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Although multiparametric magnetic resonance imaging (MRI) has high sensitivity, its lower specificity leads to a high prevalence of false-positive lesions requiring biopsy.To develop and externally validate a scoring system for MRI-detected Prostate Imaging Reporting and Data System (PIRADS)/Likert ≥3 lesions containing clinically significant prostate cancer (csPCa).The multicentre Rapid Access to Prostate Imaging and Diagnosis (RAPID) pathway included 1189 patients referred to urology due to elevated age-specific prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE); April 27, 2017 to October 25, 2019.Visual-registration or image-fusion targeted and systematic transperineal biopsies for an MRI score of ≥4 or 3 + PSA density ≥0.12 ng/ml/ml.Fourteen variables were used in multivariable logistic regression for Gleason ≥3 + 4 (primary) and Gleason ≥4 + 3, and PROMIS definition 1 (any ≥4 + 3 or ≥6 mm any grade; secondary). Nomograms were created and a decision curve analysis (DCA) was performed. Models with varying complexity were externally validated in 2374 patients from six international cohorts.The five-item Imperial RAPID risk score used age, PSA density, prior negative biopsy, prostate volume, and highest MRI score (corrected c-index for Gleason ≥3 + 4 of 0.82 and 0.80-0.86 externally). Incorporating family history, DRE, and Black ethnicity within the eight-item Imperial RAPID risk score provided similar outcomes. The DCA showed similar superiority of all models, with net benefit differences increasing in higher threshold probabilities. At 20%, 30%, and 40% of predicted Gleason ≥3 + 4 prostate cancer, the RAPID risk score was able to reduce, respectively, 11%, 21%, and 31% of biopsies against 1.8%, 6.2%, and 14% of missed csPCa (or 9.6%, 17%, and 26% of foregone biopsies, respectively).The Imperial RAPID risk score provides a standardised tool for the prediction of csPCa in patients with an MRI-detected PIRADS/Likert ≥3 lesion and can support the decision for prostate biopsy.In this multinational study, we developed a scoring system incorporating clinical and magnetic resonance imaging characteristics to predict which patients have prostate cancer requiring treatment and which patients can safely forego an invasive prostate biopsy. This model was validated in several other countries.

Cyclin-dependent kinase 6 (EC 2.7.11.22) play significant roles in numerous biological processes and triggers cell cycle events. CDK6 controlled the transcriptional regulation. A dysregulated function of CDK6 is linked with the development of progression of multiple tumor types. Thus, it is considered as an effective drug target for cancer therapy. Based on the direct roles of CDK4/6 in tumor development, numerous inhibitors developed as promising anti-cancer agents. CDK4/6 inhibitors regulate the G1 to S transition by preventing Rb phosphorylation and E2F liberation, showing potent anti-cancer activity in several tumors, including HR+/HER2- breast cancer. CDK4/6 inhibitors such as abemaciclib, palbociclib, and ribociclib, control cell cycle, provoke cell senescence, and induces tumor cell disturbance in pre-clinical studies. Here, we discuss the roles of CDK6 in cancer along with the present status of CDK4/6 inhibitors in cancer therapy. We further discussed, how structural features of CDK4/6 could be implicated in the design and development of potential anti-cancer agents. In addition, the therapeutic potential and limitations of available CDK4/6 inhibitors are described in detail. Recent pre-clinical and clinical information for CDK4/6 inhibitors are highlighted. In addition, combination of CDK4/6 inhibitors with other drugs for the therapeutic management of cancer are discussed.

Background Postoperative recurrence [POR] of Crohn’s disease following ileocolonic resection is common. The impact of immediate postoperative intra-abdominal septic complications [IASC] on endoscopic and surgical recurrence has not been elucidated. Aims To evaluate if IASC is associated with an increased risk for endoscopic and surgical POR. Methods This was a retrospective study of adult Crohn’s disease patients undergoing ileocolonic resection with primary anastomosis between 2009 and 2020. IASC was defined as anastomotic leak or intra-abdominal abscess within 90 days of the date of surgery. Multivariable logistic and Cox proportional hazard modelling were performed to assess the impact of IASC on endoscopic POR [modified Rutgeerts’ score ≥ i2b] at index postoperative ileocolonoscopy and long-term surgical recurrence. Results In 535 Crohn’s disease patients [median age 35 years, 22.1% active smokers, 35.7% one or more prior resection] had an ileocolonic resection with primary anastomosis. A minority of patients [N = 47; 8.8%] developed postoperative IASC. In total, 422 [78.9%] patients had one or more postoperative ileocolonoscopies, of whom 163 [38.6%] developed endoscopic POR. After adjusting for other risk factors for postoperative recurrence, postoperative IASC was associated with significantly greater odds (adjusted odds ratio [aOR]: 2.45 [1.23–4.97]; p = 0.01) and decreased time (adjusted hazards ratio [aHR]: 1.60 [1.04–2.45]; p = 0.03] to endoscopic POR. Furthermore, IASC was associated with increased risk (aOR: 2.3 [1.04–4.87] p = 0.03) and decreased survival-free time [aHR: 2.53 [1.31–4.87]; p = 0.006] for surgical recurrence. Conclusion IASC is associated with an increased risk for endoscopic and surgical POR of Crohn’s disease. Preoperative optimization to prevent IASC, in addition to postoperative biological prophylaxis, may help reduce the risk for endoscopic and surgical POR.

