-
European Journal of Medical Research Nov 2023There have been massive studies to develop an effective vaccine against SARS-CoV-2 which fortunately led to manage the recent pandemic, COVID-19. According to the quite... (Review)
Review
There have been massive studies to develop an effective vaccine against SARS-CoV-2 which fortunately led to manage the recent pandemic, COVID-19. According to the quite rapidly developed vaccines in a fast window time, large investigations to assess the probable vaccine-related adverse events are crucially required. COVID-19 vaccines are available of different platforms and the primary clinical trials results presented acceptable safety profile of the approved vaccines. Nevertheless, the long-term assessment of the adverse events or rare conditions need to be investigated. The present systematic review, aimed at classification of probable vaccine-related unsolicited adverse events in Iranian population through the data collection of the published case report studies.The related published case reports were explored via PubMed, Web of Science and Google scholar according to the available published data up to 14 Dec, 2022 using PRISMA guideline. Out of 437 explored studies, the relevant data were fully investigated which totally led to 40 studies, including 64 case reports with a new onset of a problem post-vaccination. The cases were then classified according to the various items, such as the type of adverse event and COVID-19 vaccines.The reported COVID-19 vaccines in the studied cases included BBIBP-CorV, ChAdOx1-S, Sputnik V and COVAXIN. The results showed that the adverse events presented in 8 different categories, including cutaneous involvements in 43.7% (n = 28), neurologic problems (n = 16), blood/vessel involvement (n = 6), cardiovascular involvement (n = 5), ocular disorders (n = 4), liver disorder/failure (n = 2), graft rejection (n = 2) and one metabolic disorder. Notably, almost 60% of the cases had no comorbidities. Moreover, the obtained data revealed nearly half of the incidences occurred after the first dose of injection and the median duration of improvement after the symptom was 10 days (range: 2-120). In addition, 73% of all the cases were either significantly improved or fully recovered. Liver failure following ChAdOx1-S vaccination was the most serious vaccine adverse event which led to death in two individuals with no related medical history.Although the advantages of COVID-19 vaccination is undoubtedly significant, individuals including with a history of serious disease, comorbidities and immunodeficiency conditions should be vaccinated with the utmost caution. This study provides a comprehensive overview and clinical implications of possible vaccine-related adverse events which should be considered in further vaccination strategies. Nevertheless, there might be a bias regarding potential under-reporting and missing data of the case reports included in the present study. Although the reported data are not proven to be the direct vaccination outcomes and could be a possible immune response over stimulation, the people the population with a medium/high risk should be monitored after getting vaccinated against COVID-19 of any platforms. This could be achieved by a carefull attention to the subjects ' medical history and also through consulting with healthcare providers before vaccination.
Topics: Humans; COVID-19; COVID-19 Vaccines; Iran; SARS-CoV-2; Vaccination; Case Reports as Topic
PubMed: 38008729
DOI: 10.1186/s40001-023-01531-7 -
Biomedicines Nov 2023Acute respiratory distress syndrome (ARDS) is often a consequence of a dysregulated immune response; therefore, immunomodulation by extracorporeal cytokine removal has... (Review)
Review
BACKGROUND
Acute respiratory distress syndrome (ARDS) is often a consequence of a dysregulated immune response; therefore, immunomodulation by extracorporeal cytokine removal has been increasingly used as an adjuvant therapy, but convincing data are still missing. The aim of this study was to investigate the effects of adjunctive hemoadsorption (HA) on clinical and laboratory outcomes in patients with ARDS.
METHODS
We performed a systematic literature search in PubMed, Embase, CENTRAL, Scopus, and Web of Science (PROSPERO: CRD42022292176). The population was patients receiving HA therapy for ARDS. The primary outcome was the change in PaO2/FiO2 before and after HA therapy. Secondary outcomes included the before and after values for C-reactive protein (CRP), lactate, interleukin-6 (IL-6), and norepinephrine (NE) doses.
RESULTS
We included 26 publications, with 243 patients (198 undergoing HA therapy and 45 controls). There was a significant improvement in PaO2/FiO2 ratio following HA therapy (MD = 68.93 [95%-CI: 28.79 to 109.06] mmHg, = 0.005) and a reduction in CRP levels (MD = -45.02 [95%-CI: -82.64; -7.39] mg/dL, = 0.026) and NE dose (MD = -0.24 [95%-CI: -0.44 to -0.04] μg/kg/min, = 0.028).
