Search

Gestational diabetes (GDM) and pre-eclampsia (PE) represents the unrecognized risk factors for reduced bone content in neonates. The present study is planned to explore the components of vitamin D metabolism and calcium transport in placenta of GDM and PE cases and its effect on the neonatal bone mass determination using bone densitometry system.We have collected serum and placenta tissues from GDM (n = 20), PE (n = 20), and healthy pregnancies (n = 20). In the present study, we found mRNA expression of oxidative stress markers, vitamin D metabolic components and calcium channels, calcium channel binding proteins, plasma membrane calcium ATPase, ATP synthase and Ca2+ release genes; Ryanodine receptors genes were assessed by quantitative real-time PCR (qRT-PCR) in placental tissue of GDM, PE, and healthy pregnancies.We observed high level of oxidative stress in both GDM and PE placenta compared to normal pregnancies. CYP2R1 and VDR mRNA expression was significantly downregulated and upregulation of CYP27B1 and CYP24A1 in GDM and PE compared with healthy cases. Similarly, calcium transporters were downregulated in GDM and PE placental tissues. In addition, CYP24A1, VDR, CaBP28K, TRPV5 and PMCA3 mRNA expression were correlated with BMC of neonates.Oxidative stress is probably relevant to disrupted vitamin D homeostasis and calcium transport in the placenta of GDM and PE cases. The altered regulatory mechanism of CYP24A1 and VDR could indicates more pronounced serum 25(OH)D reduction. Additionally, reduced BMC in the neonates of these cases might be as consequences of modified CYP24A1, VDR, CaBP28K, TRPV5 and PMCA3 mRNA expression.

To study the prevalence of mental health problems among mothers of preterm infants admitted to the neonatal intensive care unit (NICU).In this cross-sectional two-arm study, 130 mothers in each group, with either term infants not in NICU or preterm infants admitted to NICU, underwent mental health assessment using the Generalized Anxiety Disorder Scale, Centre for Epidemiologic Studies-Depression Scale, Stanford Acute Stress Reaction Questionnaire and Modified Parental Stress Scale-NICU. Their coping styles and quality of life were also assessed. Data were analyzed using SPSS IBM 25.0.Anxiety (66.2% versus 46.9%) and depression (45.4% versus 23.1%) were more common among NICU mothers. Regarding subdomains of acute stress reaction, a higher number of NICU mothers showed symptoms of anxiety, re-experience and functional impairment. For mothers with infants in NICU, sight, sound, and parental role alterations were stressful. They had reduced quality of life scores in domains of physical health, psychological health, and social relationships. Also, a higher number of these mothers exhibited problem-solving and emotion-focused coping.Preterm birth with NICU admission of the infant is more stressful for a mother than the term birth of a healthy neonate. It affects her mental health and quality of life. Both the obstetrician and the pediatrician should be mindful of this.

Introduction: Musculoskeletal pain is a common medical and socioeconomic problem worldwide. Treatment and management options most commonly include analgesics such as paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), and topical over-the-counter (OTC) preparations. Patients often use OTC topical analgesics owing to the benefits shown by clinical studies for the treatment and management of musculoskeletal injuries and disorders. The aim of this study was (1) to review the background, current understanding, and therapeutic usefulness of topical counterirritants for the management of musculoskeletal pain (2) and to evaluate the sensorial characteristics of two prototype patches containing counterirritants, designed to manage pain relief by delivering a warming or cooling sensation. Methods: Detailed literature search was conducted in PubMed, Google Scholar, and Cochrane Library databases for this review. An expert sensory panel study comprising of ten trained sensory experts was conducted to evaluate the performance of prototype patches containing counterirritants for their sensory characteristics including overall sensation, cooling, warming, and tingling sensations, as well as functional parameters such as ease of application and removal, adhesive property, odor intensity, staining on clothes, residue or greasiness, and sweat/moistness on the skin after removal. Results: Topical analgesics containing counterirritants like capsaicin, menthol, and salicylates produce analgesia by activating and then desensitizing epidermal nociceptors. Literature searches provide evidence for their use in the management of musculoskeletal pain. The expert sensory panel study showed that the sensations elicited by the prototype counterirritant patches were predominantly cooling, tingling, and low and short warming in nature, with strong adhesion, ease of application and removal, no staining, little to no residue and grease on the skin, and low lingering odor of menthol. Conclusion: Literature search supports the use of counterirritants in the treatment of musculoskeletal pain like backache, strains, and sprains. In addition, the observations from the expert sensory panel study evaluating sensory and functional parameters of counterirritant patches showed that these patches provide predominantly cooling, tingling and low short lasting warming sensations with strong adhesion, no stain and little to no residue and grease. These results support their potential as a treatment modality with increased consumer acceptance, potentially increasing treatment adherence and maximizing the effectiveness of therapies. And may be used as part of multimodal pain treatment regimens for musculoskeletal conditions.

