Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer ...(mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete.
To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing.
A literature review of PubMed/Medline, Cochrane Library, Current Contents Medicine, Web of Science, Clinical Trial.Gov, WHO-ICTRP (January 2004–November 2017), and the proceedings of major international meetings (2015/2016/2017) was performed in November 2017.
In the last few years, several new options for treatment of mCRPC have shown a survival benefit in phase III trials besides docetaxel:abiraterone, enzalutamide, cabazitaxel, radium-223, and sipuleucel-T. Radium-223 and denosumab have increased options in management of bone metastases. Currently, novel agents such as next-generation androgen receptor (AR) axis-targeting treatments, immunotherapeutics, or therapies targeting other oncogenic and genomic pathways, particularly poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors and PD-1 inhibitors, are under clinical investigation. With increasing treatment options for mCRPC, information on how to personalize management and how to select and sequence existing therapies is beginning to emerge, as are predictive biomarkers (homologous repair mutations, mismatch repair mutations, AR splice variant 7). Finally, early use of active agents in the castration-sensitive state will likely also change the clinical management of the disease when it becomes castrate resistant.
The emergence of new drugs for mCRPC has improved treatment options dramatically. Currently, systemic treatment options for mCRPC include hormonal therapy, chemotherapy, immunotherapy, and radionuclide therapy as well as bone-modifying agents and palliative or supportive measures. Further, new genetically targeted agents (PARP inhibitors and PD-1 inhibitors) are on the horizon for certain subsets of biomarker-selected patients. The best strategies for patient selection and optimal sequential use to achieve the longest cumulative survival improvement and to prevent early resistance remain unclear.
The current literature and proceedings from relevant congresses related to available systemic agents for the treatment of metastatic castration-resistant prostate cancer, including novel genetically targeted therapies, including poly(adenosine diphosphate–ribose) polymerase inhibitors and PD-1 inhibitors, were reviewed. Current therapies and ongoing developments are discussed.
In the last few years, new therapeutics for the treatment of metastatic castration-resistant prostate cancer have increased survival substantially. While promising novel agents are currently under trial, including genetically targeted therapies (poly(adenosine diphosphate–ribose) polymerase inhibitors and PD-1 inhibitors), further clinical and translational research in predictive biomarkers is needed to optimize treatment selection and sequencing strategies for existing drugs.
SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this ...systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs.
We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers' instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., <20 (96.5%, 95% CI 92.6% to 98.4%) and <25 (95.8%, 95% CI 92.3% to 97.8%), in comparison to those with Ct ≥ 25 (50.7%, 95% CI 35.6% to 65.8%) and ≥30 (20.9%, 95% CI 12.5% to 32.8%). Testing in the first week from symptom onset resulted in substantially higher sensitivity (83.8%, 95% CI 76.3% to 89.2%) compared to testing after 1 week (61.5%, 95% CI 52.2% to 70.0%). The best Ag-RDT sensitivity was found with anterior nasal sampling (75.5%, 95% CI 70.4% to 79.9%), in comparison to other sample types (e.g., nasopharyngeal, 71.6%, 95% CI 68.1% to 74.9%), although CIs were overlapping. Concerns of bias were raised across all datasets, and financial support from the manufacturer was reported in 24.1% of datasets. Our analysis was limited by the included studies' heterogeneity in design and reporting.
In this study we found that Ag-RDTs detect the vast majority of SARS-CoV-2-infected persons within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease, making them a valuable tool to fight the spread of SARS-CoV-2. Standardization in conduct and reporting of clinical accuracy studies would improve comparability and use of data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Appendectomy has been the gold standard for every form of appendicitis. In recent years, though, it has repeatedly been claimed that for acute uncomplicated appendicitis, antibiotic therapy ...can be an equivalent treatment. The aim of this meta-analysis was to determine if antibiotic therapy is a safe and effective alternative to appendectomy for acute uncomplicated appendicitis.
Methods
In a systematic literature review, relevant databases were searched for randomized studies comparing appendectomy with antibiotic treatment for uncomplicated acute appendicitis. Two independent reviewers performed study selection and data extraction. The primary endpoint was the successful treatment of appendicitis. Secondary endpoints were pain intensity, duration of hospitalization, absence from work, and the incidence of complications.
