Combating Antimicrobial Resistance: Regulatory Strategies and Institutional Capacity

Amnesia is a common, important, but rarely noted side effect of antibiotics. Apart from medical historians, few recall the severe morbidity and mortality once associated with acute bacterial infection. However, decades of antibiotic overuse and misuse have compromised the long-term availability and efficacy of these life-saving therapies. If designed and implemented appropriately, regulation can reduce the risk of bacterial infection, reserve antibiotics for circumstances where they are necessary, and rationalize the use of the most powerful agents. Regulation of antibiotic resistance can be justified, and should be guided, by both efficiency and fairness. A range of regulatory options are available--some information-based, some incentive-based, some command-and-control--each of which has indications, strengths, and weaknesses. A desired set of regulatory strategies must then be matched with the appropriate legal and regulatory institutions. A renewed focus on regulatory and institutional design has significant potential to reduce antibiotic-resistant bacterial infections and increase the effective life of existing and new antibiotics

Antitrust as Disruptive Innovation in Health Care: Can Limiting State Action Immunity Help Save a Trillion Dollars?

On February 25, 2015, the United States Supreme Court ruled in North Carolina State Board of Dental Examiners v. FTC that state licensing boards controlled by market participants are subject to federal antitrust law unless they are “actively supervised” by the state itself. The ruling may sound narrow and technical, but the significance of the case can be inferred from the number and prominence of the amici curiae who lined up to support the North Carolina State Board of Dental Examiners (“North Carolina Board”)—first when the Federal Trade Commission’s (“FTC”) internal enforcement action was appealed to the United States Court of Appeals for the Fourth Circuit, and again when that court’s decision in favor of the FTC was reviewed by the Supreme Court. This Article evaluates the potential of North Carolina State Board to serve as a “disruptive innovation” that will make health care markets more efficient. Over time, the Supreme Court’s holding might induce states to reassess waste and inefficiency in professional services, rein in self-regulatory privilege, and modify political settlements built atop the scaffolding of professional self-governance that unduly constrain markets, even when they do not explicitly violate federal antitrust law. But, that will only happen if states embrace the opening that North Carolina State Board offers to disrupt the status quo

Soluble tau species, not neurofibrillary aggregates, disrupt neural system integration in a tau transgenic model

Neurofibrillary tangles are a feature of Alzheimer disease and other tauopathies, and while they are generally believed to be markers of neuronal pathology, there is little evidence evaluating whether tangles directly impact neuronal function. To investigate the response of cells in hippocampal circuits to complex behavioral stimuli, we used an environmental enrichment paradigm to induce expression of an immediate-early gene, Arc, in the rTg4510 mouse model of tauopathy. These mice reversibly overexpress P301L tau and exhibit substantial neurofibrillary tangle deposition, neuronal loss, and memory deficits. Employing fluorescent in situ hybridization to detect Arc mRNA, we found that rTg4510 mice have impaired hippocampal Arc expression both without stimulation and in response to environmental enrichment; this likely reflects the combination of functional impairments of existing neurons and loss of neurons. However, tangle-bearing cells were at least as likely as non-tangle-bearing neurons to exhibit Arc expression in response to enrichment. Transgene suppression with doxycycline for 6 weeks resulted in increased percentages of Arc-positive cells in rTg4510 brains compared to untreated transgenics, restoring enrichment-induced Arc mRNA levels to that of wild-type controls despite the continued presence of neurofibrillary pathology. We interpret these data to indicate that soluble tau contributes to impairment of hippocampal function, while tangles do not preclude neurons from responding in a functional circuit

Evaluating Multiple Arthropod Taxa as Indicators of Invertebrate Diversity in Old Fields