Sepsis is a highly heterogeneous, life-threatening organ dysfunction primarily caused by a dysregulated immune response to counter bacterial, viral, or fungal infections, resulting in haemodynamic changes and significant morbidity and mortality across all ages. In recent times, it has become one of the foremost causes of morbidity and mortality among newborns globally. The neonates, particularly the preterm neonates, due to their immature immune systems and non-canonical microbial community acquisition in the gastrointestinal tract and other body habitats, are adversely affected compared to the elderly with immunocompromised conditions. The neonates could acquire microbiota in utero or during delivery from the mother's genital tract or postnatally from contact with hospital personnel and the immediate hospital environment after the birth. Other factors that may enhance the risk include early colonization of microbiota by pathogens that trigger dysbiosis of the gut microbiome accompanied by a dysregulated immune response, organ dysfunction, and potential death. The sepsis-linked mortality could be prevented by timely diagnosis, selective antibiotic therapy, and supportive postnatal care. Infections due to antibiotic-resistant bacteria severely restrict possible therapeutic options, thus extending hospital stays. A comprehensive analysis of the infecting pathogens, cognate host responses, and the microbiota present would certainly help formulate appropriate interventions.

ObjectiveTo evaluate whether 1% aqueous chlorhexidine gluconate (CHG) when compared with 2% aqueous chlorhexidine gluconate is non-inferior for neonatal skin antisepsis.DesignParallel, blinded, non-inferiority randomised trial.SettingLevel III, academic, neonatal intensive care unit.PatientsInfants born at 260/7to 426/7weeks of gestation from June 2019 to December 2019.InterventionsParticipants were randomised to skin antisepsis by either 1% aqueous CHG or 2% aqueous CHG.Main outcome measuresThe primary outcome was the proportion of negative skin swab cultures after skin antisepsis. Secondary outcomes were local skin reactions at 0, 6, 12 and 24 hours and plasma chlorhexidine levels in a subset of the study population.ResultsA total of 308 neonates with a median gestation age of 34 (31–37) weeks and mean birth weight of 2029 g were randomised on 685 occasions (1% CHG: n=341; 2% CHG: n=344). 93.0% of the post-antisepsis skin swabs were sterile in 1% CHG group compared with 95.6% of the swabs in the 2% CHG group (risk difference −2.7%, 95% CI −6.2% to +0.8%). The lower bound of 95% CI crossed the pre-specified absolute non-inferiority limit of 5%. Neonates developed mild dermatitis on 16 (2.3%) occasions. There was no significant difference in median plasma CHG levels in the two groups, 19.6 (12.5–36.4) and 12.6 (8.7–26.6) ng/mL, respectively.ConclusionsApplication of 1% aqueous CHG was not shown to be non-inferior to 2% chlorhexidine aqueous for skin antisepsis in neonates. There were no severe skin-related adverse events in either of the two groups.Trial registration numberCTRI/2019/06/019822; (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=33453&EncHid=&userName=CTRI/2019/06/019822)

