Category: Statistics

JAMA Netw Open. 2023 Jan 3;6(1):e2249370. doi: 10.1001/jamanetworkopen.2022.49370.

ABSTRACT

IMPORTANCE: Prevalent use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, compared with those that do not stimulate these receptors, has been associated with a lower risk of dementia. However, previous studies were limited by inclusion of individuals with prevalent hypertension and a history of antihypertensive use prior to the start of the study, which can introduce bias.

OBJECTIVE: To examine the association of new use of antihypertensive medication regimens that stimulate vs inhibit type 2 and 4 angiotensin II receptors with Alzheimer disease and related dementias (ADRD) among Medicare beneficiaries.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among 57 773 Medicare fee-for-service beneficiaries (January 1, 2006, through December 31, 2018) aged 65 years or older with incident hypertension. Data analysis was conducted from January 1 through June 30, 2022.

EXPOSURES: Initiation of antihypertensive medication regimens that stimulate or inhibit type 2 and 4 angiotensin II receptors, or mixed regimens (both stimulating and inhibiting), with the time-dependent measure being each 30-day interval.

MAIN OUTCOMES AND MEASURES: The primary outcome was time to first occurrence of ADRD (Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse definition). Cox proportional hazards regression modeling with time-dependent variables was performed to estimate the association between time-dependent treatment groups and time to ADRD, after adjusting for sociodemographic and clinical characteristics.

RESULTS: The sample included 57 773 Medicare beneficiaries (36 348 women [62.9%]; mean [SD] age, 73.8 [6.3] years; 2954 [5.1%] Black, 1545 [2.7%] Hispanic; 50 184 [86.9%] White, and 3090 [5.4%] Other individuals [the Other category included individuals of American Indian, Asian, other, or unknown race and ethnicity]). During a median of 6.9 years (IQR, 4.7-9.3 years) of follow-up, the unadjusted incidence density rate of ADRD was 2.2 cases per 100 person-years (95% CI, 2.1-2.4 cases per 100 person-years) for the group receiving regimens that stimulate type 2 and 4 angiotensin II receptors compared with 3.1 cases per 100 person-years (95% CI, 3.0-3.2 cases per 100 person-years) for the group receiving regimens that inhibit type 2 and 4 angiotensin II receptors and 2.7 cases per 100 person-years (95% CI, 2.6-2.9 cases per 100 person-years) for the group receiving mixed treatment regimens. In adjusted Cox proportional hazards regression modeling, stimulating treatment was associated with a statistically significant 16% reduction in the hazard of ADRD compared with inhibiting treatment (hazard ratio, 0.84; 95% CI, 0.79-0.90). Mixed regimen use was also associated with reduced hazards of ADRD compared with the inhibiting group (hazard ratio, 0.90; 95% CI, 0.84-0.96).

CONCLUSIONS AND RELEVANCE: This cohort study of Medicare beneficiaries suggests that use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors was associated with lower risk of ADRD compared with antihypertensive medications that inhibit these receptors. Confirmation is needed in a randomized trial.

PMID:36598787 | DOI:10.1001/jamanetworkopen.2022.49370

JAMA Dermatol. 2023 Jan 4. doi: 10.1001/jamadermatol.2022.5607. Online ahead of print.

ABSTRACT

IMPORTANCE: Keloids and hypertrophic scars (excessive scarring) are relatively understudied disfiguring chronic skin conditions with high treatment resistance.

OBJECTIVE: To evaluate established comorbidities of excessive scarring in European individuals, with comparisons across ethnic groups, and to identify novel comorbidities via a phenome-wide association study (PheWAS).

DESIGN, SETTING, AND PARTICIPANTS: This multicenter cross-sectional population-based cohort study used UK Biobank (UKB) data and fitted logistic regression models for testing associations between excessive scarring and a variety of outcomes, including previously studied comorbidities and 1518 systematically defined disease categories. Additional modeling was performed within subgroups of participants defined by self-reported ethnicity (as defined in UK Biobank). Of 502 701 UKB participants, analyses were restricted to 230078 individuals with linked primary care records.

