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Aim We explored the psychometric properties of the recently developed Tyneside Pegboard Test (TPT) for unimanual and bimanual dexterity in children with unilateral cerebral palsy (CP) and investigated the impact of sensorimotor impairments on manual dexterity. Method In this cross-sectional study, the TPT was assessed in 49 children with unilateral CP (mean age 9y 8mo, SD 1y 11mo, range 6-15y; 30 males, 19 females; 23 with right unilateral CP). All participants additionally underwent a standardized upper limb evaluation at body function and activity level. We investigated: (1) known-group, concurrent, and construct validity and (2) impact of sensorimotor impairments including spasticity, grip force, stereognosis, and mirror movements using analysis of covariance, Spearman's rank correlation (r), and multiple linear regression (R-2) respectively. Results TPT outcomes significantly differed according to the Manual Ability Classification System (p

A middle-aged man had been diagnosed as retinitis and treated with steroids previously. The patient had developed macular infarction in the course of illness. We diagnosed him to have rickettsial retinitis on the basis of clinical features and positive Weil-Felix test. The patient’s condition improved after treatment with oral antibiotics. The vasculature of the infarcted macula showed partial reperfusion late in the course of follow-up.

Systemic lupus erythematosus presenting with neuropsychiatric symptoms (NPSLE) along with posterior reversible encephalopathy syndrome (PRES) is rare. A young woman of 29 years presented with various neuropsychiatric symptoms along with low-grade fever, occasional headache, skin rash, arthralgias and gradually became non-ambulatory over last 6 months. After admission, she had an episode of generalised tonic-clonic seizure, followed by drowsiness. She was normotensive. Investigations revealed no evidence of any underlying infection, normal renal functions and electrolytes; but other parameters were supportive to a diagnosis of NPSLE. MRI brain showed vasogenic oedema characterised by symmetrical hyperintensities over posterior brain regions in T2 and fluid attenuated inversion recovery images with no restricted diffusion in diffusion weighted image suggestive of PRES. A diagnosis of NPSLE presenting with PRES, particularly in the absence of hypertension and abnormal renal functions was made, which is a rare presentation. She responded well to immunomodulatory therapy with methylprednisolone and monthly cyclophosphamide.

Background Although brain injury is known to be associated with feeding outcomes in preterm and unwell neonates, these groups are frequently excluded from studies of neonatal feeding development. This paper aims to identify the short-term feeding outcomes of infants with neonatal brain injury. Methods A retrospective cohort analysis was undertaken to ascertain the incidence of feeding disorders (full/partial tube feeding at 40 weeks) among infants with brain injury admitted to a UK neonatal unit between 2013 and 2017. Results 202 surviving infants with neonatal brain injury were included in the study. Feeding disorders were common among infants with brain injury (preterm 34%, term 34%) compared to infants without significant neurological comorbidities (preterm 9%, term 3%). The likelihood of feeding disorders increased with injury severity. Conclusions All infants with neonatal brain injury should have access to a specialist feeding therapist to maximise their feeding potential and provide support to families.

Background: Pregnancy induced hypertension( PIH) poses a great risk to the maternal and child health issues. Early diagnosis, assessment of prognosis, and appropriate management at a judicious moment can change its fate in many ways. Objective: To assess the usefulness of Doppler parameters to evaluate PIH and to predict its adverse perinatal outcome. Methodology: 49 pregnant patients were taken after applying criteria and undergone ultrasonography and doppler with follow up subsequently. Results: We found that total 63.26% of patients having abnormal Doppler parameters.Of these all of them had abnormal UA S/D ratio,26.53% had abnormal CPR,46.93% had abnormal UA PI and 48.97% had abnormal UA RI . So in our study most common abnormal Doppler parameter was alteration in UA S/D ratio. Conclusion: Doppler indices from the foetal circulation can reliably predict adverse perinatal outcome in an obstetric patient population with a high prevalence of complications such as pregnancy induced hypertension

Background: Indigenous Australians have a high rate of ischaemic heart disease (IHD). There is a paucity of local data for North Queensland regarding the clinical characteristics of Indigenous people who present to the emergency department (ED) with chest pain. The aim of the study is to compare the cardiovascular risk factors, social characteristics, and the clinical outcomes between Indigenous and non-Indigenous patients who presented with cardiac-related chest pain. Methods: This is a retrospective single-centre audit. The data was collected through chart reviews of chest pain presentations to the Townsville University Hospital Emergency Department from January to December 2017. We categorised the patients into Indigenous and non-Indigenous groups and compared their cardiac risk factors and social characteristics. We further classified the patients into three diagnosis groups and we measured the clinical outcomes in the patients with a diagnosis of cardiac-related chest pain. We used a data linkage to the Registry of Births, Deaths and Marriages for the death outcomes. A multivariable analysis was done to determine the risk of major adverse cardiac event (MACE) for Indigenous vs non-Indigenous patients. Results: Indigenous patients were over-represented making up 19.1% of the total cohort (compared with 11.1% of the North Queensland Indigenous population) and presented at a younger age (median age: 45 vs 52, p

Background: Malaria is endemic in many states of India. Though there are reports of maternal and congenital malaria from endemic areas, however, there remains a paucity of data from hilly terrains. The present study evaluated the prevalence, clinical and microbiological spectrum of maternal and congenital malaria at a tertiary health care facility in Northern India over a period of 18 months. Methods: In this observational study, mothers along with their newborns were evaluated for malaria by maternal, placental, and cord blood smear examination and rapid point-of-care diagnostic serological tests. Positive cases were confirmed by polymerase chain reaction. Mother-newborn duos were followed up till discharge from the hospital. Results: A total of 843 mothers delivered during the study period and were screened along with their newborns and placentae. A total of Ten (1.18%) mothers had evidence of malarial parasitemia (Plasmodium vivax, n=7 and Pl. falciparum, n=3), however, none of the placental and cord blood samples were positive for malaria. Overall, 127 (15.1%) neonates required admission in neonatal intensive care unit for various morbidities. Incidence of small for gestational age (SGA) was high (n=210; 24.9%). Multivariate logistic regression analysis demonstrated maternal malaria to be an independent contributor for SGA [Odds Ratio (95% Confidence Interval), 10.7 (2.06 - 49.72)]. However, only 2% variance of SGA could be explained by maternal malaria alone. Conclusions: We report an encouragingly lower incidence of maternal malaria in mothers attending for delivery and a ‘Zero’ incidence for placental and congenital malaria during the study period as compared to national data (upto 7.4% in non-immune mothers), although maternal malaria could be a causative factor for SGA.

INH Preventive Therapy (IPT) substantially reduces the risk of incidence of TB disease in pediatric household contacts of TB patients. The National TB Elimination Program (NTEP) of India prescribes a daily regimen of Isoniazid to all under-6 pediatric contacts for 6 months duration. We conducted, this exploratory prospective study (June to Nov' 2020) to assess adherence to IPT and reasons for nonadherence among child contacts of microbiologically confirmed, drug sensitive, non-PLHIV Tuberculosis patients in Delhi, India. The study outcomes included the initiation, adherence and completion of IPT. The caregivers of the child TB contacts were interviewed face to face by the field investigator. The data were entered on EpiData 3.1 and analysed with IBM SPSS 25. The INH adherence was assessed in a total of 86 household child TB contacts. IPT had been initiated in 62 (72.1%) child TB contacts of which 61 (98.4%) received INH within 1 month of starting of ATT-DOTS therapy in the index TB patient of the household. Furthermore, the failure to initiate IPT was reported by 24 (27.9%) child TB contacts. Within the cohort of child TB contacts who were not initiated with IPT, the ATT-DOTS duration in the index-TB patient was ≥5 months in 18 (75%) cases, 1-2 months in 3 (12.5%) cases, and1 month in also 3 (12.5%) cases. Reasons for non-initiation (n = 24) were reported as refusal by the family in 12 (50%) cases mostly due to concern over side-effects of the drug, while non-provision of the drug by the DOTS provider was also observed in 12 (50%) cases. The mean (SD) INH adherence in the INH initiated cohort was 5.6 (2.0) (n = 62). Reasons for INH non-adherence were attributed to forgetfulness (n = 23, 37.1%), carelessness (n = 24, 38.7%), and intermittent stopping of the medication (n = 17, 27.4%) on the child falling sick, perceived drug side effects, and running out of drug stocks. INH non-adherence defined as at-least two missed INH doses in the previous 7 days was observed in 47 (54.7%) participants (n = 86). On bivariate analysis, none of the household sociodemographic characteristics showed any statistically significant association with the rate of INH non-adherence in the child TB contacts. The findings of the present study indicate the need to periodically assess adherence and persistence to IPT in the child TB contacts as high intermittent missed dosing rates can undermine the effectiveness of IPT in preventing incident disease.