Results
Five randomized controlled studies (
n
= 1430 patients) fulfilled the inclusion criteria. Of the 727 patients treated initially with antibiotics, 272 (37.4%) underwent secondary appendectomy within 1 year (treatment effectiveness: 62.6% compared to 96.3% in the surgical group, RR 0.65, 95% CI 0.55–0.76,
p
< 0.00001). Neither duration of hospital stay (MD 0.11 days, 95% CI: − 0.22–0.43,
p
= 0.53) nor the probability of complication-free treatment (RR 1.08, 95% CI: 0.97–1.22,
p
= 0.16) were significantly different between the two treatments. Absence from work was significantly shorter in the antibiotic group (MD − 2.49 days, 95% CI: − 4.59–− 0.40,
p
= 0.02).
Conclusions
This meta-analysis shows that appendectomy is more effective than antibiotic therapy for definitive cure of acute uncomplicated appendicitis. However, since the incidence of complications does not differ between the two treatments, antibiotic therapy might be a reasonable alternative for selected patients.
Radiomics may increase the diagnostic accuracy of medical imaging for localized and metastatic RCC (mRCC). A systematic review and meta-analysis was performed. Doing so, we comprehensively searched ...literature databases until May 2020. Studies investigating the diagnostic value of radiomics in differentiation of localized renal tumors and assessment of treatment response to ST in mRCC were included and assessed with respect to their quality using the radiomics quality score (RQS). A total of 113 out of 1098 identified studies met the criteria and were included in qualitative synthesis. Median RQS of all studies was 13.9% (5.0 points, IQR 0.25-7.0 points), and RQS increased over time. Thirty studies were included into the quantitative synthesis: For distinguishing angiomyolipoma, oncocytoma or unspecified benign tumors from RCC, the random effects model showed a log odds ratio (OR) of 2.89 (95%-CI 2.40-3.39,
< 0.001), 3.08 (95%-CI 2.09-4.06,
< 0.001) and 3.57 (95%-CI 2.69-4.45,
< 0.001), respectively. For the general discrimination of benign tumors from RCC log OR was 3.17 (95%-CI 2.73-3.62,
< 0.001). Inhomogeneity of the available studies assessing treatment response in mRCC prevented any meaningful meta-analysis. The application of radiomics seems promising for discrimination of renal tumor dignity. Shared data and open science may assist in improving reproducibility of future studies.
Since the ARMA trial, there has been no multicenter randomized controlled trial that has been able to assign further mortality benefit to a particular ventilatory strategy 2. Several studies were ...close to the TCAV protocol but had to be excluded due to relevant details. ...it seems reasonable to assume, that the TCAV protocol has been modified to meet current recommendations for lung-protective ventilation. Using the TCAV protocol, TV is generated in the release-phase and is dependable from the peak expiratory flow and the concomitant rate of flow decay, which is mainly determined by the elastance of the respiratory system (ERS). Since ERS decreases when lung recruitment occurs, the higher TV within the TCAV-protocol will only occur, when lung recruits and ERS is lowered. ...strict adherence to the TCAV protocol in clinical trials has not yet been achieved due to clinical concerns in the respective studies. Airway pressure release ventilation versus low tidal volume ventilation for patients with acute respiratory distress syndrome/acute lung injury: a meta-analysis of randomized clinical trials.
IntroductionPerforated peptic ulcers are a life-threatening complication associated with high morbidity and mortality. Several treatment approaches are available. The aim of this network ...meta-analysis (NMA) is to compare surgical and alternative approaches for the treatment of perforated peptic ulcers regarding mortality and other patient-relevant outcomes.Methods and analysisA systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, CINAHL, ClinicalTrials.gov trial registry and ICTRP will be conducted with predefined search terms.To address the question of the most effective treatment approach, an NMA will be performed for each of the outcomes mentioned above. A closed network of interventions is expected. The standardised mean difference with its 95% CI will be used as the effect measure for the continuous outcomes, and the ORs with 95% CI will be calculated for the binary outcomes.Ethics and disseminationIn accordance with the nature of the data used in this meta-analysis, which involves aggregate information from previously published studies ethical approval is deemed unnecessary. Results will be disseminated directly to decision-makers (eg, surgeons, gastroenterologists) through publication in peer-reviewed journals and presentation at conferences.PROSPERO registration numberCRD42023482932.
