Tag: statistics

J Transl Med. 2023 Jan 29;21(1):54. doi: 10.1186/s12967-022-03843-4.

ABSTRACT

BACKGROUND: Clear cell sarcomas (CCSs) are translocated aggressive malignancies, most commonly affecting young adults with a high incidence of metastases and a poor prognosis. Research into the disease is more feasible when adequate models are available. By establishing CCS cell lines from a primary and metastatic lesion and isolating healthy fibroblasts from the same patient, the in vivo process is accurately reflected and aspects of clinical multistep carcinogenesis recapitulated.

METHODS: Isolated tumor cells and normal healthy skin fibroblasts from the same patient were compared in terms of growth behavior and morphological characteristics using light and electron microscopy. Tumorigenicity potential was determined by soft agar colony formation assay and in vivo xenograft applications. While genetic differences between the two lineages were examined by copy number alternation profiles, nuclear magnetic resonance spectroscopy determined arginine methylation as epigenetic features. Potential anti-tumor effects of a protein arginine N-methyltransferase type I (PRMT1) inhibitor were elicited in 2D and 3D cell culture experiments using cell viability and apoptosis assays. Statistical significance was calculated by one-way ANOVA and unpaired t-test.

RESULTS: The two established CCS cell lines named MUG Lucifer prim and MUG Lucifer met showed differences in morphology, genetic and epigenetic data, reflecting the respective original tissue. The detailed cell line characterization especially in regards to the epigenetic domain allows investigation of new innovative therapies. Based on the epigenetic data, a PRMT1 inhibitor was used to demonstrate the targeted antitumor effect; normal tissue cells isolated and immortalized from the same patient were not affected with the IC₅₀ used.

CONCLUSIONS: MUG Lucifer prim, MUG Lucifer met and isolated and immortalized fibroblasts from the same patient represent an ideal in vitro model to explore the biology of CCS. Based on this cell culture model, novel therapies could be tested in the form of PRMT1 inhibitors, which drive tumor cells into apoptosis, but show no effect on fibroblasts, further supporting their potential as promising treatment options in the combat against CCS. The data substantiate the importance of tailored therapies in the advanced metastatic stage of CCS.

PMID:36710341 | DOI:10.1186/s12967-022-03843-4

BMC Womens Health. 2023 Jan 30;23(1):39. doi: 10.1186/s12905-023-02180-y.

ABSTRACT

BACKGROUND: In Ethiopia high population growth and unintended pregnancies are posing pressures where the economy is incapable of holding overpopulation. Despite this problem, utilization of modern contraception is low in rural areas of the country, especially in the areas where polygamy is common. Therefore, this study was conducted to assess contraceptive utilization and associated factors among polygamous and monogamous women in, Ethiopia.

METHOD: A community-based comparative cross-sectional and phenomenological study design was employed from July 1 to September 30, 2021, on the total sample size of 774 selected married women of the reproductive age group by using a multistage sampling method and a purposive sampling method were used for the qualitative part of the study. A pre-tested interview with a structured questionnaire was used to collect data and key informants were interviewed using semi-structured questionnaire. Associated factors were analyzed by using bivariable and multivariable binary logistic regression models. The odds ratio, with a 95% confidence level, was used to declare a statistically significant association.

RESULT: A total of 703 married women of the reproductive age groups were interviewed, yielding a 90.89% response rate; among these married women, 352 and 351 were in monogamous and polygamous relationships. The proportion of women who use modern contraceptives was 161 (45.7%) in monogamous relationship, and 151 (43.0%) in polygamous relationships. Overall, utilization of modern contraceptives was significantly associated with educational status (AOR = 2.143, CI:1.428-3.216), religion (AOR = 1.704, CI: 1.144-2.539), undesired fertility (AOR = 3.17,CI:1.939-5.183), who decides on the number of children (AOR = 3.054, CI:1.93-4.832), getting clear information by Health care provider (AOR = 4.624, CI:3.132-6.828), family pressure (AOR = 1.855, CI:1.351-2.75), fear of social stigma (AOR = 2.482, CI:1.666-3.699), and accepts myths about contraceptives (AOR = 1.878, CI:1.278-2.761).

CONCLUSION: This study identified that utilization of modern contraception was low in the study area. The district health office and concerned stakeholders should implement interventions that scale up contraceptive use, need family involvement in decision making, addressing myths around contraceptives, helping women to get education, and training of health care providers.

PMID:36710331 | DOI:10.1186/s12905-023-02180-y

BMC Geriatr. 2023 Jan 30;23(1):53. doi: 10.1186/s12877-023-03728-1.

