ABSTRACT
BACKGROUND: Outpatient care for patients with heart valve disease (HVD) is best provided by valve clinics delivered by specialists. Modern day practice in the United Kingdom (UK) is currently poorly understood and has not been evaluated for nearly a decade. Furthermore, the COVID 19 pandemic changed the management of many chronic diseases, and how this has impacted patients with heart valve disease is unclear. METHODS: A British Heart Valve Society survey was sent to 161 hospitals throughout the UK. RESULTS: There was a general valve clinic in 46 of the 68 hospitals (68%), in 19 of 23 Heart Centres (83%) and 29 of 45 DGHs (64%). Across all settings, 3824 new patients and 17,980 follow up patients were seen in valve clinics per annum. The mean number of patients per hospital were 197 (median 150, range 48-550) for new patients and 532 (median 400, range 150-2000) for follow up. On the day echocardiography was available in 55% of valve clinics. In patients with severe HVD, serum brain natriuretic peptide (BNP) was measured routinely in 39% of clinics and exercise testing routinely performed in 49% of clinics. A patient helpline was available in 27% of clinics. 78% of centres with a valve clinic had a valve multidisciplinary team meeting (MDT). 45% centres had an MDT co-ordinator and MDT outcomes were recorded on a database in 64%. COVID-19 had a major impact on valve services in 54 (95%) hospitals. CONCLUSIONS: There has been an increase in the number of valve clinics since 2015 from 21 to 68% but the penetration is still well short of the expected 100%, meaning that valve clinics only serve a small proportion of patients requiring surveillance for HVD. COVID-19 had a major impact on the care of patients with HVD in the majority of UK centres surveyed.
Subject(s)
Tuberculosis , Humans , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Time FactorsABSTRACT
Stroke is one of the leading causes of mortality and morbidity all over the world. The economic cost for stroke disability and post stroke rehabilitation is a growing concern. Ischemic stroke comprises 80.0 - 85.0% of total stroke cases caused by thrombotic or embolic occlusion of cerebral arteries. The source of embolism may be a larger artery or cardiac. Overt heart failure is an independent predictor of long term unfavorable functional outcome in stroke patients. However, there is little research whether the acute ischemic stroke risk is associated with mild to moderate degree of Left Ventricular Systolic Dysfunction (LVSD). This study was aimed to investigate the relation between LVSD and acute ischemic stroke (AIS) and to evaluate the relation between left ventricular systolic dysfunction and severity of neurological deficits after acute ischemic stroke. This case-control study was carried out in the Department of Neurology and Department of Medicine, Mymensingh Medical College and Hospital, Bangladesh from January 2019 to December 2020. One hundred twenty (120) patients of first ever AIS and 120 age and sex matched apparently healthy controls were enrolled in the study. Severity of stroke was measured by National Institute of Health Stroke Scale (NIHSS). Left ventricular (LV) systolic function was assessed by transthoracic 2-dimensional echocardiography. Mean±SD age was 58.23±9.34 years and 55.92±9.72 years respectively in cases and controls. Male to female ratio was 1.86:1. Left ventricular systolic dysfunction of any degree was more frequent in stroke patients (23.3%) than in controls (5.8%; p<0.001). The mean±SD of LVEF were 59.21±9.68 and 63.54±6.84 among case and control groups respectively. Mild LV dysfunction was observed 16.7% in AIS patients and 5.8% in control group. Moderate LV dysfunction was found in 6.7% in AIS patients. Participants with mild LVSD had significantly higher odds of being in the cases compared to participants with no LVSD (OR: 3.48; 95% CI: 1.41-8.59). Similarly, participants with moderate LVSD were 9.74 times more likely to be in ischemic stroke group compared to participants with no LVSD (OR: 9.74; 95% CI:1.19-19.29). LVSD was associated with AIS even after adjusting for other stroke risk factors (OR: 2.7462; 95CI for OR: 1.0204, 7.3906; p=0.0435). The NIHSS was significantly negatively correlated with LVEF (r=-0.443; p<0.001). The study may conclude that Left ventricular systolic dysfunction of mild to moderate degree, is associated with acute ischemic stroke. AIS patients with higher neurological deficit also had lower LVEF.
