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Annals of Palliative Medicine Sep 2022To study and review the effectiveness of oral care interventions for palliative patients for amelioration of clinical conditions affecting oral cavity.
BACKGROUND
To study and review the effectiveness of oral care interventions for palliative patients for amelioration of clinical conditions affecting oral cavity.
METHODS
Following PRISMA standard, a systematic evaluation of articles published between 2000 and 2021 was undertaken utilising five databases on interventions studies. This comprehensive review consists of randomised controlled trials (RCTs) and specific types of non-randomised studies (NRS) examining oral care interventions for palliative patients. Three independent authors screened search records, identified related studies, extracted data and evaluated risk of bias. The key findings of each study were summarised according to the research questions and data that generated during the data extraction procedure.
RESULTS
Out of the 67 identified studies, seven were included in this review (five RCTs and two NRSs) involving head-and-neck cancer, oral cancer, oral mucositis, xerostomia and individuals with malignant disease. Interventions studied were: Ziziphus honey, artificial saliva, CAM2028-Benzydamine, morphine mouthwash, ketamine mouthwash, bethanechol tablets and caphosol with regular oral-care. The durations of interventions in the included studies were largely short-term (six weeks or less). Overall, six studies revealed good results in support of the intervention, with magnitudes of effect ranging from 13.2-10,110.0%. However, just four researches found significant changes, with magnitudes of effect ranging from 50.0-10,110.0%. Although two of the trials have not revealed significant changes in the results, investigations have indicated a reduction in oral conditions in the group with interventions. Only one trial has not indicated an improvement in oral conditions in the groups which received the interventions.
DISCUSSION
By assessing the efficacy of available oral hygiene interventions for palliative patients, this systematic review can help palliative team finds the viable strategies to apply in controlling oral problems among hospice patients. Even though only four of the seven research found a statistically significant difference, most studies found great effectiveness in favour of intervention.
Topics: Benzydamine; Bethanechol; Head and Neck Neoplasms; Humans; Ketamine; Morphine Derivatives; Mouthwashes; Palliative Care; Saliva, Artificial
PubMed: 36096743
DOI: 10.21037/apm-22-215 -
Daru : Journal of Faculty of Pharmacy,... Dec 2022Since the US Food and Drug Administration (FDA) approved ibrutinib to treat patients with refractory/relapsed mantle cell lymphoma (R/R MCL), it is used in clinical... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Since the US Food and Drug Administration (FDA) approved ibrutinib to treat patients with refractory/relapsed mantle cell lymphoma (R/R MCL), it is used in clinical trials, whether as a single agent or in combination with other chemotherapy agents. The efficacy and safety of ibrutinib administration alone or in combinations have not been studied systematically. This study systematically reviewed the efficacy and safety of ibrutinib-containing regimens for the treatment of patients with MCL.
EVIDENCE ACQUISITION
We performed a systematic search in PubMed, Cochrane CENTRAL, Embase, Web of Science, and Scopus. Then, a team of independent reviewers selected relevant studies and extracted the data.
RESULTS
From a total of 1,436 studies, 12 trials were eligible. The overall response rates (ORRs) of patients with R/R MCL receiving single-agent ibrutinib ranged between 62.7% to 93.8%, and the ORRs of ibrutinib combinations ranged from 74 to 88%. In patients with newly diagnosed MCL receiving ibrutinib and rituximab, ORR ranged from 84 to 100%. The highest progression-free survival (PFS) was reported in patients receiving ibrutinib and rituximab (43 months). The meta-analysis performed on adverse events (AEs) demonstrated that single-agent ibrutinib had a high risk of bleeding, nausea, and diarrhea.
CONCLUSION
Single-agent ibrutinib showed acceptable efficacy and safety in the treatment of patients with MCL. Moreover, combining ibrutinib with other agents such as rituximab, venetoclax, and ublituximab can increase its efficacy and reduce chemotherapy-induced resistance in most cases; however, in the case of combination therapy, patients need to be monitored more strictly in terms of AEs. In our review, the ibrutinib and rituximab combination showed promising results in patients with R/R MCL. Also, this combination showed favorable efficacy and safety in patients with newly diagnosed untreated MCL, making it a great candidate to be studied more in large and well-designed trials.
