Write This Down: A Model Market-Share Liability Statute

The 1980s featured a remarkable series of lawsuits: the DES cases. The women who brought these cases had been harmed by a drug—DES—that their mothers had taken while the future plaintiffs were in utero. Hundreds of companies manufactured DES, each unit of DES sold was chemically identical, and the harmed women were generally unable to identify the manufacturer who had filled their mothers’ prescriptions. Many of the plaintiffs could not prove causation as to a specific manufacturer and so could not bring traditional tort suits. To provide relief, some courts forged ahead with a new tort theory: market-share liability. Under this theory, plaintiffs who were harmed by a fungible product and unable to identify the manufacturer who produced the unit that harmed them could sue all manufacturers of the product and collect from each of them according to their market share. But not every court recognized this new theory. And among the courts that did, disagreement emerged as to doctrinal determinations and mechanical considerations. This Note is the first survey of both the legal and practical questions surrounding claims based on market-share liability, from whether a prospective plaintiff qualifies for such a cause of action to determining the relevant market to pleading requirements. It asserts that market-share liability furthers the purposes of tort and products-liability law, critiques existing state statutory schemes, and proposes a model statute for state legislatures to consider

Effective Functional Form of Regge Trajectories

We present theoretical arguments and strong phenomenological evidence that hadronic Regge trajectories are essentially nonlinear and can be well approximated, for phenomenological purposes, by a specific square-root form.Comment: 29 pages, LaTeX. Published versio

Patient-reported outcome measures for monitoring primary care patients with depression: the PROMDEP cluster RCT and economic evaluation.

BACKGROUND: Guidelines on the management of depression recommend that practitioners use patient-reported outcome measures for the follow-up monitoring of symptoms, but there is a lack of evidence of benefit in terms of patient outcomes. OBJECTIVE: To test using the Patient Health Questionnaire-9 questionnaire as a patient-reported outcome measure for monitoring depression, training practitioners in interpreting scores and giving patients feedback. DESIGN: Parallel-group, cluster-randomised superiority trial; 1 : 1 allocation to intervention and control. SETTING: UK primary care (141 group general practices in England and Wales). INCLUSION CRITERIA: Patients aged ≥ 18 years with a new episode of depressive disorder or symptoms, recruited mainly through medical record searches, plus opportunistically in consultations. EXCLUSIONS: Current depression treatment, dementia, psychosis, substance misuse and risk of suicide. INTERVENTION: Administration of the Patient Health Questionnaire-9 questionnaire with patient feedback soon after diagnosis, and at follow-up 10-35 days later, compared with usual care. PRIMARY OUTCOME: Beck Depression Inventory, 2nd edition, symptom scores at 12 weeks. SECONDARY OUTCOMES: Beck Depression Inventory, 2nd edition, scores at 26 weeks; antidepressant drug treatment and mental health service contacts; social functioning (Work and Social Adjustment Scale) and quality of life (EuroQol 5-Dimension, five-level) at 12 and 26 weeks; service use over 26 weeks to calculate NHS costs; patient satisfaction at 26 weeks (Medical Informant Satisfaction Scale); and adverse events. SAMPLE SIZE: The original target sample of 676 patients recruited was reduced to 554 due to finding a significant correlation between baseline and follow-up values for the primary outcome measure. RANDOMISATION: Remote computerised randomisation with minimisation by recruiting university, small/large practice and urban/rural location. BLINDING: Blinding of participants was impossible given the open cluster design, but self-report outcome measures prevented observer bias. Analysis was blind to allocation. ANALYSIS: Linear mixed models were used, adjusted for baseline depression, baseline anxiety, sociodemographic factors, and clustering including practice as random effect. Quality of life and costs were analysed over 26 weeks. QUALITATIVE INTERVIEWS: Practitioner and patient interviews were conducted to reflect on trial processes and use of the Patient Health Questionnaire-9 using the Normalization Process Theory framework. RESULTS: Three hundred and two patients were recruited in intervention arm practices and 227 patients were recruited in control practices. Primary outcome data were collected for 252 (83.4%) and 195 (85.9%), respectively. No significant difference in Beck Depression Inventory, 2nd edition, score was found at 12 weeks (adjusted mean difference -0.46, 95% confidence interval -2.16 to 1.26). Nor were significant differences found in Beck Depression Inventory, 2nd Edition, score at 26 weeks, social functioning, patient satisfaction or adverse events. EuroQol-5 Dimensions, five-level version, quality-of-life scores favoured the intervention arm at 26 weeks (adjusted mean difference 0.053, 95% confidence interval 0.013 to 0.093). However, quality-adjusted life-years over 26 weeks were not significantly greater (difference 0.0013, 95% confidence interval -0.0157 to 0.0182). Costs were lower in the intervention arm but, again, not significantly (-£163, 95% confidence interval -£349 to £28). Cost-effectiveness and cost-utility analyses, therefore, suggested that the intervention was dominant over usual care, but with considerable uncertainty around the point estimates. Patients valued using the Patient Health Questionnaire-9 to compare scores at baseline and follow-up, whereas practitioner views were more mixed, with some considering it too time-consuming. CONCLUSIONS: We found no evidence of improved depression management or outcome at 12 weeks from using the Patient Health Questionnaire-9, but patients' quality of life was better at 26 weeks, perhaps because feedback of Patient Health Questionnaire-9 scores increased their awareness of improvement in their depression and reduced their anxiety. Further research in primary care should evaluate patient-reported outcome measures including anxiety symptoms, administered remotely, with algorithms delivering clear recommendations for changes in treatment. STUDY REGISTRATION: This study is registered as IRAS250225 and ISRCTN17299295. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/42/02) and is published in full in Health Technology Assessment; Vol. 28, No. 17. See the NIHR Funding and Awards website for further award information

