Lady Hardinge Medical College

Ketogenic dietary therapies (KDTs) are established, effective nonpharmacologic treatments for intractable childhood epilepsy. For many years KDTs were implemented differently throughout the world due to lack of consistent protocols. In 2009, an expert consensus guideline for the management of children on KDT was published, focusing on topics of patient selection, pre-KDT counseling and evaluation, diet choice and attributes, implementation, supplementation, follow-up, side events, and KDT discontinuation. It has been helpful in outlining a state-of-the-art protocol, standardizing KDT for multicenter clinical trials, and identifying areas of controversy and uncertainty for future research. Now one decade later, the organizers and authors of this guideline present a revised version with additional authors, in order to include recent research, especially regarding other dietary treatments, clarifying indications for use, side effects during initiation and ongoing use, value of supplements, and methods of KDT discontinuation. In addition, authors completed a survey of their institution's practices, which was compared to responses from the original consensus survey, to show trends in management over the last 10 years.

BACKGROUND: Hepatitis E virus (HEV) infection is known to cause severe liver disease in pregnant women. It is unclear whether obstetric and fetal outcomes are worse in pregnant women with HEV infection than in women with other forms of viral hepatitis. OBJECTIVE: To compare maternal, obstetric, and fetal outcomes in pregnant women with acute viral hepatitis caused by HEV and other hepatitis viruses. DESIGN: Observational cohort. SETTING: Tertiary care hospital, New Delhi, India. PATIENTS: 220 consecutive pregnant women presenting with jaundice caused by acute viral hepatitis. MEASUREMENTS: Maternal mortality and medical complications, obstetric complications, deliveries, and fetal outcomes. RESULTS: Infection with HEV caused acute viral hepatitis in 60% of included women. Fulminant hepatic failure was more common (relative risk, 2.7 [95% CI, 1.7 to 4.2]; P = 0.001) and maternal mortality was greater (relative risk, 6.0 [CI, 2.7 to 13.3]; P < 0.001) in HEV-infected women than in non-HEV-infected women. Women with HEV infection were more likely than those with other forms of viral hepatitis to have obstetric complications (relative risk, 4.1 [CI, 1.7 to 10.2] for antepartum hemorrhage and 1.9 [CI, 1.3 to 2.7] for intrauterine fetal death; P < 0.001 for both) and poor fetal outcomes (relative risk, 1.2 [CI, 1.0 to 1.4] for preterm delivery [P = 0.005] and 1.8 [CI, 1.2 to 2.5] for stillbirth [P = 0.026]). LIMITATIONS: The findings may not apply to community settings, to women who are asymptomatic or have only minor symptoms, or in the setting of an HEV epidemic. CONCLUSIONS: Pregnant women with jaundice and acute viral hepatitis caused by HEV infection had a higher maternal mortality rate and worse obstetric and fetal outcomes than did pregnant women with jaundice and acute viral hepatitis caused by other types of viral hepatitis.

OBJECTIVE: To provide an estimate of the burden of postpartum depression in Indian mothers and investigate some risk factors for the condition. METHODS: We searched PubMed®, Google Scholar and Embase® databases for articles published from year 2000 up to 31 March 2016 on the prevalence of postpartum depression in Indian mothers. The search used subject headings and keywords with no language restrictions. Quality was assessed via the Newcastle-Ottawa quality assessment scale. We performed the meta-analysis using a random effects model. Subgroup analysis and meta-regression was done for heterogeneity and the Egger test was used to assess publication bias. FINDINGS: = 96.8%) and there was evidence of publication bias (Egger bias = 2.58; 95% confidence interval, CI: 0.83-4.33). The overall pooled estimate of the prevalence of postpartum depression was 22% (95% CI: 19-25). The pooled prevalence was 19% (95% CI: 17-22) when excluding 8 studies reporting postpartum depression within 2 weeks of delivery. Small, but non-significant differences in pooled prevalence were found by mother's age, geographical location and study setting. Reported risk factors for postpartum depression included financial difficulties, presence of domestic violence, past history of psychiatric illness in mother, marital conflict, lack of support from husband and birth of a female baby. CONCLUSION: The review shows a high prevalence of postpartum depression in Indian mothers. More resources need to be allocated for capacity-building in maternal mental health care in India.

BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.

With the many recent advances in the biomedical world, vast changes are taking place in our growing knowledge of the physiological aspects of almost all the tissues and organs of the human body. One of the most prevalent topics of discussion is the question of obesity and its effect on the metabolic changes in the human body. The original classical role of adipose tissue as an energy storage organ has been greatly modified. We now know that it is an endocrine organ, producing adipokines like leptin, adiponectin, visfatin, resistin, apelin, etc, which modulate metabolic processes in the body. Since obesity is associated with an increase in the adipose tissue mass, these hormones may be expected to be produced in increased concentrations and may thus have a significant impact on the macronutrient metabolism. Further, these adipokines may interact with long term energy modulators like insulin. Even though the scientific community has started unravelling the mysteries of the close linkage between obesity, its hormones and their physiological effects, a lot still remains to be discovered. The present discussion makes an attempt to trace the basic modern day concepts of the role of obesity in various metabolic processes.

The health status of any country depends on the socio-economic status (SES) and the per capita income of its citizens. The SES also decides the affordability and utilization of the health facilities. Constant changes in the price of goods in the country due to inflation make it mandatory to constantly update the income-based socioeconomic scales. This paper attempts to provide updates in Kuppuswamy, B.G. Prasad and udai pareek socioeconomic scales for 2017.

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. Cardiovascular and renal complications share common risk factors such as blood pressure, blood lipids, and glycemic control. Thus, chronic kidney disease may predict cardiovascular disease in the general population. The impact of diabetes on renal impairment changes with increasing age. Serum markers of glomerular filtration rate and microalbuminuria identify renal impairment in different segments of the diabetic population, indicating that serum markers as well as microalbuminuria tests should be used in screening for nephropathy in diabetic older people. The American Diabetes Association and the National Institutes of Health recommend Estimated glomerular filtration rate (eGFR) calculated from serum creatinine at least once a year in all people with diabetes for detection of kidney dysfunction. eGFR remains an independent and significant predictor after adjustment for conventional risk factors including age, sex, duration of diabetes, smoking, obesity, blood pressure, and glycemic and lipid control, as well as presence of diabetic retinopathy. Cystatin-C (Cys C) may in future be the preferred marker of diabetic nephropathy due differences in measurements of serum creatinine by various methods. The appropriate reference limit for Cys C in geriatric clinical practice must be defined by further research. Various studies have shown the importance of measurement of albuminuria, eGFR, serum creatinine and hemoglobin level to further enhance the prediction of end stage renal disease.

Free fatty acids are known to play a key role in promoting loss of insulin sensitivity in type 2 diabetes mellitus but the underlying mechanism is still unclear. It has been postulated that an increase in the intracellular concentration of fatty acid metabolites activates a serine kinase cascade, which leads to defects in insulin signaling downstream to the insulin receptor. In addition, the complex network of adipokines released from adipose tissue modulates the response of tissues to insulin. Among the many molecules involved in the intracellular processing of the signal provided by insulin, the insulin receptor substrate-2, the protein kinase B and the forkhead transcription factor Foxo 1a are of particular interest, as recent data has provided strong evidence that dysfunction of these proteins results in insulin resistance in vivo. Recently, studies have revealed that phosphoinositidedependent kinase 1-independent phosphorylation of protein kinase Cε causes a reduction in insulin receptor gene expression. Additionally, it has been suggested that mitochondrial dysfunction triggers activation of several serine kinases, and weakens insulin signal transduction. Thus, in this review, the current developments in understanding the pathophysiological processes of insulin resistance in type 2 diabetes have been summarized. In addition, this study provides potential new targets for the treatment and prevention of type 2 diabetes.

