-Saharan Africa, 25.5 million people are living with human immunodeficiency virus (HIV), representing 70% of the global total. The need for second-line antiretroviral therapy (ART) is projected to increase in the next decade in keeping with the expansion of treatment provision. Outcome data are required to inform policy.
METHODS
We performed a systematic review and meta-analysis of studies reporting the virological outcomes of protease inhibitor (PI)-based second-line ART in sub-Saharan Africa. The primary outcome was virological suppression (HIV-1 RNA <400 copies/mL) after 48 and 96 weeks of treatment. The secondary outcome was the proportion of patients with PI resistance. Pooled aggregate data were analyzed using a DerSimonian-Laird random effects model.
RESULTS
By intention-to-treat analysis, virological suppression occurred in 69.3% (95% confidence interval [CI], 58.2%-79.3%) of patients at week 48 (4558 participants, 14 studies), and in 61.5% (95% CI, 47.2%-74.9%) at week 96 (2145 participants, 8 studies). Preexisting resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) increased the likelihood of virological suppression. Major protease resistance mutations occurred in a median of 17% (interquartile range, 0-25%) of the virological failure population and increased with duration of second-line ART.
CONCLUSIONS
One-third of patients receiving PI-based second-line ART with continued NRTI use in sub-Saharan Africa did not achieve virological suppression, although among viremic patients, protease resistance was infrequent. Significant challenges remain in implementation of viral load monitoring. Optimizing definitions and strategies for management of second-line ART failure is a research priority.
PROSPERO REGISTRATION
CRD42016048985.
Topics: Africa South of the Sahara; Antiretroviral Therapy, Highly Active; Drug Resistance, Viral; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Male; Mutation; Observational Studies as Topic; Randomized Controlled Trials as Topic; Reverse Transcriptase Inhibitors; Sustained Virologic Response; Treatment Outcome; Viral Load; Viremia
PubMed: 29272346
DOI: 10.1093/cid/cix1108 -
Primary Care Diabetes Feb 2022This systematic review and meta-analysis aimed to synthesize the latest evidence on the effect of dipeptidyl peptidase-4 (DPP-IV) inhibitor in patients with COVID-19. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This systematic review and meta-analysis aimed to synthesize the latest evidence on the effect of dipeptidyl peptidase-4 (DPP-IV) inhibitor in patients with COVID-19.
METHODS
We performed a systematic literature search from the PubMed, Scopus, Embase, and Clinicaltrials.gov up until 15 July 2021. Studies that met the following criteria were included: prospective or retrospective observational studies or case series or randomized controlled trials (RCTs) reporting DPP-IV inhibitor use in patients with COVID-19 and mortality. The intervention group was patients receiving DPP-IV inhibitor. The control group was patients that did not receive DPP-IV inhibitor. The outcome was mortality reported as odds ratio (OR).
RESULTS
There were 11 studies consisting of 5950 patients in this meta-analysis. DPP-IV inhibitor use was associated with reduced mortality (OR 0.75 [0.56, 0.99], p = 0.043, I: 42.9, p = 0.064) compared to those that did not receive DPP-IV inhibitor. Sensitivity analysis using the fixed-effect model (OR 0.75 [0.63, 0.88], p < 0.001, I: 42.9, p = 0.064) also showed mortality benefit. The association between DPP-IV inhibitor and mortality was not significantly affected by age (p = 0.540), sex (p = 0.054), hypertension (p = 0.320), location (continent; p = 0.532), and retrospective/prospective nature of the study (p = 0.840). However, the association was affected by metformin (OR 1.03 [95% CI 1.01, 1.06], p = 0.010) and ACEI/ARB use (OR 1.06 [95% CI 1.02, 1.10], p = 0.004).
CONCLUSION
This meta-analysis showed that DPP-IV inhibitor was associated with reduced mortality in patients with COVID-19.
Topics: COVID-19; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Humans; Hypoglycemic Agents; SARS-CoV-2
PubMed: 34952805
DOI: 10.1016/j.pcd.2021.12.008 -
Journal of Medical Virology Oct 2022Recommended treatment regimen for human immune deficiency virus (HIV) infection includes protease inhibitors/ritonavir (PIs/r) combined with two-nucleoside... (Meta-Analysis)
Meta-Analysis Review
Recommended treatment regimen for human immune deficiency virus (HIV) infection includes protease inhibitors/ritonavir (PIs/r) combined with two-nucleoside reverse-transcriptase inhibitors (2NRTIs), which enable to achieve and maintain viral suppression, restore, and preserve immune function. However, there were inconsistent findings on the levels of interleukin-6 (IL-6) levels. Systematic review and meta-analysis were performed to quantify the pooled effects of PIs/r-based antiretroviral therapy (ART) on serum/plasma IL-6 levels in people living with the HIV (PLHIV). PubMed, Web of Science, and Embase were searched from the earliest record to November 4, 2020. Data analysis was conducted on Stata version 16 and Review Manager 5.3. A random-effect model was used to compute a pooled effect size and weighted mean difference (WMD) was considered the summary effect size. Heterogeneity between studies was estimated by Cochrane's Q test (χ test) and I statistic and subgroup analysis were performed to explore the source of heterogeneity. Initial search identified 3098 records and 5 studies (7 trials) met inclusion criteria. The pooled mean difference in serum/plasma IL-6 levels from baseline to follow-up was 0.534 pg/ml (95% confidence interval: -0.012, 1.08, P = 0.05, I = 76.4%). In subgroup analysis, there was a significant association between increased serum/plasma IL-6 levels and age group ≥ 35 years old, baseline CD4 counts < 350 cell/mm , and mean viral load ≥ 4.5 log10 copies/ml. We found that serum/plasma IL-6 levels increased after combined ART among treatment-naïve individuals who initiated a successful combination of PIs/r with 2NRTIs. This result also highlights the need to monitor serum/plasma IL-6 levels during antiviral therapy, which may aid in the effective future treatment of systemic inflammation and related disorders following elevated IL-6 levels.
Topics: Adult; Anti-HIV Agents; Anti-Retroviral Agents; CD4 Lymphocyte Count; HIV Infections; HIV Protease Inhibitors; Humans; Interleukin-6; Protease Inhibitors; Ritonavir; Viral Load
PubMed: 35665943
DOI: 10.1002/jmv.27912