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Blood Cancer Journal Mar 2024Induction regimens for multiple myeloma (MM) commonly include bortezomib, which has typically been administered twice weekly despite studies demonstrating comparable...
Induction regimens for multiple myeloma (MM) commonly include bortezomib, which has typically been administered twice weekly despite studies demonstrating comparable efficacy and less peripheral neuropathy (PN) with once-weekly bortezomib. We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed MM. We analyzed 2497 US patients aged 18-70 years treated with commercial first-line bortezomib using nationwide Flatiron Health electronic health record-derived data, including 910 (36.4%) patients who received twice-weekly and 1522 (63.2%) who received once-weekly bortezomib. Once-weekly bortezomib use increased over time, from 57.7% in 2017 to 73.1% in 2022. Multivariate analysis identified worsened performance status and more recent year of diagnosis with higher odds of receiving once-weekly bortezomib. Real-world progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable. PN rates were higher in patients receiving twice-weekly bortezomib (34.7% versus 18.5%, p < 0.001). In conclusion, once-weekly bortezomib is clearly associated with similar efficacy and fewer toxicities compared to twice-weekly bortezomib. Our findings support once-weekly bortezomib as a standard-of-care regimen for newly diagnosed patients with MM.
Topics: Humans; Bortezomib; Multiple Myeloma; Drug Administration Schedule; Treatment Outcome; Disease-Free Survival; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone
PubMed: 38519476
DOI: 10.1038/s41408-024-01034-6 -
The Journals of Gerontology. Series A,... Oct 2021Deficit accumulation frailty indices (FIs) are widely used to characterize frailty. FIs vary in number and composition of items; the impact of this variation on...
BACKGROUND
Deficit accumulation frailty indices (FIs) are widely used to characterize frailty. FIs vary in number and composition of items; the impact of this variation on reliability and clinical applicability is unknown.
METHOD
We simulated 12 000 studies using a set of 70 candidate deficits in 12 080 community-dwelling participants 65 years and older. For each study, we varied the number (5, 10, 15, 25, 35, 45) and composition (random selection) of items defining the FI and calculated descriptive and predictive estimates: frailty score, prevalence, frailty cutoff, mortality odds ratio, predicted probability of mortality for FI = 0.28 (prevalence threshold), and FI cutoff predicting 10% mortality over the follow-up. We summarized the estimates' medians and spreads (0.025-0.975 quantiles) by number of items and calculated intraclass correlation coefficients (ICCs).
RESULTS
Medians of frailty scores were 0.11-0.12 with decreasing spreads from 0.04-0.24 to 0.10-0.14 for 5-item and 45-item FIs. The median cutoffs identifying 15% as frail was 0.19-0.20 and stable; the spreads decreased with more items. However, medians and spreads for the prevalence of frailty (median: 11%-3%), mortality odds ratio (median: 1.24-2.19), predicted probability of mortality (median: 8%-17%), and FI cutoff predicting 10% mortality (median: 0.38-0.20) varied markedly. ICC increased from 0.19 (5-item FIs) to 0.84 (45-item FIs).
CONCLUSIONS
Variability in the number and composition of items of individual FIs strongly influences their reliability. Estimates using FIs may not be sufficiently stable for generalizing results or direct application. We propose avenues to improve the development, reporting, and interpretation of FIs.
Topics: Aged; Aging; Canada; Frail Elderly; Frailty; Humans; Longitudinal Studies; Reproducibility of Results
PubMed: 34097017
DOI: 10.1093/gerona/glab161 -
Archives of Public Health = Archives... Feb 2021Along with a nutritional transition in Sub-Saharan Africa, the prevalence of non-communicable diseases is increasing rapidly. We assess the association between food...
BACKGROUND
Along with a nutritional transition in Sub-Saharan Africa, the prevalence of non-communicable diseases is increasing rapidly. We assess the association between food intake and cardiometabolic risk factors in a rural population in Uganda.
