Azithromycin therapy for prevention of chronic lung disease of prematurity (AZTEC): a multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Systematic reviews have reported conflicting evidence on whether macrolide antibiotics reduce rates of chronic lung disease of prematurity (CLD) in at-risk preterm infants born at less than 30 weeks' gestation, including in those colonised with pulmonary Ureaplasma spp. Since an adequately powered trial has been lacking, we aimed to assess if the macrolide azithromycin improved survival without the development of physiologically defined moderate or severe CLD in preterm infants. METHODS: AZTEC was a multicentre, double-blind, randomised, placebo-controlled trial conducted in 28 tertiary neonatal intensive care units in the UK. Infants were eligible if they were born at less than 30 weeks' gestation and had received at least 2 h of either non-invasive (continuous positive airway pressure or humidified high flow nasal cannula therapy) or invasive respiratory support (via endotracheal tube) within 72 h of birth. Eligible infants were randomly allocated in a 1:1 ratio using random permuted blocks of four to receive either intravenous azithromycin at 20 mg/kg per day for 3 days followed by 10 mg/kg for 7 days, or to placebo. Allocation was stratified by centre and gestational age at birth (<28 weeks vs ≥28 weeks). Azithromycin and placebo vials were encased in tamper-evident custom cardboard cartons to ensure masking for clinicians, parents, and the research team. The primary outcome was survival without development of physiologically defined moderate or severe CLD at 36 weeks' postmenstrual age. Outcomes and safety were analysed on an intention-to-treat basis (all randomly allocated infants, regardless of any post-randomisation events). The study was registered with ISRCRN (11650227) and is closed. FINDINGS: Infants were recruited between Oct 9, 2019, and March 22, 2022. 799 (53·1%) of 1505 eligible infants underwent random allocation; three infants were withdrawn, including consent to use their data, leaving 796 infants for analysis. Survival without moderate or severe CLD occurred in 166 (42%) of 394 infants in the intervention group and 179 (45%) of 402 in the placebo group (three-level adjusted OR [aOR] 0·84, 95% CI 0·55-1·29, p=0·43). Pulmonary Ureaplasma spp colonisation did not influence treatment effect. Overall, seven serious adverse events were reported for the azithromycin group (five graded as severe, two as moderate), and six serious adverse events were reported in the placebo group (two severe, two moderate, and two mild), as assessed by the local principal investigators. INTERPRETATION: Since prophylactic use of azithromycin did not improve survival without development of physiologically-defined CLD, regardless of Ureaplasma spp colonisation, it cannot be recommended in clinical practice. FUNDING: UK National Institute for Health and Care Research.

A Site-Based Analysis of Relationship Between Clinicopathological Factors and Their Influence on Locoregional Recurrence in Oral Squamous Cell Carcinoma.

In India, oral cancers are the major cause of cancer-related death. Tongue and buccal mucosa being the major subsites in oral cancer have varying clinicopathological presentations. This study is intended to know the difference in clinicopathological behavior of these two subsites. This retrospective study included 474 patients of which 232 patients had tongue cancer and 242 patients had buccal alveolar complex (BAC) cancer. Comparison between the pathological characters including pattern of nodal involvement was analyzed. Disease-free survival (DFS) and factors influencing the DFS were analyzed and compared using Cox regression analysis. Mean age of the study population was 52.7 years. Tongue oral squamous cell carcinoma (OSCC) differed significantly from BAC OSCC in terms of age of presentation, tumor staging, and perineural invasion. Among neck nodal involvement, tongue OSCC commonly involved level IIa (p < 0.001) whereas BAC involved level Ib (p < 0.001). At a median follow-up of 27 months, 141 patients had disease recurrence, tongue OSCC commonly recurred in neck (p = 0.008), and BAC OSCC relapsed at primary site (p = 0.001). Patients older than 45 years with BAC cancer had lesser risk of recurrence (HR, 0.30; 95% CI, 0.2-0.5; p < 0.0001). Pathological tumor stage in tongue cancer (HR, 14.9; 95% CI, 2.6-84.8; p = 0.002) and grade of tumor differentiation in BAC OSCC (HR, 9.2; 95% CI, 1.9-43.3; p < 0.005) were the most significant factors that influenced tumor recurrence. There was a significant difference in factors influencing disease recurrence among tongue and BAC OSCC. Also, pattern of nodal metastasis and pattern of recurrence were different. Hence, further research on OSCC may be done site specific. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01750-8.

