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ESMO Open Aug 2023Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression on ≥1 human epidermal growth factor receptor 2 (HER2)-targeted therapies. However, interstitial lung disease (ILD) and cardiotoxicity are the most significant toxicities associated with T-DXd. Therefore, we conducted a systematic review and meta-analysis to assess the incidence and severity of these toxicities in mBC patients treated with T-DXd.
MATERIALS AND METHODS
We searched PubMed, Cochrane, and Scopus databases, and conferences websites for randomized clinical trials and nonrandomized studies of intervention including HER2-low or HER2-positive mBC patients who received at least one dose of T-DXd. Statistical analysis was carried out using R software.
RESULTS
We included 15 studies comprising 1970 patients with a mean follow-up of 13.3 months. Median age ranged from 53 to 59 years, 61.9% were non-Asian, and 67.4% had hormone receptor-positive mBC. In a pooled analysis, the incidence of ILD was 11.7% [222 patients; 95% confidence interval (CI) 9.1% to 15.0%]. Patients receiving T-DXd dose of 6.4 mg/kg developed a significantly higher rate of ILD (22.7%) compared to those receiving a dose of 5.4 mg/kg (9.3%) (P < 0.01). Most cases of ILD (80.2%; 174/217 patients) were mild (grade 1 or 2). Grade 3 or 4 ILD was reported in 29 patients (13.4%), and grade 5 in 14 patients (6.4%). The incidence of decreased left ventricular ejection fraction (LVEF) was 1.95% (95% CI 0.65% to 3.73%), and the QT interval (QTi) prolongation was 7.77% (95% CI 2.74% to 20.11%). Most patients were asymptomatic, but four had LV dysfunction and heart failure (0.26%).
CONCLUSIONS
In this meta-analysis of 1970 patients with mBC, treatment with T-DXd was associated with a 11.7% incidence of ILD, 7.7% incidence of prolonged QTi, and 1.9% incidence of reduced LVEF. Early detection and management of T-DXd-related toxicity by a multidisciplinary team may ultimately improve patient outcomes.
Topics: Humans; Middle Aged; Female; Breast Neoplasms; Cardiotoxicity; Incidence; Stroke Volume; Ventricular Function, Left; Lung Diseases, Interstitial
PubMed: 37481956
DOI: 10.1016/j.esmoop.2023.101613 -
Respiratory Medicine Sep 2023The clinical spectrum of connective tissue disease-associated interstitial lung disease (CTD-ILD) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The clinical spectrum of connective tissue disease-associated interstitial lung disease (CTD-ILD) and rheumatoid arthritis-associated interstitial lung disease (RA-ILD) ranges from asymptomatic findings on radiographic imaging to a rapidly progressive illness leading to respiratory failure and death. The treatment is always challenging due to the paucity of proven effective treatments. Nintedanib and pirfenidone are recently approved antifibrotics in idiopathic pulmonary fibrosis. This study aimed to investigate the efficacy and safety of antifibrotic agents in the treatment of CTD-ILD and RA-ILD.
METHODS
Relevant databases were searched for randomized controlled trials that compared pirfenidone or nintedanib with placebo in patients with CTD-ILD and RA-ILD. The primary outcome was the change in forced vital capacity (FVC). The odds ratio or risk ratio with 95% confidence interval (CI) was estimated for categorical data, and the mean difference with 95% CI was estimated for continuous data. The I statistic was used to assess heterogeneity, and meta-analysis was performed when possible.
RESULTS
Ten studies with a total of 880 participants met the inclusion criteria. Of these, four studies were included in the meta-analysis. According to the pooled result, the annual decline of FVC was significantly decreased in the antifibrotic agent arm compared to that in the placebo arm (MD 70.58 mL/yr, 95% CI 40.55 to 100.61).
CONCLUSION
This review suggests a potential benefit and safety of antifibrotic treatment in slowing the decline of FVC in patients with CTD-ILD and RA-ILD. Further large-sample, random-controlled, high-quality trials are needed to provide more evidence in the decision-making regarding the use of antifibrotics in this group of patients.
