Synthesis of quercetin derivatives as cytotoxic against breast cancer MCF-7 cell line in vitro and in silico studies.

Background: Quercetin being antioxidant and antiproliferative agent acts by inhibiting CDK2, with an increase in cancer prevalence there is a need to profile quercetin derivatives as CDK2 inhibitors. Materials & method: Schiff bases of quercetin were synthesized as cytotoxic agents against the MCF7 cell line. FTIR, 1H-NMR and 13C-NMR, CHNS/O analysis were employed along with in vivo and in silico activities. Results & conclusion: 2q, 4q, 8q and 9q derivatives have maximum cytotoxic effect with IC50 values 39.7 ± 0.7, 36.65 ± 0.25, 35.49 ± 0.21 and 36.99 ± 0.45, respectively. Molecular docking also confirmed these results 8q has the highest binding potential of -9.165 KJ/mole making it a potent inhibitor of CDK2. These derivatives can be used as lead compounds as potent CDK2 inhibitors.

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Comparison of parent or caregiver-completed development screening tools with Bayley Scales of Infant Development: a systematic review and meta-analysis.

BACKGROUND: Parent/caregiver-completed developmental testing (PCDT) is integral to developmental care in children; however, there is limited information on its accuracy. In this systematic review, we compared the diagnostic accuracy of PCDT with concurrently administered Bayley Scales of Infant Development for detection of developmental delay (DD) in children below 4 years of age. METHODS: We searched databases PubMed, Embase, CINAHL, PsycINFO and Google Scholar until November 2023. Bivariate and multiple thresholds summary receiver operating characteristics were used to obtain the summary sensitivity and specificity with 95% CIs. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used for risk of bias assessment. RESULTS: A total of 38 studies (31 in the meta-analysis) were included. Ages and Stages Questionnaire (ASQ) and Parent Report of Children's Abilities-Revised (PARCA-R) were the most commonly evaluated PCDTs. ASQ score >2 SD below the mean had an overall sensitivity of 0.72 (0.6, 0.82) and 0.63 (0.50, 0.75) at a median specificity of 0.89 (0.82, 0.94) and 0.81 (0.76, 0.86) for diagnosing moderate to severe DD and severe DD, respectively. PARCA- R had an overall sensitivity of 0.69 (0.51, 0.83) at median specificity of 0.75 (0.64, 0.83) for predicting severe DD. Participant selection bias and partial verification bias were found in over 50% of the studies. The certainty of evidence was low for the studied outcomes. CONCLUSIONS: The most commonly studied parental tools, ASQ and PARCA-R, have moderate to low sensitivity and moderate specificity for detecting DD in young children. High risk of bias and heterogeneity in the available data can potentially impact the interpretation of our results. PROSPERO REGISTRATION NUMBER: CRD42021268629.

Combined Rotational excimer lASER coronary atherectomy (RASER) in non-crossable, non-dilatable coronary artery disease: observations from a single center.

BACKGROUND: Balloon non-crossable stenoses represent a challenging subset of coronary artery disease (CAD). They are clinically associated with patients who are older, frailer, and with multi-morbidities, and angiographically with increased tortuosity and coronary artery calcification. Combined rotational (RA) excimer laser coronary atherectomy (ELCA), or RASER, may facilitate stent delivery and deployment in non-crossable, non-dilatable severely calcified lesions. In this study, we assessed preliminary safety and efficacy of the RASER hybrid technique. METHODS: RASER feasible percutaneous coronary intervention (PCI) procedures performed at a large tertiary hospital in the northeast of England were retrospectively analyzed from September 1, 2008, to February 28, 2022. Major endpoints were in-hospital death from any cause, as well as procedural and angiographic success, defined by stent delivery with less than 50% residual stenosis and without clinical or angiographic complications, respectively. RESULTS: From 74 unique cases, there were 28 RASER, 24 ELCA/RA, 16 balloon angioplasty ± stenting, and 6 medically treated patients. In-hospital mortality rate was 5.2%, including 1 ELCA- and 3 RASER-treated patients. Successful stent delivery was achieved in significantly more RASER-treated patients compared to ELCA/RA- or balloon-treated patients: 96.4% (27/28), 25% (6/24), and 31.3% (5/16) respectively (P less than .001). CONCLUSIONS: In our retrospective, single-center study, patients with CAD who were deemed appropriate for RASER PCI had a high peri-procedural mortality rate. In this context, adjunctive RASER therapy provides acceptable safety and efficacy as a bailout strategy, with at least 3 out of 5 patients achieving satisfactory procedural and angiographic results. Randomized controlled trials are needed to comprehensively compare the clinical outcomes of high-risk RASER PCI vs conservative medical therapy.

