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BMJ Open Aug 2019Despite the publication of hundreds of trials on gout and hyperuricemia, management of these conditions remains suboptimal. We aimed to assess the quality and...
OBJECTIVES
Despite the publication of hundreds of trials on gout and hyperuricemia, management of these conditions remains suboptimal. We aimed to assess the quality and consistency of guidance documents for gout and hyperuricemia.
DESIGN
Systematic review and quality assessment using the appraisal of guidelines for research and evaluation (AGREE) II methodology.
DATA SOURCES
PubMed and EMBASE (27 October 2016), two Chinese academic databases, eight guideline databases, and Google and Google scholar (July 2017).
ELIGIBILITY CRITERIA
We included the latest version of international and national/regional clinical practice guidelines and consensus statements for diagnosis and/or treatment of hyperuricemia and gout, published in English or Chinese.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently screened searched items and extracted data. Four reviewers independently scored documents using AGREE II. Recommendations from all documents were tabulated and visualised in a coloured grid.
RESULTS
Twenty-four guidance documents (16 clinical practice guidelines and 8 consensus statements) published between 2003 and 2017 were included. Included documents performed well in the domains of scope and purpose (median 85.4%, range 66.7%-100.0%) and clarity of presentation (median 79.2%, range 48.6%-98.6%), but unsatisfactory in applicability (median 10.9%, range 0.0%-66.7%) and editorial independence (median 28.1%, range 0.0%-83.3%). The 2017 British Society of Rheumatology guideline received the highest scores. Recommendations were concordant on the target serum uric acid level for long-term control, on some indications for urate-lowering therapy (ULT), and on the first-line drugs for ULT and for acute attack. Substantially inconsistent recommendations were provided for many items, especially for the timing of initiation of ULT and for treatment for asymptomatic hyperuricemia.
CONCLUSIONS
Methodological quality needs improvement in guidance documents on gout and hyperuricemia. Evidence for certain clinical questions is lacking, despite numerous trials in this field. Promoting standard guidance development methods and synthesising high-quality clinical evidence are potential approaches to reduce recommendation inconsistencies.
PROSPERO REGISTRATION NUMBER
CRD42016046104.
Topics: Consensus; Gout; Gout Suppressants; Humans; Hyperuricemia; Practice Guidelines as Topic; Uric Acid
PubMed: 31446403
DOI: 10.1136/bmjopen-2018-026677 -
BMC Musculoskeletal Disorders Dec 2022Studies reporting on the population burden of people living with shoulder pain show wide heterogeneity in terms of case definition, study samples, and occurrence. This...
BACKGROUND AND OBJECTIVES
Studies reporting on the population burden of people living with shoulder pain show wide heterogeneity in terms of case definition, study samples, and occurrence. This systematic review aims to summarize evidence pertaining to the prevalence and incidence of shoulder pain, including variability based on sex and geography. We also explored the potential influence of methodological limitations and important sources of heterogeneity (case definition and reference period) on reported estimates of shoulder pain prevalence.
DATABASES AND DATA TREATMENT
The study protocol was registered on Prospero under CRD42021243140. We searched EMBASE, CINAHL, Web of Science and Medline from inception to March 2021. Study selection, data extraction and risk of bias assessment was conducted by a team of three researchers. We performed a narrative synthesis of the data, using forest plots to summarize study findings, and stratified data presentation to explore the potential association of risk of bias, case definition, and reference period with estimates of prevalence and incidence of shoulder pain.
RESULTS
We obtained data from 61 studies reporting data from high-, middle- and low-income countries. The overall risk of bias was low, with most rated as "low-risk" and no studies rated as "high-risk". The community prevalence of shoulder pain varied widely across the countries included in our review, with a median of 16% (range 0.67 to 55.2%). Longer reference periods were typically associated with higher prevalence estimates. Primary care prevalence ranged from 1.01 to 4.84% (median 2.36%). Estimates were generally higher for women than men and were higher in high-income nations. The incidence of shoulder pain ranged from 7.7 to 62 per 1000 persons per year (median 37.8 per 1000 persons per year). Risk of bias did not clearly explain variability in study findings, but there was considerable variation in study samples, methods used, and a relative absence of data from low-income countries.
CONCLUSIONS
Our review demonstrates that a significant proportion of the population across the world will experience shoulder pain daily, yearly, and throughout a lifetime. Regional gaps in evidence and methodological inconsistencies must be addressed in order to establish a more definitive global burden.
