State insurance mandates and off‐label use of chemotherapy

Access to cancer drugs used off‐label is important to cancer patients but may drive up healthcare costs with little evidence of clinical benefit. We hypothesized that state health insurance mandates for private insurers to provide coverage for off‐label use of cancer drugs cause higher rates of off‐label use. We used Truven MarketScan data from 1999 to 2007 on utilization of 35 infused chemotherapy drugs in private health plans in the United States, covering the period when eight states implemented off‐label coverage laws. We studied trends in off‐label use of drugs, distinguishing between appropriate and inappropriate off‐label use according to drug compendia, and estimated difference‐in‐difference regressions of the effect of state laws on off‐label use. We estimate 41% of utilization was off‐label, including 17% of use conservatively defined as inappropriate. Trends show gradual declines in off‐label use over time. We also find no discernable effect of state laws mandating coverage of off‐label use of cancer drugs on utilization patterns under multiple empirical specifications. Our conclusion is that policymakers should consider shifting away from mandating coverage as a way to ensure access to drugs off‐label and towards incentivizing adherence to clinical practice guidelines to improve the quality and value of off‐label use.     

<Emphasis Type="Italic">αvβ</Emphasis>3 Integrin Receptor Targeting and Near-Infrared Imaging of Solid Tumors Using Surface-Modified Nanoliposomes

Purpose

Abundance of receptors on tumor vasculature presents a prominent target for theranostic applications. The alphavbeta3 integrin receptors expressed on vascular endothelial cells during angiogenesis were therefore considered targets for imaging. Non-invasive visualization of tumor growth and/or delivery systems can appreciate tumor localization and disposition kinetics of carriers, respectively. Herein, we report near-infrared fluorescence imaging (NIRFI) of solid tumors using targeted fluorescence nanoliposomes in vivo.

Methods

Fluorescence nanoliposomes surface modified with cRGD-peptide were injected into CD1 athymic (nu/nu) mice bearing C6 glioblastoma xenografts (300 mm³). At different time points, mice were subjected to NIRFI for visualization of tumor xenografts and nanocarrier tracing in vivo.

Results

NIRFI showed tumor localization of 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl indotricarbocyanine iodide (DiR₁₈)-incorporated-targeted liposomes with maximum tumor-to-tissue occurring at 24-h post-liposome administration. Interaction of integrin receptors with targeted liposomes had contributed to an intense NIRF signal. Molecular studies showed an elevated expression of alphavbeta3 integrin receptors in tumor xenografts.

Conclusion

From the studies, it can be concluded that non-invasive localization of tumors and tracing of liposome carriers had been achieved using receptor targeting and NIRFI approaches.

     

Pharmacologic Prophylaxis,Postoperative INR,and Risk of Venous Thromboembolism after Hepatectomy

Introduction

Pharmacologic prophylaxis (PP) is recommended for patients undergoing general surgical procedures with at least moderate risk of venous thromboembolism (VTE). The role of PP in patients undergoing hepatectomy is controversial, however, due to concerns regarding postoperative liver dysfunction and bleeding.

Methods

We conducted a retrospective analysis of a prospectively maintained institutional database in order to clarify the relationship between PP, postoperative INR, and risk of VTE.

Results

Postoperative VTE occurred in 55 of 2,147 patients (2.6 %) and was independently associated with advanced age, higher BMI, longer procedure time, and development of a major complication, as well as higher postoperative INR (≥1.5 versus <1.5: OR 2.50, P?=?0.006). Patients undergoing more extensive liver resection with higher postoperative INR were less likely to receive PP, but receipt of PP demonstrated no relationship with either VTE incidence or hemorrhagic complications.

Conclusions

In this large single-institution study, incidence of VTE was not associated with PP but was associated with higher postoperative INR, contrary to the notion that postoperative liver dysfunction is protective against VTE. The interplay between prothrombotic and antithrombotic mechanisms in posthepatectomy patients must be more completely characterized before broad recommendations can be made regarding PP use in these patients.     

Assessment of atmospheric dispersion and radiological impact from the Fukushima accident in a 40-km range using a simulation approach