Background Algorithms for predicting retinopathy of prematurity (ROP) requiring treatment need to be validated in Indian settings to determine if the burden of screening can be reduced without compromising the sensitivity of existing gestation and weight-based cut offs. Objective To evaluate the performance of the available algorithms namely, WINROP (Weight, Insulin-like growth factor I, Neonatal ROP), CHOP-ROP (children’s Hospital of Philadelphia ROP) and ROPScore in predicting type 1 ROP and time from alarm to treatment by each algorithm. Study design Ambispective observational. Setting Tertiary care neonatal intensive care unit in India. Participants Neonates less than 32 weeks or less than 1500 g born between July, 2013 to June, 2019 (N=578), who underwent ROP screening. Primary outcome Sensitivity, specificity and time from alarm to treatment by each algorithm. Results The sensitivity and specificity of WINROP was 85% and 36%, for CHOP-ROP it was 54% and 71%, and for ROPScore it was 73% and 67%, respectively in detecting type 1 ROP. A total of 50/51 (98%) of neonates with type 1 ROP underwent treatment at median gestation of 9 weeks and median time from alarm to treatment by WINROP, CHOP-ROP and ROPScore was 7, 7 and 3 weeks, respectively. Conclusion WINROP, CHOP-ROP and ROPScore were not sensitive enough to replace the gestational age, weight and risk factor-based screening criteria for type 1 ROP.

Introduction: Oral drugs are commonly prescribed for the treatment of acute pain. Other than these agents, certain anticonvulsants and antidepressants are also prescribed for chronic pain. Although being effective in providing pain relief, oral administration frequently results in systemic adverse drug reactions (ADRs), which may prevent their ongoing use and result in their discontinuation. Topical analgesics are useful to provide symptomatic benefits seen with oral agents but devoid of the systemic ADRs. Essential oils extracted from plants, some of which are known analgesic compounds like methyl salicylate, eucalyptus oil, clove oil, menthol, turpentine oil which form contents of the newly launched Iodex rapid action spray along with excipients. The aim of this study was to evaluate the sensorial profiling of newly launched Iodex rapid action spray in meeting the consumer expectations as topical pain relief spray. The other objective was to validate consumer perception of the product’s sensorial claims and appeal. Methods: This study was a prospective, blinded, monadic comparison, consumer sensory study conducted in 3 different cities in India. Participants were pre-recruited to try 3 different pain relief spray formulations, 30 min session per day. One product to be tested each day. The participants had to use the product and answer the questionnaire online. Only Sensorial aspects were checked. Results: Comparing the market sample 1 (Iodex rapid action spray) vs other formulations, all 3 products got very high level of consumer agreement. For the monadic score, market sample 1 was equal to if not better to than the other two i.e., market sample 2 and market sample 3 in regard to the sensory and participant liking claims. Conclusion: Market sample 1 (Iodex rapid action spray) got very high level of consumer agreement. Market sample 1 (Iodex rapid action spray) is equal to if not better to than the other two i.e., market sample 2 and market sample 3 regards to the sensory and liking claims.

BackgroundSepsis severity scores are used in clinical practice and trials to define risk groups. There are limited data to derive hospital-based sepsis severity scores for neonates and young infants in high-burden low- and middle-income country (LMIC) settings where trials are urgently required. We aimed to create linked sepsis severity and recovery scores applicable to hospitalized neonates and young infants in LMIC which could be used to inform antibiotic trials.Methods & FindingsA prospective observational cohort study was conducted across 19 hospitals in 11 countries in sub-Saharan Africa, Asia, Latin America and Europe. Infants aged 3204 infants were enrolled between 2018-2020. Median age was 5 days (IQR 2-15), 90.4% (n=2,895) were A related NeoSep Recovery Score based on evolving post-baseline clinical signs and supportive care discriminated well between infants who died or survived the following day or subsequent few days. The area under the ROC curve for score on day 2 and death in the following 5 days was 0.82 (95%CI 0.78-0.85) and 0.85 (95%CI 0.78-0.93) in the derivation and validation data, respectively.ConclusionThe baseline NeoSep Severity Score predicted 28-day mortality and could identify infants with high risk of mortality for inclusion in hospital-based sepsis trials. The NeoSep Recovery Score predicts day-by-day inpatient mortality and could, with further validation, help to identify poor response to antibiotics.Author SummaryWhy was this study done?➣Evidence to guide hospital-based antibiotic treatment of sepsis in neonates and young infants is scarce, and clinical trials are particularly urgent in low- and middle-income (LMIC) settings where antimicrobial resistance threatens to undermine existing guidelines➣There is limited data to inform the design of antibiotic trials in LMIC settings, particularly to define risk stratification and inclusion and escalation criteria in hospitalised neonates and young infantsWhat did the researchers do and find?➣To our knowledge this is the first global, prospective, hospital-based observational study of clinically diagnosed neonatal sepsis across 4 continents including LMIC settings, with extensive daily data collection on clinical status, antibiotic use and outcomes.➣There was a high mortality among infants with sepsis in LMIC hospital settings. 4 non-modifiable and 6 modifiable factors predicted mortality and were included in a NeoSep Severity score which defines patterns of mortality risk at baseline➣A NeoSep Recovery Score including the same modifiable factors (with the addition of cyanosis) predicted mortality on the following day during the course of treatment.What do these findings mean?➣The NeoSep Severity Score and NeoSep Recovery score are now informing inclusion and escalation criteria in the NeoSep1 antibiotic trial (ISRCTN48721236) which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis➣The NeoSep Severity Score could be used to predict mortality at baseline in future studies of targeting resources in routine care. With further validation, the NeoSep Recovery Score could potentially be used to identify poor response to empiric antibiotic treatment

