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Diabetes & Metabolic Syndrome 2021This study aims to synthesize evidence on dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in COVID-19 patients and factors affecting it. (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
This study aims to synthesize evidence on dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in COVID-19 patients and factors affecting it.
METHODS
We performed a systematic literature search from PubMed, Scopus, and Embase databases from inception of databases up until 7 March 2021. Studies that met all of the following criteria were included: 1) observational studies or randomized controlled trials that report COVID-19 patients, 2) reporting DPP-4 inhibitor use, 3) mortality, and 4) mortality based on DPP-4 inhibitor use. The exposure was DPP-4 inhibitor, defined as DPP-4 inhibitor use that started prior to COVID-19 hospitalization. The control group was patients with no exposure to DPP-4 inhibitor. The outcome was mortality. The pooled effect estimate was reported as risk ratio (RR).
RESULTS
There were 4,477 patients from 9 studies in this systematic review and meta-analysis. 31% of (15%, 46%) the patients use DPP-4 inhibitor. Mortality occurs in 23% (15%, 31%) of the patients. DPP-4 inhibitor was associated with lower mortality in patients with COVID-19 (RR 0.76 [0.60, 0.97], p = 0.030, I2: 44.5%, p = 0.072). Meta-regression analysis showed that the association between DPP-4 inhibitor and mortality was significantly affected by metformin (RR 1.02 [1.00, 1.04], p = 0.048) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB) use (RR 1.04 [1.01, 1.07], p = 0.006), but not age (p = 0.759), sex (reference: male, p = 0.148), and hypertension (p = 0.218).
CONCLUSION
DPP-4 inhibitor use was associated with lower mortality in COVID-19 patients, and the association was weaker in patients who were also taking metformin and/or ACE inhibitors.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; COVID-19; Comorbidity; Diabetes Mellitus; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Hypertension; Male; Metformin; Mortality; Regression Analysis; SARS-CoV-2
PubMed: 33838614
DOI: 10.1016/j.dsx.2021.03.027 -
BMJ Clinical Evidence Jul 2008Infection with the human immunodeficiency virus (HIV) usually leads to 8-10 years of asymptomatic infection before immune function deteriorates and AIDS develops.... (Review)
Review
INTRODUCTION
Infection with the human immunodeficiency virus (HIV) usually leads to 8-10 years of asymptomatic infection before immune function deteriorates and AIDS develops. Without treatment, about 50% of infected people will die of AIDS over 10 years. With treatment, prognosis depends on age, CD4 cell count, and initial viral load.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of preventive interventions? What are the effects of different antiretroviral drug treatment regimens in HIV infection? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 17 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: combination treatments containing either CCR5 inhibitors or fusion inhibitors; early diagnosis and treatment of sexually transmitted diseases (STDs); early and delayed antiretroviral treatment using triple antiretroviral regimens; non-nucleoside reverse transcriptase inhibitor (NNRTI) based triple regimens; nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor-based triple regimens (standard, and boosted); post-exposure prophylaxis in healthcare workers; and presumptive mass treatment of sexually transmitted diseases (STDs).
Topics: CD4 Lymphocyte Count; HIV Infections; Humans; Reverse Transcriptase Inhibitors
PubMed: 19445740
DOI: No ID Found -
Drugs & Aging Jul 2013Sulfonylureas have been linked to increased risk of hypoglycemia. Hypoglycemia may lead to falls, and falls may lead to fracture. However, studies quantifying the... (Review)
Review
BACKGROUND
Sulfonylureas have been linked to increased risk of hypoglycemia. Hypoglycemia may lead to falls, and falls may lead to fracture. However, studies quantifying the association between sulfonylureas and fractures are sparse and yield inconsistent results.
OBJECTIVE
The purpose of this article was to review the literature regarding sulfonylurea use and falls or fall-related fractures among older adults with type 2 diabetes mellitus and to delineate areas for future research.
DATA SOURCES
We searched MEDLINE (1966-March 2012) and CINAHL (1937-March 2012) for studies of patients with type 2 diabetes mellitus living in the community or nursing homes.
