Category: Statistics

Cardiovasc Diabetol. 2022 Aug 24;21(1):163. doi: 10.1186/s12933-022-01601-w.

ABSTRACT

Cardiovascular (CV) outcome trials (CVOTs) of type 2 diabetes mellitus (T2DM) therapies have mostly used randomized comparison with placebo to demonstrate non-inferiority to establish that the investigational drug does not increase CV risk. Recently, several glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium glucose cotransporter 2 inhibitors (SGLT-2i) demonstrated reduced CV risk. Consequently, future T2DM therapy trials could face new ethical and clinical challenges if CVOTs continue with the traditional, placebo-controlled design. To address this challenge, here we review the methodologic considerations in transitioning to active-controlled CVOTs and describe the statistical design of a CVOT to assess non-inferiority versus an active comparator and if non-inferiority is proven, using novel methods to assess for superiority versus an imputed placebo. Specifically, as an example of such methodology, we introduce the statistical considerations used for the design of the “Effect of Tirzepatide versus Dulaglutide on Major Adverse Cardiovascular Events (MACE) in Patients with Type 2 Diabetes” trial (SURPASS CVOT). It is the first active-controlled CVOT assessing antihyperglycemic therapy in patients with T2DM designed to demonstrate CV efficacy of the investigational drug, tirzepatide, a dual glucose-dependent insulinotropic polypeptide and GLP-1 RA, by establishing non-inferiority to an active comparator with proven CV efficacy, dulaglutide. To determine the efficacy margin for the hazard ratio, tirzepatide versus dulaglutide, for the composite CV outcome of death, myocardial infarction, or stroke (MACE-3), which is required to claim superiority versus an imputed placebo, the lower bound of efficacy of dulaglutide compared with placebo was estimated using a hierarchical Bayesian meta-analysis of placebo-controlled CVOTs of GLP-1 RAs. SURPASS CVOT was designed so that when the observed upper bound of the 95% confidence interval of the hazard ratio is less than the lower bound of efficacy of dulaglutide, it demonstrates non-inferiority to dulaglutide by preserving at least 50% of the CV benefit of dulaglutide as well as statistical superiority of tirzepatide to a theoretical placebo (imputed placebo analysis). The presented methods adding imputed placebo comparison for efficacy assessment may serve as a model for the statistical design of future active-controlled CVOTs.

PMID:36002856 | DOI:10.1186/s12933-022-01601-w

BMC Health Serv Res. 2022 Aug 24;22(1):1082. doi: 10.1186/s12913-022-08471-8.

ABSTRACT

BACKGROUND: Changes in everyday work with regard to working time models have reached the medical profession. The number of physicians working part-time is steadily increasing. At the same time, however, the population’s need for care is also rising. This can reinforce the impending shortage of doctors in the future. The aim was to investigate differences in work-privacy conflict and burnout among physicians working full-time or part-time.

METHOD: The present study includes data from a baseline survey of the long-term study of physicians with different medical backgrounds. The analysis focused on a sub-sample of 598 physicians (not self-employed). The two main outcomes under investigation-burnout and work-privacy conflict-were measured using the Copenhagen Burnout Inventory adapted for health care professionals, as well as the associated subscale of the Copenhagen Psychosocial Questionnaire (COPSOQ). Data analyses included descriptive statistics followed by regression models.

RESULTS: Descriptive analyses show, that 31.8% of physicians are working part-time, whereas 68.2% are working full-time. The part-time subsample is significantly older, and female physicians are more likely to work part-time. With regard to workload and work-privacy conflict, significant differences between part-time and full-time physicians were only observed in terms of work-privacy-conflict. However, regression analysis underline the importance of possible confounding variables (such as medical setting) within the relationship between job size and job-related well-being.

DISCUSSION: Differences in working hour arrangements (full-time or part-time work) are only accompanied by less work-privacy conflict. No differences with regard to burnout (patient-related, work-related or personal) could be obtained. Rather, the data suggests that other job-related variables may play a role and should be further investigated.

PMID:36002851 | DOI:10.1186/s12913-022-08471-8

BMC Med Inform Decis Mak. 2022 Aug 24;22(1):223. doi: 10.1186/s12911-022-01972-w.