Subject(s)
Ischemic Stroke , Stroke , Ventricular Dysfunction, Left , Humans , Male , Female , Middle Aged , Aged , Ischemic Stroke/complications , Case-Control Studies , Ventricular Dysfunction, Left/complications , Ventricular Function, Left , Stroke/complicationsABSTRACT
BACKGROUND: Evidence of the effectiveness of the WHO-recommended design of longer individualized regimens for multidrug- or rifampicin-resistant TB (MDR/RR-TB) is limited.OBJECTIVES: To report end-of-treatment outcomes for MDR/RR-TB patients from a 2015-2018 multi-country cohort that received a regimen consistent with current 2022 WHO updated recommendations and describe the complexities of comparing regimens.METHODS: We analyzed a subset of participants from the endTB Observational Study who initiated a longer MDR/RR-TB regimen that was consistent with subsequent 2022 WHO guidance on regimen design for longer treatments. We excluded individuals who received an injectable agent or who received fewer than four likely effective drugs.RESULTS: Of the 759 participants analyzed, 607 (80.0%, 95% CI 77.0-82.7) experienced successful end-of-treatment outcomes. The frequency of success was high across groups, whether stratified on number of Group A drugs or fluoroquinolone resistance, and ranged from 72.1% to 90.0%. Regimens were highly variable regarding composition and the duration of individual drugs.CONCLUSIONS: Longer, all-oral, individualized regimens that were consistent with 2022 WHO guidance on regimen design had high frequencies of treatment success. Heterogeneous regimen compositions and drug durations precluded meaningful comparisons. Future research should examine which combinations of drugs maximize safety/tolerability and effectiveness.
Subject(s)
Antitubercular Agents , Tuberculosis, Multidrug-Resistant , Humans , Antitubercular Agents/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Rifampin/therapeutic use , Drug Therapy, Combination , Treatment Outcome , World Health OrganizationABSTRACT
BACKGROUND: The WHO provides standardized outcome definitions for rifampicin-resistant (RR) and multidrug-resistant (MDR) TB. However, operationalizing these definitions can be challenging in some clinical settings, and incorrect classification may generate bias in reporting and research. Outcomes calculated by algorithms can increase standardization and be adapted to suit the research question. We evaluated concordance between clinician-assigned treatment outcomes and outcomes calculated based on one of two standardized algorithms, one which identified failure at its earliest possible recurrence (i.e., failure-dominant algorithm), and one which calculated the outcome based on culture results at the end of treatment, regardless of early occurrence of failure (i.e., success-dominant algorithm).METHODS: Among 2,525 patients enrolled in the multi-country endTB observational study, we calculated the frequencies of concordance using cross-tabulations of clinician-assigned and algorithm-assigned outcomes. We summarized the common discrepancies.RESULTS: Treatment success calculated by algorithms had high concordance with treatment success assigned by clinicians (95.8 and 97.7% for failure-dominant and success-dominant algorithms, respectively). The frequency and pattern of the most common discrepancies varied by country.CONCLUSION: High concordance was found between clinician-assigned and algorithm-assigned outcomes. Heterogeneity in discrepancies across settings suggests that using algorithms to calculate outcomes may minimize bias.
