-
HIV Research & Clinical Practice Oct 2023The high-burden regions of Sub-Saharan Africa, which accounted for greater than 70% of the HIV epidemic, are disproportionately affected by the high rates of TB... (Review)
Review
BACKGROUND
The high-burden regions of Sub-Saharan Africa, which accounted for greater than 70% of the HIV epidemic, are disproportionately affected by the high rates of TB coinfection. This might be explained by, the low immune tolerance of the population due to malnutrition and chronic infections aggravating immune suppression. In this review, we discuss the immunopathogenesis of this common co-infection that causes significant morbidity and mortality in people living with HIV globally.
METHODS
We used published studies using a two-step search strategy. Initial search of Pub Med Central and Google Scholar was undertaken followed by an analysis of the keywords. A second search using all the reference list of all identified reports and articles was searched for additional studies. Literature published as of January 1, 1981, that meets the inclusion criteria were considered. Qualitative data was extracted from papers included in the review.
RESULT
Mortality occurs at both ends of the immunological spectrum of TB at one end HIV uninfected patient dies from asphyxiation from acute massive hemoptysis due to cavitary TB; at the other end, and far more frequently HIV-infected patient with disseminated TB dies from overwhelming infection with less evidence of focal pathology. There is no clear sign that the HIV-TB epidemic is slowing, especially considering the emergence of increasingly drug-resistant strains of MTB. A major challenge for the future is to discover immune correlates of TB protection and TB disease risk. Failure to define this conclusively has hindered TB prevention strategies, including the design of new TB vaccines to replace BCG, which provides only shortlived efficacy, prevents severe forms of the extra-pulmonary disease and is contraindicated in PLHIV.
CONCLUSION
Understanding TB and HIV infection through immunological advances needs to be combined to describe the complex interactions between TB and HIV and the effects of ART. The complex interactions between the individual components of innate and acquired immune responses to TB and HIV infection is also likely to be the next step forward.
Topics: Humans; HIV Infections; Coinfection; Malnutrition; Tuberculosis, Miliary; Immune Tolerance
PubMed: 37916817
DOI: No ID Found -
Cureus Sep 2023This systematic review and meta-analysis determine how frequently and how seriously gastrointestinal manifestations affect people with type 2 diabetes mellitus on... (Review)
Review
This systematic review and meta-analysis determine how frequently and how seriously gastrointestinal manifestations affect people with type 2 diabetes mellitus on tirzepatide. Tirzepatide is a recently developed drug that attempts to enhance type 2 diabetics' ability to regulate their blood sugar levels and promote weight reduction. Despite its potential benefits, clinical trials have revealed that the medication may lead to gastrointestinal side effects, including nausea, vomiting, decreased appetite, dyspepsia, constipation, and diarrhea. These side effects may negatively affect the drug's efficacy and patient tolerance. A comprehensive search of electronic databases such as PubMed, Web of Science, and Cochrane Library, was conducted to find pertinent studies reporting on the frequency and severity of gastrointestinal symptoms in type 2 diabetes patients receiving tirzepatide. This systematic review follows the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Study selection, data extraction, and quality assessment were performed. Six randomized controlled trials with a total of 4,586 patients were included. Most patients received tirzepatide to regulate their blood sugar levels and promote weight reduction, and the comparators were placebo, glucagon-like peptide one receptor agonists drugs, and insulin degludec. The dose of tirzepatide was 5mg, 10mg, and 15mg weekly. The incidence rate of nausea in patients who receive tirzepatide was 20.43%, while the incidence rate in the comparators was 10.47%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.90; 95% CI, 1.89 to 4.44; P ≤ 0.00001). The incidence rate of vomiting in patients who receive tirzepatide was 9.05%, while the rate in the comparators was 4.86%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.69; 95% CI, 1.67 to 4.36; P ≤ 0.0001). The incidence rate of constipation in patients who receive tirzepatide was 2.54%, while the rate in the comparators was 0.856%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 3.08; 95% CI, 1.83 to 5.20; P ≤ 0.0001). The incidence rate of decreased appetite in patients who receive tirzepatide was 9.64%, while the rate in the comparators was 2.88%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 5.04; 95% CI, 3.01 to 8.45; P ≤ 0.00001). The incidence rate of diarrhea in patients who receive tirzepatide was 16.24%, while the rate in the comparators was 8.63%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.07; 95% CI, 1.60 to 2.68; P ≤ 0.00001). The incidence rate of dyspepsia in patients who receive tirzepatide was 7.13%, while the rate in the comparators was 3.31%, and it was significantly higher in the tirzepatide arm than in the comparators (RR, 2.52; 95% CI, 1.58 to 4.01; P ≤ 0.0001). Tirzepatide usage is linked to a significant prevalence of gastrointestinal symptoms, including nausea, constipation, decreased appetite, dyspepsia, diarrhea, and vomiting, in people with type 2 diabetes. These findings may influence clinical decision-making and patient counseling on the use of tirzepatide and have significant implications for the medication's tolerance and efficacy. To find ways to reduce these negative effects and improve therapy for type 2 diabetes patients, more research is required.
