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European Urology Open Science Jan 2023The advent of immune check inhibitors (ICIs) has tremendously changed the prognosis of metastatic renal cell carcinoma (mRCC), adding an unseen substantial overall... (Review)
Review
CONTEXT
The advent of immune check inhibitors (ICIs) has tremendously changed the prognosis of metastatic renal cell carcinoma (mRCC), adding an unseen substantial overall survival benefit. These agents could be administered alone or in combination with anti-vascular endothelial growth factor (anti-VEGF) therapies. So far, treatment allocation is based only on clinical stratification risk models.
OBJECTIVE
Herein, we aimed to report the different molecular classifications reported in the first-line treatment of mRCC and discuss the awaited clinical implications in terms of treatment selection.
EVIDENCE ACQUISITION
Medline database as well as European Society for Medical Oncology (ESMO)/American Society of Clinical Oncology (ASCO) conference proceedings were searched to identify biomarker studies. Inclusion criteria comprised randomized and nonrandomized clinical trials that included patients treated in the first line of mRCC setting, patients treated with anti-VEGF therapies or ICIs, biological modeling, and available survival outcomes.
EVIDENCE SYNTHESIS
Four classification models were identified with subsequent clinical implications: Beuselinck model (34 gene signatures), IMmotion150, Hakimi, and JAVELIN 101 model. Tumor profiling shows distinct outcomes when treated with one or other combination. Patients are clustered into two gene signatures: angiogenic and proinflammatory (as per JAVELIN). The first is more likely to respond to therapy that includes anti-VEGF agents, while the best outcomes are obtained with an ICI combination with the second.
CONCLUSIONS
The findings presented here were mostly derived from ancillary registered studies of new drugs in the setting of mRCC. Further validation is needed, which sets new paradigms for investigation in clinical research based on tumor biology for treatment allocation and not only on clinical stratification tools.
PATIENT SUMMARY
First-line treatment of metastatic kidney includes immunotherapy alone or in combination with antiangiogenic therapy. However, clinical practice demonstrated that the "one treatment fits all" strategy might not be the best approach. In fact, recent studies showed that the addition of immunotherapy agents will not benefit all patients equally, and some still respond either equally to or better than anti-vascular endothelial growth factor alone. This review revealed biomarker modeling that impacts treatment selection. Recent tumor profiling into "angiogenic signature" more sensitive to angiogenic agents versus "immune signature" more likely to achieve the best response with immunotherapy should be validated. Tumor biology features might be more powerful than clinical classification for a tailored treatment approach.
PubMed: 36573246
DOI: 10.1016/j.euros.2022.11.006 -
Annals of Medicine and Surgery (2012) Feb 2024Stroke remains one of the leading complications of sickle cell anaemia (SCA) in children. Traditionally, SCA treatment focused on symptom relief. However, the high... (Review)
Review
BACKGROUND
Stroke remains one of the leading complications of sickle cell anaemia (SCA) in children. Traditionally, SCA treatment focused on symptom relief. However, the high incidence of strokes in children has prompted a reevaluation of treatment, particularly hydroxyurea, for secondary stroke prevention. This study assesses hydroxyurea's effectiveness and safety in preventing secondary strokes in paediatric SCA patients.
METHODS
This systematic review followed a pre-defined protocol registered with PROSPERO. Comprehensive searches were conducted across PubMed, Embase, Scopus, MEDLINE, Google Scholar, and the Cochrane Library up to August 2023. Studies were included involving paediatric SCA patients at risk of secondary stroke, assessing hydroxyurea as the primary intervention.
RESULTS
A total of six studies meeting inclusion criteria were included. The effectiveness of hydroxyurea in preventing secondary strokes, with variable responses reported across studies. Adverse effects, including mild neutropenia, are associated with hydroxyurea treatment but with variability in reported toxicity levels.
CONCLUSION
Hydroxyurea holds promise in preventing recurrent strokes in children with SCA, though its efficacy and safety profiles vary among individuals. Optimal dosages and treatment durations require further investigation, necessitating vigilant monitoring of haematological parameters. Future research should refine dosing strategies, consider individual patient characteristics, assess long-term effects, and explore ancillary benefits beyond stroke prevention.
