Tag: statistics

Pediatr Pulmonol. 2024 Mar 19. doi: 10.1002/ppul.26975. Online ahead of print.

ABSTRACT

BACKGROUND: Fetal exposure to tobacco smoking throughout pregnancy is associated with wheezing in infancy. We investigated the influence of in utero smoking exposure on lung ventilation homogeneity and the relationship between lung ventilation inhomogeneity at 7 weeks of age and wheezing in the first year of life.

METHODS: Maternal smoking was defined as self-reported smoking of tobacco or validated by exhaled (e)CO > 6 ppm. Lung function data from healthy infants (age 5-9 weeks) born to asthmatic mothers and parent-reported respiratory questionnaire data aged 12 months were collected in the Breathing for Life Trial (BLT) birth cohort. Tidal breathing analysis and SF₆ -based Multiple Breath Washout testing were performed in quiet sleep. Descriptive statistics and regression analysis were used to assess associations.

RESULTS: Data were collected on 423 participants. Infants born to women who self-reported smoking during pregnancy (n = 42) had higher lung clearance index (LCI) than those born to nonsmoking mothers (7.90 vs. 7.64; p = .030). Adjusted regression analyzes revealed interactions between self-reported smoking and LCI (RR: 1.98, 95% CI: 1.07-3.63, 0.028, for each unit increase in LCI) and between eCO > 6 ppm and LCI (RR: 2.25, 95% CI: 1.13-4.50, 0.022) for the risk of wheeze in the first year of life.

CONCLUSION: In utero tobacco smoke exposure induces lung ventilation inhomogeneities. Furthermore, an interaction between smoke exposure and lung ventilation inhomogeneities increases the risk of having a wheeze in the first year of life.

PMID:38501326 | DOI:10.1002/ppul.26975

Clin Transl Sci. 2024 Mar;17(3):e13772. doi: 10.1111/cts.13772.

ABSTRACT

Genetic variants affect drug responses, making pre-emptive genotyping crucial for averting serious adverse events (SAEs) and treatment failure. However, assessing the benefits of pre-emptive genotyping based on genetic distribution, drug exposure, and demographics is challenging. This study aimed to estimate the population-level benefits of pre-emptive genotyping in the Korean population using nationwide cohort data. We reviewed actionable gene-drug combinations recommended by both the Clinical Pharmacogenomics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) as of February 2022, identifying high-risk phenotypes. We collected reported risk reduction from genotyping and standardized it into population attributable risks. Healthcare reimbursement costs for SAEs and treatment failures were obtained from the Health Insurance Review and Assessment Service Statistics in 2021. The benefits of pre-emptive genotyping for a specific group were determined by multiplying drug exposure from nationwide cohort data by individual genotyping benefits. We identified 31 gene-drug-event pairs, with CYP2D6 and CYP2C19 demonstrating the greatest benefits for both male and female patients. Individuals aged 65-70 years had the highest individual benefit from pre-emptive genotyping, with $84.40 for men and $100.90 for women. Pre-emptive genotyping, particularly for CYP2D6 and CYP2C19, can provide substantial benefits.

PMID:38501281 | DOI:10.1111/cts.13772

Hypertension. 2024 Mar 19. doi: 10.1161/HYPERTENSIONAHA.123.22142. Online ahead of print.

ABSTRACT

BACKGROUND: Coarctation of the aorta (CoA) often leads to hypertension) posttreatment. Evidence is lacking for the current >20 mm Hg peak-to-peak blood pressure (BP) gradient (BPGpp) guideline, which can cause aortic thickening, stiffening, and dysfunction. This study sought to find the BPGpp severity and duration that avoid persistent dysfunction in a preclinical model and test if predictors translate to hypertension status in patients with CoA.

METHODS: Rabbits (n=75; 5-12/group) were exposed to mild, intermediate, or severe CoA (≤12, 13-19, ≥20 mm Hg BPGpp) for ≈1, 3, or 22 weeks using dissolvable and permanent sutures with thickening, stiffening, contraction, and endothelial function evaluated via multivariate regression. Relevance to patients with CoA (n=239; age, 0.01-46 years; median 3.7 months) was tested by retrospective review of predictors (preoperative BPGpp, surgical age, etc.) versus follow-up hypertension status.

RESULTS: CoA duration and severity were predictive of aortic remodeling and active dysfunction in rabbits, and hypertension in patients with CoA. Interaction between patient age and BPGpp at surgery contributed significantly to hypertension, similar to rabbits, suggesting preclinical findings translate to patients. Machine learning decision tree analysis uncovered that preoperative BPGpp and surgical age predict risk of hypertension along with residual postoperative BPGpp.

CONCLUSIONS: These findings suggest the current BPGpp threshold determined decades ago is likely too high to prevent adverse coarctation-induced aortic remodeling. The results and decision tree analysis provide a foundation for revising CoA treatment guidelines considering the interaction between CoA severity and duration to limit the risk of hypertension.