Topics: Female; Humans; Shoulder Pain; Geography
PubMed: 36476476
DOI: 10.1186/s12891-022-05973-8 -
Obesity Reviews : An Official Journal... Dec 2022The dose-response association between sedentary time and the risk of metabolic syndrome is unclear, which indicates an important knowledge gap in public health. The... (Meta-Analysis)
Meta-Analysis Review
The dose-response association between sedentary time and the risk of metabolic syndrome is unclear, which indicates an important knowledge gap in public health. The objective of this study was to determine the categorical and continuous dose-response associations between sedentary time and the risk of metabolic syndrome. A systematic literature search of English articles published in PubMed, CINHAL, Embase, and Web of Science Core Collection prior to June 2022 was conducted. All cohort and cross-sectional studies that examined the association between sedentary time and the risk of metabolic syndrome were considered, and duplicate and non-related studies were excluded. Data extraction using a standardized chart and quality assessment using two appraisal tools were also performed. Two independent reviewers were involved in these processes. In categorical meta-analyses, the pooled effect sizes for metabolic syndrome associated with different categories of sedentary time were calculated by comparing the highest and intermediate with the lowest categories. In continuous meta-analyses, the linear and nonlinear dose-response associations were estimated using generalized least squares and restricted cubic spline models, respectively. Data were collected and analyzed from March to June 2022. Four prospective cohort studies and 22 cross-sectional studies with 105,239 participants and 16,185 MetS cases were included in this study. In categorical analyses, both intermediate (median duration: 4.11 h/day; pooled OR: 1.17, 95% CI: 1.08-1.26, P < 0.001) and high levels (median duration: 7.26 h/day; pooled OR: 1.71, 95% CI: 1.43-2.04, P < 0.001) of total sedentary time were significantly associated with an increased risk of metabolic syndrome. Similarly, a significant association between screen time and the risk of metabolic syndrome was also found in intermediate (median duration: 2.22 h/day; pooled OR: 1.20, 95% CI: 1.10-1.32, P < 0.001) and high levels (median duration: 3.40 h/day; pooled OR: 1.63, 95% CI: 1.44-1.86, P < 0.001) of exposure. Of note, these associations were significantly stronger in women. Different patterns of the behavior-disease association were not observed in children, adolescents, and adults. The findings of continuous meta-analyses could not provide solid evidence for the linearity and nonlinearity of the behavior-disease association. This study demonstrated that long-time sedentary behavior was associated with a higher risk of MetS independent of physical activity and the patterns of association varied by gender instead of age. These findings have implications for future guideline recommendations on physical activity, sedentary behavior, and prevention of metabolic syndrome.
Topics: Child; Adolescent; Adult; Humans; Female; Sedentary Behavior; Metabolic Syndrome; Cross-Sectional Studies; Prospective Studies; Exercise
PubMed: 36261077
DOI: 10.1111/obr.13510 -
The Cochrane Database of Systematic... Mar 2018Survivors of critical illness often experience a multitude of problems that begin in the intensive care unit (ICU) or present and continue after discharge. These can... (Review)
Review
BACKGROUND
Survivors of critical illness often experience a multitude of problems that begin in the intensive care unit (ICU) or present and continue after discharge. These can include muscle weakness, cognitive impairments, psychological difficulties, reduced physical function such as in activities of daily living (ADLs), and decreased quality of life. Early interventions such as mobilizations or active exercise, or both, may diminish the impact of the sequelae of critical illness.
OBJECTIVES
To assess the effects of early intervention (mobilization or active exercise), commenced in the ICU, provided to critically ill adults either during or after the mechanical ventilation period, compared with delayed exercise or usual care, on improving physical function or performance, muscle strength and health-related quality of life.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase and CINAHL. We searched conference proceedings, reference lists of retrieved articles, databases of trial registries and contacted experts in the field on 31 August 2017. We did not impose restrictions on language or location of publications.
SELECTION CRITERIA
We included all randomized controlled trials (RCTs) or quasi-RCTs that compared early intervention (mobilization or active exercise, or both), delivered in the ICU, with delayed exercise or usual care delivered to critically ill adults either during or after the mechanical ventilation period in the ICU.