Mahmoud M Habibullah,1,2 Syam Mohan,3,4 Nabeel Kashan Syed,5 Hafiz A Makeen,5 Qazi Mohammad Sajid Jamal,6 Hani Alothaid,7 Farkad Bantun,8 Alaa Alhazmi,1,2 Ali Hakamy,2,9 Yahia A Kaabi,1 Ghalia Samlan,10 Mohtashim Lohani,11 Neelaveni Thangavel,12 Mohamed Ahmed Al-Kasim5 1Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 2SMIRES for Consultation in Specialized Medical Laboratories, Jazan University, Jazan, Saudi Arabia; 3Substance Abuse and Toxicology Research Center, Jazan University, Jazan, Saudi Arabia; 4School of Health Science, University of Petroleum and Energy Studies, Dehradun, Uttarakhand, India; 5Pharmacy Practice Research Unit, Department of Clinical Pharmacy, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia; 6Department of Health Informatics, College of Public Health and Health Informatics, Qassim University, Al Bukayriyah, Saudi Arabia; 7Department of Basic Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al-Baha, Saudi Arabia; 8Department of Microbiology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 9Respiratory Therapy Department, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 10Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia; 11Emergency Medical Services Department, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 12Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jazan University, Jazan, Saudi ArabiaCorrespondence: Mahmoud M Habibullah, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Al Maarefah Road, Jazan, Saudi Arabia, Tel +966 556644205, Email mhabibullah@jazanu.edu.saIntroduction: Numerous drugs with potent toxicity against cancer cells are available for treating malignancies, but therapeutic efficacies are limited due to their inefficient tumor targeting and deleterious effects on non-cancerous tissue. Therefore, two improvements are mandatory for improved chemotherapy 1) novel delivery techniques that can target cancer cells to deliver anticancer drugs and 2) methods to specifically enhance drug efficacy within tumors. The loading of inert drug carriers with anticancer agents and peptides which are able to bind (target) tumor-related proteins to enhance tumor drug accumulation and local cytotoxicity is a most promising approach.Objective: To evaluate the anticancer efficacy of Chitosan nanoparticles loaded with human growth hormone hGH fragment 176– 191 peptide plus the clinical chemotherapeutic doxorubicin in comparison with Chitosan loaded with doxorubicin alone.Methods: Two sets of in silico experiments were performed using molecular docking simulations to determine the influence of hGH fragment 176– 191 peptide on the anticancer efficacy of doxorubicin 1) the binding affinities of hGH fragment 176– 191 peptide to the breast cancer receptors, 2) the effects of hGH fragment 176– 191 peptide binding on doxorubicin binding to these same receptors. Further, the influence of hGH fragment 176– 191 peptide on the anticancer efficacy of doxorubicin was validated using viability assay in Human MCF-7 breast cancer cells.Results: In silico analysis suggested that addition of the hGH fragment to doxorubicin-loaded Chitosan nanoparticles can enhance doxorubicin binding to multiple breast cancer protein targets, while photon correlation spectroscopy revealed that the synthesized dual-loaded Chitosan nanoparticles possess clinically favorable particle size, polydispersity index, as well as zeta potential.Conclusion: These dual-loaded Chitosan nanoparticles demonstrated greater anti-proliferative activity against a breast cancer cell line (MCF-7) than doxorubicin-loaded Chitosan. This dual-loading strategy may enhance the anticancer potency of doxorubicin and reduce the clinical side effects associated with non-target tissue exposure.Keywords: anticancer potency, nanoparticles, cytotoxicity, docking analysis

Spinacia oleracea (SO) exhibits radical scavenging and tyrosinase inhibition activity indicating potential as a depigmenting agent.To develop and characterize a stable emulsified system containing SO extract through ultra-high pressure homogenization, evaluate skin permeability, and enumerate in vivo performance in terms of melanin index, skin spots analysis, and related skin physiological parameters.Free radical scavenging and tyrosinase inhibition potential of SO extract was quantified through DPPH radical scavenging and mushroom tyrosinase inhibition assay, respectively. Six SO extract loaded ultra-high pressure emulsified systems (UHSO) were developed using ultra-high pressure homogenizer and assessed for size and polydispersity index (PDI). Among the prepared formulations, the optimized formulation (UHSO6) was subjected to 90 days stability studies performed at 8°C, 25°C, 40°C, and 40°C+75% RH (relative humidity) for organoleptic features, pH, and rheology. Ex vivo skin permeability studies were performed on abdominal skin from male albino rat. Changes in skin physiological parameters were evaluated in healthy female volunteers (n = 13) for 12 weeks utilizing mexameterSO extract exhibited promising antioxidant (88±0.0096%) and tyrosinase inhibition potential (90.6 ± 0.0015 mg of Kojic Acid Eq/g of extract). Optimized UHSO was found to be stable with respect to stability evaluation, globule size (1110 nm), zeta potential (-27.6), and PDI (0.34). Ex vivo skin permeation of UHSO was significantly higher than SO loaded coarse emulsion. Moreover, the formulation showed a significant decrease in skin melanin, spot count, and spot % area, whereas skin hydration index was improved significantly.Stable SO extract loaded emulsion system was successfully developed by a novel, cost-effective technique of ultra-high pressure homogenization which showed improved performance in terms of skin permeation and other skin physiological parameters.

The link between gender nonconformity and psychopathology may be due in part to negative childhood experiences resulting from other people’s reactions to gender nonconformity. The aim of this study was to test whether recalled perceived levels of parental and peer acceptance of childhood gender nonconforming behaviors and play mediate the relationship of childhood gender nonconformity with depression and social anxiety in adulthood. We also tested whether this relationship was moderated by sexual orientation and, among gay men, whether internalized homophobia was an additional mediator. All variables were measured in a large sample of male participants using self-report (n = 449 gay men, age: M = 27.8 years, SD = 6.69; andn = 296 heterosexual men, age: M = 27.4 years, SD = 6.57) in Poland. Gay men reported more childhood gender nonconformity than heterosexual men. The relationship between gender nonconformity and depressive symptoms as well as social anxiety symptoms was significant in both gay and heterosexual men. Among gay men, this relationship was partially mediated by peer but not parental acceptance of the measured aspects of gender nonconformity and internalized homophobia. Among heterosexual men, recalled perceived parental acceptance of gender nonconformity partially mediated the relationship between gender nonconformity and depressive and social anxiety symptoms. Our findings were partially in line with those found in Western European and North American samples. Although the two groups differed in their recalled perceived gender nonconformity, they did not differ in their depression or social anxiety scores. Nevertheless, childhood gender nonconformity may be an indirect risk associated with mental health symptoms, irrespective of sexual orientation. Its higher prevalence among nonheterosexual individuals makes it a particular risk for this group.

Animal studies support RCT findings of improved liver function and short-term benefits using repurposed Granulocyte Colonic Stimulating Factor GCSF in adults with decompensated cirrhosis. We describe the protocol for phase 2 RCT of sequential Kasai-GCSF under an FDA-approved IND to test that GCSF improves early bile flow and post-Kasai biliary atresia BA clinical outcome. Immediate post-Kasai neonates, age 15-180 days, with biopsy-confirmed type 3 BA, without access to early liver transplantation, will be randomized 1:1 to standard of care SOC + GCSF at 10 ug/kg in 3 daily doses within 4 days of Kasai vs SOC + NO-GCSF (ClinicalTrials.gov NCT0437391). They will be recruited from children's hospitals in Vietnam, Pakistan and one US center. The primary objective is to demonstrate that GCSF decreases the proportion of subjects with a 3-month post-Kasai serum Total Bilirubin ≥ 34 umol/L by 20%, (for a = 0.05, b = 0.80, i.e., calculated sample size of 218 subjects). The secondary objectives are to demonstrate that the frequency of post-Kasai cholangitis at 6-month and 24-month transplant-free survival are improved. The benefits are that GCSF is an affordable BA adjunct therapy, especially in developing countries, to improve biliary complications, enhance quality of liver and survival while diminishing costly liver transplantation.Clinical trial registration: A phase 1 for GCSF dose and safety determination under ClinicalTrials.gov identifier NCT03395028 was completed in 2019. The current Phase 2 trial was registered under NCT04373941.