CLINICAL TRIAL REGISTRATION
PROSPERO; No: CRD42022369112; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Antifibrotic Agents; Lung Diseases, Interstitial; Connective Tissue Diseases; Idiopathic Pulmonary Fibrosis; Vital Capacity
PubMed: 37315742
DOI: 10.1016/j.rmed.2023.107329 -
Neurology and Therapy Aug 2023Alzheimer's disease (AD) is a disease continuum from pathophysiologic, biomarker and clinical perspectives. With the advent of advanced technologies, diagnosing and...
INTRODUCTION
Alzheimer's disease (AD) is a disease continuum from pathophysiologic, biomarker and clinical perspectives. With the advent of advanced technologies, diagnosing and managing patients is evolving.
METHODS
A systematic literature review (SLR) of practice guidelines for mild cognitive impairment (MCI) and AD dementia was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic literature review (SLR) aimed to summarize current clinical practice guidelines for screening, testing, diagnosis, treatment and monitoring in the AD continuum. The results of this SLR were used to propose a way forward for practice guidelines given the possible introduction of biomarker-guided technology using blood- or plasma-based assays and disease-modifying treatments (DMTs) targeted for early disease.
RESULTS
53 clinical practice guidelines were identified, 15 of which were published since 2018. Screening for asymptomatic populations was not recommended. Biomarker testing was not included in routine diagnostic practice. There was no consensus on which neurocognitive tests to use to diagnose and monitor MCI or AD dementia. Pharmacologic therapies were not recommended for MCI, while cholinesterase inhibitors and memantine were recommended for AD treatment.
DISCUSSION
The pre-2018 and post-2018 practice guidelines share similar recommendations for screening, diagnosis and treatment. However, once DMTs are approved, clinicians will require guidance on the appropriate use of DMTs in a clinical setting. This guidance should include strategies for identifying eligible patients and evaluating the DMT benefit-to-risk profile to facilitate shared decision-making among physicians, patients and care partners.
CONCLUSION
Regular evidence-based updates of existing guidelines for the AD continuum are required over the coming decades to integrate rapidly evolving technologic and medical scientific advances and bring emerging approaches for management of early disease into clinical practice. This will pave the way toward biomarker-guided identification and targeted treatment and the realization of precision medicine for AD.
PubMed: 37261607
DOI: 10.1007/s40120-023-00504-6 -
International Journal of Infectious... Sep 2023The burden of asymptomatic dengue infections is understudied. Therefore, we systematically reviewed the literature to estimate the global prevalence of asymptomatic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The burden of asymptomatic dengue infections is understudied. Therefore, we systematically reviewed the literature to estimate the global prevalence of asymptomatic dengue infections.
METHODS
We searched cross-sectional studies reporting the prevalence of asymptomatic dengue infections from PubMed, Scopus, and Embase. Prevalence of asymptomatic dengue infections was pooled and reported as proportions with a 95% confidence interval (CI). This systematic review protocol was a priori registered in The International Prospective Register of Systematic Reviews (Reg: No. CRD42020218446).
RESULTS
We included 41 studies with 131,953 cases in our analysis. The overall pooled prevalence of asymptomatic dengue infections was 59.26% (95% CI: 43.76-74.75, I = 99.93%), with 65.52% (95% CI: 38.73-92.32, I = 99.95%) during outbreaks and 30.78% (95% CI: 21.39-40.16, I = 98.78%) during non-outbreak periods. The pooled prevalence among the acutely infected individuals was 54.52% (95% CI: 17.73-46.76, I = 99.91%), whereas, among primary and secondary asymptomatic dengue infections, it was 65.36% (95% CI: 45.76-84.96, I = 98.82) and 48.99% (95% CI: 27.85-70.13, I = 99.08%) respectively.