ABSTRACT

BACKGROUND: Around the world, advances in public health and changes in clinical interventions have resulted in increased life expectancy. Multimorbidity is becoming more of an issue, particularly in countries where the population is rapidly ageing. We aimed to determine the prevalence of multimorbidity and disease-specific multimorbidity and examine its association with demographic and socioeconomic characteristics among older adults in India and its states.

METHODS: The individual data from the longitudinal ageing study in India (LASI) were used for this study, with 11 common chronic conditions among older adults aged 60 and above years (N = 31,464). Descriptive statistics were used to report the overall prevalence of multimorbidity and disease-specific burden of multimorbidity. Multinomial logistic regression has been used to explore the factors associated with multimorbidity.

RESULTS: Prevalence of single morbidity was 30.3%, and multimorbidity was 32.1% among older people in India. Multimorbidity was higher among females and in urban areas and increased with age and among those living alone. Hypertension, arthritis and thyroid were highly prevalent among females and chronic lung diseases and stroke were highly prevalent among males. The older people in the state of Kerala had a high prevalence of multimorbidity (59.2%). Multimorbidity was found to be more likely in older age groups of 75-79 years (RR-1.69; CI: 1.53-1.87) and 80 years and above (RR-1.40; CI: 1.27-1.56) and in the Western (RR-2.16; CI: 1.90-2.44) and Southern regions (RR-2.89; CI: 2.57-3.24). Those who were living with a spouse (RR-1.60; CI: 1.15-2.23) were more likely to have multimorbidity. Disease-specific multimorbidity was high in chronic heart disease (91%) and low in angina (64.8%).

CONCLUSIONS: The findings suggest that multimorbidity has a positive relationship with advancing age, and disease-specific burden of multimorbidity is higher among chronic heart patients. Comorbidity, especially among those who already have chronic heart disease, stroke, cholesterol or thyroid disorder can have severe consequences on physical functioning, therefore, disease-specific health management needs to be enhanced.

PMID:36710322 | DOI:10.1186/s12877-023-03728-1

Acta Parasitol. 2023 Jan 30. doi: 10.1007/s11686-023-00661-6. Online ahead of print.

ABSTRACT

PURPOSE: Neosporosis is an important widespread parasitic infection caused by N. caninum. It infects a wide range of warm-blooded animals as intermediate hosts and dogs as the definitive host. Nevertheless, there are a number of questions regarding the life cycle and epidemiological aspects of N. caninum. Also, the role of felids (domestic and non-domestic) in the life cycle of N. caninum has been little described. Therefore, this study was conducted to evaluate the global prevalence of N. caninum in domestic and wild felids.

METHODS: PubMed, Scopus, Google Scholar, Web of Science, and ScienceDirect databases were searched for articles published on the prevalence of N. caninum in felids until Aprill 2, 2022 and the reference lists of retrieved articles were screened. A random-effects meta-analysis model was used to estimate the pooled prevalence and 95% confidence interval. Heterogeneity among studies was evaluated using Cochran’s Q and the I² statistic.

RESULTS: After exclusion of irrelevant articles and duplication removal, 30 studies were eligible for quantitative analysis including 20 studies on domestic cats and 10 studies on wild felids. The overall prevalence of neosporosis infection in cats was 15% (95% CI 10-21%) that was significantly higher in wild felids (26%, 95% CI 13-38%) than in domestic cats (11%, 95% CI 6-16%) (P = 0.03). There was no significant difference in pooled prevalence between male and female domestic cats (P = 0.75). Regarding continent, the lowest prevalence of neosporosis infection was in Asia (9%, 95% CI 1-20%) and the highest was in North America (43.6%, 95% CI 33.9-53.2%) and Africa (18%, 95% CI 9-46%). Higher prevalence was obtained when using the NAT with 22% (95% CI 7-37%), compared to the IFAT (17%, 95% CI 9-24%) and ELISA (6%, 95% CI 2-9%) (P = 0.01).

CONCLUSION: The findings highlighted the importance of felids as potential intermediate hosts of neosporosis despite the fact that the source of the parasite for these animals was unknown. Further studies should be performed to investigate the role of this top predator (felids) in maintaining both domestic and sylvatic cycles of Neospora caninum.

PMID:36710305 | DOI:10.1007/s11686-023-00661-6

J Hum Genet. 2023 Jan 30. doi: 10.1038/s10038-023-01124-6. Online ahead of print.