PubMed: 37908927
DOI: 10.7759/cureus.46091 -
Biomedicines Sep 2023This umbrella review aimed to determine the various drugs used to treat trigeminal neuralgia (TN) and to evaluate their efficacies as well as side effects by surveying... (Review)
Review
This umbrella review aimed to determine the various drugs used to treat trigeminal neuralgia (TN) and to evaluate their efficacies as well as side effects by surveying previously published reviews. An online search was conducted using PubMed, CRD, EBSCO, Web of Science, Scopus, and the Cochrane Library with no limits on publication date or patients' gender, age, and ethnicity. Reviews and meta-analyses of randomized controlled trials pertaining to drug therapy for TN, and other relevant review articles added from their reference lists, were evaluated. Rapid reviews, reviews published in languages other than English, and reviews of laboratory studies, case reports, and series were excluded. A total of 588 articles were initially collected; 127 full-text articles were evaluated after removing the duplicates and screening the titles and abstracts, and 11 articles were finally included in this study. Except for carbamazepine, most of the drugs had been inadequately studied. Carbamazepine and oxcarbazepine continue to be the first choice for medication for classical TN. Lamotrigine and baclofen can be regarded as second-line drugs to treat patients not responding to first-line medication or for patients having intolerable side effects from carbamazepine. Drug combinations using carbamazepine, baclofen, gabapentin, ropivacaine, tizanidine, and pimozide can yield satisfactory results and improve the tolerance to the treatment. Intravenous lidocaine can be used to treat acute exaggerations and botulinum toxin-A can be used in refractory cases. Proparacaine, dextromethorphan, and tocainide were reported to be inappropriate for treating TN. Anticonvulsants are successful in managing trigeminal neuralgia; nevertheless, there have been few studies with high levels of proof, making it challenging to compare or even combine their results in a statistically useful way. New research on other drugs, combination therapies, and newer formulations, such as vixotrigine, is awaited. There is conclusive evidence for the efficacy of pharmacological drugs in the treatment of TN.
PubMed: 37892981
DOI: 10.3390/biomedicines11102606 -
Experimental and Therapeutic Medicine Nov 2023Vortioxetine is a novel drug for the treatment of major depressive disorder (MDD). It has been reported that vortioxetine exhibits positive effect on the acute stage of...
Εfficacy and safety of vortioxetine (Lu AA21004) in the treatment of adult patients with major depressive disorder: A systematic review and a meta‑analysis of randomized controlled trials.
Vortioxetine is a novel drug for the treatment of major depressive disorder (MDD). It has been reported that vortioxetine exhibits positive effect on the acute stage of MDD, while it can effectively prevent the recurrence of MDD during the maintenance period. Currently, the results of systematic reviews on vortioxetine are insufficient since several efficacy measures, such as the 24-Items Hamilton Rating Scale for Depression (HADRS-24) total score and other safety factors have not been evaluated. Therefore, the present study aimed to evaluate the efficacy and safety of different doses of vortioxetine on the treatment of adult patients with MDD via assessing more efficacy and safety indicators. The clinical, double-blind, parallel and randomized controlled trials (RCTs) on the effect of vortioxetine on MDD were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and clinical trial registration websites from database inception to November 2022. A total of two investigators independently screened the included references and independently evaluated their quality. The meta-analysis was performed using Revman 5.0 software. The present systematic review was registered in PROSPERO (registration no. CRD42018106343). In the present study 11 RCTs were included, with a total of 4,908 adult patients with MDD. More specifically, 1,158 patients were included in the 5-mg vortioxetine group, 736 in the 10-mg group, 298 in the 15-mg group, 864 in the 20-mg group and 1,852 in the placebo group. All 11 studies were randomized, double-blinded and parallel control trials, and all publications were evaluated as high quality. The meta-analysis results showed that patients in the 5-, 10- and 20-mg vortioxetine groups exhibited significantly higher Montgomery-Asberg Depression Rating Scale (MADRS) response (≥50%) and remission (≤10%) rates compared with the placebo group (P<0.05). The pooled analysis also revealed a statistically significant change in the total score of HADRS-24, MADRS, Sheehan Disability Scale (SDS), Clinical Global Impression Scale-Improvement (CGI-I) and HADRS-24 response rate in the 10- and 20-mg vortioxetine groups compared with the placebo group (P<0.05). However, no statistically significant changes in the total score of HADRS-24, MADRS, SDS, CGI-I and HADRS-24 response rate were obtained in the 5-mg group compared with the placebo group (P>0.05). Furthermore, the most common adverse events were nausea, hyperhidrosis, insomnia and vomiting, the incidence of which was increased with higher doses of vortioxetine. Overall, the results suggested that vortioxetine administration at doses of 5-20 mg was significantly effective and safe compared with placebo in the treatment of MDD. However, 5 mg vortioxetine displayed no difference in the HADRS-24, MADRS, SDS and CGI-I total scores, and HADRS-24 response rate. Furthermore, patient treatment with increasing vortioxetine doses was associated with good tolerance and high safety. Nevertheless, more multi-center, high-quality and long-term RCTs are still needed to support the aforementioned findings.