Norfloxacin derivatives as DNA gyrase and urease inhibitors: synthesis, biological evaluation and molecular docking.

Background: DNA gyrase and urease enzymes are important targets for the treatment of gastroenteritis, appendicitis, tuberculosis, urinary tract infections and Crohn's disease. Materials & methods: Esterification of norfloxacin was performed to enhance DNA gyrase and urease enzyme inhibition potential. Structure elucidation and chemical characterization were done through spectral (1H NMR, Fourier transform IR, 13C NMR) and carbon, hydrogen, nitrogen and sulfur analysis along with molecular docking. Results & conclusion: The majority of derivatives exhibited significant results but the 3e derivative showed maximum bactericidal, DPPH scavenging (96%), DNA gyrase and urease enzyme inhibitory activity with IC50 of 0.15 ± 0.24 and 1.14 ± 0.11 µM respectively which was further supported by molecular docking studies. So, the active derivatives can serve as a lead compound for the treatment of various pathological conditions.

Intracoronary imaging in PCI for acute coronary syndrome: Insights from British Cardiovascular Intervention Society registry.

BACKGROUND: While previous studies have demonstrated the superiority of ICI-guided PCI over an angiography-based approach, there are limited data on all-comer ACS patients. This study aimed to identify the characteristics and in-hospital outcomes of patients undergoing intracoronary imaging (ICI) guided percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). METHODS: All patient undergoing PCI for ACS in England and Wales between 2006 and 2019 were retrospectively analyzed and stratified according to ICI utilization. The outcomes assessed were in-hospital all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE) using multivariable logistic regression models. RESULTS: 598,921 patients underwent PCI for ACS, of which 41,716 (7.0 %) had ICI which was predominantly driven by IVUS use (5.6 %). ICI use steadily increased from 1.4 % in 2006 to 13.5 % in 2019. Adjusted odds of mortality (OR 0.69, 95%CI 0.58-0.83) and MACCE (OR 0.77, 95%CI 0.73-0.83) were significantly lower in the ICI group. The association between ICI and improved outcomes varied according to vessel treated with both left main stem (LMS) and LMS/left anterior descending (LAD) PCI associated with significantly lower odds of mortality (OR 0.34, 95%CI 0.27-0.44, OR 0.51 95%CI 0.45-0.56) and MACCE (OR 0.44 95%CI 0.35-0.54, OR 0.67 95%CI 0.62-0.72) respectively. CONCLUSIONS: Although ICI use has steadily increased, less than one in seven patients underwent ICI-guided PCI. The association between ICI use and improved in-hospital outcomes was mainly observed in PCI procedures involving LMS and LAD.

Early experience of intravascular lithotripsy in unprotected calcified left main coronary artery disease.

BACKGROUND: Treatment of unprotected severely calcified left main coronary artery (LMCA) disease is a complex interventional procedure. Intravascular lithotripsy (IVL) and rotational atherectomy (RA) are safe and effective methods of treating coronary calcification in the non-LMCA setting. This retrospective analysis assessed the feasibility of IVL versus RA in unprotected LMCA disease. METHODS: We analyzed IVL and RA procedures performed at a large tertiary hospital in the Northeast of England from January 1, 2019 to April 31, 2022. Major safety and efficacy endpoints were procedural and angiographic success, defined by stent delivery with <50 % residual stenosis and without clinical or angiographic complications, respectively. Another important clinical endpoint was the composite of major adverse cardiac events (MACE) at 1 year. RESULTS: From 242 patients, 44 had LMCA IVL, 81 had LMCA RA and 117 had non-LMCA IVL. Patients with LMCA disease were older and more likely to have aortic stenosis. IVL was a second-line or bailout technique in 86.4 % LMCA and 92.2 % non-LMCA cases. Procedural and angiographic success rates were ≥ 84 % across all groups (p > 0.05). In 3 LMCA IVL and 3 LMCA RA cases arrhythmias and cardiac tamponade complicated the procedures respectively. At 1 year, MACE occurred in 10/44 (22.7 %) LMCA IVL, 16/81 (19.8 %) LMCA RA and 25/117 (21.4 %) cases (p > 0.05). CONCLUSION: In our single center retrospective analysis, IVL is feasible in unprotected calcified LMCA as a second-line and third-line adjuvant calcium modification technique. Its use in unprotected calcified LMCA disease should be formalized with the undertaking of large randomized controlled trials.

