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BMC Genomics Jun 2024Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous...
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation.
METHODS
Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS.
RESULTS
A gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10; OR = 4.73, p = 2 × 10; OR = 2.3, p = 7.49 × 10, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10).
CONCLUSIONS
In a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2.
Topics: Female; Humans; Male; Amyotrophic Lateral Sclerosis; Ethnicity; Genetic Predisposition to Disease; Genetic Variation; European People; East Asian People; African People; Hispanic or Latino; Middle Eastern People; South Asian People
PubMed: 38951798
DOI: 10.1186/s12864-024-10538-1 -
BMC Pediatrics Jun 2024The relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the...
BACKGROUND
The relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the Hp-infection occurrence in newly-diagnosed pediatric-patients with IBD compared to no-IBD patients. Additionally, we aimed to examine differences in clinical-activity-index(CAI) and endoscopic-severity-score(ESS)between IBD-patients with and without Hp-infection, at baseline and at 1-year-follow-up(FU), after eradication-therapy(ET).
METHODS
IBD diagnosis was based on Porto-criteria, and all patients underwent gastroscopy at baseline and 1-year FU. For Crohn's-disease(CD) and ulcerative colitis(UC), IBD-CAI and -ESS were classified using PCDAI/SES-CD and PUCAI/UCEIS, respectively.
RESULTS
76 IBD-patients were included in the study[35 F(46.1%),median-age 12(range 2-17)]. CD and UC were diagnosed in 29(38.2%) and 45(59.2%)patients, respectively, and unclassified-IBD in two(2.6%)patients. Non-IBD patients were 148[71 F(48.0%),median-age 12(range 1-17)]. Hp-infection at baseline was reported in 7(9.2%) and 18(12.2%)IBD and non-IBD patients, respectively(p = 0.5065). The 7 IBD patients with Hp infection were compared to 69 IBD patients without Hp-infection at baseline evaluation, and no significant differences were reported considering CAI and ESS in these two groups. At 1-year FU, after ET, IBD patients with Hp infection improved, both for CAI and ESS, but statistical significance was not reached.
CONCLUSION
The occurrence of Hp-infection did not differ between IBD and no-IBD patients. No differences in CAI or ESS were observed at the diagnosis, and after ET no worsening of CAI or ESS was noted at one-year FU, between Hp-positive and -negative IBD patients.
Topics: Humans; Helicobacter Infections; Child; Male; Female; Adolescent; Prospective Studies; Helicobacter pylori; Child, Preschool; Colitis, Ulcerative; Crohn Disease; Severity of Illness Index; Inflammatory Bowel Diseases; Gastroscopy; Follow-Up Studies; Anti-Bacterial Agents
PubMed: 38951792
DOI: 10.1186/s12887-024-04902-z -
BMC Anesthesiology Jun 2024Awake extubation and deep extubation are commonly used anesthesia techniques. In this study, the safety of propofol-assisted deep extubation in the dental treatment of... (Observational Study)
Observational Study
PURPOSE
Awake extubation and deep extubation are commonly used anesthesia techniques. In this study, the safety of propofol-assisted deep extubation in the dental treatment of children was assessed.
MATERIALS AND METHODS
Children with severe caries who received dental treatment under general anesthesia and deep extubation between January 2017 and June 2023 were included in this study. Data were collected on the following variables: details and time of anesthesia, perioperative vital signs, and incidence of postoperative complications. The incidence of laryngeal spasm (LS) was considered to be the primary observation indicator.
RESULTS
The perioperative data obtained from 195 children undergoing dental treatment was reviewed. The median age was 4.2 years (range: 2.3 to 9.6 years), and the average duration of anesthesia was 2.56 h (range 1 to 4.5 h). During intubation with a videoscope, purulent mucus was found in the pharyngeal cavity of seven children (3.6%); LS occurred in five of them (2.6%), and one child developed a fever (T = 37.8 °C) after discharge. Five children (2.6%) experienced emergence agitation (EA) in the recovery room. Also, 13 children (6.7%) experienced epistaxis; 10 had a mild experience and three had a moderate experience. No cases of airway obstruction (AO) and hypoxemia were recorded. The time to open eyes (TOE) was 16.3 ± 7.2 min. The incidence rate of complications was 23/195 (11.8%). Emergency tracheal reintubation was not required. Patients with mild upper respiratory tract infections showed a significantly higher incidence of complications (P < 0.001).