BackgroundNeonatal sepsis is a leading cause of child mortality, and increasing antimicrobial resistance threatens progress towards the Sustainable Development Goals. Evidence to guide antibiotic treatment for sepsis in neonates and young infants from randomized controlled trials or observational studies in low- and middle-income countries (LMICs) is scarce. We aimed to describe patterns of antibiotic use, pathogens and outcomes in LMIC hospital settings globally to inform future clinical trials on the management of neonatal sepsis.Methods & FindingsHospitalised infants aged 206 different empiric antibiotic combinations were used, which were structured into 5 groups that were developed from the World Health Organisation (WHO) AWaRe classification. 25.9% (n=814) of infants started a WHO first line regimen (Group 1 -Access, penicillin-based regimen) and 13.8% (n=432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2- ‘Low’ Watch). The largest group (34.0%, n=1068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3 – ‘Medium’ Watch), 18.0% (n=566) started a carbapenem (Group 4 – ‘High’ Watch), and 1.8% (n=57) started a Reserve antibiotic (Group 5, largely colistin-based). Predictors of starting non-WHO recommended regimens included lower birth weight, longer in-hospital stay, central vascular catheter use, previous culture positive sepsis or antibiotic exposure, previous surgery and greater sepsis severity. 728/2880 (25.3%) of initial regimens in Group 1-4 were escalated, mainly to carbapenems, and usually for clinical indications (n=480; 65.9%).564 infants (17.6%) isolated a pathogen from their baseline blood culture, of which 62.9% (n=355) had a Gram-negative organism, predominantlyKlebsiella pneumoniae(n=132) andAcinetobacterspp. (n=72). These leading Gram-negatives were both mostly resistant to WHO-recommended regimens, and also resistant to carbapenems in 32.6% and 71.4% of cases respectively. MRSA accounted for 61.1% ofStaphylococcus aureus(n=54) isolates.Overall, 350/3204 infants died (11.3%; 95%CI 10.2-12.5%), with 17.7% case fatality rate among infants with a pathogen in baseline culture (95%CI 14.7-20.1%, n=99/564). Gram-negative infections accounted for 75/99 (75.8%) of pathogen-positive deaths, especiallyKlebsiella pneumoniae(n=28; 28.3%), andAcinetobacterspp. (n=24; 24.2%).ConclusionA very wide range of antibiotic regimens are now used to treat neonatal sepsis globally. There is common use of higher-level Watch antibiotics, frequent early switching and very infrequent de-escalation of therapy. Future hospital based neonatal sepsis trials will ideally need to account for the multiple regimens used as standard of care globally and include both empiric first line regimens and subsequent switching in the trial design.Author SummaryWhy was this study done?➢Increasing trends in antimicrobial resistance (AMR) disproportionately affect neonates and young infants with sepsis in LMIC settings and undermine the effectiveness of WHO-recommended antibiotics.➢Despite this, longitudinal data on antibiotic management strategies and outcomes of affected hospitalised neonates and young infants in LMIC settings are extremely limited, impeding the design of robust antibiotic trials.What did the researchers do and find?➢To our knowledge this is the first global, prospective, hospital-based observational study of clinically diagnosed neonatal sepsis across 4 continents including LMIC settings, with daily data on clinical status, antibiotic use and outcomes.➢There was a high mortality among infants with culture positive sepsis (almost 1 in 5), and a significant burden of antibiotic resistance.➢This study highlights wide variations in standard of care for sepsis in neonates and young infants with more than 200 different antibiotic combinations, significant divergence from WHO-recommended regimens, and frequent switching of antibiotics.What do these findings mean?➢These data demonstrate that patterns of routine antibiotic use are now markedly divergent from global guidance➢There is an urgent need for randomised controlled trials to address optimal empiric first and second line antibiotic treatment strategies in LMIC hospital settings with a significant AMR burden.➢Data from this study can inform the design of multicentre hospital-based neonatal antibiotic trials in LMIC settings.➢The wide range of multiple antibiotic regimens routinely used as Standard of Care (SOC) suggests the need for novel trial designs.

