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Balloon valvuloplasty and surgical aortic valvotomy have been the treatment mainstays for congenital aortic stenosis in children. Choice of intervention often differs depending upon centre bias with limited relevant, comparative literature.
This study aims to provide an unbiased, contemporary matched comparison of these balloon and surgical approaches.
Retrospective analysis of patients with congenital aortic valve stenosis who underwent balloon valvuloplasty (Queensland Children’s Hospital, Brisbane) or surgical valvotomy (Royal Children’s Hospital, Melbourne) between 2005 and 2016. Patients were excluded if pre-intervention assessment indicated ineligibility to either group. Propensity score matching was performed based on age, weight, and valve morphology.
Sixty-five balloon patients and seventy-seven surgical patients were included. Overall, the groups were well matched with 18 neonates/25 infants in the balloon group and 17 neonates/28 infants in the surgical group. Median age at balloon was 92 days (range 2 days – 18.8 years) compared to 167 days (range 0 days – 18.1 years) for surgery (rank-sum p = 0.08). Mean follow-up was 5.3 years. There was one late balloon death and two early surgical deaths due to left ventricular failure. There was no significant difference in freedom from reintervention at latest follow-up (69% in the balloon group and 70% in the surgical group, p = 1.0).
Contemporary analysis of balloon aortic valvuloplasty and surgical aortic valvotomy shows no difference in overall reintervention rates in the medium term. Balloon valvuloplasty performs well across all age groups, achieving delay or avoidance of surgical intervention.
Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12–23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.
This study aimed to analyse the results of chyle fistula testing using the SD LipidoCare system in patients who had undergone neck dissections performed in our hospital in 2019.
Sixty patients who underwent neck dissections from March 2019 to November 2019 were identified based on their medical records.
Post-operative chyle fistulas were observed in 3 of 60 patients (5 per cent). All patients who developed chyle fistulas had undergone left-sided neck dissections. Within 3 minutes, the SD LipidoCare test had produced triglyceride results of 49, 56 and 207 mg/dl in the three patients. The remaining 57 patients measured ‘low’ for triglycerides on the SD LipidoCare test system.
The SD LipidoCare test quickly and accurately diagnosed chyle fistulas in patients who had undergone neck dissections. All patients improved with conservative treatment following the early diagnosis of chyle fistulas.
Previous studies have reported the basic reproduction number (R0) of coronavirus disease from publicly reported data that lack information such as onset of symptoms, presence of importations or known super-spreading events. Using data from the Republic of Korea, we illustrated how estimates of R0 can be biased and provided improved estimates with more detailed data. We used COVID-19 contact trace system in Korea, which can provide symptom onset date and also serial intervals between contacted people. The total R0 was estimated as 2.10 (95% confidence interval (CI) 1.84–2.42). Also, early transmission of COVID-19 differed by regional or social behaviours of the population. Regions affected by a specific church cluster, which showed a rapid and silent transmission under non-official religious meetings, had a higher R0 of 2.40 (95% CI 2.08–2.77).
Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.
Self-assembly, a process in which molecules, polymers, and particles are driven by local interactions to organize into patterns and functional structures, is being exploited in advancing silicon electronics and in emerging, unconventional electronics. Silicon electronics has relied on lithographic patterning of polymer resists at progressively smaller lengths to scale down device dimensions. Yet, this has become increasingly difficult and costly. Assembly of block copolymers and colloidal nanoparticles allows resolution enhancement and the definition of essential shapes to pattern circuits and memory devices. As we look to a future in which electronics are integrated at large numbers and in new forms for the Internet of Things and wearable and implantable technologies, we also explore a broader material set. Semiconductor nanoparticles and biomolecules are prized for their size-, shape-, and composition-dependent properties and for their solution-based assembly and integration into devices that are enabling unconventional manufacturing and new device functions.
