Ending TB in South-East Asia: flagship priority and response transformation.

Over the decades, the global tuberculosis (TB) response has evolved from sanatoria-based treatment to DOTS (Directly Observed Therapy Shortcourse) strategy and the more recent End TB Strategy. The WHO South-East Asia Region, which accounted for 45% of new TB patients and 50% of deaths globally in 2021, is pivotal to the global fight against TB. "Accelerate Efforts to End TB" by 2030 was adopted as a South-East Asia Regional Flagship Priority (RFP) in 2017. This article illustrates intensified and transformed approaches to address the disease burden following the adoption of RFP and new challenges that emerged during the COVID-19 pandemic. TB case notifications improved by 25% and treatment success rates improved by 6% between 2016 and 2019 due to interventions ranging from galvanising political commitments to empowering and engaging communities. Cumulative TB programme budget allocations in 2022 reached US$ 1.4 billion, about two and a half times the budget in 2016. An ambitious Regional Strategic Plan towards ending TB, 2021-2025, identifies priority interventions that will need investments of up to US$ 3 billion a year to fully implement them. Moving forward, countries in the Region need to leverage RFP and take up intensified, people-centred, holistic interventions for prevention, diagnosis, treatment and care of TB with commensurate investments and cross-ministerial and multi-sectoral coordination.

Venous Thromboembolism Risk Assessment in Hospitalized Cancer Patients: A Single Center Study.

This study aimed to identify predictors of venous thromboembolism (VTE) in hospitalized cancer patients and develop a predictive model using demographic, clinical, and laboratory data. Our analysis showed that patient groups categorized under a very high risk, and high risk, patients with low hemoglobin levels and renal disease were at a significantly increased risk of developing VTE. We developed a VTE risk-assessment model (RAM) with moderate discriminatory performance, high specificity, and negative predictive value, indicating its potential utility in identifying patients without VTE risk. However, the model's positive predictive value and sensitivity were low due to the low prevalence of VTE within the analyzed population. Future studies are needed to analyze additional predictive factors, and to validate the effectiveness of our VTE RAM to safely rule out VTE, compare it with other VTE RAMs in hospitalized cancer patients, and address any limitations of our study.

Ultra-sensitive detection and scavenging of arsenic ions and ciprofloxacin using 3D multipurpose hemicellulose based aerogel: Adsorption mechanism and RSM optimization.

Trace level detection and efficient removal of arsenite ions (As (III)) and ciprofloxacin (CPR) antibiotic was achieved using hemicellulose based ratiometric fluorescent aerogel. Hemicellulose derived from rice straw was oxidised to dialdehyde hemicellulose followed by crosslinking using chitosan via a Schiff base reaction (C = N) yielding a highly porous 3D fluorescent aerogel (CS@DAHCA). Various factors governing adsorption were analyzed by applying response surface methodology (RSM) approach. CS@DAHCA exhibited ultra-trace level monitoring with the limit of detection of 3.529 pM and 55.2 nM for As (III) and CPR, respectively. The CS@DAHCA showed maximum adsorption capacity of 185 µg g-1 and 454 mg g-1 for As (III) and CPR, respectively. Finally, the feasibility of CS@DAHCA was ascertained for real water samples confirming it as promising candidate for remediation of As (III) and CPR.

In silico structural and mechanical insights into bedaquiline resistance associated with high-grade non-synonymous mutations in atpE, mmpR5, and pepQ.