Aim To learn how to achieve high-quality, effective coverage of Kangaroo Mother Care (KMC), defined as 8 hours or more of skin-to-skin contact per day and exclusive breastfeeding in district Sonipat in North India, and to develop and evaluate an implementation model. Methods We conducted implementation research using a mixed-methods approach, including formative research, followed by repeated, rapid cycles of implementation, evaluation and refinement until a model with the potential for high and effective coverage was reached. Evaluation of this model was conducted over a 12-month period. Results Formative research findings informed the final implementation model. Programme learning was critical to achieve high coverage. The model included improving the identification of small babies, creating KMC wards, modification in hospitalisation criteria, private sector engagement and in-built programme learning to refine implementation progress. KMC was initiated in 87% of eligible babies. At discharge, 85% received skin-to-skin contact care, 60% effective KMC and 80% were exclusively breastfed. At home, 7-day post discharge, 81% received skin-to-skin care and 79% were exclusively breastfed in the previous 24 hours. Conclusion Achieving high KMC coverage is feasible in the study setting using a model responsive to the local context and led by the Government. publishedVersion

To compare disease regression in cases of Fluorescein Angiography (FA) guided laser vs. conventional laser treatment in infants with Aggressive retinopathy of prematurity (AROP).60 eyes of 30 infants of AROP were randomized into two groups. In both the group's FA was done once. Montage of the fundus, FA images was created and the vascular area, avascular areas, and skip areas after laser treatment were demarcated and measured. In group 1, FA-guided laser treatment was done whereas in group 2 they were lasered without seeing FA. Infants were followed up every week to look for skip areas and disease regression.The mean vascular retinal area in group 1 and group 2 on fundus images was 302.7 sq. mm and 245.8 sq. mm respectively, while the same on FA was 285.2 sq. mm and 221.3 sq. mm respectively, suggesting overestimation of the vascular area on fundus imaging compared to FA which enabled more objective estimation of avascular loop areas. Retinal skip areas in group 1 and group 2 after 1st laser were 18.7 sq. mm and 73.1 sq. mm respectively (P = 0.001), after 2nd laser was 3.7 sq. mm and 19.2 sq. mm (P = 0.003), which suggests FA-guided laser led to significantly fewer skip areas. Infants had regression in 4.1 ± 0.3 wks and 4.2 ± 0.4 wks in groups 1 and 2, respectively.FA-guided laser ensured lesser skip areas and more complete laser treatment, though regression was similar in both groups.

BackgroundProperly fitting continuous positive airway pressure (CPAP) interface is critical to the efficacy and safety of nasal CPAP therapy in preterm. Unfortunately, there is a perception that CPAP interfaces being used in Indian neonatal intensive care units do not fit well and cause a high rate of nasal injury.ObjectivesTo determine the nasal anthropometric dimensions in preterm (MethodsIn this cross-sectional study, relevant anterior nasal parameters were measured by three dimensional imaging in 32 preterm newborn (26+0–34+6 weeks) and compared with commercially available 17 short binasal CPAP prongs of multiple sizes made by five manufacturers. Dimensions for best-suited interfaces were generated for Indian neonates.ResultsThe mean (SD) gestation and birth weight of enrolled neonates were 30.6 (3.0) weeks and 1338 (575) g, respectively. The inter prong distance was narrower than the upper bound of the 95% CI of the columellar width in Hudson type CPAP interfaces in ConclusionsThere is mismatch between nasal prongs and nose dimension of Indian neonates resulting in possible erosion of columella and distension of nostrils.

