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ESMO Open Oct 2022Androgen-deprivation therapy (ADT) historically represented the milestone for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Recently, combining... (Meta-Analysis)
Meta-Analysis Review
Addition of androgen receptor-targeted agents to androgen-deprivation therapy and docetaxel in metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis.
BACKGROUND
Androgen-deprivation therapy (ADT) historically represented the milestone for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Recently, combining androgen receptor-targeted agents (ARTA) or docetaxel with ADT significantly improved clinical outcomes in this setting. The efficacy of the combined use of an ARTA with docetaxel and ADT (triplet), however, was unknown, and often conflicting data derived from subgroup analysis of randomized phase III trials. In order to better define the benefits and risks of the triplet in mHSPC, we carried out a systematic review and meta-analysis of available clinical trials.
METHODS
A literature search with no data restriction using Medline/PubMed, the Cochrane Library, and American Society of Clinical Oncology/European Society for Medical Oncology (ASCO/ESMO) Meeting abstracts was carried out up to April 2022. The meta-analysis was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statements. Overall survival (OS) was the primary endpoint; progression-free survival (PFS) and safety were secondary endpoints. For OS and PFS, summary hazard ratios (HRs) were calculated; for safety, risk ratio (RR) was assessed. Random- or fixed-effects models were used, depending on studies heterogeneity.
RESULTS
Five randomized clinical trials fulfilled the prespecified inclusion criteria. The triplet significantly improved OS (fixed-effect, HR = 0.74; P < 0.00001) and PFS (fixed-effect; HR = 0.50 for clinical PFS, HR = 0.49 for radiological PFS; P < 0.0001) compared with docetaxel plus ADT. We did not show heterogeneity between treatment efficacy and the disease burden, metachronous versus synchronous presentation, concomitant versus sequential strategy. Compared with docetaxel + ADT, the triplet did not increase the risk of adverse events (AEs) (RR = 1.00, P = 0.27 for any-grade AEs; RR = 1.13, P = 0.14 for severe AEs), except for severe hypertension (RR = 1.73, P = 0.001).
CONCLUSIONS
Emerging evidence supports the combination of an ARTA plus docetaxel and ADT in mHSPC patients. Given the availability of several strategies in this setting, clinical characteristics and drug safety profile may help clinicians select the appropriate treatment for mHSPC patients who are more likely to benefit from treatment intensification.
Topics: Male; Humans; Docetaxel; Androgen Antagonists; Prostatic Neoplasms; Androgens; Receptors, Androgen; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Agents
PubMed: 36152486
DOI: 10.1016/j.esmoop.2022.100575 -
The Cochrane Database of Systematic... Oct 2012Cervical cancer is the second most common cancer among women up to 65 years of age and is the most frequent cause of death from gynaecological cancers worldwide. A... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cervical cancer is the second most common cancer among women up to 65 years of age and is the most frequent cause of death from gynaecological cancers worldwide. A woman's risk of developing cervical cancer by 65 years of age ranges from 0.69% in developed countries to 1.38% in developing countries. Although screening by Pap smear should mean early detection at a curable stage for most women, many still present with advanced or metastatic disease with a worse prognosis. The addition of platinum-based chemotherapy to radiotherapy has improved outcome compared to radiotherapy alone; however, 30% to 50% fail to respond to treatment or develop recurrent disease. There are no standard treatment options for these patients, although platinum-based chemotherapy is frequently used and trials are on-going.
OBJECTIVES
To compare different types and combinations of cytotoxic chemotherapy for the treatment of metastatic/recurrent cervical cancer.
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2012), MEDLINE (1950 to January 2012) and EMBASE (1980 to January 2012). The reference lists from these and those of review articles were also checked.
SELECTION CRITERIA
All randomised controlled trials (RCTs) involving chemotherapy for metastatic/recurrent cervical cancer. Trials involving radiotherapy, chemoradiotherapy, intra-arterial chemotherapy, biological agents or immunomodulators were excluded.
DATA COLLECTION AND ANALYSIS
Three review authors independently reviewed trials for inclusion and data extraction and assessed risk of bias.