ABSTRACT

BACKGROUND: Although treatment decisions for localized prostate cancer (LPC) are preference-sensitive, the extent to which individuals with LPC receive preference-concordant treatment is unclear. In a sample of individuals with LPC, the purpose of this study was to (a) assess concordance between the influence of potential adverse treatment outcomes and treatment choice; (b) determine whether receipt of a decision aid predicts higher odds of concordance; and (c) identify predictors of concordance from a set of participant characteristics and influential personal factors.

METHODS: Participants reported the influence of potential adverse treatment outcomes and personal factors on treatment decisions at baseline. Preference-concordant treatment was defined as (a) any treatment if risk of adverse outcomes did not have a lot of influence, (b) active surveillance if risk of adverse outcomes had a lot of influence, or (c) radical prostatectomy or active surveillance if risk of adverse bowel outcomes had a lot of influence and risk of other adverse outcomes did not have a lot of influence. Data were analyzed using descriptive statistics and logistic regression.

RESULTS: Of 224 participants, 137 (61%) pursued treatment concordant with preferences related to adverse treatment outcomes. Receipt of a decision aid did not predict higher odds of concordance. Low tumor risk and age ≥ 60 years predicted higher odds of concordance, while attributing a lot of influence to the impact of treatment on recreation predicted lower odds of concordance.

CONCLUSIONS: Risk of potential adverse treatment outcomes may not be the foremost consideration of some patients with LPC. Assessment of the relative importance of patients’ stated values and preferences is warranted in the setting of LPC treatment decision making.

CLINICAL TRIAL REGISTRATION: NCT01844999 ( www.

CLINICALTRIALS: gov ).

PMID:36002847 | DOI:10.1186/s12911-022-01972-w

BMC Nutr. 2022 Aug 24;8(1):87. doi: 10.1186/s40795-022-00587-8.

ABSTRACT

BACKGROUND: Adolescent is the population whose age between 10-19 years old. They are undergoing rapid growth, development and are one of the nutritionally at-risk groups who should need attention. Adolescent undernutrition is a worldwide problem. Even if this stage brings the second window of opportunity to break the intergenerational cycle of undernutrition little is known specifically in the study area. This study was conducted to assess the prevalence of undernutrition and its associated factors among school adolescent girls in Abuna Gindeberet district, Central Ethiopia, 2021.

METHODS: Institution-based cross-sectional quantitative study design was conducted in Abuna Gindeberet district among 10-19 years adolescent girls attending primary and secondary schools from January 1-30, 2021. A systematic random sampling technique was used to select 587 adolescent girls. Data were collected by using interviewer-administered structured and anthropometric measurements. Data were coded, then entered into the Epi-info version 7.2.2.6 and exported to SPSS version 25 and WHO Anthro plus for analysis. Logistic regression analysis was done to identify predictors of under nutrition. Level of statistical significance was declared at p-value < 0.05.

RESULTS: The overall magnitude of stunting and thinness were 15.4% [95% CI (12-18)] and 14.2% [95% CI (11-17)] respectively. Number of meals per day [AOR = 3.62, 95% C.I (2.16, 6.05)], adolescent girls of lower grades [AOR = 2.08, 95% C.I (1.07, 4.04)] and who did not begin menstruation [AOR = 1.71, 95% C.I (1.06, 2.73)] were significantly associated with stunting. Adolescent girls engaged in vigorous intensity activities [AOR = 2.51, 95% C.I (1.14, 5.54)], poor dietary diversity score [AOR = 4.05, 95% C.I (1.43, 11.46)] and adolescent age [AOR = 3.77, 95% C.I (1.06, 13.37)] were significantly associated with thinness among adolescent girls.

CONCLUSIONS: Adolescent girl’s undernutrition is a public health problem in the study area. The number of meals per day, adolescent girls of lower grades and who did not begin menstruation were significantly associated with stunting as well as adolescent girls engaged in vigorous-intensity activities; poor dietary diversity score and adolescent age were significantly associated with thinness among adolescent girls. Therefore, government and other stakeholders should focus on these identified factors to improve the nutritional status of adolescent girls.

PMID:36002840 | DOI:10.1186/s40795-022-00587-8

BMC Biol. 2022 Aug 24;20(1):191. doi: 10.1186/s12915-022-01392-2.