STUDY SELECTION
The search algorithms combined three domains: (1) diabetic patients, (2) sulfonylurea medications, and (3) fractures or falls. We included only publications in English that pertained to human subjects. We found 9 randomized trials and 12 non-experimental studies that met the inclusion criteria.
STUDY APPRAISAL AND SYNTHESIS METHODS
The guidelines provided by the Cochrane handbook or Agency for Healthcare Research and Quality (AHRQ) Methods Guide are too general to distinguish the quality of included non-experimental studies, so we developed several specific domains based on those general guidelines. These domains included study design, study population, follow-up time, comparison group, exposure definition, outcome definition, induction period, confounding adjustment, and attrition or missing data. The data were not amenable to a meta-analysis.
RESULTS
No clinical trials included fracture as a primary endpoint. Most clinical trials excluded older adults. Most studies were not designed to evaluate the risk of sulfonylureas on fractures or falls. Studies did not show an increased risk of falls/fractures with sulfonylurea.
LIMITATIONS
The data available from existing studies suffer from methodological limitations including insufficient events, lack of primary endpoints, exclusion of older adults, and lack of clarity or inappropriate comparison groups.
CONCLUSION
Future studies are needed to appropriately estimate the effect of sulfonylureas on falls or fall-related fractures in older adults who are at increased risk for hypoglycemia, the hypothesized mechanism for fractures related to sulfonylurea therapy.
Topics: Accidental Falls; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Fractures, Bone; Humans; Metformin; Sulfonylurea Compounds; Thiazolidinediones
PubMed: 23609875
DOI: 10.1007/s40266-013-0081-0 -
The Journal of Trauma and Acute Care... Feb 2016Ulinastatin (UTI) and thymosin α1 (Tα1) have been investigated for their immunoregulatory properties in patients with severe sepsis. However, it is unclear whether... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Ulinastatin (UTI) and thymosin α1 (Tα1) have been investigated for their immunoregulatory properties in patients with severe sepsis. However, it is unclear whether immunomodulatory therapy using UTI combined with Tα1 (UCT), UTI alone (UA), or Tα1 alone (TA) improves the disease outcome. The objective of this study was to analyze the effectiveness of UCT, UA, and TA for the treatment of severe sepsis.
METHODS
PubMed, EMBASE, and Cochrane Library databases were investigated from inception to September 2015. Randomized controlled trials (RCTs) examining the treatment of patients with severe sepsis by UCT, UA, and TA were defined as eligible. Data were analyzed using Review Manager 5.3, and the RCTs were evaluated by the Cochrane Handbook 5.1.0. The quality of the evidence was evaluated according to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE).
RESULTS
Ten articles and 12 studies were included in this systematic review and meta-analysis. The primary outcome measures indicated that UCT was associated with significantly lower 28-day mortality (risk ratio [RR], 0.67; 95% confidence interval [CI], 0.57-0.80; p < 0.00001; n = 915; GRADE rating, moderate) and 90-day mortality (RR, 0.75; 95% CI, 0.61-0.93; p = 0.009; n = 547; GRADE rating, moderate); UA was associated with no significant difference in the 28-day mortality (RR, 0.60; 95% CI, 0.30-1.20; p = 0.15; n = 182; GRADE rating, low), and there was no report on 90-day mortality; TA was associated with significantly lower 28-day mortality (RR, 0.72; 95% CI, 0.55-0.93; p = 0.01; n = 494; GRADE rating, low), but there was no significant difference in the 90-day mortality (RR, 0.84; 95% CI, 0.54-1.31; p = 0.45; n = 91; GRADE rating, very low). In the secondary outcome measures, there was obvious heterogeneity in the length of the intensive care unit stay and that of the mechanical ventilation, length of the antibiotics and vasopressor use, and 28-day Acute Physiology and Chronic Health Evaluation II (APACHE II) scores.
CONCLUSION
Treatment of severe sepsis with UCT reduced both the 28-day and the 90-day mortality, whereas treatment with TA reduced only the 28-day mortality. The effects of UCT, UA, and TA on intensive care unit stay, mechanical ventilation, antibiotics and vasopressor use, and 28-day APACHE II scores of septic patients are still unclear. Additional high-quality RCTs are needed to define clearly the guidelines for the treatment of severe sepsis.