Risk prediction models for cardiovascular disease (CVD) death developed from patients without vascular disease may not be suitable for myocardial infarction (MI) survivors. Prediction of mortality risk after MI may help to guide secondary prevention. Using national electronic record data from the Veterans Health Administration 2002 to 2012, we developed risk prediction models for CVD death and all-cause death based on 5-year follow-up data of 100,601 survivors of MI using Cox proportional hazards models. Model performance was evaluated using a cross-validation approach. During follow-up, there were 31,622 deaths and 12,901 CVD deaths. In men, older age, current smoking, atrial fibrillation, heart failure, peripheral artery disease, and lower body mass index were associated with greater risk of death from CVD or all-causes, and statin treatment, hypertension medication, estimated glomerular filtration rate level, and high body mass index were significantly associated with reduced risk of fatal outcomes. Similar associations and slightly different predictors were observed in women. The estimated Harrell's C-statistics of the final model versus the cross-validation estimates were 0.77 versus 0.77 in men and 0.81 versus 0.77 in women for CVD death. Similarly, the C-statistics were 0.75 versus 0.75 in men, 0.78 versus 0.75 in women for all-cause mortality. The predicted risk of death was well calibrated compared with the observed risk. In conclusion, we developed and internally validated risk prediction models of 5-year risk for CVD and all-cause death for outpatient survivors of MI. Traditional risk factors, co-morbidities, and lack of blood pressure or lipid treatment were all associated with greater risk of CVD and all-cause mortality.

BACKGROUND: Globally, neonatal mortality accounts for almost half of all deaths in children younger than 5 years. Aetiological agents of neonatal infection are difficult to identify because the clinical signs are non-specific. Using data from the Aetiology of Neonatal Infections in south Asia (ANISA) cohort, we aimed to describe the spectrum of infectious aetiologies of acute neonatal illness categorised post-hoc using the 2015 WHO case definitions of critical illness, clinical severe infection, and fast breathing only. METHODS: Eligible infants were aged 0-59 days with possible serious bacterial infection and healthy infants enrolled in the ANISA study in Bangladesh, India, and Pakistan. We applied a partial latent class Bayesian model to estimate the prevalence of 27 pathogens detectable on PCR, pathogens detected by blood culture only, and illness not attributed to any infectious aetiology. Infants with at least one clinical specimen available were included in the analysis. We assessed the prevalence of these aetiologies according to WHO's case definitions of critically ill, clinical severe infection, and infants with late onset, isolated fast breathing. For the clinical severe definition, we compared the prevalence of signs by bacterial versus viral aetiology. FINDINGS: There were 934 infants (992 episodes) in the critically ill category, 3769 (4000 episodes) in the clinical severe infection category, and 738 (771 episodes) in the late-onset isolated fast breathing category. We estimated the proportion of illness attributable to bacterial infection was 32·7% in infants in the critically ill group, 15·6% in the clinical severe infection group, and 8·8% among infants with late-onset isolated fast breathing group. An infectious aetiology was not identified in 58-82% of infants in these categories. Among 4000 episodes of clinical severe infection, those with bacterial versus viral attribution had higher proportions of hypothermia, movement only when stimulated, convulsions, and poor feeding. INTERPRETATION: Our modelled results generally support the revised WHO case definitions, although a revision of the most severe case definition could be considered. Clinical criteria do not clearly differentiate between young infants with and without infectious aetiologies. Our results highlight the need for improved point-of-care diagnostics, and further study into neonatal deaths and episodes with no identified aetiology, to ensure antibiotic stewardship and targeted interventions. FUNDING: The Bill and Melinda Gates Foundation.

There are conflicting data assessing the impact of isolated post-operative anastomotic inflammation on future disease progression. The aim of this study was to determine the relative risk of severe disease progression in post-operative Crohn's disease (CD) patients with isolated anastomotic disease.Retrospective cohort study of adult CD patients undergoing ileocolonic resection between 2009 and 2020. Patients with a post-operative ileocolonoscopy ≤18 months from surgery and ≥1 subsequent ileocolonoscopy were included. Disease activity was assessed using the modified Rutgeerts' score (RS). Primary outcome was severe endoscopic progression, defined as i3 or i4 disease, on immediate subsequent ileocolonoscopy and during entire post-operative follow-up. Secondary outcome was surgical recurrence.One hundred and ninety-nine CD patients had an ileocolonoscopy ≤18 months from surgery, index RS of i0-i2b and ≥1 subsequent ileocolonoscopy. At index ileocolonoscopy, 34.7% had i0 disease, 16.1% i1, 24.6% i2a and 24.6% i2b. On multivariable logistic regression, i2b disease was associated with severe endoscopic progression compared to i0 or i1 (aOR 5.53; P 0.001) and i2a disease patients (aOR 2.63; P = 0.03). However, i2a disease did not confer increased risk compared to i0 or i1 disease (P = 0.09). Furthermore, i2b patients experienced severe endoscopic progression significantly earlier than i0 or i1 disease (aHR 4.68; P 0.001), whereas i2a disease did not differ from i0 or i1 disease (P = 0.25). Surgical recurrence was not associated with index RS i0-i2b (P = 0.86).Post-operative ileal disease recurrence, not isolated anastomotic inflammation, confers increased risk for severe endoscopic disease progression. Location of CD recurrence may impact optimal management strategies.

Lean NAFLD may differ from NAFLD found in overweight or obese patients. We used the UK biobank to conduct a cross-sectional study that examined features that distinguish lean NAFLD from overweight or obese NAFLD.MRI-PDFF data were used to identify patients with NAFLD, with NAFLD defined as PDFF ≥ 5%. BMI patient cohorts were identified, with lean defined as a BMI 25, and overweight or obese defined as a BMI ≥ 25. Variables of interest to fatty liver disease, including single nucleotide polymorphisms, were chosen from the UK biobank data portal. Logistic regression was used to generate models predictive of NAFLD in each cohort.1007 patients had NAFLD, and of these, 871 had BMI ≥ 25, and 136 BMI 25. Factors associated with NAFLD in patients with BMI 25 included male sex, white blood cell count, red blood cell count, triglycerides, ALT, creatinine, visceral adipose tissue, rs58542926 T, and rs738409 G. In contrast, factors associated with NAFLD in patients with BMI ≥ 25 included male sex, waist circumference, HDL cholesterol, triglycerides, serum glucose, ALT, creatinine, urate, visceral adipose tissue, rs1260326 T, rs1044498 C, rs58542926 T, and rs738409 G. For lean patients, our generated prediction score had an AUC of 0.92, sensitivity of 0.90 and specificity of 0.81. For overweight or obese patients, the prediction score had an AUC of 0.86, sensitivity of 0.87 and specificity of 0.70.Our analysis suggests that lean and overweight or obese NAFLD are distinct entities. We have developed a risk score incorporating both clinical and genetic factors that accurately classify lean patients with NAFLD, with the potential to serve as a tool for screening purposes.

