Considerations to increase rates of breast cancer screening across populations.

OBJECTIVES: COVID-19 has caused considerable drops in utilization of breast cancer screening services during the pandemic, especially among certain racial and ethnic groups. Members of the Community Oncology Alliance (COA)-including the COA president, South Carolina oncologist Kashyap Patel, MD-have reported increases in patients, particularly those of color, presenting with stage III and IV cancer at diagnosis. According to data released by the Biden administration, more than 9.5 million recommended cancer screenings had been missed in the United States as a result of the COVID-19 pandemic, as of February 2022. President Joe Biden and First Lady Jill Biden, EdD, aim to address this in the 2022 revitalized Cancer Moonshot Initiative. The findings made by COA as well as by Avalere also suggest that the pandemic has exacerbated existing health care disparities. METHODS: Using a multipayer database, we analyzed breast cancer screening rates for 2 periods-March 1 to September 30, 2019, and March 1 to September 30, 2020-among Medicare fee-for-service (FFS), managed Medicaid, and commercial insurance beneficiaries to understand the potential impact of the COVID-19 pandemic on adherence to the US Preventive Services Task Force breast cancer screening recommendations, which are currently undergoing review. Screening rates were evaluated across 5 racial/ethnic groups and by payer type. RESULTS: Mean monthly mammogram screening rates among eligible White Medicare FFS beneficiaries dropped to 0.6% in April 2020, but these screening rates recovered to 6.5% by June 2020. Screening rates for eligible Black Medicare FFS beneficiaries recovered on a pace slightly slower than that of White beneficiaries, but more rapidly than that of other groups. By comparison, American Indian/Alaska Native beneficiaries had a mean monthly screening rate of 0.5% in April 2020, which recovered to 3.1% in June 2020; these were below 2019 screening rates of 4.2% for April and 3.9% for June. Differences in screening rates by payer type were also observed. Patients with commercial insurance had higher screening rates compared with those covered by Medicare FFS and managed Medicaid. CONCLUSIONS: Our principal finding shows that mean breast cancer screening rates decreased in April 2020 across all payers, but recovery to prepandemic screening levels has occurred more slowly among certain racial and ethnic minority groups. Differences in recovery rates by payer type highlight a strong relationship between income level and screening utilization.

The cost savings of biosimilars can help increase patient access and lift the financial burden of health care systems.

BACKGROUND: Biologics have provided improved clinical benefits to patients, but they come at a huge expense due to the high costs associated with their development and manufacturing. Biosimilars, which have been clinically studied and have demonstrated to be efficacious and safe, are more cost-effective versions of biologics, however, their uptake has been slow in the United States (US) compared to in the European Union (EU). OBJECTIVES: In this analysis, we review the challenges to increased biosimilar use in the US and the successful strategies employed to increase biosimilar uptake in the EU. CONCLUSIONS: Greater utilization of biosimilars in the US is an achievable goal but the federal government, pharmaceutical companies, and medical associations/institutions will need to work together to address patient and physician concerns and to remove incentives for using more expensive treatment options.

Innovative cost-effective method to repair lacrimal cannaliculi laceration - finding proximal end and stent.

Purpose: To explore a new technique to find out the proximal end of lacerated canaliculi and a new material for the stent. Methods: Surgery was performed on 9 eyes of 9 patients using a 5/0 prolene suture needle as a modified probe. Prolene suture was inserted as a stent and left in place for two months. All the data were analyzed. Results: The surgery was successful in all cases and the prolene were removed after two months. The mean follow-up time after the tube removal was 3.8 months (range 3-6 months). No other complications associated with the prolene sutures were noticed except for epiphora and corneal irritation in three cases. All the tubes were removed successfully without any difficulty. No iatrogenic injuries occurred during prolene removal. Conclusions: The reported surgical technique is a very cost-effective option for lacrimal canalicular laceration repair.

Optimizing vancomycin dosage regimens in relation to high-flux haemodialysis.

Objectives: To develop a population pharmacokinetic (PK) model for vancomycin in adults receiving high-flux haemodialysis (HFHD) in an effort to optimize vancomycin dosing in this population. Methods: A population PK model using NONMEM was developed using retrospective data collected from 48 vancomycin courses administered to patients (n = 37) receiving HFHD. Fixed-dose [1.5 g loading dose (LD), 1 g maintenance dose (MD)], literature-adapted weight-based (WBL; 20 mg/kg LD, 10 mg/kg MD) and hospital-adapted weight-based (WBH; 25-30 mg/kg LD, 20-25 mg/kg MD) dosage regimens were then simulated using the Monte Carlo method. The PTA was an AUC24/MIC ≥400 with success being a PTA ≥90%. Results: The data were best described using a two-compartment model. It was observed that fixed-dose and WBL dosage regimens resulted in a PTA ≤90% for most days. The WBH dosing achieved a PTA ≥90% on most days, but there were supratherapeutic concentrations with repeated dosing of vancomycin. If HFHD was delayed by 48-72 h after the LD, the PTA would fall below 90%. A dose-optimized regimen was developed: 30 mg/kg LD and 10 mg/kg MD given on HFHD days. An additional dose of 500 mg or 1 g was administered 24 h after the LD if HFHD occurred 48-72 h post-LD. This dose-optimized regimen afforded a PTA ≥90% on all days of therapy and achieved clinically acceptable pre-haemodialysis concentrations. Conclusions: Current vancomycin dosage regimens used clinically do not achieve a PTA ≥90% for most days of therapy for people receiving HFHD. A dose-optimized regimen was developed, which could be implemented in clinical practice.