ABSTRACT

BACKGROUND: Natural killer (NK) cells represent a critical component of the innate immune system’s response against cancer and viral infections, among other diseases. To distinguish healthy host cells from infected or tumor cells, killer immunoglobulin receptors (KIR) on NK cells bind and recognize Human Leukocyte Antigen (HLA) complexes on their target cells. However, NK cells exhibit great diversity in their mechanism of activation, and the outcomes of their activation are not yet understood fully. Just like the HLAs they bind, KIR receptors exhibit high allelic diversity in the human population. Here we provide a method to identify KIR allele variants from whole exome sequencing data and uncover novel associations between these variants and various molecular and clinical correlates.

RESULTS: In order to better understand KIRs, we have developed KIRCLE, a novel method for genotyping individual KIR genes from whole exome sequencing data, and used it to analyze approximately sixty-thousand patient samples in The Cancer Genome Atlas (TCGA) and UK Biobank. We were able to assess population frequencies for different KIR alleles and demonstrate that, similar to HLA alleles, individuals’ KIR alleles correlate strongly with their ethnicities. In addition, we observed associations between different KIR alleles and HLA alleles, including HLA-B*53 with KIR3DL2*013 (Fisher’s exact FDR = 7.64e-51). Finally, we showcased statistically significant associations between KIR alleles and various clinical correlates, including peptic ulcer disease (Fisher’s exact FDR = 0.0429) and age of onset of atopy (Mann-Whitney U FDR = 0.0751).

CONCLUSIONS: We show that KIRCLE is able to infer KIR variants accurately and consistently, and we demonstrate its utility using data from approximately sixty-thousand individuals from TCGA and UK Biobank to discover novel molecular and clinical correlations with KIR germline variants. Peptic ulcer disease and atopy are just two diseases in which NK cells may play a role beyond their “classical” realm of anti-tumor and anti-viral responses. This tool may be used both as a benchmark for future KIR-variant-inference algorithms, and to better understand the immunogenomics of and disease processes involving KIRs.

PMID:36002830 | DOI:10.1186/s12915-022-01392-2

BMC Health Serv Res. 2022 Aug 24;22(1):1080. doi: 10.1186/s12913-022-08446-9.

ABSTRACT

BACKGROUND: Large-scale detection has great potential to bring benefits for containing the COVID-19 epidemic and supporting the government in reopening economic activities. Evaluating the true regional mobile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus nucleic acid testing capacity is essential to improve the overall fighting performance against this epidemic and maintain economic development. However, such a tool is not available in this issue. We aimed to establish an evaluation index system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity and provide suggestions for improving the capacity level.

METHODS: The initial version of the evaluation index system was identified based on massive literature and expert interviews. The Delphi method questionnaire was designed and 30 experts were consulted in two rounds of questionnaire to select and revise indexes at all three levels. The Analytic Hierarchy Process method was used to calculate the weight of indexes at all three levels.

RESULTS: The evaluation index system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity, including 5 first-level indexes, 17 second-level indexes, and 90 third-level indexes. The response rates of questionnaires delivered in the two rounds of consultation were 100 and 96.7%. Furthermore, the authority coefficient of 30 experts was 0.71. Kendall’s coordination coefficient differences were statistically significant (P < 0.001). The weighted values of capacity indexes were established at all levels according to the consistency test, demonstrating that ‘Personnel team construction’ (0.2046) came first amongst the five first-level indexes, followed by ‘Laboratory performance building and maintenance’ (0.2023), ‘Emergency response guarantee’ (0.1989), ‘Information management system for nucleic acid testing resources’ (0.1982) and ‘Regional mobile nucleic acid testing emergency response system construction’ (0.1959).

CONCLUSION: The evaluation system for assessing the regional mobile SARS-CoV-2 virus nucleic acid testing capacity puts forward a specific, objective, and quantifiable evaluation criterion. The evaluation system can act as a tool for diversified subjects to find the weak links and loopholes. It also provides a measurable basis for authorities to improve nucleic acid testing capabilities.

PMID:36002820 | DOI:10.1186/s12913-022-08446-9

BMC Med Ethics. 2022 Aug 24;23(1):85. doi: 10.1186/s12910-022-00824-6.

ABSTRACT

BACKGROUND: Research and academic institutions use various delivery channels to deliver Research Integrity (RI) education in their communities. Yet there is no consensus on the best delivery method and the effectiveness of these channels in inculcating a positive RI culture varies across institutions. Hence, this study aimed to understand the preferences of the research community in Nanyang Technological University (NTU), Singapore.

