Category: Statistics

Clin J Am Soc Nephrol. 2021 Jun;16(6):908-915. doi: 10.2215/CJN.16871020. Epub 2021 Jun 11.

ABSTRACT

BACKGROUND AND OBJECTIVES: On the basis of earlier observations, we evaluated the association between overweight and obesity and rapid progression of autosomal dominant polycystic kidney disease in participants in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 trial. More importantly, we also determined whether efficacy of tolvaptan was attenuated in individuals with baseline overweight or obesity.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 1312 study participants with relatively early-stage autosomal dominant polycystic kidney disease (mean eGFR 78±22 ml/min per 1.73 m²) who were at high risk of rapid progression were categorized by body mass index (BMI; calculated using nonkidney weight) as normal weight (18.5-24.9 kg/m²; n=670), overweight (25.0-29.9 kg/m²; n=429), or obese (≥30 kg/m²; n=213). Linear and multinomial logistic regression models were used to determine the association of baseline overweight and obesity with change in total kidney volume (TKV) over the 3-year study period.

RESULTS: In fully adjusted models, higher BMI was associated with greater annual percent change in TKV (difference of 1.20 [95% confidence interval (95% CI), 0.85 to 1.55] per five-unit higher BMI). Overweight and obesity were associated with higher odds of annual percent change in TKV of ≥7% versus <5% (overweight: odds ratio, 2.04 [95% CI, 1.45 to 2.87]; obese: odds ratio, 4.31 [95% CI, 2.83 to 6.57] versus normal weight). eGFR decline did not differ according to BMI (fully adjusted difference in decline of -0.95 [95% CI, -2.32 to 0.40] ml/min per 1.73 m² per year per five-unit higher BMI). The three-way interaction (treatment×time×BMI group) was not statistically significant in linear mixed models with an outcome of TKV (log-transformed estimated coefficient comparing the treatment effect for overweight versus normal weight: 0.56% [95% CI, -0.70% to 1.84%] per year; P=0.38; obese versus normal weight: 0.07% [95% CI, -1.47% to 1.63%] per year; P=0.93) or eGFR (estimated coefficient comparing overweight versus normal weight: -0.07 [95% CI, -0.95 to 0.82] ml/min per 1.73 m² per year; P=0.88; obese versus normal weight: 0.22 [95% CI, -0.93 to 1.36] ml/min per 1.73 m² per year; P=0.71).

CONCLUSIONS: Overweight and particularly obesity are strongly and independently associated with kidney growth, but not eGFR slope, in the TEMPO 3:4 trial, and tolvaptan efficacy is irrespective of BMI categorization.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4, NCT00428948.

PMID:34117082 | DOI:10.2215/CJN.16871020

BMJ Open. 2021 Jun 11;11(6):e048119. doi: 10.1136/bmjopen-2020-048119.

ABSTRACT

INTRODUCTION: Mothers with gestational diabetes mellitus (GDM) are at increased risk of pregnancy-related complications and developing type 2 diabetes after delivery. Diet and physical activity-based interventions may prevent GDM, but variations in populations, interventions and outcomes in primary trials have limited the translation of available evidence into practice. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to assess the differential effects and cost-effectiveness of diet and physical activity-based interventions in preventing GDM and its complications.

METHODS: The International Weight Management in Pregnancy Collaborative Network database is a living repository of IPD from randomised trials on diet and physical activity in pregnancy identified through a systematic literature search. We shall update our existing search on MEDLINE, Embase, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment Database without language restriction to identify relevant trials until March 2021. Primary researchers will be invited to join the Network and share their IPD. Trials including women with GDM at baseline will be excluded. We shall perform a one and two stage random-effect meta-analysis for each intervention type (all interventions, diet-based, physical activity-based and mixed approach) to obtain summary intervention effects on GDM with 95% CIs and summary treatment-covariate interactions. Heterogeneity will be summarised using I² and tau² statistics with 95% prediction intervals. Publication and availability bias will be assessed by examining small study effects. Study quality of included trials will be assessed by the Cochrane Risk of Bias tool, and the Grading of Recommendations, Assessment, Development and Evaluations approach will be used to grade the evidence in the results. A model-based economic analysis will be carried out to assess the cost-effectiveness of interventions to prevent GDM and its complications compared with usual care.

