Diagnostic Accuracy of Physical Examination and Pulse Oximetry for Critical Congenital Cardiac Disease Screening in Newborns

Background: Newborns with a critical congenital heart disease left undiagnosed and untreated have a substantial risk for serious complications and subsequent failure to thrive. Prenatal ultrasound screening is not widely available, nor is postnatal echocardiography. Physical examination is the standard for postnatal screening. Pulse oximetry has been proposed in numerous studies as an alternative screening method. This systematic review and meta-analysis aims to determine the diagnostic accuracies of both screening methods separately and combined. Methods: A systematic literature search of the Embase, PubMed, and Global Health databases up to 30 November 2023 was conducted with the following keywords: critical congenital heart disease, physical examination, clinical scores, pulse oximetry, and echocardiography. The search included all studies conducted in the newborn period using both physical examination and pulse oximetry as screening methods and excluded newborns admitted to the intensive care unit. All studies were assessed for risk of bias and applicability concerns using the QUADAS-2 score. The review adhered to the PRISMA 2020 statement guideline. Results: Out of 2711 articles, 20 articles were selected as eligible for meta-analysis. Cumulatively, the sample included 872,549 screened newborns. The pooled sensitivity of the physical examination screening method was found to be 0.69 (0.66–0.73 (95% CI)) and specificity was found to be 0.98 (0.98–0.98). For the pulse oximetry screening method, the pooled sensitivity and specificity yielded 0.78 (0.75–0.82) and 0.99 (0.99–0.99), respectively. The combined method of screening yielded improved diagnostic characteristics at a sensitivity and specificity of 0.93 (0.91–0.95) and 0.98 (0.98–0.98, respectively. Conclusions: The evidence indicates that combining both physical examination and pulse oximetry to screen for critical congenital heart disease exceeds the accuracy of either separate method. The main limitation is that solely newborns with suspected critical congenital heart disease were subjected to the reference standard. We recommend adapting both methods to screen for critical congenital heart diseases, especially in settings lacking standard fetal ultrasound screening. To increase the sensitivity further, we recommend increasing the screening time window and employing the peripheral perfusion index

Impact of children's respiratory allergies on caregivers.

Background. Despite the great attention that has been paid to HRQoL in children with respiratory allergy, few studies have addressed this aspect in relation to caregivers. The aim of our study was to evaluate the impact of childhood respiratory allergies on caregivers by means of a new method. Methods. 119 parents of children suffering from allergies (75 suffering from asthma and 44 suffering from rhinitis) were recruited from three Italian Allergy Units. Parents were asked to complete the Disease Impact On Caregiver (DIOC), a new non disease specific questionnaire, validated on the Italian population. The questionnaire consists of 31 items grouped in four factors (Performance, Personal gratification, Psychophysical endurance, Socio-emotional domain) and covers the life aspects that could be affected by the assistance duties towards an ill family member. Results. Child's asthma resulted to have a worse impact on many aspects of a parents' life than rhinitis. Differences resulted to be statistically significant in 19 aspects out of the 31 assessed. The worse impact of asthma versus rhinitis was confirmed in the following domains: Performance (24.0±18.2 vs 11.5±17.8), Personal gratification (26.3±20.5 vs 12.1±16.5) and Psychophysical endurance (35.0±24.8 vs 18.8±21.7). In the Socio-emotional domain no difference emerged. Conclusions. Compared to parents of rhinitics, parents of asthmatic children appear to be more compromised in their resistance to stress, mood, emotional stability, amount of spare time and leisure activities. Our results suggest the need of giving the due attention to these problems both in clinical practice and in research, in order to avoid possible interferences of the caregiver's distress in the optimization of treatment outcome

Tumor infiltrating lymphocytes expanded from pediatric neuroblastoma display heterogeneity of phenotype and function

Adoptive transfer of ex vivo expanded tumor infiltrating lymphocytes (TILs) has led to clinical benefit in some patients with melanoma but has not demonstrated convincing efficacy in other solid cancers. Whilst the presence of TILs in many types of cancer is often associated with better clinical prognosis, their function has not been systematically evaluated across cancer types. Responses to immunological checkpoint inhibitors in a wide range of cancers, including those for which adoptive transfer of expanded TILs has not shown clinical benefit, has clearly delineated a number of tumor type associated with tumor-reactive lymphocytes capable of effecting tumor remissions. Neuroblastoma is an aggressive childhood solid cancer in which immunotherapy with GD2-directed antibodies confers a proven survival advantage through incompletely understood mechanisms. We therefore evaluated the feasibility of ex vivo expansion of TILs from freshly resected neuroblastoma tumors and the potential therapeutic utility of TIL expansions. TILs were successfully expanded from both tumor biopsies or resections. Significant numbers of NKT and γδT cells were identified alongside the mixed population of cytotoxic (CD8+) and helper (CD4+) T cells of both effector and central memory phenotypes. Isolated TILs were broadly non-reactive against autologous tumor and neuroblastoma cell lines, so enhancement of neuroblastoma killing was attained by transducing TILs with a second-generation chimeric antigen receptor (CAR) targeting GD2. CAR-TILs demonstrated antigen-specific cytotoxicity against tumor cell lines. This study is the first to show reproducible expansion of TILs from pediatric neuroblastoma, the high proportion of innate-like lymphocytes, and the feasibility to use CAR-TILs therapeutically