CONCLUSION
The majority of dengue cases are asymptomatic and may play a significant role in disease transmission. Public health strategies aimed at dengue outbreak response and mitigation of disease burden should include early detection of asymptomatic cases.
Topics: Humans; Prevalence; Cross-Sectional Studies; Asymptomatic Infections; Coinfection; Dengue
PubMed: 37463631
DOI: 10.1016/j.ijid.2023.07.010 -
Emerging Microbes & Infections Dec 2023Balancing the potentially serious outcomes of asymptomatic brucellosis and "waiting" for treatment in clinical practice is an urgent issue. Therefore, we assessed the... (Meta-Analysis)
Meta-Analysis
Balancing the potentially serious outcomes of asymptomatic brucellosis and "waiting" for treatment in clinical practice is an urgent issue. Therefore, we assessed the follow-up outcomes and epidemiological characteristics of asymptomatic brucellosis in the absence of treatment to provide evidence-based clinical clues. We searched eight databases in which 3610 studies from 1990 to 2021 were related to the follow-up outcomes of asymptomatic brucellosis. Thirteen studies, involving 107 cases, were finally included. Regarding the follow-up outcomes, we examined the presence or absence of symptoms and decreased serum agglutination test (SAT) titre. During the 0.5-18 months follow-up period, the pooled prevalence of appearing symptomatic was 15.4% (95% CI 2.1%-34.3%), cases that remained asymptomatic were 40.3% (95% CI 16.6%-65.8%), and decreased SAT titre was observed in 36.5% (95% CI 11.6%-66.1%). Subgroup analysis indicated that the pooled prevalence of appearing symptomatic with follow-up times of less than 6 months, 6-12 months, and 12-18 months was 11.5%, 26.4%, and 47.6%, respectively. The student subgroup had a higher prevalence of symptoms (46.6%) than the occupational and family populations. In conclusion, asymptomatic brucellosis has a high likelihood of appearing symptomatic and its severity may be underestimated. Active screening of occupational and family populations should be enhanced, and special attention should be paid to high-titre students for early intervention, if necessary. Additionally, future prospective, long-term, and large-sample follow-up studies are essential.
Topics: Humans; Follow-Up Studies; Brucellosis; Agglutination Tests; Prevalence
PubMed: 36849445
DOI: 10.1080/22221751.2023.2185464 -
Arquivos Brasileiros de Cirurgia... 2023Asymptomatic cholelithiasis is a highly prevalent disease, and became more evident after the currently greater access to imaging tests. Therefore, it is increasingly...
BACKGROUND
Asymptomatic cholelithiasis is a highly prevalent disease, and became more evident after the currently greater access to imaging tests. Therefore, it is increasingly necessary to analyse the risks and benefits of performing a prophylactic cholecystectomy.
AIMS
To seek the best evidence in order to indicate prophylactic cholecystectomy or conservative treatment (clinical follow-up) in patients with asymptomatic cholelithiasis.
METHODS
A systematic review was performed using the PubMed/Medline database, according to PRISMA protocol guidelines. The review was based on studies published between April 26, 2001 and January 07, 2022, related to individuals older than 18 years., The following terms/operators were used for search standardization: (asymptomatic OR silent) AND (gallstones OR cholelithiasis).
RESULTS
We selected 18 studies eligible for inference production after applying the inclusion and exclusion criteria. Also, the Tokyo Guideline (2018) was included for better clarification of some topics less or not addressed in these studies.
CONCLUSIONS
Most evidence point to the safety and feasibility of conservative treatment (clinical follow-up) of asymptomatic cholelithiasis. However, in post-cardiac transplant patients and those with biliary microlithiasis with low preoperative surgical risk, a prophylactic cholecystectomy is recommended. To establish these recommendations, more studies with better levels of evidence must be conducted.