Impact of high-flux haemodialysis on the probability of target attainment for oral amoxicillin/clavulanic acid combination therapy.

Clearance of small molecules such as amoxicillin and clavulanic acid is expected to increase during high-flux haemodialysis, which may result in lower concentrations and thus reduced efficacy. To date, clearance of amoxicillin/clavulanic acid (AMC) during high-flux haemodialysis remains largely unexplored. Using published pharmacokinetic parameters, a two-compartment model with first-order input was simulated to investigate the impact of high-flux haemodialysis on the probability of target attainment (PTA) of orally administered AMC combination therapy. The following pharmacokinetic/pharmacodynamic targets were used to calculate the PTA. For amoxicillin, the time that the free concentration remains above the minimum inhibitory concentration (MIC) of ≥50% of the dosing period (≥50%ƒT>MIC) was used. For clavulanic acid, the time that the free concentration was >0.1 mg/L of ≥45% of the dosing period (≥45%ƒT>0.1 mg/L) was used. Dialysis clearance reported in low-flux haemodialysis for both compounds was doubled to represent the likely clearance during high-flux haemodialysis. Monte Carlo simulations were performed to produce concentration-time profiles over 10 days in 1000 virtual patients. Seven different regimens commonly seen in clinical practice were explored. When AMC was dosed twice daily, the PTA was mostly ≥90% for both compounds regardless of when haemodialysis commenced. When administered once daily, the PTA was 20-30% for clavulanic acid and ≥90% for amoxicillin. The simulations suggest that once-daily orally administered AMC in patients receiving high-flux haemodialysis may result in insufficient concentrations of clavulanic acid to effectively treat infections, especially on days when haemodialysis occurs.

Pharmacokinetics and safety of oseltamivir in patients with end-stage renal disease treated with automated peritoneal dialysis.

AIMS: Patients with end-stage renal disease (ESRD) are at increased risk of developing complications associated with influenza infection. Oseltamivir is indicated for influenza treatment in ESRD patients, but the disposition is poorly understood in this patient population. This study aimed to characterize the pharmacokinetics and tolerability of oseltamivir in automated peritoneal dialysis (APD) and construct a pharmacokinetic model to assist with optimized dosing. METHODS: Ten adults with ESRD were prescribed an aggressive APD regimen consisting of three continuous cycler-assisted peritoneal dialysis (CCPD) sessions during the day and two continuous ambulatory (CAPD) sessions overnight. Oseltamivir was administered as a single 75 mg dose, immediately before APD treatment. RESULTS: Oseltamivir was rapidly eliminated via first-pass metabolism, with most of the dose (Fraction metabolized = 0.964) reaching the circulation as the active metabolite, oseltamivir carboxylate. This metabolite was cleared slowly and was quantifiable throughout the sampling interval. The disposition of oseltamivir and oseltamivir carboxylate was described by a two- and a one-compartment model, respectively. Metabolite clearance by CCPD [0.32 l h(-1) (70 kg)(-1) ] was 1.9-fold faster than via CAPD [0.17 l h(-1) (70 kg)(-1) ], with renal elimination being dominant in patients with residual urine production. Model simulations showed that a single 75 mg dose attained target exposures in patients with negligible or low urine clearance. However, higher doses are recommended for further investigation in patients with high residual renal function. In all patients, oseltamivir was well tolerated. CONCLUSIONS: In APD patients with anuria or low residual renal elimination, a single 75 mg dose of oseltamivir produced exposures at the upper end of the safety margin.

Population pharmacokinetics of fluconazole in critically ill patients receiving continuous venovenous hemodiafiltration: using Monte Carlo simulations to predict doses for specified pharmacodynamic targets.

Fluconazole is a widely used antifungal agent that is extensively reabsorbed in patients with normal renal function. However, its reabsorption can be compromised in patients with acute kidney injury, thereby leading to altered fluconazole clearance and total systemic exposure. Here, we explore the pharmacokinetics of fluconazole in 10 critically ill anuric patients receiving continuous venovenous hemodiafiltration (CVVHDF). We performed Monte Carlo simulations to optimize dosing to appropriate pharmacodynamic endpoints for this population. Pharmacokinetic profiles of initial and steady-state doses of 200 mg intravenous fluconazole twice daily were obtained from plasma and CVVHDF effluent. Nonlinear mixed-effects modeling (NONMEM) was used for data analysis and to perform Monte Carlo simulations. For each dosing regimen, the free drug area under the concentration-time curve (fAUC)/MIC ratio was calculated. The percentage of patients achieving an AUC/MIC ratio greater than 25 was then compared for a range of MIC values. A two-compartment model adequately described the disposition of fluconazole in plasma. The estimate for total fluconazole clearance was 2.67 liters/h and was notably 2.3 times faster than previously reported in healthy volunteers. Of this, fluconazole clearance by the CVVHDF route (CL(CVVHDF)) represented 62% of its total systemic clearance. Furthermore, the predicted efficiency of CL(CVVHDF) decreased to 36.8% when filters were in use >48 h. Monte Carlo simulations demonstrated that a dose of 400 mg twice daily maximizes empirical treatment against fungal organisms with MIC up to 16 mg/liter. This is the first study we are aware of that uses Monte Carlo simulations to inform dosing requirements in patients where tubular reabsorption of fluconazole is probably nonexistent.