Pattern formation of reaction-diffusion system having self-determined flow in the amoeboid organism of Physarum plasmodium

The amoeboid organism, the plasmodium of Physarum polycephalum, behaves on the basis of spatio-temporal pattern formation by local contraction-oscillators. This biological system can be regarded as a reaction-diffusion system which has spatial interaction by active flow of protoplasmic sol in the cell. Paying attention to the physiological evidence that the flow is determined by contraction pattern in the plasmodium, a reaction-diffusion system having self-determined flow arises. Such a coupling of reaction-diffusion-advection is a characteristic of the biological system, and is expected to relate with control mechanism of amoeboid behaviours. Hence, we have studied effects of the self-determined flow on pattern formation of simple reaction-diffusion systems. By weakly nonlinear analysis near a trivial solution, the envelope dynamics follows the complex Ginzburg-Landau type equation just after bifurcation occurs at finite wave number. The flow term affects the nonlinear term of the equation through the critical wave number squared. Contrary to this, wave number isn't explicitly effective with lack of flow or constant flow. Thus, spatial size of pattern is especially important for regulating pattern formation in the plasmodium. On the other hand, the flow term is negligible in the vicinity of bifurcation at infinitely small wave number, and therefore the pattern formation by simple reaction-diffusion will also hold. A physiological role of pattern formation as above is discussed.Comment: REVTeX, one column, 7 pages, no figur

Newborn Screening for Critical Congenital Heart Disease in a Low-Resource Setting; Research Protocol and Preliminary Results of the Tanzania Pulse Oximetry Study

Background: Critical Congenital Heart Disease (CCHD) is the leading cause of early new-born mortality. Its early detection and intervention is crucial for the survival of affected new-born. Pulse Oximetry (POX) has shown to be one of the feasible, accurate and cost-effective tools in screening CCHD in developed nations, it is yet to be practiced and established as standard of care in a low-resource setting. Objectives: This paper reports on the research protocol and preliminary results of an ongoing study regarding the performance of POX in detecting CCHD in new-borns in a low resource setting. Secondary objectives include investigating the burdens of CCHD and outcome at 12 months of age. Methods: The Tanzanian Pulse Oximetry Study (TPOXS) is a prospective cohort study which plans to enrol 30,000 mothers and new-borns delivered at two referral hospitals in Tanzania. New-borns are offered POX test 12 hours after birth, those positively undergoes echocardiography examinations. Confirmed with CCHD are placed under observation for up to first birthday. Results: During a 5-months pilot period, a total of 1,592 infants at the Muhimbili National Hospital, received POX test . 65% of them were post-caesarean section and 52% being male. Most babies delivered through Spontaneous Vertex Delivery (SVD) were promptly discharge and did not get screened. The detection-rate of CCHD was 2.5 per 1,000 live births (at 95% confidence interval [CI] 0.9 to 6.7 per 1000 live birth); with a POX false positive rate of 0.6%. Seven false-positive infants out of 10 were found to carry significant other neonatal conditions, including persistent pulmonary hypertension of the new-born, transient tachypnoeic and neonatal sepsis. Conclusion: This paper provides the protocol of the ongoing TPOXS with the preliminary results showing prevalence matching closely the global data. It shows acceptability of POX screening for CCHD in a well-prepared low resource setting