Subject(s)
Algorithms , Tuberculosis, Multidrug-Resistant , Humans , Rifampin/therapeutic use , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapyABSTRACT
Silyl-amino-propyl-3-oxa-glutaramic acid (SAPOGA) functionalized titania has been synthesized for highly efficient solid phase sequestration of thorium and uranyl ions from an aqueous acidic waste stream. The XRD pattern suggested that the grafting was performed on the anatase phase, leading to a rougher surface resulting in better interaction with actinides. The successful grafting of SAPOGA bridging was confirmed using spectroscopic methods. The Langmuir isotherm and the intraparticle diffusion-based kinetics model were found to be operative with sorption capacities of 231 mg g-1 and 458 mg g-1 and rate constants of 51 mg g-1 min-1 and 48 mg g-1 min-1 for U and Th, respectively. The entropy driven sequestration process was thermodynamically favourable (ΔGU = -6.0 kJ mol-1 and ΔGTh = -9.1 kJ mol-1) and endothermic in nature. The experimentally corroborated complexation pattern was assisted by density functional theory (DFT) calculations, which gave further insight into the metal-ligand interaction.
ABSTRACT
OBJECTIVES: Preterm birth (PTB) increases the risk of various acute and chronic morbidities and premature mortality in children under 5 years of age. The present study examines the association between different maternal obstetric factors and PTB. In addition, this study estimates the risk of neonatal mortality among children born preterm. STUDY DESIGN: Retrospective two-stage stratified sample design. METHODS: The weighted prevalence of PTB was estimated using data on 148,746 most recent institutional births from the National Family Health Survey (NFHS)-4, 2015-16. The Poisson regression model was used to investigate the association between maternal obstetric factors and PTB. Using Cox's proportional hazard model, the risk of neonatal mortality among PTBs was estimated. RESULTS: Maternal obstetric factors, such as minimal antenatal care, delivery complications, history of previous caesarean delivery and delivery at private health facilities, were significantly associated with an increased risk of PTB. The survival probability of preterm babies sharply declined in the first week of life and thereafter was found to stabilise. The risk of mortality in the first 28 days of life increased 2.5-fold if the baby was born preterm. Optimising antenatal care was found to lower the likelihood of PTB and improve their chances of survival. CONCLUSION: Antenatal care services and delivery care practices in private facilities were strongly associated with the incidence and survival of PTB. Evaluating associations of history of caesarean births on future pregnancies can help understand their deleterious effects on PTB. Affordable, accessible and available antenatal care services, in both public and private facilities, can increase the survival rates of PTBs.
Subject(s)
Premature Birth , Child , Child, Preschool , Female , Humans , Infant Mortality , Infant, Low Birth Weight , Infant, Newborn , Pregnancy , Premature Birth/epidemiology , Prenatal Care , Retrospective Studies , Risk FactorsABSTRACT
A series of praseodymium (Pr3+ ) ion activated Sr3 Gd(1-x) (PO4 )3 :xPr3+ (0 ≤ x ≤ 2.0 mol%) phosphors were prepared and their structural, compositional and luminescence properties were investigated. The X-ray diffraction profiles indicate that the studied phosphors crystallized into body centred cubic structure and the Pr3+ ions have no influence on Sr3 Gd(PO4 )3 phase. The high-resolution scanning electron microscopy images show the agglomeration of particles that are inter-connected and form irregular shape Sr3 Gd(PO4 )3 structures. The excitation transitions corresponding to Pr3+ :3 H4 â 3 P2,1,0 transitions at 445, 471 and 483 nm, respectively, matched well with the emission of blue-light-emitting diode (LED) chip. The emission spectra show strong reddish-orange luminescence through 1 D2 â 3 H4 transition when excited at 445 nm blue wavelength. The synthesized phosphors have the potential to be used as reddish-orange lighting devices.