Background overview and rationale We co-developed a multi-component virtual care solution (TtLIVE) for the home mechanical ventilation (HMV) population using the aTouchAway™ platform (Aetonix). The TtLIVE intervention includes (1) virtual home visits; (2) customizable care plans; (3) clinical workflows that incorporate reminders, completion of symptom profiles, and tele-monitoring; and (4) digitally secure communication via messaging, audio, and video calls; (5) Resource library including print and audiovisual material. Objectives and brief methods Our primary objective is to evaluate the TtLIVE intervention compared to a usual care control group using an eight-center, pragmatic, parallel-group single-blind (outcome assessors) randomized controlled trial. Eligible patients are children and adults newly transitioning to HMV in Ontario, Canada. Our target sample size is 440 participants (220 each arm). Our co-primary outcomes are a number of emergency department (ED) visits in the 12 months after randomization and change in family caregiver (FC) reported Pearlin Mastery Scale score from baseline to 12 months. Secondary outcomes also measured in the 12 months post randomization include healthcare utilization measured using a hybrid Ambulatory Home Care Record (AHCR-hybrid), FC burden using the Zarit Burden Interview, and health-related quality of life using the EQ-5D. In addition, we will conduct a cost-utility analysis over a 1-year time horizon and measure process outcomes including healthcare provider time using the Care Coordination Measurement Tool. We will use qualitative interviews in a subset of study participants to understand acceptability, barriers, and facilitators to the TtLIVE intervention. We will administer the Family Experiences with Care Coordination (FECC) to interview participants. We will use Poisson regression for a number of ED visits at 12 months. We will use linear regression for the Pearlin Mastery scale score at 12 months. We will adjust for the baseline score to estimate the effect of the intervention on the primary outcomes. Analysis of secondary outcomes will employ regression, causal, and linear mixed modeling. Primary analysis will follow intention-to-treat principles. We have Research Ethics Board approval from SickKids, Children’s Hospital Eastern Ontario, McMaster Children’s Hospital, Children’s Hospital-London Health Sciences, Sunnybrook Hospital, London Health Sciences, West Park Healthcare Centre, and Ottawa Hospital. Discussion This pragmatic randomized controlled single-blind trial will determine the effectiveness and cost-effectiveness of the TtLIVE virtual care solution compared to usual care while providing important data on patient and family experience, as well as process measures such as healthcare provider time to deliver the intervention. Trial registration ClinicalTrials.gov NCT04180722. Registered on November 27, 2019.

Natural products have been the focus of biomedical and pharmaceutical research to develop new therapies in recent years. 2-methoxy-6-acetyl-7-methyljuglone (2-methoxystypandrone, MAM) a natural bioactive juglone derivative, is known to have various levels of pharmacotherapeutic efficacies as an anti-inflammatory, anticancer, antioxidant, antimicrobial, and anti-HIV activities. MAM fights cancer progression by inducing apoptosis, necroptosis and deregulating signaling pathways through H2O2-induced JNK/iNOS/NO and MAPK, ERK1/2 pathways, JNK activation, and the RIP1/RIP3 complex. In this review, we summarize the pharmacological importance of MAM in the field of drug discovery. Furthermore, this review not only emphasizes the medicinal properties of MAM, but also discusses its potential efficacy in future medicinal products.

COVID-19 has created shortages of personal protective equipment. In resource-constrained situations, limited cycles of disinfection and extended use of gloves is recommended by the U.S. Centers for Disease Control and Prevention to conserve supplies. However, these guidelines are based on limited evidence. In this study, serial cycles of hand hygiene were performed on gloved hands using an ethanol-based hand rub (six and 10 cycles), 0.1% sodium hypochlorite (bleach) solution (10 cycles), or soap and water (10 cycles) on latex and nitrile medical exam gloves from the United States and India. A modified water-leak test evaluated glove integrity after repeated applications of these disinfecting agents. When aggregated, dilute bleach demonstrated the lowest difference between treatment and control arms: -2.5 percentage points (95% CI: -5.3 to 0.3) for nitrile, 0.6 percentage points (95% CI: -2.6 to 3.8) for non-powdered latex. For U.S.-purchased gloves tested with six and 10 applications of ethanol-based hand rub, the mean difference in failure risk between treatment and control gloves was within the prespecified non-inferiority margin of five percentage points or less, though some findings were inconclusive since outside the margin. The aggregated difference in failure risk between treatment and control was 3.5 percentage points (0.6 to 6.4) for soap and water, and 2.3 percentage points (-0.5 to 5.0) and 5.0 percentage points (1.8 to 8.2) for 10 and 6 applications of ethanol-based hand rub, respectively. Most leaks occurred in the interdigital webs (35%) and on the fingers (34%). This indicates that some combinations of glove types and disinfection methods may allow for extended use. Ten applications of dilute bleach solution had the least impact on glove integrity. However, the majority of glove and exposure combinations were inconclusive. Additional testing of specific glove and disinfectant combinations may inform future strategies to guide extended use during glove shortages. Additional considerations, not evaluated here, include duration of use, disinfectant chemical permeation, and the effects of hand temperature, movement, and manipulation of instruments on glove integrity.

Parkinson's disease (PD) is the second leading neurodegenerative disease worldwide. Important advances in monitoring and treatment have been made in recent years. This article reviews literature on utility of smartphone applications in monitoring PD symptoms that may ultimately facilitate improved patient care, and on movement modulation as a potential therapeutic.Novel mobile phone applications can provide one-time and/or continuous data to monitor PD motor symptoms in person or remotely, that may support precise therapeutic adjustments and management decisions. Apps have also been developed for medication management and treatment.Smartphone applications provide a wide array of platforms allowing for meaningful short-term and long-term data collection and are also being tested for intervention. However, the variability of the applications and the need to translate complicated sensor data may hinder immediate clinical applicability. Future studies should involve stake-holders early in the design process to promote usability and streamline the interface between patients, clinicians, and PD apps.

Purpose: We aimed to examine if same-sex partnership in men is associated with cardiovascular disease (CVD) and whether this relationship can be explained by accumulated risk factors in late adoles...

OBJECTIVES: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors.METHODS: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors.RESULTS: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32).CONCLUSION: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years.

Background: An estimated 7 million episodes of severe newborn infections occur annually worldwide, with half a million newborn deaths, most oc-curring in low-and middle-income countries. Whilst injectable antibiotics are necessary to treat the infection, supportive care is also crucial in ending preventable mortality and morbidity. This study uses multi-country data to assess gaps in coverage, quality, and documentation of supportive care, considering implications for measurement. Methods: The EN-BIRTH study was conducted in five hospitals in Bangla-desh, Nepal, and Tanzania (July 2017-July 2018). Newborns with an ad-mission diagnosis of clinically-defined infection (sepsis, meningitis, and/or pneumonia) were included. Researchers extracted data from inpatient case notes and interviews with women (usually the mothers) as the primary fam-ily caretakers after discharge. The interviews were conducted using a struc-tured survey questionnaire. We used descriptive statistics to report coverage of newborn supportive care components such as oxygen use, photothera-py, and appropriate feeding, and we assessed the validity of measurement through survey-reports using a random-effects model to generate pooled estimates. In this study, key supportive care components were assessment and correction of hypoxaemia, hyperbilirubinemia, and hypoglycaemia. Results: Among 1015 neonates who met the inclusion criteria, 89% had an admission clinical diagnosis of sepsis. Major gaps in documentation and care practices related to supportive care varied substantially across the par-ticipating hospitals. The pooled sensitivity was low for the survey-reported oxygen use (47%; 95% confidence interval (CI) = 30%-64%) and moderate for phototherapy (60%; 95% CI = 44%-75%). The pooled specificity was high for both the survey-reported oxygen use (85%; 95% CI = 80%-89%) and phototherapy (91%; 95% CI = 82%-97%). Conclusions: The women's reports during the exit survey consistently un-derestimated the coverage of supportive care components for managing infection. We have observed high variability in the inpatient documents across facilities. A standardised ward register for inpatient small and sick newborn care may capture selected supportive care data. However, tracking the detailed care will require standardised individual-level data sets linked to newborn case notes. We recommend investments in assessing the im-plementation aspects of a standardised inpatient register in resource-poor settings.