Can we predict urethral length of boys? - An observational study.

INTRODUCTION: An additional knowledge about normal anatomy of urethra in boys can improve clinical outcome of any urological interventions. This will also reduce catheter related complications like intra vesical knotting and urethral injuries. At present there is no systematic data available which has studied the urethral length of boys. We have done this study to analyse the length of urethra in boys. AIM: The aim of the study is to measure the urethral length in Indian children from the age of 1 year till 15 years and plot a nomogram. Furthermore to analyse the influence of anthropometry on urethral length and derived a formula to predict the urethral length in boys. STUDY DESIGN: This is a single institution prospective observational study. After obtaining clearance from the institutional review board, a total of 180 children from the age of 1-15 were recruited for the study. The urethral length was measured during Foley's catheter removal. Other data like age, weight, and height of the patient are collected and the obtained values were analysed with SPSS software. The acquired figures were further used to derive formulae to predict urethral length. RESULTS: A nomogram of urethral length based on age was plotted. With collected figures, five separate formulae were derived to calculate the urethral length based on the age, height and weight. Furthermore for day-to-day use we have deduced a formulas to calculate urethral length which are simplified forms of original formulae. DISCUSSION: The length of urethra of a new-born male is 5 cm, which attains 8 cm by three years of age and to 17 cm by adulthood. There were attempts to measure the urethral length in adults using cystoscopy, Foley's catheter and different imaging techniques like Magnetic Resonance Imaging and dynamic retrograde urethrography. Simplified formulae which has been derived from this study for clinical use is Urethral length = 8.7 + Age (in year) × 0.55 CONCLUSION: Our results will complement the current anatomical understanding of the urethra. This evades some rare complications of catheterisation and facilitate reconstructive procedures.

Trends in prevalence and determinants of severe and moderate anaemia among women of reproductive age during the last 15 years in India.

BACKGROUND: Anaemia is a serious global public health problem that disproportionally affects children, adolescent girls, and women of reproductive age, especially pregnant women. Women of reproductive age are more vulnerable to anaemia, particularly severe and moderate anaemia leads to adverse outcomes among pregnant women. Despite continuous Government efforts, anaemia burden still poses a serious challenge in India. The objective of this study is to assess the trends in prevalence and determinants of severe and moderate anaemia among women of reproductive age between 15 and 49 years. METHOD: We used three rounds of the large-scale National Family Health Survey (NFHS) India, conducted on a representative sample of households using a cross-sectional design across the country in 2005-06, 2015-16 and 2019-2021. We included all the women aged 15 to 49 years in our analysis. We used the same haemoglobin (Hb) cut-off values for all the three rounds of surveys to ensure comparability. Generalized linear regression analyses with log link were done. Survey weights were incorporated in the analysis. RESULTS: The prevalence of severe or moderate Anaemia (SMA) in non-pregnant women was 14.20%, 12.43% and 13.98%; it was 31.11%, 25.98% and 26.66% for pregnant women in 2006, 2016 and 2021 respectively. The decline in SMA prevalence was 1.54% in non-pregnant women, whereas it was 14.30% in pregnant women in 15 years. Women who were poor, and without any formal education had a higher risk for severe and moderate Anaemia. CONCLUSION: Despite the intensive anaemia control program in India, SMA has not declined appreciably in non-pregnant women during the last two decades. Despite the decline, the prevalence of SMA was about 26% in pregnant women which calls for a comprehensive review of the existing anaemia control programmes and there must be targeted programmes for the most vulnerable and high-risk women such as rural, poor and illiterate women of reproductive age to reduce the burden of anaemia among them.

