Cost of Drug Wastage From Dose Modification and Discontinuation of Oral Anticancer Drugs.

Importance: Oral chemotherapy is often dispensed to patients as a 1-month supply, with pill dose and package size predetermined by the drug manufacturer; thus, changing the patient dosage may waste the remaining initial drug supply. The cost of pills wasted due to dose modification and discontinuation is often unreported. Objective: To estimate the cost of pill wastage due to dose modification and discontinuation for oral anticancer drugs that were recently approved by the US Food and Drug Administration (FDA) or that are commonly prescribed. Design, Setting, and Participants: This retrospective cross-sectional economic evaluation initially identified 26 oral anticancer drugs newly approved between January 1, 2020, and August 31, 2022, from the FDA website and the top 50 best-selling pharmaceuticals in 2021 abstracted from the Drug Discovery Trends website managed by Drug Discovery and Development. The monthly costs of each agent were extracted from the Micromedex RED BOOK database. The FDA package insert, and in some cases PubMed, of each identified drug and indication was searched (matching on trial registration number) for information on registration trials. Information extracted for each drug included the name of the drug approved, drug target, cost of the drug, number of pills per bottle, available strengths, indication, name of the trial, number of patients exposed to treatment drug, number of dose level reductions, median duration of treatment, percentage of patients who received dose reduction, and percentage of dose discontinuation. All variables included in calculations were derived from the package insert or original trial publication. Main Outcomes and Measures: The cost of wastage for selected oral anticancer drugs due to dose reduction or discontinuation and the percentage of wastage in comparison with the total cost of treatment. Results: After removing duplicates, 22 oral anticancer medications were included in the study. Because some drugs had more than 1 indication, data from 35 clinical trials were analyzed. Eight of the medications (covering 9 indications) had pill strengths divisible at each dose-reduction level; thus the cost of reduction for these pills was assumed to be zero. Two medications did not allow for dose reduction. The median cost of wastage from dose reduction and discontinuation was $1750 (range, $43-$27 200), with a mean cost of $4290 (SD, $5720) per patient. The median percentage of wastage from the total cost of treatment was 1.04% (range, 0.04%-10.80%) with a mean of 1.78% (SD, 2.21%). Conclusions and Relevance: This economic evaluation found that due to both the high cost per pill and limited pill strength availability, the mean cost of wastage associated with dose reduction or discontinuation was $4290 per patient. These results suggest that to reduce the financial burden for patients with cancer, regulatory bodies should enforce availability of pill strengths that will limit pill wastage during dose modification or recommend that drug manufacturers issue credit for unused pills.

Patterns of Industry Payments to Urologists From 2014-2018.

OBJECTIVES: To evaluate the patterns of financial transaction between industry and urologists in the first 5 years of reporting in the Open Payments Program (OPP) by comparing transactions over time, between academic and nonacademic urologists, and by provider characteristics among academic urologists. METHODS: The Center for Medicare & Medicaid Services OPP database was queried for General Payments to urologists from 2014-2018. Faculty at ACGME-accredited urology training programs were identified and characterized via publicly available websites. Industry transfers were analyzed by year, practice setting (academic vs nonacademic), provider characteristics, and AUA section. Payment nature and individual corporate contributions were also summarized. RESULTS: A total of 12,521 urologists - representing 75% of the urology workforce in any given year - received $168 million from industry over the study period. There was no significant trend in payments by year (P = .162). Urologists received a median of $1602 over the study period, though 14% received >$10,000. Payment varied significantly by practice setting (P <.001), with nonacademic urologists receiving more but smaller payments than academic urologists. Among academic urologists, gender (P <.001), department chair status (P <.001), fellowship training (P <.001), and subspecialty (P <.001) were significantly associated with amount of payment from industry. Annual payments from industry varied significantly by AUA section. CONCLUSION: Reporting of physician-industry transactions has not led to a sustained decline in transactions with urologists. Significant differences in industry interaction exist between academic and nonacademic urologists, and values transferred to academic urologists varied by gender, chair status, subspecialty, and AUA section.

Pain assessment tools for older adults with dementia in long-term care facilities: a systematic review.

AIM: The aim of this review is to document pain assessment tools used primarily for older adults in long-term care facilities and compare self-report and observer-rated tools. METHODS: A literature search was conducted in Ovid MEDLINE®, Embase, Cochrane and PsycINFO. Keywords included 'dementia', 'pain management' and 'managing pain'. RESULTS: Of 1033 references, 23 articles were selected for inclusion. Six tools were self-rated and 18 tools were administered by an observer. 13 studies evaluated the reliability/validity of their scales; four studies compared different scales against each other. CONCLUSION: Self-report should be the first-line approach when possible, with observational assessment used as a supplementary tool. Reliable observational tools have been shortened, and shown to maintain high reliability/validity, and positive psychometric properties.

Organobromine compound profiling in human adipose: Assessment of sources of bromophenol.