LEVEL OF EVIDENCE
Systematic review, level IV.
Topics: Adjuvants, Immunologic; Drug Therapy, Combination; Glycoproteins; Humans; Sepsis; Thymalfasin; Thymosin; Trypsin Inhibitors
PubMed: 26517783
DOI: 10.1097/TA.0000000000000909 -
AIDS Reviews Mar 2021Efavirenz- and protease inhibitor (PI)-based regimens remain viable options across the globe. We conducted a meta-analysis to compare the effectiveness of... (Meta-Analysis)
Meta-Analysis
Efavirenz- and protease inhibitor (PI)-based regimens remain viable options across the globe. We conducted a meta-analysis to compare the effectiveness of efavirenz-based regimens relative to PI-based regimens. EMBASE, PubMed, Cochrane, and clinicaltrials.gov were searched for randomized controlled trials conducted between 1987 and 2018 comparing efavirenz- with PI-based regimens. This was followed by title, abstract, and full-text screens. The quality of selected studies was assessed using the Cochrane risk of bias tool. Meta-analysis of the odds of virological suppression was conducted using the robust variance estimation approach. Fifteen studies met the inclusion criteria and totaled 6712 patients (efavirenz arm = 3339; PI arm = 3373), of which 1610 (24.0%) were females. Follow-up ranged from 24 to 144 weeks. Mean/median age ranged from 33 to 44 years. Mean/median baseline CD4 count ranged from 32 to 557 cells/mL while mean/median baseline viral load ranged from log10 4.5 to log10 5.5 copies/mL. Meta-analysis showed that patients receiving efavirenz-based regimens had 37% higher odds of virological suppression compared to PI-based regimens (odds ratio = 1.37, 95% confidence interval = 1.06-1.77, p = 0.02). The Egger test suggested the presence of publication bias (B = 0.927, t = 2.214, p = 0.033). The main threat to the quality of evidence was attrition bias. Regarding virological suppression, efavirenzbased regimens were more effective than PI-based regimens and, therefore, might be ideal for the management of treatment naïve patients with HIV in settings where NNRTIs and PIs are used.
Topics: Adult; Alkynes; Anti-HIV Agents; Benzoxazines; CD4 Lymphocyte Count; Cyclopropanes; Female; HIV Infections; HIV Protease Inhibitors; Humans; Reverse Transcriptase Inhibitors; Treatment Outcome; Viral Load
PubMed: 33105473
DOI: 10.24875/AIDSRev.20000098 -
Journal of Investigative Medicine : the... May 2024Advances in human immunodeficiency virus (HIV) treatment, including combination antiretroviral therapy (cART), have transformed HIV into a chronic condition. Kidney... (Review)
Review
Advances in human immunodeficiency virus (HIV) treatment, including combination antiretroviral therapy (cART), have transformed HIV into a chronic condition. Kidney diseases cause morbidity and mortality in patients living with HIV (PLWH), though cART has permitted kidney transplants with acceptable post-transplant graft and patient survival. Risk of allograft rejection remains high, which may be related to interactions between cART, specifically protease inhibitors (PI), and immunosuppressants prescribed post-transplant. This systematic review evaluates renal transplant outcomes in PLWH treated with PI- vs non-PI-based cART. A search strategy was generated with terms related to renal transplant, HIV, and cART and run on PubMed, Embase, Scopus, and Cochrane. Studies were evaluated using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on Covidence by two reviewers and then evaluated for bias. Of 803 studies, 9 were included. Included papers were prospective or retrospective cohort studies or chart reviews of adult patients. Outcome measures included acute graft rejection, graft survival, and patient survival. One study had significant results demonstrating that PI-based therapy was correlated with increased graft rejection rates. Two studies demonstrated significant graft survival benefit to non-PI-based therapy, while one demonstrated significant benefit to PI-based therapy. Two studies found significant patient survival benefit to non-PI-based therapy. For each outcome measure, remaining data suggested improved outcomes with non-PI-based therapies without achieving statistical significance. The results demonstrate superior outcomes in PLWH taking non-PI-based cART, though the paucity of significant results suggests that PLWH who require PI-based cART for virological control may continue their regimen safely post-kidney transplant.