Topics: Adult; Humans; Lymphoma, Mantle-Cell; Rituximab; Pyrimidines; Pyrazoles
PubMed: 36057010
DOI: 10.1007/s40199-022-00444-w -
Efficacy and safety of ruxolitinib in steroid-refractory graft-versus-host disease: A meta-analysis.Frontiers in Immunology 2022Ruxolitinib is an important treatment for steroid refractory graft-versus-host disease (SR-GVHD). Therefore, we reported the updated results of a systematic review and... (Meta-Analysis)
Meta-Analysis
Ruxolitinib is an important treatment for steroid refractory graft-versus-host disease (SR-GVHD). Therefore, we reported the updated results of a systematic review and meta-analysis of ruxolitinib as treatment for SR-GVHD. In addition, we wanted to compare the efficacy and safety between children and adults with SR-GVHD. Overall response rate (ORR) after ruxolitinib treatment was chosen as the primary end point. Complete response rate (CRR), infection, myelosuppression, and overall survival (OS) were chosen as secondary end points. A total of 37 studies were included in this meta-analysis, and 1,580 patients were enrolled. ORR at any time after ruxolitinib treatment was 0.77 [95% confidence interval (CI): 0.68-0.84] and 0.78 (95% CI: 0.74-0.81), respectively, for SR-aGVHD and SR-cGVHD. CRR at any time after ruxolitinib treatment was 0.49 (95% CI: 0.40-0.57) and 0.15 (95% CI: 0.10-0.23), respectively, for SR-aGVHD and SR-cGVHD. The ORRs at any time after treatment was highest in mouth SR-cGVHD, followed by skin, gut, joints and fascia, liver, eyes, esophagus, and lung SR-cGVHD. The incidence rate of infections after ruxolitinib treatment was 0.61 (95% CI: 0.45-0.76) and 0.47 (95% CI: 0.31-0.63), respectively, for SR-aGVHD and SR-cGVHD. The incidence rates of overall (grades I-IV) and severe (grades III-IV) cytopenia were 53.2% (95% CI: 16.0%-90.4%) and 31.0% (95% CI: 0.0-100.0%), respectively, for SR-aGVHD, and were 28.8% (95% CI:13.0%-44.6%) and 10.4% (95% CI: 0.0-27.9%), respectively, for SR-cGVHD. The probability rate of OS at 6 months after treatment was 63.9% (95% CI: 52.5%-75.2%) for SR-aGVHD. The probability rates of OS at 6 months, 1 year, and 2 years after treatment were 95% (95% CI: 79.5%-100.0%), 78.7% (95% CI: 67.2%-90.1%), and 75.3% (95% CI: 68.0%-82.7%), respectively, for SR-cGVHD. The ORR, CRR, infection events, and myelosuppression were all comparable between children and adults with SR-GVHD. In summary, this study suggests that ruxolitinib is an effective and safe treatment for SR-GVHD, and both children and adults with SR-GVHD could benefit from ruxolitinib treatment.
Topics: Adult; Child; Graft vs Host Disease; Humans; Nitriles; Pyrazoles; Pyrimidines; Steroids
PubMed: 35990629
DOI: 10.3389/fimmu.2022.954268 -
PloS One 2022Hematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hematopoietic stem cell transplantation (HSCT) for haematological disorders. Graft-versus-host disease (GVHD), a cause of morbidity and mortality is treated with corticosteroids. However, patients with steroid-refractory GVHD after HSCT have a poor prognosis. Ruxolitinib, a selective Janus kinase inhibitor, is a novel treatment strategy for steroid-refractory GVHD.
OBJECTIVES
To assess the efficacy of ruxolitinib for the treatment of steroid-refractory GVHD and analyse its adverse effects.
STUDY DESIGN
Meta-analysis.
SEARCH METHODS
Randomised controlled trials (RCTs) and non-RCTs of ruxolitinib-based therapy in patients with steroid-refractory GVHD were found in the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, and Web of Science in March 2021. Outcomes included overall response rate, survival, and adverse effects. The Methodological Index for Non-randomised Studies (MINORS) and the Cochrane collaboration risk-of-bias tool were used to assess methodological quality. Funnel plots, Egger's test, and the trim and fill method were used to assess publication bias.