Bromophenols (BRPs) have been widely detected in human tissues, however, relative proportions from natural products and/or anthropogenic flame retardants are not clear. 21 polybrominated diphenyl ethers (PBDEs), 15 MeO/OH-PBDEs, and 10 BRPs were simultaneously quantified in adipose collected from people from New York City, USA. An in vitro assay utilizing human liver microsomes was performed for detected predominant organobromine. High concentrations of 2,4,6-triBRP and PBDEs were observed, and extremely low concentrations of naturally occurring MeO/OH-PBDEs were detected. Similar biotransformatioin rates of BRPs and MeO/OH-PBDEs indicated that the relative high concentration of 2,4,6-triBRP in humans was not of natural origin. Significant correlation observed between concentrations of 2,4,6-triBRP and BDE-209 suggested that the two chemicals may share a common source. Both 2,4,6-triBRP and BDE-209 were detected in commercial ABS resins, suggesting that plastic products made from ABS resins could be potential sources of co-exposure of the two compounds for humans.

A whole life cycle assessment on effects of waterborne PBDEs on gene expression profile along the brain-pituitary-gonad axis and in the liver of zebrafish.

Polybrominated diphenyl ethers (PBDEs) are now found ubiquitously in the aquatic environment and biota, and there is a growing concern that PBDEs may disrupt endocrine systems, leading to reproductive impairments of aquatic animals. In our study, zebrafish (Danio rerio) were exposed to the 5 ng/L, 1 µg/L and 50 µg/L of DE-71 for the duration of the whole life cycle (120 days, from eggs to adults). The expression of selected genes along the brain-pituitary-gonadal (BPG) axis and liver, and the levels of plasma sex hormones were examined. In male fish, up-regulation of GnRH in brain, FSHß and LHß in pituitary, FSH-receptor, LH-receptor, and CYP19a in testis was clearly evident, while down-regulation of CYP11a and 3ß-HSD was found in testis. In female fish, a 2.4-fold up-regulation of 3ß-HSD was found in ovary upon exposure to 50 µg/L of DE-71. GnRH in brain, FSHß and LHß in pituitary were also up-regulated, while ERß, TH and TPH in brain and GnRH-receptor in pituitary were significantly down-regulated. Hepatic ERα, AR and VTG in males were all down-regulated, while hepatic ERα and AR in female were up-regulated. Serum estradiol (E2) was reduced in both male and female upon exposure to DE-71, while significant increases in serum testosterone (T) and 11-keto-testosterone (11-KT) were only found in male but not female fish. The ratio of T/E2 as well as the ratio of 11-KT/E2 in male fish increased in a dose-dependent manner upon exposure to DE-71. Our overall results showed that whole life exposure of DE-71 altered the expression of regulatory genes and receptors at all three levels of the BPG axis in zebrafish, and the responses are sex dependent. The observed disruption of GnRH and GtHs can be further related to the subsequent disruption in both levels and balance sex steroid hormones.

Rapid magnetic-mediated solid-phase extraction and pre-concentration of selected endocrine disrupting chemicals in natural waters by poly(divinylbenzene-co-methacrylic acid) coated Fe3O4 core-shell magnetite microspheres for their liquid chromatography-tandem mass spectrometry determination.

A new Fe(3)O(4)/poly(divinylbenzene-co-methacrylic acid) core-shell magnetite microspheric material have been successfully developed as magnetic-mediated solid-phase extraction micro-particle sorbent in dispersion mode (MM-SPE-MP) for the determination of selected estrogenic endocrine disrupting chemicals (EDCs), namely: estrone (E1), 17beta-estradiol (E2), estriol (E3), 17alpha-ethynylestradiol (EE2) and bisphenol-A (BPA), in natural water, via quantification by HPLC tandem mass spectrometry. The magnetite Fe(3)O(4) core of this MM-SPE-MP sorbent was fabricated by a solvothermal approach and the thin layer of amphipolar poly(divinylbenzene-co-methacrylic acid) (pDVB-MAA) coating was established via suspension polymerization. The resultant core-shell MM-SPE-MP sorbent material was characterized by electron microscopy, X-ray diffraction and Fourier-transformed infrared spectroscopy. Particle size distribution of the core-shell microspheres was within the range 300-700 nm in diameter and the thickness of the pDVB-MAA coating was ca. 10nm. This magnetite microspheric material can be easily dispersed in aqueous samples and retrieved by the application of external magnetic field via a small piece of permanent magnet. The MM-SPE-MP process for the selected estrogenic EDCs involved the dispersion of the core-shell microspheric sorbent in water samples with sonication, followed by magnetic aided retrieval of the sorbent and solvent (methanol) desorption of extracted EDCs for LC-MS/MS analysis. Partition equilibrium for all the selected EDCs onto this MM-SPE-MP sorbent was achieved within 15 min. Recoveries of the EDCs were in ranges of 56-111%. Analytes with smaller K(OW) value showed relatively lower recovery (and relatively longer equilibration time for partitioning). Method detection limits achieved were found to be 1-36 pg ml(-1) (n=3), while the repeatability was 6-34% (p<0.05, n=3). This work demonstrates the usefulness of MM-SPE-MP in the rapid and highly sensitive monitoring of trace organic contaminants in natural waters.

