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The European Respiratory Journal Jun 2024Asthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain.... (Review)
Review
BACKGROUND
Asthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain. This was the first systematic review with the objective of summarizing evidence on HZ burden in adults with asthma.
METHODS
A global systematic literature review (SLR) and meta-analysis was conducted (Medline and Embase, 2003-2024), on HZ burden (incidence, risk, complications) in adults (≥18 years) with asthma.
RESULTS
There were 19 studies included on HZ outcomes in adults with asthma. Pooled HZ incidence per 1000 person-years was 5.71 (95% confidence interval [CI] 4.68-6.96) in ≥18-year-olds (4.20 [3.09-5.70] in <60-year-olds 10.33 [9.17-11.64] in ≥60-year-olds). The pooled rate ratio for developing HZ was 1.23 [1.11-1.35] in ≥18-year-olds, and 1.36 [1.15-1.61] in ≥50-year-olds. The risk of HZ was higher in people with asthma using systemic corticosteroids; long-acting beta-agonists plus inhaled corticosteroids; and "add-on therapy". Asthma was also associated with an increased risk of post-herpetic neuralgia (odds ratio, OR 1.21 [1.06-1.37]) and HZ ophthalmicus (OR 1.9 [1.1-3.2]).Differences in study design, setting, case definitions, and follow-up durations led to heterogeneity.
CONCLUSIONS
This SLR and meta-analysis found that adults with asthma have an increased risk of HZ, with higher risks in older age groups, and in those on certain treatments, such as oral corticosteroids. HZ vaccines are available for adults, including those with comorbidities such as asthma, and can be considered as part of integrated respiratory care.
PubMed: 38901886
DOI: 10.1183/13993003.00462-2024 -
Journal of the National Cancer Institute Jun 2024
PubMed: 38866699
DOI: 10.1093/jnci/djae132 -
Infectious Diseases and Therapy May 2024Respiratory syncytial virus (RSV) can cause severe respiratory infections in adults; however, information on associated sequelae is limited. This systematic literature... (Review)
Review
INTRODUCTION
Respiratory syncytial virus (RSV) can cause severe respiratory infections in adults; however, information on associated sequelae is limited. This systematic literature review aimed to identify sequelae in adults within 1 year following RSV-related hospitalization or resolution of acute infection.
METHODS
Studies were identified from Embase, MEDLINE, LILACS, SciELO, and grey literature. Random-effects meta-analyses using restricted maximum likelihood were used to calculate the proportions and relative risks of sequelae in patients with RSV compared with controls (patients with RSV-negative influenza-like illness, influenza, and parainfluenza) per follow-up period, population, and treatment setting, where possible.
RESULTS
Twenty-one relevant studies covering the period from 1990 to 2019 were included. Among the general population, the most frequent clinical sequela was sustained function loss (33.5% [95% CI 27.6-39.9]). Decline in lung function and cardiovascular event or congestive heart failure were also identified. Utilization sequelae were readmission (highest at > 6 months after discharge) and placement in a skilled nursing facility. The only subpopulation with data regarding sequelae was transplant patients. Among lung transplant patients, the most frequently reported clinical sequelae were decline in lung function, followed by graft dysfunction and bronchiolitis obliterans syndrome. Pooled relative risks were calculated for the following sequela with controls (primarily influenza-positive patients): cardiovascular event (general population) and pulmonary impairment (hematogenic-transplant patients) both 1.4 (95% CI 1.0-2.0) and for readmission (general population) 1.2 (95% CI 1.1-1.3).
CONCLUSIONS
Although less data are available for RSV than for influenza or other lower respiratory tract infections, RSV infection among adults is associated with medically important sequelae, with a prevalence similar to other respiratory pathogens. RSV sequelae should be included in disease burden estimates.