CONCLUSIONS
Propofol-assisted deep extubation is a suitable technique that can be used for pediatric patients who exhibited non-cooperation in the outpatient setting. Epistaxis represents the most frequently encountered complication. Preoperative upper respiratory tract infection significantly increases the risk of complications. The occurrence of EA was notably lower than reported in other studies.
Topics: Humans; Airway Extubation; Child, Preschool; Retrospective Studies; Propofol; Child; Male; Female; Anesthetics, Intravenous; Anesthesia, General; Postoperative Complications; Laryngismus; Intubation, Intratracheal; Anesthesia, Dental
PubMed: 38951786
DOI: 10.1186/s12871-024-02599-2 -
BMC Public Health Jun 2024Nitrite inhalants (poppers) are associated with HIV transmission and commonly used among young men who have sex with men (YMSM), a group at increased risk for HIV....
Nitrite inhalants (poppers) are associated with HIV transmission and commonly used among young men who have sex with men (YMSM), a group at increased risk for HIV. Significant research gaps exist in understanding the context in which YMSM use poppers. Qualitative interviews were conducted with 15 YMSM (22-31 years) with HIV to better understand the context in which poppers are used and their impacts on HIV care outcomes, such as care retention and antiretroviral adherence. The Social Ecological Model was applied to understand intrapersonal, interpersonal, community, and system level influences on popper use. Factors influencing popper use included: ubiquity of popper use in sexual settings, introduction to poppers by casual sexual partners, patient-HIV provider communication surrounding poppers, neighborhood, substance use and HIV care systems, and the legal status of poppers. Implications for clinical care, public health, policy, and future research are discussed.
Topics: Humans; Male; HIV Infections; Adult; Homosexuality, Male; Qualitative Research; Young Adult; Nitrites; Interviews as Topic
PubMed: 38951768
DOI: 10.1186/s12889-024-19284-1 -
BMC Pregnancy and Childbirth Jun 2024Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain...
Does the implementation of revised American College of Cardiology and American Heart Association (ACC/AHA) guidelines improve the identification of stillbirths and preterm births in hypertensive pregnancies: a population-based cohort study from South Asia and sub-Saharan Africa.
BACKGROUND
Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes.
METHODS
We conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP) < 120 mm Hg and diastolic blood pressure (dBP) < 80 mm Hg), elevated blood pressure (sBP 120-129 and dBP < 80), stage 1 hypertension (sBP 130-139 or dBP 80-89, or both), and stage 2 hypertension (sBP ≥ 140 or dBP ≥ 90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (≥ 140/90) and revised ACC/AHA (≥ 130/80) thresholds using normal blood pressure as reference group.
RESULTS
From May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8, 95% CI 1.4, 2.3). The JNC 7 hypertension cut-off of ≥ 140/90 was significantly associated with a higher risk of preterm births (RR 1.6, 95% CI 1.2, 2.2) and stillbirths (RR 3.6, 95% CI 2.5, 5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7 and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes.
CONCLUSION
The ACC/AHA criteria (≥ 130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension.
Topics: Humans; Female; Pregnancy; Premature Birth; Stillbirth; Adult; Hypertension, Pregnancy-Induced; Practice Guidelines as Topic; United States; Pakistan; Cohort Studies; American Heart Association; Bangladesh; Tanzania; Young Adult; Blood Pressure; Infant, Newborn; Asia, Southern
PubMed: 38951766
DOI: 10.1186/s12884-024-06637-2 -
BMC Cancer Jul 2024The number of cancer survivors has increased in recent decades, and the majority of them suffer from sequelae of their disease and treatment. This study, which is part...