Diamagnetically stabilized levitation control of an intraluminal magnetic capsule.

Controlled navigation promotes full utilization of capsule endoscopy for reliable real-time diagnosis in the gastrointestinal (GI) tract, but intermittent natural peristalsis can disturb the navigational control, destabilize the capsule and take it out of levitation. The focus of the present work was to develop an economical and effective real-time magnetic capsule-guiding system that can operate in the presence of naturally existing peristalsis while retaining navigational control. A real-size magnetic navigation system that can handle peristaltic forces of up to 1.5 N was designed utilizing the computer-aided design (CAD) system Maxwell 3D (Ansoft, Pittsburg, PA) and was verified using a small-size physical experimental setup. The proposed system contains a pair of 50 cm diameter, 10,000-turn copper electromagnets with a 10 cm x 10 cm ferrous core driven by currents of up to 300 A and can successfully maintain position control over the levitating capsule during peristalsis. The addition of bismuth diamagnetic casing for stabilizing the levitating capsule was also studied. A modeled magnetic field around the diamagnetically cased permanent magnet was shown to be redistributed aligning its interaction with the external electromagnets, thus stabilizing the levitating capsule. In summary, a custom-designed diamagnetically facilitated capsule navigation system can successfully steer an intraluminal magnet-carrying capsule.

Qualitative assessment of undetectable melanin distribution in lightly pigmented irides.

A longstanding issue in biomedical research concerns the biophysical factors affecting the color diversity of the human irides and its connection with ocular diseases. Although the pigmentation and morphological characteristics of heavily and moderately pigmented irides have been extensively discussed in the literature, similar studies are scarce for lightly pigmented irides. We present computer experiments indicating that the spectral signature of these specimens may be directly affected by still undetectable melanin distributions in the outermost iridal layers. Our findings represent in silico evidence of this relationship which, in turn, may have implications in the investigation of the higher risk of death from metastatic ocular melanoma verified in individuals with light-colored irides.

Risk assessment of trace elements in the stomach contents of Indo-Pacific Humpback Dolphins and Finless Porpoises in Hong Kong waters.

The potential health risks due to inorganic substances, mainly metals, was evaluated for the two resident marine mammals in Hong Kong, the Indo-Pacific Humpback Dolphin (Sousa chinensis) and the Finless Porpoise (Neophocaena phocaenoides). The stomachs from the carcasses of twelve stranded dolphins and fifteen stranded porpoises were collected and the contents examined. Concentrations of thirteen trace elements (Ag, As, Cd, Co, Cr, Cs, Cu, Hg, Mn, Ni, Se, V and Zn) were determined by inductively coupled plasma mass spectrometer (ICP-MS). An assessment of risks of adverse effects was undertaken using two toxicity guideline values, namely the Reference Dose (RfD), commonly used in human health risk assessment, and the Toxicity Reference Value (TRV), based on terrestrial mammal data. The levels of trace metals in stomach contents of dolphins and porpoises were found to be similar. Risk quotients (RQ) calculated for the trace elements showed that risks to the dolphins and porpoises were generally low and within safe limits using the values based on the TRV, which are less conservative than those based on the RfD values. Using the RfD-based values the risks associated with arsenic, cadmium, chromium, copper, nickel and mercury were comparatively higher. The highest RQ was associated with arsenic, however, most of the arsenic in marine organisms should be in the non-toxic organic form, and thus the calculated risk is likely to be overestimated.

An assessment of the risks associated with polychlorinated biphenyls found in the stomach contents of stranded Indo-Pacific Humpback Dolphins (Sousa chinensis) and Finless Porpoises (Neophocaena phocaenoides) from Hong Kong waters.

The risks to Indo-Pacific Humpback Dolphins and Finless Porpoises associated with polychlorinated biphenyls (PCBs) were assessed. Stomach contents from twelve stranded Humpback Dolphins and sixteen stranded Finless Porpoises were collected. Concentrations of total and isomer-specific PCBs in the stomach contents were determined using dual-column gas chromatography equipped with electron capture detectors (GC-ECD). Risks due to the PCBs were assessed in three scenarios, based on total PCBs (summation of 41 PCB congeners), total toxicity equivalency (TEQs) and PCB 118, using the toxicity reference values (TRVs) as the threshold effects benchmarks. The calculated risk quotients (RQs) showed that risks due to PCBs were generally low or negligible. Specifically, RQs from total TEQs and total PCBs for Finless Porpoises are below one, suggesting that PCBs should be a low risk for the Finless Porpoise in Hong Kong waters. However, the Humpback Dolphin has RQs larger than 1 for total TEQs and total PCBs when the 95th percentile data were used in the evaluation. This indicates that further investigation may be needed to examine more closely the potential impact of toxic contaminants in the habitat of the Humpback Dolphin.