Depression follow-up monitoring with the PHQ-9: open cluster-randomised controlled trial.

BACKGROUND: Outcome monitoring of depression is recommended but lacks evidence of patient benefit in primary care. AIM: To test monitoring depression using the PHQ-9 questionnaire with patient feedback. DESIGN AND SETTING: Open cluster-randomised controlled trial in 141 group practices. METHOD: Adults with new depressive episodes were recruited through records searches and opportunistically. EXCLUSION CRITERIA: dementia, psychosis, substance misuse, suicide risk. The PHQ-9 questionnaire was to be administered soon after diagnosis, and 10-35 days later. PRIMARY OUTCOME: Beck Depression Inventory (BDI-II) score at 12 weeks. SECONDARY OUTCOMES: BDI-II at 26 weeks; Work and Social Adjustment Scale and EuroQol EQ-5D-5L quality of life at 12 and 26 weeks; antidepressant treatment, mental health service use, adverse events, and Medical Informant Satisfaction Scale over 26 weeks. RESULTS: 302 intervention arm patients were recruited and 227 controls. At 12 weeks 252 (83.4%) and 195 (85.9%) were followed-up respectively. Only 41% of intervention arm patients had a GP follow-up PHQ-9 recorded. There was no significant difference in BDI-II score at 12 weeks (mean difference -0.46; 95% CI -2.16,1.26), adjusted for baseline depression, baseline anxiety, sociodemographic factors, and clustering by practice). EQ-5D-5L quality of life scores were higher in the intervention arm at 26 weeks (adjusted mean difference 0.053; 95% CI 0.093,0.013). A clinically significant difference in depression at 26 weeks could not be ruled out. No significant differences were found in social functioning, adverse events, or satisfaction. In a per-protocol analysis, antidepressant use and mental health contacts were significantly greater in intervention arm patients with a recorded follow-up PHQ-9. CONCLUSIONS: No evidence was found of improved depression outcome at 12 weeks from monitoring. The findings of possible benefits over 26 weeks warrant replication, investigating possible mechanisms, preferably with automated delivery of monitoring and more instructive feedback

Patients with allergic rhinitis and allergic asthma share the same pattern of eosinophil and neutrophil degranulation after allergen challenge