EXPOSURES: Keloid or hypertrophic scar diagnoses.

MAIN OUTCOMES AND MEASURES: Previously studied disease associations (hypertension, uterine leiomyoma, vitamin D deficiency, atopic eczema) and phenotypes defined in the PheWAS Catalog.

RESULTS: Of the 972 people with excessive scarring, there was a higher proportion of female participants compared with the 229 106 controls (65% vs 55%) and a lower proportion of White ethnicity (86% vs 95%); mean (SD) age of the total cohort was 64 (8) years. Associations were identified with hypertension and atopic eczema in models accounting for age, sex, and ethnicity, and the association with atopic eczema (odds ratio [OR], 1.68; 95% CI, 1.36-2.07; P < .001) remained statistically significant after accounting for additional potential confounders. Fully adjusted analyses within ethnic groups revealed associations with hypertension in Black participants (OR, 2.05; 95% CI, 1.13-3.72; P = .02) and with vitamin D deficiency in Asian participants (OR, 2.24; 95% CI, 1.26-3.97; P = .006). The association with uterine leiomyoma was borderline significant in Black women (OR, 1.93; 95% CI, 1.00-3.71; P = .05), whereas the association with atopic eczema was significant in White participants (OR, 1.68; 95% CI, 1.34-2.12; P < .001) and showed a similar trend in Asian (OR, 2.17; 95% CI, 1.01-4.67; P = .048) and Black participants (OR, 1.89; 95% CI, 0.83-4.28; P = .13). The PheWAS identified 110 significant associations across disease systems; of the nondermatological, musculoskeletal disease and pain symptoms were prominent.

CONCLUSIONS AND RELEVANCE: This cross-sectional study validated comorbidities of excessive scarring in UKB with comprehensive coverage of health outcomes. It also documented additional phenome-wide associations that will serve as a reference for future studies to investigate common underlying pathophysiologic mechanisms.

PMID:36598763 | DOI:10.1001/jamadermatol.2022.5607

J Trauma Acute Care Surg. 2023 Jan 5. doi: 10.1097/TA.0000000000003858. Online ahead of print.

ABSTRACT

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of morbidity and mortality in the pediatric population. Microglia and infiltrating monocyte-derived macrophages (MDMs) are crucial immune cells that modulate the neuroinflammatory response following TBI. Using C34, a novel pharmacologic TLR4 inhibitor, we investigated the intricate interactions between these cells in a murine TBI model.

METHODS: A murine controlled cortical impact (CCI) model was utilized, and the results were analyzed on post-injury days (PID) 1, 7, 28 and 35. The experimental groups are (1) Sham C57BL/6 wild-type (WT), (2) TBI WT, (3) Sham WT + C34 and (4) TBI WT + C34. Real-time PCR (qRT-PCR) was used to quantify gene expression associated with microglial activation, apoptotic pathways and type 1 interferon pathway. Flow cytometry was used to isolate microglia and infiltrating monocytes. Brain lesion volumes were assessed using MRI. Last, neurocognitive outcomes were evaluated using the Morris Water Maze (MWM) test. Student’s T-test and One-way ANOVA were used for statistical analysis with significance achieved when p < 0.05.

RESULTS: TLR4 inhibition leads to improved neurological sequela post-TBI, possibly due to an increase in infiltrating anti-inflammatory monocytes and a decrease in IRF7 during acute inflammation, followed by a reduction in apoptosis and M2 microglial expression during chronic inflammation.

CONCLUSIONS: TLR4 inhibition with C34 skews infiltrating monocytes towards an anti-inflammatory phenotype leading to enhanced neurocognitive outcomes. Moreover, although M2 microglia have been consistently shown as inducers of neuroprotection, our results clearly demonstrate their detrimental role during the chronic phases of healing post-TBI.Study type: Original Research (Basic Science).

PMID:36598757 | DOI:10.1097/TA.0000000000003858

Int J Immunopathol Pharmacol. 2023 Jan-Dec;37:3946320221149849. doi: 10.1177/03946320221149849.