BACKGROUND: The number of rotator cuff repairs performed worldwide is increasing every year. However, there are still controversies regarding when rehabilitation after surgery should start. OBJECTIVES: To assess and to compare clinical and biomechanical outcomes of patients who were randomised and allocated to early or conservative rehabilitation after rotator cuff repairs. METHODS: Twenty patients were randomised to two treatment groups. The biomechanical assessments were performed before surgery and at three and six months, consisting of 3D kinematics and muscle activity from 5 muscles (upper trapezius, anterior deltoid, middle deltoid, posterior deltoid and biceps brachii) from six movement tasks. In addition, the Oxford Shoulder Score and EQ-5D-5L were also recorded. At 12 months an ultrasound scan was performed to check the repair integrity. RESULTS: Overall, both groups had similar results for function and health-related quality of life. However, at six months patients in the early group had better range of motion (ROM) than those in the conservative group, especially for shoulder flexion (Early: median = 152.1° vs Conservative: median = 140.0°). The number of re-tear events was higher in the early group (5 vs 1), and of these only two patients reported symptoms at 12 months. CONCLUSION: Early rehabilitation may improve ROM but it does not seem to be superior to a conservative management in improving function and quality of life. In addition, more re-tear events were observed in the early group. However, the results should be interpreted with caution due to the small sample size.

Background Older adults dually eligible for Medicare and Medicaid have particularly high food insecurity prevalence and health care use. Objective To determine whether participation in the Supplemental Nutrition Assistance Program (SNAP), which reduces food insecurity, is associated with lower health care use and cost for older adults dually eligible for Medicare and Medicaid. Design An incident user retrospective cohort study design was used. The association between participation in SNAP and health care use and cost using outcome regression was assessed and supplemented by entropy balancing, matching, and instrumental variable analyses. Setting North Carolina, September 2016 through July 2020. Participants Older adults (aged ≥65 years) dually enrolled in Medicare and Medicaid but not initially enrolled in SNAP. Measurements Inpatient admissions (primary outcome), emergency department visits, long-term care admissions, and Medicaid expenditures. Results Of 115 868 persons included, 5093 (4.4%) enrolled in SNAP. Mean follow-up was approximately 22 months. In outcome regression analyses, SNAP enrollment was associated with fewer inpatient hospitalizations (-24.6 [95% CI, -40.6 to -8.7]), emergency department visits (-192.7 [CI, -231.1 to -154.4]), and long-term care admissions (-65.2 [CI, -77.5 to -52.9]) per 1000 person-years as well as fewer dollars in Medicaid payments per person per year (-$2360 [CI, -$2649 to -$2071]). Results were similar in entropy balancing, matching, and instrumental variable analyses. Limitation Single state, no Medicare claims data available, and possible residual confounding. Conclusion Participation in SNAP was associated with fewer inpatient admissions and lower health care costs for older adults dually eligible for Medicare and Medicaid. Primary funding source National Institutes of Health.

BACKGROUND: Targeted therapies for advanced non-small cell lung cancer (NSCLC) with oncogenic drivers have caused a paradigm shift in care. Biomarker testing is needed to assess eligibility for these therapies. Pulmonologists often perform bronchoscopy, providing tissue for both pathologic diagnosis and biomarker analysis. We performed this survey to define the existing knowledge and practices regarding the pulmonologists’ role in biomarker testing for advanced NSCLC. RESEARCH QUESTION: What is the current knowledge and practice of pulmonologists regarding biomarker testing and targeted therapies in advanced NSCLC? STUDY DESIGN AND METHODS: This cross-sectional study was performed using an electronic survey of a random sample of 7,238 pulmonologists. Questions focused on diagnostic steps and biomarker analyses for NSCLC. RESULTS: A total of 453 pulmonologists responded. Respondents vary by reported lung cancer patient volume, ranging from 51% evaluating one to four new cases per month to 19% evaluating > 10 cases per month. Interventional training, academic practice setting, and higher volume of endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) were associated with increased knowledge of practice guidelines for the number of recommended passes during EBUS-TBNA (P < .05). Academic pulmonologists more commonly performed or referred for EBUS-TBNA than community pulmonologists (96% and 83%, respectively; P < .0005). Higher testing rates were associated with interventional training, academic setting, and the presence of an institutional policy, whereas lower testing rates were associated with general pulmonologists, practice in community settings, and lack of a guiding institutional policy (P < .05). INTERPRETATION: Substantial differences among pulmonologists’ evaluation of advanced NSCLC, variation in knowledge of available biomarkers and the importance of targeted therapies, and differences in institutional coordination likely lead to underutilization of biomarker testing. Interventional training appears to drive improved knowledge and practice for biomarker testing more than practice setting. Improvements are needed in tissue acquisition and interdisciplinary coordination to ensure universal and comprehensive testing for eligible patients.

We report the case of a 30-year-old normotensive, nondiabetic lady diagnosed case of Systemic Lupus Erythematosus(SLE); who came with the complaints of limb claudication. After clinical and lab evaluation she was diagnosed as a case of Takayasus Arteritis along with SLE. Though the co- existence of SLE and Takayasu’s Disease is very rare, we should search for the development of arterial occlusive diseases in SLE cases if the patient has got suspicious symptoms. J MEDICINE 2021; 22: 146-149

Context: Tuberculosis (TB) is a common infectious disorder in developing countries. A significant load of patients with extrapulmonary TB are diagnosed in our institute, mostly involving the spine. Aim: We aimed to present our experience in the surgical management of spinal TB. Setting and Design: This was a retrospective observational study. Materials and Methods: Seventy patients (year 2016–2018) who underwent surgical management with minimum of 1-year follow-up (17 patients lost during follow-up) were graded as per the American Spinal Injury Association (ASIA) grading system for neurological deficits. All were surgically treated with laminectomy and epidural abscess drainage/transpedicular debridement of granulation with/without spinal stabilization. Thoracic and lumbar cases were managed by posterior approach; among them, 12 patients who had no significant cord compression and good ASIA grade with facet involvement (requiring fusion) underwent minimally invasive pedicle screw fixation. Cervical cases were managed mostly by anterior approach. All patients received Anti-tubercular treatment (ATT) post operatively as per protocol postoperatively, following which magnetic resonance imaging (MRI) spine was done. Statistical Analysis: Data were analyzed using SPSS software version 18.0 (SPSS Inc. Released in 2009. PASW Statistics for Windows, version 18.0. Chicago, IL, USA: SPSS Inc.). The continuous variables were analyzed using descriptive statistics using mean and standard deviation. Results: The average age was 42.5 years. The most common location was thoracic (28 patients), followed by lumbar (20 patients), cervical (16 patients), and thoracolumbar (6 patients). Twenty patients had epidural abscess with cord compression. All patients who presented within 4 weeks of onset of symptoms showed a statistically significant improvement postsurgery. Sixteen patients with epidural abscess had good neurological recovery immediately after surgery (ASIA B to ASIA D/E). Four patients with epidural abscess with late presentation remained ASIA A after surgery. All patients had good fusion rates (follow-up X-ray) at 1 year. After ATT course completion, all patients had complete eradication of disease (MRI spine). Conclusion: Surgical treatment for spinal TB, if performed early (within 4 weeks) with good decompression, results in satisfactory clinical outcome with early improvement in the neurological deficits. Posterior approach to the spine with decompression and fixation gives good results, and minimally invasive procedures further help lessen muscle dissection, less pain, and early mobilization.