METHODS
The present study was based on data from a household-based case-control study of diabetic and non-diabetic households in Southwestern Uganda, 2012-2013. We analysed food intake in 359 individuals age ≥ 13 years from 87 households, using a household food frequency questionnaire, and measures of glycated haemoglobin (HbA1c), height and weight. We used multinomial logistic regression to model abnormal HbA1c (≥5.7%) and weight status (underweight, normal weight and overweight) as an outcome of total food intake and by nine food groups. Results were reported as odds ratios (OR) with 95% confidence intervals (CI). Models were adjusted for three nested sets of covariates.
RESULTS
The diet primarily consisted of staple food (cassava and plantain). High-Glycaemic Index staple food was the most consumed food group (median = 14 servings/week, p25-p75: 11-17). Milk, meat, fish and vegetables were the least consumed food groups (medians: 0-3 servings/week). Median intake of sugary food was 6 servings/week (p25-p75: 2-9). The OR of having abnormal HbA1c or being overweight increased with every weekly serving of food (1.02, 95% CI: 1.00-1.04 and 1.01 95% CI: 1.00-1.03, respectively). Of specific food groups, each weekly serving of meat increased the OR of being overweight with 33% (95% CI: 1.08-1.64), and fruit intake decreased the OR of abnormal HbA1c (0.94, 95% CI: 0.88-1.00), though this latter association was attenuated after adjustment for weight status, aerobic capacity, and socioeconomic status.
CONCLUSION
Diet was monotonous, mainly consisting of cassava and plantain, and increasing food intake was associated with abnormal HbA1c and overweight. To prevent non-communicable diseases a diet with higher intake of fish and vegetables, and less sugary food is recommended.
PubMed: 33632319
DOI: 10.1186/s13690-021-00547-x -
JAMA Network Open Jun 2018Based on efficacy results from pivotal randomized clinical trials, PD-1 (programmed cell death 1) inhibitors, such as nivolumab and pembrolizumab, have been approved to... (Meta-Analysis)
Meta-Analysis
A Comparison of Response Patterns for Progression-Free Survival and Overall Survival Following Treatment for Cancer With PD-1 Inhibitors: A Meta-analysis of Correlation and Differences in Effect Sizes.
IMPORTANCE
Based on efficacy results from pivotal randomized clinical trials, PD-1 (programmed cell death 1) inhibitors, such as nivolumab and pembrolizumab, have been approved to treat various cancers. Response patterns with varying effects on progression-free survival (PFS) and overall survival (OS) have been reported for these drugs.
OBJECTIVE
To compare 2 outcomes for PD-1 inhibitors: the correlation between PFS and OS and the differences in treatment effect size between PFS and OS.
DATA SOURCES
A systematic search of PubMed, Google Scholar, the Cochrane Library, Web of Science, and conference abstracts for randomized clinical trials of nivolumab and pembrolizumab published in English.
STUDY SELECTION
Randomized clinical trials of nivolumab or pembrolizumab in adults with solid-tissue cancers with a nonimmunotherapy control.
DATA EXTRACTION AND SYNTHESIS
Two reviewers screened the studies for selection and extracted data on medians and hazard ratios (HRs) for PFS and OS. A pooled meta-analysis was conducted.
MAIN OUTCOMES AND MEASURES
Across all trials, correlation coefficients between median PFS and median OS and between PFS benefit and OS benefit as well as the HRs of PFS and OS were assessed. The difference in treatment effect sizes between PFS and OS was assessed using a ratio of HRs (rHR). Subgroup analyses were conducted to observe differences based on drug, tumor type, and timing of therapy.
RESULTS
Ten randomized clinical trials that included 4653 patients and met inclusion criteria were identified, as were 2 others (comprising 764 patients) in which nivolumab or pembrolizumab was used following treatment with ipilimumab. The correlations between median PFS and median OS (r = 0.676; R2 = 0.457; P = .09) and the correlations between the change in PFS and the change in OS (r = 0.474; R2 = 0.225; P = .28) were not significant. However, the correlation between HRs of PFS and OS was significant (r = 0.637; R2 = 0.406; P = .048). Using random-effects meta-analysis, the protective effects of treatment were greater for OS than for PFS (pooled rHR, 1.18; 95% CI, 1.06-1.31; P = .002). There was no statistical evidence for heterogeneity across the studies (Q = 6.24; P = .72; I2 = 0%). Subgroup analyses showed some differences in the treatment effect sizes based on drug type, tumor type, and line of therapy.