ETHICS AND DISSEMINATION: Ethics approval is not required. The study is registered on the International Prospective Register of Systematic Reviews (CRD42020212884). Results will be submitted for publication in peer-reviewed journals.

PMID:34117047 | DOI:10.1136/bmjopen-2020-048119

BMJ Open Diabetes Res Care. 2021 Jun;9(1):e001950. doi: 10.1136/bmjdrc-2020-001950.

ABSTRACT

INTRODUCTION: Patients with diabetes mellitus are risk of premature death. In this study, we developed a machine learning-driven predictive risk model for all-cause mortality among patients with type 2 diabetes mellitus using multiparametric approach with data from different domains.

RESEARCH DESIGN AND METHODS: This study used territory-wide data of patients with type 2 diabetes attending public hospitals or their associated ambulatory/outpatient facilities in Hong Kong between January 1, 2009 and December 31, 2009. The primary outcome is all-cause mortality. The association of risk variables and all-cause mortality was assessed using Cox proportional hazards models. Machine and deep learning approaches were used to improve overall survival prediction and were evaluated with fivefold cross validation method.

RESULTS: A total of 273 678 patients (mean age: 65.4±12.7 years, male: 48.2%, median follow-up: 142 (IQR=106-142) months) were included, with 91 155 deaths occurring on follow-up (33.3%; annualized mortality rate: 3.4%/year; 2.7 million patient-years). Multivariate Cox regression found the following significant predictors of all-cause mortality: age, male gender, baseline comorbidities, anemia, mean values of neutrophil-to-lymphocyte ratio, high-density lipoprotein-cholesterol, total cholesterol, triglyceride, HbA1c and fasting blood glucose (FBG), measures of variability of both HbA1c and FBG. The above parameters were incorporated into a score-based predictive risk model that had a c-statistic of 0.73 (95% CI 0.66 to 0.77), which was improved to 0.86 (0.81 to 0.90) and 0.87 (0.84 to 0.91) using random survival forests and deep survival learning models, respectively.

CONCLUSIONS: A multiparametric model incorporating variables from different domains predicted all-cause mortality accurately in type 2 diabetes mellitus. The predictive and modeling capabilities of machine/deep learning survival analysis achieved more accurate predictions.

PMID:34117050 | DOI:10.1136/bmjdrc-2020-001950

Clin J Am Soc Nephrol. 2021 Jun;16(6):862-869. doi: 10.2215/CJN.18841220. Epub 2021 Jun 11.

ABSTRACT

BACKGROUND AND OBJECTIVES: AKI is associated with poor short- and long-term outcomes. Questions remain about the frequency and timing of AKI, and whether AKI is a cause of death in extremely low gestational age neonates.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Recombinant Erythropoietin for Protection of Infant Kidney Disease Study examines the kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo Neuroprotection study, a randomized, placebo-controlled trial of recombinant human erythropoietin. We included 900 of 941 patients enrolled in Preterm Epo Neuroprotection. Baseline characteristics were compared by primary exposure (severe AKI versus none/stage 1 AKI) using unadjusted logistic regression models. Cox regression models estimated the relationship between severe AKI and death after adjustment for potential confounders. Time-dependent AKI was modeled as a binary outcome and a categorical variable by stage of AKI. We fit Cox models using time-dependent AKI status lagged by <7 days before death. Landmark analyses examined the relationship of death with development of severe AKI.

RESULTS: Severe AKI occurred in 168 of 900 (19%, 95% confidence interval, 17% to 20%) neonates, and stage 3 AKI occurred in 60 (7%, 95% confidence interval, 5% to 8%). Stage 3 AKI occurring 7 days before death (hazard ratio, 3.88; 95% confidence interval, 1.26 to 11.96), intraventricular hemorrhage (hazard ratio, 2.01; 95% confidence interval, 1.01 to 3.99) and sepsis (hazard ratio, 2.85; 95% confidence interval, 1.12 to 7.22) were all independently associated with death. Severe AKI occurring 7 days before death (hazard ratio, 2.21; 95% confidence interval, 0.92 to 5.26) was associated with death but not statistically significant. In a landmark analysis, after adjusting for potential confounders, late (after day 14 and before day 28) severe AKI was strongly associated with higher hazard of death (hazard ratio, 4.57; 95% confidence interval, 1.82 to 11.5).