ABSTRACT
SETTING: Governmental health facilities performing TB diagnostics in Manicaland, Zimbabwe. OBJECTIVE: To investigate the effect of making Xpert® MTB/RIF the primary TB diagnostic for all patients presenting with presumptive TB on 1) the number of samples investigated for TB, 2) the proportion testing TB-positive, and 3) the proportion of unsuccessful results over time. DESIGN: This retrospective study used data from GeneX-pert downloads, laboratory registers and quality assurance reports between 1 January 2017 and 31 December 2018. RESULTS: The total number of Xpert tests performed in Manicaland increased from 3,967 in the first quarter of 2017 to 7,011 in the last quarter of 2018. Mycobacterium tuberculosis DNA was detected in 4.9-8.6% of the samples investigated using Xpert, with a higher yield in 2017 than in 2018. The overall proportion of unsuccessful Xpert assays due to "no results", errors and invalid results was 6.3%, and highly variable across sites. CONCLUSION: Roll out of more sensitive TB diagnostics does not necessarily result in an increase of microbiologically confirmed TB diagnosis. While the number of samples tested using Xpert increased, the proportion of TB-positive tests decreased. GeneXpert soft- and hardware infrastructure needs to be strengthened to reduce the rate of unsuccessful assays and therefore, costs and staff time.
LIEU: Centres de soins gouvernementaux réalisant des tests diagnostiques de la TB au Manicaland, Zimbabwe. OBJECTIF: Analyser l'effet de l'utilisation du test Xpert® MTB/RIF en tant que test diagnostique principal de la TB chez tous les patients suspects de TB sur 1) le nombre d'échantillons analysés pour TB, 2) la proportion d'échantillons testés positifs à la TB et 3) la proportion de résultats infructueux au fil du temps. MÉTHODE: Cette étude rétrospective a utilisé les données extraites du système GeneXpert, des registres de laboratoire et des rapports d'assurance qualité entre le 1er janvier 2017 et le 31 décembre 2018. RÉSULTATS: Le nombre total de tests Xpert réalisés au Manicaland a augmenté, de 3 967 au premier trimestre 2017 à 7 011 au dernier trimestre 2018. L'ADN de Mycobacterium tuberculosis a été détecté dans 4,98,6% des échantillons analysés par test Xpert, avec un rendement plus élevé en 2017 qu'en 2018. La proportion globale de tests Xpert infructueux en raison d'une « absence de résultat ¼, d'erreurs ou de résultats non valides était de 6,3%, avec une forte variation en fonction des sites. CONCLUSION: Le déploiement de tests diagnostiques de la TB plus sensibles n'entraîne pas nécessairement une hausse des diagnostics de TB confirmés microbiologiquement. Alors que le nombre d'échantillons testés par test Xpert a augmenté, la proportion de tests positifs pour la TB a diminué. L'infrastructure du matériel et du logiciel GeneXpert doit être renforcée pour réduire le taux de tests infructueux, et donc les coûts et le temps consacré par le personnel à la réalisation de ces tests.
ABSTRACT
The quantitative structure-property relationship (QSPR) method is commonly used to predict different physicochemical characteristics of interest of chemical compounds with an objective to accelerate the process of design and development of novel chemical compounds in the biotechnology and healthcare industries. In the present report, we have employed a QSPR approach to predict the different properties of the aminoglycoside-derived polymers (i.e. polymer DNA binding and aminoglycoside-derived polymers mediated transgene expression). The final QSPR models were obtained using the partial least squares (PLS) regression approach using only specific categories of two-dimensional descriptors and subsequently evaluated considering different internationally accepted validation metrics. The proposed models are robust and non-random, demonstrating excellent predictive ability using test set compounds. We have also developed different kinds of consensus models using several validated individual models to improve the prediction quality for external set compounds. The present findings provide new insight for exploring the design of an aminoglycoside-derived polymer library based on different identified physicochemical properties as well as predict their property before their synthesis.