METHODS: An online survey was conducted on NTU research community to understand their experience with, and preference for each RI education mode offered in NTU. The RI education modes surveyed in the general ranking question are Data Management Plan (DMP) workshops, Epigeum e-Learning, Compass e-newsletter (email), and NTU policy on Research Integrity and Responsible Conduct of Research. There were 242 responses, comprising 50% research students, 32.2% research staff and 17.8% faculty members. Non-parametric statistical techniques were used to analyse preferences across different RI education modes and within sub-groups (i.e., fields, age, native language, roles in research community).

RESULTS: More than 92% of respondents subscribed to the importance of RI education, but with different preferences for education modes. With respect to RI education in NTU, Compass e-newsletters were ranked the lowest (p < 0.05). Most felt that they were too wordy and unengaging, making it difficult to absorb information. Similarly, Epigeum e-Learning (p < 0.05) and ‘policy’ (p < 0.05) were found to be too lengthy in presentation. The compulsory NTU RI education modes (Epigeum e-learning and ‘policy’) enjoyed higher participation rates of 70-80% compared with 32-37% for the self-regulated modes (DMP workshop and e-newsletter). This suggests that regulatory mechanisms are still necessary to promote participation in RI education, and thus, core RI education content should be made compulsory in research/academic institutions. Although Epigeum is a compulsory course, some may not have participated in the programme due to technical issues or they might have forgotten to participate in the programme within the permissible timeframe. For all four RI education modes in NTU, the lack of awareness was among the top cited reasons for not participating.

CONCLUSIONS: Most NTU researchers perceived RI education positively although they may have reservations for some approaches. Conversely, e-Learning is favored over all the other modes except for the mode of Policy. Findings from this study are useful for improving the design of RI education strategies to be more appealing to the research community by enhancing user experience in terms of user-friendliness, relevance to specialisation, providing concise information and better presentation of materials For institutions with similar modes of RI education as NTU, these results may be relevant in improving participation rates and presentation of RI education modes, such as the use of infographics and more concise information.

PMID:36002817 | DOI:10.1186/s12910-022-00824-6

BMC Pediatr. 2022 Aug 24;22(1):501. doi: 10.1186/s12887-022-03537-2.

ABSTRACT

BACKGROUND: Prolonged recovery is a severe issue in patients after Fontan operation. However, predictive factors related to this issue are not adequately evaluated. The present study aimed to investigate potential predictive factors which can predict Fontan postoperative recovery.

METHODS: We retrospectively reviewed the perioperative medical records of patients with Fontan surgery between January 2015 and December 2018, and divided patients with > 75%ile cardiac intensive care unit stay into prolonged recovery group. The others were assigned to standard recovery group. Patients that died or underwent a Fontan takedown were excluded. Statistical analysis was performed to compare data difference of the two groups.

RESULTS: 282/307 cases fulfilled the inclusion criteria. Seventy patients were considered in prolonged recovery and 212 patients were defined as standard recovery. Pre- and intra-operative data showed a higher incidence of heterotaxy syndrome, longer cardiopulmonary bypass and aortic cross-clamp time in the prolonged recovery group. Postoperative information analysis displayed that ventilation time, oxygen index after extubation, hemodynamic data, inotropic score (IS), drainage volume, volume resuscitation, pulmonary hypertension (PH) treatment, and surgical reintervention were significantly different between the two groups. Higher IS postoperatively, and PH treatment and higher fluid resuscitation within two days were independent predictive factors for prolonged recovery in our multivariate model. C-statistic model showed a high predictive ability in prolonged recovery by using the three factors.

CONCLUSIONS: Ventilation time, higher IS in postoperative day, and PH treatment and higher fluid resuscitation within two days were independent risk factors and have a high predictability for Fontan prolonged recovery.

PMID:36002809 | DOI:10.1186/s12887-022-03537-2

BMC Geriatr. 2022 Aug 25;22(1):704. doi: 10.1186/s12877-022-03393-w.