CONCLUSIONS
Based on our findings, HA resulted in a significant improvement in oxygenation and a reduction in NE dose and CRP levels in patients treated with ARDS. Properly designed RCTs are still needed.
PubMed: 38002070
DOI: 10.3390/biomedicines11113068 -
The Cochrane Database of Systematic... Jan 2021This is an updated version of the Cochrane Review previously published in 2018. Epilepsy is a common neurological disorder characterised by recurrent seizures. Most... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an updated version of the Cochrane Review previously published in 2018. Epilepsy is a common neurological disorder characterised by recurrent seizures. Most people with epilepsy have a good prognosis and their seizures are well controlled by a single antiepileptic drug, but up to 30% develop drug-resistant epilepsy, especially people with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCTs) of gabapentin, when used as an add-on treatment for drug-resistant focal epilepsy.
OBJECTIVES
To evaluate the efficacy and tolerability of gabapentin when used as an add-on treatment for people with drug-resistant focal epilepsy.
SEARCH METHODS
For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) on 11 August 2020. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialised Registers of Cochrane Review Groups including Epilepsy. We imposed no language restrictions.
SELECTION CRITERIA
Randomised, placebo-controlled, double-blind, add-on trials of gabapentin in people with drug-resistant focal epilepsy. We also included trials using an active drug control group or comparing different doses of gabapentin.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: seizure frequency, seizure freedom, treatment withdrawal (any reason) and adverse effects. Primary analyses were intention-to-treat. We also undertook sensitivity best-case and worst-case analyses. We estimated summary risk ratios (RR) for each outcome and evaluated dose-response in regression models.
MAIN RESULTS
We identified no new studies for this update, therefore, the results and conclusions are unchanged. In the previous update of this review, we combined data from six trials in meta-analyses of 1206 randomised participants. The overall risk ratio (RR) for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 studies, 1206 participants; moderate-certainty evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (95% CI 19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (95% CI 8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-certainty evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-certainty evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-certainty evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-certainty evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-certainty evidence). There was no evidence of a difference for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-certainty evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-certainty evidence). Overall, the studies were at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall certainty of the evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide CIs.
AUTHORS' CONCLUSIONS
Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy, and seems to be fairly well-tolerated. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types. Further trials are needed to assess the long-term effects of gabapentin, and to compare gabapentin with other add-on drugs.
Topics: Adult; Anticonvulsants; Child; Cyclohexanecarboxylic Acids; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Gabapentin; Humans; Intention to Treat Analysis; Patient Dropouts; Randomized Controlled Trials as Topic; gamma-Aminobutyric Acid
PubMed: 33434292
DOI: 10.1002/14651858.CD001415.pub4 -
Health Science Reports Mar 2022Scientists and healthcare workers have expressed their concerns on the impacts of the COVID-19 pandemic on vaccination coverage in children and adolescents. Therefore,... (Review)
Review
BACKGROUND AND AIMS
Scientists and healthcare workers have expressed their concerns on the impacts of the COVID-19 pandemic on vaccination coverage in children and adolescents. Therefore, we aimed to systematically review the studies addressing this issue worldwide.
METHODS
We conducted a systematic search of relevant studies using the keywords on databases of PubMed, Web of Science, and Cochrane on May 22, 2021. The identified records were imported into EndNote software and underwent a two-phase screening process consisting of title/abstract and full-text screenings against inclusion criteria. The data of the included studies were summarized into a table and the findings were analyzed in a systematic approach.
RESULTS
From 26 eligible studies, 21 studies demonstrated decreased vaccination rates in the children during the COVID-19 pandemic, while three studies found increased or no significant changes only in influenza vaccination. The two remaining studies from Brazil and Sweden also showed no significant changes in vaccination rates in the children during the pandemic.
CONCLUSION
Most of the reports worldwide reported a decline or delay in vaccination at the time of the COVID-19 pandemic. A sustained catch-up program seems to be necessary, especially in low-income countries, to avoid any vaccine dose missing. Facilitating the vaccination process is recommended, such as decreasing the waiting time for vaccination at the health center, addressing the fear and concerns related to COVID infection for parents, and enhancing vaccine availability, and promoting access in remote areas. Countries should ensure proper vaccination to prevent future pandemics related to vaccine-preventable diseases.