Subject(s)
Aminoglycosides/chemistry , DNA/metabolism , Polymers/chemistry , Polymers/pharmacology , Quantitative Structure-Activity Relationship , Gene Expression/drug effects , Least-Squares Analysis , Polymers/metabolism , TransgenesABSTRACT
This study reports for the first-time antioxidant activity and flavonoid composition of KP onion landrace which is useful for future breeding programs and to obtain geographical indication (GI) tag for the benefit of farmers. The present study was aimed to determine antioxidant capacity and flavonoid composition of bulbs of red onion (Allium cepa L.) landrace 'Krishnapuram' (KP) from India using high-performance liquid chromatography (HPLC)-Electrospray Ionization (ESI)-multistage Ion Trap Mass Spectrometry (ITMS). The antioxidant activity was assayed by Ferric Reducing Antioxidant Power (FRAP) and hypochlorous acid (HClO)-induced oxidative damage in human erythrocytes. The total phenolic (TPC) contents in KP onion bulb extract (with 80% methanol) found to be 1.10 ± 0.2 mg GAE/g FW and 38.88 ± 1.0 lM QE/g. The FRAP activity measured for the bulb extract was 13.20 ± 0.1 µM QE/g. KP onion bulb extracts protected red blood cells (RBC) effectively (23%) against the oxidative damage induced by HClO. HPLC-ESI-ITMS analysis showed the presence of eight flavonols and five anthocyanins. Quercetin 3,4' -O-diglucoside (384.71 ± 0.49 mg/kg FW) and cyanidin 3-(6â³-malonylglucoside) (20.95 ± 0.60 mg/kg FW) were detected as major flavonol and anthocyanin, respectively. The study suggests that KP onion has a considerable antioxidant activity due to the presence of high TPC. Moreover, quercetin glucosides are found to be more abundant than quercetin. The differences in quercetin glycosides content among different red onions could be useful for breeding programmes in the future.
Subject(s)
Antioxidants/analysis , Flavonoids/analysis , Onions/chemistry , Chromatography, High Pressure Liquid , Plant Roots/chemistry , Spectrometry, Mass, Electrospray IonizationABSTRACT
BACKGROUND: Early coronavirus disease 2019 (COVID-19) diagnosis prior to laboratory testing results is crucial for infection control in hospitals. Models exist predicting COVID-19 diagnosis, but significant concerns exist regarding methodology and generalizability. AIM: To generate the first COVID-19 diagnosis risk score for use at the time of hospital admission using the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) checklist. DESIGN: A multivariable diagnostic prediction model for COVID-19 using the TRIPOD checklist applied to a large single-centre retrospective observational study of patients with suspected COVID-19. METHODS: 581 individuals were admitted with suspected COVID-19; the majority had laboratory-confirmed COVID-19 (420/581, 72.2%). Retrospective collection was performed of electronic clinical records and pathology data. RESULTS: The final multivariable model demonstrated AUC 0.8535 (95% confidence interval 0.8121-0.8950). The final model used six clinical variables that are routinely available in most low and high-resource settings. Using a cut-off of 2, the derived risk score has a sensitivity of 78.1% and specificity of 86.8%. At COVID-19 prevalence of 10% the model has a negative predictive value (NPV) of 96.5%. CONCLUSIONS: Our risk score is intended for diagnosis of COVID-19 in individuals admitted to hospital with suspected COVID-19. The score is the first developed for COVID-19 diagnosis using the TRIPOD checklist. It may be effective as a tool to rule out COVID-19 and function at different pandemic phases of variable COVID-19 prevalence. The simple score could be used by any healthcare worker to support hospital infection control prior to laboratory testing results.
Subject(s)
COVID-19 , COVID-19 Testing , Hospitals , Humans , Retrospective Studies , SARS-CoV-2ABSTRACT
Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field. In December 2019, the WHO issued their second 'Rapid Communication´ related to RR-TB management. This reiterated their prior recommendation that a majority of people with RR/MDR-TB receive all-oral treatment regimens, and now allow for specific shorter duration regimens to be used programmatically as well. Many TB programs need clinical advice as they seek to roll out such regimens in their specific setting. In this Perspective, we highlight our early experiences and lessons learned from working with National TB Programs, adult and pediatric clinicians and civil society, in optimizing treatment of RR/MDR-TB, using shorter, highly-effective, oral regimens for the majority of people with RR/MDR-TB.