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding Bill & Melinda Gates Foundation.

A 24-year-old young man presented to us with total limbal stem cell deficiency (LSCD) in the right eye 1 year post ocular chemical burn. The patient subsequently underwent limbal biopsy in the healthy contralateral eye and autologous simple limbal epithelial transplantation in the right eye. The patient was followed up with sequential imaging of the cornea with high-resolution anterior segment optical coherence tomography (HR-ASOCT) for 3 years. The serial HR-ASOCT imaging in the operated eye showed regeneration of the epithelium from the limbal transplant over the human amniotic membrane (hAM) with integration of the transplant within the cornea with subepithelial retention of the hAM. Over the long-term follow-up, thinning of the hAM and thickening of the epithelium was noted. At 3 years, the cornea maintained an intact epithelium with no signs of recurrence of LSCD.

Hyperparathyroidism leading to hypercalcaemia is a rare cause of acute pancreatitis with debatable association. The diagnosis of hyperparathyroidism is frequently overlooked or delayed as symptoms are non-specific and serum calcium is not routinely measured in acute pancreatitis. Early diagnosis and treatment of hyperparathyroidism may reduce the chances of complications. We report a 35-year-old woman, who was admitted with recurrent episodes of acute pancreatitis. She was previously diagnosed with gall-stone induced acute pancreatitis, had undergone laparoscopic cholecystectomy, but the recurrence of acute pancreatitis suggested an alternative aetiology and provoked extensive investigations. Serum calcium was found to be elevated. No additional risk factor for pancreatitis was found. Further workup revealed primary hyperparathyroidism, which was due to a functioning parathyroid adenoma. She has undergone parathyroidectomy followed by an uneventful recovery. She subsequently conceived and is now in her first trimester, without any recurrence of acute pancreatitis since her surgery.

Background India is home to a large number of thalassemic children. Despite malnutrition being an essential determinant of their therapeutic goals and quality of life (QoL), it was hardly ever explored. With this background, this study aimed to estimate the proportion of β-thalassemia major (β-TM) children experiencing malnutrition, its attributes, and impact on their QoL. Methods This cross-sectional, hospital-based, analytical observational study was conducted among 328 β-TM children attending the thalassemia day care unit of a medical college from May 2016 to April 2017, with a structured schedule. Data were analyzed following appropriate statistical methods using SPSS statistical package ver. 16.0 (SPSS Inc., Chicago, IL, USA). Results Among the study participants, 48.2% were malnourished with a mean body mass index of 13.9 kg/m2 . In the multivariable logistic regression model, participants' age (adjusted odds ratio [AOR], 1.15; 95% confidence interval [CI], 1.02-1.29), caste (AOR, 2.11; 95% CI, 1.23-3.60), mothers' educational level (AOR, 2.05; 95% CI, 1.22- 3.44), blood transfusion frequency (AOR, 1.25; 95% CI, 1.16-1.31), and palpable spleen size (AOR, 1.22; 95% CI, 1.08-1.37) were significant predictors of malnutrition after adjusting for pre-transfusion hemoglobin level and hemolytic facies status. In multiple linear regression analysis, malnutrition negatively impacted total QoL (unstandardized beta [standard error], -4.4 [1.7]; P=0.009) and various domains of the study participants except the social and school domains adjusted for age, sex, caste, place of residence, parents' educational level, and socioeconomic status. Conclusion Almost half of the study participants had malnutrition. Malnutrition had a negative impact on their QoL.

Background CH5126766 (also known as VS-6766, and previously named R05126766), a novel MEK-pan-RAF inhibitor, has shown antitumour activity across various solid tumours; however, its initial development was limited by toxicity. We aimed to investigate the safety and toxicity profile of intermittent dosing schedules of CH5126766, and the antitumour activity of this drug in patients with solid tumours and multiple myeloma harbouring RAS-RAF-MEK pathway mutations. Methods We did a single-centre, open-label, phase 1 dose-escalation and basket dose-expansion study at the Royal Marsden National Health Service Foundation Trust (London, UK). Patients were eligible for the study if they were aged 18 years or older, had cancers that were refractory to conventional treatment or for which no conventional therapy existed, and if they had a WHO performance status score of 0 or 1. For the dose-escalation phase, eligible patients had histologically or cytologically confirmed advanced or inetastatic solid tumours. For the basket doseexpansion phase, eligible patients had advanced or metastatic solid tumours or multiple myeloma harbouring RAS-RAF-MEK pathway mutations. During the dose-escalation phase, we evaluated three intermittent oral schedules (28-day cycles) in patients with solid tumours: (1) 4.0 mg or 3.2 mg CH5126766 three times per week; (2) 4.0 mg CH5126766 twice per week; and (3) toxicity-guided dose interruption schedule, in which treatment at the recommended phase 2 dose (4.0 mg CH5126766 twice per week) was de-escalated to 3 weeks on followed by 1 week off if patients had prespecified toxic effects (grade 2 or worse diarrhoea, rash, or creatinine phosphokinase elevation). In the basket dose-expansion phase, we evaluated antitumour activity at the recommended phase 2 dose, determined from the dose-escalation phase, in biomarker-selected patients. The primary endpoints were the recommended phase 2 dose at which no more than one out of six patients had a treatment-related dose-limiting toxicity, and the safety and toxicity profile of each dosing schedule. The key secondary endpoint was investigator-assessed response rate in the dose-expansion phase. Patients who received at least one dose of the study drug were evaluable for safety and patients who received one cycle of the study drug and underwent baseline disease assessment were evaluable for response. This trial is registered with ClinicalTrials.gov, NCT02407509. Findings Between June 5,2013, and Jan 10,2019,58 eligible patients were enrolled to the study: 29 patients with solid tumours were included in the dose-escalation cohort and 29 patients with solid tumours or multiple myeloma were included in the basket dose-expansion cohort (12 non-small-cell lung cancer, five gynaecological malignancy, four colorectal cancer, one melanoma, and seven multiple myeloma). Median follow-up at the time of data cutoff was 2.3 months (IQR 1.6-3.5). Dose-limiting toxicities included grade 3 bilateral retinal pigment epithelial detachment in one patient who received 4.0 mg CH5126766 three times per week, and grade 3 rash (in two patients) and grade 3 creatinine phosphokinase elevation (in one patient) in those who received 3.2 mg CH5126766 three times per week. 4.0 mg CH5126766 twice per week (on Monday and Thursday or Tuesday and Friday) was established as the recommended phase 2 dose. The most common grade 3-4 treatment-related adverse events were rash (11 [19%] patients), creatinine phosphokinase elevation (six [11%1), hypoalbuminaemia (six [11%]), and fatigue (four [7%1). Five (9%) patients had serious treatment-related adverse events. There were no treatment-related deaths. Eight (14%) of 57 patients died during the trial due to disease progression. Seven (27% [95% CI 11.6-47.8]) of 26 response-evaluable patients in the basket expansion achieved objective responses. Interpretation To our knowledge, this is the first study to show that highly intermittent schedules of a RAF-MEK inhibitor has antitumour activity across various cancers with RAF-RAS-MEK pathway mutations, and that this inhibitor is tolerable. CH5126766 used as a monotherapy and in combination regimens warrants further evaluation. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