MAIN RESULTS
There were no data comparing best supportive care with chemotherapy. Cisplatin-based regimens are the most widely used and therefore we have concentrated on these trials. In terms of response rates some non-platinum regimens are equivalent but toxicity is higher. The most common cisplatin regimen was 50 mg/m(2) day 1 q21days. Higher doses had similar survivals. There was no direct comparison between single-agent cisplatin and carboplatin. Overall survival (OS) and progression-free survival (PFS) were not adequately reported and quality of life (QoL) outcomes were incompletely documented. Combination regimens were more toxic than single agents, but in the limited reported data this did not appear to adversely affect QoL.No significant difference in response rate by site of recurrence was found, although there was a trend towards improved response when the main site of disease was beyond the previously irradiated pelvis.
AUTHORS' CONCLUSIONS
Combination cisplatin-based chemotherapy could be a viable option for patients of good performance status with recurrent/metastatic cervical cancer, but further trials that report adequate survival and QoL data are sought. Response rates and improvements in survival are low. Cisplatin-based combinations have significant toxicity. Outcomes are poor and novel cytotoxic/biological agents and optimal scheduling need further investigation. Future trials need to stratify for and perform planned subgroup analysis with respect to previous treatment and site of recurrence.
Topics: Adult; Age Factors; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Uterine Cervical Neoplasms; Young Adult
PubMed: 23076924
DOI: 10.1002/14651858.CD006469.pub2 -
BMC Surgery Aug 2018A wide variety of hemostats are available as adjunctive measures to improve hemostasis during surgical procedures if residual bleeding persists despite correct... (Review)
Review
BACKGROUND
A wide variety of hemostats are available as adjunctive measures to improve hemostasis during surgical procedures if residual bleeding persists despite correct application of conventional methods for hemorrhage control. Some are considered active agents, since they contain fibrinogen and thrombin and actively participate at the end of the coagulation cascade to form a fibrin clot, whereas others to be effective require an intact coagulation system. The aim of this study is to provide an evidence-based approach to correctly select the available agents to help physicians to use the most appropriate hemostat according to the clinical setting, surgical problem and patient's coagulation status.
METHODS
The literature from 2000 to 2016 was systematically screened according to PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses] protocol. Sixty-six articles were reviewed by a panel of experts to assign grade of recommendation (GoR) and level of evidence (LoE) using the GRADE [Grading of Recommendations Assessment, Development and Evaluation] system, and a national meeting was held.
RESULTS
Fibrin adhesives, in liquid form (fibrin glues) or with stiff collagen fleece (fibrin patch) are effective in the presence of spontaneous or drug-induced coagulation disorders. Mechanical hemostats should be preferred in patients who have an intact coagulation system. Sealants are effective, irrespective of patient's coagulation status, to improve control of residual oozing. Hemostatic dressings represent a valuable option in case of external hemorrhage at junctional sites or when tourniquets are impractical or ineffective.
CONCLUSIONS
Local hemostatic agents are dissimilar products with different indications. A knowledge of the properties of each single agent should be in the armamentarium of acute care surgeons in order to select the appropriate product in different clinical conditions.
Topics: Administration, Topical; Emergencies; Hemorrhage; Hemostatics; Humans; Wounds and Injuries
PubMed: 30157821
DOI: 10.1186/s12893-018-0398-z -
International Journal of Molecular... Apr 2024In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic... (Review)
Review
In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question "What therapeutic targets have been used in in silico analysis for the treatment of obesity?" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an "unclear risk of bias" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity.
Topics: Humans; Obesity; Animals; Computer Simulation; Molecular Docking Simulation; Anti-Obesity Agents; Lipase; Molecular Targeted Therapy
PubMed: 38731918
DOI: 10.3390/ijms25094699 -
Journal of Medical Virology Sep 2021The newborn coronaivus disease 2019 (COVID-19) pandemic has become the foremost concern of health system worldwide. Interferon typeI (IFN-I) are among the well-known... (Review)
Review
The newborn coronaivus disease 2019 (COVID-19) pandemic has become the foremost concern of health system worldwide. Interferon typeI (IFN-I) are among the well-known antiviruses. Hence IFN-α have gained much attention as a treatment for COVID-19 recently. To sum up the efficiency of IFN-α against COVID-19, we searched PubMed, SCOPUS, and EMBASE, from the date of genesis to the 1st of October 2020. Discharge from hospital and virus clearance considered as primary and secondary outcomes, respectively. We compared the aforementioned outcomes of patients treated with standard care protocol and the patients treated with IFN-α in addition to standard care protocol. Out of 356 identified records, 14 studies were subjected for full-text screening. Finally, a systematic review was performed with inclusion of five studies. Majority of the participants were males (ranged from 43.50% to 90.0%). We found that time of viral clearance and polymerase chain reaction negative (days) in most studies were decreased in the INF-α + standard care group. The mean days of virus's clearance in INF-α group and standard group reported 27.3 and 32.43. Likewise, the average days of hospitalization was found also lower in INF-α group (18.55 vs. 24.36). This study provides a stand to conclude that early administration of INF-α may be accounted as a promising treatment of COVID-19.