CONCLUSIONS: Severe AKI occurs frequently in extremely low gestational age neonates. Stage 3 AKI is associated with mortality, and this association is present 7 days before death.

PMID:34117080 | DOI:10.2215/CJN.18841220

BMJ Open. 2021 Jun 11;11(6):e047000. doi: 10.1136/bmjopen-2020-047000.

ABSTRACT

OBJECTIVE: To determine the association of meteorological factors and air pollutants (MFAPs) with fracture and to estimate the effect size/time lag.

DESIGN: This is a nationwide population-based ecological study from 2008 to 2017.

SETTING: Eight large metropolitan areas in Korea.

PARTICIPANTS: Of 8 093 820 patients with fractures reported in the Korea National Health Insurance database, 2 129 955 were analysed after the data set containing patient data (age, sex and site of fractures) were merged with MFAPs. Data on meteorological factors were obtained from the National Climate Data Center of the Korea Meteorological Administration. Additionally, data on air pollutants (atmospheric particulate matter ≤2.5 µm in diameter (PM_2.5), PM₁₀, ozone, nitrogen dioxide, sulfur dioxide and carbon monoxide) were obtained from the Air Korea database.

PRIMARY AND SECONDARY OUTCOME MEASURES: We hypothesised that there would be an association between MFAPs and the incidence of fracture. A generalised additive model was used while factoring in the non-linear relationship between MFAPs and fractures as well as a time lag ≤7 days. Multivariate analysis was performed. Backward elimination with an Akaike information criterion was used to fit the multivariate model.

RESULTS: Overall, in eight urban areas, 2 129 955 patients with fractures were finally analysed. These included 370 344, 187 370, 173 100, 140 358, 246 775, 6501, 228 346, 57 183 and 719 978 patients with hip, knee, shoulder, elbow, wrist, hand, ankle, foot and spine fractures, respectively. Various MFAPs (average temperature, daily rain, wind speed, daily snow and PM_2.5) showed significant association with fractures, with positive correlations at time lags 7, 5-7, 5-7, 3-7 and 6-7 days, respectively.

CONCLUSIONS: Various MFAPs could affect the occurrence of fractures. The average temperature, daily rain, wind speed, daily snow and PM_2.5 were most closely associated with fracture. Thus, improved public awareness on these MFAPs is required for clinical prevention and management of fractures.

PMID:34117046 | DOI:10.1136/bmjopen-2020-047000

Health Promot Int. 2021 Jun 11:daab085. doi: 10.1093/heapro/daab085. Online ahead of print.

ABSTRACT

Concerning the determinants of health literacy (HL) mostly socio-demographic or -economic factors have been considered, much less so psychological factors such as self-efficacy. To date, it has mostly been considered to explain the relationship of HL and health outcomes. However, self-efficacy could also be an important determinant for HL. This study therefore examines the effect of self-efficacy on comprehensive HL within the general population in Germany. Data from the German HL Survey (HLS-GER), a cross-sectional, computer-assisted personal interview study among 2000 respondents aged 15+ years in 2014 were used. Self-efficacy was measured using the German version of general self-efficacy short scale (ASKU), comprehensive HL was measured using the German version of the European Health Literacy Survey Questionnaire (HLS-EU-Q47). Correlation and multi-variate linear regression analyses were performed to analyze independent effects of socio-demographic factors-age, gender, social status, educational level and migration background-functional HL and self-efficacy on comprehensive HL. Self-efficacy and comprehensive HL are statistically significantly correlated (Spearman’s Rho = 0.405; p < 0.01), respondents with better self-efficacy had better HL scores. Both concepts are significantly associated with most socio-demographic factors and functional HL. Self-efficacy showed the strongest association with HL in the multivariate analyses (model 2: β =0.310, p < 0.001). The effect size of the other predictors decreased, when adding self-efficacy into the equation, but remained statistically significant. Self-efficacy is a rather strong predictor of comprehensive HL. Future research and measures to improve HL should therefore take self-efficacy adequately into account.