Context The effect of physiological changes in night-time cortisol and glucagon on endogenous glucose production (EGP) and nocturnal glycemia are unknown. Objective To determine the effects of changes in cortisol and glucagon on EGP during the night. Design Two overnight protocols were conducted. In Protocol 1, endogenous cortisol was blocked with metyrapone and hydrocortisone infused either at constant (constant) or increasing (variable) rates to mimic basal or physiological nocturnal cortisol concentrations. In Protocol 2, endogenous glucagon was blocked with somatostatin and exogenous glucagon was infused at either basal or elevated rates to mimic nocturnal glucagon concentrations observed in nondiabetic (ND) and type 2 diabetes (T2D) individuals. EGP was measured using [3-3H] glucose and gluconeogenesis estimated with 2H2O in all studies. Setting Mayo Clinic Clinical Research Trials Unit, Rochester, MN, US. Participants In Protocol 1, 34 subjects (17 ND and 17 T2D) and in Protocol 2, 39 subjects (21 ND and 18 T2D) were studied. Main Outcome Measures Endogenous glucose production Results EGP, gluconeogenesis, and glycogenolysis were higher with variable than with constant cortisol at 7 am in T2D subjects. In contrast, nocturnal EGP did not differ in ND subjects between variable and constant cortisol. While elevated glucagon increased EGP, glycogenolysis, and gluconeogenesis in ND, the data in T2D subjects indicated that EGP and gluconeogenesis but not glycogenolysis were higher during the early part of the night. Conclusion Nocturnal hyperglucagonemia, but not physiological rise in cortisol, contributes to nocturnal hyperglycemia in T2D due to increased gluconeogenesis.

Background: Sorafenib for advanced hepatocellular carcinoma (HCC) is dose adjusted by toxicity. Preliminary studies have suggested an association between plasma concentrations of sorafenib and its main metabolite (M2) and clinical outcomes. This study aimed to validate these findings and establish target values for sorafenib trough concentrations. Methods: Patients with advanced HCC were prospectively recruited within a multicenter phase II study (SORAMIC). Patients with blood samples available at trough level were included for this pharmacokinetic (PK) substudy. Trough plasma concentrations of sorafenib and its main metabolite (M2) were associated with sorafenib-related toxicity and overall survival (OS). Results: Seventy-four patients were included with a median OS of 19.7 months (95% CI 16.1–23.3). Patients received sorafenib for a median of 51 weeks (IQR 27–62) and blood samples were drawn after a median of 25 weeks (IQR 10–42). Patients had a median trough concentration of 3217 ng/ml (IQR 2166–4526) and 360 ng/ml (IQR 190–593) with coefficients of variation of 65% and 146% for sorafenib and M2, respectively. Patients who experienced severe sorafenib-related toxicity received a lower average daily dose (551 vs 730 mg/day, p = .003), but showed no significant differences in sorafenib (3298 vs 2915 ng/ml, p = .442) or M2 trough levels (428 vs 283 ng/ml, p = .159). Trough levels of sorafenib or M2 showed no significant association with OS. Conclusions: In patients with advanced HCC treated with sorafenib, the administered dose, trough levels of sorafenib or M2, and clinical outcomes were poorly correlated. Toxicity-adjusted dosing remains the standard for sorafenib treatment.

[Background]: Currently, data on treatment, outcome, and prognostic factors in children with tuberculous meningitis (TBM) in Europe are limited. To date, most existing data on TBM originate from adult studies, or studies conducted in low-resource settings., [Methods]: We designed a multicenter, retrospective study involving 27 pediatric healthcare institutions in 9 European countries via an established pediatric TB research network, before and after the 2014 revision of World Health Organization (WHO) dosing recommendations., [Results]: Of 118 children, 39 (33.1%) had TBM grade 1, 68 (57.6%) grade 2, and 11 (9.3%) grade 3. Fifty-eight (49.1%) children received a standard 4-drug treatment regimen; other commonly used drugs included streptomycin, prothionamide, and amikacin. Almost half of the patients (48.3%; 56/116) were admitted to intensive care unit, with a median stay of 10 (interquartile range [IQR] 4.5–21.0) days. Of 104 children with complete outcome data, 9.6% (10/104) died, and only 47.1% (49/104) recovered fully. Main long-term sequelae included spasticity of 1 or more limbs and developmental delay both in 19.2% (20/104), and seizure disorder in 17.3% (18/104). Multivariate regression analyses identified microbiological confirmation of TBM, the need for neurosurgical intervention, and mechanical ventilation as risk factors for unfavorable outcome., [Conclusions]: There was considerable heterogeneity in the use of TB drugs in this cohort. Despite few children presenting with advanced disease and the study being conducted in a high-resource setting, morbidity and mortality were high. Several risk factors for poor outcome were identified, which may aid prognostic predictions in children with TBM in the future., TPtbnet is supported by the Deutsche Gesellschaft für Internationale Zusammenarbeit. M. Te. was supported by a Clinical Lectureship provided by the UK National Institute for Health Research (NIHR), and by a grant from the Technology Strategy Board/Innovate UK. R. B. R. is funded by an NIHR Academic Clinical Lectureship at the London School of Hygiene & Tropical Medicine (grant number CL-2018-20-001). A. N.-J. was supported by Subvencions per a la Intensificació de Facultatius Especialistes (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016–2020; ref. SLT008/18/00193). O. N. is supported by Consejeria de Salud y Familias, Servicio Andaluz de Salud 2020 (grant number A1-0049-2020).

Introduction: The U.S. Department of Veterans Affairs (VA), in partnership with the Opioid Overdose Education and Naloxone Distribution (OEND) Program, implemented the National Academic Detailing Service to deliver naloxone education to providers with patients at-risk for opioid-related overdose. Methods: We administered a 26-item online survey to VA providers to explore their perceptions about prescribing naloxone for opioid overdose emergencies and their experience with academic detailing between August 2017 and April 2018. Responses were analyzed using descriptive statistics to (1) explore their current perceptions of naloxone prescribing and their experience with academic detailing, (2) identify differences across provider types [primary care providers (PCP), specialists, and others], and (3) assess perceived naloxone prescribing behavior change after an academic detailing visit. Results: Providers (N = 137) indicated that they were practicing at a level that was consistent with VA goals to promote take-home naloxone to reverse opioid-related overdose events. Average domain scores were similar across PCP, specialist, and other provider types. Specialists reported a higher average attitude domain score (+.56, P = .011) and perceived barriers domain score (+.82, P = .009) than PCPs. Most providers agreed that they prescribed naloxone more frequently due to academic detailing (53%) and indicated that they synthesized information from the academic detailer to change their naloxone prescribing practice (60%). Discussion: VA providers’ perceptions of take-home naloxone were aligned with current evidence-based practice. Moreover, providers reported increasing their naloxone prescribing and synthesizing OEND-related information after an academic detailing interaction. Understanding providers’ perceptions can be used to improve and enhance the academic detailing program’s effectiveness.

Background Sex differences in stroke outcomes have been noted, but whether this extends to stroke recurrence is unclear. We examined sex differences in recurrent stroke using data from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. Patients and methods We assessed the risk of recurrent stroke in women compared to men using data from the POINT trial. Adults >18 years old were randomized within 12 hours of onset of minor ischemic stroke or transient ischemic attack (TIA), and followed for up to 90 days for ischemic stroke, our primary outcome. We used Cox proportional hazards model adjusted for demographics and stroke risk factors to evaluate the association between sex and stroke recurrence. We used interaction term testing and prespecified subgroup analyses to determine if the association between sex and recurrent stroke differed by age (60 years old), locale (US versus non-US), and index event type (stroke versus TIA). Last, we evaluated whether sex modified the effect of common stroke risk factors on stroke recurrence. Results Of 4,881 POINT trial participants with minor stroke or high-risk TIA, 2,195 (45%) were women. During the 90-day follow-up period, 267 ischemic strokes occurred; 121 were in women and 146 in men. The cumulative risk of recurrent ischemic stroke was not significantly different among women (5.76%; 95% CI, 4.84%–6.85%) compared to men (5.67%; 95% CI, 4.83%–6.63%). Women were not at a different risk of recurrent ischemic stroke compared to men (hazard ratio [HR], 1.02; 95% CI, 0.80–1.30) in unadjusted models or after adjusting for covariates. However, there was a significant interaction of age with sex (P=0.04). Among patients Discussion and Conclusion Among patients with minor stroke or TIA, the risk of recurrent ischemic stroke and the impact of common stroke risk factors did not differ between men and women.