Clinical resistance against bedaquiline (BDQ) remains intractable to anti-tuberculosis therapies since its introduction to the market over a decade ago. Herein, we investigated the structural and mechanical aspects of BDQ resistance in AtpE, MmpR5, and PepQ. The known target-specific resistant single non-synonymous mutations were refined to high-grade candidates. Thus, 7 (AtpE), 5 (MmpR5), and 1 (PepQ) single nucleotide polymorphisms (SNPs) and one insertion frameshift mutation in MmpR5 were recreated at the molecular level, and these phenotypic models were then directed to stringent dynamics to define time-scaled changes. The AtpE variants destabilized the structure; mainly, L59V, E61D, and I66M were detrimental to the complex fitness, while L74V and L114P boosted the BDQ binding to MmpR5. The first three and last two alterations gave rise to loss- and gain-of-function to AtpE and MmpR5, respectively. Hence, these five mutants are functionally relevant and therapeutically targetable hotspots of BDQ resistance. There were no noticeable changes in PepQ data analysis. The present study revealed that MmpR5 mutations confer BDQ resistance, whereas AtpE and PepQ SNPs display low susceptibility. These results were tallied with the published findings, which testified to the pursued method's reliability and accuracy. We hope these data and inferences could be helpful for the futuristic design of novel TB drugs.Communicated by Ramaswamy H. Sarma.

Identification of Healthy Tissue from Malignant Tissue in Surgical Margin Using Raman Spectroscopy in Oral Cancer Surgeries.

Accurate identification of tissue types in surgical margins is essential for ensuring the complete removal of cancerous cells and minimizing the risk of recurrence. The objective of this study was to explore the clinical utility of Raman spectroscopy for the detection of oral squamous cell carcinoma (OSCC) in both tumor and healthy tissues obtained from surgical resection specimens during surgery. This study enrolled a total of 64 patients diagnosed with OSCC. Among the participants, approximately 50% of the cases were classified as the most advanced stage, referred to as T4. Raman experiments were conducted on cryopreserved tissue samples collected from patients diagnosed with OSCC. Prominent spectral regions containing key oral biomarkers were analyzed using the partial least squares-support vector machine (PLS-SVM) method, which is a powerful multivariate analysis technique for discriminant analysis. This approach effectively differentiated OSCC tissue from non-OSCC tissue, achieving a sensitivity of 95.7% and a specificity of 93.3% with 94.7% accuracy. In the current study, Raman analysis of fresh tissue samples showed that OSCC tissues contained significantly higher levels of nucleic acids, proteins, and several amino acids compared to the adjacent healthy tissues. In addition to differentiating between OSCC and non-OSCC tissues, we have also explored the potential of Raman spectroscopy in classifying different stages of OSCC. Specifically, we have investigated the classification of T1, T2, T3, and T4 stages based on their Raman spectra. These findings emphasize the importance of considering both stage and subsite factors in the application of Raman spectroscopy for OSCC analysis. Future work will focus on expanding our tissue sample collection to better comprehend how different subsites influence the Raman spectra of OSCC at various stages, aiming to improve diagnostic accuracy and aid in identifying tumor-free margins during surgical interventions.

Cerebral Sinovenous Thrombosis in Infants and Children: A Practical Approach to Management.

Cerebral sinovenous thrombosis (CSVT) is a rare, yet potentially devastating disorder, associated with acute complications and long-term neurologic sequelae. Consensus-based international pediatric CSVT treatment guidelines emphasize early clinical-radiologic recognition and prompt consideration for anticoagulation therapy. However, lack of clinical trials has precluded evidence-based patient selection, anticoagulant choice, optimal monitoring parameters and treatment duration. Consequently, uncertainties and controversies persist regarding anticoagulation practices in pediatric CSVT. This review focuses on commonly encountered issues that continue to pose questions and raise debates regarding anticoagulation therapy among pediatric neurologists and hematologists.

Hemostatic and Thrombotic Considerations in the Diagnosis and Management of Childhood Arterial Ischemic Stroke: A Narrative Review.

