How are pay-for-performance schemes in healthcare designed in low- and middle-income countries? Typology and systematic literature review.

BACKGROUND: Pay for performance (P4P) schemes provide financial incentives to health workers or facilities based on the achievement of pre-specified performance targets and have been widely implemented in health systems across low and middle-income countries (LMICs). The growing evidence base on P4P highlights that (i) there is substantial variation in the effect of P4P schemes on outcomes and (ii) there appears to be heterogeneity in incentive design. Even though scheme design is likely a key determinant of scheme effectiveness, we currently lack systematic evidence on how P4P schemes are designed in LMICs. METHODS: We develop a typology to classify the design of P4P schemes in LMICs, which highlights different design features that are a priori likely to affect the behaviour of incentivised actors. We then use results from a systematic literature review to classify and describe the design of P4P schemes that have been evaluated in LMICs. To capture academic publications, Medline, Embase, and EconLit databases were searched. To include relevant grey literature, Google Scholar, Emerald Insight, and websites of the World Bank, WHO, Cordaid, Norad, DfID, USAID and PEPFAR were searched. RESULTS: We identify 41 different P4P schemes implemented in 29 LMICs. We find that there is substantial heterogeneity in the design of P4P schemes in LMICs and pinpoint precisely how scheme design varies across settings. Our results also highlight that incentive design is not adequately being reported on in the literature - with many studies failing to report key design features. CONCLUSIONS: We encourage authors to make a greater effort to report information on P4P scheme design in the future and suggest using the typology laid out in this paper as a starting point

Real-time interferometric refractive index change measurement for the direct detection of enzymatic reactions and the determination of enzyme kinetics

Back scatter interferometry (BSI) is a sensitive method for detecting changes in the bulk refractive index of a solution in a microfluidic system. Here we demonstrate that BSI can be used to directly detect enzymatic reactions and, for the first time, derive kinetic parameters. While many methods in biomedical assays rely on detectable biproducts to produce a signal, direct detection is possible if the substrate or the product exert distinct differences in their specific refractive index so that the total refractive index changes during the enzymatic reaction. In this study, both the conversion of glucose to glucose-6-phosphate, catalyzed by hexokinase, and the conversion of adenosine-triphosphate to adenosine di-phosphate and mono-phosphate, catalyzed by apyrase, were monitored by BSI. When adding hexokinase to glucose solutions containing adenosine-triphosphate, the conversion can be directly followed by BSI, which shows the increasing refractive index and a final plateau corresponding to the particular concentration. From the initial reaction velocities, KM was found to be 0.33 mM using Michaelis⁻Menten kinetics. The experiments with apyrase indicate that the refractive index also depends on the presence of various ions that must be taken into account when using this technique. This study clearly demonstrates that measuring changes in the refractive index can be used for the direct determination of substrate concentrations and enzyme kinetics

Protostellar accretion traced with chemistry. High resolution C18O and continuum observations towards deeply embedded protostars in Perseus

Context: Understanding how accretion proceeds is a key question of star formation, with important implications for both the physical and chemical evolution of young stellar objects. In particular, very little is known about the accretion variability in the earliest stages of star formation. Aims: To characterise protostellar accretion histories towards individual sources by utilising sublimation and freeze-out chemistry of CO. Methods: A sample of 24 embedded protostars are observed with the Submillimeter Array (SMA) in context of the large program "Mass Assembly of Stellar Systems and their Evolution with the SMA" (MASSES). The size of the C$^{18}$O emitting region, where CO has sublimated into the gas-phase, is measured towards each source and compared to the expected size of the region given the current luminosity. The SMA observations also include 1.3 mm continuum data, which are used to investigate whether a link can be established between accretion bursts and massive circumstellar disks. Results: Depending on the adopted sublimation temperature of the CO ice, between 20% and 50% of the sources in the sample show extended C$^{18}$O emission indicating that the gas was warm enough in the past that CO sublimated and is currently in the process of refreezing; something which we attribute to a recent accretion burst. Given the fraction of sources with extended C$^{18}$O emission, we estimate an average interval between bursts of 20000-50000 yr, which is consistent with previous estimates. No clear link can be established between the presence of circumstellar disks and accretion bursts, however the three closest known binaries in the sample (projected separations <20 AU) all show evidence of a past accretion burst, indicating that close binary interactions may also play a role in inducing accretion variability.Comment: Accepted for publication in A&A, 21 pages, 13 figure

Atrial fibrillation, liver cirrhosis, thrombosis, and bleeding:A Danish population-based cohort study