Topics: Humans; Cholecystectomy; Gallstones
PubMed: 37466567
DOI: 10.1590/0102-672020230029e1747 -
Medicina (Kaunas, Lithuania) Sep 2023Asymptomatic bacteriuria (ASB) is prevalent in kidney transplant recipients (KTRs) and is hypothesized to heighten the risk of subsequent urinary tract infections... (Meta-Analysis)
Meta-Analysis Review
Asymptomatic bacteriuria (ASB) is prevalent in kidney transplant recipients (KTRs) and is hypothesized to heighten the risk of subsequent urinary tract infections (UTIs). Whether antibiotic treatment of ASB in KTRs is beneficial has not been elucidated. We carried out a systematic review and meta-analysis of all randomized controlled trials (RCTs) and quasi-RCTs that examined the merits of managing asymptomatic bacteriuria in KTRs. The primary outcomes were rates of symptomatic urinary tract infections (UTIs) and antimicrobial resistance. : Five studies encompassing 566 patients were included. No significant difference in symptomatic UTI rates was found between antibiotics and no treatment groups (relative risk (RR) 1.05, 95% confidence interval (CI) = 0.78-1.41), with moderate heterogeneity (I = 36%). Antibiotic treatment was found to present an uncertain risk for the development of drug-resistant strains (RR = 1.51, 95% CI = 0.95-2.40, I = 0%). In all trials, no significant difference between study arms was demonstrated regarding patient and graft outcomes, such as graft function, graft loss, hospitalization due to UTI, all-cause mortality, or acute rejection. : The practice of screening and treating kidney transplant patients for asymptomatic bacteriuria does not curtail the incidence of future symptomatic UTIs, increase antimicrobial resistance, or affect graft outcomes. Whether early treatment of ASB after kidney transplantation (<2 months) is beneficial requires more RCTs.
Topics: Humans; Bacteriuria; Kidney Transplantation; Randomized Controlled Trials as Topic; Anti-Bacterial Agents; Hospitalization
PubMed: 37763718
DOI: 10.3390/medicina59091600 -
Heliyon Sep 2023Dengue infection is spreading worldwide. The clinical spectrum is broad and includes asymptomatic infections. This review provides an overview of the different... (Review)
Review
OBJECTIVES
Dengue infection is spreading worldwide. The clinical spectrum is broad and includes asymptomatic infections. This review provides an overview of the different proportions of asymptomatic infections described in epidemiological studies according to definitions, study designs, and detection methods.
METHODS
Medline and Embase databases were searched without restriction of date or language. Studies were included if they reported data on the incidence or prevalence of asymptomatic dengue infections. The data were summarized and classified according to the definitions of the term 'asymptomatic'.
RESULTS
A total of 74 studies were included. The mean proportion of asymptomatic infections among dengue-infected persons was 54% in 50 included studies. The prevalence of dengue infections detected in healthy persons was 0.2% in 24 included studies. The term 'asymptomatic' has been used to refer to 'clinically undetectable infection', but also to 'undiagnosed infection' or 'mild infection'. Only 8% were clinically undetectable laboratory-confirmed dengue infections.
CONCLUSION
The proportion of asymptomatic dengue infections varied greatly. Studies proving data on clinically undetectable laboratory-confirmed dengue infections were very few, but provided consistent results of low proportions of asymptomatic infections. These data challenge the assumption that the majority of dengue cases are asymptomatic.
PubMed: 37809992
DOI: 10.1016/j.heliyon.2023.e20069 -
BMC Infectious Diseases Sep 2023Although many studies on asymptomatic norovirus infection in outbreaks have been conducted globally, structured data (important for emergency management of outbreaks) on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although many studies on asymptomatic norovirus infection in outbreaks have been conducted globally, structured data (important for emergency management of outbreaks) on the prevalence of this epidemic are still not available. This study assessed the global prevalence of asymptomatic norovirus infection in outbreaks.
METHODS
We identified publications on asymptomatic infections from norovirus outbreaks by searching the PubMed, Embase, Cochrane Library, Medline, and Web of Science databases and screening references from the articles reviewed. Prevalence of asymptomatic norovirus infection in outbreaks was employed as the primary summary data. The random-effects model of the meta-analysis was fitted to generate estimates of the prevalence in the overall and subgroup populations.