Although rare in children, arterial ischemic stroke (AIS) is associated with increased mortality and neurological morbidity. The incidence of AIS after the neonatal period is approximately 1-2/100,000/year, with an estimated mortality of 3-7%. A significant proportion of children surviving AIS experience life-long neurological deficits including hemiparesis, epilepsy, and cognitive delays. The low incidence of childhood AIS coupled with atypical clinical-presentation and lack of awareness contribute to delay in diagnosis and consequently, the early initiation of treatment. While randomized-clinical trials have demonstrated the efficacy and safety of reperfusion therapies including thrombolysis and endovascular thrombectomy in appropriately-selected adult patients, similar data for children are unavailable. Consequently, clinical decisions surrounding reperfusion therapy in childhood AIS are either extrapolated from adult data or based on local experience. The etiology of childhood AIS is multifactorial, often occurring in the setting of both acquired and congenital risk-factors including thrombophilia. While multiple studies have investigated the association of thrombophilia with incident childhood AIS, its impact on stroke recurrence and therefore duration and intensity of antithrombotic therapy is less clear. Despite these limitations, a significant progress has been made over the last decade in the management of childhood AIS. This progress can be attributed to international consortiums, and in selected cohorts to federally-funded clinical trials. In this narrative review, the authors have systematically appraised the literature and summarize the hemostatic and thrombotic considerations in the diagnosis and management of childhood AIS focusing on the evidence supporting reperfusion therapies, relevance of thrombophilia testing, and duration and drug choices for secondary-prophylaxis.

Raman Spectral Characterization of Urine for Rapid Diagnosis of Acute Kidney Injury.

Acute kidney injury (AKI) is a common syndrome characterized by various etiologies and pathophysiologic processes that deteriorate kidney function. The aim of this study is to identify potential biomarkers in the urine of non-acute kidney injury (non-AKI) and AKI patients through Raman spectroscopy (RS) to predict the advancement in complications and kidney failure. Selected spectral regions containing prominent peaks of renal biomarkers were subjected to partial least squares linear discriminant analysis (PLS-LDA). This discriminant analysis classified the AKI patients from non-AKI subjects with a sensitivity and specificity of 97% and 100%, respectively. In this study, the RS measurements of urine specimens demonstrated that AKI had significantly higher nitrogenous compounds, porphyrin, tryptophan and neopterin when compared with non-AKI. This study's specific spectral information can be used to design an in vivo RS approach for the detection of AKI diseases.

Intravenous iron therapy in the pediatric sleep clinic: a single institution experience.

STUDY OBJECTIVES: Initial reports of intravenous (IV) iron administration have been promising for children with restless legs syndrome, periodic limb movement disorder, and restless sleep disorder. The aim of the current study was to evaluate further the clinical response to IV iron supplementation in children seen in a pediatric sleep clinic. METHODS: We performed a retrospective chart review of children cared for in a single pediatric sleep clinic who also underwent IV iron infusion. Pre and post IV data regarding their sleep symptoms and ferritin levels were abstracted. RESULTS: Overall, 63 pediatric sleep patients underwent IV iron infusion, mostly with ferric carboxymaltose (n = 60), for restless legs syndrome (n = 30), periodic limb movement disorder (n = 22), and restless sleep disorder (n = 17). Of the 59 patients with clinical follow-up, 39 (73%) noted improvement in at least 1 symptom, and 14 (26%) did not notice improvement or noticed worsening symptoms. Of the 59 patients with preinfusion and postinfusion labs, the average ferritin level increased from 21.7 (13.3) to 147.9 (120.9) µg/L, P < .001. Comparing patients who experienced clinical improvement vs those who did not, there were no statistically significant differences in change in ferritin levels (P = .278), sex (P = .452), or age (P = .391). Ferritin change with infusion according to diagnostic subgroups (restless legs syndrome/periodic limb movement disorder/restless sleep disorder) was examined, and no significant differences were noted (F(2,56) = 0.852, P = .432). In terms of immediate adverse reactions to the IV infusion, 7 (11%) experienced at least 1 side effect, with the most common being behavior change (n = 6) or gastrointestinal discomfort (n = 4); no episodes of anaphylaxis or extravasation were noted. CONCLUSIONS: These data provide additional support for the efficacy and safety of IV iron for pediatric restless legs syndrome, periodic limb movement disorder, and restless sleep disorder recalcitrant to oral iron. CITATION: Ingram DG, Al-Shawwa B, DelRosso LM, Sharma M. Intravenous iron therapy in the pediatric sleep clinic: a single institution experience. J Clin Sleep Med. 2022;18(11):2545-2551.