PubMed: 37840562
DOI: 10.3892/etm.2023.12214 -
Critical Reviews in Oncology/hematology Dec 2023The advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has been transformative for the treatment of advanced renal cell carcinoma (RCC).... (Review)
Review
The advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has been transformative for the treatment of advanced renal cell carcinoma (RCC). Their efficacy post-surgical resection remains a contentious point. Various phase 3 RCTs have assessed their potency. Amongst evaluated agents, sunitinib and pembrolizumab have demonstrated notable disease-free survival benefits. Sunitinib's potential is diminished due to absence of clear overall survival (OS) benefits and side-effect profile. Pembrolizumab shows better tolerance, conclusive OS data are forthcoming. This scenario underscores the pressing need for advanced risk stratification methods and discovery of novel biomarkers. Existing strategies, largely pre-dating TKI and ICI therapeutic era, lack sufficient accuracy in predicting relapse-risk. Our review offers a comprehensive analysis of key phase 3 RCTs, focusing on TKIs, mTOR-inhibitors, and ICIs for adjuvant RCC treatment. The intent is to shed light on the intricate landscape of RCC treatment, guiding future research directions for optimizing patient outcomes.
Topics: Humans; Carcinoma, Renal Cell; Sunitinib; Kidney Neoplasms; Neoplasm Recurrence, Local; Disease-Free Survival
PubMed: 37748694
DOI: 10.1016/j.critrevonc.2023.104144 -
Diabetes Research and Clinical Practice Oct 2023To assess the prevalence variation in pregnancy outcomes of the different phenotypes of gestational diabetes mellitus (GDM). (Meta-Analysis)
Meta-Analysis Review
AIMS
To assess the prevalence variation in pregnancy outcomes of the different phenotypes of gestational diabetes mellitus (GDM).
MATERIALS
Cohort, cross sectional and case control studies grouping together pregnant women with GDM, based on the results of oral glucose tolerance test(OGTT) and reporting pregnancy outcomes in each group, were included. The primary outcomes were (i)large for gestational age and ii)hypertensive disorders of pregnancy (HDP). The secondary outcomes included (i)insulin treatment, ii)admission to neonatal intensive care unit, iii)preterm birth, iv)small for gestational age and v)caesarean section. The pooled proportions of the outcomes of interest were calculated for each phenotype.
RESULTS
8 studies (n = 20.928 women with GDM) were included. The pooled prevalence of LGA, HDP and insulin treatment were 20 %, 8 % and 24 % respectively in women with abnormal fasting plasma glucose,10 %, 6 % and 9 % respectively in women with abnormal post-load plasma glucose and 14 %,14 % and 30 % in women with abnormal combined plasma glucose.