PubMed: 35224217
DOI: 10.1002/hsr2.516 -
JCO Clinical Cancer Informatics Dec 2021There is a need for an improved understanding of clinical and biologic risk factors in pediatric cancer to improve patient outcomes. Machine learning (ML) represents the...
PURPOSE
There is a need for an improved understanding of clinical and biologic risk factors in pediatric cancer to improve patient outcomes. Machine learning (ML) represents the application of computational inference from advanced statistical methods that can be applied to increasing amount of data available for study in pediatric oncology. The goal of this systematic review was to systematically characterize the state of ML in pediatric oncology and highlight advances and opportunities in the field.
METHODS
We conducted a systematic review of the Embase, Scopus, and MEDLINE databases for applications of ML in pediatric oncology. Query results from all three databases were aggregated and duplicate studies were removed.
RESULTS
A total of 42 unique articles that examined the applications of ML in pediatric oncology met inclusion criteria for review. We identified 20 studies of CNS tumors, 13 of solid tumors, and nine of leukemia. ML tasks included classification, prediction of treatment response, and dose optimization with a variety of methods being used including neural network, k-nearest neighbor, random forest, naive Bayes, and support vector machines. Strengths of the identified studies included matching or outperforming physician comparators via automated analysis and predicting therapeutic response. Common limitations included significant heterogeneity in reporting standards, clinical applicability, small sample sizes, and missing external validation cohorts.
CONCLUSION
We identified areas where ML can enhance clinical care in ways that may not otherwise be achievable. Although ML promises enormous potential in improving diagnostics, decision making, and monitoring for children with cancer, the field remains in early stages and future work will be aided by standards and guidelines to ensure rigorous methodologic design and maximizing clinical utility.
Topics: Artificial Intelligence; Bayes Theorem; Child; Humans; Machine Learning; Medical Oncology; Risk Factors
PubMed: 34910588
DOI: 10.1200/CCI.21.00102 -
Clinical Microbiology and Infection :... May 2022Detailed reporting is essential in non-inferiority randomized controlled trials (NI-RCTs) to assess evidence quality, as these trials inform standards of care. (Review)
Review
BACKGROUND
Detailed reporting is essential in non-inferiority randomized controlled trials (NI-RCTs) to assess evidence quality, as these trials inform standards of care.
OBJECTIVES
The primary objective was to evaluate the methodological and reporting quality of antifungal NI-RCTs.
DATA SOURCES
Medline, EMBASE, the Cochrane CENTRAL and the United States Federal Drug Administration (FDA) drugs database were searched to 9 September 2020.
STUDY ELIGIBILITY CRITERIA
NI-RCTs differing by antifungal formulation, type, dose, administration and/or duration were included. Articles were independently assessed in duplicate using quality indicators developed by the Consolidated Standards of Reporting Trials (CONSORT) group.
PARTICIPANTS
Patients enrolled in antifungal trials for prophylactic and therapeutic use.
METHODS
The Cochrane RoB 2.0 tool was used to assess risk of bias. Descriptive statistics were used; all statistical tests were two sided.
RESULTS
Of 32 included studies, 22 (68.7%) did not justify the NIM. Handling of missing data was not described in 20 (62.5%). Intention-to-treat (ITT) and per-protocol (PP) analyses were both reported in 12/32 (37.5%) studies. Eleven of 32 studies (34.3%) reported potentially misleading conclusions. Industry-financed studies were more likely to report only the ITT analysis (n = 14/27, 51.9%). Methodological and reporting quality was unaffected by publication year; risk of bias from missing data changed over time. Overall risk of bias across included studies was moderate to high, with high risk in randomization process (n = 8/32, 25%), missing outcome data (n = 5/32, 15.6%), and selection of reported result (n = 9/32, 28.1%).
CONCLUSIONS
Justification of the non-inferiority margin, reporting of ITT and PP analyses, missing data handling description, and ensuring conclusions are consistent with reported data is necessary to improve CONSORT adherence. Small sample size and overall risk of bias are study limitations. (Systematic Review Registration Number PROSPERO CRD42020219497).