Assessment of country implementation of the WHO global health sector strategy on sexually transmitted infections (2016-2021).

BACKGROUND: In 2016, WHO launched the Global Health Sector Strategy on STIs, 2016-2021 (GHSS) to provide guidance and benchmarks for country achievement by 2020 and four global targets for achievement by 2030. METHODS: A country survey jointly developed by experienced technical personnel at WHO Headquarters (HQ) and WHO regional offices was reviewed and distributed by WHO regional advisors to 194 WHO Member States in September-March 2020. The survey sought to assess implementation and prioritization of STI policy, surveillance, service delivery, commodity availability, and surveillance based on targets of the GHSS. RESULTS: A majority (58%, 112/194) of countries returned a completed survey reflecting current (2019) STI activities. The regions with the highest survey completion rates were South-East Asia Region (91%, 10/11), Region of the Americas (71%, 25/35) and Western Pacific Region (67%, 18/27). Having a national STI strategy was reported by 64% (72/112) and performing STI surveillance activities by 88% (97/110) of reporting countries. Availability of STI services within primary health clinics was reported by 88% of countries (99/112); within HIV clinics by 92% (103/112), and within reproductive health services by 85% (95/112). Existence of a national strategy to eliminate mother-to-child transmission of HIV and syphilis (EMTCT) was reported by 70% of countries (78/112). Antimicrobial resistance (AMR) monitoring for gonococcal infection (gonorrhoea) was reported by 64% (57/89) of reporting countries with this laboratory capacity. Inclusion of HPV vaccine for young women in the national immunization schedule was reported by 59% (65/110) and availability of cervical cancer screening was reported by 91% (95/104). Stockouts of STI medicines, primarily benzathine penicillin, within the prior four years were reported by 34% (37/110) of countries. CONCLUSIONS: Mechanisms to support improvements to STI service delivery through national-level policy, commitment, programming and surveillance are needed to operationalize, accelerate and monitor progress towards achievement of the 2030 global STI strategy targets.

Demographics in Children Presenting With Acute Neurologic Deficits Concerning for Stroke: An Evaluation of the Stroke Alert Process.

Objective: To assess the demographics and clinical characteristics of children presenting with acute neurologic symptoms concerning for stroke. Background: Stroke leads to significant morbidity in the pediatric population. Stroke protocols were created as a means to help identify and triage these children. Despite implementation of these protocols, there have been few population-based studies evaluating the demographics and clinical features of children presenting with acute strokelike symptoms. Methods: A retrospective chart review of patients for whom the stroke alert process was activated from September 2016 through August 2018 at Children's Mercy Hospital. Results: There were a total of 61 activations. Acute ischemic stroke or transient ischemic attack comprised 18% and was the second leading diagnoses after seizure with postictal (Todd) paralysis (20%). Two activations were candidates for mechanical thrombectomy, and none received tissue plasminogen activator (tPA). Children with acute ischemic stroke / transient ischemic attack were likely to be younger in age (median 4 years, interquartile range [IQR] 3-9) compared to those with nonischemic stroke diagnoses (median 12.5 years, IQR 7-15.3) (P = .010). The anatomical location of acute ischemic stroke was widespread, including both anterior and posterior circulations. Past medical history, family history, racial demographics, sex, and initial presenting symptoms were not predictive of the diagnosis of acute ischemic stroke / transient ischemic attack. 38% of activations with diagnoses other than transient ischemic attack / acute ischemic stroke required urgent treatment, with 16% requiring intensive care unit admission. Conclusion: Acute ischemic stroke / transient ischemic attack comprised nearly one-fifth of all pediatric stroke activations, highlighting the importance of developing protocols for early recognition and evaluation of children who present with symptoms concerning for stroke.

Seroprevalence and burden of hepatitis C virus infection in WHO South-East Asia Region: A systematic review.

