OBJECTIVES: To evaluate the benefits and harms of tamoxifen or tamoxifen plus any other anticancer drugs compared with no intervention, placebo, any type of standard care, or alternative treatment in adults with hepatocellular carcinoma, irrespective of sex, administered dose, type of formulation, and duration of treatment.
SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, three other databases, and major trials registries, and handsearched reference lists up to 26 March 2024.
ELIGIBILITY CRITERIA: Parallel-group randomised clinical trials including adults (aged 18 years and above) diagnosed with advanced or unresectable hepatocellular carcinoma. Had we found cross-over trials, we would have included only the first trial phase. We did not consider data from quasi-randomised trials for analysis.
OUTCOMES: Our critical outcomes were all-cause mortality, serious adverse events, and health-related quality of life. Our important outcomes were disease progression, and adverse events considered non-serious.
RISK OF BIAS: We assessed risk of bias using the RoB 2 tool.
SYNTHESIS METHODS: We used standard Cochrane methods and Review Manager. We meta-analysed the outcome data at the longest follow-up. We presented the results of dichotomous outcomes as risk ratios (RR) and continuous data as mean difference (MD), with 95% confidence intervals (CI) using the random-effects model. We summarised the certainty of evidence using GRADE.
INCLUDED STUDIES: We included 10 trials that randomised 1715 participants with advanced, unresectable, or terminal stage hepatocellular carcinoma. Six were single-centre trials conducted in Hong Kong, Italy, and Spain, while three were conducted as multicentre trials in single countries (France, Italy, and Spain), and one trial was conducted in nine countries in the Asia-Pacific region (Australia, Hong Kong, Indonesia, Malaysia, Myanmar, New Zealand, Singapore, South Korea, and Thailand). The experimental intervention was tamoxifen in all trials. The control interventions were no intervention (three trials), placebo (six trials), and symptomatic treatment (one trial). Co-interventions were best supportive care (three trials) and standard care (one trial). The remaining six trials did not provide this information. The number of participants in the trials ranged from 22 to 496 (median 99), mean age was 63.7 (standard deviation 4.18) years, and mean proportion of men was 74.7% (standard deviation 42%). Follow-up was three months to five years.
SYNTHESIS OF RESULTS: Ten trials evaluated oral tamoxifen at five different dosages (ranging from 20 mg per day to 120 mg per day). All trials investigated one or more of our outcomes. We performed meta-analyses when at least two trials assessed similar types of tamoxifen versus similar control interventions. Eight trials evaluated all-cause mortality at varied follow-up points. Tamoxifen versus the control interventions (i.e. no treatment, placebo, and symptomatic treatment) results in little to no difference in mortality between one and five years (RR 0.99, 95% CI 0.92 to 1.06; 8 trials, 1364 participants; low-certainty evidence). In total, 488/682 (71.5%) participants died in the tamoxifen groups versus 487/682 (71.4%) in the control groups. The separate analysis results for one, between two and three, and five years were comparable to the analysis result for all follow-up periods taken together. The evidence is very uncertain about the effect of tamoxifen versus no treatment on serious adverse events at one-year follow-up (RR 0.44, 95% CI 0.19 to 1.06; 1 trial, 36 participants; very low-certainty evidence). A total of 5/20 (25.0%) participants in the tamoxifen group versus 9/16 (56.3%) participants in the control group experienced serious adverse events. One trial measured health-related quality of life at baseline and at nine months' follow-up, using the Spitzer Quality of Life Index. The evidence is very uncertain about the effect of tamoxifen versus no treatment on health-related quality of life (MD 0.03, 95% CI -0.45 to 0.51; 1 trial, 420 participants; very low-certainty evidence). A second trial found no appreciable difference in global health-related quality of life scores. No further data were provided. Tamoxifen versus control interventions (i.e. no treatment, placebo, or symptomatic treatment) results in little to no difference in disease progression between one and five years' follow-up (RR 1.02, 95% CI 0.91 to 1.14; 4 trials, 720 participants; low-certainty evidence). A total of 191/358 (53.3%) participants in the tamoxifen group versus 198/362 (54.7%) participants in the control group had progression of hepatocellular carcinoma. Tamoxifen versus control interventions (i.e. no treatment or placebo) may have little to no effect on adverse events considered non-serious during treatment, but the evidence is very uncertain (RR 1.17, 95% CI 0.45 to 3.06; 4 trials, 462 participants; very low-certainty evidence). A total of 10/265 (3.8%) participants in the tamoxifen group versus 6/197 (3.0%) participants in the control group had adverse events considered non-serious. We identified no trials with participants diagnosed with early stages of hepatocellular carcinoma. We identified no ongoing trials.