ABSTRACT

OBJECTIVE: Airway inflammation is a prominent feature of asthma and may play an important role in disease pathophysiology. Despite the increasing incidence of asthma worldwide, reliable diagnostic biomarkers are lacking and widely lead to asthma misdiagnosis. Neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation, in addition to NLR-alanine aminotransferase ratio (NAR) and NLR-albumin ratio (NBR). The aim of this study was to evaluate associations of NLR, NAR, and NBR with diagnosis of childhood asthma to determine if they can aid clinical childhood asthma diagnosis.

METHODS: This retrospective case-control study included 89 children with asthma and 53 healthy children from the Wuxi Children’s Hospital affiliated with Nanjing Medical University. We applied various statistical tests to the dataset: Mann-Whitney U test to compare characteristics of the case and control groups; chi-squared test to compare categorical variables; Kruskal-Wallis test to compare statistical differences of asthma indicators among groups; receiver operating characteristic (ROC) curves to assess the diagnostic value of indices; and Spearman correlation analysis to evaluate relationships between NLR and lactate dehydrogenase, albumin, aspartate transaminase, and alanine transaminase levels.

RESULTS: Compared with controls, the asthma case group had significantly higher white blood cell (p < 0.01), neutrophil, lactate dehydrogenase, C-reactive protein, and NLR levels (p < 0.01) and significantly lower lymphocyte (p = 0.001), platelet (p = 0.039), and albumin levels (p = 0.04). We determined optimal cutoff levels for several metrics: 1.723 for NLR, with sensitivity of 0.73 and specificity of 0.906; 0.135 for NAR, with sensitivity of 0.685 and specificity of 0.887; and 0.045 for NBR, with sensitivity of 0.674 and specificity of 0.906. The areas under the curve (AUCs) were 0.824 for NLR, 0.788 for NAR, 0.818 for NBR, and 0.83 for the combination of NLR + NAR + NBR.

CONCLUSION: The combination of NLR, NAR, and NBR biomarkers distinguished asthmatic ones suffering from exacerbation of the condition from healthy children. Thus, our results indicate NLR + NAR + NBR could be used as a clinical biomarker for asthma in children.

PMID:36598755 | DOI:10.1177/03946320221149849

J Nucl Cardiol. 2023 Jan 4. doi: 10.1007/s12350-022-03173-4. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular risk models are based on traditional risk factors and investigations such as imaging tests. External validation is important to determine reproducibility and generalizability of a prediction model. We performed an external validation of t the Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS) model, developed from a cohort of patients undergoing stress myocardial perfusion imaging.

METHODS: We included 3623 patients with suspected or known coronary artery disease undergoing stress single-photon emission computer tomography (SPECT) myocardial perfusion imaging at our academic center between January 2001 and December 2019.

RESULTS: In our study population, the J-ACCESS model underestimated the risk of major adverse cardiac events (cardiac death, nonfatal myocardial infarction, and severe heart failure requiring hospitalization) within three-year follow-up. The recalibrations and updated of the model slightly improved the initial performance: C-statistics increased from 0.664 to 0.666 and Brier score decreased from 0.075 to 0.073. Hosmer-Lemeshow test indicated a logistic regression fit only for the calibration slope (P = .45) and updated model (P = .22). In the update model, the intercept, diabetes, and severity of myocardial perfusion defects categorized coefficients were comparable with J-ACCESS.

CONCLUSION: The external validation of the J-ACCESS model as well as recalibration models have a limited value for predicting of three-year major adverse cardiac events in our patients. The performance in predicting risk of the updated model resulted superimposable to the calibration slope model.

PMID:36598749 | DOI:10.1007/s12350-022-03173-4

World J Pediatr. 2023 Jan 4. doi: 10.1007/s12519-022-00657-8. Online ahead of print.

ABSTRACT

BACKGROUND: The survival of preterm infants has improved over the last decade, but impaired brain development leading to poor neurological outcomes is still a major comorbidity associated with prematurity. The aim of this study was to evaluate the effect of nutrition on neurodevelopment in preterm infants and identify markers for improved outcomes.