BACKGROUND: This systematic review was aimed to estimate hepatitis C virus (HCV) seroprevalence and burden in disease in WHO South East Asia Region (SEAR). METHODS: Electronic databases (PubMed, Scopus, Embase, and Google Scholar) and websites of non-indexed national medical journals, government and international health agencies were searched to identify English language literature published between 1991 and June 2020. We selected the studies reporting HCV seroprevalence in asymptomatic general (low-risk) and high-risk adult populations, that is, persons living with HIV (PLHIV), persons who inject drugs (PWID), sex workers, persons on maintenance hemodialysis (MHD), people in prison, and men sex with men (MSM). Seroprevalence data were combined to estimate weighted pooled prevalence (95% confidence interval) in each group and in each country, using the random-effects model. Estimated pooled seroprevalences were multiplied with estimated populations at risk to estimate the overall HCV burden. RESULTS: The analysis included 538 studies (35 Bangladesh, 6 Bhutan, 2 DPR Korea, 323 India, 43 Indonesia, 2 Maldives, 18 Myanmar, 29 Nepal, 11 Sri Lanka, 67 Thailand, and 2 Timor-Leste). In SEAR, the weighted pooled anti-HCV seroprevalence was estimated as 0.84% (0.56-1.12) in low-risk population and 13.67% (10.95-16.40) in PLHIV, 51.44% (43.67-59.20) in PWID, 25.80% (20.34-32.09) in MHD, 8.39% (5.84-11.51) in prison inmates, 2.69% (1.43-4.13) in people with high-risk sex behavior, and 11.43% (8.61-14.74) in MSM. The total HCV burden in low-risk and high-risk populations in SEAR countries was estimated as 12.45 million and 1.65 million, respectively. CONCLUSION: Our estimates of HCV seroprevalence and burden should help the respective countries in planning their HCV elimination strategies.

Terrible twos: intravenous iron ameliorates a toddler's iron deficiency and sleep disturbance.

The relation between iron deficiency and restless legs syndrome has been widely described and investigated in both adults and children. However, the diagnosis of restless legs syndrome relies on patients voicing their symptoms, which is very difficult for patients younger than age 5 years. Frequently, we evaluate children between ages 2 and 4 years whom parents describe as "restless sleepers," "difficult to settle down," or having "frequent awakening" or "bedtime resistance." Parents are concerned that their child's poor sleep quality is leading to daytime dysfunction such as increased sleepiness, behavioral outbursts, or hyperactivity. Many of these children are diagnosed with behavioral insomnia of childhood, and behavior modification therapy is recommended with variable degrees of success. Herein, we describe a 2-year-old with similar symptoms of restless sleep, bedtime resistance, and daytime sleepiness who was found to have an underlying iron deficiency without anemia that was treated successfully with iron infusion. We highlight the importance of evaluating for underlying iron deficiency even without anemia in patients with restless sleep and associated poor daytime behavior. We also describe some common challenges associated with iron therapy and clarify iron therapeutic targets. CITATION: Al-Shawwa B, Sharma M, Ingram DG. Terrible twos: intravenous iron ameliorates a toddler's iron deficiency and sleep disturbance. J Clin Sleep Med. 2022;18(2):677-680.

Classification of COVID-19 by using supervised optimized machine learning technique.

In recent two years, covid-19 diseases is the most harmful diseases in entire world. This disease increase the high mortality rate in several developed countries. Earlier identification of covid-19 symptoms can avoid the over illness or death. However, there are several researchers are introduced different methodology to identification of diseases symptoms. But, identification and classification of covid-19 diseases is the difficult task for every researchers and doctors. In this modern world, machine learning techniques is useful for several medical applications. This study is more focused in applying machine learning classifier model as SVM for classification of diseases. By improve the classification accuracy of the classifier by using hyper parameter optimization technique as modified cuckoo search algorithm. High dimensional data have unrelated, misleading features, which maximize the search space size subsequent in struggle to process data further thus not contributing to the learning practise, So we used a hybrid feature selection technique as mRMR (Minimum Redundancy Maximum Relevance) algorithm. The experiment is conducted by using UCI machine learning repository dataset. The classifier is conducted to classify the two set of classes such as COVID-19, and normal cases. The proposed model performance is analysed by using different parametric metrics, which are explained in result section.