Topics: Antifungal Agents; Bias; Humans; Intention to Treat Analysis; Randomized Controlled Trials as Topic; Sample Size; United States
PubMed: 34763055
DOI: 10.1016/j.cmi.2021.11.003 -
Frontiers in Oncology 2021Reirradiation using brachytherapy (BT) and external beam radiation therapy (EBRT) are salvage strategies with locally radiorecurrent prostate cancer. This systematic...
BACKGROUND
Reirradiation using brachytherapy (BT) and external beam radiation therapy (EBRT) are salvage strategies with locally radiorecurrent prostate cancer. This systematic review describes the oncologic and toxicity outcomes for salvage BT and EBRT [including Stereotactic Body Radiation Therapy (SBRT)].
METHODS
An International Prospective Register of Systematic Reviews (PROSPERO) registered (#211875) study was conducted using Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. EMBASE and MEDLINE databases were searched from inception to December 2020. For BT, both low dose rate (LDR) and high dose rate (HDR) BT techniques were included. Two authors independently assessed study quality using the 18-item Modified Delphi technique.
RESULTS
A total of 39 eligible studies comprising 1967 patients were included (28 BT and 11 SBRT). In 35 studies (90%), the design was single centre and/or retrospective and no randomised prospective studies were found. Twelve BT studies used LDR only, 11 HDR only, 4 LDR or HDR and 1 pulsed-dose rate only. All EBRT studies used SBRT exclusively, four with Cyberknife alone and 7 using both Cyberknife and conventional linear accelerator treatments. Median (range) modified Delphi quality score was 15 (6-18). Median (range) follow-up was 47.5 months (13-108) (BT) and 25.4 months (21-44) (SBRT). For the LDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 71% (48-89.5) and 52.5% (20-79). For the HDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 74% (63-89) and 51% (45-65). For the SBRT studies, the median (range) 2-year bRFS for the SBRT group was 54.9% (40-80). Mean (range) acute and late grade≥3 GU toxicity rates for LDR-BT/HDR-BT/SBRT were 7.4%(0-14)/2%(0-14)/2.7%(0-8.7) and 13.6%(0-30)/7.9%(0-21.3%)/2.7%(0-8%). Mean (range) acute and late grade≥3 GI toxicity rates for LDR-BT/HDR-BT/SBRT were 6.5%(0-19)/0%/0.5%(0-4%) and 6.4%(0-20)/0.1%(0-0.9)/0.2%(0-1.5). One third of studies included Patient Reported Outcome Measures (PROMs).
CONCLUSIONS
Salvage reirradiation of radiorecurrent prostate cancer using HDR-BT or SBRT provides similar biochemical control and acceptable late toxicity. Salvage LDR-BT is associated with higher late GU/GI toxicity. Challenges exist in comparing BT and SBRT from inconsistencies in reporting with missing data, and prospective randomised trials are needed.
PubMed: 34568012
DOI: 10.3389/fonc.2021.681448 -
Naunyn-Schmiedeberg's Archives of... Feb 2024Hydroxychloroquine (HCQ) has been repurposed and used for the treatment of COVID-19 patients; however, its efficacy remains controversial, maybe partly due to the... (Meta-Analysis)
Meta-Analysis
Hydroxychloroquine (HCQ) has been repurposed and used for the treatment of COVID-19 patients; however, its efficacy remains controversial, maybe partly due to the dosage, ranging from 200 to 800 mg/day, reported in different studies. Indeed, HCQ low dose (≤ 2.4 g/5 days) showed a lower risk of side effects compared to high doses. In this study, we performed a systematic review and meta-analysis to investigate the effect of low-dose HCQ used alone on three outcomes including in-hospital mortality, the need for mechanical ventilation, and ICU admission in COVID-19 patients. A systematic review of English literature was conducted from January 2020 to April 2022, in PubMed, Cochrane Library, and Google Scholar. Studies reporting a dosage of 400 mg twice the first day, followed by 200 mg twice for four days were included. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models. Eleven studies (12,503 patients) were retained in the quantitative analysis, four observational cohort studies, and seven RCTs. When pooling both observational and RCTs, low-dose HCQ was associated with decreased mortality (OR = 0.73, 95% CI: [0.55-0.97], I = 58%), but not with mechanical ventilation need (OR = 1.03, 95% CI: [0.56-1.89], I = 67%) and ICU admission rate (OR = 0.70, 95% CI: [0.42-1.17], I = 47%). However, no effect was observed when pooling only RCTs. Despite RCTs limitations, treatment with low-dose HCQ was not associated with improvement in mortality, mechanical ventilation need and ICU admission rate in COVID-19 patients.