To compare the effect of intact umbilical cord milking (MUC) and delayed cord clamping (DCC) on venous hematocrit at 48 (±6) hours in late preterm and term neonates (350/7–426/7 wk). Randomized trial. All late preterm and term neonates (350/7–426/7 wk) neonates born in the labor room and maternity operation theatre of tertiary care unit were included. We randomly allocated enrolled neonates to MUC group (cord milked four times towards the baby while being attached to the placenta; n=72) or DCC group (cord clamped after 60 seconds; n=72). Primary outcome was venous hematocrit at 48 (±6) hours of life. Additional outcomes were venous hematocrit at 48 (±6) hours in newborns delivered through lower segment caesarean section (LSCS), incidence of polycythemia requiring partial exchange transfusion, incidence of hyperbilirubinemia requiring phototherapy, and venous hematocrit and serum ferritin levels at 6 (±1) weeks of age. The mean (SD) hematocrit at 48 (±6) hours in the MUC group was higher than in DCC group [57.7 (4.3) vs. 55.9 (4.4); P=0.002]. Venous hematocrit at 6 (±1) weeks was higher in MUC than in DCC group [mean (SD), 37.7 (4.3) vs. 36 (3.4); mean difference 1.75 (95% CI 0.53 to 2.9); P=0.005]. Other parameters were similar in the two groups. MUC leads to a higher venous hematocrit at 48 (±6) hours in late preterm and term neonates when compared with DCC.

Computational fluid dynamics (CFD) combined with the discrete element method (DEM) are powerful tools for analyzing dense gas–solid flows. However, the computational cost of CFD–DEM will be unfeasibly great when simulating large-scale engineering applications with billions of particles. Accordingly, the coarse-grained (CG) CFD–DEM method is applied to solve this problem. This investigated method replaces several smaller particles with larger ones called parcels, aiming to reduce the number of particles and fully consider the collision of particles between composition parcels and the collision of particles within composition parcels. First, high-speed photography verifies the numerical simulation's reliability. Then, the CG CFD–DEM was used to analyze the transient spatial distribution, transient average velocity, pressure drop, bed height, and the mixing state of particles in a dense gas–solid fluidized bed. The CG CFD–DEM was also compared with the CFD–DEM results, which showed a good agreement with the calculation results and proved the accuracy and applicability of the method. Finally, the computation time of the CG CFD–DEM was evaluated, showing a significant decrease in computation time with an increasing coarse ratio ( k). This investigation can provide theoretical reference for the numerical simulation of the CG CFD–DEM method in dense gas–solid flow.

CO2-enhanced gas recovery (CO2-EGR) is a promising, environment-friendly technology to produce more natural gas from depleted reservoirs and simultaneously sequester CO2. The subsurface flow in the heterogeneous reservoir is usually different from homogenous one, and the heterogeneity significantly affects the gas recovery. The effects of heterogeneity and the optimization of CO2 injection strategy are the key factors in CO2-EGR. Thus, one of the goals of this paper is to conduct simulations of CO2-EGR in both homogeneous and heterogeneous reservoirs to evaluate the effects of reservoir heterogeneity on CO2-EGR. The second goal is to perform optimization studies to determine optimal CO2 injection time and injection rate for achieving optimal natural gas recovery. The CO2-EGR simulations were conducted in a 3D reservoir model with a 'five-spot' well pattern by using the multi-phase simulator TOUGH2. The results show that the layers with low permeability as well as gravity segregation retard upward migration of CO2 and promote horizontal displacement efficiency. The breakthrough time of CO2 and reservoir space of underexploited natural gas directly affect the gas recovery. The optimal injection time is determined as the depleted stage, and the corresponding injection rate is optimized by using a genetic algorithm (GA) integrated with TOUGH2. The optimization of CO2 injection parameters leads to recovery factors (RFs) reaching 62.83% and 64.75% in the homogeneous and heterogeneous cases while simultaneously obtaining the economic benefit of about 8.67 and 8.95 million USD. This study shows significant economic potential as well as environmental benefits of using CO2-EGR in the depleted gas reservoir by optimizing the CO2 injection parameters. The findings of this work could assist in determining the optimal injection strategy for using CO2-EGR in industrial scale gas reservoirs.