Subject(s)
Rifampin , Tuberculosis, Multidrug-Resistant , Adult , Antitubercular Agents/therapeutic use , Child , Clinical Protocols , Humans , Rifampin/therapeutic use , Time Factors , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapyABSTRACT
In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with the objective of reducing barriers to access to the new and repurposed TB drugs. Here we describe the major implementation challenges encountered in 17 endTB countries. We provide insights on how national TB programmes and other stakeholders can scale-up the programmatic use of new and repurposed TB drugs, while building scientific evidence about their safety and efficacy. For any new drug or diagnostic, multiple market barriers can slow the pace of scale-up. During 2015-2019, endTB was successful in increasing the number of patients receiving new and repurposed TB drugs in 17 countries. The endTB experience has many lessons, which are relevant to country level introduction of new TB drugs, as well as non-TB drugs and diagnostics. For example: the importation of TB drugs is possible even in the absence of registration; emphasis on good clinical monitoring is more important than pharmacovigilance reporting; national guidelines and expert committees can both facilitate and hinder innovative practice; clinicians use new and repurposed TB drugs when they are available; data collection to generate scientific evidence requires financial and human resources; pilot projects can drive national scale-up.
Subject(s)
Antitubercular Agents , Tuberculosis , Humans , Antitubercular Agents/adverse effects , Pharmacovigilance , Tuberculosis/drug therapy , Drug RepositioningABSTRACT
SETTING: Active pharmacovigilance (PV) is recommended for TB programmes, notably for multidrug-resistant TB (MDR-TB) patients treated with new drugs. Launched with the support of UNITAID in April 2015, endTB (Expand New Drug markets for TB) facilitated treatment with bedaquiline (BDQ) and/or delamanid of >2600 patients in 17 countries, and contributed to the creation of a central PV unit (PVU).OBJECTIVE: To explain the endTB PVU process by describing the serious adverse events (SAEs) experienced by patients who received BDQ-containing regimens.DESIGN: The overall PV strategy was in line with the 'advanced´ WHO active TB drug safety monitoring and management (aDSM) system. All adverse events (AEs) of clinical significance were followed up; the PVU focused on signal detection from SAEs.RESULTS and CONCLUSION: Between 1 April 2015 and 31 March 2019, the PVU received and assessed 626 SAEs experienced by 417 BDQ patients. A board of MDR-TB/PV experts reviewed unexpected and possibly drug-related SAEs to detect safety signals. The experts communicated on clusters of risks factors, notably polypharmacy and off-label drug use, encouraging a patient-centred approach of care. Organising advanced PV in routine care is possible but demanding. It is reasonable to expect local/national programmes to focus on clinical management, and to limit reporting to aDSM systems to key data, such as the SAEs.
Subject(s)
Pharmacovigilance , Tuberculosis, Multidrug-Resistant , Antitubercular Agents/adverse effects , Diarylquinolines/adverse effects , Humans , Off-Label Use , Tuberculosis, Multidrug-Resistant/drug therapyABSTRACT
BACKGROUND: Systematic screening for TB using automated chest radiography (ACR) with computer-aided detection software (CAD4TB) has been implemented at scale in Karachi, Pakistan. Despite evidence supporting the use of ACR as a pre-screen prior to Xpert® MTB/RIF diagnostic testing in presumptive TB patients, there has been no data published on its use in mass screening in real-world settings.METHOD: Screening was undertaken using mobile digital X-ray vehicles at hospital facilities and community camps. Chest X-rays were offered to individuals aged ≥15 years, regardless of symptoms. Those with a CAD4TB score of ≥70 were offered Xpert testing. The association between Xpert positivity and CAD4TB scores was examined using data collected between 1 January and 30 June 2018 using a custom-built data collection tool.RESULTS: Of the 127 062 individuals screened, 97.2% had a valid CAD4TB score; 11 184 (9.1%) individuals had a CAD4TB score ≥70. Prevalence of Xpert positivity rose from 0.7% in the <50 category to 23.5% in the >90 category. The strong linear association between CAD4TB score and Xpert positivity was found in both community and hospital settings.CONCLUSION: The strong association between CAD4TB scores and Xpert positivity provide evidence that an ACR-based pre-screening performs well when implemented at scale in a high-burden setting.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Aged , Humans , Mass Screening , Pakistan/epidemiology , Radiography , Sensitivity and Specificity , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis, Pulmonary/diagnostic imaging , Tuberculosis, Pulmonary/epidemiologySubject(s)