DATA COLLECTION AND ANALYSIS
Two researchers independently screened titles and abstracts and assessed full-text articles against the inclusion criteria of this review. We resolved any disagreement through discussion with a third review author as required. We presented data descriptively using mean differences or medians, risk ratios and 95% confidence intervals. A meta-analysis was not possible due to the heterogeneity of the included studies. We assessed the quality of evidence with GRADE.
MAIN RESULTS
We included four RCTs (a total of 690 participants), in this review. Participants were adults who were mechanically ventilated in a general, medical or surgical ICU, with mean or median age in the studies ranging from 56 to 62 years. Admitting diagnoses in three of the four studies were indicative of critical illness, while participants in the fourth study had undergone cardiac surgery. Three studies included range-of-motion exercises, bed mobility activities, transfers and ambulation. The fourth study involved only upper limb exercises. Included studies were at high risk of performance bias, as they were not blinded to participants and personnel, and two of four did not blind outcome assessors. Three of four studies reported only on those participants who completed the study, with high rates of dropout. The description of intervention type, dose, intensity and frequency in the standard care control group was poor in two of four studies.Three studies (a total of 454 participants) reported at least one measure of physical function. One study (104 participants) reported low-quality evidence of beneficial effects in the intervention group on return to independent functional status at hospital discharge (59% versus 35%, risk ratio (RR) 1.71, 95% confidence interval (CI) 1.11 to 2.64); the absolute effect is that 246 more people (95% CI 38 to 567) per 1000 would attain independent functional status when provided with early mobilization. The effects on physical functioning are uncertain for a range measures: Barthel Index scores (early mobilization: median 75 control: versus 55, low quality evidence), number of ADLs achieved at ICU (median of 3 versus 0, low quality evidence) or at hospital discharge (median of 6 versus 4, low quality evidence). The effects of early mobilization on physical function measured at ICU discharge are uncertain, as measured by the Acute Care Index of Function (ACIF) (early mobilization mean: 61.1 versus control: 55, mean difference (MD) 6.10, 95% CI -11.85 to 24.05, low quality evidence) and the Physical Function ICU Test (PFIT) score (5.6 versus 5.4, MD 0.20, 95% CI -0.98 to 1.38, low quality evidence). There is low quality evidence that early mobilization may have little or no effect on physical function measured by the Short Physical Performance Battery score at ICU discharge from one study of 184 participants (mean 1.6 in the intervention group versus 1.9 in usual care, MD -0.30, 95% CI -1.10 to 0.50), or at hospital discharge (MD 0, 95% CI -1.00 to 0.90). The fourth study, which examined postoperative cardiac surgery patients did not measure physical function as an outcome.Adverse effects were reported across the four studies but we could not combine the data. Our certainty in the risk of adverse events with either mobilization strategy is low due to the low rate of events. One study reported that in the intervention group one out of 49 participants (2%) experienced oxygen desaturation less than 80% and one of 49 (2%) had accidental dislodgement of the radial catheter. This study also found cessation of therapy due to participant instability occurred in 19 of 498 (4%) of the intervention sessions. In another study five of 101 (5%) participants in the intervention group and five of 109 (4.6%) participants in the control group had postoperative pulmonary complications deemed to be unrelated to intervention. A third study found one of 150 participants in the intervention group had an episode of asymptomatic bradycardia, but completed the exercise session. The fourth study reported no adverse events.
AUTHORS' CONCLUSIONS
There is insufficient evidence on the effect of early mobilization of critically ill people in the ICU on physical function or performance, adverse events, muscle strength and health-related quality of life at this time. The four studies awaiting classification, and the three ongoing studies may alter the conclusions of the review once these results are available. We assessed that there is currently low-quality evidence for the effect of early mobilization of critically ill adults in the ICU due to small sample sizes, lack of blinding of participants and personnel, variation in the interventions and outcomes used to measure their effect and inadequate descriptions of the interventions delivered as usual care in the studies included in this Cochrane Review.
Topics: Activities of Daily Living; Adult; Critical Illness; Early Ambulation; Exercise; Humans; Intensive Care Units; Muscle Strength; Quality of Life; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 29582429
DOI: 10.1002/14651858.CD010754.pub2 -
Therapeutic Advances in Chronic Disease 2022Although data on the effects of liraglutide and semaglutide in patients with diabetes have been reviewed, their therapeutic outcomes in obese/overweight individuals... (Review)
Review
BACKGROUND & OBJECTIVE
Although data on the effects of liraglutide and semaglutide in patients with diabetes have been reviewed, their therapeutic outcomes in obese/overweight individuals without diabetes have not been summarized. We conducted a systematic review to evaluate their effects on the latter population.