Background Post‐COVID multisystem hyperinflammatory syndrome in children (MISC) has clinical and laboratory similarities with Kawasaki disease (KD). Inflammatory markers like C‐reactive protein (CRP), interleukin 6 (IL6) as well as N‐terminal probrain natriuretic peptide (NT‐proBNP) are elevated in both. This study attempts a comparative analysis of the 3 markers in an attempt at early differentiation for planning appropriate management. Methodology This analytical study conducted at the Institute of Child Health, Kolkata, India compared the levels of the above 3 markers at admission between 72 patients with KD, 30% of whom had coronary artery lesions (CALs) collected over a period of 18 months (Jan 2017‐June 2018), with 71 MISC patients over a period of 6 months (July 2020‐December 2020). The non‐parametric Mann‐Whitney U test was used to test for similarity in distributions of the samples of CRP, NT‐proBNP and IL6 in KD and MISC patients using correction factor for similar ranks. The 3 parameters were compared using receiver operating characteristic (ROC) curve analysis. Results Mean IL6 value in KD was 83.22 pg/mL and in MISC 199.91 pg/mL, which was not found to be statistically significant (P = .322 > .05).However mean NT‐proBNP (914.91 pg/mL) with CRP level (96.32 mg/L) in KD was significantly lower (P 935.7 pg/mL and >99.55 mg/L respectively might act as a guide to differentiate between them.

Background Patient surveillance using repeated biomarker measurements presents an opportunity to detect and treat disease progression early. Frequent surveillance testing using biomarkers is recommended and routinely conducted in several diseases, including cancer and diabetes. However, frequent testing involves tradeoffs. Although surveillance tests provide information about current disease status, the complications and costs of frequent tests may not be justified for patients who are at low risk of progression. Predictions based on patients’ earlier biomarker values may be used to inform decision making; however, predictions are uncertain, leading to decision uncertainty. Methods We propose the Personalized Risk-Adaptive Surveillance (PRAISE) framework, a novel method for embedding predictions into a value-of-information (VOI) framework to account for the cost of uncertainty over time and determine the time point at which collection of biomarker data would be most valuable. The proposed sequential decision-making framework is innovative in that it leverages the patient’s longitudinal history, considers individual benefits and harms, and allows for dynamic tailoring of surveillance intervals by considering the uncertainty in current information and estimating the probability that new information may change treatment decisions, as well as the impact of this change on patient outcomes. Results When applied to data from cystic fibrosis patients, PRAISE lowers costs by allowing some patients to skip a visit, compared to an “always test” strategy. It does so without compromising expected survival, by recommending less frequent testing among those who are unlikely to be treated at the skipped time point. Conclusions A VOI-based approach to patient monitoring is feasible and could be applied to several diseases to develop more cost-effective and personalized strategies for ongoing patient care. Highlights In many patient-monitoring settings, the complications and costs of frequent tests are not justified for patients who are at low risk of disease progression. Predictions based on patient history may be used to individualize the timing of patient visits based on evolving risk. We propose Personalized Risk-Adaptive Surveillance (PRAISE), a novel method for personalizing the timing of surveillance testing, where prediction modeling projects the disease trajectory and a value-of-information (VOI)–based pragmatic decision-theoretic framework quantifies patient- and time-specific benefit-harm tradeoffs. A VOI-based approach to patient monitoring could be applied to several diseases to develop more personalized and cost-effective strategies for ongoing patient care.

Background: In the primary analysis of the phase 3 MAIA trial (median follow-up 28·0 months), a significant improvement in progression-free survival was observed with daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in transplantation-ineligible patients with newly diagnosed multiple myeloma. Here, we report the updated efficacy and safety results from a prespecified interim analysis for overall survival. Methods: MAIA is an ongoing, multicentre, randomised, open-label, phase 3 trial that enrolled patients at 176 hospitals in 14 countries across North America, Europe, the Middle East, and the Asia-Pacific region. Eligible patients were aged 18 years or older, had newly diagnosed multiple myeloma, had an Eastern Cooperative Oncology Group performance status score of 0–2, and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation because of their age (≥65 years) or comorbidities. Patients were randomly assigned (1:1) using randomly permuted blocks (block size 4) by an interactive web response system to receive 28-day cycles of intravenous daratumumab (16 mg/kg, once per week during cycles 1–2, once every 2 weeks in cycles 3–6, and once every 4 weeks thereafter) plus oral lenalidomide (25 mg on days 1–21 of each cycle) and oral dexamethasone (40 mg on days 1, 8, 15, and 22 of each cycle; daratumumab group) or lenalidomide and dexamethasone alone (control group). Randomisation was stratified by International Staging System disease stage, geographical region, and age. Neither patients nor investigators were masked to treatment assignment. The primary endpoint was progression-free survival, which was centrally assessed, and a secondary endpoint was overall survival (both assessed in the intention-to-treat population). The safety population included patients who received at least one dose of the study treatment. The results presented here are from a prespecified interim analysis for overall survival, for which the prespecified stopping boundary was p=0·0414. This trial is registered with ClinicalTrials.gov, NCT02252172. Findings: Between March 18, 2015, and Jan 15, 2017, 952 patients were assessed for eligibility, of whom 737 patients were enrolled and randomly assigned to the daratumumab group (n=368) or the control group (n=369). At a median follow-up of 56·2 months (IQR 52·7–59·9), median progression-free survival was not reached (95% CI 54·8–not reached) in the daratumumab group versus 34·4 months (29·6–39·2) in the control group (hazard ratio [HR] 0·53 [95% CI 0·43–0·66]; p15%) grade 3 or higher treatment-emergent adverse events were neutropenia (197 [54%] patients in the daratumumab group vs 135 [37%] patients in the control group), pneumonia (70 [19%] vs 39 [11%]), anaemia (61 [17%] vs 79 [22%]), and lymphopenia (60 [16%] vs 41 [11%]). Serious adverse events occurred in 281 (77%) patients in the daratumumab group and 257 (70%) patients in the control group. Treatment-related deaths occurred in 13 (4%) patients in the daratumumab group and ten (3%) patients in the control group. Interpretation: Daratumumab plus lenalidomide and dexamethasone increased overall survival and progression-free survival in patients ineligible for stem-cell transplantation with newly diagnosed multiple myeloma. There were no new safety concerns. Our results support the frontline use of daratumumab plus lenalidomide and dexamethasone for patients with multiple myeloma who are ineligible for transplantation. Funding: Janssen Research & Development.