PubMed: 38333270
DOI: 10.1097/MS9.0000000000001660 -
Journal of Substance Abuse Treatment Mar 2020Economic evaluations provide evidence that informs stakeholders on how to efficiently allocate real and financial healthcare resources. The purpose of this study was to...
Economic evaluations provide evidence that informs stakeholders on how to efficiently allocate real and financial healthcare resources. The purpose of this study was to review and discuss the integration of economic evaluations into the National Drug Abuse Treatment Clinical Trials Network (CTN) since its inception, as well as expectations for the future of this relationship. A systematic review was performed on published and planned CTN economic evaluations in the CTN dissemination library and PubMed. The well-established Drummond checklist was used to evaluate the comprehensiveness and methodological rigor of published articles. One hundred thirty-eight ancillary, follow-up, or original protocols were reviewed, and 78 potentially relevant published articles were identified. A total number of 14 protocols included an economic evaluation. Of these, 6 protocols were completed, 2 were reported as active, and 6 were reported as in-development at the time of this review. Of the 78 published articles, 9 met the inclusion criteria. As gauged by the Drummond checklist, the quality of CTN published economic evaluations were found to improve over time, and recent published articles were identified as guides to cutting-edge economic research. As the CTN continues to grow and mature, it is imperative that high-quality economic evaluations are incorporated alongside trials in order to maximize the public health impact of the CTN.
Topics: Cost-Benefit Analysis; Humans; Substance-Related Disorders
PubMed: 32220406
DOI: 10.1016/j.jsat.2020.02.002 -
European Radiology Nov 2020The objective of this systematic review was to evaluate the key imaging manifestations of COVID-19 on chest CT in adult patients by providing a comprehensive review of...
OBJECTIVE
The objective of this systematic review was to evaluate the key imaging manifestations of COVID-19 on chest CT in adult patients by providing a comprehensive review of the published literature.
METHODS
We performed a systematic literature search from the PubMed, Google Scholar, Embase, and WHO databases for studies mentioning the chest CT imaging findings of adult COVID-19 patients.
RESULTS
A total of 45 studies comprising 4410 patients were included. Ground glass opacities (GGO), in isolation (50.2%) or coexisting with consolidations (44.2%), were the most common lesions. Distribution of GGOs was most commonly bilateral, peripheral/subpleural, and posterior with predilection for lower lobes. Common ancillary findings included pulmonary vascular enlargement (64%), intralobular septal thickening (60%), adjacent pleural thickening (41.7%), air bronchograms (41.2%), subpleural lines, crazy paving, bronchus distortion, bronchiectasis, and interlobular septal thickening. CT in early follow-up period generally showed an increase in size, number, and density of GGOs, with progression into mixed areas of GGOs plus consolidations and crazy paving, peaking at 10-11 days, before gradually resolving or persisting as patchy fibrosis. While younger adults more commonly had GGOs, extensive/multilobar involvement with consolidations was prevalent in the older population and those with severe disease.
CONCLUSION
This review describes the imaging features for diagnosis, stratification, and follow-up of COVID-19 patients. The most common CT manifestations are bilateral, peripheral/subpleural, posterior GGOs with or without consolidations with a lower lobe predominance. It is pertinent to be familiar with the various imaging findings to positively impact the management of these patients.
KEY POINTS
• Ground glass opacities (GGOs), whether isolated or coexisting with consolidations, in bilateral and subpleural distribution, are the most prevalent chest CT findings in adult COVID-19 patients. • Follow-up CT shows a progression of GGOs into a mixed pattern, reaching a peak at 10-11 days, before gradually resolving or persisting as patchy fibrosis. • Younger people tend to have more GGOs. Older or sicker people tend to have more extensive involvement with consolidations.
Topics: Adult; Betacoronavirus; COVID-19; Coronavirus Infections; Disease Progression; Female; Humans; Lung; Male; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Tomography, X-Ray Computed; Young Adult
PubMed: 32474632
DOI: 10.1007/s00330-020-06975-7 -
The Cochrane Database of Systematic... May 2021There is growing interest in paying for performance (P4P) as a means to align the incentives of healthcare providers with public health goals. Rigorous evidence on the...