ABSTRACT

Old-age needs are multifaceted and require multiple support sources, yet caregiving roles for older Nigerians are largely shifted to adult children. However, the children also declining capacity to respond. The extent to which older adults access support from other sources remains under-researched. This study investigates the patterns and determinants of access to complementary supports among older adults in South-Western Nigeria, taking Oyo State as the case study. The study is cross-sectional and utilized primary data of 827 older adults aged ≥ 65 years selected using a multi-stage sampling design. Box plot was used to determine the patterns while multiple ordinary least square regression was used to predict the determinants of access to complementary support. Expressed in percentage, the median complementary support score of older adults in Oyo State was 30 (interquartile range [IQR] = 24) with a slightly higher score for men (median = 32, IQR = 24) compared to women (median = 28, IQR = 20). Access to complementary support was lower for the widow(er)s, the lower socioeconomic group and self-dependent older adults across genders, and for urban women with secondary/higher education compared to the otherwise groups. Increased access to complementary support was significantly associated with primary/no education (β = 4.365; p < 0.01 95% C.I. = 1.511-7.218), affiliation to Islamic/Traditional religion (β = 5.100; p < 0.001; 95% C.I. = 3.000-7.200), rich wealth status (β = 3.315; p < 0.05; 95% C.I. = 0.667-5.963) and depending on both self and children/family for income (β = 5.510; p < 0.05; 95% C.I. = 1.710-9.309) with some gender disparities. However, reduced complementary support was associated with ages 80 years or over (β = -3.649; p < 0.05; 95% C.I. = -6.460 – -0.838) and widowhood (β = -6.285; p < 0.001; 95% C.I. = -8.556 – -4.015). The study suggests the need for welfare plans among professional, social, and religious groups, institutionalised social support systems, and community engagement to escalate welfare support for older adults. It also recommends intensified attention on the more vulnerable groups, especially the widows, childless and lower socioeconomic groups.

PMID:36002807 | DOI:10.1186/s12877-022-03393-w

BMC Microbiol. 2022 Aug 24;22(1):206. doi: 10.1186/s12866-022-02619-6.

ABSTRACT

BACKGROUND: The first two weeks of post-hatch (PH) growth in broilers (meat-type birds) are critical for gut development and microbiota colonization. In the current broiler production system, chicks may not receive feed and water for 24 to 72 h due to variations in hatching time and hatchery management. Post-hatch feed delay affects body weight, feed efficiency, mortality, and gut development. The goal of this study was to investigate changes in the microbiome in broiler chickens early PH and the effect of delayed access to feed on the microbiota.

RESULTS: Chicks either received feed and water immediately after hatch or access to feed was delayed for 48 h to mimic commercial hatchery settings (treatment, TRT). Both groups were sampled (n = 6) at -48, 0, 4 h, and 1 (24 h), 2 (48 h), 3 (72 h), 4 (96 h), 6 (144 h), 8 (192 h), 10 (240 h), 12 (288 h) and 14 (336 h) days PH. Ileal (IL) and cecal (CE) epithelial scrapings (mucosal bacteria, M) and digesta (luminal bacteria, L) were collected for microbiota analysis. Microbiota was determined by sequencing the V3-V4 region of bacterial 16S rRNA and analyzed using QIIME2. The microbiota of early ileal and cecal samples were characterized by high abundance of unclassified bacteria. Among four bacterial populations (IL-L, IL-M, CE-L, CE-M), IL-M was the least affected by delayed access to feed early PH. Both alpha and beta diversities were affected by delayed access to feed PH in IL-L, CE-M and CE-L. However, the development effect was more pronounced. In all four bacterial populations, significant changes due to developmental effect (time relative to hatch) was observed in taxonomic composition, with transient changes of bacterial taxa during the first two weeks PH. Delayed access to feed has limited influence on bacterial composition with only a few genera and species affected in all four bacterial populations. Predicted function based on 16S rRNA was also affected by delayed access to feed PH with most changes in metabolic pathway richness observed in IL-L, CE-L and CE-M.

CONCLUSIONS: These results show transient changes in chicken microbiota biodiversity during the first two weeks PH and indicate that delayed access to feed affects microbiota development. Proper microbiota development could be an important factor in disease prevention and antibiotic use in broiler chickens. Moreover, significant differences in response to delayed access to feed PH between luminal and mucosal bacterial populations strongly suggests the need for separate analysis of these two populations.

PMID:36002800 | DOI:10.1186/s12866-022-02619-6