BACKGROUND: With deteriorating ecosystems, the health of mankind is at risk. Future health care professionals must be trained to recognize the interdependence of health and ecosystems to address the needs of their patients and communities. Health issues related to, e.g. climate change and air pollution, are not, however, generally included in medical education. OBJECTIVES: To assess the inclusion of climate change and air pollution in medical curricula and to guide the International Federation of Medical Students' Associations' (IFMSA) Vision of Climate Change in the Medical Curriculum. METHODS: A study comprising three surveys (March 2019, August 2019, March 2020) explored medical students' perceptions of the current status of formal and non-formal elements of climate change and air pollution and health in their medical programs. RESULTS: Respondents originated from 2817 medical schools in 112 countries. Only 15% of medical schools have incorporated climate change and health into the curriculum. Students led climate-related activities in an additional 12% of medical schools. With regard to air pollution and health, only 11% of medical schools have formal education on the topic. CONCLUSIONS: It is crucial to acknowledge the current omissions from medical curricula and the importance of meaningful student involvement in curriculum transformation.

In a prospective study of 144 consecutive male patients with psychosexual disorders, comprising 93 with Dhat syndrome with or without impotence or premature ejaculation, 21 with premature ejaculation, and 30 suffering only impotence, the commonest associated psychiatric illness was neurotic depression (39%) followed by anxiety neurosis (21%), while 31% did not receive a psychiatric diagnosis. The common presenting a symptoms of Dhat syndrome were weakness (71%), fatigue (69%), palpitations (69%), and sleeplessness (62%). After random allocation into groups, four types of treatment were given: an anti-anxiety drug, an antidepressant, a placebo, or counselling. The best response was seen with the anti-anxiety and antidepressant drugs. Twenty-one patients dropped out of treatment; 15 of whom were from the counselling group.

An outbreak of chikungunya virus is currently ongoing in many countries in Indian Ocean since January 2005. The current outbreak appears to be the most severe and one of the biggest outbreaks caused by this virus. India, where this virus was last reported in 1973, is also amongst affected countries. Chikungunya virus has affected millions of the people in Africa and Southeast Asia, since it was first reported in 1952 in Tanzania. Even then, natural history of this disease is not fully understood. The intra-outbreak studies, point towards recent changes in the viral genome facilitating the rapid spread and enhanced pathogenecity. The available published scientific literature on chikungunya virus was searched to understand the natural history of this disease, reasons for the current outbreak and the causes behind re-emergence of the virus in India. The paucity of the scientific information on various epidemiological aspects of chikungunya virus threatens off an epidemic as control of spread of virus might be difficult in the absence of appropriate knowledge. There is an immediate need of the research on chikungunya virus, for an effective vaccine besides strengthening the existing diagnostic laboratory facilities. The current outbreak can also be taken as a lesson for establishment of a system for continuous surveillance of diseases, considered disappeared from the countries. The re-emergence and epidemics are unpredictable phenomena but the impact of such events can be ameliorated by appropriate knowledge and by being in the right state of preparedness.