BACKGROUND
There is growing interest in paying for performance (P4P) as a means to align the incentives of healthcare providers with public health goals. Rigorous evidence on the effectiveness of these strategies in improving health care and health in low- and middle-income countries (LMICs) is lacking; this is an update of the 2012 review on this topic.
OBJECTIVES
To assess the effects of paying for performance on the provision of health care and health outcomes in low- and middle-income countries.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and 10 other databases between April and June 2018. We also searched two trial registries, websites, online resources of international agencies, organizations and universities, and contacted experts in the field. Studies identified from rerunning searches in 2020 are under 'Studies awaiting classification.'
SELECTION CRITERIA
We included randomized or non-randomized trials, controlled before-after studies, or interrupted time series studies conducted in LMICs (as defined by the World Bank in 2018). P4P refers to the transfer of money or material goods conditional on taking a measurable action or achieving a predetermined performance target. To be included, a study had to report at least one of the following outcomes: patient health outcomes, changes in targeted measures of provider performance (such as the delivery of healthcare services), unintended effects, or changes in resource use.
DATA COLLECTION AND ANALYSIS
We extracted data as per original review protocol and narratively synthesised findings. We used standard methodological procedures expected by Cochrane. Given diversity and variability in intervention types, patient populations, analyses and outcome reporting, we deemed meta-analysis inappropriate. We noted the range of effects associated with P4P against each outcome of interest. Based on intervention descriptions provided in documents, we classified design schemes and explored variation in effect by scheme design.
MAIN RESULTS
We included 59 studies: controlled before-after studies (19), non-randomized (16) or cluster randomized trials (14); and interrupted time-series studies (9). One study included both an interrupted time series and a controlled before-after study. Studies focused on a wide range of P4P interventions, including target payments and payment for outputs as modified by quality (or quality and equity assessments). Only one study assessed results-based aid. Many schemes were funded by national governments (23 studies) with the World Bank funding most externally funded schemes (11 studies). Targeted services varied; however, most interventions focused on reproductive, maternal and child health indicators. Participants were predominantly located in public or in a mix of public, non-governmental and faith-based facilities (54 studies). P4P was assessed predominantly at health facility level, though districts and other levels were also involved. Most studies assessed the effects of P4P against a status quo control (49 studies); however, some studies assessed effects against comparator interventions (predominantly enhanced financing intended to match P4P funds (17 studies)). Four studies reported intervention effects against both comparator and status quo. Controlled before-after studies were at higher risk of bias than other study designs. However, some randomised trials were also downgraded due to risk of bias. The interrupted time-series studies provided insufficient information on other concurrent changes in the study context. P4P compared to a status quo control For health services that are specifically targeted, P4P may slightly improve health outcomes (low certainty evidence), but few studies assessed this. P4P may also improve service quality overall (low certainty evidence); and probably increases the availability of health workers, medicines and well-functioning infrastructure and equipment (moderate certainty evidence). P4P may have mixed effects on the delivery and use of services (low certainty evidence) and may have few or no distorting unintended effects on outcomes that were not targeted (low-certainty evidence), but few studies assessed these. For secondary outcomes, P4P may make little or no difference to provider absenteeism, motivation or satisfaction (low certainty evidence); but may improve patient satisfaction and acceptability (low certainty evidence); and may positively affect facility managerial autonomy (low certainty evidence). P4P probably makes little to no difference to management quality or facility governance (low certainty evidence). Impacts on equity were mixed (low certainty evidence). For health services that are untargeted, P4P probably improves some health outcomes (moderate certainty evidence); may improve the delivery, use and quality of some health services but may make little or no difference to others (low certainty evidence); and may have few or no distorting unintended effects (low certainty evidence). The effects of P4P on the availability of medicines and other resources are uncertain (very low certainty evidence). P4P compared to other strategies For health outcomes and services that are specifically targeted, P4P may make little or no difference to health outcomes (low certainty evidence), but few studies assessed this. P4P may improve service quality (low certainty evidence); and may have mixed effects on the delivery and use of health services and on the availability of equipment and medicines (low certainty evidence). For health outcomes and services that are untargeted, P4P may make little or no difference to health outcomes and to the delivery and use of health services (low certainty evidence). The effects of P4P on service quality, resource availability and unintended effects are uncertain (very low certainty evidence). Findings of subgroup analyses Results-based aid, and schemes using payment per output adjusted for service quality, appeared to yield the greatest positive effects on outcomes. However, only one study evaluated results-based aid, so the effects may be spurious. Overall, schemes adjusting both for quality of service and rewarding equitable delivery of services appeared to perform best in relation to service utilization outcomes.
