Auditing the prescription drug consumer price index in a changing marketplace.

Changes in the dynamics of prescription drug markets have raised issues regarding whether the United States Bureau of Labor Statistics' (BLS') Prescription Drug Consumer Price Index (CPI-Rx) has adequately kept up with the evolving marketplace. The CPI-Rx limits its sampling frame to retail outpatient outlets and excludes prescription pharmaceuticals dispensed in non-retail settings such as hospitals, physician/clinic outpatient facilities, and nursing homes. Thus, the CPI-Rx overlooks the increasingly important specialty pharmaceuticals dispensed in non-retail settings, whose transactions are instead captured in the overall hospital and professional services component of the medical care CPI. Specialty drugs now account for about 55% of all U.S. drug spending, double the share of a decade earlier. To the extent specialty drug price growth differs from that of traditional pharmaceuticals, the CPI-Rx could provide an inaccurate measure of overall drug price inflation. We calculate a chained Laspeyres CPI using data from the Merative™ MarketScan® Databases for the years 2010-2019 and IQVIA-designated specialty drugs and offer evidence showing that by not sampling specialty drugs in non-retail settings, the CPI-Rx has understated overall U.S. prescription drug inflation by just under 75 basis points annually. We discuss implications for health care policy and suggest the BLS examine the feasibility of publishing an overall pharmaceutical price index incorporating both traditional and specialty pharmaceuticals dispensed in retail and non-retail settings.

Effects of metformin on wild fathead minnows (Pimephales promelas) using in-lake mesocosms in a boreal lake ecosystem.

Due to its widespread use for the treatment of Type-2 diabetes, metformin is routinely detected in surface waters globally. Laboratory studies have shown that environmentally relevant concentrations of metformin can adversely affect the health of adult fish, with effects observed more frequently in males. However, the potential risk to wild fish populations has yet to be fully elucidated and remains a topic of debate. To explore whether environmentally relevant metformin exposure poses a risk to wild fish populations, the present study exposed wild fathead minnows (Pimephales promelas) to 5 or 50 µg/L metformin via 2 m diameter in-lake mesocosms deployed in a natural boreal lake in Northern Ontario at the International Institute for Sustainable Development - Experimental Lakes Area (IISD-ELA). Environmental monitoring was performed at regular intervals for 8-weeks, with fish length, weight (body, liver and gonad), condition factor, gonadosomatic index, liver-somatic index, body composition (water and biomolecules) and hematocrit levels evaluated at test termination. Metabolic endpoints were also evaluated using liver, brain and muscle tissue, and gonads were evaluated histologically. Results indicate that current environmental exposure scenarios may be sufficient to adversely impact the health of wild fish populations. Adult male fish exposed to metformin had significantly reduced whole body weight and condition factor and several male fish from the high-dose metformin had oocytes in their testes. Metformin-exposed fish had altered moisture and lipid (decrease) content in their tissues. Further, brain (increase) and liver (decrease) glycogen were altered in fish exposed to high-dose metformin. To our knowledge, this study constitutes the first effort to understand metformin's effects on a wild small-bodied fish population under environmentally relevant field exposure conditions.

Investing in Certified Community Behavioral Health Centers to Fulfill Their Promise.

Certified community behavioral health centers (CCBHCs) were established under section 223 of the Protecting Access to Medicare Act of 2014. CCBHCs had the goal of expanding access to care for people with behavioral health needs "regardless of ability to pay and place of residence." The authors used descriptive tables and a heat map to compare the geographic distribution of CCBHCs with county-level rates of mental illness, poverty, and population density. Regression models were employed to determine which county-level characteristics are most strongly associated with the establishment of a CCBHC. The authors found that population density is a stronger predictor of CCBHC presence than are rates of poverty or serious mental illness. Holding all other local characteristics constant, the authors observed that going from the population density typical of the most rural counties to that of the most urban counties was associated with an approximately 28-percentage-point increase (from 7% to 35%) in the likelihood of being served by a CCBHC. Expanding CCBHC services to areas with lower population densities likely requires an approach that is different from the current method of allocation of grant funds by the Substance Abuse and Mental Health Services Administration (SAMHSA). Two features of the program might be modified. The first would build on flexibilities incorporated into the most recent round of SAMHSA grantmaking, which explicitly aim to build infrastructure and capacity to develop a CCBHC. A second modification might seek to identify which certification requirements are essential to supporting CCBHC quality and access and eliminate nonessential requirements.