AUTHORS' CONCLUSIONS: Based on the low- and very low-certainty evidence, the effects of tamoxifen on all-cause mortality, disease progression, serious adverse events, health-related quality of life, and adverse events considered non-serious in adults with advanced, unresectable, or terminal stage hepatocellular carcinoma when compared with no intervention, placebo, or symptomatic treatment could not be established. Our findings are mostly based on trials at high risk of bias with insufficient power (fewer than 100 participants), and a lack of trial data on clinically important outcomes. Therefore, firm conclusions cannot be drawn. Trials comparing tamoxifen administered with any other anticancer drug versus standard care, usual care, or alternative treatment as control interventions were lacking. Evidence on the benefits and harms of tamoxifen in participants at the early stages of hepatocellular carcinoma was also lacking.
FUNDING: This Cochrane review had no dedicated funding.
REGISTRATION: Protocol available via DOI: 10.1002/14651858.CD014869.
OBJECTIVES: To evaluate the benefits and harms of gene therapy in people with hepatocellular carcinoma, irrespective of sex, administered dose, and type of formulation.
SEARCH METHODS: We identified randomised clinical trials through electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We searched five online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The date of last search was 20 January 2023.
SELECTION CRITERIA: We aimed to include randomised clinical trials assessing any type of gene therapy in people diagnosed with hepatocellular carcinoma, irrespective of year, language of publication, format, or outcomes reported.
DATA COLLECTION AND ANALYSIS: We followed Cochrane methodology and used Review Manager to prepare the review. The primary outcomes were all-cause mortality/overall survival (whatever data were provided), serious adverse events during treatment, and health-related quality of life. The secondary outcomes were proportion of people with disease progression, adverse events considered non-serious, and proportion of people without improvement in liver function tests. We assessed risk of bias of the included trials using RoB 2 and the certainty of evidence using GRADE. We presented the results of time-to-event outcomes as hazard ratios (HR), dichotomous outcomes as risk ratios (RR), and continuous outcomes as mean difference (MD) with their 95% confidence intervals (CI). Our primary analyses were based on intention-to-treat and outcome data at the longest follow-up.
MAIN RESULTS: We included six randomised clinical trials with 364 participants. The participants had unresectable (i.e. advanced inoperable) hepatocellular carcinoma. We found no trials assessing the effects of gene therapy in people with operable hepatocellular carcinoma. Four trials were conducted in China, one in several countries (from North America, Asia, and Europe), and one in Egypt. The number of participants in the six trials ranged from 10 to 129 (median 47), median age was 55.2 years, and the mean proportion of males was 72.7%. The follow-up duration ranged from six months to five years. As the trials compared different types of gene therapy and had different controls, we could not perform meta-analyses. Five of the six trials administered co-interventions equally to the experimental and control groups. All trials assessed one or more outcomes of interest in this review. The certainty of evidence was very low in five of the six comparisons and low in the double-dose gene therapy comparison. Below, we reported the results of the primary outcomes only. Pexastimogene devacirepvec (Pexa-Vec) plus best supportive care versus best supportive care alone There is uncertainty about whether there may be little to no difference between the effect of Pexa-Vec plus best supportive care compared with best supportive care alone on overall survival (HR 1.19, 95% CI 0.78 to 1.82; 1 trial (censored observation at 20-month follow-up), 129 participants; very low-certainty evidence) and on serious adverse events (RR 1.42, 95% CI 0.60 to 3.33; 1 trial at 20 months after treatment, 129 participants; very low-certainty evidence). The trial reported quality of life narratively as "assessment of quality of life and time to symptomatic progression was confounded by the high patient dropout rate." Adenovirus-thymidine kinase with ganciclovir (ADV-TK/GCV) plus liver transplantation versus liver transplantation alone There is uncertainty about whether ADV-TK/GCV plus liver transplantation may benefit all-cause mortality at the two-year follow-up (RR 0.39, 95% CI 0.20 to 0.76; 1 trial, 45 