Background A randomised trial designed to compare three and two doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India was converted to a cohort study after suspension of HPV vaccination in trials by the Indian Government. In this Article, the revised aim of the cohort study was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years post vaccination. Methods In the randomised trial, unmarried girls aged 10-18 years were recruited from nine centres across India and randomly assigned to either two doses or three doses of the quadrivalent HPV vaccine (Gardasil [Merck Sharp & Dohme, Whitehouse Station, NJ, USA]; 0·5 mL administered intramuscularly). After suspension of recruitment and vaccination, the study became a longitudinal, prospective cohort study by default, and participants were allocated to four cohorts on the basis of the number vaccine doses received per protocol: the two-dose cohort (received vaccine on days 1 and 180 or later), three-dose cohort (days 1, 60, and 180 or later), two-dose default cohort (days 1 and 60 or later), and the single-dose default cohort. Participants were followed up yearly. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Married participants were screened for cervical cancer as they reached 25 years of age. Unvaccinated women age-matched to the married vaccinated participants were recruited to serve as controls. Vaccine efficacy against persistent HPV 16 and 18 infections (the primary endpoint) was analysed for single-dose recipients and compared with that in two-dose and three-dose recipients after adjusting for imbalance in the distribution of potential confounders between the unvaccinated and vaccinated cohorts. This trial is registered with ISRCTN, ISRCTN98283094, and ClinicalTrials.gov, NCT00923702. Findings Vaccinated participants were recruited between Sept 1, 2009, and April 8, 2010 (date of vaccination suspension), and followed up over a median duration of 9·0 years (IQR 8·2-9·6). 4348 participants had three doses, 4980 had two doses (0 and 6 months), and 4949 had a single dose. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95·4% (95% CI 85·0-99·9) in the single-dose default cohort (2135 women assessed), 93·1% (77·3-99·8) in the two-dose cohort (1452 women assessed), and 93·3% (77·5-99·7) in three-dose recipients (1460 women assessed). Interpretation A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and 18, the genotypes responsible for nearly 70% of cervical cancers, to that provided by two or three doses. Funding Bill & Melinda Gates Foundation.

Melanoma is a kind of skin cancer which occurs due to too much exposure of melanocyte cells to the dangerous UV radiations, that gets damaged and multiplies uncontrollably. This is popularly known as malignant melanoma and is comparatively less heard of than certain other types of skin cancers; however it can be more detrimental as it swiftly spreads if not detected and attended at a primary stage. The differentiation between benign and melanocytic lesions sometimes may be confusing, but the symptoms of the disease can reasonably be discriminated by a profound investigation of its histopathological and clinical characteristics. In the recent past, Deep Convolutional Neural Networks (DCNNs) have advanced in accomplishing far better results. The necessity of the present day is to have faster and computationally efficient mechanisms for diagnosis of the deadly disease. This paper makes an effort to showcase a deep learning-based ‘Keras’ algorithm, which is established on the implementation of DCNNs to investigate melanoma from dermoscopic and digital pictures and provide swifter and more accurate result as contrasted to standard CNNs. The main highlight of this paper, basically stands in its incorporation of certain ambitious notions like the segmentation performed by a culmination of a moving straight line with a sequence of points and the application of the concept of triangular neutrosophic number based on uncertain parameters. The experiment was done on a total of 40,676 images obtained from four commonly available datasets— International Symposium on Biomedical Imaging (ISBI) 2017, International Skin Imaging Collaboration (ISIC) 2018, ISIC 2019 and ISIC 2020 and the end result received was indeed motivating. It attained a Jac score of 86.81% on ISIC 2020 dataset and 95.98%, 95.66% and 94.42% on ISBI 2017, ISIC 2018 and ISIC 2019 datasets, respectively. The present research yielded phenomenal output in most instances in comparison to the pre-defined parameters with the similar types of works in this field.

Purpose The purpose of this study was to evaluate the prevalence of SARS-CoV-2 in human postmortem ocular tissues of asymptomatic donors and its implications on our eye banking protocols. Methods The expression of SARS-CoV-2 RNA was assessed by reverse transcription-polymerase chain reaction in corneal rims and conjunctival tissues from 100 donors who were found suitable for transplantation as per the donor screening guidelines of the Global Alliance of Eye Bank Associations. The donor's clinical history and cause of death were assessed for secondary analysis. Results Of 200 ocular tissues (100 corneal and 100 conjunctival) from the same 1 eye of 100 surgical-intended donors, between September 2020 and April 2021, the overall positivity rate for SARS-CoV-2 was ~1% (2/200). Both the ocular samples that tested positive were conjunctival biopsies (2/100, 2%), whereas corneal samples were negative (0/100, 0%) in both donors. The causes of donor death were trauma in 51 donors, suicide in 33, cardiac arrest in 7, electric shock in 5, metabolic cause in 2, malignancy in 1, and snake bite in 1. None of the donors had a medical history suggestive of COVID infection or possible contact. None of the recipients from the donors were reported to have any systemic adverse event after keratoplasty until the follow-up of 6 weeks. Conclusions The overall prevalence of SARS-CoV-2 was 1% (2% for conjunctival and 0% for corneal samples, P value = 0.5) in the donors who were found suitable for cornea recovery and transplantation. The findings of exceptionally low positive rates in our samples validate the criticality of history-based donor screening and do not support the necessity of postmortem PCR testing as a criterion for procurement and subsequent use for corneal transplantation.

Gait is a behavioural biometric which sometimes changes due to diseases but it is still a strong identification metric that is widely used in forensic works, state biometric preserve sectors, and medical laboratories. Gait analysis sometimes helps to identify person’s present mental state which reflects on physiological therapy for improved biological system. There are various gait measurement forms which expand the research area from crime detection to medical enhancement. Many research works have been done so far for gait recognition. Many researchers focused on skeleton image of people to extract gait features and many worked on stride length. Various sensors have been used to detect gait in various light forms. This paper is a brief survey of works on gait recognition, collected from various sources of science and technology literature. We have discussed few efficient models that worked best as well as we have discussed about few data sets available.

Using a matched case control design conducted at MRC Gambia in 2015, we measured vitamin D levels in pairs of asymptomatic children with discordant tuberculin skin test status despite the same sleeping proximity to the same adult TB index case. Median ages of groups (infected; 10.0 years, uninfected 8.8 years) were not significantly different (p = 0.13). Mean vitamin D levels were 2.05 ng/mL (95% CI − 0.288 to 4.38) higher in 24 highly TB-exposed uninfected children compared with 24 matched highly TB-exposed infected children (p = 0.08). The findings warrant further investigation in larger studies to understand the implications and significance. Conclusion: Vitamin D levels were higher in TB-uninfected children compared with TB-infected despite equal high exposure to a TB case. What is Known:• Paediatrics TB represents one of the leading causes of child death globally.• Current literature shows an inconsistent relationship between vitamin D deficiency and increased risk of TB disease however a large Phase 3 trial of vitamin D supplementation in (largely vitamin D deficient) Mongolian children did not find any association with TB infection rates. What is New:• This study adds to the literature in a vitamin D sufficient paediatric population whereby children with equal exposure to a household TB case with no evidence of TB infection have higher levels of vitamin D compared with matched children with TB infection.

The possibility of a massive oil spill in the Red Sea is increasingly likely. The Safer, a deteriorating oil tanker containing 1.1 million barrels of oil, has been deserted near the coast of Yemen since 2015 and threatens environmental catastrophe to a country presently in a humanitarian crisis. Here, we model the immediate public health impacts of a simulated spill. We estimate that all of Yemen’s imported fuel through its key Red Sea ports would be disrupted and that the anticipated spill could disrupt clean-water supply equivalent to the daily use of 9.0–9.9 million people, food supply for 5.7–8.4 million people and 93–100% of Yemen’s Red Sea fisheries. We also estimate an increased risk of cardiovascular hospitalization from pollution ranging from 5.8 to 42.0% over the duration of the spill. The spill and its potentially disastrous impacts remain entirely preventable through offloading the oil. Our results stress the need for urgent action to avert this looming disaster. The possibility of a huge oil spill off the coast of Yemen, already in crisis, is increasingly likely. This study projects the likely spill extent and impacts to public health, food, water and air.