Improving Labor Outcomes among People with Mild or Moderate Mental Illness through Law and Policy Reform.

Mild and moderate mental illnesses can hinder labor force participation, lead to work interruptions, and hamper earning potential. Targeted interventions have proven effective at addressing these problems. But their potential depends on labor protections that enable people to take advantage of these interventions while keeping jobs and income.

Lasting scars: The impact of depression in early adulthood on subsequent labor market outcomes.

A growing body of evidence indicates that poor health early in life can leave lasting scars on adult health and economic outcomes. While much of this literature focuses on childhood experiences, mechanisms generating these lasting effects-recurrence of illness and interruption of human capital accumulation-are not limited to childhood. In this study, we examine how an episode of depression experienced in early adulthood affects subsequent labor market outcomes. We find that, at age 50, people who had met diagnostic criteria for depression when surveyed at ages 27-35 earn 10% lower hourly wages (conditional on occupation), work 120-180 fewer hours annually, and earn 24% lower annual wage incomes. A portion of this income penalty (21%-39%) occurs because depression is often a chronic condition, recurring later in life. But a substantial share (25%-55%) occurs because depression in early adulthood disrupts human capital accumulation, by reducing work experience and by influencing selection into occupations with skill distributions that offer lower potential for wage growth. These lingering effects of early depression reinforce the importance of early and multifaceted intervention to address depression and its follow-on effects in the workplace.

Gone Too Soon: priorities for action to prevent premature mortality associated with mental illness and mental distress.

Globally, too many people die prematurely from suicide and the physical comorbidities associated with mental illness and mental distress. The purpose of this Review is to mobilise the translation of evidence into prioritised actions that reduce this inequity. The mental health research charity, MQ Mental Health Research, convened an international panel that used roadmapping methods and review evidence to identify key factors, mechanisms, and solutions for premature mortality across the social-ecological system. We identified 12 key overarching risk factors and mechanisms, with more commonalities than differences across the suicide and physical comorbidities domains. We also identified 18 actionable solutions across three organising principles: the integration of mental and physical health care; the prioritisation of prevention while strengthening treatment; and the optimisation of intervention synergies across social-ecological levels and the intervention cycle. These solutions included accessible, integrated high-quality primary care; early life, workplace, and community-based interventions co-designed by the people they should serve; decriminalisation of suicide and restriction of access to lethal means; stigma reduction; reduction of income, gender, and racial inequality; and increased investment. The time to act is now, to rebuild health-care systems, leverage changes in funding landscapes, and address the effects of stigma, discrimination, marginalisation, gender violence, and victimisation.

Fourier-synthesis approach for static charge-density reconstruction from theoretical structure factors of CaB6.

In a pilot study, electron-density (ED) and ED Laplacian distributions were reconstructed for the challenging case of CaB6 (Pearson symbol cP7) with conceptually fractional B-B bonds from quantum-chemically calculated structure-factor sets with resolutions 0.5 Å-1 ≤ [sin(θ)/λ]max ≤ 5.0 Å-1 by means of Fourier-synthesis techniques. Convergence of norm deviations of the distributions obtained with respect to the reference ones was obtained in the valence region of the unit cell. The QTAIM (quantum theory of atoms in molecules) atomic charges, and the ED and ED Laplacian values at the characteristic critical points of the Fourier-synthesized distributions have been analysed for each resolution and found to display a convergent behaviour with increasing resolution. The presented method(exponent) (ME) type of Fourier-synthesis approach can qualitatively reconstruct all characteristic chemical bonding features of the ED from valence-electron structure-factor sets with resolutions of about 1.2 Å-1 and beyond, and from all-electron structure-factor sets with resolutions of about 2.0 Å-1 and beyond. Application of the ME type of Fourier-synthesis approach for reconstruction of ED and ED Laplacian distributions at experimental resolution is proposed to complement the usual extrapolation to infinite resolution in Hansen-Coppens multipole model derived static ED distributions.