participants; very low-certainty evidence). The trial did not report serious adverse events other than mortality or quality of life. Double-dose ADV-TK/GCV plus liver transplantation versus liver transplantation alone There is uncertainty about whether double-dose ADV-TK/GCV plus liver transplantation versus liver transplantation may benefit all-cause mortality at five-year follow-up (RR 0.40, 95% CI 0.22 to 0.73; 1 trial, 86 participants; low-certainty evidence). The trial did not report serious adverse events other than mortality or quality of life. Recombinant human adenovirus-p53 with hydroxycamptothecin (rAd-p53/HCT) versus hydroxycamptothecin alone There is uncertainty about whether there may be little to no difference between the effect of rAd-p53/HCT versus hydroxycamptothecin alone on the overall survival at 12-month follow-up (RR 3.06, 95% CI 0.16 to 60.47; 1 trial, 48 participants; very low-certainty evidence). The trial did not report serious adverse events or quality of life. rAd-p53/5-Fu (5-fluorouracil) plus transarterial chemoembolisation versus transarterial chemoembolisation alone The trial included 46 participants. We had insufficient data to assess overall survival. The trial did not report serious adverse events or quality of life. E1B-deleted (dl1520) adenovirus versus percutaneous ethanol injection The trial included 10 participants. It did not report data on overall survival, serious adverse events, or health-related quality of life. One trial did not provide any information on sponsorship; one trial received a national research grant, one trial by the Pedersen foundation, and three were industry-funded trials. We found five ongoing randomised clinical trials.
AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effects of gene therapy on the studied outcomes because of high risk of bias and imprecision of outcome results. The trials were underpowered and lacked trial data on clinically important outcomes. There was only one trial per comparison, and we could not perform meta-analyses. Therefore, we do not know if gene therapy may reduce, increase, or have little to no effect on all-cause mortality or overall survival, or serious adverse events in adults with unresectable hepatocellular carcinoma. The impact of gene therapy on adverse events needs to be investigated further. Evidence on the effect of gene therapy on health-related quality of life is lacking.
METHODS: Eight databases were searched, with the search period was limited to April 2024. Quality assessment of the included randomized controlled trials was performed according to the criteria for evaluating randomized controlled trials in the Cochrane Handbook for Systematic Reviews of Interventions. The RevMan 5.4 software was used for the data analysis.
RESULTS: Nine randomized controlled trials were included in this systematic review and meta-analysis. The quality of the included studies was relatively high. The results showed that laughter therapy can effectively improve cancer patients' stress, anxiety, depression, pain, and fatigue, but has no effect on sleep quality.
CONCLUSIONS: Laughter therapy is a low-cost, easy-to-implement intervention that may have potential benefits in improving psychological symptoms (stress, anxiety, and depression) and physical symptoms (pain and fatigue) among cancer patients. Laughter therapy has the characteristics of high safety, strong interaction, and strong feasibility. It may promote communication between patients and between patients and medical healthcare, enhance the trust relationship between medical staff, and potentially improve the quality of life for cancer patients. Healthcare professionals should consider laughter therapy as a potential adjunctive therapy, but its implementation should be tailored to individual patient needs and supported by robust evidence.
OBJECTIVES: To determine the benefits and harms of acupuncture (e.g. needle acupuncture with or without electrical stimulation; laser acupuncture; non-penetrating types of manual or embedded acupressure) on mortality and morbidity in neonates with HIE, compared with 1) no treatment, 2) placebo or sham treatment, 3) any pharmacologic treatment, or 4) different types of acupuncture.
SEARCH METHODS: We searched CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the WHO ICTRP in March 2023. We conducted a search of the grey literature to identify reports of trials conducted by or referenced in research by CORDIS EU, National Institute for Health and Care Excellence (NICE), and NHSGGC Paediatrics for Health Professionals. We also checked the reference lists of relevant articles to identify additional studies.