Design, Synthesis, and Biological Evaluation of Dexibuprofen Derivatives as Novel Anti-Inflammatory, Antioxidant and Molecular Docking Studies.

Prodrugs of dexibuprofen having ester moieties instead of free carboxylic acid which involves in gastrointestinal side effects have been synthesized. Dexibuprofen acid was condensed with different alcohols/phenols to afford the ester prodrugs. All of the synthesized prodrugs were characterized by their physical attributes, elemental analysis, FT-IR, 1 H-NMR, and 13 C-NMR spectroscopy. The in vitro anti-inflammatory studies was done by chemiluminescence technique reflect prodrugs have been more potent, owing to the different chemical structures. Lipoxygenase enzyme inhibition assay was also assess and found compound DR7 with IC50 =19.8 µM), DR9 (IC50 =24.8 µM) and DR3 (IC50 =47.2 µM) as compared with Dexibuprofen (IC50 =156.6 µM). It was also evaluated for docking studies revealed that DR7 has found to be more potent anti-inflammatory against 5-LOX (3 V99) as well as analgesic against COX-II (5KIR) enzyme. Anti-oxidant activities were also performed, DR3 (86.9 %), DR5 (83.5 %), DR7 (93.9 %) and DR9 (87.4 %) were found to be more anti-oxidant as compared to (2S)-2-[4-(2-methylpropyl)phenyl]propanoic acid (52.7 %).

A Comprehensive Approach to Derivatization: Elemental Composition, Biochemical, and In Silico Studies of Metformin Derivatives Containing Copper and Zinc Complexes.

The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1-MCu9) and Zn II (MZn1-MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and 13C-NMR spectroscopy. Screening for inhibitory activity against the enzymes α-amylase and α-glucosidase, and molecular simulations performed in Schrödinger were used to assess the synthesized derivatives' biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski's rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development.

Interventions for reducing late-onset sepsis in neonates: an umbrella review.

OBJECTIVES: Neonatal sepsis is one of the leading causes of neonatal deaths in neonatal intensive care units. Hence, it is essential to review the evidence from systematic reviews on interventions for reducing late-onset sepsis (LOS) in neonates. METHODS: PubMed and the Cochrane Central were searched from inception through August 2020 without any language restriction. Cochrane reviews of randomized clinical trials (RCTs) assessing any intervention in the neonatal period and including one or more RCTs reporting LOS. Two authors independently performed screening, data extraction, assessed the quality of evidence using Cochrane Grading of Recommendations Assessment, Development and Evaluation, and assessed the quality of reviews using a measurement tool to assess of multiple systematic reviews 2 tool. RESULTS: A total of 101 high-quality Cochrane reviews involving 612 RCTs and 193,713 neonates, evaluating 141 interventions were included. High-quality evidence showed a reduction in any or culture-proven LOS using antibiotic lock therapy for neonates with central venous catheters (CVC). Moderate-quality evidence showed a decrease in any LOS with antibiotic prophylaxis or vancomycin prophylaxis for neonates with CVC, chlorhexidine for skin or cord care, and kangaroo care for low birth weight babies. Similarly, moderate-quality evidence showed reduced culture-proven LOS with intravenous immunoglobulin prophylaxis for preterm infants and probiotic supplementation for very low birth weight (VLBW) infants. Lastly, moderate-quality evidence showed a reduction in fungal LOS with the use of systemic antifungal prophylaxis in VLBW infants. CONCLUSIONS: The overview summarizes the evidence from the Cochrane reviews assessing interventions for reducing LOS in neonates, and can be utilized by clinicians, researchers, policymakers, and consumers for decision-making and translating evidence into clinical practice.