Chemical communication in wood frog (Rana sylvatica) tadpoles is influenced by early-life exposure to naphthenic acid fraction compounds.

Environmental pollutants can disrupt chemical communication between aquatic organisms by interfering with the production, transmission, and/or detection of, as well as responses to, chemical cues. Here, we test the hypothesis that early-life exposure to naphthenic acid fraction compounds (NAFCs) from oil sands tailings disrupts antipredator-associated chemical communication in larval amphibians. Wild adult wood frogs (Rana sylvatica) captured during their natural breeding period were combined (1 female:2 males) in six replicate mesocosms filled with either uncontaminated lakewater or with NAFCs isolated from an active tailings pond in Alberta, Canada, at nominal 5 mg/L concentrations. Egg clutches were incubated and tadpoles maintained in their respective mesocosms for ∼40 days post-hatch. Tadpoles (Gosner stage 25-31) were then transferred individually to trial arenas filled with uncontaminated water and exposed to one of six chemical alarm cue (AC) stimuli solutions following a 3 × 2 × 2 design (3 AC types × 2 stimulus carriers × 2 rearing exposure groups). Relative to control tadpoles, NAFC-exposed tadpoles demonstrated higher baseline activity levels (line crosses and direction changes) when introduced to uncontaminated water. Antipredator responses differed in graded fashion with AC type, with control ACs eliciting the greatest latency to resume activity, water the least, and NAFC-exposed ACs intermediate. Pre- to post-stimulus difference scores were non-significant in control tadpoles, while NAFC-exposed tadpoles demonstrated significantly greater variation. While this suggests that exposure to NAFCs from fertilization through hatching may have interfered with AC production, it is unclear whether the quality or quantity of cues was affected. There was also no clear evidence that NAFC carrier water interfered with ACs or the alarm response in unexposed control tadpoles. These results emphasize the importance of understanding how behavioral and physiological effects of early-life NAFC exposure on critical antipredator responses may persist across life history stages.

Toward Greater Accountability in Mental Health Care.

Lack of accountability contributes to the gap between best practices and potential outcomes. Few mental health providers routinely practice evidence-based care. In fact, within the mental health field, there is significant controversy over the use of evidence-based practices. Lack of accountability affects individuals receiving care at the patient level, provider level, and systems level. The authors identify several impediments to accountability in behavioral health care. These include failure to develop a diverse, well-trained workforce; challenges in measurement; misalignment of payment incentives; and misguided regulations. Accountability arrangements typically consist of several elements: a clear articulation of goals, objectives, or standards; metrics so that progress toward achieving goals can be tracked; and consequences for insurers, providers, and professionals for achieving or failing to achieve objectives. To advance system goals, the full complement of accountability tools should be consistently applied to all sources of behavioral health care and supports. The authors focus on three sets of accountability tools-performance metrics, payment incentives, and regulatory standards-that when implemented thoughtfully can help move the field toward more positive outcomes in behavioral health.

A holistic view of innovation incentives and pharmaceutical policy reform.

The Inflation Reduction Act is set to transform how Medicare pays for prescription drugs, most notably by enabling Medicare to negotiate for the prices of certain high-cost medications. The pharmaceutical industry argues it will drastically reduce innovation, but a full analysis of its impacts on innovation requires considering not merely the number of new drugs produced but their clinical value. Several features of the negotiation process aim to minimize its impacts on innovation, particularly for drugs with high clinical value. The Biden Administration has also implemented several policies alongside the Inflation Reduction Act, such as the Advanced Research Projects Agency for Health and a National Biotechnology and Biomanufacturing Initiative, that are designed to reward and promote clinically valuable innovation. Taken together, these policies should go a long way toward mitigating any negative impacts on new drug development and may even better promote the development of higher-value drugs.

