The value of FDG-PET/CT imaging in the assessment, monitoring, and management of COVID-19.

The pathogenesis of Coronavirus Disease 2019 (COVID-19) involves cytokine-driven recruitment and accumulation of inflammatory cells at sites of infection. These activated neutrophils, monocytes, and effector T cells are highly glycolytic and thus appear as [18]F-labeled fluorodeoxyglucose (FDG) avid sites on positron emission tomography (PET) imaging. FDG-PET-computed tomography (FDG-PET/CT) is a highly sensitive modality for the detection, monitoring, and assessing response related to COVID-19 disease activity that holds significant clinical relevance. To date, concerns over cost, access, and undue radiation exposure have limited the use of FDG-PET/CT in COVID-19 to a small number of individuals where PET-based interventions were already indicated. In this review, we summarize the existing literature on the use of FDG-PET in the detection and monitoring of COVID-19 with particular focus on several areas of clinical relevance that warrant future research: (1) incidental early detection of subclinical COVID-19 in patients who have undergone FDG-PET for other underlying diseases, (2) standardized quantitative assessment of COVID-19 disease burden at specific points in time, and (3) analysis of FDG-PET/CT data leading to better characterization of COVID-19 pathogenesis. Employing FDG-PET/CT for these purposes may allow for the earliest detection of COVID-19-associated venous thromboembolism (VTE), standardized monitoring of disease progression and response to treatment, and better characterization of the acute and chronic complications of this disease.

Mesenchymal stromal cell therapy compared to SGLT2-inhibitors and usual care in treating diabetic kidney disease: A cost-effectiveness analysis.

BACKGROUND AND OBJECTIVES: To simulate the cost-effectiveness of Mesenchymal Stromal Cell (MSC) therapy compared to sodium/glucose co-transporter 2 inhibitors (SGLT2i) or usual care (UC) in treating patients with Diabetic Kidney Disease (DKD). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This Markov-chain Monte Carlo model adopted a societal perspective and simulated 10,000 patients with DKD eligible for MSC therapy alongside UC using a lifetime horizon. This cohort was compared with an SGLT2i alongside UC arm and a UC only arm. Model input data were extracted from the literature. A threshold of $47,000 per quality-adjusted life year and a discount rate of 3% were used. The primary outcome measure was incremental net monetary benefit (INMB). Sensitivity analysis was conducted to examine: parameter uncertainty; threshold effects regarding MSC effectiveness and cost; and INMB according to patient age (71 vs 40 years), sex, and jurisdiction (UK, Italy and Ireland). RESULTS: While MSC was more cost-effective than UC, both the UC and MSC arms were dominated by SLGT2i. Relative to SGLT2i, the INMB's for MSC and UC were -$4,158 and -$10,085 respectively indicating that SGLT2i, MSC and UC had a 64%, 34% and 1% probability of being cost-effective at the given threshold, respectively. This pattern was consistent across most scenarios; driven by the relatively low cost of SGLT2i and demonstrated class-effect in delaying kidney failure and all-cause mortality. When examining younger patients at baseline, SGLT2i was still the most cost-effective but MSC performed better against UC given the increased lifetime benefit from delaying progression to ESRD. CONCLUSIONS: The evidence base regarding the effectiveness of MSC therapy continues to evolve. The potential for these therapies to reverse kidney damage would see large improvements in their cost-effectiveness as would targeting such therapies at younger patients and/or those for whom SGLT2i is contra-indicated.

The impact of chronic kidney disease on developed countries from a health economics perspective: A systematic scoping review.

Chronic kidney disease (CKD) affects over 10% of the global population and poses significant challenges for societies and health care systems worldwide. To illustrate these challenges and inform cost-effectiveness analyses, we undertook a comprehensive systematic scoping review that explored costs, health-related quality of life (HRQoL) and life expectancy (LE) amongst individuals with CKD. Costs were examined from a health system and societal perspective, and HRQoL was assessed from a societal and patient perspective. Papers published in English from 2015 onward found through a systematic search strategy formed the basis of the review. All costs were adjusted for inflation and expressed in US$ after correcting for purchasing power parity. From the health system perspective, progression from CKD stages 1-2 to CKD stages 3a-3b was associated with a 1.1-1.7 fold increase in per patient mean annual health care cost. The progression from CKD stage 3 to CKD stages 4-5 was associated with a 1.3-4.2 fold increase in costs, with the highest costs associated with end-stage renal disease at $20,110 to $100,593 per patient. Mean EuroQol-5D index scores ranged from 0.80 to 0.86 for CKD stages 1-3, and decreased to 0.73-0.79 for CKD stages 4-5. For treatment with renal replacement therapy, transplant recipients incurred lower costs and demonstrated higher HRQoL scores with longer LE compared to dialysis patients. The study has provided a comprehensive updated overview of the burden associated with different CKD stages and renal replacement therapy modalities across developed countries. These data will be useful for the assessment of new renal services/therapies in terms of cost-effectiveness.

