Category: Nevin Manimala

Cancer Epidemiol Biomarkers Prev. 2022 Jun 14:cebp.0314.2022-3-18 10:35:08.940. doi: 10.1158/1055-9965.EPI-22-0314. Online ahead of print.

ABSTRACT

BACKGROUND: Gonadotoxic treatment-related infertility has a significant impact on quality of life in childhood cancer survivors. Genome-wide association analyses to delineate the risk of infertility in childhood cancer survivors have not been previously reported.

METHODS: Leveraging genotype data from a large survivor cohort, the Childhood Cancer Survivor Study (CCSS), we investigated the role of Single Nucleotide Polymorphisms (SNPs) on future pregnancy or siring a pregnancy in survivors without pelvic, testicular, or brain radiation who had ever been married. We calculated sex-stratified hazard ratios, using Cox proportional hazards modeling, adjusting for birth cohort (before 1965 vs. 1965 or later) and doses of relevant chemotherapies; replication was attempted in the independent St. Jude Lifetime Cohort study (SJLIFE).

RESULTS: In the CCSS cohort, nine SNPs were found to be suggestive (p-value <10-7) or statistically significantly (p-value <5×10-8) associated with pregnancy, however, none of the SNPs were replicated in SJLIFE. Cohorts differed based on the overall pregnancy rate, frequency of sterilizing procedures and birth cohort.

CONCLUSIONS: We were not able to replicate our findings of SNPs associated with pregnancy in childhood cancer survivors.

IMPACT: Future attempts at replication should be considered in cohorts treated in a comparable era. Additionally, understanding the role of genetics in fertility in childhood cancer survivors may be better approached using more advanced sequencing techniques.

PMID:35700038 | DOI:10.1158/1055-9965.EPI-22-0314

Cancer Epidemiol Biomarkers Prev. 2022 Jun 14:cebp.0123.2022-2-12 14:42:56.847. doi: 10.1158/1055-9965.EPI-22-0123. Online ahead of print.

ABSTRACT

BACKGROUND: Testicular germ cell tumors (TGCTs), histologically classified as seminomas and non-seminomas, are believed to arise from primordial gonocytes, with the maturation process blocked when are subjected to DNA methylation reprogramming. Single-nucleotide polymorphisms (SNPs) in DNA methylation machinery and folate-dependent one-carbon metabolism genes have been postulated to influence the proper establishment of DNA methylation.

METHODS: In this pathway-focused investigation we evaluated the association between 273 selected tag SNPs from 28 DNA methylation-related genes and TGCT risk. We carried out association analysis at individual SNP and gene-based level using summary statistics from the Genome Wide Association Study meta-analysis recently conducted by the international Testicular Cancer Consortium on 10,156 TGCT cases and 179,683 controls.

RESULTS: In individual SNP analyses, seven SNPs, four mapping within MTHFR, were associated with TGCT risk after correction for multiple testing (q-value ≤.05). Queries of public databases showed that three of these SNPs were associated with MTHFR changes in enzymatic activity (rs1801133) or expression level in testis tissue (rs12121543, rs1476413). Gene-based analyses revealed MTHFR (q-value=8.4×10-4), MECP2 (q-value=2×10-3) and ZBTB4 (q-value=0.03) as the top TGCT-associated genes. Stratifying by tumor histology, four MTHFR SNPs were associated with seminoma. In gene-based analysis MTHFR was associated with risk of seminoma (q-value=2.8×10-4), but not with non-seminomatous tumors (q-value=0.22).

CONCLUSIONS: Genetic variants within MTHFR, potentially having an impact on the DNA methylation pattern, are associated with TGCT risk.

IMPACT: This finding suggests that TGCT pathogenesis could be associated to the folate cycle status, and this relation could be partly due to hereditary factors.

PMID:35700037 | DOI:10.1158/1055-9965.EPI-22-0123

Int J Environ Health Res. 2022 Jun 14:1-11. doi: 10.1080/09603123.2022.2088704. Online ahead of print.

ABSTRACT

Analyzing the effects of interventions from a theoretical and statistical perspective that allows understanding these dynamic relationships of obesity etiology can be a more efficient and innovative way of understanding the phenomenon’s complexity. Thus, we aimed to analyze the pattern of cardiovascular risk factors between-participants, and the effects within-participants of a multidisciplinary intervention on cardiovascular risk factors in overweight children. This is a randomized clinical trial, and 41 participated in this study. A multicomponent intervention (physical activities, nutritional and psychological counseling) was performed for 10 weeks. Anthropometric and hemodynamics measurements, lipid and glucose profile, cardiorespiratory fitness, and left ventricular mass were evaluated. A network analysis was done. Considering patterns in the network at baseline, WC, WHR, BMI, and Fat were the main variables for cardiovascular risks. Group was the most critical variable in the within-participant network. Participating in a multicomponent intervention and decreasing body fat promoted beneficial cardiovascular factors.