PMID:38501250 | DOI:10.1161/HYPERTENSIONAHA.123.22142

Hypertension. 2024 Mar 19. doi: 10.1161/HYPERTENSIONAHA.123.22418. Online ahead of print.

ABSTRACT

BACKGROUND: Whether individuals with gestational diabetes (GDM) had an increased risk of hypertension remains unclear. We conducted a systematic literature review and meta-analysis to examine the association between GDM and hypertension and performed a quantitative bias analysis to quantify the impact of uncontrolled confounding due to antenatal psychological stress.

METHODS: We searched databases (PUBMED, EMBASE, and Web of Science) through 2022/11. Eligible studies were cohort studies that reported the association of GDM with hypertension. We assessed the risk of bias using the Newcastle-Ottawa Scale for cohort studies. We pooled adjusted risk ratios with 95% CIs using a random effects model. We performed the quantitative bias analysis using the bias formula.

RESULTS: We included 15 cohort studies, with a total of 3 959 520 (GDM, 175 378; non-GDM, 3 784 142) individuals. During the follow-up of 2 to 20 years, 106 560 cases of hypertension were reported. We found that GDM was associated with a higher risk of hypertension (pooled risk ratio, 1.78 [95% CI, 1.47, 2.17]). The risk ratio was lower among cohorts assessing incident (1.58 [95% CI, 1.29, 1.95]) than prevalent hypertension (2.60 [95% CI, 2.40, 2.83]). However, other subgroup analyses showed no differences. The quantitative bias analysis revealed that if the uncontrolled confounder of antenatal psychological stress was additionally adjusted, the positive association between GDM and hypertension would attenuate slightly (≤18%) but remains positive.

CONCLUSIONS: Limitations of this study included residual confounding and discrepancies in GDM and hypertension ascertainments. Our findings indicate that GDM is positively associated with hypertension after the index pregnancy.

PMID:38501243 | DOI:10.1161/HYPERTENSIONAHA.123.22418

Environ Microbiol. 2024 Mar;26(3):e16615. doi: 10.1111/1462-2920.16615.

ABSTRACT

Microbial communities are commonly characterised through the metabarcoding of environmental DNA. This DNA originates from both viable (including dormant and active) and dead organisms, leading to recent efforts to distinguish between these states. In this study, we further these approaches by distinguishing not only between viable and dead cells but also between dormant and actively growing cells. This is achieved by sequencing both rRNA and rDNA, in conjunction with propidium monoazide cross-linked rDNA, to partition the active, dormant and relic fractions in environmental samples. We apply this method to characterise the diversity and assemblage structure of these fractions of microeukaryotes in intertidal sediments during a wet-dry-rewet incubation cycle. Our findings indicate that a significant proportion of microeukaryotic phylotypes detected in the total rDNA pools originate from dormant and relic microeukaryotes in the sediments, both in terms of richness (dormant, 13 ± 2%; relic, 47 ± 5%) and read abundance (dormant, 20 ± 7%; relic, 14 ± 5%). The richness and sequence proportion of dormant microeukaryotes notably increase during the transition from wet to dry conditions. Statistical analyses suggest that the dynamics of diversity and assemblage structure across different activity fractions are influenced by various environmental drivers. Our strategy offers a versatile approach that can be adapted to characterise other microbes in a wide range of environments.

PMID:38501240 | DOI:10.1111/1462-2920.16615

Cancer Med. 2024 Mar;13(5). doi: 10.1002/cam4.6776.

ABSTRACT

Mivavotinib (TAK-659/CB-659), a dual SYK/FLT3 inhibitor, reduced immunosuppressive immune cell populations and suppressed tumor growth in combination with anti-PD-1 therapy in cancer models. This dose-escalation/expansion study investigated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of mivavotinib plus nivolumab in patients with advanced solid tumors. Patients received oral mivavotinib 60-100 mg once-daily plus intravenous nivolumab 3 mg/kg on days 1 and 15 in 28-day cycles until disease progression or unacceptable toxicity. The dose-escalation phase evaluated the recommended phase II dose (RP2D; primary endpoint). The expansion phase evaluated overall response rate (primary end point) at the RP2D in patients with triple-negative breast cancer (TNBC). During dose-escalation (n = 24), two dose-limiting toxicities (grade 4 lipase increased and grade 3 pyrexia) occurred in patients who received mivavotinib 80 mg and 100 mg, respectively. The determined RP2D was once-daily mivavotinib 80 mg plus nivolumab 3 mg/kg. The expansion phase was terminated at ~50% enrollment (n = 17) after failing to meet an ad hoc efficacy futility threshold. Among all 41 patients, common treatment-emergent adverse events (TEAEs) included dyspnea (48.8%), aspartate aminotransferase increased, and pyrexia (46.3% each). Common grade ≥3 TEAEs were hypophosphatemia and anemia (26.8% each). Mivavotinib plasma exposure was generally dose-proportional (60-100 mg). One patient had a partial response. Mivavotinib 80 mg plus nivolumab 3 mg/kg was well tolerated with no new safety signals beyond those of single-agent mivavotinib or nivolumab. Low response rates highlight the challenges of treating unresponsive tumor types, such as TNBC, with this combination and immunotherapies in general. TRIAL REGISTRATION ID: NCT02834247.