Cash Transfer to Adolescent Girls and Young Women to Reduce Sexual Risk Behavior (CARE): Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: The HIV epidemic in Eastern and Southern Africa is characterized by a high incidence and prevalence of HIV infection among adolescent girls and young women (AGYW) aged 15-24 years. For instance, in some countries, HIV prevalence in AGYW aged 20-24 years exceeds that in AGYW aged 15-19 years by 2:1. Sauti (meaning voices), a project supported by the United States Agency for International Development, is providing HIV combination prevention interventions to AGYW in the Shinyanga region, Tanzania. OBJECTIVE: The aim of this study is to determine the impact of cash transfer on risky sexual behavior among AGYW receiving cash transfer and HIV combination prevention interventions. This paper describes the research methods and general protocol of the study. Risky sexual behavior will be assessed by herpes simplex virus type 2 (HSV-2) incidence, compensated sex (defined as sexual encounters motivated by exchange for money, material support, or other benefits), and intergenerational sex (defined as a sexual partnership between AGYW and a man 10 or more years older). Through a qualitative study, the study seeks to understand how the intervention affects the structural and behavioral drivers of the HIV epidemic. METHODS: The trial employs audio computer-assisted self-interviewing, participatory group discussions (PGDs), and case studies to collect data. A total of 30 matched villages (15 intervention and 15 control clusters) were randomized to either receive cash transfer delivered over 18 months in addition to other HIV interventions (intervention arm) or to receive other HIV interventions without cash transfer (control arm). Study participants are interviewed at baseline and 6, 12, and 18 months to collect data on demographics, factors related to HIV vulnerabilities, family planning, sexual risk behavior, gender-based violence, and HSV-2 and HIV infections. A total of 6 PGDs (3 intervention, 3 control) were conducted at baseline to describe perceptions and preferences of different intervention packages, whereas 20 case studies are used to monitor and unearth the dynamics involved in delivery and uptake of cash transfer. RESULTS: The study was funded in June 2017; enrollment took place in December 2017. A total of two rounds of the follow-up survey are complete, and one round has yet to be conducted. The results are expected in December 2019 and will be disseminated through conferences and peer-reviewed publications. CONCLUSIONS: This study will document the synergetic impact of cash transfer in the presence of HIV combination prevention interventions on risky sexual behavior among out-of-school AGYW. The results will strengthen the evidence of cash transfer in the reduction of risky sexual behavior and provide feasible HIV prevention strategies for AGYW. TRIAL REGISTRATION: Clinicaltrials.gov NCT03597243; https://clinicaltrials.gov/ct2/show/NCT03597243. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14696

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Prevalence and correlates of partner violence among adolescent girls and young women: Evidence from baseline data of a cluster randomised trial in Tanzania.

BACKGROUND: Little has been documented about partner violence among adolescent girls and young women (AGYW) who are out of school, a factor associated with HIV acquisition. To understand areas for prioritising HIV prevention intervention efforts, we explored the prevalence and correlates of partner violence among out of school AGYW in Shinyanga, Tanzania. METHODS: A cross-sectional analysis of data from AGYW aged 15-23 years recruited in a cluster randomised trial conducted between October and December 2017 was used to examine correlates of partner violence. Data were collected through an Audio Computer-Assisted Self-interview. Multivariate logistic regression analysis was used to evaluate the association. RESULTS: 2276 (75.5%) AGYW were sexually active. Of these, 816 (35.9%) reported having experienced violence from partners in the last six months. After adjusting for other covariates, being formerly married (AOR = 1.55, 95% CI:1.02, 2.37), having children (AOR = 1.79, 95% CI:1.47, 2.16), anxiety and depression symptoms (AOR = 3.27, 95%CI: 2.15, 4.96), having engaged in sex work in the past six months (AOR = 1.92, 95% CI: 1.45, 2.53) and economic deprivation (AOR = 1.61, 95% CI: 1.34,1.92) were significantly associated with partner violence. CONCLUSIONS: Almost one in three sexually active AGYW had experienced partner violence in the 6 months preceding the survey. The findings underscore the need for future research to focus on understanding the reasons and dynamics underlying high level of partner violence among AGYW. Furthermore, there is a need for implementing intervention programs that aim to reduce economic deprivation among AGYWs and address social norms and structures perpetuating violence against AGYW. TRIAL REGISTRATION: ClinicalTrials.gov-ID NCT03597243

Effects of Extreme Precipitation to the Distribution of Infectious Diseases in Taiwan, 1994–2008

The incidence of extreme precipitation has increased with the exacerbation of worldwide climate disruption. We hypothesize an association between precipitation and the distribution patterns that would affect the endemic burden of 8 infectious diseases in Taiwan, including water- and vector-borne infectious diseases. A database integrating daily precipitation and temperature, along with the infectious disease case registry for all 352 townships in the main island of Taiwan was analysed for the period from 1994 to 2008. Four precipitation levels, <130 mm, 130–200 mm, 200–350 mm and >350 mm, were categorized to represent quantitative differences, and their associations with each specific disease was investigated using the Generalized Additive Mixed Model and afterwards mapped on to the Geographical Information System. Daily precipitation levels were significantly correlated with all 8 mandatory-notified infectious diseases in Taiwan. For water-borne infections, extreme torrential precipitation (>350 mm/day) was found to result in the highest relative risk for bacillary dysentery and enterovirus infections when compared to ordinary rain (<130 mm/day). Yet, for vector-borne diseases, the relative risk of dengue fever and Japanese encephalitis increased with greater precipitation only up to 350 mm. Differential lag effects following precipitation were statistically associated with increased risk for contracting individual infectious diseases. This study’s findings can help health resource sector management better allocate medical resources and be better prepared to deal with infectious disease outbreaks following future extreme precipitation events