METHODS
We searched the PubMed, EMBASE, Cochrane, CNKI, and Wanfang databases. Studies regarding obese/overweight adults without diabetes treated with liraglutide/semaglutide compared with other active agents or placebos were accessed. The primary outcomes were the proportions of adults with at least 5% and 10% weight reduction. The secondary outcomes included metabolic indicators and adverse events.
RESULTS
Eighteen studies with 10,938 obese/overweight adults without diabetes were included. When stratified by the categories of at least 5% and 10% weight loss, the pooled data showed medians 27.7% and 10.3% of control groups versus 65.3% and 30.7% of liraglutide 3 mg once daily, respectively; whereas medians 47.6% and 20.4% of control groups vs 86.6% and 75.3% of semaglutide 2.4 mg once weekly were found in the two categories, respectively. Both agents either improved or had no impact on lipid or glycemia. Liraglutide or semaglutide therapy had discontinuation rates of 2.4%-11.4% which overlapped with 0.7%-8.6% in control groups. The frequency of adverse events was comparable between the treatment groups and the control groups (66.5%-95.8% vs 46.9%-96.1%), which were mild to moderate graded by studies.
CONCLUSION
Liraglutide and semaglutide therapy led to a clinically relevant (⩾5%) weight loss of 48.2%-88.7% among obese/overweight adults without diabetes. Both liraglutide and semaglutide are associated with weight loss and are well-tolerated.
PubMed: 35813188
DOI: 10.1177/20406223221108064 -
Journal of Periodontology May 2018A wide selection of Interdental Oral Hygiene (IOH) aids is available to consumers. Recommendations for selection are, however, limited by the lack of direct comparisons... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A wide selection of Interdental Oral Hygiene (IOH) aids is available to consumers. Recommendations for selection are, however, limited by the lack of direct comparisons in available studies. We aimed to assess the comparative efficacy of IOH aids using Bayesian Network Meta-Analysis (BNMA).
METHODS
Two independent reviewers performed a systematic literature review of randomized clinical trials assessing IOH aids, based on a focused question. Gingival inflammation (Gingival Index (GI), Bleeding-on-probing (BOP)) was the primary outcome and plaque and probing depth were secondary outcomes A random-effects arm-based BNMA model was run for each outcome; posterior medians and 95% credible-intervals (CIs) summarized marginal distributions of parameters.
RESULTS
A two-phase selection process identified 22 trials assessing 10 IOH aids as brushing adjuncts. Interdental brushes (IB) yielded the largest reduction in GI (0.23 [95% CI: 0.09, 0.37]) as toothbrushing adjuncts, followed by water-jet (WJ) (0.19 [95% CI: 0.14, 0.24]). Rankings based on posterior probabilities revealed that IB and WJ had the highest probability of being "best" (64.7% and 27.4%, respectively) for GI reduction, whereas the probability for toothpick and floss being the "best" IOH aids was near zero. Notably, except for toothpicks, all IOH aids were better at reducing GI as compared with control.
CONCLUSIONS
BNMA enabled us to quantitatively evaluate IOH aids and provide a global ranking of their efficacy. Interdental brushes and water-jets ranked high for reducing gingival bleeding, whereas toothpicks and floss ranked last. The patient-perceived benefit of IOH aids is not clear because gingival inflammation measures are physical indicators of periodontal health.
Topics: Bayes Theorem; Dental Devices, Home Care; Dental Plaque Index; Gingivitis; Humans; Inflammation; Oral Hygiene; Toothbrushing
PubMed: 29520910
DOI: 10.1002/JPER.17-0368 -
JAMA Network Open Oct 2021Short-term and long-term persistent postacute sequelae of COVID-19 (PASC) have not been systematically evaluated. The incidence and evolution of PASC are dependent on...
IMPORTANCE
Short-term and long-term persistent postacute sequelae of COVID-19 (PASC) have not been systematically evaluated. The incidence and evolution of PASC are dependent on time from infection, organ systems and tissue affected, vaccination status, variant of the virus, and geographic region.
OBJECTIVE
To estimate organ system-specific frequency and evolution of PASC.