Backgrounds:. Azithromycin mass drug administration (MDA) is a key part of the strategy for controlling trachoma. This systematic review aimed to comprehensively summarize the present studies of azithromycin MDA on trachoma; provide an overview of the impact of azithromycin MDA on trachoma in different districts; and explore the possible methods to enhance the effectiveness of azithromycin MDA in hyperendemic districts. Methods:. PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov were searched up to February 2021 with no language restriction. Studies reporting the effect of azithromycin MDA on trachoma were included. Mathematical modeling studies, animal studies, case reports, and reviews were excluded. The trachomatous inflammation-follicular (TF) 30.0%), especially with baseline TF >50.0%, annual MDA was unable to achieve the TF 10.0% is not appropriate for all eligible districts.

Introduction Cochlear implantation (CI) is an underutilized treatment for hearing loss in the United States for reasons which remain unclear. This study explores self-identified barriers to CI employing a survey of adults who qualified for CI. Methods A single-institutional review of CI candidates between December 2010 and December 2018 was performed to identify patients who did not pursue surgery. A 21-question survey was developed, aimed at rating patients' concerns regarding CI, including surgical risks, adaptation, costs, time commitment, loss of residual hearing, and lack of benefit, among others. Current hearing aid usage and familiarity with other CI users were also analyzed. The survey was administered to patients who did not pursue CI and a control group who eventually did pursue CI, via email or telephone. Results There were 199 patients who initially did not pursue CI. Fifty-two survey responses were received, comprised of 27 patients who did not pursue CI and 25 patients who did. A belief that CI would not significantly improve the ability to communicate was the most common reported barrier, followed by the postoperative recovery process, risks of surgery, and risks of losing music appreciation. Anesthetic risk and cost were the least important reasons not to pursue CI. Half of patients reported concerns regarding the period of adjustment with the CI. Conclusion The decision not to pursue CI despite eligibility is multifactorial and includes concern for minimal hearing benefit and perioperative risks. These factors should be taken into consideration when counseling patients on CI surgery.

Background Donor-derived cell-free DNA (dd-cfDNA) in plasma is an established noninvasive biomarker for allograft injury and rejection. A single-nucleotide polymorphism (SNP)–based massively multiplexed polymerase chain reaction methodology can be used to quantify dd-cfDNA in kidney transplant recipients. In this study we describe our clinical experience in using a SNP-based dd-cfDNA assay for the management of active rejection in renal transplant recipients. Methods To assess the clinical utility of a clinically available SNP-based massively multiplexed polymerase chain reaction dd-cfDNA assay, we analyzed biopsy data contemporaneous to dd-cfDNA results at 33 participating clinics and calculated the rate of rejection in dd-cfDNA-matched biopsy results. Results A total of 1347 dd-cfDNA test samples from 879 patients were accessioned from October 3, 2019, to November 2, 2020. The dd-cfDNA testing classified 25.2% (340/1347) of samples as high-risk (dd-cfDNA fraction ≥ 1%). Clinical follow-up was available for 32.1% (109/340) of the high-risk results, which included samples from 28 patients with definitive biopsy results within 2 weeks of dd-cfDNA testing. Pathology reports indicated a 64% (18/28) rate of active rejection in biopsy result–matched samples. Total cfDNA measurements indicated a skewed distribution and a correlation with dd-cfDNA-derived patient risk classification. Conclusions This is the first report showing the impact of dd-cfDNA on patient management in a multicenter real-world clinical cohort. The data indicate that incorporating dd-cfDNA testing into practice may improve physician decision making regarding renal allograft recipients.