Resection and reconstruction with and without neoadjuvant denosumab in campanacci grade III giant cell tumors of proximal humerus: a retrospective comparative study.

BACKGROUND: Giant cell tumors (GCT) of the proximal humerus are rarely reported case that requires complex surgeries due to involvement of the shoulder joint. Therefore, we report the first retrospective comparative study where the postoperative functional outcomes, recurrence rate and complications in patients who underwent arthrodesis of shoulder after resection of grade III GCT with and without neoadjuvant denosumab are compared. METHODS: A retrospective review of eight cases of grade III GCT of proximal humerus receiving resection and fibular strut graft and arthrodesis between January 2014 and December 2019 is performed. They were stratified into two groups: one group of four patients received once-weekly denosumab 120 mg for 4-weeks before resection and reconstruction, while the other group of four patients did not receive denosumab before surgery. Primary outcomes included the functional outcomes assessed by revised Musculoskeletal tumor society (MSTS) score and shoulder pain and disability index (SPDI) at 6-weeks and 12-months postoperatively while secondary outcomes included complications and recurrences. RESULTS: There was no significant difference in terms of SPDI at 6 weeks and 12 months, MSTS at 12 months, complications, recurrence among denosumab and non-denosumab groups. At 6-weeks follow-up, a significantly better pain score in SPDI and MSTS was acquired in the denosumab group. CONCLUSIONS: Resection and reconstruction with or without neoadjuvant denosumab for Grade III GCT of proximal humerus had similar functional outcomes and with no major differences in recurrence and complications. Hence, postoperative pain relief while long-term benefits were not discovered with the use of neoadjuvant denosumab.

The Dilemma of Repeat In-Stent Restenosis: Can Intravascular Lithotripsy Provide an Alternative Approach to an Age-old Problem?

In-stent restenosis (ISR) has always been considered a conundrum for interventional cardiologists. Despite many technical advances in the past 20 years aimed at reducing its occurrence, this area of interventional cardiology remains challenging. Here, we present a novel use of intravascular lithotripsy therapy (IVL) in a patient with repeat ISR, in whom IVL treatment has provided excellent procedural and follow-up results. Here, we present a 79-year-old man with previous ISR to a left circumflex artery (LCX) stent presenting with angina. An elective coronary angiogram confirmed recurrent ISR in the LCX. This was treated by IVL, which provided an excellent procedural result. The patient made an uneventful recovery and was discharged the same day with a follow-up 90 days postprocedure, at which point they were asymptomatic from angina. IVL is a relatively simple technique to modify ISR with a short learning curve. This case presentation highlights a novel use of IVL in a subclass of patients that remains challenging for the interventional cardiology community.

Synthesis, antimicrobial and molecular docking study of structural analogues of 3-((5-(dimethylcarbamoyl)pyrrolidin-3-yl)thio)-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]heptane-2-carboxylic acid.

The goal of the current work was to create structural analogues of a beta lactam antibiotic that might be possibly effective against bacterial resistant strains. FTIR, 1H NMR, 13C NMR, and CHNS analyses were used to perform the spectroscopic study on the compounds M1-8. The effects of the aforementioned substances on gram-positive and gram-negative bacterial strains were investigated. Most of the eight compounds had antibacterial activity that was lower than or equivalent to that of the original medication, but two molecules, M2 and M3, surprisingly, had stronger antibacterial activity. The findings of synthesized analogues against alpha-glucosidase and DPPH inhibition were found to be modest, whereas M2, M3, and M7 strongly inhibited the urease. To comprehend the potential mode of action, a molecular docking research was conducted against urease and -amylase. The research may help in the quest for novel chemical compounds that would be effective against bacteria that are resistant to antibiotics.

Antenatal Magnesium Sulfate for Preterm Neuroprotection: A Single-Center Experience from Kuwait Tertiary NICU.