SELECTION CRITERIA: We included randomized controlled trials (RCTs) or quasi-RCTs and cluster-randomized trials. We included studies where participants were term infants (37 weeks or greater) and late preterm infants (34 + 0 to 36 + 6 weeks' gestation) 10 days of age or less, with evidence of peripartum asphyxia. We included studies on acupuncture (e.g. needle acupuncture with or without electrical stimulation; laser acupuncture; non-penetrating types of manual or embedded acupressure). We included studies where acupuncture was compared with: 1) no treatment; 2) placebo or sham treatment; 3) any pharmacologic treatment; or 4) different types of acupuncture.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all-cause mortality at the latest follow-up, major neurodevelopmental disability in children aged 18 to 24 months and aged 3 to 5 years, adverse events until hospital discharge, and length of hospital stay.
MAIN RESULTS: We included four studies (enrolling 464 infants) that compared acupuncture with no treatment. The studies ranged in size from 60 to 200 infants. Three studies were conducted in China and one in Russia. None of the four studies reported on any of the prespecified outcomes of our review. We did not identify any ongoing studies.
AUTHORS' CONCLUSIONS: There is limited availability of studies addressing this specific population. The included studies did not assess mortality, long-term neurodevelopmental outcomes, or adverse effects of acupuncture. We are unable to draw any conclusions about the benefits and harms of acupuncture for HIE in neonates. In light of the current limitations, clinicians are urged to approach the use of acupuncture in neonates with HIE cautiously, as there is no evidence to support its routine application. The available trials assessed surrogate outcomes that have a relatively small impact on newborns, and failed to report important outcomes such as mortality and long-term neurodevelopmental outcomes. Other available trials were performed on older infants who had experienced neonatal HIE. Given the lack of available evidence, well-designed randomized controlled trials with relevant outcomes such as mortality and neurodevelopmental outcomes are essential to evaluate the efficacy and safety of acupuncture for HIE in neonates.
METHOD: Electronic search via Web of Science, MEDLINE via PubMed, Scopus, and Cochrane CENTRAL registry as well as manual search were done from June 2024 to July 2024 for relevant publication from inception until June 2024. The articles were assessed by 2 independent reviewers and deemed relevant when the interventional studies reported on periodontal outcomes after adjunctive APC were used in NSPT. The studies were excluded if it was not in English or unpublished. The risk of bias for each study was assessed using the Cochrane risk-of-bias tool (RoB 2). Fixed effect meta-analysis was conducted to measure the summary effect for change of periodontal pocket depth (PPD) and Clinical Attachment Level (CAL). The statistical heterogeneity between studies was also calculated using I2 test.
RESULT: A total of 607 records were found in the four electronic databases. Following the removal of duplicates and initial title screening, 16 full text articles from electronic search and 7 articles from manual search were assessed resulting in 13 studies included in the systematic review. The overall risk of bias showed most studies have moderate to high risk of bias. The fixed-effect meta-analysis showed summary effects favored the adjunctive use of APC in nonsurgical periodontal therapy but with high heterogeneity between the studies, particularly for CAL.
CONCLUSION: The evidence on APC as adjunct in NSPT is limited by the small number of studies, moderate to high risk of bias in most studies and significant heterogeneity in the results.
METHODS AND ANALYSIS: The systematic review, will be conducted by extensively searching different databases such as PubMed, Web of Science, Scopus, Wiley and ProQuest to identify randomised controlled trials (with no time frame) which relate to the administration of probiotics to patients with colorectal cancer. The search strategy will include words like colorectal cancer, probiotics, Bifidobacterium, clinical trials etc. A systematic search of databases was performed between 17 and 20 January 2020. Two reviewers will independently review the studies and also search the reference lists of the eligible studies to obtain more references. Data will be extracted from the eligible studies using standardised data extraction form. After assessing the risk of bias, qualitative analysis will be used to synthesise the systematic review.
ETHICS AND DISSEMINATION: This is a protocol for a systematic review; therefore, it doesn't require any ethics approval. We intend to disseminate the protocol in a peer reviewed journal.
METHODS: We assessed the use of composite outcomes in neonatal RCTs included in Cochrane Neonatal reviews published till November 2017. Two authors reviewed the components of the composite outcomes to compare their patient importance and computed the ratios of effect sizes and event rates between the components, with an a priori threshold of 1.5, indicating a substantial difference. Descriptive statistics were presented.