PMID:35699999 | DOI:10.1080/09603123.2022.2088704

JMIR Form Res. 2022 Jun 14;6(6):e34366. doi: 10.2196/34366.

ABSTRACT

BACKGROUND: Approximately 1 in 5 American adults experience mental illness every year. Thus, mobile phone-based mental health prediction apps that use phone data and artificial intelligence techniques for mental health assessment have become increasingly important and are being rapidly developed. At the same time, multiple artificial intelligence-related technologies (eg, face recognition and search results) have recently been reported to be biased regarding age, gender, and race. This study moves this discussion to a new domain: phone-based mental health assessment algorithms. It is important to ensure that such algorithms do not contribute to gender disparities through biased predictions across gender groups.

OBJECTIVE: This research aimed to analyze the susceptibility of multiple commonly used machine learning approaches for gender bias in mobile mental health assessment and explore the use of an algorithmic disparate impact remover (DIR) approach to reduce bias levels while maintaining high accuracy.

METHODS: First, we performed preprocessing and model training using the data set (N=55) obtained from a previous study. Accuracy levels and differences in accuracy across genders were computed using 5 different machine learning models. We selected the random forest model, which yielded the highest accuracy, for a more detailed audit and computed multiple metrics that are commonly used for fairness in the machine learning literature. Finally, we applied the DIR approach to reduce bias in the mental health assessment algorithm.

RESULTS: The highest observed accuracy for the mental health assessment was 78.57%. Although this accuracy level raises optimism, the audit based on gender revealed that the performance of the algorithm was statistically significantly different between the male and female groups (eg, difference in accuracy across genders was 15.85%; P<.001). Similar trends were obtained for other fairness metrics. This disparity in performance was found to reduce significantly after the application of the DIR approach by adapting the data used for modeling (eg, the difference in accuracy across genders was 1.66%, and the reduction is statistically significant with P<.001).

CONCLUSIONS: This study grounds the need for algorithmic auditing in phone-based mental health assessment algorithms and the use of gender as a protected attribute to study fairness in such settings. Such audits and remedial steps are the building blocks for the widespread adoption of fair and accurate mental health assessment algorithms in the future.

PMID:35699997 | DOI:10.2196/34366

J Med Internet Res. 2022 Jun 13;24(6):e34307. doi: 10.2196/34307.

ABSTRACT

BACKGROUND: Upper extremity (UE) impairment affects up to 80% of stroke survivors and accounts for most of the rehabilitation after discharge from the hospital release. Compensation, commonly used by stroke survivors during UE rehabilitation, is applied to adapt to the loss of motor function and may impede the rehabilitation process in the long term and lead to new orthopedic problems. Intensive monitoring of compensatory movements is critical for improving the functional outcomes during rehabilitation.

OBJECTIVE: This review analyzes how technology-based methods have been applied to assess and detect compensation during stroke UE rehabilitation.

METHODS: We conducted a wide database search. All studies were independently screened by 2 reviewers (XW and YF), with a third reviewer (BY) involved in resolving discrepancies. The final included studies were rated according to their level of clinical evidence based on their correlation with clinical scales (with the same tasks or the same evaluation criteria). One reviewer (XW) extracted data on publication, demographic information, compensation types, sensors used for compensation assessment, compensation measurements, and statistical or artificial intelligence methods. Accuracy was checked by another reviewer (YF). Four research questions were presented. For each question, the data were synthesized and tabulated, and a descriptive summary of the findings was provided. The data were synthesized and tabulated based on each research question.

RESULTS: A total of 72 studies were included in this review. In all, 2 types of compensation were identified: disuse of the affected upper limb and awkward use of the affected upper limb to adjust for limited strength, mobility, and motor control. Various models and quantitative measurements have been proposed to characterize compensation. Body-worn technology (25/72, 35% studies) was the most used sensor technology to assess compensation, followed by marker-based motion capture system (24/72, 33% studies) and marker-free vision sensor technology (16/72, 22% studies). Most studies (56/72, 78% studies) used statistical methods for compensation assessment, whereas heterogeneous machine learning algorithms (15/72, 21% studies) were also applied for automatic detection of compensatory movements and postures.

CONCLUSIONS: This systematic review provides insights for future research on technology-based compensation assessment and detection in stroke UE rehabilitation. Technology-based compensation assessment and detection have the capacity to augment rehabilitation independent of the constant care of therapists. The drawbacks of each sensor in compensation assessment and detection are discussed, and future research could focus on methods to overcome these disadvantages. It is advised that open data together with multilabel classification algorithms or deep learning algorithms could benefit from automatic real time compensation detection. It is also recommended that technology-based compensation predictions be explored.