Exact correction factor for estimating the OR in the presence of sparse data with a zero cell in 2 × 2 tables.

In case-control studies, odds ratios (OR) are calculated from 2 × 2 tables and in some instances, we observe small cell counts or zero counts in one of the cells. The corrections to calculate the ORs in the presence of empty cells are available in literature. Some of these include Yates continuity correction and Agresti and Coull correction. However, the available methods provided different corrections and the situations where each could be applied are not very apparent. Therefore, the current research proposes an iterative algorithm of estimating an exact (optimum) correction factor for the respective sample size. This was evaluated by simulating data with varying proportions and sample sizes. The estimated correction factor was considered after obtaining the bias, standard error of odds ratio, root mean square error and the coverage probability. Also, we have presented a linear function to identify the exact correction factor using sample size and proportion.

Reduction in prevalence of spousal physical violence against women in India: evidence from three national surveys.

Spousal physical violence (PV) against women is considered to be major health issue in developing countries. Lifetime physical violence is a composite outcome consists of hit, kick, beat, slap and threatened with weapon, perpetrated by the husband. The study aims to examine changes in prevalence and specific risk factors for PV from 1998 to 2016 in India. This study analyzed data from a cross sectional epidemiological survey in 1998-1999, NFHS-3 (2005-2006) and NFHS-4 (2015-2016) data. There was a significant decline of about 10% (95% CI: 8.8%-11.1%) in PV. Major risk factors for change in PV were husband's use of alcohol, illiteracy and socio-economic status of the household. The Protection of Women from Domestic Violence Act may have played a role in reducing the PV. Even though there was a decline in PV, actions have to be implemented from the root level to ensure women empowerment.

Difference in clinical presentation and their significance in oral squamous cell carcinoma: A retrospective analysis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) remains the most common cancer among Indian men. OSCC involving the tongue and bucco alveolar complex (BAC) behaves differently. Nevertheless, the differences in clinical features and symptoms between the two subsites and their relation to pathology remain largely unexplored. STUDY DESIGN: The study compared various clinical parameters and pathological factors between tongue cancer patients and patients with BAC cancer. RESULTS: Among 474 patients, 232 had tongue cancer and 242 had BAC cancer. Except for the ulcer, 30% of patients with OSCC were asymptomatic at presentation. Compared to tongue cancers, lesions confined to BAC present at an advanced stage (P = 0.006). Multivariate analysis showed that dysphagia in tongue cancer (P = 0.020) and external swelling or lesion in BAC cancers (P = 0.002) were significant predictors of an advanced stage of the disease. On histopathology, perineural invasion (PNI) was significantly associated with tongue (P = 0.008) compared to BAC cancers (P = 0.015). Cancers of the tongue with pain and referred otalgia had a significantly higher depth of invasion (DOI), compared to those without pain (DOI - no pain 6.9 mm, pain 9.9 mm, and referred otalgia 11.4 mm). CONCLUSIONS: Patients with OSCC present late and in an advanced stage of the disease. Among tongue cancers, clinical history of pain was significantly associated with DOI and PNI, the significance of which needs to be prospectively analyzed. Clinical history in OSCC can be used as predicting factor for an advanced pathological stage of the disease. It also had an influence on various pathological characters, which is subsite specific.

ZFTA (Zinc Finger Translocation Associated) Fusion in Supratentorial Ependymomas: Low Prevalence in South Asians and No Correlation with Survival.