The Social Health Protection Initiative (SHPI) was introduced initially in Pakistan in Khyber Pakhtunkhwa Province. The initiative aimed to provide the lowest socioeconomic group of the population with in-patient healthcare services, which otherwise would be financially hard to obtain. It is one of the flagship projects of the Provincial Government to contribute towards the United Nations Sustainable Development Goals and universal health coverage.To assess consumer choice of health facility and its determinants for public versus private sector health facilities by people enrolled in SHPI.We used secondary data of availed health services from February 2016 to September 2017 under SHPI. A proxy outcome variable, visit to health facility, was used to determine consumer choice between public and private sector health facilities. The treatment group (health services received by beneficiaries) was used as an independent variable controlled for age groups, cost groups, and geographic location of health facilities. All statistical analyses were performed by SPSS version 20.Most beneficiaries chose private over public health facilities (90.25%). The adjusted odds of visiting a public sector health facility for surgical and obstetrics/gynaecological services were 0.12 [95% confidence interval (CI): 0.10-0.16] and 0.11 (95% CI: 0.09-0.14) respectively, when compared to medical services.SHPI beneficiaries have lesser odds of visiting a public hospital over a private one. The choice may be affected by factors such as age of the beneficiary, cost of health services, and geographic location of health facilities.اختيار المستفيدين للمرفق الصحي في أدنى فئة اجتماعية واقتصادية من السكان في المخطط الحديث للتمويل الصحي على جانب الطلب في باكستان.سدرة مالك، نافيد صادق، سعيد أنور، عمير قاضي.بدأت مبادرة الحماية الصحية الاجتماعية في باكستان في مقاطعة خيبر بختونخوا. وكانت المبادرة تهدف إلى تزويد أدنى فئة اجتماعية واقتصادية من السكان بخدمات الرعاية الصحية للمرضى الداخليين، التي لولا ذلك لواجهوا صعوبة مالية في الحصول عليها. وهي أحد المشاريع الرئيسية لحكومة المقاطعة للمساهمة في تحقيق أهداف الأمم المتحدة للتنمية المستدامة والتغطية الصحية الشاملة.هدفت هذه الدراسة الى تقييم اختيار المستفيدين المُسجَّلين في المبادرة للمرفق الصحي ومُدِّدات اختيارهم لمرافق القطاع العام الصحية مقابل مرافق القطاع الخاص.استخدمنا بيانات ثانوية بشأن الخدمات الصحية التي قُدِّمت من فبراير/ شباط 2016، حتى سبتمبر/ أيلول 2017، في إطار المبادرة. واستُخدم متغير مخرجات بديل، هو زيارة المرفق الصحي، لتحديد اختيار المستفيد بين المرافق الصحية للقطاعين العام والخاص. واتُّذت مجموعة العلاج (الخدمات الصحية التي تلقاها المستفيدون) متغيرًا مستقلًّ مُضبطًا للفئات العمرية وفئات التكلفة والموقع الجغرافي للمرافق الصحية. وأُجريت جميع التحليلات الإحصائية بالنسخة 20 من برنامج SPSS.فضَّل معظم المستفيدين المرافق الصحية الخاصة على المرافق الصحية العامة (90.25٪). ومع ذلك، بلغت نسبة الأرجحية المُصحَّحة لزيارة مرفق صحي في القطاع العام من أجل الخدمات الجراحية وخدمات أمراض النساء 0.12 [فاصل الثقة 95٪: 0.10-0.16] و 0.11 [فاصل الثقة 95٪: 0.09-0.14) على التوالي، عند مقارنتها بالخدمات الطبية.احتمالات زيارة المستفيدين من مبادرة الحماية الصحية الاجتماعية لمستشفى عام أقل من احتمالات زيارتهم لمستشفى خاص. وقد يتأثر الاختيار بعوامل مثل عمر المستفيد، وتكلفة الخدمات الصحية، والموقع الجغرافي للمرافق الصحية.Choix des établissements de santé par les usagers appartenant au groupe socio-économique le plus bas dans le cadre d’un nouveau programme de financement de la santé axé sur la demande mis en œuvre au Pakistan.L’initiative de protection sociale de la santé (Social Health Protection initiative, SHPI) a été initialement mise en place au Pakistan dans la province de Khyber Pakhtunkhwa. Son objectif était de fournir au groupe socio-économique le plus bas de la population des services des soins hospitaliers, dont l’accès serait autrement financièrement difficile. Il s’agit de l’un des projets phares du gouvernement provincial visant à contribuer à la réalisation des objectifs de développement durable des Nations Unies et à la mise en place de la couverture sanitaire universelle.Évaluer le choix des établissements de santé par les personnes inscrites à l’initiative de protection sociale de la santé et les facteurs qui déterminent ce choix entre les établissements du secteur public et ceux du secteur privé.Nous avons utilisé les données secondaires des services de santé dispensés de février 2016 à septembre 2017 dans le cadre de l’initiative de protection sociale de la santé. Une variable de résultat de substitution – la fréquentation d’un établissement de santé – a été utilisée pour déterminer le choix des usagers entre les établissements de santé des secteurs public et privé. Le groupe de traitement (services de santé dispensés aux bénéficiaires) a été utilisé comme variable indépendante qui a été contrôlée pour les groupes d’âge, les groupes de coûts et l’emplacement géographique des établissements de santé. Toutes les analyses statistiques ont été réalisées à l’aide du logiciel SPSS version 20.La plupart des bénéficiaires ont préféré les établissements de santé privés aux établissements publics (90,25 %). Cependant, les probabilités ajustées de se rendre dans un établissement de santé du secteur public pour des services chirurgicaux et gynécologiques étaient de 0,12 [intervalle de confiance (IC) à 95 % : 0,10 à 0,16] et de 0,11 (IC à 95 % : 0,09 à 0,14) respectivement, par rapport aux services médicaux.Les bénéficiaires de l’initiative de protection sociale de la santé sont moins susceptibles de se rendre dans un hôpital public que dans un hôpital privé. Le choix peut être influencé par des facteurs tels que l’âge du bénéficiaire, le coût des services de santé et l’emplacement géographique des établissements de santé.

The presence of intricate carbon skeletons in natural compounds enhances their bioactivity spectrum with unique modes of action at several targets in various dreadful diseases like cancer. The present study was designed to purify the molecules from Thymus linearis and elucidate their antiproliferative activity. The compounds were isolated from the active methanolic extract of Thymus linearis through column chromatography and characterized by various spectroscopic techniques. Antiproliferative activity of isolated compounds was evaluated using MTT assay on cancer and normal cell lines. Mechanism of cell death was elucidated using flow cytometric, microscopic, and Western blot analysis. Four compounds, Sitosterol, Chrysin, 3β-hydroxylup-12-en-28-oic acid (3BH), and β-Sitosterol glycoside, were isolated. Among these, 3BH was most potent antiproliferative agent across all cell lines under study, HCT-116 being the most affected one. 3BH was demonstrated to downregulate PI3Ksubunits (p110α and p85α), downstream pAktSer473 and prompted G1 phase cell cycle arrest. The cell cycle CDK inhibitor p27 and p21 were upregulated with simultaneous downregulation of cyclin D1 and cyclin E in HCT-116 cells. This was accompanied by apoptosis, as depicted by decrease in Bcl-2/Bax ratio, with increase in active caspases-3 and caspase-9, cleavage of PARP-1, the generation of reactive oxygen species (ROS), and the loss of mitochondrial membrane potential. The findings established that 3BH induced cell death in HCT-116 cells by modulating PI3K/Akt signaling axis, impeding cell cycle, and instigating apoptosis.

The coronavirus disease (COVID-19) is a highly transmitted disease that spreads all over the globe in a short period. Environmental pollutants are considered one of the carriers to spread the COVID-19 pandemic through health damages. Carbon emissions, PM2.5 emissions, nitrous oxide emissions, GHG, and other GHG emissions are mainly judged separately in the earlier studies in different economic settings. The study hypothesizes that environmental pollutants adversely affect healthcare outcomes, likely to infected people by contagious diseases, including coronavirus cases. The subject matter is vital to analyze the preventive healthcare theory by using different environmental pollutants on the COVID-19 factors: total infected cases, total death cases, and case fatality ratio, in a large cross-section of 119 countries. The study employed the generalized least square (GLS) method for robust inferences. The results show that GHG and CO2 emissions are critical factors likely to increase total coronavirus cases and death rates. On the other hand, nitrous oxide, carbon, and transport emissions increase the case fatality ratio through healthcare damages. The study concludes that stringent environmental policies and improving healthcare infrastructure can control coronavirus cases across countries.

Background Postoperative pain after complex revision spine surgery, especially for the treatment of persistent spinal pain syndrome (PSPS), is frequently severe and can be debilitating, requiring the use of intravenous and oral opioids. To the best of our knowledge, the present study is the first to evaluate the effectiveness and safety of a continuous infusion regional anesthesia pump placed after thoracopelvic fusion for the treatment of PSPS. Methods We performed a retrospective comparative study of consecutive patients who had undergone thoracopelvic fusion for PSPS. The patients included in the present study had either had a continuous infusion regional anesthesia pump placed during surgery or had not (control). Demographics, use of preoperative and postoperative opioids, postoperative adverse events, length of hospital stay, and 90-day readmission were recorded. Results The patients in the pump group (n = 14) had used fewer opioids during their hospital stay compared with the control group (n = 12; P = 0.6). This difference was greater for postoperative days 1 and 2 (P = 0.3 and P = 0.2, respectively). No significant difference was found in opioid usage during the first 14 days after surgery (P = 0.8) or at the 3-month postoperative follow-up evaluation (P = 0.8). Furthermore, no significant difference was found between the 2 groups in terms of postoperative complications. The pump group had a 1.4-day shorter hospital stay (P = 0.7). The control group had more 90-day readmissions than did the pump group (P = 0.2). Conclusions Despite showing a trend toward less usage of opioids during the first 2 days after surgery and a shorter hospital stay with no increased complications in the pump group, the study data failed to demonstrate a statistically significant difference between the two groups.