BACKGROUND
The number of cancer survivors has increased in recent decades, and the majority of them suffer from sequelae of their disease and treatment. This study, which is part of the larger research project OPTILATER, aims to explore different aspects of care services for long-term survivors (≥ 5 years after initial cancer diagnosis) in Germany. The study places an emphasis on the situation of people from different age groups, with different socio-demographic and cultural backgrounds, and sexually and gender diverse individuals.
METHODS
To investigate experiences related to follow-up care, focus groups (n = 2) will be conducted with members of patient advisory councils and advocacy groups, representatives of communities, healthcare workers and networks, as well as members of Associations of Statutory Health Insurance Physicians. Guided interviews will be carried out with patients and relatives (n = 40) to investigate needs, barriers and obstacles in terms of follow-up care. On this basis, additional focus groups (n = 2) will be carried out to derive possible scenarios for improving the consideration of needs. Focus groups and interviews will follow a semi-structured format and will be analysed content-analytically. Focus groups and interviews will be conducted online, recorded, transcribed, and analysed independently by two persons.
DISCUSSION
The qualitative approach is considered suitable because of the exploratory research aims. The identification of experiences and barriers can reveal disparities and optimization potential in the care of long-term cancer survivors.
Topics: Humans; Cancer Survivors; Qualitative Research; Female; Male; Focus Groups; Neoplasms; Germany; Health Services Needs and Demand; Middle Aged; Adult; Aged
PubMed: 38951760
DOI: 10.1186/s12885-024-12527-9 -
BMC Pediatrics Jun 2024Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and... (Observational Study)
Observational Study
PURPOSE
Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3-4 weeks of life in at-risk patients.
METHODS
A single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05.
RESULTS
In the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3-4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3-4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation.
CONCLUSIONS
MBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.
Topics: Humans; Fibroblast Growth Factor-23; Infant, Newborn; Female; Fibroblast Growth Factors; Biomarkers; Prospective Studies; Male; Bone Diseases, Metabolic; Infant, Premature, Diseases; Infant, Premature
PubMed: 38951759
DOI: 10.1186/s12887-024-04897-7 -
BMC Pediatrics Jul 2024Although most children with febrile seizures (FS) have a favorable prognosis, some experience recurrence within 1-3 years. Age, peak temperature, and family history are...
BACKGROUND
Although most children with febrile seizures (FS) have a favorable prognosis, some experience recurrence within 1-3 years. Age, peak temperature, and family history are now recognized as important risk factors for FS recurrence, yet studies in this area are lacking in China. This study aimed to investigate the risk factors for FS recurrence in children in Nantong, China, and to develop a prediction model.
METHODS
This retrospective cohort study analyzed 463 children diagnosed with febrile seizures (FS) who presented to the Affiliated Hospital of Nantong University between January 2015 and June 2020. Basic information, disease characteristics, and laboratory and imaging data were collected. A follow-up survey was conducted one year post-discharge to assess the recurrence status of FS in children. Univariate logistic regression and random forest models were used to identify and rank the predictive ability of risk factors for recurrence.
RESULTS
Of the 463 children with FS, 70 experienced recurrences within 1 year of discharge, resulting in a one-year recurrence rate of 15%. Age (OR = 0.61, 95% CI: 0.46, 0.80, P < 0.001), duration of the first episode (OR = 1.03, 95% CI: 1.00, 1.06, P = 0.040), and peak temperature (OR = 0.68, 95% CI: 0.47, 0.98, P = 0.036) were identified as independent risk factors for FS recurrence. Age had the highest relative importance in predicting FS recurrence, followed by the duration of the first episode, with an area under the ROC curve of 0.717.
CONCLUSION
Young age and duration of the first seizure are important independent risk factors for FS recurrence and are key considerations for predicting recurrence. Further research is needed to confirm the potential use of Neutrophil-lymphocyte ratio (NLR) as a predictor of FS recurrence.
Topics: Humans; Seizures, Febrile; Retrospective Studies; Risk Factors; Recurrence; Male; Female; China; Infant; Child, Preschool; Age Factors; Follow-Up Studies; Child; Prognosis
PubMed: 38951748
DOI: 10.1186/s12887-024-04895-9 -
Korean Journal of Anesthesiology Jul 2024This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children's hospital in South Korea.