EVIDENCE REVIEW
PubMed (MEDLINE), Scopus, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases were searched from December 2019 through March 2021. A total of 2100 studies were identified from databases and through cited references. Studies providing data on PASC in children and adults were included. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for abstracting data were followed and performed independently by 2 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. The main outcome was frequency of PASC diagnosed by (1) laboratory investigation, (2) radiologic pathology, and (3) clinical signs and symptoms. PASC were classified by organ system, ie, neurologic; cardiovascular; respiratory; digestive; dermatologic; and ear, nose, and throat as well as mental health, constitutional symptoms, and functional mobility.
FINDINGS
From a total of 2100 studies identified, 57 studies with 250 351 survivors of COVID-19 met inclusion criteria. The mean (SD) age of survivors was 54.4 (8.9) years, 140 196 (56%) were male, and 197 777 (79%) were hospitalized during acute COVID-19. High-income countries contributed 45 studies (79%). The median (IQR) proportion of COVID-19 survivors experiencing at least 1 PASC was 54.0% (45.0%-69.0%; 13 studies) at 1 month (short-term), 55.0% (34.8%-65.5%; 38 studies) at 2 to 5 months (intermediate-term), and 54.0% (31.0%-67.0%; 9 studies) at 6 or more months (long-term). Most prevalent pulmonary sequelae, neurologic disorders, mental health disorders, functional mobility impairments, and general and constitutional symptoms were chest imaging abnormality (median [IQR], 62.2% [45.8%-76.5%]), difficulty concentrating (median [IQR], 23.8% [20.4%-25.9%]), generalized anxiety disorder (median [IQR], 29.6% [14.0%-44.0%]), general functional impairments (median [IQR], 44.0% [23.4%-62.6%]), and fatigue or muscle weakness (median [IQR], 37.5% [25.4%-54.5%]), respectively. Other frequently reported symptoms included cardiac, dermatologic, digestive, and ear, nose, and throat disorders.
CONCLUSIONS AND RELEVANCE
In this systematic review, more than half of COVID-19 survivors experienced PASC 6 months after recovery. The most common PASC involved functional mobility impairments, pulmonary abnormalities, and mental health disorders. These long-term PASC effects occur on a scale that could overwhelm existing health care capacity, particularly in low- and middle-income countries.
Topics: COVID-19; Fatigue; Humans; Lung Diseases; Mental Disorders; Mobility Limitation; Muscle Weakness; Nervous System Diseases; Survivors
PubMed: 34643720
DOI: 10.1001/jamanetworkopen.2021.28568 -
Journal of Clinical Anesthesia Dec 2022Intraoperative hypotension (IOH) is common in noncardiac surgery and is associated with serious postoperative complications. Hypotension Prediction Index (HPI) has shown... (Review)
Review
Intraoperative hypotension (IOH) is common in noncardiac surgery and is associated with serious postoperative complications. Hypotension Prediction Index (HPI) has shown high sensitivity and specificity for predicting hypotension and may reduce IOH in noncardiac surgery. We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the applications and effects of HPI in reducing hypotension during noncardiac surgery. We comprehensively searched the PubMed, Embase, Cochrane Library, Google Scholar, and http://ClinicalTrials.gov databases to identify RCTs conducted before May 2022. The primary outcome measures were the time-weighted average (TWA) of hypotension and the area under the hypotensive threshold (65 mmHg). Secondary outcomes were the incidence and duration of hypotension and the percentage of hypotensive time during surgery. The Cochrane Risk of Bias (RoB) tool was used to assess the quality of selected studies. We conducted data synthesis for median differences and assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We included five studies with a total of 461 patients. Limited evidence suggested that HPI-guided intraoperative hemodynamics management leads to lower a) TWA of hypotension (median of difference of medians [MDM], -0.27 mmHg; 95% confidence interval [CI], -0.38, -0.01), b) area under the hypotensive threshold (MDM, -60.28 mmHg*min; 95% CI, -74.00, -1.30), c) incidence of hypotension (MDM, -4.50; 95% CI, -5.00, -4.00), d) total duration of hypotension (MDM, -12.80 min; 95% CI, -16.11, -3.39), and e) percentage of hypotension (MDM, -5.80; 95% CI, -6.65, -4.82) than routine hemodynamic management during noncardiac surgery. However, only very low- to low-quality evidence on the benefit of intraoperative HPI-based hemodynamic management is available. Our review revealed that HPI has the potential to reduce the occurrence, duration, and severity of IOH during noncardiac surgery compared to standard intraoperative care with proper adherence to the protocol. Systematic review registration PROSPERO CRD42022333834.