BACKGROUND: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines.METHODS: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set.RESULTS: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children CONCLUSIONS: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly.

Background: Lesbian, gay, bisexual, and asexual adolescents are at increased risk of poor mental health outcomes but it remains unknown whether this disparity emerges from early childhood and through to adolescence. This study tested sexual orientation disparities in the developmental trajectories of emotional and behavioral difficulties from ages 5 to 14 years, and the influence of early life adversities upon them. Methods: The Millennium Cohort Study, a British birth cohort, was used (4,838 boys and 5,016 girls). Parent-report emotional and behavioral difficulties at ages 5, 7, 11, and 14 were measured using the Strength and Difficulties Questionnaire. Sexual orientation was measured via sexual attraction at age 17. Early life adversities in the first 5 years of life, including parental age at birth, birthweight, duration of breastfeeding, parent–child relationship quality, and parental absence, were collected prospectively. Results: Latent growth modeling suggested that, for both sexes, sexual orientation disparities in emotional and behavioral difficulties increased from age 5 to 14 years. Homosexual and bisexual girls displayed significantly greater emotional and behavioral difficulties than heterosexual girls at ages 7, 11, and 14. Homosexual and bisexual boys displayed significantly greater emotional and behavioral difficulties than heterosexual boys at ages 11 and 14. Asexual boys and girls displayed significantly greater emotional and behavioral difficulties than their heterosexual counterparts at all four ages. For both sexes, sexual orientation disparities in emotional and behavioral difficulties only reduced slightly in magnitude after controlling for early life adversities. Conclusions: Sexual minority disparities in emotional and behavioral difficulties increased from childhood to early adolescence, possibly due to the accumulation of susceptibility to minority-related stressors. Sex and early life adversity may contribute to these developmental disparities.

Heart failure (HF) is associated with morbidity, rehospitalization and polypharmacy. The incidence rate of mortality in HF patients with polypharmacy is poorly studied. We examine the association of polypharmacy with mortality risk in incident hospitalized HF patients with a primary diagnosis after discharge from the hospital using Quebec administrative databases, Canada from 1999 to 2015. Polypharmacy, cardiovascular (CV) polypharmacy and non-CV polypharmacy were respectively defined as exposure to ≥ 10 drugs, ≥ 5 CV drugs and ≥ 5 non-CV drugs within three months prior to the case or the control selection date. We conducted a nested case–control study to estimate rate ratios (RR) of all-cause mortality using a multivariate conditional logistic regression during one-year of follow-up. We identified 12,242 HF patients with a mean age of 81.6 years. Neither CV polypharmacy (RR 0.97, 95%CI 0.82–1.15) nor non-CV polypharmacy (RR 0.93, 95%CI 0.77–1.12) were associated with lower mortality risk. However, all polypharmacy (RR 1.31, 95%CI 1.07–1.61) showed an association with mortality risk. Myocardial infarction, valvular disease, peripheral artery disease, diabetes, major bleeding, chronic kidney disease, high comorbidity score, high Frailty score, hydralazine and spironolactone users were associated with increasing mortality risk, ranging from 15 to 61%, while use of angiotensin II inhibitors, beta-blockers, statins, anticoagulant, and antiplatelets were associated with lower risk, ranging from 23 to 32%.

International medical graduates (IMGs) have made significant contributions in the field of hand surgery in terms of bringing in skill, innovation, research, and leadership and have gone onto mentor the next generations of hand surgeons. In this article, we have highlights some such contributions. We also highlight various pathways that IMGs take to establish their practice in the United States and the various challenges and hurdles they face.

Objective: To determine the impact of translocation t(1;19) in paediatric patients diagnosed with precursor B-cell acute lymphoblastic leukaemia. Methods: The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data from January 2012 to January 2018 of paediatric patients diagnosed with precursor B-cell acute lymphoblastic leukaemia. Data of patients having t(1;19) translocation with or without complex karyotype formed group A, while data of patients without any cytogenetic abnormality formed the control group B. Relapse and event-free survival were calculated and the outcomes were compared between the groups. Data was analysed using SPSS 20. Results: Of the 450 subjects whose data was analysed, 84(18.7%) were included; 25(30%) in group A and 59(70%) were in group B. There were 21(84%) males and 4(16%) females in group A with mean age on presentation 3.68±0.6 years compared to 41(69.4%) males and 18(30.5%) females with mean age on presentation 4.0±0.92 (p>0.05). There were no differences between the groups in terms of baseline markers (p>0.05). The relapse and event-free survival rates were also not significantly different between the groups (p>0.05). Conclusion: There was no significant difference related to outcomes of precursor B-cell acute lymphoblastic leukaemia patients having t(1;19) translocation with or without complex karyotype and those without any cytogenetic abnormality, indicating that translocation t(1;19)-positive patients do not need treatment intensification. Key Words: Acute Pre-B ALL, Children, t (1;19), Oncoprotein E2A-PBX1.

BackgroundWithin Kashmir, which is one of the topographically distinct areas in the Himalayan belt of India, a total of 2,236 cumulative deaths occurred by the end of the second wave. We aimed to conduct this population-based study in the age group of 7 years and above to estimate the seropositivity and its attributes in Kashmir valley.MethodsWe conducted a community-based household-level cross-sectional study, with a multistage, population-stratified, probability-proportionate-to-size, cluster sampling method to select 400 participants from each of the 10 districts of Kashmir. We also selected a quota of healthcare workers, police personnel, and antenatal women from each of the districts. Households were selected from each cluster and all family members with age 7 years or more were invited to participate. Information was collected through a standardized questionnaire and entered into Epicollect 5 software. Trained healthcare personnel were assigned for collecting venous blood samples from each of the participants which were transferred and processed for immunological testing. Testing was done for the presence of SARS-CoV-2-specific anti-spike IgM, IgG antibodies, and anti-nucleocapsid IgG antibodies. Weighted seropositivity was estimated along with the adjustment done for the sensitivity and specificity of the test used.FindingsThe data were collected from a total of 4,229 participants from the general population within the 10 districts of Kashmir. Our results showed that 84.84% (95% CI 84.51–85.18%) of the participants were seropositive in the weighted imputed data among the general population. In multiple logistic regression, the variables significantly affecting the seroprevalence were the age group 45–59 years (odds ratio of 0.73; 95% CI 0.67–0.78), self-reported history of comorbidity (odds ratio of 1.47; 95% CI 1.33–1.61), and positive vaccination history (odds ratio of 0.85; 95% CI 0.79–0.90) for anti-nucleocapsid IgG antibodies. The entire assessed variables showed a significant role during multiple logistic regression analysis for affecting IgM anti-spike antibodies with an odds ratio of 1.45 (95% CI 1.32–1.57) for age more than 60 years, 1.21 (95% CI 1.15–1.27) for the female gender, 0.87 (95% CI 0.82–0.92) for urban residents, 0.86 (95% CI 0.76–0.92) for self-reported comorbidity, and an odds ratio of 1.16 (95% CI 1.08–1.24) for a positive history of vaccination. The estimated infection fatality ratio was 0.033% (95% CI: 0.034–0.032%) between 22 May and 31 July 2021 against the seropositivity for IgM antibodies.InterpretationDuring the second wave of the SARS-CoV-2 pandemic, 84.84% (95% CI 84.51–85.18%) of participants from this population-based cross-sectional sample were seropositive against SARS-CoV-2. Despite a comparatively lower number of cases reported and lower vaccination coverage in the region, our study found such high seropositivity across all age groups, which indicates the higher number of subclinical and less severe unnoticed caseload in the community.