BACKGROUND: Supratentorial ependymomas (STEs) are an aggressive group of ependymomas, topographically distinct from their posterior fossa and spinal counterparts. Zinc finger translocation associated (ZFTA) fusion-positive cases have been reported to account for the majority of STEs, although data on its association with poorer outcomes are inconsistent. MATERIALS AND METHODS: We assessed the prevalence of the ZFTA fusion by reverse-transcription polymerase chain reaction and fluorescence in situ hybridization in a cohort of 61 patients (68 samples) with STE. Our primary outcome was to determine the role of the ZFTA fusion on progression-free and overall survival of patients with STE. Our secondary objectives were to assess the impact of ZFTA fusion on nuclear factor (NF)-kB pathway signaling via surrogate markers of this pathway, namely COX-2, CCND1, and L1 cell adhesion molecule. RESULTS: ZFTA fusion was noted in 21.3% of STEs in our cohort. The presence of this rearrangement did not significantly impact the progression-free or overall survival of patients with STEs and was not associated with upregulation of markers of the NF-kB pathway. Only gross total resection was significantly associated with better progression-free survival. CONCLUSIONS: In contradiction to previous reports from across the world, the ZFTA fusion is far less prevalent among our population. It does not appear to drive NF-kB signaling or significantly affect outcomes. Gross total resection must be attempted in all cases of STE and adjuvant radiation and/or chemotherapy employed when gross total resection is not achieved.

Implementation and outcomes of enhanced recovery protocols in pediatric surgery: a systematic review and meta-analysis.

BACKGROUND: This systematic review examines the feasibility and safety of implementing Enhanced recovery after Surgery (ERAS) protocols in children. STUDY DESIGN: A systematic search of Medline, PubMed, and the Cochrane library for papers describing ERAS implementation in children between January 2000 and January 2021. The systematic review was performed according to the PRISMA statement. The meta-analysis was done using R Software (Ver 4.0.2). p value of < 0.05 was considered statistically significant. RESULTS: Sixteen studies, describing a total of 1723 patients, were included in the meta-analysis. An average of 15 (range 11-16) relevant components were implemented with an overall compliance close to 84%. The time to initiate feeds and reach full enteral nutrition was reduced in ERAS group with mean difference (MD) of - 21.20 h (95% CI - 22.80, - 19.59, p < 0.01), and - 2.20 days (95% CI - 2.72, - 1.71, p < 0.01), respectively. The use of opioids for postoperative analgesia was reduced with MD of -0.86 morphine equivalents mg/kg (95% CI - 1.40, - 0.32, p < 0.01). The length of hospital stay showed a significant reduction with MD of -2.54 days (95% CI - 2.94, - 2.13, p < 0.01). There was no difference in the complication and readmission rates between the groups. CONCLUSION: ERP implementation in pediatric perioperative care is a viable option in a variety of surgical settings. There is clear evidence of a decrease in hospital stay duration with no increase in complication or readmission rates. The length of hospital stay reduced in inverse proportion to the number of ERAS elements implemented. Parental satisfaction is increased by initiating enteral feeding early, minimizing catheter and drain use, and reducing opioid use.

Analysis of Early Impact of COVID-19 on Presentation and Management of Oral Cancers - an Experience from a Tertiary Care Hospital in South India.

Oral cancers are the leading cause of cancer-related death in Indian men. Currently steps to contain the transmission and treatment of COVID-19 pandemic have crippled the entire health care system. With hospitals running short of resources, the oncological practice became standstill, especially during the initial phase. This is a retrospective study among patients who presented to our tertiary care hospital in early 3 months of COVID-19 era(ECE) with respect to pre-COVID-19 era(PCE). The study includes patients discussed in multidisciplinary tumor board(MDT)(421 in ECE Vs 31 in PCE) and those who underwent surgery(192 in ECE Vs 26 in PCE). The presentation and outcomes of oral carcinoma were compared between the two eras. There was a significant drop in the number of patients who presented during ECE. Though mean age and gender remained comparable between groups, there was a statistical difference in relation to demographic profile of patient (p value < 0.001). Among operated during ECE, 80% had a significantly advanced tumor stage (p value < 0.034) and advanced composite stage (p value < 0.049). Among patients discussed in MDT during ECE, 38.7% were deemed inoperable which is double the number when compared with PCE (p value < 0.009). Results of our study showed a higher incidence of advanced stage disease during ECE, with many patient turning inoperable. Thus, the survival of newly diagnosed oral carcinoma patients will be worser. In the management of oral cancer both early stage and advanced stage should have the same priority. Immediate resumption of safe oncology services is mandatory to curtail the current issues.