In this study, radiation doses and lifetime attributable health risk to the members of public in a 40-km impact zone around the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) were assessed for the airborne releases that occurred during 11–31 March 2011 from the loss of coolant accident associated with the east Japan earthquake and tsunami event. High-resolution simulations with FLEXPART-WRF Lagrangian particle dispersion model were made using available source term estimates for four significant isotopes (Cs134, Cs137, I131, Xe133). Radiation risk models were adopted to estimate the health risk for leukemia, breast, thyroid, and all solid cancers using simulated distributed lifetime organ doses. The simulations indicate occurrence of hotspots in the spatial activity deposition and radiation dose distribution with high values in the northwest and south-southwest land sectors in a 40-km radius. Large activity depositions (10⁶ to 10⁸ Bq/m² of Cs137 between 12 and 31 March 2011) and external air doses (10 to 100 μSv/h) are simulated in the above sectors. The simulated air dose rates are found to match with observed doses at 85 % of the monitor stations within a factor of 5. It is estimated that the groundshine and ingestion dose are the principal contributors of the effective dose. Simulated average effective dose during the first year of exposure varied as ~150 mSv in the first few kilometers to 2 mSv at 40 km. The risk incidence was estimated to be high for infants compared to the children and adult age group for all types of cancers. The first 0–20-km range of the FDNPP is characterized with high risk for all types of cancers, for example, 10 to 20 in 10,000 adults for leukemia. The analysis shows that the immediate implementation of countermeasures of evacuation in the 0–20-km zone, sheltering in the 20–40-km zone, and food restrictions by Japan actually reduced significant health risks to the population living near FDNPP. Simulated yearly distribution of total dose indicates that people of evacuated zone can be rehabilitated in about 16 years in the 5–10-km area and 7 years in the 10–20-km area with minimum risk, whereas the near reactor zone of 0–5 km and areas along the plume footprint up to 20 km in the northwest sector of FDNPP require special attention and reclamation measures for rehabilitation. This study demonstrates a total simulation-based approach for estimating the radiation risk for the Fukushima case and helps to assess the time attainment of low risk for inhabitation of the people in the affected areas.     

Melatonin protects neurons from singlet oxygen-induced apoptosis

Abstract: Singlet oxygen (O₂[¹Δg]) is a very reactive molecule that can be produced by living cells and may contribute to cytotoxicity. The pineal hormone melatonin has been reported to possess potent antioxidant activity, and to be capable of scavenging O₂(¹Δg). We investigated whether melatonin might reduce the neurotoxic action of O₂(^lΔg). The cytotoxic effect of singlet oxygen was studied in primary cultures of cerebellar granule neurons pretreated with a photosensitive dye, rose bengal, and exposed to light—a procedure that generates O₂(¹Δg). We found that this procedure triggers neuronal death, which is preceded by mitochondrial impairment (assayed by the rate of the reduction of MTT, 3-[4,5-di-methylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, into formazan), and by DNA fragmentation—a marker of apoptosis. DNA fragmentation was determined in situ by terminal deoxynucleotidyl transferase assay; cell death was assayed with 0.4% trypan blue solution—viable cells with an intact membrane are not permeable to trypan blue; dead cells are, and thus, they are stained blue. Neuroprotection was obtained with the pineal hormone melatonin. In a cell-free system, melatonin also protected the enzyme creatine kinase (EC 2.7.3.2) from the rose bengal-induced injury. The results suggest that melatonin might counteract the cytotoxic action of singlet oxygen. Further studies are needed to clarify the exact role singlet oxygen and melatonin might play in neurodegenerative diseases.     

Prevalence of drug resistance under the DOTS strategy in Hyderabad, South India, 2001-2003.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to at least isoniazid (INH) and rifampicin (RMP), is considered a threat to TB control. Implementation of DOTS ensures high cure rates and prevents MDR. OBJECTIVE: To study the prevalence of MDR-TB from a retrospective analysis of the data in a tuberculosis unit where DOTS was implemented over a period of 6 years through public private mix (PPM). METHODS: Drug susceptibility testing of Mycobacterium tuberculosis samples isolated from the cultures of newly registered and retreatment sputum smear-positive cases during 2001-2003. RESULTS: During the study, 909 sputum-positive cases were registered and analysed. Of these, 714 were new and 195 were retreatment sputum-positive cases. INH resistance was found in 3.2% (23) of new and 9.2% (18) of retreatment cases. RMP resistance was present in 1.5% (11) of new and 7.2% (14) of retreatment cases. MDR was present only in 0.14% (1) of new and 2% (4) of retreatment cases. New cases had cure rates of 96% compared to 85% in retreatment cases. CONCLUSION: The prevalence of MDR-TB is low where success rates are high.     

2018 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in atrial fibrillation (AF) management. This 2018 Focused Update addresses: (1) anticoagulation in the context of cardioversion of AF; (2) the management of antithrombotic therapy for patients with AF in the context of coronary artery disease; (3) investigation and management of subclinical AF; (4) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (5) acute pharmacological cardioversion of AF; (6) catheter ablation for AF, including patients with concomitant AF and heart failure; and (7) an integrated approach to the patient with AF and modifiable cardiovascular risk factors. The recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards. Individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included as Supplementary Material and are available on the CCS Web site. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF guidelines recommendations, from 2010 to the present 2018 Focused Update, which is provided in the Supplementary Material.