AUTHORS' CONCLUSIONS
The evidence base on the impacts of P4P schemes has grown considerably, with study quality gradually increasing. P4P schemes may have mixed effects on outcomes of interest, and there is high heterogeneity in the types of schemes implemented and evaluations conducted. P4P is not a uniform intervention, but rather a range of approaches. Its effects depend on the interaction of several variables, including the design of the intervention (e.g., who receives payments ), the amount of additional funding, ancillary components (such as technical support) and contextual factors (including organizational context).
Topics: Bias; Controlled Before-After Studies; Developing Countries; Humans; Interrupted Time Series Analysis; Non-Randomized Controlled Trials as Topic; Quality Improvement; Quality of Health Care; Reimbursement, Incentive
PubMed: 33951190
DOI: 10.1002/14651858.CD007899.pub3 -
EClinicalMedicine May 2024Sedation is routinely administered to critically ill patients to alleviate anxiety, discomfort, and patient-ventilator asynchrony. However, it must be balanced against...
BACKGROUND
Sedation is routinely administered to critically ill patients to alleviate anxiety, discomfort, and patient-ventilator asynchrony. However, it must be balanced against risks such as delirium and prolonged intensive care stays. This study aimed to investigate the effects of different levels of sedation in critically ill adults.
METHODS
Systematic review with meta-analysis and trial sequential analysis (TSA) of randomised clinical trials including critically ill adults admitted to the intensive care unit. CENTRAL, MEDLINE, Embase, LILACS, and Web of Science were searched from their inception to 13 June 2023. Risks of bias were assessed using the Cochrane risk of bias tool. Primary outcome was all-cause mortality. Aggregate data were synthesised with meta-analyses and TSA, and the certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO: CRD42023386960.
FINDINGS
Fifteen trials randomising 4352 patients were included, of which 13 were assessed high risk of bias. Meta-analyses comparing lighter to deeper sedation showed no evidence of a difference in all-cause mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.83-1.06; p = 0.28; 15 trials; moderate certainty evidence), serious adverse events (RR 0.99, CI 0.92-1.06; p = 0.80; 15 trials; moderate certainty evidence), or delirium (RR 1.01, 95% CI 0.94-1.09; p = 0.78; 11 trials; moderate certainty evidence). TSA showed that when assessing mortality, a relative risk reduction of 16% or more between the compared interventions could be rejected.
INTERPRETATION
The level of sedation has not been shown to affect the risks of death, delirium, and other serious adverse events in critically ill adult patients. While TSA suggests that additional trials are unlikely to significantly change the conclusion of the meta-analyses, the certainty of evidence was moderate. This suggests a need for future high-quality studies with higher methodological rigor.
FUNDING
None.
PubMed: 38572080
DOI: 10.1016/j.eclinm.2024.102569 -
Virchows Archiv : An International... Oct 2021Cutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagnostically challenging. Ancillary cytogenetic techniques to detect... (Meta-Analysis)
Meta-Analysis
Genome-wide copy number variations as molecular diagnostic tool for cutaneous intermediate melanocytic lesions: a systematic review and individual patient data meta-analysis.
Cutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagnostically challenging. Ancillary cytogenetic techniques to detect genome-wide copy number variations (CNVs) might provide a valuable tool to allow accurate classification as benign (nevus) or malignant (melanoma). However, the CNV cut-off value to distinguish intermediate lesions from melanoma is not well defined. We performed a systematic review and individual patient data meta-analysis to evaluate the use of CNVs to classify intermediate melanocytic lesions. A total of 31 studies and 431 individual lesions were included. The CNV number in intermediate lesions (median 1, interquartile range [IQR] 0-2) was significantly higher (p<0.001) compared to that in benign lesions (median 0, IQR 0-1) and lower (p<0.001) compared to that in malignant lesions (median 6, IQR 4-11). The CNV number displayed excellent ability to differentiate between intermediate and malignant lesions (0.90, 95% CI 0.86-0.94, p<0.001). Two CNV cut-off points demonstrated a sensitivity and specificity higher than 80%. A cut-off of ≥3 CNVs corresponded to 85% sensitivity and 84% specificity, and a cut-off of ≥4 CNVs corresponded to 81% sensitivity and 91% specificity, respectively. This individual patient data meta-analysis provides a comprehensive overview of CNVs in cutaneous intermediate melanocytic lesions, based on the largest pooled cohort of ambiguous melanocytic neoplasms to date. Our meta-analysis suggests that a cut-off of ≥3 CNVs might represent the optimal trade-off between sensitivity and specificity in clinical practice to differentiate intermediate lesions from melanoma.