ABSTRACT

Sexual maturation is a complex physiological process that involves multiple variables, such as genetic and environmental factors. Among females, age at menarche (AM) is a critical milestone for sexual maturation. This study aimed to identify genetic markers of AM using nationwide population cohort data in Taiwan. Females with self-reported AM between 10 and 16 years (N = 39,827) were eligible for the final analysis. To identify genetic signals related to AM, we conducted a genome-wide association study using a linear regression model and split-half meta-analysis method to verify our findings. The Functional Mapping and Annotation web-based platform was used for positional mapping and gene-based and gene-set analyses. The meta-analysis identified four significant loci, i.e., LIN28B (pooled P = 1.39 × 10^-21), NOL4 (pooled P = 8.94 × 10^-9), GPR45 (pooled P = 4.19 × 10^-11), and LOC105373831 (pooled P = 4.37 × 10^-8), that were associated with AM. MAGMA gene-based analysis revealed that LIN28B (P = 1.13 × 10^–8), NOL4 (P = 2.27 × 10^–7), RXRG (P = 4.34 × 10-⁷), ETV5 (P = 1.75 × 10^-6), and HACE1 (P = 1.82 × 10^–6) were significantly associated with AM, while the gene-set analysis identified a significantly enriched pathway involving mTOR signaling complex (FDR corrected P = 1.28 × 10^–2). The results replicated evidence for several genetic markers associated with AM in the Taiwanese female population. Our analysis identified a novel locus (rs7239368) in NOL4 associated with AM (β = 0.051 ± 0.009 years, pooled P = 8.94 × 10^-9), whereas additional research is needed to validate its molecular role in sexual maturation.

PMID:36710296 | DOI:10.1038/s10038-023-01124-6

Eur J Health Econ. 2023 Jan 30. doi: 10.1007/s10198-022-01557-4. Online ahead of print.

ABSTRACT

This paper studies how opioid analgesic sales are empirically related to socioeconomic disparities in France, with a focus on poverty. This analysis is made possible using the OpenHealth database, which provides retail sales data for opioid analgesics available on the French market. We exploit firm-level data for each of the 94 departments in Metropolitan France between 2008 and 2017. We show that increases in the poverty rate are associated with increases in sales: a one percentage point increase in poverty is associated with approximately a 5% increase in mild opioid sales. Our analysis further shows that opioid sales are positively related to the share of middle-aged people and individuals with basic education only, while they are negatively related to population density. The granularity and longitudinal nature of these data allow us to control for a large pool of potential confounding factors. Our results suggest that additional interventions should be more intensively addressed toward the most deprived areas. We conclude that a combination of policies aimed at improving economic prospects and strictly monitoring access to opioid medications would be beneficial for reducing opioid-related harm.

PMID:36710287 | DOI:10.1007/s10198-022-01557-4

Am J Ophthalmol. 2023 Jan 27:S0002-9394(23)00013-2. doi: 10.1016/j.ajo.2023.01.001. Online ahead of print.

NO ABSTRACT

PMID:36710241 | DOI:10.1016/j.ajo.2023.01.001

Eur Urol. 2023 Jan 27:S0302-2838(23)00056-8. doi: 10.1016/j.eururo.2023.01.020. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies indicate that the benefit of short-term androgen deprivation therapy (ADT) with radiotherapy (RT) for prostate cancer depends on competing risks.

OBJECTIVE: To determine whether a quantitative method to stratify patients by risk for competing events (omega score) could identify subgroups that selectively benefit from ADT.

DESIGN, SETTING, AND PARTICIPANTS: An ancillary analysis of NRG/RTOG 9408 phase 3 trial (NCT00002597) involving 1945 prostate cancer patients was conducted.

INTERVENTION: Short-term ADT.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We applied generalised competing event regression models incorporating age, performance status, comorbidity, T category, Gleason score (GS), and prostate-specific antigen (PSA), to stratify patients according to relative hazards for primary cancer-related events (distant metastasis or prostate cancer death) versus competing noncancer mortality. We tested interactions between ADT and subgroups defined by standard risk criteria versus relative risk (RR) using the omega score.

RESULTS AND LIMITATIONS: T2b, higher GS, and higher PSA were associated with an increased RR for cancer-related versus competing mortality events (a higher omega score); increased age and comorbidity were associated with a decreased omega score. Of 996 patients with low-risk/favourable intermediate-risk (FIR) disease, 286 (28.7%) had a high omega score (≥0.314). Of 768 patients with unfavourable intermediate-risk disease, 175 (22.8%) had a low omega score. The overall discordance in risk classification was 26.1%. Both standard criteria and omega score identified significant interactions for the effect of ADT on cancer-related events and late mortality in low- versus high-risk subgroups. Within the low-risk/FIR subgroup, a higher omega score identified patients in whom ADT significantly reduced cancer events and improved event-free survival. Limitations are the need for external/prospective validation and lower RT doses than contemporary standards.

CONCLUSIONS: Stratification based on competing event risk is useful for identifying prostate cancer patients who selectively benefit from ADT.

