Longitudinal evaluation of physician payment reform and team-based care for chronic disease management and prevention

Background:

We evaluated a large-scale transition of primary care physicians to blended capitation models and team-based care in Ontario, Canada, to understand the effect of each type of reform on the management and prevention of chronic disease.

Methods:

We used population-based administrative data to assess monitoring of diabetes mellitus and screening for cervical, breast and colorectal cancer among patients belonging to team-based capitation, non–team-based capitation or enhanced fee-for-service medical homes as of Mar. 31, 2011 (n = 10 675 480). We used Poisson regression models to examine these associations for 2011. We then used a fitted nonlinear model to compare changes in outcomes between 2001 and 2011 by type of medical home.

Results:

In 2011, patients in a team-based capitation setting were more likely than those in an enhanced fee-for-service setting to receive diabetes monitoring (39.7% v. 31.6%, adjusted relative risk [RR] 1.22, 95% confidence interval [CI] 1.18 to 1.25), mammography (76.6% v. 71.5%, adjusted RR 1.06, 95% CI 1.06 to 1.07) and colorectal cancer screening (63.0% v. 60.9%, adjusted RR 1.03, 95% CI 1.02 to 1.04). Over time, patients in medical homes with team-based capitation experienced the greatest improvement in diabetes monitoring (absolute difference in improvement 10.6% [95% CI 7.9% to 13.2%] compared with enhanced fee for service; 6.4% [95% CI 3.8% to 9.1%] compared with non–team-based capitation) and cervical cancer screening (absolute difference in improvement 7.0% [95% CI 5.5% to 8.5%] compared with enhanced fee for service; 5.3% [95% CI 3.8% to 6.8%] compared with non–team-based capitation). For breast and colorectal cancer screening, there were no significant differences in change over time between different types of medical homes.

Interpretation:

The shift to capitation payment and the addition of team-based care in Ontario were associated with moderate improvements in processes related to diabetes care, but the effects on cancer screening were less clear.Health care systems with a strong primary care orientation have better health outcomes, lower costs and fewer disparities across population subgroups.¹ Countries around the world have been experimenting with reforms to improve the delivery of primary care, changing the way physicians are organized and paid. In the United States, several national organizations^2,3 and policy experts^4,5 have advocated a shift away from fee for service toward capitation or blended payments, and in 2015, the Centers for Medicare and Medicaid Services brought in blended payment in primary care, introducing a non–visit-based payment for chronic care management.⁶Patient-centred medical homes have provided an opportunity to transition physicians to new payment models, but they also necessitate changes in care delivery, including incorporation of team-based care, enhancement of access for patients, coordination of care and a focus on quality and safety.^7–9 Evidence suggests that team-based care is a particularly important element in improving the management and prevention of chronic disease and reducing related costs.¹⁰ Early evaluations of patient-centred medical home pilots were promising,^11,12 but a recent study of large-scale implementation showed limited improvements in the quality of chronic disease care and no reduction in health care utilization or total costs over 3 years.¹³Before 2002, primary care physicians in Ontario, Canada, were almost universally paid through a fee-for-service system. Over the past decade, more than three-quarters have transitioned to patient-centred medical homes.^14,15 About half of Ontario physicians working in patient-centred medical homes have shifted to blended capitation payments, with a portion of these physicians working in groups that also receive government funding for nonphysician health professionals to enable team-based care. However, about 40% of physicians in patient-centred medical homes still receive most of their income through fee-for-service payments. This natural health policy experiment offers a unique opportunity to compare the effectiveness of different payment models and team-based care. Early studies have shown small differences in the quality of cardiovascular¹⁶ and diabetes mellitus¹⁷ care between physicians receiving capitation payments and those receiving fee-for-service payments, but no studies have assessed changes in quality of care over time.We evaluated a large-scale transition of primary care physicians to blended capitation models and team-based care to understand the effect of each type of reform on chronic disease management and prevention over time.     

Targeted retroviral gene delivery using ultrasound

BACKGROUND: Achieving specificity of delivery represents a major problem limiting the clinical application of retroviral vectors for gene therapy, whilst lack of efficiency and longevity of gene expression limit non-viral techniques. Ultrasound and microbubble contrast agents can be used to effect plasmid DNA delivery. We therefore sought to evaluate the potential for ultrasound/microbubble-mediated retroviral gene delivery. METHODS: An envelope-deficient retroviral vector, inherently incapable of target cell entry, was combined with cationic microbubbles and added to target cells. The cells were exposed to pulsed 1 MHz ultrasound for 5 s and subsequently analysed for marker gene expression. The acoustic pressure profile of the ultrasound field, to which transduction efficiency was related, was determined using a needle hydrophone. RESULTS: Ultrasound-targeted gene delivery to a restricted area of cells was achieved using virus-loaded microbubbles. Gene delivery efficiency was up to 2% near the beam focus. Significant transduction was restricted to areas exposed to > or = 0.4 MPa peak-negative acoustic pressure, despite uniform application of the vector. An acoustic pressure-dependence was demonstrated that can be exploited for targeted retroviral transduction. The mechanism of entry likely involves membrane perturbation in the vicinity of oscillating microbubbles, facilitating fusion of the viral and cell membranes. CONCLUSIONS: We have established the basis of a novel retroviral vector technology incorporating favourable aspects of existing viral and non-viral gene delivery vectors. In particular, transduction can be controlled by means of ultrasound exposure. The technology is ideally suited to targeted delivery following systemic vector administration.     