Background Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen–drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen–drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level. Findings On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62–6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911–1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9–35·3), and lowest in Australasia, at 6·5 deaths (4·3–9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000–1 270 000) deaths attributable to AMR and 3·57 million (2·62–4·78) deaths associated with AMR in 2019. One pathogen–drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000–100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae. Interpretation To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen–drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

ObjectivesTo investigate if intravenous fentanyl or intravenous ketamine can provide adequate analgesia in preterm infants undergoing laser photocoagulation for retinopathy of prematurity (ROP).DesignOpen-label randomised trial.SettingTertiary care institution.ParticipantsPreterm infants who underwent laser photocoagulation for ROP.InterventionsInfants were randomised to receive fentanyl as intravenous bolus dose of 2 µg/kg, followed by an intravenous infusion of 1 µg/kg/hour increased to a maximum of 3 µg/kg/hour or intravenous ketamine as bolus dose of 0.5 mg/kg, followed by further intermittent intravenous bolus doses of 0.5 mg/kg to a maximum of 2 mg/kg in the initial phase and intravenous fentanyl (bolus of 2 µg/kg followed by infusion of 2 µg/kg/hour to a maximum of 5 µg/kg/hour) or intravenous ketamine (bolus dose of 1 mg/kg followed by intermittent bolus doses of 0.5 mg/kg to a maximum of 4 mg/kg) in the revised regimen phase.Main outcome measuresProportion of infants with adequate analgesia defined as the presence of both: (1) all the Premature Infant Pain Profile-Revised scores measured every 15 min less than seven and (2) proportion of the procedure time the infant spent crying less than 5%.Secondary outcomes included apnoea, cardiorespiratory or haemodynamic instability, feed intolerance and urinary retention requiring catheterisation during and within 24 hours following the procedure.ResultsA total of 97 infants were randomised (fentanyl=51, ketamine=46). The proportions of infants with adequate analgesia were 16.3% (95% CI 8.5% to 29%) with fentanyl and 4.5% (95% CI 1.3% to 15.1%) with ketamine. Ten infants (19.6%) in the fentanyl group and seven infants (15.2%) in the ketamine group had one or more side effects. In view of inadequate analgesia with both the regimens, the study steering committee recommended using a higher dose of intravenous fentanyl and intravenous ketamine. Consequently, we enrolled 27 infants (fentanyl=13, ketamine=14). With revised regimens, the proportions of infants with adequate analgesia were higher: 23.1% (95% CI 8.2% to 50.2%) with fentanyl and 7.1% (95% CI 1.3% to 31.5%) with ketamine. However, higher proportions of infants developed apnoea (n=4; 30.7%), need for supplemental oxygen (n=5, 38.4%) and change in cardiorespiratory scores (n=7; 53.8%) with fentanyl but none with ketamine.ConclusionsFentanyl-based and ketamine-based drug regimens provided adequate analgesia only in a minority of infants undergoing laser photocoagulation for ROP. More research is needed to find safe and effective regimens that can be employed in resource constrained settings.Trial registration numberCTRI/2018/03/012878.

OBJECTIVE To study the profile of retinopathy of prematurity (ROP) among outborn and inborn babies at a tertiary-care centre. METHODOLOGY In a prospective observational study from 2015-2016, outborn and inborn babies eligible for ROP screening were evaluated for ROP profile and treatment results. RESULTS 532 outborns and 38 inborns had ROP. Respi-ratory distress, sepsis and apnea were present in 81.3%, 51.5% and 36.2% of outborns with ROP and 68.4%, 39.4% and 36.8% of inborns with ROP. Type 1 ROP was noted in 49.2% eyes of outborns with ROP and 36.8% eyes of inborns with ROP. Type 1 ROP regressed with laser in 97.3% and 100% eyes of outborn and inborn with ROP, respectively. Stage 4, 5 and sequelae were noted in 5.2%, 22.8% and 4.6% eyes of outborns with ROP, respectively, but none in inborns. CONCLUSIONS Quality neonatal care and timely screening ensured lesser ROP-related morbidity in inborns as compared to outborns.