CONCLUSIONS
Pregnant women with abnormal fasting plasma glucose, present with the highest prevalence of LGA, while those with abnormal combined plasma glucose, present with the highest prevalence of HDP. Pregnant women with abnormal post-load plasma glucose present with the lowest need for insulin treatment.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Diabetes, Gestational; Pregnancy Outcome; Glucose Tolerance Test; Blood Glucose; Cesarean Section; Cross-Sectional Studies; Premature Birth; Phenotype; Insulins
PubMed: 37742806
DOI: 10.1016/j.diabres.2023.110913 -
Frontiers in Endocrinology 2023Glucose-dependent insulinotropic polypeptide (GIP) confers a variety of metabolic benefits in type 2 diabetes mellitus (T2DM). This meta-analysis was conducted to... (Meta-Analysis)
Meta-Analysis
AIMS
Glucose-dependent insulinotropic polypeptide (GIP) confers a variety of metabolic benefits in type 2 diabetes mellitus (T2DM). This meta-analysis was conducted to investigate the impact of dipeptidyl peptidase 4 (DPP4) inhibitors on GIP levels in T2DM patients.
METHODS
Medline (PubMed), CENTER (Cochrane Library), and Embase (Ovid) were searched and randomized controlled trials (RCTs) evaluating the impact of DPP4 inhibitors on fasting and postprandial GIP levels were obtained. For postprandial GIP, only studies with the data of GIP changes reported as the total area under the curve (AUC) using a meal or oral glucose tolerance test were included. A random-effects model was used for data pooling after incorporating heterogeneity.
RESULTS
Overall, 14 RCTs with 541 T2DM patients were included. Compared to placebo/no treatment, the use of DPP4 inhibitors significantly increased the fasting GIP level (standard mean difference [SMD]: 0.77, 95% confidence interval [CI]: 0.48-1.05, <0.001; 52%) and postprandial AUC (SMD: 1.33, 95% CI: 1.02-1.64, <0.001; 65%). Influence analysis by excluding one dataset at a time showed consistent results. Sensitivity analyses only including studies with radioimmunoassay showed also consistent results (fasting GIP: SMD: 0.75, 95% CI: 0.51-1.00, P<0.001; I0%; and postprandial AUC: SMD: 1.48, 95% CI: 1.18-1.78, <0.001; 54%). Further subgroup analyses demonstrated that the influence of DPP4 inhibitors on fasting and postprandial GIP levels in T2DM patients was not significantly changed by study characteristics such as study design, patient mean age, baseline glycated hemoglobin (HbA1c) concentration, body mass index (BMI), background treatment, treatment duration, or method for postprandial GIP measurement (all for subgroup effects <0.05).
CONCLUSION
The use of DPP4 inhibitors effectively increases the fasting and postprandial GIP concentrations in T2DM patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022356716.
Topics: Humans; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Gastric Inhibitory Polypeptide; Glucose
PubMed: 37635974
DOI: 10.3389/fendo.2023.1203187 -
Frontiers in Nutrition 2023Acarbose (ACB) seems to be an effective drug in the management of cardiovascular risk factors. However, no previous meta-analysis of randomized controlled trials (RCTs)...
The effects of acarbose treatment on cardiovascular risk factors in impaired glucose tolerance and diabetic patients: a systematic review and dose-response meta-analysis of randomized clinical trials.
Acarbose (ACB) seems to be an effective drug in the management of cardiovascular risk factors. However, no previous meta-analysis of randomized controlled trials (RCTs) has been done to evaluate the effects of ACB on cardiovascular risk factors on impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2D), and type 1 diabetes mellitus (T1D). We comprehensively searched electronic databases including Scopus, Web of Science, and PubMed for RCTs for related keywords up to September 2022. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence interval (CI). The pooled analysis demonstrated that ACB treatment had a significant effect on fasting blood glucose (FBG) (WMD = -3.55 mg/dL; 95%CI: -6.29, -0.81; = 0.011), fasting insulin (WMD = -6.73 pmoL/L; 95%CI: -10.37, -3.10; < 0.001), HbA1c [WMD = -0.32%; 95%CI: -0.45, -0.20; < 0.001], body weight (WMD = -1.25 kg; 95%CI: -1.79, -0.75; < 0.001), body mass index (BMI) (WMD = -0.64 kg/m; 95%CI: -0.92, -0.37; < 0.001), tumor necrosis factor-alpha (TNF-α) (WMD = -2.70 pg/mL, 95%CI: -5.25, -0.16; = 0.037), leptin (WMD = -1.58 ng/mL; 95%CI: -2.82, -0.35; = 0.012), alanine transaminase (ALT) (WMD = 0.71 U/L; 95%CI: -0.31, 1.85; = 0.164), triglyceride (TG) (WMD = -13.89 mg/dL; 95%CI: -20.69, -7.09; < 0.001), total cholesterol (TC) (WMD = -2.26 mg/dL; 95%CI: -4.18, -0.34; = 0.021), systolic blood pressure (SBP) (WMD = -1.29 mmHg; 95%CI: -2.44, -0.15; = 0.027), and diastolic blood pressure (DBP) (WMD = 0.02 mmHg; 95%CI: -0.41, 0.45; = 0.925) in an intervention group, compared with a placebo group. The non-linear dose-response analysis showed that ACB reduces the TC in trial duration by >50 weeks, and 180 mg/day is more effective for the decrement of CRP. ACB can improve lipid profiles, glycemic indices, anthropometric indices, and inflammatory markers in T2D, T1D, and IGT patients.