RESULTS
In total, 1470 studies were identified; 19 studies (17 non-RCTs, 2 RCTs) involving 1358 patients met our inclusion criteria. Survival rates at the longest follow-up in non-RCTs, were 57.5% (95% CI 46.9-67.4) and 80.3% (95% CI 69.7-87.9) for acute GVHD (aGVHD) and chronic GVHD (cGVHD), respectively. In non-RCTs, the overall response was 74.9% (95% CI 66.6-81.8, I2 = 49%) in aGVHD and 73.1% (95% CI 62.5-81.6, I2 = 49%) in cGVHD. In aGVHD, the response rates were gastrointestinal, 61.4-90.2%; skin, 52.5-80.6%; and liver, 41.8-71.8%. In cGVHD, the response rates were gastrointestinal, 30.1-70.4%; skin, 30.1-84.4%; lung, 27.0-83.0%; and mouth 3.5-98.1%. In addition, a lower aGVHD grade and moderate cGVHD were associated with a better clinical response. Common adverse events were cytopenia and infectious complications.
CONCLUSIONS
Our systematic review and meta-analysis indicated that ruxolitinib therapy could be a potentially effective and safe treatment for patients with steroid-refractory GVHD.
Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Nitriles; Pyrazoles; Pyrimidines; Steroids
PubMed: 35905125
DOI: 10.1371/journal.pone.0271979 -
Cardiovascular Therapeutics 2022Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates the effectiveness and safety of both NOACs versus standard of care (SoC) in real-world practice.
METHODS
Real-world evidence (RWE) studies were identified through a systematic literature review conducted between January 2012 and July 2020, using Embase, MEDLINE, and the websites of cardiological, hematological, and oncological associations. Eligible RWE studies recruited adult patients with deep vein thrombosis and/or pulmonary embolism and presented a comparison between rivaroxaban and apixaban versus SoC, consisting either of vitamin K antagonists, heparins, or combinations thereof. Hazard ratios (HRs) for the comparison between NOACs and SoC were extracted from the relevant studies or estimated based on the reported binary data. The between-treatment contrasts were reported as HRs with associated 95% confidence intervals.
RESULTS
A total of 65 RWE studies were identified and considered relevant for the meta-analysis. Compared with SoC, both rivaroxaban and apixaban were associated with reduced risks of recurrent VTE and a lower rate of major bleeding events. Patients treated with rivaroxaban were at a lower risk of all-cause death compared with those receiving SoC (HR = 0.56 [0.39-0.80]), while evidence for apixaban from the identified studies was insufficient to demonstrate a statistically significant change in mortality (HR = 0.66 [0.30-1.47]).
CONCLUSION
This analysis indicates that in real-world practice, rivaroxaban and apixaban are associated with a lower risk of recurrent VTE and major bleeding events compared with SoC. Survival benefit in patients treated with rivaroxaban was also observed.
Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thromboembolism
PubMed: 35801133
DOI: 10.1155/2022/2756682 -
Value in Health : the Journal of the... Jun 2022The study objective was to investigate the economic value of tumor-agnostic therapies when only single-arm effectiveness data are available at launch by applying...
OBJECTIVES
The study objective was to investigate the economic value of tumor-agnostic therapies when only single-arm effectiveness data are available at launch by applying multiple methodologies to establish comparative effectiveness.
METHODS
In the absence of direct comparative data, 3 methods were used to estimate the counterfactual: (1) a historical control based on a systematic literature review for each tumor site from the larotrectinib trials, (2) an intracohort comparison using the previous line of therapy time to progression from larotrectinib trials, and (3) a nonresponder control that applied outcomes for larotrectinib nonresponders. Cost-effectiveness was modeled using the partitioned survival approach. Stochastic parameter uncertainty was assessed in a probabilistic sensitivity analysis (PSA). A triangulated estimate of the mean cost-effectiveness result was generated combining all 3 counterfactual estimates.
RESULTS
Incremental cost-effectiveness ratios were similar across the 3 methodologies in the deterministic analysis ranging from £83 868 (95% uncertainty interval [UI] £65 698-£107 668) to £104 922 per quality-adjusted life-year (95% UI £80 132-£139 658). PSA results for each method substantially overlapped when plotted on the cost-effectiveness plane. Weighting PSA results for each method equally in the triangulation method produced an incremental cost-effectiveness ratios of £95 587 per quality-adjusted life-year gained (95% UI £70 449-£137 431).
CONCLUSIONS
In the absence of direct comparative data, different methods of estimating a counterfactual are possible, each with strengths and limitations. Triangulating results across the methods provides a composite view of the total uncertainty and a more consistent estimation of the cost-effectiveness of the tumor-agnostic intervention compared with choosing a single method.