RESULTS: We extracted 7,766 outcomes in 2,134 RCTs in 312 systematic reviews. Among them, 55 composite outcomes (0.7%) were identified in 46 RCTs. The vast majority (92.7%) of composite outcomes had 2 components, with death being the most common component (included 51 times [92.7%]). The components in nearly three-quarters of the composite outcomes (n = 40 [72.7%]) had different patient importance, while the effect sizes and event rates differed substantially between the components in 27 (49.1%) and 35 (63.6%) outcomes, respectively, with up to 43-fold difference in the event rates observed.
CONCLUSIONS: The majority of composite outcomes in neonatal RCTs had different patient importance with contrasting effect sizes and event rates between the components. In patient communication, clinicians should highlight individual components, rather than the composites, with explanation on the relationship between the components, to avoid misleading impression on the effect of the intervention. Future trials should report the estimates of all individual components alongside the composite outcomes presented.
Objective: This paper illustrates a significant perspective of some of the challenges faced while conducting a randomized controlled trial exploring the impact of a multi-component intervention that included strategy- and process-based prospective memory (PM) training among Malaysian older adults.
Methods: The current study was a randomized controlled trial (RCT) and therefore the challenges were presented in accordance with the CONSORT statement style.
Results: A discussion on how these issues were addressed is provided.
Conclusion: Some suggestions were presented to help researchers plan and create interventions for similar studies and to support a practical method of addressing all related challenges.
METHODS: Patients with primary breast and colorectal cancer undergoing elective surgery are recruited from two tertiary hospitals. Eligible patients are assigned into one of the three intervention arms: (i) Group SS will receive ONS in addition to their normal diet up to 14 days preoperatively and postoperatively up to discharge; (ii) Group SS-E will receive ONS in addition to their normal diet up to 14 days preoperatively, postoperatively up to discharge and for an extended 90 days after discharge; and (iii) Group DS will receive ONS in addition to their normal diet postoperatively up to discharge from the hospital. The ONS is a standard formula fortified with lactium to aid in sleep for recovery. The primary endpoints include changes in weight, body mass index (BMI), serum albumin and prealbumin levels, while secondary endpoints are body composition (muscle and fat mass), muscle strength (handgrip strength), energy and protein intake, sleep quality, haemoglobin, inflammatory markers (transferrin, high sensitivity C-reactive protein, interleukin-6), stress marker (saliva cortisol), length of hospital stay and postoperative complication rate.
DISCUSSION: This trial is expected to provide evidence on whether perioperative supplementation in breast and colorectal cancer patients presenting with high BMI and not severely malnourished but undergoing the stress of surgery would be beneficial in terms of nutritional and clinical outcomes.
TRIAL REGISTRATION: ClinicalTrial.gov NCT04400552. Registered on 22 May 2020, retrospectively registered.
METHODS AND RESULTS: Individual patient data for 16 922 patients from five randomized clinical trials and 46 914 patients from two HF registries were included. The registry patients were categorized into trial-eligible and non-eligible groups using the most commonly used inclusion and exclusion criteria. A total of 26 104 (56%) registry patients fulfilled the eligibility criteria. Unadjusted all-cause mortality rates at 1 year were lowest in the trial population (7%), followed by trial-eligible patients (12%) and trial-non-eligible registry patients (26%). After adjustment for age and sex, all-cause mortality rates were similar between trial participants and trial-eligible registry patients [standardized mortality ratio (SMR) 0.97; 95% confidence interval (CI) 0.92-1.03] but cardiovascular mortality was higher in trial participants (SMR 1.19; 1.12-1.27). After full case-mix adjustment, the SMR for cardiovascular mortality remained higher in the trials at 1.28 (1.20-1.37) compared to RCT-eligible registry patients.
CONCLUSION: In contemporary HF registries, over half of HFrEF patients would have been eligible for trial enrolment. Crude clinical event rates were lower in the trials, but, after adjustment for case-mix, trial participants had similar rates of survival as registries. Despite this, they had about 30% higher cardiovascular mortality rates. Age and sex were the main drivers of differences in clinical outcomes between HF trials and observational HF registries.