Objectives: The study aimed to evaluate the impact of antenatal exposure of magnesium sulfate (MgSO4) on short- and long-term outcomes in preterm neonates born less than 32 weeks gestation. Methods: Single-center retrospective cohort study of 229 neonates born between 24 and 32 weeks gestation was conducted from January 2018 through December 2018 in a level III neonatal care unit in Kuwait. Antenatal MgSO4 exposure was collected from the medical records, and the indication was for neuroprotection effect. Brain MRI was done on 212 neonates (median gestational age 36 weeks), and brain injury was assessed using the Miller's score. Neurodevelopmental outcome was assessed by Bayley-III scales of infant development at 36 months corrected age (N = 146). The association of exposure to MgSO4 with brain injury and neurodevelopmental outcomes was examined using multivariable regression analysis adjusting for gestational age at MRI and variables with p value <0.05 on univariate analysis. Results: Among the 229 neonates, 47 received antenatal MgSO4. There were no differences between the groups in gestational age and birth weight. MgSO4 exposure was not associated with an increased risk of necrotizing enterocolitis, chronic lung disease, retinopathy of prematurity, and mortality. The incidence of cerebellar hemorrhage was significantly less in the MgSO4 group (0% vs. 16%, p value = 0.002). Neonates who received MgSO4 had lower risks of grade 3-4 intraventricular hemorrhage (IVH) adjusted OR 0.248 (95% CI: 0.092, 0.66), p = 0.006; moderate-severe white matter injury (WMI) adjusted odd ratio 0.208 (95% CI: 0.044, 0.96), p = 0.046; and grade 3-4 IVH and/or moderate-severe WMI adjusted OR 0.23 (95% CI: 0.06, 0.84), p = 0.027. Neurodevelopmental assessment at 36 months corrected age showed better motor (adjusted beta coefficient 1.08 [95% CI: 0.099, 2.06]; p = 0.031) and cognitive composite scores (adjusted beta coefficient 1.29 [95% CI: 0.36, 2.22]; p = 0.007) in the MgSO4 group. Conclusion: Antenatal exposure to MgSO4 in preterm neonates less than 32 weeks was independently associated with lower risks of brain injury and better motor and cognitive outcomes.

Morphological and Physiological Characteristics of Ruptured Plaques in Native Arteries and Neoatherosclerotic Segments: An OCT-Based and Computational Fluid Dynamics Study.

Background: Intravascular imaging has been used to assess the morphology of lesions causing an acute coronary syndrome (ACS) in native vessels (NV) and identify differences between plaques that ruptured (PR) and caused an event and those that ruptured without clinical manifestations. However, there is no data about the morphological and physiological characteristics of neoatherosclerotic plaques that ruptured (PR-NA) which constitute a common cause of stent failure. Methods: We retrospectively analyzed data from patients admitted with an acute myocardial infarction that had optical coherence tomography (OCT) imaging of the culprit vessel before balloon pre-dilation. OCT pullbacks showing PR were segmented at every 0.4 mm. The extent of the formed cavity, lipid and calcific tissue, thrombus, and macrophages were measured, and the fibrous cap thickness (FCT) and the incidence of micro-channels and cholesterol crystals were reported. These data were used to reconstruct a representative model of the native and neoatherosclerotic lesion geometry that was processed with computational fluid dynamics (CFD) techniques to estimate the distribution of the endothelial shear stress and plaque structural stress. Result: Eighty patients were included in the present analysis: 56 had PR in NV (PR-NV group) and 24 in NA segments (PR-NA group). The PR-NV group had a larger minimum lumen area (2.93 ± 2.03 vs. 2.00 ± 1.26 mm2, p = 0.015) but similar lesion length and area stenosis compared to PR-NA group. The mean FCT (186 ± 65 vs. 232 ± 80 µm, p = 0.009) and the lipid index was smaller (16.7 ± 13.8 vs. 25.9 ± 14.1, p = 0.008) while the of calcific index (8.3 ± 9.5 vs. 2.2 ± 1.6%, p = 0.002) and the incidence of micro-channels (41.4 vs. 12.5%, p = 0.013) was higher in the PR-NV group. Conversely, there was no difference in the incidence of cholesterol crystals, thrombus burden or the location of the rupture site between groups. CFD analysis revealed higher maximum endothelial shear stress (19.1 vs. 11.0 Pa) and lower maximum plaque structural stress (38.8 vs. 95.1 kPa) in the PR-NA compared to the PR-NV model. Conclusion: We reported significant morphological and physiological differences between culprit ruptured plaques in native and stented segments. Further research is needed to better understand the causes of these differences and the mechanisms regulating neoatherosclerotic lesion destabilization.

Where is the 'C' in antenatal care and postnatal care: A multi-country survey of availability of antenatal and postnatal care in low- and middle-income settings.