Importance: Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE); however, the superiority of specific treatments and combinations remains unclear. Objective: To map the use and safety of immunotherapies in individuals with NMDARE, identify early predictors of poor functional outcome and relapse, evaluate changes in immunotherapy use and disease outcome over the 14 years since first reports of NMDARE, and assess the Anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score. Data Sources: Systematic search in PubMed from inception to January 1, 2019. Study Selection: Published articles including patients with NMDARE with positive NMDAR antibodies and available individual immunotherapy data. Data Extraction and Synthesis: Individual patient data on immunotherapies, clinical characteristics at presentation, disease course, and final functional outcome (modified Rankin Scale [mRS] score) were entered into multivariable logistic regression models. Main Outcomes and Measures: The planned study outcomes were functional outcome at 12 months from disease onset (good, mRS score of 0 to 2; poor, mRS score greater than 2) and monophasic course (absence of relapse at 24 months or later from onset). Results: Data from 1550 patients from 652 articles were evaluated. Of these, 1105 of 1508 (73.3%) were female and 707 of 1526 (46.3%) were 18 years or younger at disease onset. Factors at first event that were significantly associated with good functional outcome included adolescent age and first-line treatment with therapeutic apheresis, corticosteroids plus intravenous immunoglobulin (IVIG), or corticosteroids plus IVIG plus therapeutic apheresis. Factors significantly associated with poor functional outcome were age younger than 2 years or age of 65 years or older at onset, intensive care unit admission, extreme delta brush pattern on electroencephalography, lack of immunotherapy within the first 30 days of onset, and maintenance IVIG use for 6 months or more. Factors significantly associated with nonrelapsing disease were rituximab use or maintenance IVIG use for 6 months or more. Adolescent age at onset was significantly associated with relapsing disease. Rituximab use increased from 13.5% (52 of 384; 2007 to 2013) to 28.3% (311 of 1100; 2013 to 2019) (P < .001), concurrent with a falling relapse rate over the same period (22% [12 of 55] in 2008 and earlier; 10.9% [35 of 322] in 2017 and later; P = .006). Modified NEOS score (including 4 of 5 original NEOS items) was associated with probability of poor functional status at 1 year (20.1% [40 of 199] for a score of 0 to 1 points; 43.8% [77 of 176] for a score of 3 to 4 points; P = .05). Conclusions and Relevance: Factors influencing functional outcomes and relapse are different and need to be considered independently in development of evidence-based optimal management guidelines of patients with NMDARE.

Pigmented purpuric dermatoses are a spectrum of disorders characterized by a distinct purpuric rash, mainly localized to the lower limbs, which are morphologically dissimilar but histopathologically indistinguishable. Their etiology remains obscure. They are rather resistant to treatment. Although diagnosed quite straightforwardly, the disease entity remains an enigma and a therapeutic challenge. The current narration discusses the outline of the epidemiology, etiopathogenesis, clinical features, histopathology and management of these disorders. The current review, hopefully, may once again rekindle interest in the entity, for it has been sparingly reported or discussed for the benefit of under- and/or postgraduates and those in practice, including family physicians.

INTRODUCTION: Laparoscopic cholecystectomy (LC) is one of the most common laparoscopic procedures being performed by general surgeons all over the world. Preoperative prediction of the risk of conversion or difficulty of operation is an important aspect of planning laparoscopic surgery. The purpose of our prospective study was to analyze various risk factors and to predict difficulty and degree of difficulty preoperatively by the use of a scoring system. MATERIALS: This prospective study was conducted in the department of surgery, Lady Hardinge Medical College and associated Dr Ram Manohar Lohia Hospital, Delhi, India. The parameters considered in the preoperative scoring method were old age, male sex, history of hospitalization, obesity, previous abdominal surgery scar, palpable gall bladder, wall thickness of gall bladder, pericholecystic collection and impacted stone. A total of 210 patients were included in the study. RESULTS: We found that history of hospitalization, palpable gall bladder, impacted stone and gall bladder wall thickness were statistically significant factors for prediction of difficult laparoscopic cholecystectomy. Sensitivity and specificity of this preoperative scoring method were found to be 95.74% and 73.68% respectively. Positive predictive values of this scoring method were 90% and 88% for easy and difficult cases respectively. Area under ROC curve was 0.86. Conversion rate from laparoscopic to open cholecystectomy was found to be 4.28%. CONCLUSION: With the help of accurate prediction, high risk patient may be informed before hand regarding the probability of conversion and hence they may have a chance to make arrangements accordingly. On the other hand, surgeons also may have to schedule the time and team for the operation appropriately. Surgeons can also be aware about the possible complications that may arise in high risk patients.

Interface of diabetes and psychiatry has fascinated both endocrinologists and mental health professionals for years. Diabetes and psychiatric disorders share a bidirectional association -- both influencing each other in multiple ways. The current article addresses different aspects of this interface. The interaction of diabetes and psychiatric disorders has been discussed with regard to aetio-pathogenesis, clinical presentation, and management. In spite of a multifaceted interaction between the two the issue remains largely unstudied in India.