MATERIALS AND METHODS: Randomized controlled comparing MIE versus OE were searched from PubMed and other electronic databases between January 1991 and March 2019. Thirteen outcome variables were analyzed. Random effects model was used to calculate the effect size. The meta-analysis was prepared in accordance with PRISMA guidelines.
RESULTS: Four randomized controlled trials totaling 569 patients were analyzed. For MIE, there was a significantly reduction of 67% in the odds of pulmonary complications. For operating time, MIE was nonsignificantly 29 minutes longer. MIE was associated with nonsignificantly less blood loss of 443.98 mL. There was nonsignificant 60% reduction in the odds of total complications and 51% reduction in the odds of medical complications favoring MIE group. For delayed gastric emptying, there was a nonsignificant reduction of 75% in the odds ratio favoring the MIE group. For postoperative anastomotic leak, there was a nonsignificant increase of 48% in the odds ratio for MIE group. For gastric necrosis, chylothorax, reintervention and 30-day mortality, no difference was observed for both groups. There was a nonsignificant reduction in the length of hospital stay of 7.98 days and intensive care unit stay of 2.7 days favoring MIE.
CONCLUSIONS: MIE seems to be superior to OE for only pulmonary complications. All the other perioperative variables were comparable however, the trend is favoring the MIE. Therefore, the routine use of MIE presently may only be justifiable in high volume esophagogastric units.
DESIGN: The search was conducted in PubMed, Ebscohost, ProQuest, and Scopus databases till June 2021. Children undergoing pulpotomy therapy in primary molars treated with ferric sulfate (FS) and bioactive endodontic materials were evaluated for clinical and radiographic success. Meta-analysis was performed on a random-effects model to assess the success at 6,12,18, and 24 months. The quality of studies was evaluated using the Cochrane risk of bias tool for randomized trials RESULTS: No significant difference was observed between Mineral trioxide aggregate (MTA) and FS at 24 months for both clinical [RR0.98 (95%CI 0.15,6.34), I2 = 0%] and radiographic [RR0.74 (95%CI: 0.23,2.43), I2 = 0%] success. At 6 months [RR1.36 (95%CI: 0.10,19.34), I2 = 33%], no difference was observed in the clinical [RR1.00 (95%CI: 0.95,1.05), I2 = 0%] and radiographic success [RR0.99 (95%CI: 0.88,1.11), I2 = 51%] between Biodentine (BD), FS and radiographic success of calcium enriched cement and FS [RR0.25 (95%CI: 0.03, 2.22), I2 = 0%].
CONCLUSION: Amongst bioactive materials, MTA and FS demonstrated equal success rates in both clinical and radiographic outcomes with follow-up periods of up to 24 months. Future, high-quality trials are required to verify the result of the current review.
OBJECTIVE: The systematic review and meta-analysis in this study aimed to explore the effect of exercise intervention on health-related quality of life of colorectal cancer survivors.
METHODS: The current study followed guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020) to identify relevant literature. Comprehensive searches were conducted using EBSCOhost, Web of Science (WOS), Scopus, Science Direct, and PubMed. The inclusion criteria included are randomised control trials studies written in English, with no restrictions for the time of publication that reported the effects of exercise intervention on health-related quality of live among colorectal cancer survivors. Meta-analysis was conducted by pooling the mean and standard deviation of post-intervention scores across randomised control trial studies using a random effects model.
RESULT: A total of 467 articles were identified but only seven articles were randomised control trials (RCT) (n = 7) with PEDro scores ranging from 6 to 9 showing good internal validity were included in the review. The results of the meta-analysis of pooled data from six RCTs studies on HRQoL showed no significant effect of exercise intervention on HRQoL in the intervention group compared to control group [SMD = 0.25; 95% CI; -0.0, 0.51; Z = 1.88; p = 0.06; I2 = 30.8%].
CONCLUSION: This meta-analysis provides key insights into the effect of exercise on the health-related quality of life (HRQoL) of colorectal cancer (CRC) survivors. Therefore, more experimental studies should be carried out with rigorous methodology to evaluate the effectiveness of exercise interventions before it is recommended as a routine activity in post-treatment management for CRC survivors.
AREAS COVERED: This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs.
EXPERT OPINION: We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.