PMID:38501219 | DOI:10.1002/cam4.6776

JAMA. 2024 Mar 19. doi: 10.1001/jama.2024.2934. Online ahead of print.

ABSTRACT

IMPORTANCE: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial.

OBJECTIVE: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU).

DESIGN, SETTING, AND PARTICIPANTS: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023.

INTERVENTIONS: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU.

MAIN OUTCOMES AND MEASURES: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days.

RESULTS: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital.

CONCLUSION AND RELEVANCE: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04425031.

PMID:38501214 | DOI:10.1001/jama.2024.2934

JAMA. 2024 Mar 19. doi: 10.1001/jama.2024.3376. Online ahead of print.

NO ABSTRACT

PMID:38501213 | DOI:10.1001/jama.2024.3376

J Sex Med. 2024 Mar 18:qdae019. doi: 10.1093/jsxmed/qdae019. Online ahead of print.

ABSTRACT

BACKGROUND: Genital self-image is among the factors affecting women’s sexual function.

AIM: The present study aimed to determine changes in the genital self-image and its relationship with women’s sexual function in the third trimester of pregnancy and postpartum.

METHODS: The participants of this prospective cohort study included 301 eligible pregnant women chosen through stratified random sampling with proportional allocation from comprehensive health centers in Gorgan, Iran. The Persian version of the 7-item Female Genital Self-Image Scale, the 6-item Female Sexual Function Index, and Depression Anxiety and Stress Scale 21 were filled in a self-report manner on 2 occasions: (1) 30 to 37 weeks of pregnancy and (2) 12 to 16 weeks (± 2 weeks) postpartum. Finally, the data were analyzed using SPSS 24 software.

OUTCOMES: Outcomes included Female Genital Self-Image Scale and Female Sexual Function Index changes from pregnancy to postpartum according to the childbirth mode.

RESULTS: The mean age of participants was 29.66 ± 5.27 years. These values for the genital self-image scores of women during pregnancy (19.18 ± 3.25) and postpartum (19.43 ± 3.57) were not significantly different (P = .30). Also, this difference was not statistically significant regarding the mode of delivery in 2 groups of women with vaginal birth (P = .62) and cesarean section (P = .14). The mean Female Sexual Function Index scores during pregnancy (15.15 ± 6.73) and postpartum (17.52 ± 6.46) were significantly different (P = .001). In addition, this difference was significant in women with vaginal birth (P = .004) and cesarean section (P = .001).

CLINICAL IMPLICATIONS: Clinicians should inform women/couples about changes in female sexual function and address genital self-image as a factor involved in female sexual function during pregnancy and postpartum.Strengths and Limitations: Because the participants of this study were women in the third trimester of pregnancy, the obtained results may not be generalized to pregnant women in the first and second trimesters of pregnancy or even to different postpartum periods (ie, midterm and long term).

CONCLUSION: The results showed that the female genital self-image is not significantly different during pregnancy and postpartum, or with the mode of delivery. However, the female sexual function score in postpartum is higher than in pregnancy, regardless of the mode of delivery.

PMID:38501193 | DOI:10.1093/jsxmed/qdae019

Nurs Manag (Harrow). 2024 Mar 19. doi: 10.7748/nm.2024.e2104. Online ahead of print.

ABSTRACT

BACKGROUND: There is increasing research interest in the relationship between ethical leadership and deviant workplace behaviour. Ethical leadership encompasses altruism, courage, ethical orientation, integrity and fairness. Examples of deviant workplace behaviours include theft, fraud, sabotage, assault, abuse, manipulation and bullying. It appears that when leaders are fair and emphasise ethical conduct, followers are less inclined to engage in deviant workplace behaviour.

AIM: To investigate the relationship between nurses’ self-rated levels of deviant workplace behaviour and perceived levels of ethical leadership in managers.

METHOD: For this descriptive correlational study, 355 nurses from one university hospital in Egypt responded to an online questionnaire comprising the Ethical Leadership Scale and the Workplace Deviance Behavior Scale. Descriptive and inferential statistics were used to explore results and examine the relationships between study variables.

RESULTS: There was a statistically significant negative relationship between respondents’ self-rated levels of deviant workplace behaviour and their perceptions of levels of ethical leadership in managers. The results appeared to confirm previous research. Nurses who feel that they are treated fairly by their managers tend to have positive attitudes towards work, colleagues and management.

CONCLUSION: Ethical leadership on the part of managers is a significant determinant of nurses’ behaviour in the workplace and should therefore be fostered by healthcare organisations.

PMID:38501169 | DOI:10.7748/nm.2024.e2104