BACKGROUND
This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children's hospital in South Korea.
METHODS
A retrospective analysis of pediatric procedural sedation with chloral hydrate between January 1, 2021, and March 30, 2022, was performed. The collected data included patient characteristics, sedation history, and procedure. Multivariable regression analysis was performed to identify the risk factors for procedural sedation failure and complications.
RESULTS
A total of 6691 procedural sedation were included in the analysis; sedation failure following chloral hydrate (50 mg/kg) occurred in 1457 patients (21.8%) and was associated with a higher rate of overall complications compared to those with successful sedation (17.5% [225 / 1457] vs. 6.2% [322 / 5234]; P < 0.001; odds ratio, 3.236). In the multivariable regression analysis, the following factors were associated with increased risk of sedation failure: general ward or intensive care unit inpatient (compared with outpatient); congenital syndrome; oxygen dependency; history of sedation failure or complications with chloral hydrate; procedure more than 60 min; and magnetic resonance imaging, radiotherapy, or procedures with painful or intense stimuli (all P values < 0.05). Factors contributing to the complications included general ward inpatient, congenital syndromes, congenital heart disease, preterm birth, oxygen dependency, history of complications with chloral hydrate, and current sedation failure with chloral hydrate (all P values < 0.05).
CONCLUSIONS
To achieve successful sedation with chloral hydrate, the patient's sedation history, risk factors, and the type and duration of the procedure should be considered.
PubMed: 38951746
DOI: 10.4097/kja.24125 -
Scientific Reports Jul 2024This study was performed to analyze fingertip capillary blood sampling in pediatric patients using microcapillary blood collection tubes and microhematocrit tubes and to...
This study was performed to analyze fingertip capillary blood sampling in pediatric patients using microcapillary blood collection tubes and microhematocrit tubes and to compare the blood cell analysis results obtained via these two blood collection methods. Finger capillary blood was collected from 110 outpatients using microcapillary blood collection tubes and microhematocrit tubes and complete blood count analysis was performed with a Sysmex XS-900i hematology analyzer and manual microscopy for blood cell morphology. Paired data was evaluated for agreement and bias using the microhematocrit samples as the reference group and the samples from the microcapillary blood collection tubes as the observation group. The two blood collection methods demonstrated good agreement for measuring red blood cell (RBC) parameters (i.e., RBC, Hb, Hct, MCV, MCH and MCHC), wherein the relative bias was > allowable total error (TEa) in 0.91%, 1.82%, 11.82%, 1.82%, 0.91% and 8.18% of the parameter measures, respectively. According to industry requirements, the proportion of samples meeting the acceptable bias level should be > 80%. Additionally, the estimated biases at each medical decision level were within clinically acceptable levels for RBC, Hb, Hct, and MCV. However, the proportion of WBC and PLT counts with relative bias > TEa was 25.45% and 35.45%, respectively. Furthermore, the relative bias of the WBC count at the medical decision level of 0.5 × 10/L and that of the PLT counts at the medical decision levels of 10 × 10/L and 50 × 10/L were clinically significant. Bland-Altman analysis further showed a mean bias of 0.66 × 10/L (95% LoA, - 0.79 to 2.11) for the WBC count and 39 × 10/L (95% LoA, - 46 to 124) for the PLT count from the blood samples collected in the microcapillary blood collection tubes compared with the counts of those collected in the microhematocrit tubes. Neutrophil, monocyte, lymphocyte, eosinophil, and PLT counts increased significantly in the microcapillary blood collection tubes compared with those in the microhematocrit tubes, along with an elevated number of instrument false alarms (P < 0.05). The two capillary blood collection devices exhibit performance differences. Therefore, clinicians should pay attention to the variation in results caused by different blood collection methods.
Topics: Humans; Blood Specimen Collection; Female; Child; Male; Blood Cell Count; Child, Preschool; Fingers; Infant; Adolescent; Capillaries; Leukocyte Count
PubMed: 38951565
DOI: 10.1038/s41598-024-64448-z