Melanoma/secondary , Neck/pathology , Skin Neoplasms/pathology , Spinal Cord Neoplasms/secondary , Thoracic Vertebrae/pathology , Humans , Magnetic Resonance Imaging , Male , Melanoma/diagnostic imaging , Melanoma/surgery , Middle Aged , Neurosurgical Procedures , Spinal Cord Neoplasms/diagnostic imaging , Spinal Cord Neoplasms/surgery , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery , Treatment OutcomeABSTRACT
In the current study, we have developed predictive quantitative structure-activity relationship (QSAR) models for cellular response (foetal rate lung fibroblast proliferation) and protein adsorption (fibrinogen adsorption (FA)) on the surface of tyrosine-derived biodegradable polymers designed for tissue engineering purpose using a dataset of 66 and 40 biodegradable polymers, respectively, employing two-dimensional molecular descriptors. Best four individual models have been selected for each of the endpoints. These models are developed using partial least squares regression with a unique combination of six and four descriptors for cellular response and protein adsorption, respectively. The generated models were strictly validated using internal and external metrics to determine the predictive ability and robustness of proposed models. Subsequently, the validated individual models for each response endpoints were used for the generation of 'intelligent' consensus models ( http://teqip.jdvu.ac.in/QSAR_Tools/DTCLab/ ) to improve the quality of predictions for the external data set. These models may help in prediction of virtual polymer libraries for rational design/optimization for properties relevant to biomedical applications prior to their synthesis.
Subject(s)
Biocompatible Materials/chemistry , Fibrinogen/chemistry , Models, Molecular , Polymers/chemistry , Adsorption/drug effects , Biocompatible Materials/pharmacology , Cell Physiological Phenomena/drug effects , Least-Squares Analysis , Molecular Structure , Polymers/pharmacology , Quantitative Structure-Activity Relationship , Reproducibility of ResultsABSTRACT
OBJECTIVES: The aim of the study was to investigate the extent of and factors associated with incorrect dosing of antiretroviral therapy (ART) in HIV-infected children in Harare, Zimbabwe. METHODS: All children aged 0-10 years and children aged 11-17 years who weighed < 35 kg and taking ART were recruited from the paediatric HIV clinic at Harare Hospital. Their current doses of ART drugs were compared against doses recommended by the national guidelines. RESULTS: Among 309 children recruited [55% male; median age 7 years (interquartile range (IQR) 5-10 years)], the median CD4 count was 899 cells/µL and the median duration of their current ART regimen was 11.2 months (IQR 4.9-17.1 months). Overall, 110 (35.6%) children were prescribed incorrect doses of at least one drug component within their ART regimen; 64 (20.7%) under-dosed and 49 (15.9%) over-dosed on at least one drug. Children receiving a higher than recommended dose of at least one drug were younger compared with correctly dosed children (median 6 versus 7 years, respectively; P = 0.001), had been on their current ART regimen for a shorter time (median 7.2 versus 13 months, respectively; P = 0.003) and were less likely to be receiving a three-drug fixed-dose combination (FDC; 42.9 versus 63.3%, respectively; P = 0.009). Those who were under-dosed were also less likely to be on a three-drug FDC (25 versus 63.3%, respectively; P < 0.001). CONCLUSIONS: Over a third of children were prescribed incorrect doses of ART. Children taking triple-drug FDCs were likely to be correctly dosed. Our study highlights the importance of weight monitoring at each clinical contact, training of health care providers on paediatric drug dosing and the need for wider availability of FDCs for children.