PubMed: 38789901
DOI: 10.1007/s40121-024-00974-7 -
Expert Review of Anticancer Therapy Jul 2024This study aimed to estimate the toxicities of PARP inhibitors (PARPis), based on randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS)... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
This study aimed to estimate the toxicities of PARP inhibitors (PARPis), based on randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS) database.
METHODS
Four electronic databases were searched from inception to 16 April 2024, for RCTs of approved PARPis. The primary and secondary outcomes were grade 3-5 adverse events (AEs) and grade 3-5 hematological AE, respectively. We conducted network meta-analyses to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of outcomes. A disproportionality analysis was conducted to estimate the signals of hematological AEs associated with PARPis from the FAERS database.
RESULTS
Overall, 27 RCTs involving 11,067 patients with cancer were included. Olaparib had the best safety profile for any grade 3-5 AEs and hematological AEs among four approved PARPis. Olaparib did not increase the risk of thrombocytopenia (RR: 1.48; 95%CI: 0.64-3.39), but other PARPis did. Furthermore 14,780 hematological AE reports associated with PARPis were identified in the FAERS database, and all PARPis were associated with strong hematological AE signals. Hematological AEs mainly occurred within the first 3 months (80.84%) after PARPi initiation.
CONCLUSION
Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months.
REGISTRATION
PROSPERO (CRD42022385274).
Topics: Humans; Poly(ADP-ribose) Polymerase Inhibitors; Neoplasms; Randomized Controlled Trials as Topic; Pharmacovigilance; Hematologic Diseases; Adverse Drug Reaction Reporting Systems; Antineoplastic Agents; Databases, Factual; Phthalazines; Piperazines
PubMed: 38761169
DOI: 10.1080/14737140.2024.2357822 -
Clinical Reviews in Allergy & Immunology Apr 2024An acute aseptic meningitis has been occasionally observed on intravenous polyclonal human immunoglobulin therapy. Since case reports cannot be employed to draw... (Meta-Analysis)
Meta-Analysis Review
An acute aseptic meningitis has been occasionally observed on intravenous polyclonal human immunoglobulin therapy. Since case reports cannot be employed to draw inferences about the relationships between immunoglobulin therapy and meningitis, we conducted a systematic review and meta-analysis of the literature. Eligible were cases, case series, and pharmacovigilance studies. We found 71 individually documented cases (36 individuals ≤ 18 years of age) of meningitis. Ninety percent of cases presented ≤ 3 days after initiating immunoglobulin therapy and recovered within ≤ 7 days (with a shorter disease duration in children: ≤ 3 days in 29 (94%) cases). In 22 (31%) instances, the authors noted a link between the onset of meningitis and a rapid intravenous infusion of immunoglobulins. Cerebrospinal fluid analysis revealed a predominantly neutrophilic (N = 46, 66%) pleocytosis. Recurrences after re-exposure were observed in eight (N = 11%) patients. Eight case series addressed the prevalence of meningitis in 4089 patients treated with immunoglobulins. A pooled prevalence of 0.6% was noted. Finally, pharmacovigilance data revealed that meningitis temporally associated with intravenous immunoglobulin therapy occurred with at least five different products. In conclusion, intravenous immunoglobulin may cause an acute aseptic meningitis. The clinical features remit rapidly after discontinuing the medication.
Topics: Humans; Meningitis, Aseptic; Immunoglobulins, Intravenous; Acute Disease; Child; Adolescent; Pharmacovigilance; Child, Preschool; Immunization, Passive
PubMed: 38739354
DOI: 10.1007/s12016-024-08989-1 -
Journal of Oncology Pharmacy Practice :... Jul 2024This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis.
METHOD
We conducted a comprehensive search across international databases and reference lists of articles to compile all relevant published evidence evaluating the efficacy and safety of L-AMB versus other antifungals (NLAMB) for secondary prophylaxis against invasive fungal infections. Pooled estimates were calculated after data transformation to evaluate mortality, breakthrough infections, and the frequency of adverse effects, including hypokalemia and nephrotoxicity. Comparisons of breakthrough fungal infection and mortality between the L-AMB and NLAMB groups were performed.