COVID‐19 pandemic has affected over 100 countries in a matter of weeks. People's response toward social distancing in the emerging pandemic is uncertain. In this study, we evaluated the influence of information (formal and informal) sources on situational awareness of the public for adopting health‐protective behaviors such as social distancing. For this purpose, a questionnaire‐based survey was conducted. The hypothesis proposed suggests that adoption of social distancing practices is an outcome of situational awareness which is achieved by the information sources. Results suggest that information sources, formal (P = .001) and informal (P = 0.007) were found to be significantly related to perceived understanding. Findings also indicate that social distancing is significantly influenced by situational awareness, P = .000. It can, therefore, be concluded that an increase in situational awareness in times of public health crisis using formal information sources can significantly increase the adoption of protective health behavior and in turn contain the spread of infectious diseases., Highlights Reducing mortality caused by COVID‐19 can be achieved by awareness.Situation awareness can be increased by formal information sources.Increased situational awareness lead to adoption of health protective behavior.

Background: The emergence of the COVID-19 epidemic threw the world into turmoil. The medical community bore the brunt of the pandemic's toll. Long work hours, and a lack of personal protective equipment (PPE) and social support all had an influence on mental health. Methods: This cross-sectional study was conducted among Lumbini Medical College Teaching Hospital students and employees in Palpa, Nepal. Data entailing their demographic details, pre-existing comorbidities, or death in the family due to COVID-19 was collected using a self-administered survey. In addition, the level of fear, anxiety, obsession, and functional impairment due to COVID-19 was recorded using previously validated respective scales. Results: In total, 403 health-care workers and trainees participated in our study. The average age of the study participants was 23±4 years, and more than half of them (n=262, 65%) were females. A significant association was found between fear score with age (p-value=0.04), gender (p-value Conclusion: This study revealed various socio-demographic characteristics as risk factors for psychological stress in the people related to the health-care profession of Nepal during the COVID-19 pandemic. A viable answer to this quandary might be adequate psychosocial intervention by health-care authorities, increased social support, and the introduction of better mental health management measures for the front-line medical workers.

AIM Tooth-level prognostic systems can be used for treatment planning and risk assessment. This retrospective longitudinal study aimed to evaluate the prognostic performance of 10 different tooth-level risk assessment systems in terms of their ability to predict periodontal-related tooth loss (TLP). MATERIALS AND METHODS Data were retrieved retrospectively from patients who received surgical and non-surgical periodontal treatment. Data on medical history and smoking status at baseline and the last maintenance visit were collected. Ten tooth-level prognostic systems were compared using both univariate and multivariate Cox proportional hazard regression models to analyse the prognostic capability of each system for predicting TLP risk. RESULTS One-hundred and forty-eight patients with 3787 teeth, followed-up for a mean period of 26.5 ± 7.4 years, were evaluated according to 10 different tooth-level prognostic systems, making up a total of 37,870 individual measurements. All compared prognostic systems were able to stratify the risk of TLP at baseline when different classes of association were compared. After controlling for maintenance, age, and gender, all systems exhibited excellent predictive capacity for TLP with no system scoring a Harrell's C-index less than 0.925. CONCLUSIONS All tooth-level prognostic systems displayed excellent predictive capability for TLP. Overall, the Miller and McEntire system may have shown the best discrimination and model fit, followed by the Nunn et al. system.

Considering that antimicrobial resistance (AMR) is a global challenge, there is a dire need to gauge the knowledge, attitude, and practice (KAP) of clinicians in endemic countries. The aim of the current multicenter, cross-sectional study was to highlight the knowledge, aptitude and practice gaps in antimicrobial (AM) stewardship and AMR among practicing doctors working in public tertiary care teaching hospitals of Lahore, Pakistan. A KAP survey, based on a self-administered questionnaire containing 45 questions, was conducted among 336 clinicians practicing in 6 randomly selected hospitals of Lahore, Pakistan. Overall, 92% of the clinicians considered AMR as a worldwide problem but only 66% disagreed that cold and flu symptoms require antibiotics. Moreover, around 68% doctors felt confident about their practice in AM but still 96% felt need to get more knowledge about AM. Need to establish courses on rational antibiotic use was demanded by 84% of participants. The main contributing factors considered for AMR by the doctors included excessive AM usage in medical profession (87.1%) and multiple antibiotics per prescription (76.4%). Pharmacologically, AM spectrum was accurately chosen by 1.4% (ampicillin), 0.003% (erythromycin) and 0% (levofloxacin). Clinically, a more than 50% of clinicians used miscellaneous AM for empirical therapy of respiratory tract infection and cholecystitis. The data was analyzed using Statistical Package for Social Sciences (SPSS) version 25. The knowledge of clinicians is relatively poor in AM spectrum and drugs of choice for certain infections. However, they know about their short comings with positive approach towards improvement.

The world faces a high alert of coronavirus disease 2019 (COVID-19), leading to a million deaths and could become infected to reach a billion numbers. A sizeable amount of scholarly work has been available on different aspects of social-economic and environmental factors. At the same time, many of these studies found the linear (direct) causation between the stated factors. In many cases, the direct relationship is not apparent. The world is unsure about the possible determining factors of the COVID-19 pandemic, which need to be known through conducting nonlinearity (indirect) relationships, which caused the pandemic crisis. The study examined the nonlinear relationship between COVID-19 cases and carbon damages, managing financial development, renewable energy consumption, and innovative capability in a cross section of 65 countries. The results show that inbound foreign direct investment first increases and later decreases because of the increasing coronavirus cases. Further, the rise and fall in the research and development expenditures and population density exhibits increasing coronavirus cases across countries. The continued economic growth initial decreases later increase by adopting standardized operating procedures to contain coronavirus disease. The inter-temporal relationship shows that green energy source and carbon damages would likely influence the coronavirus cases with a variance of 17.127% and 5.440%, respectively, over a time horizon. The policymakers should be carefully designing sustainable healthcare policies, as the cost of carbon emissions leads to severe healthcare issues, which are likely to get exposed to contagious diseases, including COVID-19. The sustainable policy instruments, including renewable fuels in industrial production, advancement in cleaner production technologies, the imposition of carbon taxes on dirty production, and environmental certifications, are a few possible remedies that achieve healthcare sustainability agenda globally.