Topics: Adult; Antiviral Agents; Clinical Trials as Topic; Female; Humans; Interferon-alpha; Male; Middle Aged; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34101851
DOI: 10.1002/jmv.27072 -
Drug Safety Jun 2021Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic...
INTRODUCTION AND OBJECTIVE
Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic review was to explore the evidence in the literature on the safety and efficacy of their use as monotherapy and combination therapy in COVID-19 management.
METHODS
After prospectively registering the study protocol with the Open Science Framework, we searched PubMed, Google Scholar, clinicaltrials.gov, various pre-print servers and reference lists for relevant records published until 16 February, 2021 using appropriate search strategies. Baseline features and data pertaining to efficacy and safety outcomes were extracted separately for IVM monotherapy, DOXY monotherapy, and IVM + DOXY combination therapy. Methodological quality was assessed based on the study design.
RESULTS
Out of 200 articles screened, 19 studies (six retrospective cohort studies, seven randomised controlled trials, five non-randomised trials, one case series) with 8754 unique patients with multiple stages of COVID-19 were included; four were pre-prints and one was an unpublished clinicaltrials.gov document. The comparator was standard care and 'hydroxychloroquine + azithromycin' in seven and three studies respectively, and two studies were placebo controlled; six studies did not have a comparator. IVM monotherapy, DOXY monotherapy and IVM + DOXY were explored in eight, five and five studies, respectively; one study compared IVM monotherapy and IVM + DOXY with placebo. While all studies described efficacy, the safety profile was described in only six studies. Efficacy outcomes were mixed with some studies concluding in favour of the intervention and some studies displaying no significant benefit; barring one study that described 9/183 patients with erosive esophagitis and non-ulcer dyspepsia with IVM + DOXY (without causality assessment details), there were no new safety signals of concern with any of the three interventions considered. The quality of studies varied widely, with five studies having a 'good' methodological quality.
CONCLUSIONS
Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management.
SYSTEMATIC REVIEW PROTOCOL REGISTRATION DETAILS
Open Science Framework: https://osf.io/n7r2j .
Topics: Anti-Infective Agents; Doxycycline; Drug Therapy, Combination; Humans; Ivermectin; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33864232
DOI: 10.1007/s40264-021-01066-y -
Health Technology Assessment... Feb 2004To examine the clinical effectiveness and cost-effectiveness of oral capecitabine for locally advanced and metastatic breast cancer in relation to its licensed... (Comparative Study)
Comparative Study Review
OBJECTIVE
To examine the clinical effectiveness and cost-effectiveness of oral capecitabine for locally advanced and metastatic breast cancer in relation to its licensed indications.
DATA SOURCES
Twenty-three electronic databases and other databases of ongoing research and Internet resources, bibliographies of retrieved articles and industry submissions.
REVIEW METHODS
Two reviewers independently screened and assessed all titles and/or abstracts including economic evaluations. Randomised controlled trials (RCTs) and observational studies that investigated capecitabine monotherapy, in patients pretreated with an anthracycline-containing regimen or a taxane, or capecitabine in combination with docetaxel, in patients pretreated with an anthracycline-containing regimen, were included. The economic evaluation was based on data reported in the manufacturer's submission.
RESULTS
For capecitabine monotherapy, 12 uncontrolled observational studies were identified. The methodological quality of the studies was low. Capecitabine demonstrated antitumour activity, but was associated with a particular risk of hand-foot syndrome and diarrhoea. Economic evaluation was hampered by the poor quality of the published studies, but compared indirectly with vinorelbine, capecitabine was associated with lower costs and improved patient outcomes. For capecitabine in combination with docetaxel, one RCT was identified. Combination therapy was superior to single-agent docetaxel in terms of survival, time to disease progression and overall response. Adverse events occurred more frequently with combination therapy. The economic evaluation demonstrated an overall improved QALY score for combination therapy with a slight reduction in costs.