PATIENT SUMMARY: We analysed the effectiveness of androgen deprivation therapy (ADT) for localised prostate cancer among patients, defined by the relative risk (RR) for cancer versus noncancer events. Among patients with traditional low-risk/favourable intermediate-risk disease, those with a higher RR benefitted from short-term ADT.

PMID:36710205 | DOI:10.1016/j.eururo.2023.01.020

J Thromb Haemost. 2022 Dec 30:S1538-7836(22)19071-9. doi: 10.1016/j.jtha.2022.12.021. Online ahead of print.

ABSTRACT

BACKGROUND: Thrombophilia predisposes to venous thromboembolism (VTE) because of acquired or hereditary factors. Among them, it has been suggested that gene mutations of the factor V Leiden (FVL) or prothrombin G20210A mutation (PGM) might reduce the risk of bleeding, but little data exist for patients treated using anticoagulants.

OBJECTIVES: To assess whether thrombophilia is protective against bleeding.

METHODS: This multicentre, multinational, prospective cohort study evaluated adults receiving long-term anticoagulants after a VTE event. We analyzed the incidence of major bleeding as the primary outcome, according to the genotype for FVL and PGM (wild-type and heterozygous/homozygous carriers).

RESULTS: Of 2260 patients with genotype testing, during a median follow-up of 3 years, 106 patients experienced a major bleeding event (17 intracranial and 7 fatal). Among 439 carriers of FVL, 19 experienced major bleeding and there were no differences between any mutation vs wild-type (hazard ratio [HR], 0.89 [0.53-1.49]; p = .66). The comparison of major bleeding events between the 158 patients with any-PGM mutation (heterozygous or homozygous) vs wild-type also showed a nonstatistically significant difference with HR of 0.53 (0.19-1.43), p = .21. However, multivariate analysis demonstrated that major bleeds or clinically relevant nonmajor bleeding were statistically less likely for patients with either FVL and/or PGM compared with patients with both wild-type factor V and prothrombin genes (HR, 0.73; 95% CI = 0.55-0.97; p = .03).

CONCLUSION: This study demonstrates that thrombophilia, defined as the presence of either FVL or the prothrombin G20210A mutation, is related with a lower rate of major/clinically relevant nonmajor bleeding while on anticoagulants in the extended treatment for VTE.

PMID:36710196 | DOI:10.1016/j.jtha.2022.12.021

J Dairy Sci. 2023 Jan 27:S0022-0302(23)00018-8. doi: 10.3168/jds.2022-22041. Online ahead of print.

ABSTRACT

Lowering the dietary protein content can reduce N excretions and NH₃ emissions from manure and increase milk N efficiency of dairy cows. However, milk yield (MY) and composition can be compromised due to AA deficiency. Methionine and Lys are known as first limiting EAA for dairy cows, and recently His is also mentioned as limiting, especially in grass-based or low-protein diets. To examine this, a trial was conducted with a 3-wk pre-experimental adaptation period (diet 16.5% crude protein), followed by a depletion period of 4 wk, in which 39 cows (average ± standard deviation: 116 ± 29.3 d in milk, 1.8 ± 1.2 lactations, 638 ± 73.2 kg of body weight, and 32.7 ± 5.75 kg MY/d) received a low-protein diet (CTRL) (14.5% crude protein). Then, taking into account parity, His plasma concentration, and MY, cows were randomly assigned to 1 of 3 treatment groups during the rumen-protected (RP) AA period of 7 wk; (1) CTRL; (2) CTRL + RP-Met + RP-Lys (MetLys); (3) CTRL + RP-Met + RP-Lys + RP-His (MetLysHis). Products were dosed, assuming requirements for digestible (d) Met, dLys, and dHis being, respectively, 2.4%, 7.0%, and 2.4% of intestinal digestible protein. In the cross-back period of 5 wk, all cows received the CTRL diet. During the last week of each period, a N balance was conducted by collecting total urine and spot samples of feces. Total feces production was calculated using the inert marker TiO₂. Statistical analysis was performed with a linear mixed model with cow as random effect and data of the last week of the pre-experimental period used as covariate for the animal performance variables. No effect of supplementing RP-Met and RP-Lys nor RP-Met, RP-Lys, and RP-His on feed intake, milk performance, or milk N efficiency was observed. However, the plasma AA profile indicated additional supply of dMet, dLys, and dHis. Nevertheless, evaluation of the AA uptake relative to the cow’s requirements showed that most EAA (exclusive Arg and Thr) were limiting over the whole experiment. Only dHis was sufficiently supplemented during the RP-AA period due to an overestimation of the diet’s dMet and dLys supply in the beginning of the trial. The numerically increased milk urea N and urinary N excretion when RP-Met, RP-Lys, and RP-His were added to the low-protein diet suggest an increased catabolism of the excess His.

PMID:36710179 | DOI:10.3168/jds.2022-22041