Introduction and expansion of the SARS-CoV-2 B.1.1.7 variant and reinfections in Qatar: A nationally representative cohort study

BackgroundThe epidemiology of the SARS-CoV-2 B.1.1.7 (or Alpha) variant is insufficiently understood. This study’s objective was to describe the introduction and expansion of this variant in Qatar and to estimate the efficacy of natural infection against reinfection with this variant.Methods and findingsReinfections with the B.1.1.7 variant and variants of unknown status were investigated in a national cohort of 158,608 individuals with prior PCR-confirmed infections and a national cohort of 42,848 antibody-positive individuals. Infections with B.1.1.7 and variants of unknown status were also investigated in a national comparator cohort of 132,701 antibody-negative individuals. B.1.1.7 was first identified in Qatar on 25 December 2020. Sudden, large B.1.1.7 epidemic expansion was observed starting on 18 January 2021, triggering the onset of epidemic’s second wave, 7 months after the first wave. B.1.1.7 was about 60% more infectious than the original (wild-type) circulating variants. Among persons with a prior PCR-confirmed infection, the efficacy of natural infection against reinfection was estimated to be 97.5% (95% CI: 95.7% to 98.6%) for B.1.1.7 and 92.2% (95% CI: 90.6% to 93.5%) for variants of unknown status. Among antibody-positive persons, the efficacy of natural infection against reinfection was estimated to be 97.0% (95% CI: 92.5% to 98.7%) for B.1.1.7 and 94.2% (95% CI: 91.8% to 96.0%) for variants of unknown status. A main limitation of this study is assessment of reinfections based on documented PCR-confirmed reinfections, but other reinfections could have occurred and gone undocumented.ConclusionsIn this study, we observed that introduction of B.1.1.7 into a naïve population can create a major epidemic wave, but natural immunity in those previously infected was strongly associated with limited incidence of reinfection by B.1.1.7 or other variants.

Laith Abu-Raddad and colleagues describe the introduction and expansion of the SARS-CoV-2 B.1.1.7 variant in a national cohort in Qatar.     

Differential response of Scots pine seedlings to variable intensity and ratio of red and far‐red light

We investigated the response to increasing intensity of red (R) and far‐R (FR) light and to a decrease in R:FR ratio in Pinus sylvestris L. (Scots pine) seedling. The results showed that FR high‐irradiance response for hypocotyl elongation may be present in Scots pine and that this response is enhanced by increasing light intensity. However, both hypocotyl inhibition and pigment accumulation were more strongly affected by the R light compared with FR light. This is in contrast to previous reports in Arabidopsis thaliana (L.) Heynh. In the angiosperm, A. thaliana R light shows an overall milder effect on inhibition of hypocotyl elongation and on pigment biosynthesis compared with FR suggesting conifers and angiosperms respond very differently to the different light regimes. Scots pine shade avoidance syndrome with longer hypocotyls, shorter cotyledons and lower chlorophyll content in response to shade conditions resembles the response observed in A. thaliana. However, anthocyanin accumulation increased with shade in Scots pine, which again differs from what is known in angiosperms. Overall, the response of seedling development and physiology to R and FR light in Scots pine indicates that the regulatory mechanism for light response may differ between gymnosperms and angiosperms.     

Relationship between stability and flexibility in the most flexible region of Photinus pyralis luciferase

Firefly luciferase is a protein with a large N-terminal and a small C-terminal domain. B-factor analysis shows that its C-terminal is much more flexible than its N-terminal. Studies on hyperthermophile proteins have been shown that the increased thermal stability of hyperthermophile proteins is due to their enhanced conformational rigidity and the relationship between flexibility, stability and function in most of proteins is on debate. Two mutations (D474K and D476N) in the most flexible region of firefly luciferase were designed. Thermostability analysis shows that D476N mutation doesn't have any significant effect but D474K mutation destabilized protein. On the other hand, flexibility analysis using dynamic quenching and limited proteolysis demonstrates that D474K mutation became much more flexible than wild type although D476N doesn't have any significant difference. Intrinsic and ANS fluorescence studies demonstrate that D476N mutation is brought about by structural changes without significant effect on thermostability and flexibility. Molecular modeling reveals that disruption of a salt bridge between D(474) and K(445) accompanying with some H-bond deletion may be involved in destabilization of D474K mutant.     