RESULT
We identified 10 studies. The cumulative frequency of patients using L-AMB was 148, compared to 341 patients in the NLAMB group. The mortality rates in the L-AMB and NLAMB groups were 10% and 0%, respectively. However, based on the odds ratio, the mortality in the L-AMB group was lower than that in the NLAMB group. No significant difference was observed in breakthrough invasive fungal infections between the L-AMB and NLAMB groups. The frequencies of nephropathy and hypokalemia in the L-AMB group were 36% and 18%, respectively.
CONCLUSION
Our findings indicate a lower incidence of mortality in the L-AMB group compared to the NLAMB group. No statistically significant difference was observed in the incidence of breakthrough infection between the two groups. L-AMB administration is associated with nephropathy and hypokalemia. However, the refusal to continue treatment due to adverse effects is not significantly high.
Topics: Amphotericin B; Humans; Antifungal Agents; Invasive Fungal Infections; Mycoses; Secondary Prevention; Hypokalemia
PubMed: 38720564
DOI: 10.1177/10781552241241317 -
Paediatric Drugs May 2024In adults, sodium-glucose cotransporter type 2 inhibitors have revolutionised the treatment of type 2 diabetes mellitus, heart failure, and chronic kidney disease.
INTRODUCTION
In adults, sodium-glucose cotransporter type 2 inhibitors have revolutionised the treatment of type 2 diabetes mellitus, heart failure, and chronic kidney disease.
OBJECTIVE
We aimed to review information on compassionate use, clinical pharmacology, efficacy, and safety of dapagliflozin and empagliflozin in children.
METHODS
We conducted a systematic review of published clinical trials, case reports, and observational studies in Medline, Excerpta Medica, and Web of Science databases from inception to September 2023. For the two randomised controlled trials on type 2 diabetes mellitus (T2DM), we implemented a meta-analysis on the primary outcome (mean difference in glycosylated haemoglobin [HbA1c] between intervention and placebo groups). Review Manager (RevMan), version 5.4.1, was used for this purpose.
RESULTS
Thirty-five articles (nine case reports, ten case series, one prospective non-controlled trial, four controlled randomised trials, two surveys, six pharmacokinetic studies, and three pharmacovigilance studies) were selected, in which 415 children were exposed to either dapagliflozin or empagliflozin: 189 diabetic patients (mean age 14.7 ± 2.9 years), 32 children with glycogen storage disease type Ib (GSD Ib), glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency, or severe congenital neutropenia type 4 (8.5 ± 5.1 years), 47 children with kidney disease or heart failure (11.2 ± 6.1 years), 84 patients in pharmacokinetic studies (15.1 ± 2.3 years), and 63 patients in toxicological series. The effect of dapagliflozin and empagliflozin in T2DM was demonstrated by HbA1c reduction in two randomised trials among a total of 177 adolescents, with a mean HbA1c difference of -0.82% (95% confidence interval -1.34 to -0.29) as compared to placebo (no heterogeneity, I = 0%). Dosage ranged between 5 and 20 mg (mean 11.4 ± 3.7) once daily for dapagliflozin and between 5 and 25 mg (mean 15.4 ± 7.4) once daily for empagliflozin. Among the paediatric cases of GSD Ib, empagliflozin 0.1-1.3 mg/kg/day improved neutropenia, infections, and gastrointestinal health. Dapagliflozin (mean dosage 6.9 ± 5.2 mg once daily) was well-tolerated in children with chronic kidney disease and heart failure. Side effects were generally mild, the most frequent being hypoglycaemia in children with GSD Ib (33% of patients) or T2DM (14% of patients) on concomitant hypoglycaemic drugs. Diabetic ketoacidosis is rare in children.
CONCLUSION
Early evidence suggests that dapagliflozin and empagliflozin are well tolerated in children. A clinical pharmacology rationale currently exists only for adolescents with diabetes mellitus.