Topics: Humans; COVID-19; COVID-19 Drug Treatment; Hydroxychloroquine; Respiration, Artificial; Observational Studies as Topic; Randomized Controlled Trials as Topic
PubMed: 37639021
DOI: 10.1007/s00210-023-02688-y -
The Cochrane Database of Systematic... Nov 2022Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on... (Review)
Review
BACKGROUND
Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. Nonetheless, size of effect, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated.
OBJECTIVES
To assess whether and at which doses systemic corticosteroids are effective and safe in the treatment of people with COVID-19, to explore equity-related aspects in subgroup analyses, and to keep up to date with the evolving evidence base using a living systematic review approach.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 6 January 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for people with COVID-19. We included any type or dose of systemic corticosteroids and the following comparisons: systemic corticosteroids plus standard care versus standard care, different types, doses and timings (early versus late) of corticosteroids. We excluded corticosteroids in combination with other active substances versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs. We rated the certainty of the evidence using the GRADE approach for the following outcomes: all-cause mortality up to 30 and 120 days, discharged alive (clinical improvement), new need for invasive mechanical ventilation or death (clinical worsening), serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections.
MAIN RESULTS
We included 16 RCTs in 9549 participants, of whom 8271 (87%) originated from high-income countries. A total of 4532 participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 3766). These studies included participants mostly older than 50 years and male. We also identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design. Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo We included 11 RCTs (8019 participants), one of which did not report any of our pre-specified outcomes and thus our analyses included outcome data from 10 studies. Systemic corticosteroids plus standard care compared to standard care probably reduce all-cause mortality (up to 30 days) slightly (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.84 to 0.97; 7898 participants; estimated absolute effect: 274 deaths per 1000 people not receiving systemic corticosteroids compared to 246 deaths per 1000 people receiving the intervention (95% CI 230 to 265 per 1000 people); moderate-certainty evidence). The evidence is very uncertain about the effect on all-cause mortality (up to 120 days) (RR 0.74, 95% CI 0.23 to 2.34; 485 participants). The chance of clinical improvement (discharged alive at day 28) may slightly increase (RR 1.07, 95% CI 1.03 to 1.11; 6786 participants; low-certainty evidence) while the risk of clinical worsening (new need for invasive mechanical ventilation or death) may slightly decrease (RR 0.92, 95% CI 0.84 to 1.01; 5586 participants; low-certainty evidence). For serious adverse events (two RCTs, 678 participants), adverse events (three RCTs, 447 participants), hospital-acquired infections (four RCTs, 598 participants), and invasive fungal infections (one study, 64 participants), we did not perform any analyses beyond the presentation of descriptive statistics due to very low-certainty evidence (high risk of bias, heterogeneous definitions, and underreporting). Different types, dosages or timing of systemic corticosteroids We identified one RCT (86 participants) comparing methylprednisolone to dexamethasone, thus the evidence is very uncertain about the effect of methylprednisolone on all-cause mortality (up to 30 days) (RR 0.51, 95% CI 0.24 to 1.07; 86 participants). None of the other outcomes of interest were reported in this study. We included four RCTs (1383 participants) comparing high-dose dexamethasone (12 mg or higher) to low-dose dexamethasone (6 mg to 8 mg). High-dose dexamethasone compared to low-dose dexamethasone may reduce all-cause mortality (up to 30 days) (RR 0.87, 95% CI 0.73 to 1.04; 1269 participants; low-certainty evidence), but the evidence is very uncertain about the effect of high-dose dexamethasone on all-cause mortality (up to 120 days) (RR 0.93, 95% CI 0.79 to 1.08; 1383 participants) and it may have little or no impact on clinical improvement (discharged alive at 28 days) (RR 0.98, 95% CI 0.89 to 1.09; 200 participants; low-certainty evidence). Studies did not report data on clinical worsening (new need for invasive mechanical ventilation or death). For serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections, we did not perform analyses beyond the presentation of descriptive statistics due to very low-certainty evidence. We could not identify studies for comparisons of different timing and systemic corticosteroids versus other active substances. Equity-related subgroup analyses We conducted the following subgroup analyses to explore equity-related factors: sex, age (< 70 years; ≥ 70 years), ethnicity (Black, Asian or other versus White versus unknown) and place of residence (high-income versus low- and middle-income countries). Except for age and ethnicity, no evidence for differences could be identified. For all-cause mortality up to 30 days, participants younger than 70 years seemed to benefit from systemic corticosteroids in comparison to those aged 70 years and older. The few participants from a Black, Asian, or other minority ethnic group showed a larger estimated effect than the many White participants. Outpatients with asymptomatic or mild disease There are no studies published in populations with asymptomatic infection or mild disease.