Simulation with a colour indicator to help reduce contamination during airway management in COVID-19 times: An experience from a tertiary centre in India.

BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic has initiated modified protocols for aerosol-generating procedures. A simulation study using dye was conducted to highlight contamination at intubation and extubation and to encourage adherence to the new COVID-19 protocol among anaesthesia personnel in our institution. METHODS: A video demonstrating the new COVID-19 protocols was circulated in the Department of Anaesthesiology a week prior to the study. Thirty teams, each comprising an anaesthesia resident and a staff technician, were enroled. Each team was asked to demonstrate the steps of preparation, intubation and extubation on a mannequin in a COVID-19 scenario. Checklists were used to assess points of contamination and adherence to the protocols. Following debriefing, a repeat simulation was conducted. The use of a dye highlighted the points of contamination. The study subjects provided feedback on the usefulness of the session and practical difficulties encountered in adapting to the new protocols. RESULTS: The average contamination scores decreased by 3.4 (95% confidence interval (CI): 2.4-4.4, P < 0.001) in the post-debrief session. Adherence to the steps of the modified protocol improved by a score of 2.7 (CI: 3.6-1.83) among anaesthesiologists and by 4.3 (CI: 5.3-3.3) among technicians. Further, 93% felt that the use of the colour indicator reinforced awareness of the possible points of contamination. CONCLUSION: Simulation with a low-fidelity mannequin by using colour indicator for secretions is an effective teaching tool to reduce health hazards during airway management in COVID-19 times.

Apnoeic Oxygenation during Simulated Difficult Intubation in Obese Patients: Comparison of Buccal Ring, Adair and Elwyn Tube Versus Nasal Cannula: A Prospective Randomized Controlled Trial.

Background: Apnoeic oxygenation is an established method of increasing safe apnoea times during intubation and this is of more importance in obese patients. The usefulness of buccal Ring, Adair and Elwyn (RAE) oxygenation has been established in previous studies, however a head-to-head comparison with nasal cannula (NC) is lacking. Aim: The aim of this study was to compare apnoea time with buccal RAE (BR) versus NC in obese patients. Setting and Design: This was a prospective, nonblinded randomized controlled trial conducted in a tertiary hospital where fifty American Society of Anaesthesiologists Physical Status Class I and II, obese patients with body mass index ≥30, posted for elective surgery were included. Materials and Methods: Following adequate preoxygenation and standard induction of anaesthesia, a prolonged simulated difficult laryngoscopy was performed during which oxygen was provided via either BR or NC. The primary outcome was time to desaturation to <95% or 10 min, which ever occurred first. Other outcomes recorded were lowest saturation, time to resaturation and highest end tidal carbon di oxide. Statistical Analysis: Mean with standard deviation (SD) or median with inter quartile range were used for continuous variables and absolute number with percentage were used for categorical variables. The primary outcome was analyzed using Kaplan-Meier survival curves, and log-rank tests were applied. Results: Patient characteristics were similar in both arms. The mean apnoea time in seconds (SD) in the BR group, 375.3 (116.6) was higher than the NC group 316.1 (94.1), P = 0.054. From the Kapan Meier curves the probability of desaturating to <95% was earlier in the NC group than the BR group (P = 0.092). The other outcomes were similar in both groups. Conclusion: This is the first study that demonstrates that oxygenation via a BR is better than NC in providing apnoeic oxygenation in obese patients and can safely be used when NC are contraindicated.