PMID:34115848 | DOI:10.1093/heapro/daab085

Ann Hum Genet. 2021 Jun 11. doi: 10.1111/ahg.12438. Online ahead of print.

ABSTRACT

Bone mineral density (BMD) and whole-body lean mass (WBLM) are two important phenotypes of osteoporosis and sarcopenia. Previous studies have shown that BMD and lean mass were phenotypically and genetically correlated. To identify the novel common genetic factors shared between BMD and WBLM, we performed the conditional false discovery rate (cFDR) analysis using summary data of the genome-wide association study of femoral neck BMD (n = 53,236) and WBLM (n = 38,292) from the Genetic Factors for Osteoporosis Consortium (GEFOS). We identified eight pleiotropic Single Nucleotide Polymorphism (SNPs) (PLCL1 rs11684176 and rs2880389, JAZF1 rs198, ADAMTSL3 rs10906982, RFTN2/MARS2 rs7340470, SH3GL3 rs1896797, ST7L rs10776755, ANKRD44/SF3B1 rs11888760) significantly associated with femoral neck BMD and WBLM (ccFDR < 0.05). Bayesian fine-mapping analysis showed that rs11888760, rs198, and rs1896797 were the possible functional variants in the ANKRD44/SF3B1, JAZF1i, and SH3GL3 loci, respectively. Functional annotation suggested that rs11888760 was likely to comprise a DNA regulatory element and linked to the expression of RFTN2 and PLCL1. PLCL1 showed differential expression in laryngeal posterior cricoarytenoid muscle between rats of 6 months and 30 months of age. Our findings, together with PLCL1’s potential functional relevance to bone and skeletal muscle function, suggested that rs11888760 was the possible pleiotropic functional variants appearing to coregulate both bone and muscle metabolism through regulating the expression of PLCL1. The findings enhanced our knowledge of genetic associations between BMD and lean mass and provide a rationale for subsequent functional studies of the implicated genes in the pathophysiology of diseases, such as osteoporosis and sarcopenia.

PMID:34115876 | DOI:10.1111/ahg.12438

Acta Obstet Gynecol Scand. 2021 Jun 11. doi: 10.1111/aogs.14212. Online ahead of print.

ABSTRACT

INTRODUCTION: Some women keep on recalling intense labor pain experienced at childbirth to a degree that it may negatively affect their life during the postpartum period or lead them to request a cesarean section (CS) in the subsequent delivery. This longitudinal study aimed to assess the impact of severe recalled labor pain from the previous birth on the preference of and delivery by an elective CS in the subsequent delivery. Further, we investigated if co-occurring maternal demographic, somatic, and mental health factors related to the previous and subsequent delivery explain parts of a potential association.

MATERIAL AND METHODS: The study sample comprised 1135 parous women from the Akershus Birth Cohort. Severe recalled labor pain was assessed by a numeric rating scale at pregnancy week 17, and at pregnancy week 32 the preference of an elective CS for the subsequent delivery was assessed. Information on actual delivery by elective CS in the subsequent delivery was drawn from the electronic birth record. Logistic regression analyses were conducted to examine the impact of severe recalled labor pain on elective CS.

RESULTS: Severe recalled labor pain at the previous birth was associated with a preference of an elective CS (OR 3.57, 95% CI 2.25-5.67) and actual delivery by elective CS (OR 4.71, 95% CI 2.32-9.59). This association remained statistically significant for the preference of an elective CS (aOR 2.12, 95% CI 1.24-3.62), but diminished for delivery by elective CS (aOR 2.30, 95% CI 0.99-5.35) when adjusting for a variety of covariates. Factors related to previous childbirth such as passed years since previous birth, assisted vaginal delivery, anal sphincter lesions, overall birth experience, and fear of childbirth were also linked to preference and delivery by an elective CS.