Pyometra is one of the most common diseases in intact bitches. The aim of the present communication was to evaluate the effectiveness of medical treatment for the close pyometra in a bitch. The diagnosis of pyometra was made by correlating the history and clinical signs with the findings of abdominal palpation and ultrasonography. The physiological, haematological and biochemical parameters were evaluated before and after treatment. Treatment of canine pyometra using a combination of progesterone receptor blocker (Mifepristone), anti-prolactin (Cabergoline) along with supportive therapy showed very efficacious alternative option over traditional ovario-hysterectomy (OHE) or which are critical for operative procedure.

To describe clinical and multimodal imaging characteristics of punctate inner retinal toxoplasmosis (PIRT) as an atypical presentation of ocular toxoplasmosis (OT).Retrospective review of OT cases ...

Objective: Till date, a very few prospective studies have examined the association between serum homocysteine levels and the risk of stroke and stroke subtypes in Indian populations. Methods: A prospective, case - control study of Indian subjects 10–90 years of age was conducted using frozen serum samples from 103 participants in cardiovascular risk surveys collected from December 2017 to November 2018. By the end of 103, we identified 55 incidents of severe strokes, one control subject per case was selected by matching for sex, age, community, year of serum storage, and fasting status. Serum total homocysteine levels were measured by Cobas c-311. Results: Compared with control subjects, total (n_206), hemorrhagic (n_106), and ischemic (n_87) strokes had higher geometric mean values of total homocysteine and higher proportions of homocysteine −25.0 μ mol/L. Homocysteine was estimated after adjustment for body mass index, smoking, alcohol intake, hypertension, and other cardiovascular risk factors. The excess risk of total and ischemic strokes did not vary significantly according to sex, age, smoking status, or hypertensive status. Conclusion: High total homocysteine concentrations were associated with the increased risk of total stroke, more specifically ischemic stroke) Capsuloganglionic and frontoparietal infarct (8 each)., among Indian men and women.

This article is the work product of the Continuous Ketone Monitoring Consensus Panel, which was organized by Diabetes Technology Society and met virtually on April 20, 2021. The panel consisted of 20 US-based experts in the use of diabetes technology, representing adult endocrinology, pediatric endocrinology, advanced practice nursing, diabetes care and education, clinical chemistry, and bioengineering. The panelists were from universities, hospitals, freestanding research institutes, government, and private practice. Panelists reviewed the medical literature pertaining to ten topics: (1) physiology of ketone production, (2) measurement of ketones, (3) performance of the first continuous ketone monitor (CKM) reported to be used in human trials, (4) demographics and epidemiology of diabetic ketoacidosis (DKA), (5) atypical hyperketonemia, (6) prevention of DKA, (7) non-DKA states of fasting ketonemia and ketonuria, (8) potential integration of CKMs with pumps and automated insulin delivery systems to prevent DKA, (9) clinical trials of CKMs, and (10) the future of CKMs. The panelists summarized the medical literature for each of the ten topics in this report. They also developed 30 conclusions (amounting to three conclusions for each topic) about CKMs and voted unanimously to adopt the 30 conclusions. This report is intended to support the development of safe and effective continuous ketone monitoring and to apply this technology in ways that will benefit people with diabetes.

Weight loss is an effective strategy for the management of hypertension, and bariatric surgery is the most effective weight loss and maintenance strategy for obesity. The importance of bariatric surgery in the long-term management of hypertension and which operation is most effective is less clear. We compared the effectiveness of vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) for remission and relapse of hypertension after surgery in the ENGAGE CVD cohort study (Effectiveness of Gastric Bypass Versus Gastric Sleeve for Cardiovascular Disease). Operations were done by 23 surgeons across 9 surgical practices. Hypertension remission and relapse were assessed in each year of follow-up beginning 30 days and up to 5 years postsurgery. We used a local instrumental variable approach to account for selection bias in the choice of VSG or RYGB. The study population included 4964 patients with hypertension at the time of surgery (n=3186 VSG and n=1778 RYGB). At 1 year, 27% of patients with RYGB and 28% of patients with VSG achieved remission. After 5 years, without accounting for relapse, 42% of RYGB and 43% of VSG patients had experienced hypertension remission. After accounting for relapse, only 17% of RYGB and 18% of VSG patients remained in remission 5 years after surgery. There were no statistically significant differences between VSG and RYGB for hypertension remission, relapse, or mean systolic and diastolic blood pressure at any time during follow-up.

Introduction: [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 has emerged as a promising radiopharmaceutical for targeting PSMA in metastatic castrate-resistant prostate carcinoma (mCRPC). ...

Background The randomized, double-blind, phase 3 ASPECT-NP trial evaluated the efficacy of 3 g of ceftolozane/tazobactam (C/T) versus 1 g of meropenem infused every 8 h for 8 to 14 days for treatment of adults with hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP). We assessed the probability of target attainment and compared efficacy outcomes from ASPECT-NP in participants with augmented renal clearance (ARC) versus those with normal renal function. Methods Baseline renal function was categorized as normal renal function (creatinine clearance 80–130 mL/min) or ARC (creatinine clearance > 130 mL/min). Population pharmacokinetic models informed Monte Carlo simulations to assess probability of target attainment in plasma and pulmonary epithelial lining fluid. Outcomes included 28-day all-cause mortality and clinical cure and per-participant microbiologic cure rates at the test-of-cure visit. Results A > 99% and > 80% probability of target attainment was demonstrated for ceftolozane and tazobactam, respectively, in simulated plasma and epithelial lining fluid. Within treatment arms, 28-day all-cause mortality rates in participants with normal renal function (C/T, n = 131; meropenem, n = 123) and ARC (C/T, n = 96; meropenem, n = 113) were comparable (data comparisons presented as rate; treatment difference [95% CI]) (C/T: normal renal function, 17.6%; ARC, 17.7%; 0.2 [− 9.6 to 10.6]; meropenem: normal renal function, 20.3%; ARC, 17.7%; − 2.6 [− 12.6 to 7.5]). Clinical cure rates at test-of-cure were also comparable across renal function groups within treatment arms (C/T: normal renal function, 57.3%; ARC, 59.4%; − 2.1 [− 14.8 to 10.8]; meropenem: normal renal function, 59.3%; ARC, 57.5%; 1.8 [− 10.6 to 14.2]). Per-participant microbiologic cure rates at test-of-cure were consistent across renal function groups within treatment arms (C/T: normal renal function, 72.2% [n/N = 70/97]; ARC, 71.4% [n/N = 55/77]; 0.7 [− 12.4 to 14.2]; meropenem: normal renal function, 75.0% [n/N = 66/88]; ARC, 70.0% [n/N = 49/70]; 5.0 [− 8.7 to 19.0]). Conclusions C/T and meropenem resulted in 28-day all-cause mortality, clinical cure, and microbiologic cure rates that were comparable between participants with ARC or normal renal function. In conjunction with high probability of target attainment, these results confirm that C/T (3 g) every 8 h is appropriate in patients with HABP/VABP and ARC. Trial registration ClinicalTrials.gov identifier: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11.