PubMed: 38666448
DOI: 10.1177/10815589241252595 -
Journal of the American Academy of... Aug 2021
Meta-Analysis
Topics: Dipeptidyl-Peptidase IV Inhibitors; Drug Eruptions; Humans; Pemphigoid, Bullous
PubMed: 30296540
DOI: 10.1016/j.jaad.2018.09.048 -
BMJ Clinical Evidence Mar 2012Among people with diabetes, about 40% of those aged 45 years, and more than 60% of those aged 75 years or over, will have a blood pressure over 140/90 mmHg. Major... (Review)
Review
INTRODUCTION
Among people with diabetes, about 40% of those aged 45 years, and more than 60% of those aged 75 years or over, will have a blood pressure over 140/90 mmHg. Major cardiac events occur in approximately 5% of people with diabetes and untreated hypertension each year, and the risk is higher in those with other risk factors, such as diabetic nephropathy.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of antihypertensives in people with diabetes and hypertension? What are the effects of different blood pressure targets in people with diabetes and hypertension? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: alpha-blockers, angiotensin II receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, blood pressure targets (lower or higher), calcium-channel blockers, and diuretics.
Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Humans; Hypertension
PubMed: 22456232
DOI: No ID Found -
HIV Medicine May 2014Treatment simplification involving induction with a ritonavir (RTV)-boosted protease inhibitor (PI) replaced by a nonboosted PI (i.e. atazanavir) has been shown to be a... (Meta-Analysis)
Meta-Analysis Review
A meta-analysis of the efficacy and safety of unboosted atazanavir compared with ritonavir-boosted protease inhibitor maintenance therapy in HIV-infected adults with established virological suppression after induction.
OBJECTIVES
Treatment simplification involving induction with a ritonavir (RTV)-boosted protease inhibitor (PI) replaced by a nonboosted PI (i.e. atazanavir) has been shown to be a viable option for long-term antiretroviral therapy. To evaluate the clinical evidence for this approach, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating efficacy and safety in patients with established virological suppression.
METHODS
Several databases were searched without limits on time or language. Searches of conferences were also conducted. RCTs were included if they compared a PI/RTV regimen to unboosted atazanavir, after induction with PI/RTV. The meta-analysis was conducted using a random effects model for the proportion achieving virological suppression (i.e. HIV RNA < 50 and <400 HIV-1 RNA copies/mL), CD4 cell counts, lipid levels and liver function tests. Dichotomous outcomes were reported as risk ratios (RRs) and continuous outcomes as mean differences (MDs).
RESULTS
Five studies (n = 1249) met the inclusion criteria. The meta-analysis demonstrated no statistically significant difference in efficacy (i.e. HIV RNA < 50 copies/mL) between PI/RTV and unboosted atazanavir [RR = 1.04; 95% confidence interval (CI) 0.99 to 1.10], with no heterogeneity. Findings were similar in a subanalysis of studies where atazanavir/RTV was the only PI/RTV used during induction. Additional efficacy results support these findings. A significant reduction in total cholesterol (P < 0.00001), triglycerides (P = 0.0002), low-density lipoprotein (LDL) cholesterol (P = 0.009) and hyperbilirubinaemia (P = 0.02) was observed with unboosted atazanavir vs. PI/RTV.
CONCLUSIONS
The meta-analysis demonstrated that switching patients with virological suppression from an RTV-boosted PI to unboosted atazanavir leads to improvements in safety (i.e. blood parameter abnormalities) without sacrificing virological efficacy.
Topics: Atazanavir Sulfate; Drug Substitution; Drug Therapy, Combination; HIV Infections; Humans; Maintenance Chemotherapy; Oligopeptides; Protease Inhibitors; Pyridines; Randomized Controlled Trials as Topic; Ritonavir
PubMed: 24314017
DOI: 10.1111/hiv.12118 -
Cardiovascular Drugs and Therapy Dec 2016
Meta-Analysis Review
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cholesterol, LDL; Humans; Hypercholesterolemia; PCSK9 Inhibitors
PubMed: 27830381
DOI: 10.1007/s10557-016-6703-0