Self-testing is an effective tool to bridge the testing gap for several infectious diseases; however, its performance in detecting SARS-CoV-2 using antigen-detection rapid diagnostic tests (Ag-RDTs) ...has not been systematically reviewed. This study aimed to inform WHO guidelines by evaluating the accuracy of COVID-19 self-testing and self-sampling coupled with professional Ag-RDT conduct and interpretation. Articles on this topic were searched until November 7th, 2022. Concordance between self-testing/self-sampling and fully professional-use Ag-RDTs was assessed using Cohen's kappa. Bivariate meta-analysis yielded pooled performance estimates. Quality and certainty of evidence were evaluated using QUADAS-2 and GRADE tools. Among 43 studies included, twelve reported on self-testing, and 31 assessed self-sampling only. Around 49.6% showed low risk of bias. Overall concordance with professional-use Ag-RDTs was high (kappa 0.91 95% confidence interval (CI) 0.88-0.94). Comparing self-testing/self-sampling to molecular testing, the pooled sensitivity and specificity were 70.5% (95% CI 64.3-76.0) and 99.4% (95% CI 99.1-99.6), respectively. Higher sensitivity (i.e., 93.6% 95% CI 90.4-96.8 for Ct < 25) was estimated in subgroups with higher viral loads using Ct values as a proxy. Despite high heterogeneity among studies, COVID-19 self-testing/self-sampling exhibits high concordance with professional-use Ag-RDTs. This suggests that self-testing/self-sampling can be offered as part of COVID-19 testing strategies.Trial registration: PROSPERO: CRD42021250706.
During the COVID-19 pandemic, antigen diagnostic tests were frequently used for screening, triage, and diagnosis. Novel instrument-based antigen tests (iAg tests) hold the promise of outperforming ...their instrument-free, visually-read counterparts. Here, we provide a systematic review and meta-analysis of the SARS-CoV-2 iAg tests' clinical accuracy.
We systematically searched MEDLINE (via PubMed), Web of Science, medRxiv, and bioRxiv for articles published before November 7th, 2022, evaluating the accuracy of iAg tests for SARS-CoV-2 detection. We performed a random effects meta-analysis to estimate sensitivity and specificity and used the QUADAS-2 tool to assess study quality and risk of bias. Sub-group analysis was conducted based on Ct value range, IFU-conformity, age, symptom presence and duration, and the variant of concern.
We screened the titles and abstracts of 20,431 articles and included 114 publications that fulfilled the inclusion criteria. Additionally, we incorporated three articles sourced from the FIND website, totaling 117 studies encompassing 95,181 individuals, which evaluated the clinical accuracy of 24 commercial COVID-19 iAg tests. The studies varied in risk of bias but showed high applicability. Of 24 iAg tests from 99 studies assessed in the meta-analysis, the pooled sensitivity and specificity compared to molecular testing of a paired NP swab sample were 76.7% (95% CI 73.5 to 79.7) and 98.4% (95% CI 98.0 to 98.7), respectively. Higher sensitivity was noted in individuals with high viral load (99.6% 95% CI 96.8 to 100 at Ct-level ≤ 20) and within the first week of symptom onset (84.6% 95% CI 78.2 to 89.3), but did not differ between tests conducted as per manufacturer's instructions and those conducted differently, or between point-of-care and lab-based testing.
Overall, iAg tests have a high pooled specificity but a moderate pooled sensitivity, according to our analysis. The pooled sensitivity increases with lower Ct-values (a proxy for viral load), or within the first week of symptom onset, enabling reliable identification of most COVID-19 cases and highlighting the importance of context in test selection. The study underscores the need for careful evaluation considering performance variations and operational features of iAg tests.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This meta-analysis examines the outcomes of patients undergoing surgery with vascular resection for retroperitoneal sarcoma. A systematic literature search based on Preferred Reporting Items for ...Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted, identifying five comparative retrospective cohort studies published from 2015 to 2021, with a total of 1,417 patients (180 in the vascular resection (VR) group and 1,237 in the control (no VR) group). The meta-analysis found that 30-day morbidity rates, as classified by Clavien-Dindo classification > 3, were higher in the VR group compared to the no VR group (46% versus 25%, odds ratio (OR): 1.84, 95% confidence interval (CI): 0.39-8.69, p=0.44). Local recurrence rates during the follow-up period were similar between the two groups (30% versus 30%, OR: 1.46, 95% CI: 0.50-4.25, p=0.49). However, distant recurrence was more frequent in the VR group (32% versus 8.5%, OR: 2.54, 95% CI: 1.05-6.13, p=0.04). In conclusion, although oncovascular procedures are feasible for patients with retroperitoneal sarcomas, the long-term outcomes appear to be worse when compared to procedures that do not involve vessel resections.
PDF