&lt;sec&gt;&lt;title&gt;Study Design&lt;/title&gt;&lt;p&gt;Cross-sectional study.&lt;/p&gt;&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;Purpose&lt;/title&gt;&lt;p&gt;To evaluate the prevalence and various risk factors for low back pain (LBP) in young adults in India.&lt;/p&gt;&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;Overview of Literature&lt;/title&gt;&lt;p&gt;LBP is an emerging problem in adolescents, with an incidence that is the highest in the third decade of life worldwide. Various risk factors such as obesity, smoking, family history, stress, and exercise have been described in the literature. This study was conducted because of paucity of data in the Indian literature.&lt;/p&gt;&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;Methods&lt;/title&gt;&lt;p&gt;A total of 1,355 (741 males and 641 females) young Indian Administrative Service aspirants and medical postgraduate aspirants aged 18–35 years were enrolled in the study. The subjects completed a detailed, semi-structured questionnaire that gathered data regarding their sociodemographic profile and factors considered to be risk factors for LBP. Anthropometric measurements, including height and weight, were measured and body mass index was calculated.&lt;/p&gt;&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;Results&lt;/title&gt;&lt;p&gt;Most subjects (90.6%) were aged 20–29 years (mean, 24.49; range, 18–35 years). Results indicated that the following factors were associated with LBP in young adults: marital status, previous history of spine problems, strenuous exercise, job satisfaction, monotony, stress, daily number of studying hours, and family history of spine problems (&lt;italic&gt;p&lt;/italic&gt;&amp;lt;0.05). However, age, sex, smoking, alcoholism, coffee intake, mode and duration of travel, diet, frequency of weightlifting, wearing heels, studying posture, and frequency and type of sports activities were not associated with LBP.&lt;/p&gt;&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;Conclusions&lt;/title&gt;&lt;p&gt;The study identified various modifiable and non-modifiable risk factors that precipitated LBP in young adult Indians. Identifying these risk factors at an early stage will prevent LBP progression to a chronic disease state, thereby improving an individual's quality of life and increasing productivity.&lt;/p&gt;&lt;/sec&gt;

Dermatophytosis has attained unprecedented dimensions in recent years in India. Its clinical presentation is now multifarious, often with atypical morphology, severe forms and unusually extensive disease in all age groups. We hesitate to call it an epidemic owing to the lack of population-based prevalence surveys. In this part of the review, we discuss the epidemiology and clinical features of this contemporary problem. While the epidemiology is marked by a stark increase in the number of chronic, relapsing and recurrent cases, the clinical distribution is marked by a disproportionate rise in the number of cases with tinea corporis and cruris, cases presenting with the involvement of extensive areas, and tinea faciei.

BACKGROUND: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. METHODS AND FINDINGS: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-"Low" Watch). The largest group (34.0%, n = 1,068) 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) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. CONCLUSION: Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT03721302).

Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

BACKGROUND: Neurocognitive deficits exist in euthymic patients with bipolar disorder, but relationships between symptoms, psychosocial and neurological factors remain uncertain. AIMS: To measure neurocognitive function in bipolar disorder and explore links to sub-syndromal mood symptoms, soft neurological signs and psychosocial impairment. METHOD: Attention, memory and executive function were tested in 37 euthymic patients with bipolar disorder and 37 controls. Psychosocial functioning, soft neurological signs and residual mood symptoms were assessed. RESULTS: Performances on tests reflecting executive function and verbal memory (but not attention) were significantly poorer in the bipolar disorder group. Sub-syndromal mood symptoms produced small cognitive effects, predominantly on verbal memory. Soft neurological signs, especially frontal signs, were marked; some patients showed marked social disability which correlated strongly with soft neurological signs but weakly with executive dysfunction, which was linked to illness episodes. CONCLUSIONS: Cognitive dysfunction, social dysfunction and soft signs occur in euthymic patients with bipolar disorder and may represent trait deficits.