Biodiversity, often quantified by species richness, is commonly used to evaluate and monitor the health of ecosystems and as a tool for conservation planning. The use of one or more focal taxa as surrogates or indicators of larger taxonomic diversity can greatly expedite the process of biodiversity measurement. This is especially true when studying diverse and abundant invertebrate fauna. Before indicator taxa are employed, however, research into their suitability as indicators of greater taxonomic diversity in an area is needed. We sampled invertebrate diversity in old fields in southern Michigan using pitfall trapping and morphospecies designations after identification to order or family. Correlation analysis was used to assess species richness relationships between focal arthropod taxa and general invertebrate diversity. Relationships were assessed at two fine spatial scales: within sampling patches, and locally across four sampling patches. Cumulative richness of all assessed taxa increased proportionately with cumulative invertebrate richness as sampling intensity increased within patches. At the among-patch scale, we tentatively identified Hemiptera and Coleoptera as effective indicator taxa of greater invertebrate richness. Although Hymenoptera, Araneae and Diptera exhibited high species richness, their total richness within patches was not associated with overall invertebrate richness among patches. Increased sampling throughout the active season and across a greater number of habitat patches should be conducted before adopting Hemiptera and Coleoptera as definitive indicators of general invertebrate richness in the Great Lakes region. Multiple sampling techniques, in addition to pitfall trapping, should also be added to overcome capture biases associated with each technique

Estimating the Effect of Damages Caps in Medical Malpractice Cases: Evidence from Texas

Using claim-level data, we estimate the effect of Texas\u27s 2003 cap on non-economic damages on jury verdicts, post-verdict payouts, and settlements in medical malpractice cases closed during 1988–2004. For pro-plaintiff jury verdicts, the cap affects 47-percent of verdicts and reduces mean allowed non-economic damages, mean allowed verdict, and mean total payout by 73-percent, 38-percent, and 27-percent, respectively. In total, the non-econ cap reduces adjusted verdicts by $156M, but predicted payouts by only$60M. The impact on payouts is smaller because a substantial portion of the above-cap damage awards were not being paid to begin with. In cases settled without trial, the non-econ cap affects 18-percent of cases and reduces predicted mean total payout by 18-percent. The non-econ cap has a smaller impact on settled cases than tried cases because settled cases tend to involve smaller payouts. The impact of the non-econ cap varies across plaintiff categories. Deceased, unemployed, and (likely) elderly plaintiffs suffer a larger percentage reduction in payouts than living, employed, and non-elderly plaintiffs. We also simulate the effects of different caps and find substantial differences in cap stringency across states. Different caps reduce aggregate payouts in tried cases (all cases) by between 16-percent and 65-percent (7-percent and 42-percent). Caps on total damages have especially large effects

Defense Costs and Insurer Reserves in Medical Malpractice and Other Personal Injury Cases: Evidence from Texas, 1988-2004

We study defense costs for commercially insured personal injury tort claims in Texas over 1988–2004, and insurer reserves for those costs. We rely on detailed case-level data on defense legal fees and expenses, and Texas state bar data on lawyers’ hourly rates. We study medical malpractice (“med mal”) cases in detail, and other types of cases in less detail. Controlling for payouts, real defense costs in med mal cases rise by 4.6 percent per year, roughly doubling over this period. The rate of increase is similar for legal fees and for other expenses. Real hourly rates for personal injury defense counsel are flat. Defense costs in med mal cases correlate strongly with payouts, both in ordinary least squares (OLS) and in an instrumental variable analysis. They also correlate with the stage at which a case is resolved, and case duration. Mean duration declined over time. Med mal insurers predominantly use outside counsel. Case-level variation in initial expense reserves predicts a small fraction of actual defense costs. In other areas of tort litigation (auto, general commercial, multi-peril, and other professional liability), defense costs rose by 2.2 percent per year. Defense costs in these cases are predicted by the same factors as in med mal cases, plus the presence of multiple defendants. Insurer reserving practices raise some puzzles. Med mal insurers did not react to the sustained rise in defense costs by adjusting their expense reserves, either in real dollars or relative to reserves for payouts. Thus, expense reserves declined substantially relative to defense costs. In other litigation areas, expense reserves rose along with defense costs

Primary debulking surgery for metastatic cervical adenocarcinoma: A case report

• The case presented is that of a primary debulking surgery for presumed ovarian cancer. • Final pathology revealed diffusely metastatic endocervical adenocarcinoma. • After primary chemotherapy, the patient has remained disease-free 30 months after surgery

Do Defendants Pay What Juries Award? Post-Verdict Haircuts in Texas Medical Malpractice Cases, 1988–2003