Chronic kidney disease, health-related quality of life and their associated economic burden among a nationally representative sample of community dwelling adults in England.

Chronic kidney disease (CKD) affects up to 15% of the adult population and is strongly associated with other non-communicable chronic diseases including diabetes. However, there is limited information on a population basis of the relationship between CKD and health-related quality of life (HRQoL) and the consequent economic cost. We investigated this relationship in a representative sample in England using the 2010 Health Survey for England. Multivariable Tobit models were used to examine the relationship between HRQoL and CKD severity. HRQoL was converted to quality adjusted life year (QALY) measures by combining decrements in quality of life with reductions in life expectancy associated with increased disease severity. QALYs were adjusted for discounting and monetised using the UK threshold for reimbursement of £30,000. The QALYs were then used in conjunction with forecasted prevalence to estimate the HRQoL burden associated with CKD among individuals with diabetes up to 2025. Individuals with more severe CKD had lower HRQoL compared to those with better kidney function. Compared to those with normal/low normal kidney function and stage 1 CKD, those with stage 2, stage 3 with albuminuria and stage 4/5 CKD experienced a decrement of 0.11, 0.18 and 0.28 in their utility index, respectively. Applying the UK reimbursement threshold for a QALY, the monetised lifetime burden of reduced HRQoL due to stage 2, stage 3 with albuminuria and stage 4/5 CKD were £103,734; £83,399; £125,335 in males and £143,582; £70,288; £203,804 in females, respectively. Utilizing the predicted prevalence of CKD among individuals with diabetes mellitus, the economic burden of CKD per million of individuals with diabetes is forecasted at approximately £11.4 billion in 2025. In conclusion, CKD has a strong adverse impact on HRQoL in multiple domains. The estimated economic burden of CKD among individuals with diabetes mellitus in the UK is projected to rise markedly over time.

Comparison of low versus high tacrolimus levels in kidney transplantation: assessment of efficacy by protocol biopsies.

BACKGROUND: The use of calcineurin inhibitors is generally guided by drug blood levels. However, those levels are chosen based on clinical experience, lacking adequate titration studies. METHODS: In these analyses, we compared clinical and histologic endpoints in two groups of kidney transplant recipients: in the first (HiTAC, January 2000 to June 2002, n=245) tacrolimus levels were significantly higher than in the second (LoTAC, July 2002 to September 2004, n=330). This change in drug levels (15% reduction) was made in an attempt to reduce the incidence of polyoma virus nephropathy (PVAN). Other immunosuppressive medications were unchanged during these two time periods. RESULTS: The recipient and donor demographics were not statistically different between the two groups. Compared to HiTAC, at one year posttransplant LoTAC had: 1) lower incidence of PVAN (10.5% vs. 2.5%, P<0.0001); 2) lower fasting glucose levels; 3) higher iothalamate glomerular filtration rate (52+/-19 vs. 59+/-17 ml/min/m, P<0.0001); and 4) on protocol one-year biopsies, lower incidence and severity of interstitial fibrosis (67% vs. 45%, P=0.003) and tubular atrophy (82% vs., 66%, P=0.01). The incidence and severity of acute rejection episodes was similar between both groups (7.8% versus 7.6%). CONCLUSIONS: Modest reductions in tacrolimus exposure early posttransplant are associated with significant beneficial effects for the patient and the allograft without an increased immunologic risk.

Integrated program enhancements increased utilization of Farmers' Market Nutrition Program.

Three New York State agencies undertook a state-wide initiative in 2001 to enhance the effectiveness of the Special Supplemental Program for Women, Infants, and Children (WIC) Farmers' Market Nutrition Program (FMNP) for both families and farmers. The program enhancements included four components intended to influence market and consumer behavior: hiring a state-wide Cornell Cooperative Extension staff member to initiate and coordinate FMNP promotion efforts; increased collaboration among state-level agencies; local-level community capacity-building; and dissemination of newly developed nutrition education resources. Because components were overlapping and potentially synergistic, the total effect was considered. To test the hypothesis that the enhancements increased Program utilization as measured by redemption rates, a time-series, quasi-experimental design was employed in which observed 2001 redemption was tested for departure from earlier trends. Linear regression showed FMNP coupon redemption rates from 1996 through 2000 decreased 2.36% annually (P = 0.002). This trend was interrupted in 2001 when actual redemption exceeded predicted redemption by >2.2% (P < 0.055). Alternate explanations for this shift were deemed improbable. These findings show that FMNP goals were advanced through a coordinated, collaborative initiative with activities at state and local levels, resulting in increased utilization of FMNP benefits by WIC participants and increased income to local farmers.