Topics: Cost-Benefit Analysis; Humans; Pyrazoles; Pyrimidines; Quality-Adjusted Life Years
PubMed: 35667773
DOI: 10.1016/j.jval.2021.11.1354 -
World Journal of Urology Oct 2022The treatment landscape in metastatic renal cell carcinoma (mRCC) has evolved dramatically in recent years. Within the German guideline committee for RCC we evaluated...
PURPOSE
The treatment landscape in metastatic renal cell carcinoma (mRCC) has evolved dramatically in recent years. Within the German guideline committee for RCC we evaluated current medical treatments and gave recommendations.
METHODS
A systematic review of published evidence for medical treatment of mRCC was performed (July 2016-August 2019) to cover the duration from last guideline update in 2016. Evidence was graded according to SIGN ( http://www.sign.ac.uk/pdf/sign50.pdf ). Recommendations were made on the basis of a nominal group work with consensus approach and included patient advocates and shareholder of the German RCC treatment landscape. Each recommendation was graded according to its strength as strong recommendation (A) or recommendation (B). Expert statements were given, where appropriate.
RESULTS
Strong first-line recommendations (IA) exist for axitinib + pembrolizumab (all risk categories) and ipilimumab + nivolumab (intermediate or poor risk only). Axitinib + avelumab is a recommended first-line treatment across patients with any risk category (IB). In patients who are not candidates for immune check point inhibitor (ICI) combinations, targeted agents should be offered as an alternative treatment. Subsequent treatment after ICI-based combinations remain ill-defined and no standard of care can be formulated.
CONCLUSION
ICI-based combinations are the first-line standard of care and should be considered accordingly. There is an unmet medical need for pivotal studies that define novel standards in patients with failure of ICI-based combinations.
Topics: Axitinib; Carcinoma, Renal Cell; Humans; Ipilimumab; Kidney Neoplasms; Nivolumab
PubMed: 35562599
DOI: 10.1007/s00345-022-04015-1 -
Pain Nov 2022Burrowing behaviour is used to assess pain-associated behaviour in laboratory rodents. To gain insight into how models of disease-associated persistent pain and... (Meta-Analysis)
Meta-Analysis
Burrowing behaviour is used to assess pain-associated behaviour in laboratory rodents. To gain insight into how models of disease-associated persistent pain and analgesics affect burrowing behaviour, we performed a systematic review and meta-analysis of studies that assessed burrowing behaviour. A systematic search in March 2020 and update in September 2020 was conducted in 4 databases. Study design characteristics and experimental data were extracted, followed by a random-effects meta-analysis. We explored the association between burrowing and monofilament-induced limb withdrawal. Dose response relationship was investigated for some analgesics. Forty-five studies were included in the meta-analysis, in which 16 model types and 14 drug classes were used. Most experiments used rat (79%) and male (72%) animals. Somatic inflammation and trauma-induced neuropathy models were associated with reduced burrowing behaviour. Analgesics (nonsteroidal anti-inflammatory drug and gabapentinoids) attenuated burrowing deficits in these models. Reporting of measures to reduce risk of bias was unclear except for randomisation which was high. There was not a correlation ( R2 = 0.1421) between burrowing and monofilament-induced limb withdrawal. Opioids, gabapentin, and naproxen showed reduced burrowing behaviour at high doses, whereas ibuprofen and celecoxib showed opposite trend. The findings indicate that burrowing could be used to assess pain-associated behaviour. We support the use of a portfolio of composite measures including spontaneous and stimulus-evoked tests. The information collected here could help in designing experiments involving burrowing assessment in models of disease-associated pain.
Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Celecoxib; Disease Models, Animal; Gabapentin; Ibuprofen; Male; Naproxen; Pain; Rats; Rodentia
PubMed: 35353780
DOI: 10.1097/j.pain.0000000000002632 -
Current Oncology (Toronto, Ont.) Jan 2022Patients with epithelial ovarian cancer (EOC), treated with niraparib maintenance, present with haematological and gastrointestinal toxicities. Limited data exist on... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with epithelial ovarian cancer (EOC), treated with niraparib maintenance, present with haematological and gastrointestinal toxicities. Limited data exist on niraparib safety assessment.