Objective To evaluate the clinical profile and outcome of neonates with non-immune hydrops (NIH). Methods Data of all the NIH cases admitted to neonatal intensive care unit at our center, New Delhi from January, 2010 to October, 2017 were extracted from hospital records, which included clinical profile and outcomes. Results Of the 17,299 total births, 27 neonates were identified to have NIH. Antenatal interventions were undertaken in five (18.5%) cases. The most common etiology of NIH was cardiac (n=5; 18.5%). Two babies with chylothorax were successfully managed with octreotide infusions. Overall survival rate of NIH was 70.3% (n=19). All neonates with a suspected genetic syndrome died. Conclusion Multidisciplinary team including obstetricians, pediatric surgeons, geneticists and neonatologists can improve outcome in neonates with NIH.

Clinical trials are essential to test the safety and efficacy of new treatments in any population. The paucity of drug trials especially in the neonatal population has led to the widespread use of unlicensed or off-label medications, exposing them to the risks of drug toxicity and ineffective treatment. Ethical and operational challenges are no longer considered valid excuses for not conducting drug trials in neonates. We recently participated in a combined phase-2 and phase-3 trial investigating a new indigenous goat lung surfactant extract (GLSE) for the treatment of respiratory distress syndrome (RDS) in preterm neonates. In this article, we share pertinent challenges faced by us during the trial to better inform and foster-positive discussion among drug developers, administrators, regulatory authorities, patient advocacy groups, and researchers. Also, we provide many tools developed for the GLSE trial that can be modified and used by prospective trialists.

Despite evidence suggesting use of relaxation technique beneficial for all human beings, it is one of the less commonly used approach for postpartum mothers. Aim To assess the impact of relaxation technique on stress, anxiety and milk output among the postpartum mothers of hospitalized neonates in NICU. Materials and methods In a non-blinded randomized controlled trial with total enumeration sampling technique, screening of NICU admission was done daily based on inclusion criteria. From total 160 admissions over a period of 6 month, 74 postpartum mothers meet the inclusion criteria whose neonates were born preterm (26–33 weeks gestation) and admitted consecutively to the level-III NICU at AIIMS Hospital in New Delhi, India. Total 57 mothers agree to participate, they were enrolled and randomly assigned to experimental (n1 = 29) and control (n2 = 28) groups using a computer generated random allocation sequence. There were total seven dropouts with the final sample size of 25 in each group. Baseline data including socio-demographic profile, maternal stress and anxiety were collected using subject data sheet, standardized Parental Stress Scale (PSS): NICU and Perinatal Anxiety Screening Scale (PASS) on 4 ± 2 postpartum day. An audio assisted relaxation technique of 30 min duration, was developed under the guidance of yoga therapist, which included deep breathing (5 min), Suksham Vyayam (8 min), Anulom-Vilom (5 min), Brahmari (5 min), Progressive Muscle Relaxation (PMR) (5 min), and deep breathing (2 min). The experimental group was administered audio assisted relaxation technique followed by every day practice for 10 days, while the control group continued to receive the routine care. The impact of the relaxation technique on stress, and anxiety of mothers along with milk output was assessed after 10 days of enrolment. Results Baseline characteristics and pre-intervention mean maternal stress (3.9 ± 0.5 vs. 3.8 ± 0.5, p = 0.34) and anxiety scores (31.12 ± 11.4 vs. 31.08 ± 12.0, p = 0.99) were comparable in both the groups. There was significant reduction observed in maternal stress (2.9 ± 0.5 vs. 3.6 ± 0.6) and anxiety scores (19.8 ± 6.7 vs. 28.18 ± 11.7, p ≤ 0.05) and improvement in milk output (69.2 ± 19.3 vs. 54.1 ± 22.5, p ≤ 0.05) in experimental group as compared to control group. Conclusion Use of relaxation technique may have significant role in reducing maternal stress and anxiety and improving the milk output. This trial is registered with Clinical Trials Registry India (CTRI/2018/06/014471).

Objective To compare the prevalence of vitamin K deficiency after intramuscular vitamin K or no treatment in neonates with sepsis on prolonged (>7 days) antibiotic therapy.