CONCLUSIONS: Women with severe recalled labor pain were about twice as likely to prefer an elective CS compared to women without severe recalled pain. For actual delivery, the significant association with severe recalled pain diminished after adjustment for covariates. However, sample size was small and irrespective of severe recalled labor pain, preference of elective CS was statistically significantly associated with actual delivery by elective CS.

PMID:34115883 | DOI:10.1111/aogs.14212

PLoS One. 2021 Jun 11;16(6):e0252646. doi: 10.1371/journal.pone.0252646. eCollection 2021.

ABSTRACT

In this study, we investigated serum epidermal growth factor (EGF) in an oncological population of head- and neck and pulmonary neoplasms and whether serum EGF could serve as a prognostic marker of survival and as a predictive marker for treatment response to platinum-based chemotherapy. A total of 59 oncological patients and a control group of age- and sex-matched healthy volunteers were included in this study. Pre-treatment serum EGF from both groups was determined. Patient’s and tumour characteristics and mortality were recorded during a 5-year follow up period. Baseline serum EGF significantly differed between the oncological patients and the healthy volunteers (p<0.001). Serum EGF was associated with lymph node metastasis (p = 0.004) but not with sex (p = 0.753), age (p = 1.00), TNM stage (p = 0.191) or tumour size (p = 0.077). Neither serum EGF (p = 0.81) nor age (p = 0.55) showed an effect on the patient’s survival. Tumour location was significantly associated with overall 5-year survival (p = 0.003). The predictive capacity of serum EGF of response to chemotherapy was limited (AUC = 0.606), a sensitivity of 80% and a specificity of 56% was observed resulting in a likelihood ratio of a positive and negative test equal to 1.81 and 0.36, respectively. In conclusion, serum EGF levels are 5.5 times higher in an oncological population compared to a control group. Within the oncological population, low serum EGF values are associated with the presence of lymph node metastasis. Further investigation is necessary to determine if the serum EGF levels could serve as a diagnostic biomarker.

PMID:34115785 | DOI:10.1371/journal.pone.0252646

PLoS One. 2021 Jun 11;16(6):e0253045. doi: 10.1371/journal.pone.0253045. eCollection 2021.

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy and efficiency of p16/ki-67 dual stain in the identification of CIN2+ lesions, in Greek women with ASCUS or LSIL cytology.

METHODS: A total of 200 women, 20 to 60 years old, were enrolled in the study. All samples were cytologically evaluated and performed for p16/ki-67 and high-risk HPV (HR-HPV) test. All patients were referred to colposcopy for biopsy and histological evaluation. Three cervical cancer (CC) screening strategies were designed and the total direct medical costs of the procedures during our clinical trial were evaluated, from a healthcare perspective.

RESULTS: HPV 16 as expected was the most common HR-HPV type followed by HPV 31 and HPV 51. The risk for CIN2+ was significantly higher in HPV 16/18 positive cases. p16/ki-67 demonstrated a high sensitivity for CIN2+ identification in both ASCUS and LSIL groups (90.4% and 95%, respectively). HR-HPV test with sensitivity 52.3% and 65.5%, as well as colposcopy with sensitivity 14.3% and 36% respectively in ASCUS and LSIL group, showed inferior results compared to p16/ki-67. The specificity of p16/ki-67 for ASCUS and LSIL was 97.2% and 95.2% respectively, inferior only to colposcopy: 100% and 100%, lacking however statistical significance. HR-HPV test instead, presented the lowest specificity: 76.4% and 71.4% respectively in comparison to the other two methods. From a healthcare perspective, the costs and benefits of the tests implementation for the annual screening and triaging, in three CC screening strategies, were also calculated and discussed.

CONCLUSIONS: The results of the study indicate that p16/ki-67 is a safe and rapid assay that could be used to detect CIN2+ among women with mild cervical lesions, presenting both high sensitivity and specificity and could minimize the psychological and economic burden of HPV screening.

PMID:34115809 | DOI:10.1371/journal.pone.0253045