PubMed: 37599681
DOI: 10.3389/fnut.2023.1084084 -
Clinical Reviews in Allergy & Immunology Oct 2023Taxanes in the treatment of cancer are associated with a significant incidence of hypersensitivity reactions, which may preclude their use in patients in need of first... (Review)
Review
Taxanes in the treatment of cancer are associated with a significant incidence of hypersensitivity reactions, which may preclude their use in patients in need of first line therapy. Drug desensitization induces transient immunological tolerance and has allowed the reintroduction of taxanes in highly allergic patients. Increase the knowledge of hypersensitivity reactions (HSR) during the administration of taxanes. A systematic review regarding the safety and efficacy of rapid drug desensitization (RDD) for taxanes HSR. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was registered in PROSPERO(CRD42021242324) and a comprehensive search was conducted in Medline, Embase, Web of Science and Scopus databases. 25 studies encompassing 10 countries were identified and 976 patients with initial HSR to paclitaxel (n = 707) and docetaxel (n = 284), that underwent a total of 2,396 desensitizations. The most common symptoms were cutaneous (74.6%) with paclitaxel and respiratory (72.6%) with docetaxel. Severe initial hypersensitivity reactions including anaphylaxis occurred in 39.6% and 13% of paclitaxel and docetaxel cases respectively and during the first (87.4%) or second exposure (81.5%). Patients tolerated well RDD and breakthrough reactions (BTR) occurred in 32.2% of paclitaxel-treated patients and in 20.6% of docetaxel treated patients. Premedications included corticosteroids, antihistamines and leukotriene receptor antagonists. The most commonly used protocol was the BWH 3 bags 12 steps, all protocols showed a success rate between 95-100%, with no reported deaths. RDD is a safe and effective procedure in patients with HSR to taxanes and protocols should be standardized for wide range implementation.
PubMed: 37589840
DOI: 10.1007/s12016-023-08968-y -
The Journal of Clinical Psychiatry Jul 2023Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and...
Aiming at revising the therapeutic reference range for olanzapine, the present study highlights the association between blood olanzapine levels, clinical effects, and dopamine D-receptor occupancy for oral and long-acting injectable (LAI) formulations. Databases were systematically searched for randomized controlled trials (RCTs) and uncontrolled trials concerning blood olanzapine levels in relation to clinical outcomes or D-receptor occupancy using MEDLINE (PubMed), Web of Science, PsycINFO, and Cochrane Library (March 2021, updated in December 2021). We excluded articles not written in English or German and non-human data. Search terms included , , , , and . The process of study selection followed a previously published protocol and PRISMA guidelines. A total of 2,824 articles were identified through database search and 1 article via reference list check. Thirty-four studies were suitable for qualitative synthesis, and 13 studies were included in the quantitative analysis. Reviewers performed data extraction and quality assessment of the included studies independently following the review protocol. Evidence for a relationship between blood olanzapine level and efficacy/side effects (constipation) is considered low (Level C). In total, 3 studies of moderate quality consistently showed therapeutic thresholds of around 20 ng/mL for olanzapine 12 hours post-dose. This threshold is in line with findings from positron emission tomography (PET) studies that suggest optimal drug efficacy (65%-80% D-receptor occupancy) between 17 and 44 ng/mL. We suggest a therapeutic reference range of 20-40 ng/mL for olanzapine oral and LAI formulations. In this range, optimal treatment response is expected in patients with schizophrenia and schizophrenia spectrum disorders. Side effects, especially weight gain, may already occur at therapeutic levels. However, higher plasma concentrations are in general well tolerated and should not necessarily require a dose reduction in case of good response and tolerance.
Topics: Humans; Olanzapine; Antipsychotic Agents; Reference Values; Schizophrenia; Receptors, Dopamine D2; Benzodiazepines
PubMed: 37471567
DOI: 10.4088/JCP.22r14626