CONCLUSIONS AND RELEVANCE
There was no significant correlation between OS and PFS in terms of medians and gains in medians, but their HRs were significantly correlated. The protective effects of treatment were greater for OS than for PFS. Traditional Response Evaluation Criteria in Solid Tumors-based PFS cannot capture the benefit of PD-1 inhibitors in patients with solid tumors, and OS should remain the gold standard.
Topics: Antineoplastic Agents; Antineoplastic Agents, Immunological; Disease Progression; Disease-Free Survival; Humans; Neoplasms; Programmed Cell Death 1 Receptor; Proportional Hazards Models; Randomized Controlled Trials as Topic; Survival; Treatment Outcome
PubMed: 30646078
DOI: 10.1001/jamanetworkopen.2018.0416 -
Cancer Medicine Dec 2014Cisplatin/gemcitabine association has been a standard of care for first-line regimen in advanced biliary tract cancer nevertheless oxaliplatin/gemcitabine regimen is... (Review)
Review
Cisplatin/gemcitabine association has been a standard of care for first-line regimen in advanced biliary tract cancer nevertheless oxaliplatin/gemcitabine regimen is frequently preferred. Because comparative effectiveness in clinical outcomes of cisplatin- versus oxaliplatin-containing chemotherapy is not available, a systematic review of studies assessing cisplatin/gemcitabine or oxaliplatin/gemcitabine chemotherapies in advanced biliary tract cancer was performed. Published studies evaluating cisplatin/gemcitabine or oxaliplatin/gemcitabine in advanced biliary tract cancer were included. Each study was weighted according to the number of patients included. The primary objective was to assess weighted median of medians overall survival (mOS) reported for both regimens. Secondary goals were to assess weighted median of medians progression-free survival (mPFS) and toxic effects were pooled and compared within each arm. Thirty-three studies involving 1470 patients were analyzed. In total, 771 and 699 patients were treated by cisplatin/gemcitabine and oxaliplatin/gemcitabine, respectively. Weighted median of mOS was 9.7 months in cisplatin group and 9.5 months in oxaliplatin group. Cisplatin-based chemotherapy was significantly associated with more grade 3 and 4 asthenia, diarrhea, liver toxicity, and hematological toxicity. Sensitivity analysis including only the studies with the standard regimen of cisplatin (25-35 mg/m(2) administered on days 1 and 8) showed that the weighted median of mOS increased from 9.7 to 11.7 months but Gem/CDDP regimen remained more toxic than Gemox regimen. These results suggest that the Gem/CDDP regimen with cisplatin (25-35 mg/m(2)) administered on days 1 and 8 is associated with survival advantage than Gemox regimen but with addition of toxicity.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cisplatin; Deoxycytidine; Disease-Free Survival; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Randomized Controlled Trials as Topic; Gemcitabine
PubMed: 25111859
DOI: 10.1002/cam4.299 -
Journal of Clinical Medicine Oct 2022Inhibition of the renin-angiotensin-aldosterone system (RAAS) is broadly recommended in many nephrological guidelines to prevent chronic kidney disease (CKD)... (Review)
Review
Inhibition of the renin-angiotensin-aldosterone system (RAAS) is broadly recommended in many nephrological guidelines to prevent chronic kidney disease (CKD) progression. This work aimed to analyze the robustness of randomized controlled trials (RCTs) investigating the renal and cardiovascular outcomes in CKD stages 3-5 patients treated with RAAS inhibitors (RAASi). We searched for RCTs in MEDLINE (PubMed), EMBASE databases, and the Cochrane register. Fragility indexes (FIs) for every primary and secondary outcome were calculated according to Walsh et al., who first described this novel metric, suggesting 8 as the cut-off to consider a study robust. Spearman coefficient was calculated to correlate FI to value and sample size of statistically significant primary and secondary outcomes. Twenty-two studies met the inclusion criteria, including 80,455 patients. Sample size considerably varied among the studies (median: 1693.5, range: 73-17,276). The median follow-up was 38 months (range 24-58). The overall median of both primary and secondary outcomes was 0 (range 0-117 and range 0-55, respectively). The median of FI for primary and secondary outcomes with a value lower than 0.05 was 6 (range: 1-117) and 7.5 (range: 1-55), respectively. The medians of the FI for primary outcomes with a value lower than 0.05 in CKD and no CKD patients were 5.5 (range 1-117) and 22 (range 1-80), respectively. Only a few RCTs have been shown to be robust. Our analysis underlined the need for further research with appropriate sample sizes and study design to explore the real potentialities of RAASi in the progression of CKD.