AUTHORS' CONCLUSIONS
Systemic corticosteroids probably slightly reduce all-cause mortality up to 30 days in people hospitalised because of symptomatic COVID-19, while the evidence is very uncertain about the effect on all-cause mortality up to 120 days. For younger people (under 70 years of age) there was a potential advantage, as well as for Black, Asian, or people of a minority ethnic group; further subgroup analyses showed no relevant effects. Evidence related to the most effective type, dose, or timing of systemic corticosteroids remains immature. Currently, there is no evidence on asymptomatic or mild disease (non-hospitalised participants). Due to the low to very low certainty of the current evidence, we cannot assess safety adequately to rule out harmful effects of the treatment, therefore there is an urgent need for good-quality safety data. Findings of equity-related subgroup analyses should be interpreted with caution because of their explorative nature, low precision, and missing data. We identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design, suggesting there may be possible changes of the effect estimates and certainty of the evidence in the future.
Topics: Humans; Aged; Aged, 80 and over; Adrenal Cortex Hormones; Methylprednisolone; Dexamethasone; Invasive Fungal Infections; Randomized Controlled Trials as Topic; COVID-19 Drug Treatment; Post-Acute COVID-19 Syndrome
PubMed: 36385229
DOI: 10.1002/14651858.CD014963.pub2 -
Radiotherapy and Oncology : Journal of... Jun 2024High-level evidence on hypofractionated proton therapy (PT) for localized and locally advanced prostate cancer (PCa) patients is currently missing. The aim of this study... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-level evidence on hypofractionated proton therapy (PT) for localized and locally advanced prostate cancer (PCa) patients is currently missing. The aim of this study is to provide a systematic literature review to compare the toxicity and effectiveness of curative radiotherapy with photon therapy (XRT) or PT in PCa.
METHODS
PubMed, Embase, and the Cochrane Library databases were systematically searched up to April 2022. Men with a diagnosis of PCa who underwent curative hypofractionated RT treatment (PT or XRT) were included. Risk of grade (G) ≥ 2 acute and late genitourinary (GU) OR gastrointestinal (GI) toxicity were the primary outcomes of interest. Secondary outcomes were five-year biochemical relapse-free survival (b-RFS), clinical relapse-free, distant metastasis-free, and prostate cancer-specific survival. Heterogeneity between study-specific estimates was assessed using Chi-square statistics and measured with the I2 index (heterogeneity measure across studies).
RESULTS
A total of 230 studies matched inclusion criteria and, due to overlapped populations, 160 were included in the present analysis. Significant lower rates of G ≥ 2 acute GI incidence (2 % vs 7 %) and improved 5-year biochemical relapse-free survival (95 % vs 91 %) were observed in the PT arm compared to XRT. PT benefits in 5-year biochemical relapse-free survival were maintained for the moderate hypofractionated arm (p-value 0.0122) and among patients in intermediate and low-risk classes (p-values < 0.0001 and 0.0368, respectively). No statistically relevant differences were found for the other considered outcomes.
CONCLUSION
The present study supports that PT is safe and effective for localized PCa treatment, however, more data from RCTs are needed to draw solid evidence in this setting and further effort must be made to identify the patient subgroups that could benefit the most from PT.
Topics: Humans; Male; Photons; Prostatic Neoplasms; Proton Therapy; Radiation Dose Hypofractionation
PubMed: 38561122
DOI: 10.1016/j.radonc.2024.110264