OBJECTIVE: Antenatal (ANC) and postnatal care (PNC) are logical entry points for prevention and treatment of pregnancy-related illness and to reduce perinatal mortality. We developed signal functions and assessed availability of the essential components of care. DESIGN: Cross-sectional survey. SETTING: Afghanistan, Chad, Ghana, Tanzania, Togo. SAMPLE: Three hundred and twenty-one healthcare facilities. METHODS: Fifteen essential components or signal functions of ANC and PNC were identified. Healthcare facility assessment for availability of each component, human resources, equipment, drugs and consumables required to provide each component. MAIN OUTCOME MEASURE: Availability of ANC PNC components. RESULTS: Across all countries, healthcare providers are available (median number per facility: 8; interquartile range [IQR] 3-17) with a ratio of 3:1 for secondary versus primary care. Significantly more women attend for ANC than PNC (1668 versus 300 per facility/year). None of the healthcare facilities was able to provide all 15 essential components of ANC and PNC. The majority (>75%) could provide five components: diagnosis and management of syphilis, vaccination to prevent tetanus, BMI assessment, gestational diabetes screening, monitoring newborn growth. In Sub-Saharan countries, interventions for malaria and HIV (including prevention of mother to child transmission [PMTCT]) were available in 11.7-86.5% of facilities. Prevention and management of TB; assessment of pre- or post-term birth, fetal wellbeing, detection of multiple pregnancy, abnormal lie and presentation; screening and support for mental health and domestic abuse were provided in <25% of facilities. CONCLUSIONS: Essential components of ANC and PNC are not in place. Focused attention on content is required if perinatal mortality and maternal morbidity during and after pregnancy are to be reduced. TWEETABLE ABSTRACT: ANC and PNC are essential care bundles. We identified 15 core components. These are not in place in the majority of LMIC settings.

Same-Day Discharge After Elective Percutaneous Coronary Intervention for Chronic Total Occlusion in the UK.

OBJECTIVES: This study examines the safety and feasibility of same-day discharge (SDD) in patients undergoing percutaneous coronary intervention (PCI) to coronary chronic total occlusions (CTOs) and explores independent associations of clinical and procedural characteristics with SDD. BACKGROUND: While the recently published consensus statements recommend SDD following uncomplicated CTO-PCI, there are limited studies to support this approach. METHODS: Data were obtained from the British Cardiovascular Intervention Society (BCIS) registry dataset including 21,330 patients who underwent CTO-PCI electively from 2007 to 2014 in England and Wales. We used multiple logistic regression to evaluate associations with SDD and the BCIS national risk model to examine for safety of SDD. RESULTS: Although overnight stay remained the standard of care following elective CTO-PCI, SDD practice increased from 21.7% to 44.7%. Women were less likely to have SDD than males. SDD was more common in higher CTO volume centers (36.3%) than low CTO volume centers (31.6%), and SDD patient profiles grew riskier over time, with the average age of SDD patients increasing from 61.4 years to 63.2 years. Transradial PCI was most strongly independently associated with SDD (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.80-2.09). Finally, the SDD observed 30-day mortality rates were not different vs those predicted by the BCIS risk model, and SDD was not independently associated with 30-day mortality (OR, 0.54; 95% CI, 0.25-1.15). CONCLUSION: This study illustrates that SDD is safe in selected patients undergoing CTO-PCI.

Benefit-risk analysis of maintaining essential Reproductive, Maternal, Newborn, and Child Health (RMNCH) services against risk of COVID-19 infection.

With the COVID-19 pandemic spreading across the world, its disruptive effect on the provision and utilization of non- COVID related health services have become well-documented. As countries developed mitigation strategies to help continue the delivery of essential health services through the pandemic, they needed to carefully weigh the benefits and risks of pursuing these strategies. In an attempt to assist countries in their mitigation efforts, a Benefit-Risk model was designed to provide guidance on how to compare the health benefits of sustained essential reproductive, maternal, newborn and child (RMNCH) services against the risk of SARS-CoV-2 infections incurred by the countries' populations when accessing these services. This article describes how two existing models were combined to create this model, the field-testing process carried out from November 2020 through March 2021 in six countries and the findings. The overall Benefit-Risk Ratio in the 6 countries analyzed was found to be between 13.7 and 79.2, which means that for every 13.7 to 79.2 lives gained due to increased RMNCH service coverage, there was one loss of a life related to COVID-19. In all cases and for all services, the benefit of maintaining essential health services far exceeded the risks associated with additional COVID-19 infections and deaths. This modelling process illustrated how essential health services can continue to operate during a pandemic and how mitigation measures can reduce COVID-19 infections and restore or increase coverage of essential health services. Overall, this Benefit-Risk analysis underscored the importance and value of maintaining coverage of essential health services even during public health emergencies, including the recent COVID-19 pandemic.