PubMed: 36294504
DOI: 10.3390/jcm11206184 -
Biomedical Reports May 2018Dual detection of α-fetoprotein (AFP) and free β-human chorionic gonadotropin (β-HCG) is a common screening method for Down syndrome in the second trimester and its...
Dual detection of α-fetoprotein (AFP) and free β-human chorionic gonadotropin (β-HCG) is a common screening method for Down syndrome in the second trimester and its efficacy is assessed by false-positive rate (FPR). The present study aimed to investigate the effects of the bias in median multiple of the median (mMoM) values of AFP and free β-HCG on FPR. The bias in mMoM values of AFP and free β-HCG and the bias in mMoM values under different gestational ages and weight groups were analyzed. Median equations were adjusted, and medians in LifeCycle software were replaced by local medians. Following two adjustments of the median equations, all indices including FPR, mMoM values of markers and mMoM values under different gestational ages and weight groups generally reached an ideal state. In conclusion, abnormal bias in mMoM values may prompt aberrant application of median equations, and regular monitoring of these indicators may be important for quality control in prenatal screening.
PubMed: 29725524
DOI: 10.3892/br.2018.1078 -
Journal of Athletic Training Feb 2023Significant health care disparities exist in the United States based on socioeconomic status (SES), but the role SES has in secondary school athletes' access to athletic...
CONTEXT
Significant health care disparities exist in the United States based on socioeconomic status (SES), but the role SES has in secondary school athletes' access to athletic training services has not been examined on a national scale.
OBJECTIVE
To identify differences in access to athletic training services in public secondary schools based on school SES.
DESIGN
Cross-sectional study.
SETTING
Database secondary analysis.
PATIENTS OR OTHER PARTICIPANTS
Data for 3482 public high schools.
MAIN OUTCOME MEASURE(S)
Data were gathered from the Athletic Training Locations and Services (ATLAS) database, US Census Bureau, and National Center for Education Statistics. We included schools from 5 states with the highest, middle, and lowest poverty percentages (15 states total) and collected county median household income, percentage of students eligible for free or reduced-price lunch, race and ethnicity demographics, and access to athletic training services (full-time athletic trainer [AT], part-time AT only, no AT) for each school. Data were summarized in means, SDs, medians, interquartile ranges (IQRs), frequencies and proportions, 1-way analyses of variance, and Kruskal-Wallis tests.
RESULTS
Differences were present in school SES between schools with full-time, part-time-only, and no athletic training services. Schools with greater access to athletic training services had fewer students eligible for free or reduced-price lunch (full time: 41.1% ± 22.3%, part time only: 45.8% ± 24.3%, no AT: 52.9% ± 24.9; P < .001). Similarly, county median household income was higher in schools with increased access to athletic training services (full time median [IQR]: $56 026 [$49 085-$64 557], part time only: $52 719 [$45 355-$62 105], and no AT: $49 584 [$41 094-$57 688]; P < .001).
CONCLUSIONS
Disparities in SES were seen in access to athletic training services among a national sample of public secondary schools. Access to ATs positively influences student-athletes' health care across several measures. Pilot programs or government funds have been used previously to fund athletic training services and should be considered to ensure equitable access, regardless of school SES.