PROSPERO REGISTRATION NUMBER
CRD42023438162.
Topics: Benzhydryl Compounds; Humans; Glucosides; Child; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Adolescent
PubMed: 38635113
DOI: 10.1007/s40272-024-00623-z -
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 Anesthesia, Analgesia and... Apr 2024Propofol is the most commonly used hypnotic agent used during sedation and general anesthesia (GA) practice, offering faster recovery compared to benzodiazepines.... (Review)
Review
BACKGROUND
Propofol is the most commonly used hypnotic agent used during sedation and general anesthesia (GA) practice, offering faster recovery compared to benzodiazepines. However, cardiovascular impact of propofol and pain at injection are commonly encountered side effects. Ciprofol is a novel disubstituted phenol derivative, and there is growing evidence regarding its clinical use.
METHODS
We conducted a systematic literature search (updated on 23 July 2023) to evaluate safety and efficacy of ciprofol in comparison to propofol in patients undergoing procedures under sedation or GA. We focused on randomized controlled trials (RCTs) only, extrapolating data on onset and offset, and on the side effects and the pain at injection.
RESULTS
The search revealed 14 RCTs, all conducted in China. Eight RCTs studied patients undergoing sedation, and six focused on GA. Bolus of ciprofol for sedation or induction of GA varied from 0.2 to 0.5 mg/kg. In four studies using ciprofol for maintenance of GA, it was 0.8-2.4 mg/kg/h. Ciprofol pharmacokinetics seemed characterized by slower onset and offset as compared to propofol. Pain during injection was less frequent in the ciprofol group in all the 13 studies reporting it. Eight studies reported "adverse events" as a pooled outcome, and in five cases, the incidence was higher in the propofol group, not different in the remaining ones. Occurrence of hypotension was the most commonly investigated side effects, and it seemed less frequent with ciprofol.
CONCLUSION
Ciprofol for sedation or GA may be safer than propofol, though its pharmacokinetics may be less advantageous.
PubMed: 38589912
DOI: 10.1186/s44158-024-00159-1 -
Expert Opinion on Drug Safety Apr 2024To investigate the risk of hemorrhage associated with Immune Checkpoint Inhibitors (ICIs) and characterize its clinical features.
OBJECTIVES
To investigate the risk of hemorrhage associated with Immune Checkpoint Inhibitors (ICIs) and characterize its clinical features.
METHODS
We systematically reviewed randomized clinical trials (RCTs) of hemorrhage related to ICIs and calculated odds ratios (ORs) with 95% confidence intervals (CIs). Pharmacovigilance studies were conducted by collecting ICIs-related hemorrhage cases from the FAERS database and assessing disproportionalities by reporting odds ratios (RORs) and information components (ICs).
RESULTS
A total of 79 RCTs involving 45,100 patients were finally included in the systematic review, with four published RCTs ( = 1965) and 75 unpublished RCTs ( = 43135). The primary analysis showed no significant difference in ICIs compared to the control group (OR 1.18 [95% CI 1.00-1.38], = 0.05). In subgroup analyses, anti-PD-L1 combined with anti-CTLA-4 increased the risk of hemorrhage (OR 1.95, = 0.03), and anti-CTLA-4 increased the risk of hemorrhage in the gastrointestinal system (OR 2.23, = 0.04). 3555 cases of hemorrhage from the FAERS database were included in the disproportionate analysis, and the result suggested that ICIs increased the risk of hemorrhage (IC = 0.23).
CONCLUSION
Our study suggests that ICIs increase the risk of hemorrhage, and in particular, anti-CTLA-4 significantly increases the risk of hemorrhage in the gastrointestinal system.
Topics: Humans; CTLA-4 Antigen; Databases, Factual; Hemorrhage; Immune Checkpoint Inhibitors; Pharmacovigilance; Randomized Controlled Trials as Topic
PubMed: 38556702
DOI: 10.1080/14740338.2024.2327504