Introduction: Many cardiac arrest survivors die later due to hemorrhage or thromboembolism, thought to be caused by acquired coagulopathy in post-cardiac arrest syndrome (PCAS) from shock and reperfusion injury. Understanding PCAS is a priority identified by the AHA for the prevention of complications in cardiac arrest survivors. Shock dysregulates both coagulation and fibrinolysis. The key effector enzyme thrombin (Th), is responsible for both up- and down-regulating coagulation and fibrinolysis. Measuring early Th activity may allow for predicting PCAS coagulopathy, and early medical intervention in the ED. Therefore, we aimed to characterize the time-course profile of early coagulation using an established pig model of cardiac arrest. Methods: Yorkshire pigs were anaesthetised and intubated, had VF-arrest induced by pacing, and were resuscitated per ACLS. Rotational thromboelastometry (ROTEM) was performed on whole blood at four times: baseline, intra-arrest, post-arrest, and death, using the fibrin-based test with tissue factor to initiate clotting in the presence of a platelet inhibitor cytochalasin D (FIBTEM). Clot time (CT), clot formation time (CFT), alpha-angle during clot formation (Alpha), clot amplitude at 10 min (A10), maximum clot firmness (MCF), and maximum lysis as total percentage (ML%) were quantified. The primary outcome is the overall coagulation initiation measured by CFT, while secondary outcomes include ROTEM parameters reflecting Th activity. Parameters are compared over time in SPSS using repeated measures ANOVA and Bonferroni correction. Results: Pilot data from one experiment show that cardiac arrest causes immediate early changes to coagulation that subsequently normalized with ROSC (Figure 1). CFT was impaired immediately upon cardiac arrest (2.3-fold increase), normalized with ROSC, and impaired again at death when compared with baseline. Consistent with clotting impairment, A10, Alpha, and MCF were all reduced with cardiac arrest, normalized with ROSC, and impaired again at death. Conclusion: Higher initial indices of coagulopathy in patients with cardiac arrest appear to correlate with death and thromboembolism. In this pilot, CFT is acutely modified by cardiac arrest. Since CFT is affected by overall Th activity, early Th dysregulation may be a critical driver of coagulopathy. Th may therefore be a lead target that is modifiable in the emergency post-arrest setting to decrease morbidity and mortality from PCAS in cardiac arrest survivors.
The aim of this study was to examine whether the presence of risk alleles of the norepinephrine transporter gene (SLC6A2) polymorphisms is associated with differences in regional cerebral blood flow (rCBF) measured by 99mTc-HMPAO single photon emission computerized tomography in a Korean sample of ADHD.
The present study included 24 children with ADHD (9.5±2.4 years), consisting of 20 boys and 4 girls, aged 6-16 years. We investigated the G1287A and -3081(A/T) polymorphisms of the SLC6A2. The rCBF was compared between the ADHD subjects with and without risk alleles at the G1287A polymorphism and at the -3081(A/T) polymorphism. Image analyses were performed with voxelwise t-statistics using SPM2.
1) The ADHD subjects with the A allele (risk allele) at the G1287A polymorphism showed reduced perfusion in the left middle frontal gyrus, left inferior parietal lobule, precuneus, right superior frontal gyrus, and right superior parietal lobule as compared with ADHD subjects without the A allele (p< 0.001).
2) The ADHD subjects with the A allele at the G1287A polymorphism showed increased perfusion in the right middle frontal gyrus, right middle temporal gyrus, right superior temporal gyrus, right fusiform gyrus, right precentral gyrus, and right anterior lobe of cerebellum as compared with ADHD subjects without the A allele (p< 0.001).
3) No significant perfusion differences were found between ADHD subjects with and without the T allele (risk allele) at the -3081(A/T) polymorphism.
Our findings suggest that the SLC6A2 G1287A polymorphism might exert differential effects on rCBF in children with ADHD.
Although a number of studies have examined the relationship between depression and obesity, it is still insufficient to establish the specific pattern of relationship between depression and body mass index (BMI) categories. Thus, this study was aimed to investigate the relationship between depression and BMI categories.
A cross-sectional study was conducted for a cohort of 159,390 Korean based on Kangbuk Samsung Health Study (KSHS). Study participants were classified into 5 groups by Asian-specific cut-off of BMI (18.5, 23, 25 and 30 kg/m2). The presence of depression was determined by Center for Epidemiologic Studies-Depression scales (CES-D) = 16 and = 25. The adjusted odd ratios (ORs) for depression were evaluated by multiple logistic regression analysis, in which independent variable was 5 categories of BMI and dependent variable was depression. Subgroup analysis was conducted by gender and age.
When normal group was set as a reference, the adjusted ORs for depression formed U-shaped pattern of relationship with BMI categories [underweight: 1.31 (1.14–1.50), overweight: 0.94 (0.85–1.04), obese group: 1.01 (0.91–1.12), severe obese group: 1.28 (1.05–1.54)]. This pattern of relationship was more prominent in female and young age group than male and elderly subgroup. BMI level with the lowest likelihood of depression was 18.5 kg/m2 to 25 kg/m2 in women and 23 kg/m2 to 25 kg/m2 in men.