Topics: Humans; Hypotension; Postoperative Complications; Time Factors
PubMed: 36242978
DOI: 10.1016/j.jclinane.2022.110981 -
BMJ Open Jul 2017Several societies have produced and disseminated clinical practice guidelines (CPGs) for the symptomatic management of fever in children. However, to date, the quality... (Review)
Review
INTRODUCTION
Several societies have produced and disseminated clinical practice guidelines (CPGs) for the symptomatic management of fever in children. However, to date, the quality of such guidelines has not been appraised.
OBJECTIVE
To identify and evaluate guidelines for the symptomatic management of fever in children.
METHODS
The research was conducted using PubMed, guideline websites, and Google (January 2010 to July 2016). The quality of the CPGs was independently assessed by two assessors using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument, and specific recommendations in guidelines were summarised and evaluated. Domain scores were considered of sufficient quality when >60% and of good quality when >80%.
RESULTS
Seven guidelines were retrieved. The median score for the scope and purpose domain was 85.3% (range 66.6-100%). The median score for the stakeholder involvement domain was 57.5% (range 33.3-83.3%) and four guidelines scored >60%. The median score for the rigour of development domain was 52.0% (range 14.6-98.9%), and only three guidelines scored >60%. The median score for the clarity of presentation domain was 80.9% (range 50.0-94.4%). The median score for the applicability domain was 39.3% (8.3-100%). Only one guideline scored >60%. The median score for the editorial independence domain was 48.84% (0-91.6%); only three guidelines scored >60%.
CONCLUSION
Most guidelines were recommended for use even if with modification, especially in the methodology, the applicability and the editorial independence domains. Our results could help improve reporting of future guidelines, and affect the selection and use of guidelines in clinical practice.
Topics: Child; Fever; Humans; Pediatrics; Practice Guidelines as Topic; Societies, Medical
PubMed: 28760789
DOI: 10.1136/bmjopen-2016-015404 -
Journal of Hematology & Oncology Mar 2023TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line... (Meta-Analysis)
Meta-Analysis
BACKGROUND
TP53 mutations, which are present in 5% to 10% of patients with acute myeloid leukemia (AML), are associated with treatment resistance and poor outcomes. First-line therapies for TP53-mutated (TP53m) AML consist of intensive chemotherapy (IC), hypomethylating agents (HMA), or venetoclax combined with HMA (VEN + HMA).
METHODS
We conducted a systematic review and meta-analysis to describe and compare treatment outcomes in newly diagnosed treatment-naïve patients with TP53m AML. Randomized controlled trials, single-arm trials, prospective observational studies, and retrospective studies were included that reported on complete remission (CR), CR with incomplete hematologic recovery (CRi), overall survival (OS), event-free survival (EFS), duration of response (DoR), and overall response rate (ORR) among patients with TP53m AML receiving first-line treatment with IC, HMA, or VEN + HMA.
RESULTS
Searches of EMBASE and MEDLINE identified 3006 abstracts, and 17 publications describing 12 studies met the inclusion criteria. Random-effects models were used to pool response rates, and time-related outcomes were analyzed with the median of medians method. IC was associated with the greatest CR rate of 43%, and CR rates were 33% for VEN + HMA and 13% for HMA. Rates of CR/CRi were comparable for IC (46%) and VEN + HMA (49%) but were lower for HMA (13%). Median OS was uniformly poor across treatments: IC, 6.5 months; VEN + HMA, 6.2 months; and HMA, 6.1 months. For IC, the EFS estimate was 3.7 months; EFS was not reported for VEN + HMA or HMA. The ORR was 41% for IC, 65% for VEN + HMA, and 47% for HMA. DoR was 3.5 months for IC, 5.0 months for VEN + HMA, and was not reported for HMA.
CONCLUSIONS
Despite improved responses seen with IC and VEN + HMA compared to HMA, survival was uniformly poor, and clinical benefits were limited across all treatments for patients with newly diagnosed, treatment-naïve TP53m AML, demonstrating a significant need for improved treatment for this difficult-to-treat population.
Topics: Humans; Retrospective Studies; Treatment Outcome; Leukemia, Myeloid, Acute; Progression-Free Survival; Mutation; Tumor Suppressor Protein p53; Observational Studies as Topic
PubMed: 36879351
DOI: 10.1186/s13045-023-01417-5