RESULTS
In total, 44 articles with a sample size of 8,115 asymptomatic individuals were included. The estimated pooled prevalence of asymptomatic norovirus infection in outbreaks was 21.8% (95%CI, 17.4-27.3). The asymptomatic prevalence of norovirus GII (20.1%) was similar to that of GI (19.8%); however, the proportion prevalence of asymptomatic individuals involved in the former (33.36%) was significantly higher than that of in the latter (0.92%) and the former (93.18%) was reported much more frequently than the latter (15.91%) in the included articles. These studies had significant heterogeneity (I = 92%, τ = 0.4021, P < 0.01). However, the source of heterogeneity could not be identified even after subgroup analysis of 10 possible influencing factors (geographical area, outbreak settings, outbreak seasons, sample types, norovirus genotypes, transmission routes, subjects' occupations, subjects' age, per capita national income, and clear case definition). Meta-regression analysis of these 10 factors demonstrated that the geographical area could be partly responsible for this heterogeneity (P = 0.012).
CONCLUSIONS
The overall pooled asymptomatic prevalence of norovirus in outbreaks was high, with genome II dominating. Asymptomatic individuals may play an important role in norovirus outbreaks. This knowledge could help in developing control strategies and public health policies for norovirus outbreaks.
Topics: Humans; Asymptomatic Infections; Prevalence; Disease Outbreaks; Epidemics; Norovirus
PubMed: 37700223
DOI: 10.1186/s12879-023-08519-y -
Systematic Reviews Aug 2023Subjective cognitive impairment (SCI) substantially increases dementia risk and is often conceptualised as the preclinical asymptomatic phase of the cognitive decline...
BACKGROUND
Subjective cognitive impairment (SCI) substantially increases dementia risk and is often conceptualised as the preclinical asymptomatic phase of the cognitive decline continuum. Due to the lack of pharmacological interventions available to treat SCI and reduce dementia risk, and the popularity of herbal and nutritional medicines, the primary aim of this review was to investigate the efficacy on cognitive function and safety of herbal and nutritional medicines (relative to a control) for older adults with and without SCI. The secondary aims were to describe the study characteristics and assess the methodological quality of included studies.
METHOD
Five databases (Cochrane, MEDLINE, CINAHL, PsycInfo, and EMBASE) were searched from database inception with weekly alerts established until review finalisation on 18 September 2022. Articles were eligible if they included the following: study population of older adults with and without SCI, herbal and nutritional medicines as an intervention, evaluated cognitive outcomes and were randomised control trials.
RESULTS
Data were extracted from 21/7666 eligible full-text articles, and the risk of methodological bias was assessed (with SCI = 9/21; without SCI = 12/21). Most studies (20/21) employed parallel, randomised, placebo-controlled designs and were 12 weeks in length. Herbal supplements were widely used (17/21), namely a form of Ginkgo biloba (8/21) or Bacopa monnieri (6/21). Measures of cognition varied across studies, with 14/21 reporting improvements in at least one domain of cognitive functioning over time, in the intervention group (compared to control). A total of 14/21 studies were deemed as having an overall high methodological risk of bias, 6/21 had some concerns, and only one study (using an SCI population) was assessed as having a low risk of methodological bias.
CONCLUSIONS
Overall, this review found that there is a low quality of evidence regarding the efficacy of cognitive function and safety of herbal and nutritional medicines for older adults with and without SCI, due to a high risk of bias across studies. Additionally, further work needs to be done in classifying and understanding SCI and selecting appropriate trial primary outcomes before future studies can more accurately determine the efficacy of interventions for this population.
Topics: Humans; Aged; Cognition; Cognitive Dysfunction; Databases, Factual; MEDLINE; Dementia; Randomized Controlled Trials as Topic
PubMed: 37592293
DOI: 10.1186/s13643-023-02301-6