METHODS: Totally 67 premature infants with a gestational age of 24-34 weeks and a birth weight of 450-2085 g were included. Clinical parameters and documented diet were collected from medical records. The nutritional analysis comprised the protein, fat, carbohydrate, and energy intake during different time spans. Brain development was assessed by determining deep gray matter (DGM; basal ganglia and thalamus) and lateral ventricular (LV) volumes as measured on cerebral magnetic resonance imaging scans obtained at term-equivalent age (TEA), and potential associations between nutrition and brain volumetrics were detected by regression analysis.

RESULTS: We observed a negative correlation between mean daily protein intake in the third postnatal week and MRI-measured DGM volume at TEA (P = 0.007). In contrast, head circumference at a corrected age of 35 weeks gestation (P < 0.001) and mean daily fat intake in the fourth postnatal week (P = 0.004) were positively correlated with DGM volume. Moreover, mean daily carbohydrate intake in the first postnatal week (P = 0.010) and intraventricular hemorrhage (P = 0.003) were revealed as independent predictors of LV volume.

CONCLUSION: The study emphasizes the importance of nutrition for brain development following preterm birth.

PMID:36598742 | DOI:10.1007/s12519-022-00657-8

Radiol Med. 2023 Jan 4. doi: 10.1007/s11547-022-01583-5. Online ahead of print.

ABSTRACT

PURPOSE: To compare the positive predictive values (PPVs) of BI-RADS categories used to assess pure mammographic calcifications in women with and without a previous history of breast cancer (PHBC).

MATERIALS AND METHODS: In this retrospective study, all consecutive pure mammographic calcifications (n = 320) undergoing a stereotactic biopsy between 2016 and 2018 were identified. Mammograms were evaluated in consensus by two radiologists according to BI-RADS and blinded to patient history and pathology results. Final pathologic results were used as the standard of reference. PPV of BI-RADS categories were compared between the two groups. Data were evaluated using standard statistics, Mann-Whitney U tests and Chi-square tests.

RESULTS: Two hundred sixty-eight patients (274 lesions, median age 54 years, inter-quartile range, 50-65 years) with a PHBC (n = 46) and without a PHBC (n = 222) were included. Overall PPVs were the following: BI-RADS 2, 0% (0 of 56); BI-RADS 3, 9.1% (1 of 11); BI-RADS 4a, 16.2% (6 of 37); BI-RADS 4b, 37.5% (48 of 128); BI-RADS 4c, 47.3% (18 of 38) and BI-RADS 5, 100% (4 of 4). The PPV of BI-RADS categories was similar in patients with and without a PHBC (P = .715). Calcifications were more often malignant in patients with a PHBC older than 10 years (47.3%, 9 of 19) compared to 1-2 years (25%, 1 of 4), 2-5 years (20%, 2 of 10) and 5-10 years (0%, of 13) from the first breast cancer (P = .005).

CONCLUSION: PPV of mammographic calcifications is similar in women with or without PHBC when BI-RADS classification is strictly applied. A higher risk of malignancy was observed in patients with a PHBC longer than 10 years.

PMID:36598734 | DOI:10.1007/s11547-022-01583-5

Environ Sci Pollut Res Int. 2023 Jan 4. doi: 10.1007/s11356-022-25019-9. Online ahead of print.

ABSTRACT

Anthropogenic and geological factors play an essential role in the variability of groundwater quality, resulting in a weak spatial dependence of groundwater trace elements. Thus, it is an essential study to investigate the factors affecting groundwater quality and its spatial abundance of trace elements (including As, B, and other metalloids). In this study, samples are obtained from a Permian sandstone fracture aquifer in a coal mining area. A multivariate statistical analysis, hydrogeochemistry modeling, and spatial autocorrelation analysis were used to analyze the data. The results showed that Moran index was positive for all trace elements, which had good spatial autocorrelation. The Local indicators of spatial association (LISA) indicated that trace elements were clustered. The hydrogeochemical modeling results indicated that the precipitation and stability of iron-phase minerals, such as rhodochrosite and arsenic (As) absorption on the surface of iron-phase minerals in the aquifer, may limit concentrations in the southern region. The spatial autocorrelations of both As and Boron (B) were positive (high-high) in the western areas, indicating that As contamination occurred from both natural geological causes and human coal mining activities. In contrast, B contamination was mainly linked to the influence of human agricultural or industrial activities. Over 96% of the groundwater concentrations of As (10 μg/L) and B (300 μg/L) in the study area exceeded World Health Organization (WHO) limits. Overall, the results of this work could help decision-makers involved in regional water quality management visualize disperse zones where specific anthropogenic and geological processes may threaten groundwater quality.