The inflammatory potential of diet, assessed by Empirical Dietary Inflammatory Pattern (EDIP), may play a crucial role in the development of metabolic syndrome (MetS). However, limited research on this relationship is available. We hypothesized that EDIP is positively associated with MetS and its components. This longitudinal study included 1,177 participants (526 with type 1 diabetes mellitus (T1DM) and 651 without) from the Coronary Artery Calcification in Type 1 Diabetes study. Dietary assessment and anthropometric and biochemical measurements were assessed at baseline and 14-year follow-up. MetS status was defined using the Harmonization criteria. EDIP scores were computed based on a food frequency questionnaire. Generalized linear mixed models were applied and subgroup analyses were performed by diabetes status. Mean age of study participants was 38 years and 48% were male at baseline. EDIP was positively associated with MetS (β(T3 versus T1)=0.81, p

Guided by a national cancer plan (2010–19), Morocco made significant investments in improving breast cancer detection and treatment. A breast cancer pattern-of-care study was conducted to document the socio-demographic profiles of patients and tumour characteristics, measure delays in care, and assess the status of dissemination and impact of state-of-the-art management. The retrospective study conducted among 2120 breast cancer patients registered during 2008–17 at the two premier-most oncology centres (Centre Mohammed VI or CM-VI and Institut National d’Oncologie or INO) also measured temporal trends of the different variables. Median age (49 years) and other socio-demographic characteristics of the patients remained constant over time. A significant improvement in coverage of the state-financed health insurance scheme for indigent populations was observed over time. Median interval between onset of symptoms and first medical consultation was 6 months with a significant reduction over time. Information on staging and molecular profile were available for more than 90% and 80% of the patients respectively. Approximately 55% of the patients presented at stage I/II and proportion of triple-negative cancers was 16%; neither showing any appreciable temporal variation. Treatment information was available for more than 90% of the patients; 69% received surgery with chemotherapy and/or radiation. Treatment was tailored to stage and molecular profiles, though breast conservation therapy was offered to less than one-fifth. When compared using the EUSOMA quality indicators for breast cancer management, INO performed better than CM-VI. This was reflected in nearly 25% difference in 5-year disease-free survival for early-stage cancers between the centres., Highlights • Morocco achieved significant progress in quality of breast cancer care in last decade. • Access delay reduced significantly over time but was still high at median 6 months. • More than 80% breast cancer patients had complete molecular profiles. • Many gaps still exist in quality of treatment

Background: Endometriosis is defined by the presence of endometrial glands and stroma outside the usual location. Rectal involvement is rare. It can mimic malignancy and pose a diagnostic and opera...

Glucose-responsive insulin delivery systems have the potential to improve quality of life for individuals with diabetes by improving blood sugar control and limiting the risk of hypoglycemia. However, systems with desirable insulin release kinetics and high loading capacities have proven difficult to achieve. Here, we report the development of electrostatic complexes (ECs) comprised of insulin, a polycation, and glucose oxidase (GOx). Under normoglycemic physiological conditions, insulin carries a slight negative charge and forms a stable EC with the polycation. In hyperglycemia, the encapsulated glucose-sensing enzyme GOx converts glucose to gluconic acid and lowers the pH of the microenvironment, causing insulin to adopt a positive charge. Thus, the electrostatic interactions are disrupted, and insulin is released. Using a model polycation, we conducted molecular dynamics simulations to model these interactions, synthesized ECs with > 50% insulin loading capacity, and determined in vitro release kinetics. We further showed that a single dose of ECs can provide a glycemic profile in streptozotocin-induced diabetic mice that mimics healthy mice over a 9 h period with 2 glucose tolerance tests.

There are several reasons why pediatric dentist should understand the development of dental occlusion. One of the major objectives of orthodontic treatment is to correct occlusal problems. Much of the need for this treatment could be avoided if children received the proper dental care at earlier ages. Development of occlusion is a genetically and environmentally conditioned process, which shows a great deal of individual variations, and consequently, for the development of an acceptable occlusion, quite a remarkable co-ordination of different events is necessary. The development of occlusion depends on a number of conditions, like muscular pressure, habits, availability of space, etc. This development is coincident with the growth of all tissues associated with the dental apparatus, including the nose, maxillary sinuses, facial bones and muscles. Failure in one part of the development process may lead to anomalies, or else may be compensated for by other developmental processes. Thus Proper care of the developing deciduous and permanent teeth, both at the dental office and at home, is important for the appropriate development of occlusion. and timely diagnosis followed by appropriate interception can prevent any developing malocclusion. This article is an overview which depicts (1) periods of development of occlusion, (2) outline the development of normal occlusion in the pediatric patient and (3) explain what occlusion of the teeth is and why it is important.

Introduction: With the rise of COVID-19 pandemic, the health staffs have faced resistance and disrespect by the society. They have been stigmatised unnecessarily that has been resulted from fear and poor knowledge of general population regarding spread of COVID-19 infection. Objective: To estimate the proportion of health care workers whoexperienced social stigma during COVID 19 pandemic and to determine the association of social stigma with their socio-demographic and other background characteristics. Method: A descriptive type of observational study, cross-sectional in design was carried out amonghealth care workers(HCWs) of a tertiary care hospital in Kolkataduring the COVID-19 lockdown period (19th May 2020– 20th July 2020) using a pre-designed, pre-tested, structured schedule. By simple random sampling, 422 HCWs were selected and 410 of them had given consent to participate in this study. MS Excel 2010 and SPSS v20.0 were used for data entry and binary logistic regression. Results: About 52.68 % had experienced ‘Significant Social Stigma’, 32.92% experienced ‘Insignificant Social Stigma’ and only 14.39% had ‘no stigma’. Age groups of 25-40years and mode of transport by hospital vehicle had significant association with social stigma.Conclusion: More than half of the study population experienced “Significant Social Stigma”. The HCWs who were travelling by hospital vehicles from home to attend their duties and HCWs of younger age group were stigmatised in different ways.

Globally hike in temperature provokes the heat waves, results in heat stress and becomes a silent health peril to the existing population. Today, heat stress or climatological stress is one of the dominant pathological conditions which comes in focus when the body means of handling its thermoregulatory function starts to fail, show its associated symptoms followed by eventual loss of consciousness and finally death. The condition of heat stress along with intermittent dehydration worsens the renal damage and enhances the risk of Acute Kidney Injury (AKI), results in chronic kidney disease (CKD). Therefore, CKD comes up as a leading cause of death, specifically in those patients having long-lasting medical conditions like heart problem, hypertension, diabetes and obesity etc. High temperature, work rate, humidity and working time wearing accessories, all become mitigating factors for causing heat stress. Distinguish molecular ups and downs specifically decrease production of uric acid (polyol-fructokinase pathway), increase ROS (oxidative stress), intracellular Ca2+ overload (mitochondrial dysfunctioning) and decrease NO (vascular endothelial dysfunctioning) has been responsible for the severe outcomes of Climatological Nephropathy (CN) or Heat Stress Nephropathy (HSN). However, prevention is the best approach to dealing with heat-related illness, therefore, the Government established some valuable policies as a preventive measures. This review epitomizes the alarming outcomes of the heat stress followed by recurrent dehydration and also enlightened the global talk of HSN, pathogenicity, molecular level peculiarities and recommended measures for HSN. Key words: Acute Kidney Injury, Chronic Kidney Disease, Nephropathy, Mitochondrial Dysfunctioning.

Optimal resection of breast tumors requires removing cancer with a rim of normal tissue while preserving uninvolved regions of the breast. Surgical and pathological techniques that permit rapid molecular characterization of tissue could facilitate such resections. Mass spectrometry (MS) is increasingly used in the research setting to detect and classify tumors and has the potential to detect cancer at surgical margins. Here, we describe the ex vivo intraoperative clinical application of MS using a liquid micro-junction surface sample probe (LMJ-SSP) to assess breast cancer margins. In a midpoint analysis of a registered clinical trial, surgical specimens from 21 women with treatment naïve invasive breast cancer were prospectively collected and analyzed at the time of surgery with subsequent histopathological determination. Normal and tumor breast specimens from the lumpectomy resected by the surgeon were smeared onto glass slides for rapid analysis. Lipidomic profiles were acquired from these specimens using LMJ-SSP MS in negative ionization mode within the operating suite and post-surgery analysis of the data revealed five candidate ions separating tumor from healthy tissue in this limited dataset. More data is required before considering the ions as candidate markers. Here, we present an application of ambient MS within the operating room to analyze breast cancer tissue and surgical margins. Lessons learned from these initial promising studies are being used to further evaluate the five candidate biomarkers and to further refine and optimize intraoperative MS as a tool for surgical guidance in breast cancer.