Topics: Algorithms; Cohort Studies; DNA Copy Number Variations; Genome-Wide Association Study; Humans; Melanocytes; Melanoma; Pathology, Molecular; Sensitivity and Specificity; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 33851238
DOI: 10.1007/s00428-021-03095-5 -
AIDS Care Nov 2019This systematic review identifies models of service co-location, a structural intervention strategy to remove barriers to HIV care and services, and examines their...
This systematic review identifies models of service co-location, a structural intervention strategy to remove barriers to HIV care and services, and examines their associations with HIV care outcomes. A cumulative database (e.g., MEDLINE, EMBASE) of HIV, AIDS, and STI literature was systematically searched and manual searches were conducted to identify relevant studies. Thirty-six studies were classified into six models of co-location: HIV care co-located with multiple ancillary services, tuberculosis (TB) care, non-HIV specific primary care, drug abuse treatment, prevention of mother to child transmission programs (PMTCT), and mental health care. More evidence of a positive association was seen for linkage to care and antiretroviral therapy (ART) uptake than for retention and viral suppression. Models of co-location that addressed HIV and non-HIV medical care issues (i.e., co-location with non-HIV specific primary care, PMTCT, and TB) had more positive associations, particularly for linkage to care and ART uptake, than other co-location models. While some findings are encouraging, more research with rigorous study designs is needed to strengthen the evaluation of, and evidence for, service co-location.
Topics: Child; Female; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Pregnancy; Treatment Outcome
PubMed: 30773038
DOI: 10.1080/09540121.2019.1576847 -
Frontiers in Neurology 2020Venous thromboembolism (VTE) can occur simultaneously with a cryptogenic stroke (CS) linked to patent foramen ovale (PFO), given paradox thromboembolism as potential...
Venous thromboembolism (VTE) can occur simultaneously with a cryptogenic stroke (CS) linked to patent foramen ovale (PFO), given paradox thromboembolism as potential stroke cause. However, little is known on the frequency of concomitant VTE and CS. We aimed to review the literature on the frequency of VTE in patients with CS linked to PFO (primary aim) and of ischemic stroke (IS) among patients with pulmonary embolism (PE) (secondary aim). We performed a Medline search for cohort studies, written in English, with the following characteristics: (a) enrolling patients hospitalized for an acute ischemic stroke undergoing a work-up for deep venous thrombosis (DVT) and/or PE. To be included in this review, a study had to have at least a subgroup of patients with PFO; (b) the time interval between the index stroke and the work-up had to be within 40 days and the studies had to differentiate between DVT and PE. For the secondary aim, studies had to include patients with acute PE, known PFO-status and routine brain imaging on admission or within 1 year. We found eight studies reporting on the frequency of VTE after an acute CS linked to PFO. Concerning DVT, the reported frequency ranged between 7 and 27%; concerning PE, it lied between 4.4 and 37%. Six studies assessed the frequency of ischemic brain lesions among patients with an acute PE. In all studies, the presence of PFO was associated with ischemic brain lesions, both at baseline and follow-up. VTE can be detected in patients with CS linked to PFO. While -based on the presented literature-routine screening for VTE in patients with CS linked to PFO does not appear justified, history taking, and clinical exam should consider concomitant VTE. Whenever clinically suspected, the threshold to trigger ancillary testing for VTE should be low. Among patients with an acute PE and PFO, vigilance for new neurologic deficits should be increased, with a low threshold for brain imaging.
PubMed: 32431661
DOI: 10.3389/fneur.2020.00336