PMID:36598722 | DOI:10.1007/s11356-022-25019-9

Int Ophthalmol. 2023 Jan 4. doi: 10.1007/s10792-022-02624-8. Online ahead of print.

ABSTRACT

PURPOSE: This study describes the microbiology of bacterial orbital cellulitis (OC) over an 11-year period and its clinical associations at three tertiary institutions in Adelaide, South Australia.

METHODS: Multi-centre retrospective study of the microbiology of bacterial OC between January 2012 and August 2022. Pre-septal cellulitis was excluded. Differences in means were determined by the Independent Samples t-test, and categorical data was analysed via Pearson’s Chi square. A P-value < 0.05 was statistically significant.

RESULTS: 99 patients (male: 69, mean age: 22.0 ± 23.8 years old), of which 70.7% were aged ≤ 18 years. Sinus and orbital abscess cultures had the greatest positive yield (73.7%). Frequency of organisms: Streptococcus species (34.3%), Staphylococcus aureus (28.3%), Haemophilus species (5.1%), mixed anaerobes (3.0%), Enterobacter cloacae (2.0%), Moraxella catarrhalis (1.0%), Pseudomonas aeruginosa (1.0%), Corynebacterium species (1.0%), Klebsiella pneumoniae (1.0%), Proteus mirabilis (1.0%), Citrobacter koseri (1.0%), and Enterococcus species (1.0%). Streptococcus species predominated in the paediatric population, with a statistically significant difference in mean age between Streptococcus species and Staphylococcus aureus (14.1 ± 16.5 vs 27.6 ± 24.6 years old, respectively) (P = 0.028). No organism was cultured in 32.3% of cases. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 28.6% of all Staphylococcus aureus isolates, with 50% occurring between 2021 and 2022.

CONCLUSION: Yearly microbiological trends have remained largely constant in South Australia. The causative organism was not identified in 32.3% of cases, further emphasising appropriate empirical antibiotics, and obtaining microbiology from various sources. MRSA OC remains of increased clinical and public health concern and may be associated with a more aggressive disease course.

PMID:36598712 | DOI:10.1007/s10792-022-02624-8

Med Biol Eng Comput. 2023 Jan 4. doi: 10.1007/s11517-022-02756-0. Online ahead of print.

ABSTRACT

This work studied, for the first time, the time-frequency characteristics of the vibrations underlying the first fetal heart sound (S1). To this end, the continuous wavelet transform was used to produce time-energy and time-frequency representations of S1 from where five vibrations were studied by their timing, energy, and frequency characteristics in three gestational age groups (early, G1, preterm, G2, and term, G3). Results on a dataset of 1111 S1s (9 phonocardiograms between 33 and 40 weeks) indicate that such representations uncovered a set of five well-defined, non-overlapped, and large-energy vibrations whose features presented interesting behaviors. Thus, for each group, while the timing characteristics of the five vibrations were likely to be statically different, their frequencies were similar. Also, the energies of the vibrations were likely to be different only in G2 and G3. Alternatively, while the frequencies and energies of each vibration were likely to statistically change among groups (excluding the energy of the third vibration), the timings were more likely to change only from G1 to G2 and from G2 to G3. Therefore, this methodology seems suitable to detect and study the generating vibrations of S1. Future work will test the correlation between these vibrations and the valvular events.

PMID:36598675 | DOI:10.1007/s11517-022-02756-0