Developing current procedural terminology codes that describe the work performed by machines.

The "Taxonomy of Artificial Intelligence for Medical Services and Procedures" became part of the Current Procedural Terminology (CPT®) code set effective January 1, 2022. It provides a framework for discrete and differentiable CPT codes which; are consistent with the features of the devices' output, characterize interaction between the device and the physician or other qualified health care professional, and foster appropriate payment. Descriptors include "Assistive", "Augmentative", and "Autonomous". As software increasingly augments the provision of medical services the taxonomy will foster consistent language in coding enabling patient, provider, and payer access to the benefits of innovation.

Accelerated Approval Of Cancer Drugs: No Economic Reward For Drug Makers That Conduct Confirmatory Trials.

The Food and Drug Administration uses expedited approval of drugs to speed the development and assessment of drugs that address unmet needs related to serious or life-threatening conditions. Drugs approved via this route rely on surrogate endpoints or other clinical indicators that are not direct measures of benefits to patients, such as survival or quality of life. Companies are required to conduct a clinical trial confirming that a drug provides long-term benefits that are clinically meaningful, but prompt completion of these trials frequently does not occur. Theory suggests that because confirmatory trials reduce uncertainty, they should provide an economic reward in the form of higher prices for a positive finding. We used a sample of physician-administered cancer drugs and data on average sales price to test this hypothesis. We found no significant relationship between confirmatory trial completion with a positive outcome and elevated prices. This represents a failure of the market to reward reduced uncertainty about a cancer drug's true benefits. This inefficiency would be mitigated if major payers such as Medicare built price schedules that directly rewarded completion of confirmatory trials. More completed trials would ensure that patients are receiving truly effective chemotherapies and not suffering the adverse effects of drugs that are ultimately not effective.

The acute toxicity of bitumen-influenced groundwaters from the oil sands region to aquatic organisms.

The extraction of surface mined bitumen from oil sands deposits in northern Alberta, Canada produces large quantities of liquid tailings waste, termed oil sands process-affected water (OSPW), which are stored in large tailings ponds. OSPW-derived chemicals from several tailings ponds migrating past containment structures and through groundwater systems pose a concern for surface water contamination. The present study investigated the toxicity of groundwater from near-field sites adjacent to a tailings pond with OPSW influence and far-field sites with only natural oil sands bitumen influence. The acute toxicity of unfractionated groundwater and isolated organic fractions was assessed using a suite of aquatic organisms (Pimephales promelas, Oryzias latipes, Daphnia magna, Hyalella azteca, Lampsilis spp., Ceriodaphnia dubia, Hexagenia spp., and Vibrio fischeri). Assessment of unfractionated groundwater demonstrated toxicity towards all invertebrates in at least one far-field sample, with both near-field and far-field samples with bitumen influence toxic towards P. promelas, while no toxicity was observed for O. latipes. When assessing the unfractionated groundwater and isolated organic fractions from near-field and far-field groundwater sites, P. promelas and H. azteca were the most sensitive to organic components, while D. magna and L. cardium were most sensitive to the inorganic components. Groundwater containing appreciable amounts of dissolved organics exhibited similar toxicities to sensitive species regardless of an OSPW or natural bitumen source. The lack of a clear distinction in relative acute toxicities between near-field and far-field samples indicates that the water-soluble chemicals associated with bitumen are acutely toxic to several aquatic organisms. This result, combined with the similarities in chemical profiles between bitumen-influenced groundwater originating from OSPW and/or natural sources, suggests that the industrial bitumen extraction processes corresponding to the tailings pond in this study are not contributing unique toxic substances to groundwater, relative to natural bitumen compounds present in groundwater flow systems.

