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RATIONALE India is experiencing a regional increase in cases of multidrug-resistant tuberculosis (MDR-TB). Given the complexity of MDR-TB diagnosis and care, we sought to address key knowledge gaps in MDR risk factors, care delays, and drivers of delay to help guide disease control. METHODS From 1/2018-9/2019, we conducted interviews with adults registered with the National TB Elimination Program (NTEP) for MDR (n=128) and non-MDR-TB (n=269) treatment to quantitatively and qualitatively study care pathways. We collected treatment records and GeneXpert-TB/RIF diagnostic reports. MEASUREMENT AND MAIN RESULTS MDR-TB was associated with young age, and crowded residence. GeneXpert rifampicin resistance diversity was measured at 72.5% Probe E. Median time from symptom onset to diagnosis of MDR was 90 days vs. 60 days for non-MDR, Wilcoxon-P

This letter demonstrates, for the first time, a novel, rapid automated whole blood clot retraction assay utilizing quartz crystal microbalance resonant frequency monitoring. Tissue factor is selected to initiate coagulation. The test turnaround time is 10–20 min, during which a real-time coagulation trace is recorded in parallel with a reference coagulation trace. The reference sample is the same blood sample that is treated by platelet aggregation inhibitor, and the difference between the two traces indicates the quantitative platelet effect on clotting. This differential approach enables determination of a hematocrit-independent parameter characterizing the intensity of clot retraction. In the case of samples with normal hemostatic characteristics, the intensity of retraction is a linear function of platelet count, whereas the retraction is reduced in the case of platelet hypofunction. Moreover, in combination with a clotting time parameter derived from the same coagulation trace, the method allows primary differentiation between three groups of bleeding disorders of various etiology, including platelet disorders, defects in plasma factors, and hypofibrinogenaemia.

It is well-established that alterations in cell morphology are regulated by cell signalling pathways, with the qualitative and quantitative monitoring of these intrinsic processes being of potential diagnostic value. Moreover, the deformability of red blood cells (RBCs) plays a key role in microcirculation, with alterations in rigidity correlated with disease models such as diabetes mellitus, sickle cell anaemia and sepsis. Here a novel assay for monitoring changes in deformability of RBCs is described that integrates quartz-crystal microbalance and a mathematical model, and extrapolates qualitative and quantitative information pertinent to changes in cell elasticity. The ability of this assay to differentiate reliably between normal RBCs and ones artificially rigidized in a manner consistent with the disease-state RBCs is demonstrated. This simple, benchtop assay has significant potential for application in disease cohorts where aberrant deformability of RBCs is indicative of disease progression.

Although therapeutic hypothermia (TH) is the standard of care for hypoxic ischaemic encephalopathy in high-income countries, the safety and efficacy of this therapy in low-income and middle-income countries (LMICs) is unknown. We aimed to describe the feasibility of TH using a low-cost servo-controlled cooling device and the short-term outcomes of the cooled babies in LMIC. Design: We recruited babies with moderate or severe hypoxic ischaemic encephalopathy (aged

Acute infective diarrhoea remains one of the most common causes of morbidity and mortality in children under 5 years of age. This paper reports on a 7-year experience of management of paediatric diarrhoea at King Edward VIII Hospital, Durban, in which an inpatient casefatality rate of nearly 25% was reduced to less than 7%, and the admission rate was reduced by 60% by a cumulative effect of the following measures: one of four paediatric wards was converted into a diarrhoea ward; improved attention to protocol resulted in a rapid reduction in the inpatient case-fatality rate, but further improvement resulted from a strong commitment to an efficient outpatient oral rehydration protocol to reduce the pressure on inpatient beds, as well asa simplified approach to fluid therapy; and a formula was developed based on units of 5 mVkg/h, and applicable to both oral and intravenous routes. The most important assessment of dehydrated patients is determination of a need for resuscitation. In less severely ill patients it is not necessary to calculate rehydration fluid requirements by a 'percent dehydration' formula.S Afr Med J 1995; 85: 655-658

The monitoring of bleeding and clotting risk is a critical component of patient care, as either excessive bleeding or abnormal clotting can have obvious and serious consequences for health and well-being and is related to many other co-morbidities. Classical hemostasis management has been around the monitoring of the time it takes activated blood samples to clot. Such techniques have moved from central laboratory tests to point-of-care technologies, allowing more effective management and treatment. However, such techniques are limited in the information they provide on clotting or bleeding status. There is a big move toward novel approaches which purport to be more representative of an individual's clotting and bleeding risk. These techniques are already being used in, and developed for, point-of-care applications.

The coagulation of blood plasma and the effect of fibrinogen concentration were studied with a quartz crystal microbalance (QCM), where frequency and half-width at half-maximum (bandwidth) values measured from the conductance spectrum near resonant frequency were used. Bandwidth change is an indicator of energy dissipation, allowing for an understanding of qualitative changes occurring during fibrin clot formation. Both frequency shift (Δ f ) and bandwidth shift (Δ Γ ) were dependent on the concentration of fibrinogen in plasma. We defined a sum of squares function α (= Δ f 2 /1000 + Δ Γ 2 /1000) that measures absolute changes in QCM resonant characteristics to semi-quantitatively include an overall contribution of adsorbed mass and elastic modulus components and a function β (= 1 − Δ Γ /Δ f ) that indicates qualitatively the nature of response based on its deviation from ideal Newtonian behaviour. Increasing concentration of fibrinogen resulted in an increase in the value of α , showing that a larger amount of fibrinogen results in larger amount of coupled viscoelastic mass. Changes in β indicated that the nature of changes occurring was very similar to Newtonian and that coupling of rigid-mass dominates the overall response in the early stage of coagulation and in the later stage growing elastic mass compensates some of the response.

Quartz crystal microbalance (QCM) is a sensitive technique for real-time monitoring of cell adsorption, aggregation and cell-to-surface interaction processes. However, cell adhesion time courses are usually considered as merely qualitative, being presented in terms of QCM resonant frequency shift and/or changes in the dissipation parameter, the precise physical meanings of which are not derived. In the present study, a model of cell adhesion to the QCM sensor surface was proposed. The main output parameter of the model is the rigid mass density, Mr, being related to QCM resonant frequency and dissipation with a simple expression. From this, it can be determined that Mr is the mass density of the layer formed by all directly adhered parts of the cell, being rigidly coupled to the sensor surface. We postulate that the Mr(t) value is proportional to the number of cells adhered by the time t, and that the coefficient of this proportionality is strongly dependent on cell-to-surface interaction forces.

Blood is a clinically-important analytical matrix that is routinely selected for disease monitoring. Having a clear understanding of the mechanisms involved in blood coagulation is a key consideration in haemostasis, with modern clinical practices requiring rapid, miniaturised and informative diagnostic platforms to reliably study changes in viscoelasticity (VE). Oscillatory transducers such as the Quartz Crystal Microbalance (QCM) have considerable potential in this area, provided that they present simple, linear rheometric readings which can be adequately analysed and interpreted. Hence, integrating QCM data obtained in the laboratory with mathematical modelling of acoustic interactions between quartz crystal surfaces and coagulating blood is an important consideration for modelling thrombus formation. Here, we provide a comprehensive overview of experimental and theoretical applications currently being employed to monitor and model the VE properties of coagulating blood when applied to a QCM resonator, with key emphasis on data modelling and interpretation.