Topics: Humans; United States; Cross-Sectional Studies; Sports; Athletes; Schools; Social Class
PubMed: 34623428
DOI: 10.4085/1062-6050-0240.21 -
Diabetes & Metabolism Journal Oct 2020Inflammatory cytokines are increasingly utilized to detect high-risk individuals for cardiometabolic diseases. However, with large population and assay methodological...
BACKGROUND
Inflammatory cytokines are increasingly utilized to detect high-risk individuals for cardiometabolic diseases. However, with large population and assay methodological heterogeneity, no clear reference currently exists.
METHODS
Among participants of the Cardiovascular and Metabolic Diseases Etiology Research Center cohort, of community-dwelling adults aged 30 to 64 without overt cardiovascular diseases, we presented distributions of tumor necrosis factor (TNF)-α and -β, interleukin (IL)-1α, -1β, and 6, monocyte chemoattractant protein (MCP)-1 and -3 and high sensitivity C-reactive protein (hsCRP) with and without non-detectable (ND) measurements using multiplex enzyme-linked immunosorbent assay. Then, we compared each markers by sex, age, and prevalence of type 2 diabetes mellitus, hypertension, and dyslipidemia, using the Wilcoxon Rank-Sum Test.
RESULTS
In general, there were inconsistencies in direction and magnitude of differences in distributions by sex, age, and prevalence of cardiometabolic disorders. Overall, the median and the 99th percentiles were higher in men than in women. Older participants had higher TNF-α, high sensitivity IL-6 (hsIL-6), MCP-1, hsCRP, TNF-β, and MCP-3 median, after excluding the NDs. Participants with type 2 diabetes mellitus had higher median for all assayed biomarkers, except for TNF-β, IL-1α, and MCP-3, in which the medians for both groups were 0.00 due to predominant NDs. Compared to normotensive group, participants with hypertension had higher TNF-α, hsIL-6, MCP-1, and hsCRP median. When stratifying by dyslipidemia prevalence, the comparison varied significantly depending on the treatment of NDs.
CONCLUSION
Our findings provide sex-, age-, and disease-specific reference values to improve risk prediction and diagnostic performance for inflammatory diseases in both population- and clinic-based settings.
Topics: Adult; Biomarkers; Female; Humans; Independent Living; Male; Metabolic Diseases; Middle Aged; Tumor Necrosis Factor-alpha
PubMed: 32431105
DOI: 10.4093/dmj.2019.0119 -
Journal of Radiation Oncology 2018BioZorb® is a tumor bed marker placed during partial mastectomy for targeted post-operative radiation. This study was designed to evaluate BioZorb® effect on radiation...
OBJECTIVE
BioZorb® is a tumor bed marker placed during partial mastectomy for targeted post-operative radiation. This study was designed to evaluate BioZorb® effect on radiation boost clinical target volume (CTV), planning target volume (PTV), median dose to ipsilateral lung (Gy), and heart irradiation in left-sided cancers.
METHODS
Data was collected via a retrospective cohort study with two study arms: BioZorb® intra-operative placement versus no BioZorb® placement. Patients were stratified by BMI, age, tumor laterality and volume, and cancer stage. Mean, standard deviation, median, range of cubic centimeters of clinical and planning target volume, cardiac dose in left-sided cancers, ipsilateral lung dose, and volume of ipsilateral lung receiving 20 Gy were reported.
RESULTS
Of 143 patients, median CTV (cm) was 8.7 and 14.2 ( = 0.0048), median PTV (cm) was 53.2 and 79.6 ( = 0.0010), median ipsilateral lung Gy was 7.53 and 6.74 ( = 0.0099) and volume (cc) of ipsilateral radiation lung at 20 Gy was 13.4 and 12 ( = 0.008), and median heart Gy in left-sided cancers was 2.01 and 2.21 ( = 0.9952) in BioZorb® and non-BioZorb® arms, respectively. Patients with BMIs of 25-30 had CTV medians of 7.8 and 11.1 in BioZorb® and non-BioZorb® arms, respectively ( = 0.0293).
CONCLUSION
The BioZorb® arm showed statistically significant reductions in CTV and PTV but not ipsilateral lung or heart irradiation.
PubMed: 29937986
DOI: 10.1007/s13566-017-0339-y