CONCLUSIONS
No conclusions could be drawn regarding the therapeutic benefit of capecitabine monotherapy; RCTs are required. Capecitabine appeared cost-effective compared with vinorelbine, but serious doubts remain; the poor quality of the trials may invalidate this conclusion. Based on limited evidence, combination therapy was more effective than single-agent docetaxel and likely to be cost-effective, but was associated with higher incidences of hand-foot syndrome, nausea, diarrhoea and stomatitis.
Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Cost-Benefit Analysis; Deoxycytidine; Disease Progression; Docetaxel; Drug Therapy, Combination; Female; Fluorouracil; Humans; Neoplasm Metastasis; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; State Medicine; Survival Rate; Taxoids; Treatment Outcome; United Kingdom
PubMed: 14960257
DOI: 10.3310/hta8050 -
Survey of Ophthalmology 2016Intraocular tuberculosis remains a diagnostic and management conundrum for both ophthalmologists and pulmonologists. We analyze the efficacy and safety of... (Meta-Analysis)
Meta-Analysis Review
Intraocular tuberculosis remains a diagnostic and management conundrum for both ophthalmologists and pulmonologists. We analyze the efficacy and safety of anti-tubercular therapy (ATT) in patients with intraocular tuberculosis and factors associated with favorable outcome. Twenty-eight studies are included in this review, with a total of 1,917 patients. Nonrecurrence of inflammation was observed in pooled estimate of 84% of ATT-treated patients (95% CI 79-89). There was minimal difference in the outcome between patients treated with ATT alone (85% successful outcome; 95% CI 25-100) and those with concomitant systemic corticosteroid (82%; 95% CI 73-90). The use of ATT may be of benefit to patients with suspected intraocular tuberculosis; however, this conclusion is limited by the lack of control group analysis and standardized recruitment and treatment protocols. We propose further prospective studies to better establish the efficacy of ATT and ascertain the factors associated with favorable treatment outcomes.
Topics: Anti-Inflammatory Agents; Antitubercular Agents; Disease Management; Humans; Prognosis; Tuberculosis, Ocular
PubMed: 26970263
DOI: 10.1016/j.survophthal.2016.03.001 -
Medicine Aug 2020COVID-19 is a global public health emergency. At present, there is no highly effective medicine for the prevention and treatment of 2019-nCoV. Western medicine for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
COVID-19 is a global public health emergency. At present, there is no highly effective medicine for the prevention and treatment of 2019-nCoV. Western medicine for COVID-19 is mainly based on symptomatic support therapy. Chinese herbal medicine has been used to prevent infectious diseases for thousands of years in China. Western medicine routine treatment combined with Chinese herbal medicine is an alternative clinical option but lacks evidence-based medical evidence. The systematic review protocol aims to formulate a research plan that can evaluate the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine for COVID-19.
METHODS
We will search the following eight databases: Cochrane Library, PubMed, Embase, Medline, CNKI, Wanfang, VIP, and CBM. The search time is up to the end of July 2020. Two authors will independently complete literature screening, data extraction, and risk of bias assessment. In case of disagreement, the third author will assist in the judgment. The primary outcome will be the clinical cure rate. The secondary outcome will be accounting symptoms, fever time, time of virus nucleic acid turning negative, check the condition by drawing blood, pneumonia absorption rate, patient hospitalization time, severe conversion rate and case fatality rate, adverse reactions, and adverse events. Revman 5.3 will be used for systematic reviews and meta-analysis. The report of the protocol will follow the PRISMA-P statement, and the report of the systematic review and meta-analysis will follow the PRISMA statement.
RESULTS
We will provide evidence-based medical evidence of the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine for COVID-19. The findings will be published in peer-reviewed journals.
REGISTRATION DETAILS
CRD42020190106.
Topics: Anti-Infective Agents; Antiviral Agents; COVID-19; China; Combined Modality Therapy; Coronavirus Infections; Drugs, Chinese Herbal; Female; Humans; Male; Medicine, Chinese Traditional; Pandemics; Patient Safety; Pneumonia, Viral; Severe Acute Respiratory Syndrome; Survival Analysis; Treatment Outcome; United States
PubMed: 32769922
DOI: 10.1097/MD.0000000000021616 -
Parasitology Nov 2022From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease... (Review)
Review
From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day, 200 mg day, 150 mg day and 2.5 mg kg) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.
Topics: Humans; Trypanosoma cruzi; Trypanocidal Agents; Allopurinol; Randomized Controlled Trials as Topic; Chagas Disease; Nitroimidazoles; Drug Therapy, Combination; Treatment Outcome
PubMed: 35957576
DOI: 10.1017/S0031182022001081