Progress towards achieving viral hepatitis B and C elimination in the Asia and Pacific region: Results from modelling and global reporting.

In 2016, Asia and Pacific countries endorsed action plans for reaching viral hepatitis elimination targets set in the Global Health Sector Strategy (GHSS) for Viral Hepatitis 2016-2021. We examine the region's progress by modelling disease burden and constructing the cascade of care. Between 2015 and 2020, chronic HBV prevalence declined from 4.69% to 4.30%, and HCV prevalence declined from 0.64% to 0.58%. The region achieved the 2020 target of 30% incidence reduction for HBV, whereas HCV incidence declined by 6%. Hepatocellular carcinoma incidence for HBV and HCV increased by 9% and 7%, respectively. Liver-related deaths from HBV rose by 8%, and mortality attributable to HCV plateaued. Large testing and treatment gaps remained in 2019: only 13% of chronic HBV infections were diagnosed and 25% treated; 21% of chronic HCV infection were diagnosed and 11% treated. Viral hepatitis must become national priority with adequate funding to reach elimination goals by 2030.

Health-related quality of life and fatigue in children and adults with pyruvate kinase deficiency.

Pyruvate kinase deficiency (PKD) is the most common cause of congenital nonspherocytic hemolytic anemia. Although recognition of the disease spectrum has recently expanded, data describing its impact on health-related quality of life (HRQoL) are limited. In this prospective international cohort of 254 patients (131 adults and 123 children) with PKD, we used validated measures to assess the impact of disease on HRQoL (EuroQol 5-Dimension Questionnaire, Pediatric Quality of Life Inventory Generic Core Scale version 4.0, and Functional Assessment of Cancer Therapy-Anemia) and fatigue (Patient Reported Outcomes Measurement Information System Fatigue and Pediatric Functional Assessment of Chronic Illness Therapy-Fatigue). Significant variability in HRQoL and fatigue was reported for adults and children, although individual scores were stable over a 2-year interval. Although adults who were regularly transfused reported worse HRQoL and fatigue compared with those who were not (EuroQol-visual analog scale, 58 vs 80; P = .01), this difference was not seen in children. Regularly transfused adults reported lower physical, emotional, and functional well-being and more anemia symptoms. HRQoL and fatigue significantly differed in children by genotype, with the worst scores in those with 2 severe PKLR mutations; this difference was not seen in adults. However, iron chelation was associated with significantly worse HRQoL scores in children and adults. Pulmonary hypertension was also associated with significantly worse HRQoL. Additionally, 59% of adults and 35% of children reported that their jaundice upset them, identifying this as an important symptom for consideration. Although current treatments for PKD are limited to supportive care, new therapies are in clinical trials. Understanding the impact of PKD on HRQoL is important to assess the utility of these treatments. This trial was registered at www.clinicaltrials.gov as #NCT02053480.

Developing an Algorithm for Discriminating Oral Cancerous and Normal Tissues Using Raman Spectroscopy.

The aim of this study was to investigate the clinical potential of Raman spectroscopy (RS) in detecting oral squamous cell carcinoma (OSCC) in tumor and healthy tissues in surgical resection specimens during surgery. Raman experiments were performed on cryopreserved specimens from patients with OSCC. Univariate and multivariate analysis was performed based on the fingerprint region (700-1800 cm-1) of the Raman spectra. One hundred thirty-one ex-vivo Raman experiments were performed on 131 surgical resection specimens obtained from 67 patients. The principal component analysis (PCA) and partial least square (PLS) methods with linear discriminant analysis (LDA) were applied on an independent validation dataset. Both models were able to differentiate between the tissue types, but PLS-LDA showed 100% accuracy, sensitivity, and specificity. In this study, Raman measurements of fresh resection tissue specimens demonstrated that OSCC had significantly higher nucleic acid, protein, and several amino acid contents than adjacent healthy tissues. The specific spectral information obtained in this study can be used to develop an in vivo Raman spectroscopic method for the tumor-free resection boundary during surgery.