OBJECTIVES: We examined the impact of liver cirrhosis on the risk of thromboembolic events and bleeding complications in patients with atrial fibrillation or flutter (AFF). METHODS: This population‐based cohort study used data from Danish health registries. We identified all patients with a first‐time diagnosis of AFF during 1995 to 2015, and followed them from their AFF diagnosis until the end of 2016. Patients were categorized according to the presence or absence of liver cirrhosis. We computed incidence rates per 1000 person‐years and hazard ratios (HRs) with 95% confidence intervals (CIs) based on Cox regression analyses, adjusting for age, CHA(2)DS(2)VASc score, and Charlson Comorbidity Index score. RESULTS: We identified 273 225 patients with AFF. Of these, 1463 (0.54%) had liver cirrhosis. During 0 to 5 years of follow‐up, compared to patients without liver cirrhosis, patients with liver cirrhosis had higher incidence rates and hazards of ischemic stroke (29.7 vs 21.6; HR, 1.3; 95% CI, 1.1‐1.6), venous thromboembolism (9.2 vs 5.5; HR, 1.5; 95% CI, 1.2‐2.3), but not myocardial infarction (10.2 vs 11.2; HR, 0.9; 95% CI, 0.7–1.2). Patients with liver cirrhosis also had higher rates of hemorrhagic stroke (5.8 vs 3.3; HR, 1.7; 95% CI, 1.1‐2.6), subdural hemorrhage (5.3 vs 1.6; HR, 3.2; 95% CI, 2.1‐4.9), hemorrhage of the lung or urinary tract (24.6 vs 15.2; HR, 1.6; 95% CI, 1.3–2.0), and gastrointestinal hemorrhage (34.5 vs 10.4; HR, 3.3; 95% CI, 2.7–3.9). CONCLUSION: In patients with AFF, liver cirrhosis was associated with an elevated risk of ischemic stroke, venous thromboembolism, and all evaluated bleeding complications

Size-Dependence of the Wavefunction of Self-Assembled Quantum Dots

The radiative and non-radiative decay rates of InAs quantum dots are measured by controlling the local density of optical states near an interface. From time-resolved measurements we extract the oscillator strength and the quantum efficiency and their dependence on emission energy. From our results and a theoretical model we determine the striking dependence of the overlap of the electron and hole wavefunctions on the quantum dot size. We conclude that the optical quality is best for large quantum dots, which is important in order to optimally tailor quantum dot emitters for, e.g., quantum electrodynamics experiments.Comment: 5 pages, 3 figure

Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction. A report from the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial (I-Preserve)

Background—In patients with HF and preserved ejection fraction (HFpEF), little is known about the characteristics of and outcomes in those with and without diabetes. Methods—We examined clinical and echocardiographic characteristics and outcomes in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), according to history of diabetes. Cox regression models were used to estimate hazard ratios (HR) for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses. Results—Overall, 1134 of 4128 patients (27%) had diabetes. Compared to those without diabetes, they were more likely to have a history of myocardial infarction (28% vs. 22%), higher BMI (31kg/m2 vs. 29kg/m2), worse Minnesota living with HF score (48 vs. 40), higher median NT-proBNP concentration (403 vs 320 pg/ml; all p&lt;0.01), more signs of congestion but no significant difference in LVEF. Patients with diabetes had a greater left ventricular (LV) mass and left atrial area than patients without diabetes. Doppler E wave velocity (86 vs 76 cm/sec, p&lt;0.0001) and the ratio of E/e' (11.7 vs 10.4, p=0.010) were higher in patients with diabetes. Over a median follow-up of 4.1 years, cardiovascular death or HF hospitalization occurred in 34% of patients with diabetes vs. 22% of those without diabetes; adjusted HR 1.75 (95% CI 1.49-2.05) and 28% vs. 19% of patients with and without diabetes died; adjusted HR 1.59 (1.33-1.91). Conclusions—In HFpEF, patients with diabetes have more signs of congestion, worse quality of life, higher NT-proBNP levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes on outcomes in HFPEF, and whether they are modifiable

Mass-Spectrometry Based Proteome Comparison of Extracellular Vesicle Isolation Methods:Comparison of ME-kit, Size-Exclusion Chromatography, and High-Speed Centrifugation

Extracellular vesicles (EVs) are small membrane-enclosed particles released by cells under various conditions specific to cells&rsquo; biological states. Hence, mass-spectrometry (MS) based proteome analysis of EVs in plasma has gained much attention as a method to discover novel protein biomarkers. MS analysis of EVs in plasma is challenging and EV isolation is usually necessary. Therefore, we compared differences in abundance, subtypes, and contamination for EVs isolated by high-speed centrifugation, size exclusion chromatography (SEC), and peptide-affinity precipitation (PAP/ME kit) for subsequent MS-based proteome analysis. Successful EV isolation was evaluated by nanoparticle-tracking analysis, immunoblotting, and transmission electron microscopy, while EV abundance, EV subtypes, and contamination was evaluated by label-free tandem MS. High-speed centrifugation and SEC isolates showed high EV abundance at the expense of contamination by non-EV proteins and lipoproteins, respectively. These two methods also resulted in EVs of a similar type, however, with smaller EVs in SEC isolates. PAP isolates had a relatively low EV abundance and high contamination. We consider high-speed centrifugation and SEC suitable as EV isolation for MS biomarker studies, where the choice between the two should depend on the scientific questions and whether the focus is on larger or smaller EVs or a combination of both

Risk related to pre–diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial

Background—The prevalence of pre–diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. Methods and Results—We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: &lt;6.0% [&lt;42 mmol/mol], 6.0%–6.4% [42–47 mmol/mol; pre–diabetes mellitus], and ≥6.5% [≥48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n=2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52;P&lt;0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre–diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, &gt;6.5%) and known diabetes mellitus compared with those with HbA1c&lt;6.0% was 1.39 (1.17–1.64); P&lt;0.001 and 1.64 (1.43–1.87); P&lt;0.001, respectively. Patients with pre–diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10–1.47];P&lt;0.001) compared with those with HbA1c&lt;6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. Conclusions—In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre–diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c &lt;6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status