PMID:35699982 | DOI:10.2196/34307

JMIR Form Res. 2022 Jun 13;6(6):e35194. doi: 10.2196/35194.

ABSTRACT

BACKGROUND: Chronic pain is associated with an elevated risk of suicidal ideation (SI).

OBJECTIVE: We aimed to examine if the presence or the search for Meaning in Life (MiL) are associated with less SI and explore whether MiL profiles emerge in our cohort. These profiles can be described as high presence-high search, high presence-low search, low presence-low search, and low presence-high search.

METHODS: In this observational study, we recruited 70 patients who were referred to the Multidisciplinary Pain Center of the Geneva University Hospitals and who answered positively to question 9 on the Beck Depression Inventory, 2nd Edition, investigating SI. Patients who agreed to participate in the study were further investigated; they participated in a structured diagnostic interview to screen for psychiatric diagnoses. During this interview, they completed the Meaning in Life Questionnaire and the semistructured Scale for Suicide Ideation (SSI) to assess the characteristics and severity of SI.

RESULTS: There was a statistically significant correlation between the presence of MiL subscale and the SSI. These 2 scales had a negative and statistically highly significant correlation (R=-.667; P<.001). The results also showed a negative and statistically highly significant correlation between the score of the search for MiL and the SSI (R=-.456; P<.001). The results thus pointed to the presence of MiL as a potential protective factor against the severity of SI, while the search for MiL is also a possible resiliency factor, although to a lesser extent. The profile low presence-low search grouped the vast majority (47%) of the patients; in these patients, the mean SSI score was 14.36 (SD 5.86), much higher compared with that of the other subgroups.

CONCLUSIONS: This study’s results point to MiL as a concept of interest regarding devising psychotherapeutic interventions for chronic pain patients in order to reduce the suicidal risk and more accurately determine patients’ suffering.

PMID:35699974 | DOI:10.2196/35194

Leuk Lymphoma. 2022 Jun 14:1-10. doi: 10.1080/10428194.2022.2087069. Online ahead of print.

ABSTRACT

Compared to Asian and Latin American populations, sinonasal NK- or T-cell lymphoma is rare in Europe. All patients with sinonasal NK- or T-cell lymphoma in Denmark from 1980 to 2017 were validated histologically, and the disease behavior and demographics were extracted from medical records and national registries. Prognostic factors associated with mortality were determined using survival statistics. We included 56 patients: 40 extranodal NK/T-cell lymphoma (nasal type) (ENKTCL) and 16 peripheral T-cell lymphoma (not otherwise specified) (PTCL). The median age was 66, and most patients were male (72%). The ENKTCL and PTCL 5-year overall survival was 48% and 50%, respectively; progression-free survival was 38% for both. With ENKTCL, stage and performance status increased mortality significantly (HR = 8.6; p < 0.001 and HR = 4.23; p = 0.04). In conclusion, disseminated disease had a dismal outcome and the onset of ENKTCL in this ethnically homogeneous European cohort was about a decade later than reported in Asian populations.

PMID:35699970 | DOI:10.1080/10428194.2022.2087069

JAMA Netw Open. 2022 Jun 1;5(6):e2216958. doi: 10.1001/jamanetworkopen.2022.16958.

ABSTRACT

IMPORTANCE: Breast cancer causes disproportionate disease burden among various racial and ethnic groups in the US. However, state-level temporal trends and racial and ethnic disparities and whether metabolic and lifestyle factors and screening access are associated with temporal changes remain largely unknown.

OBJECTIVES: To investigate temporal trends and racial and ethnic variations at the state level and ecological correlations between obesity, physical activity, and mammography screening and breast cancer incidence and mortality trends among women in the US.

DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted to analyze breast cancer incidence and mortality trends among women in the US from January 1, 1999, to December 31, 2017, whereas an ecological analysis was performed to assess the associations. Data were analyzed from March 1, 2021, to September 30, 2021. Population-based cancer registry data were obtained from US Cancer Statistics incidence and mortality data. Prevalence of obesity, physical activity, and mammography screening were obtained from the Behavioral Risk Factor Surveillance System.

EXPOSURES: Prevalence of obesity, physical activity, and mammography screening.

MAIN OUTCOMES AND MEASURES: Breast cancer incidence and mortality trends from 1999 to 2017 in the 50 US states and the District of Columbia.