OBJECTIVE
To evaluate niraparib safety profile, as maintenance therapy, in women with platinum-sensitive EOC.
METHODS
PubMed and Cochrane searches were carried out up to April 2021 for randomised controlled trials (RCTs) evaluating niraparib versus placebo in EOC patients with a response to platinum-based chemotherapy. Regarding the meta-analysis, for dichotomous data, the pooled risk ratio (RR) was calculated.
RESULTS
A total of 1539 patients from three RCTs revealed that niraparib-treated patients are associated with a significantly higher risk of any grade of nausea (RR, 2.15; 95% CI, 1.86 to 2.48), fatigue (RR, 1.26; 95% CI, 1.05 to 1.52, < 0.00001), anemia (RR, 6.86; 95% CI, 2.54 to 18.52, = 0.0001), thrombocytopenia (RR, 7.02; 95% CI, 1.68 to 29.38, < 0.00001), vomiting (RR, 2.51; 95% CI, 1.50 to 4.19, = 0.0005), neutropenia (RR, 2.96; 95% CI, 1.13 to 7.73, < 0.00001), headache (RR, 2.08; 95% CI, 1.57 to 2.74, < 0.00001), constipation (RR, 2.10; 95% CI, 1.72 to 2.57, < 0.00001) and insomnia (RR, 2.48; 95% CI, 1.52 to 2.89, = 0.0003) when compared with placebo. For grade 3 or 4 adverse effects, significantly higher risk was only noted for fatigue (RR,6.25; 95% CI, 1.70 to 23.05, = 0.006), anemia (RR, 16.23; 95% CI, 4.86 to 54.17, < 0.00001), thrombocytopenia (RR, 35.12; 95% CI, 12.23 to 100.82, < 0.00001) and neutropenia episodes (RR, 6.35; 95% CI, 2.08 to 19.39, = 0.001) for those taking niraparib. Notably, incidents of adverse effects and discontinuation rates were substantially lower among patients treated with an individualised niraparib dose than those treated with the standard one. Efficacy was not reduced, and no treatment-related deaths occurred during the included trials.
CONCLUSION
Niraparib is considered an effective and well-tolerated choice, with an improved safety profile, for the maintenance treatment of EOC patients.
Topics: Carcinoma, Ovarian Epithelial; Female; Humans; Indazoles; Neoplasm Recurrence, Local; Ovarian Neoplasms; Piperidines
PubMed: 35049703
DOI: 10.3390/curroncol29010029 -
PloS One 2021To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the cardiovascular safety of celecoxib compared to non-selective non-steroid anti-inflammatory drugs or placebo.
METHODS
We included randomized controlled trials of oral celecoxib compared with a non-selective NSAID or placebo in rheumatoid arthritis and osteoarthritis patients. We conducted searches in EMBASE, Cochrane CENTRAL, MEDLINE, China National Knowledge Infrastructure, VIP, Wanfang, and Chinese Biomedical Literature Database. Study selection and data extraction were done by two authors independently. The risk of bias was assessed using Cochrane's risk-of-bias Tool for Randomized Trials. The effect size was presented as a risk ratio with their 95% confidence interval.
RESULTS
Until July 22nd, 2021, our search identified 6279 records from which, after exclusions, 21 trials were included in the meta-analysis. The overall pooled risk ratio for Antiplatelet Trialists Collaboration cardiovascular events for celecoxib compared with any non-selective non-steroid anti-inflammatory drugs was 0.89 (95% confidence interval: 0.80-1.00). The pooled risk ratio for all-cause mortality for celecoxib compared with non-selective non-steroid anti-inflammatory drugs was 0.81 (95% confidence interval: 0.66-0.98). The cardiovascular mortality rate of celecoxib was lower than non-selective non-steroid anti-inflammatory drugs (risk ratio: 0.75, 95% confidence interval: 0.57-0.99). There was no significant difference between celecoxib and non-selective non-steroid anti-inflammatory drugs or placebo in the risk of other cardiovascular events.
CONCLUSION
Celecoxib is relatively safe in rheumatoid arthritis and osteoarthritis patients, independent of dose or duration. But it remains uncertain whether this would remain the same in patients treated with aspirin and patients with established cardiovascular diseases.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cardiovascular System; Celecoxib; Humans; Osteoarthritis; Patient Safety
PubMed: 34932581
DOI: 10.1371/journal.pone.0261239