Increased Thymic Cell Turnover under Boron Stress May Bypass TLR3/4 Pathway in African Ostrich

Previous studies revealed that thymus is a targeted immune organ in malnutrition, and high-boron stress is harmful for immune organs. African ostrich is the living fossil of ancient birds and the food animals in modern life. There is no report about the effect of boron intake on thymus of ostrich. The purpose of present study was to evaluate the effect of excessive boron stress on ostrich thymus and the potential role of TLR3/4 signals in this process. Histological analysis demonstrated that long-term boron stress (640 mg/L for 90 days) did not disrupt ostrich thymic structure during postnatal development. However, the numbers of apoptotic cells showed an increased tendency, and the expression of autophagy and proliferation markers increased significantly in ostrich thymus after boron treatment. Next, we examined the expression of TLR3 and TLR4 with their downstream molecular in thymus under boron stress. Since ostrich genome was not available when we started the research, we first cloned ostrich TLR3 TLR4 cDNA from thymus. Ostrich TLR4 was close to white-throated Tinamou. Whole avian TLR4 codons were under purify selection during evolution, whereas 80 codons were under positive selection. TLR3 and TLR4 were expressed in ostrich thymus and bursa of fabricius as was revealed by quantitative real-time PCR (qRT-PCR). TLR4 expression increased with age but significantly decreased after boron treatment, whereas TLR3 expression showed the similar tendency. Their downstream molecular factors (IRF1, JNK, ERK, p38, IL-6 and IFN) did not change significantly in thymus, except that p100 was significantly increased under boron stress when analyzed by qRT-PCR or western blot. Taken together, these results suggest that ostrich thymus developed resistance against long-term excessive boron stress, possibly by accelerating intrathymic cell death and proliferation, which may bypass the TLR3/4 pathway. In addition, attenuated TLRs activity may explain the reduced inflammatory response to pathogens under boron stress.     

Density,Destinations or Both? A Comparison of Measures of Walkability in Relation to Transportation Behaviors,Obesity and Diabetes in Toronto,Canada

The design of suburban communities encourages car dependency and discourages walking, characteristics that have been implicated in the rise of obesity. Walkability measures have been developed to capture these features of urban built environments. Our objective was to examine the individual and combined associations of residential density and the presence of walkable destinations, two of the most commonly used and potentially modifiable components of walkability measures, with transportation, overweight, obesity, and diabetes. We examined associations between a previously published walkability measure and transportation behaviors and health outcomes in Toronto, Canada, a city of 2.6 million people in 2011. Data sources included the Canada census, a transportation survey, a national health survey and a validated administrative diabetes database. We depicted interactions between residential density and the availability of walkable destinations graphically and examined them statistically using general linear modeling. Individuals living in more walkable areas were more than twice as likely to walk, bicycle or use public transit and were significantly less likely to drive or own a vehicle compared with those living in less walkable areas. Individuals in less walkable areas were up to one-third more likely to be obese or to have diabetes. Residential density and the availability of walkable destinations were each significantly associated with transportation and health outcomes. The combination of high levels of both measures was associated with the highest levels of walking or bicycling (p<0.0001) and public transit use (p<0.0026) and the lowest levels of automobile trips (p<0.0001), and diabetes prevalence (p<0.0001). We conclude that both residential density and the availability of walkable destinations are good measures of urban walkability and can be recommended for use by policy-makers, planners and public health officials. In our setting, the combination of both factors provided additional explanatory power.     

DNA Tetrominoes: The Construction of DNA Nanostructures Using Self-Organised Heterogeneous Deoxyribonucleic Acids Shapes

The unique programmability of nucleic acids offers alternative in constructing excitable and functional nanostructures. This work introduces an autonomous protocol to construct DNA Tetris shapes (L-Shape, B-Shape, T-Shape and I-Shape) using modular DNA blocks. The protocol exploits the rich number of sequence combinations available from the nucleic acid alphabets, thus allowing for diversity to be applied in designing various DNA nanostructures. Instead of a deterministic set of sequences corresponding to a particular design, the protocol promotes a large pool of DNA shapes that can assemble to conform to any desired structures. By utilising evolutionary programming in the design stage, DNA blocks are subjected to processes such as sequence insertion, deletion and base shifting in order to enrich the diversity of the resulting shapes based on a set of cascading filters. The optimisation algorithm allows mutation to be exerted indefinitely on the candidate sequences until these sequences complied with all the four fitness criteria. Generated candidates from the protocol are in agreement with the filter cascades and thermodynamic simulation. Further validation using gel electrophoresis indicated the formation of the designed shapes. Thus, supporting the plausibility of constructing DNA nanostructures in a more hierarchical, modular, and interchangeable manner.