Melatonin for non-operating room sedation in paediatric population: a systematic review and meta-analysis.

CONTEXT: The literature on melatonin as a sedative agent in children is limited. OBJECTIVE: To conduct a systematic review of studies assessing the efficacy and safety of melatonin for non-operating room sedation in children. METHODS: Medline, Embase, Cochrane Library and Cumulative Index to Nursing and Allied Health were searched until 9 April 2020 for studies using melatonin and reporting one of the prespecified outcomes of this review. Two authors independently assessed the eligibility, risk of bias and extracted the data. Studies with a similar study design, comparator and procedure were pooled using the fixed-effect model. RESULTS: 25 studies (clinical trials=3, observational studies=9, descriptive studies=13) were included. Melatonin was used for electroencephalogram (EEG) (n=12), brainstem evoked response audiometry (n=8) and magnetic resonance imaging (MRI) (n=5). No significant differences were noted on meta-analysis of EEG studies comparing melatonin with sleep deprivation (SD) (relative risk (RR) 1.06 (95% CI 0.99 to 1.12)), melatonin with chloral hydrate (RR 0.97 (95% CI 0.89 to 1.05)) and melatonin alone with melatonin and SD combined (RR 1.03 (95% CI 0.97 to 1.10)) for successful procedure completion. However, significantly higher sedation failure was noted in melatonin alone compared with melatonin and SD combined (RR 1.55 (95% CI 1.02 to 2.33)) for EEG. Additionally, meta-analysis showed lower sleep latency for melatonin compared with SD (mean difference -10.21 (95% CI -11.53 to -8.89) for EEG. No major adverse events were reported with melatonin. CONCLUSION: Although several studies were identified, and no serious safety concerns were noted, the evidence was not of high quality to establish melatonin's efficacy for non-operating room sedation in children.

Efficacy and Safety of Two Different Flow Rates of Nasal High-Flow Therapy in Preterm Neonates ≥28 Weeks of Gestation: A Randomized Controlled Trial.

OBJECTIVE: The study aimed to compare the efficacy and safety of two different nasal high-flow rates for primary respiratory support in preterm neonates STUDY DESIGN: In this single-center, double-blinded randomized controlled trial, preterm neonates ≥28 weeks of gestation with respiratory distress from birth were randomized to treatment with either increased nasal flow therapy (8-10 L/min) or standard nasal flow therapy (5-7 L/min). The primary outcome of nasal high-flow therapy failure was a composite outcome defined as the need for higher respiratory support (continuous positive airway pressure [CPAP] or mechanical ventilation) or surfactant therapy. RESULTS: A total of 212 neonates were enrolled. Nasal high-flow failure rate in the increased flow group was similar to the standard flow group (22 vs. 29%, relative risk = 0.81 [95% confidence interval: 0.57-1.15]). However, nasal flow rate escalation was significantly more common in the standard flow group (64 vs. 43%, p = 0.004). None of the infants in the increased flow group developed air leak syndromes. CONCLUSION: Higher nasal flow rate (8-10 L/min) when compared with lower nasal flow rate of 5 to 7 L/min did not reduce the need for higher respiratory support (CPAP/mechanical ventilation) or surfactant therapy in moderately and late preterm neonates. However, initial flow rates of 5 L/min were not optimal for most preterm infants receiving primary nasal flow therapy. KEY POINTS: · Use of high nasal flows (8-10 L/min) did not reduce the need for higher respiratory support in moderately and late preterm infants.. · Nasal flow rate of 5 L/min was not optimal for most preterms with respiratory distress from birth.. · Careful patient selection and optimized flow settings could enhance nasal flow success in neonates..