There was a U-shaped relationship between depression and BMI categories. This finding suggests that both underweight and severe obesity are associated with the increased risk for depression.
Sleep disturbances are common among cancer patients. Especially during hospitalization, not only adverse medical conditions but also ward environments can affect sleep. We have developed a program of sleep-hygiene education and sleeping pill reduction for inpatients (the i-sleep program) and applied it to cancer patients. This study aimed to explore the effect of the program.
In a general hospital with 2,715 beds, we estimated the proportion of inpatients prescribed hypnotics at admission to and discharge from the department of oncology before (2014) and after (2015) the program. In addition, we estimated the proportion of inpatients prescribed hypnotics among all inpatients in the department of oncology on the first day of each month of 2014 and 2015.
A total of 12,382 patients (2014, before) and 12,313 patients (2015, after) were admitted to oncology department of Asan Medical Center. The proportion of inpatients prescribed hypnotics as discharge medication among inpatients who had been prescribed them at the time of admission decreased significantly, from 76.0% (2014) to 69.8% (2015), after the program (RR = 0.92, 95% CI: 0.87–0.98). The proportion of inpatients newly prescribed sleeping pills after admission to the hospital did not significantly decrease (4.03% to 3.98%; RR = 0.99, 95% CI: 0.87–1.12). The mean prescription rate of sleeping pills per day was 10.02% in 2014 and 7.99% in 2015 (P = 0.03).
Although the i-sleep program did not reduce the prescription rate of sleeping pills per day, it effectively reduced the proportion of cancer patients who continued to take sleeping pills from admission until discharge.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
To investigate the association between parity and the risk of incident dementia in women.
We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).
Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.
Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations.
Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986–2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression.
We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33–1.62) to 1.05 (95% CI: 1.01–1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05).
Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.
Individuals with posttraumatic stress disorder (PTSD) are at increased risk of various chronic diseases. One hypothesized pathway is via changes in diet quality. This study evaluated whether PTSD was associated with deterioration in diet quality over time.
Data were from 51 965 women in the Nurses' Health Study II PTSD sub-study followed over 20 years. Diet, assessed at 4-year intervals, was characterized via the Alternative Healthy Eating Index-2010 (AHEI). Based on information from the Brief Trauma Questionnaire and Short Screening Scale for DSM-IV PTSD, trauma/PTSD status was classified as no trauma exposure, prevalent exposure (trauma/PTSD onset before study entry), or new-onset (trauma/PTSD onset during follow-up). We further categorized women with prevalent exposure as having trauma with no PTSD symptoms, trauma with low PTSD symptoms, and trauma with high PTSD symptoms, and created similar categories for women with new-onset exposure, resulting in seven comparison groups. Multivariable linear mixed-effects spline models tested differences in diet quality changes by trauma/PTSD status over follow-up.
Overall, diet quality improved over time regardless of PTSD status. In age-adjusted models, compared to those with no trauma, women with prevalent high PTSD and women with new-onset high PTSD symptoms had 3.3% and 3.6% lower improvement in diet quality, respectively, during follow-up. Associations remained consistent after adjusting for health conditions, sociodemographics, and behavioral characteristics.
PTSD is associated with less healthy changes in overall diet quality over time. Poor diet quality may be one pathway linking PTSD with a higher risk of chronic disease development.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Intake of the plant-derived n-3 fatty acid α-linolenic acid (ALA) has been associated with anti-atherosclerotic properties. However, information on the association between ALA intake and development of peripheral artery disease (PAD) is lacking. In this follow-up study, we investigated the association between dietary intake of ALA and the rate of PAD among middle-aged Danish men and women enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Incident PAD cases were identified through the Danish National Patient Register. Intake of ALA was assessed using a validated FFQ. Statistical analyses were performed using Cox proportional hazard regression allowing for separate baseline hazards among sexes and adjusted for established risk factors for PAD. During a median of 13·6 years of follow-up, we identified 950 valid cases of PAD with complete information on covariates. The median energy-adjusted ALA intake within the cohort was 1·76 g/d (95 % central range: 0·94–3·28). In multivariable analyses, we found no statistically significant association between intake of ALA and the rate of PAD (P = 0·339). Also, no statistically significant associations were observed in analyses including additional adjustment for co-morbidities and in sex-specific analyses. In supplemental analyses with additional adjustment for potential dietary risk factors, we found a weak inverse association of PAD with ALA intake above the median, but the association was not statistically significant (P = 0·314). In conclusion, dietary intake of ALA was not consistently associated with decreased risk of PAD.