Legal scholars, legislators, policy advocates, and the news media frequently use jury verdicts to draw conclusions about the performance of the tort system. However, actual payouts can differ greatly from verdicts. We report evidence on post-verdict payouts from the most comprehensive longitudinal study of matched jury verdicts and payouts. Using data on all insured medical malpractice claims in Texas from 1988–2003 in which the plaintiff received at least $25,000 (in 1988 dollars) following a jury trial, we find that most jury awards received “haircuts.” Seventy-five percent of plaintiffs received a payout less than the adjusted verdict (jury verdict plus prejudgment and postjudgment interest), 20 percent received the adjusted verdict (within ± 2 percent), and 5 percent received more than the adjusted verdict. Overall, plaintiffs received a mean (median) per-case haircut of 29 percent (19 percent), and an aggregate haircut of 56 percent, relative to the adjusted verdict. The larger the verdict, the more likely and larger the haircut. For cases with a positive adjusted verdict under$100,000, 47 percent of plaintiffs received a haircut, with a mean (median) per-case haircut of 8 percent (2 percent). For cases with an adjusted verdict larger than $2.5 million, 98 percent of plaintiffs received a haircut with a mean (median) per-case haircut of 56 percent (61 percent). Insurance policy limits are the most important factor in explaining haircuts. Caps on damages in death cases and caps on punitive damages are also important, but defendants often paid substantially less than the adjusted allowed verdict. Remittitur accounts for a small percentage of the haircuts. Punitive damage awards have only a small effect on payouts. Out-of-pocket payments by physicians are rare, never large, and usually unrelated to punitive damage awards. Most cases settle, presumably in the shadow of the outcome if the case were to be tried. That outcome is not the jury award, but the actual post-verdict payout. Because defendants rarely pay what juries award, jury verdicts alone do not provide a sufficient basis for claims about the performance of the tort system

How Do the Elderly Fare in Medical Malpractice Litigation, Before and After Tort Reform? Evidence from Texas

The elderly account for a disproportionate share of medical spending, but little is known about how they are treated by the medical malpractice system, or how tort reform affects elderly claimants. We compare paid medical malpractice claims brought by elderly plaintiffs in Texas during 1988–2009 to those brought by adult non-elderly plaintiffs. Controlling for healthcare utilization (based on inpatient days), elderly paid claims rose from about 20% to about 40% of the adult non-elderly rate by the early 2000s. Mean and median payouts per claim also converged, although the elderly were far less likely to receive large payouts. Tort reform strongly affected claim rates and payouts for both groups, but disproportionately reduced payouts to elderly claimants. We thus find evidence of convergence between the elderly and the adult non-elderly in both claim rates and payouts, which is interrupted by tort reform

MicroRNA profiling reveals marker of motor neuron disease in ALS models

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type to elucidate underlying disease mechanisms and to identify novel targets that inform on MN health during ALS disease time course. microRNAs (miRNAs) are short, noncoding RNAs that can shape the expression profile of a cell and thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, we used Cre recombinase-dependent miRNA tagging and affinity purification in mice. By defining thein vivomiRNA expression of MNs, all neurons, astrocytes, and microglia, we then focused on MN-enriched miRNAs via a comparative analysis and found that they may functionally distinguish MNs postnatally from other spinal neurons. Characterizing the levels of the MN-enriched miRNAs in CSF harvested from ALS models of MN disease demonstrated that one miRNA (miR-218) tracked with MN loss and was responsive to an ALS therapy in rodent models. Therefore, we have used cellular expression profiling tools to define the distinct miRNA expression of MNs, which is likely to enrich future studies of MN disease. This approach enabled the development of a novel, drug-responsive marker of MN disease in ALS rodents.SIGNIFICANCE STATEMENTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neurons (MNs) in the brain and spinal cord are selectively lost. To develop tools to aid in our understanding of the distinct expression profiles of MNs and, ultimately, to monitor MN disease progression, we identified small regulatory microRNAs (miRNAs) that were highly enriched or exclusive in MNs. The signal for one of these MN-enriched miRNAs is detectable in spinal tap biofluid from an ALS rat model, where its levels change as disease progresses, suggesting that it may be a clinically useful marker of disease status. Furthermore, rats treated with ALS therapy have restored expression of this MN RNA marker, making it an MN-specific and drug-responsive marker for ALS rodents.</jats:p