Naphthenic acid fraction components from oil sands process-affected water from the Athabasca Oil Sands Region impair murine osteoblast differentiation and function.

The extraction of bitumen from surface mining in the Athabasca Oil Sands Region (AOSR) produces large quantities of oil sands process-affected water (OSPW) that needs to be stored in settling basins near extraction sites. Chemical constituents of OSPW are known to impair bone health in some organisms, which can lead to increased fracture risk and lower reproductive fitness. Naphthenic acid fraction components (NAFCs) are thought to be among the most toxic class of compounds in OSPW; however, the effect of NAFCs on osteoblast development is largely unknown. In this study, we demonstrate that NAFCs from OSPW inhibit osteoblast differentiation and deposition of extracellular matrix, which is required for bone formation. Extracellular matrix deposition was inhibited in osteoblasts exposed to 12.5-125 mg/L of NAFC for 21 days. We also show that components within NAFCs inhibit the expression of gene markers of osteoblast differentiation and function, namely, alkaline phosphatase (Alp), osteocalcin, and collagen type 1 alpha 1 (Col1a1). These effects were partially mediated by the induction of glucocorticoid receptor (GR) activity; NAFC induces the expression of the GR activity marker genes Sgk1 (12.5 mg/L) and p85a (125 mg/L) and inhibits GR protein (125 mg/L) and Opg RNA (12.5 mg/L) expression. This study provides evidence that NAFC concentrations of 12.5 mg/L and above can directly act on osteoblasts to inhibit bone formation and suggests that NAFCs contain components that can act as GR agonists, which may have further endocrine disrupting effects on exposed wildlife.

A Community-Based Pancreatic Cancer Screening Study in High-Risk Individuals: Preliminary Efficacy and Safety Results.

INTRODUCTION: Pancreatic cancer (PC) screening recommendations have been based on studies performed solely at high-volume academic centers. To make PC screening more widely available, community-based efforts are essential. We implemented a prospective PC screening study in the community of Fairfield County, CT, and report our early safety and efficacy results. METHODS: Eligible individuals were enrolled into an investigator-initiated study and underwent a baseline and 3 annual magnetic resonance imagings/magnetic resonance cholangiopancreatographies (MRIs/MRCPs) with gadolinium, biannual blood donations for biobanking, and assessments for anxiety and depression. All MRIs were presented at a multidisciplinary board to determine whether further investigation was warranted. RESULTS: Seventy-five individuals have been enrolled and 201 MRIs performed over a 2.6-year average length of follow-up. Abnormal pancreatic findings (predominantly small cysts) were detected in 58.7% of the participants. Among these, 6.7% underwent endoscopic ultrasound, with 1 case complicated by postprocedural pancreatitis. One surgical resection was performed on a 4.7-cm intraductal papillary mucinous neoplasm with a focus on low-grade pancreatic intraepithelial neoplasia. One incidental finding of fibrosing mediastinitis was detected. Anxiety and depression scores decreased over the course of this study from 21.4% to 5.4% and 10.7% to 3.6%, respectively. DISCUSSION: This preliminary report supports the feasibility of performing MRI/magnetic resonance cholangiopancreatographies-based PC screening as part of a clinical trial in a community setting. A longer follow-up is needed to better assess safety and efficacy. To the best of our knowledge, this is the first report from a community-based PC screening effort ( clinicaltrials.gov ID: NCT03250078).

International Reference Pricing in the Context of US Drug Policy.

International reference prices (IRP), also called external reference prices, are widely used across developed nations. IRP uses the prices paid in other countries to either inform negotiations with the pharmaceutical industry or as a cap on market prices. The authors review the application of IRP to cap the prices of negotiated outcomes in the context of US proposals for changing the way prescription drug prices are established for the Medicare program. They examine the economic, political, and administrative issues associated with the use of IRP, and they summarize the evidence on the impacts of IRP.