RESULTS: A total of 4 136 123 breast cancer cases and 782 454 deaths were included in the analysis, with a significant reduction in incidence (average annual percent change [AAPC], -0.4% [95% CI, -0.6% to -0.2%)]) and mortality (AAPC, -1.7% [95% CI, -1.8% to -1.5%]) during the study period. A significant state-level variation in breast cancer incidence and mortality between White women and those of other races and ethnicities was observed. A significant positive correlation was found between obesity and breast cancer incidence (r = 0.316; P = .02) and mortality (r = 0.400; P = .004) and an inverse correlation was found between physical activity and incidence (r = -0.577; P < .001) in women 55 years or older and mammography screening and mortality trends (r = -0.644; P < .001) in women 40 years or older.

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that racial and ethnic disparities exist at the state level with regard to breast cancer incidence and mortality among women in the US. Metabolic and lifestyle factors and screening access were associated with the observed trends and racial and ethnic disparities. Interventions targeting these factors may help reduce the incidence of breast cancer and related deaths.

PMID:35699957 | DOI:10.1001/jamanetworkopen.2022.16958

Ther Innov Regul Sci. 2022 Jun 14. doi: 10.1007/s43441-022-00420-1. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: DARE-19 (NCT04350593) was a randomized trial studying the effects of dapagliflozin, an SGLT2 inhibitor, in hospitalized patients with COVID-19 pneumonia and cardiometabolic risk factors. The conduct of DARE-19 offered the opportunity to define an innovative and clinically meaningful endpoint in a new disease that would best reflect the known profile of dapagliflozin, accompanied by the statistical challenges of analysis and interpretation of such a novel endpoint.

METHODS: Hierarchical composite endpoints (HCEs) are based on clinical outcomes which, unlike traditional composite endpoints incorporate ranking of components according to clinical importance. Design of an HCE requires the clinical considerations specific to the therapeutic area under study and the mechanism of action of the investigational treatment. Statistical aspects for the clinical endpoints include the proper definition of the estimand as suggested by ICH E9(R1) for the precise specification of the treatment effect measured by an HCE.

RESULTS: We describe the estimand of the DARE-19 trial, where an HCE was constructed to capture the treatment effect of dapagliflozin in hospitalized patients with COVID-19, and was analyzed using a win odds. Practical aspects of designing new studies based on an HCE are described. These include sample size, power, and minimal detectable effect calculations for an HCE based on the win odds analysis, as well as handling of missing data and the clinical interpretability of the win odds in relation to the estimand.

CONCLUSIONS: HCEs are flexible endpoints that can be adapted for use in different therapeutic areas, with win odds as the analysis method. DARE-19 is an example of a COVID-19 trial with an HCE as one of the primary endpoints for estimating a clinically interpretable treatment effect in the COVID-19 setting.

PMID:35699910 | DOI:10.1007/s43441-022-00420-1

Hepatol Int. 2022 Jun 14. doi: 10.1007/s12072-022-10357-0. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Whether the efficacies of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in treating liver-related outcomes of decompensated chronic hepatitis B (CHB) patients are comparable remained inconclusive.

METHODS: An 8-year cohort study of 736 decompensated CHB patients was conducted, and 65 TDF-treated patients were sex, age and model for end-stage liver disease (MELD) scores-1:4 matched with 260 ETV-treated patients through propensity score-matching method.

RESULTS: Of 736 patients, 574 (78%) were male, with a mean age of 54.3 years, 438 (59.5%) had cirrhosis, 147 (20%) were positive for HBeAg, and 84 (11.6%) and 652 (88.4%) were treated with TDF and ETV, respectively. The 652 ETV-treated patients were older, had higher baseline MELD score and rates of encephalopathy, but lower ALT levels than the 84 TDF-treated patients. No significant differences were observed in the cumulative incidences of liver-related mortality or liver transplantation (1-month, 18.45 vs. 14.01%, p = 0.368; 8-year, 39.74 vs. 34.24%, p = 0.298), and hepatocellular carcinoma development (5-year, 7.21 vs.13.17%, p = 0.994; 8-year, 11.60 vs.13.17%, p = 0.857) between the matched 260 ETV- and 65 TDF-treated patients, regardless of time points. Baseline MELD score (subdistribution hazard ratio (sHR): 1.063; 95% confidence interval (CI) of sHR: 1.016-1.112) and hepatic encephalopathy (sHR: 5.127; 95% CI sHR: 3.032-8.669) were independently associated with liver-related mortality or liver transplantation in the matched patients.

CONCLUSIONS: ETV and TDF had comparable efficacy in the short- and long-term liver-related outcomes of decompensated CHB patients, and baseline liver reserve was associated with the outcomes.

PMID:35699864 | DOI:10.1007/s12072-022-10357-0