<p>Abstract</p> <p>Background</p> <p>Patients with allergic rhinitis and allergic asthma demonstrate comparable local and systemic eosinophil inflammation, and yet they present with different clinical pictures. Less is even known about the contribution of neutrophil inflammation in allergic diseases. The aim of the study was to examine the propensity and selectivity of granule release from primed systemic eosinophils and neutrophils in allergic rhinitis and allergic asthma after seasonal and experimental allergen exposure. We hypothesize that the dissimilar clinical manifestations are due to diverse eosinophil and neutrophil degranulation.</p> <p>Methods</p> <p>Nine birch pollen allergic patients with rhinitis, eight with asthma and four controls were studied during pollen season and after nasal and bronchial allergen challenge. Eosinophils and neutrophils were incubated in vitro with assay buffer and opsonized Sephadex particles for spontaneous and C3b-induced granule protein release. The released amount of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) was measured by specific radioimmunoassay.</p> <p>Results</p> <p>C3b-induced degranulation resulted in increased release of ECP and MPO from primed blood eosinophils and neutrophils in both allergic rhinitis and allergic asthma during pollen season and after both nasal and bronchial challenge (p-values 0.008 to 0.043). After bronchial challenge, the ECP release was significantly higher in the rhinitic group compared to the asthmatic group [19.8 vs. 13.2%, (p = 0.010)]. The propensity for EPO release was weak in all challenge models but followed the same pattern in both allergic groups.</p> <p>Conclusions</p> <p>Systemically activated eosinophils and neutrophils have similar patterns of degranulation after allergen exposure in allergic rhinitis and allergic asthma. The released amount of ECP, EPO and MPO was similar in all allergen challenge models in both allergic groups. Our results indicate that other mechanisms than the magnitude of eosinophil and neutrophil inflammation or the degranulation pattern of the inflammatory cells determines whether or not an allergic patient develops asthma.</p

Effects of Mountain Pine Beetle on Fuels and Expected Fire Behavior in Lodgepole Pine Forests, Colorado, USA

In Colorado and southern Wyoming, mountain pine beetle (MPB) has affected over 1.6 million ha of predominantly lodgepole pine forests, raising concerns about effects of MPB-caused mortality on subsequent wildfire risk and behavior. Using empirical data we modeled potential fire behavior across a gradient of wind speeds and moisture scenarios in Green stands compared three stages since MPB attack (Red [1–3 yrs], Grey [4–10 yrs], and Old-MPB [∼30 yrs]). MPB killed 50% of the trees and 70% of the basal area in Red and Grey stages. Across moisture scenarios, canopy fuel moisture was one-third lower in Red and Grey stages compared to the Green stage, making active crown fire possible at lower wind speeds and less extreme moisture conditions. More-open canopies and high loads of large surface fuels due to treefall in Grey and Old-MPB stages significantly increased surface fireline intensities, facilitating active crown fire at lower wind speeds (>30–55 km/hr) across all moisture scenarios. Not accounting for low foliar moistures in Red and Grey stages, and large surface fuels in Grey and Old-MPB stages, underestimates the occurrence of active crown fire. Under extreme burning conditions, minimum wind speeds for active crown fire were 25–35 km/hr lower for Red, Grey and Old-MPB stands compared to Green. However, if transition to crown fire occurs (outside the stand, or within the stand via ladder fuels or wind gusts >65 km/hr), active crown fire would be sustained at similar wind speeds, suggesting observed fire behavior may not be qualitatively different among MPB stages under extreme burning conditions. Overall, the risk (probability) of active crown fire appears elevated in MPB-affected stands, but the predominant fire hazard (crown fire) is similar across MPB stages and is characteristic of lodgepole pine forests where extremely dry, gusty weather conditions are key factors in determining fire behavior

Influence of Age, Circadian and Homeostatic Processes on Inhibitory Motor Control: A Go/Nogo Task Study

INTRODUCTION: The contribution of circadian system and sleep pressure influences on executive performance as a function of age has never been studied. The aim of our study was to determine the age-related evolution of inhibitory motor control (i.e., ability to suppress a prepotent motor response) and sustained attention under controlled high or low sleep pressure conditions. METHODS: 14 healthy young males (mean age = 23 ± 2.7; 20-29 years) and 11 healthy older males (mean age = 68 ± 1.4; 66-70 years) were recruited. The volunteers were placed for 40 hours in "constant routine". In the "Sleep Deprivation SD" condition, the volunteer was kept awake for 40 hours to obtain a high sleep pressure condition interacting with the circadian process. In the "NAP" condition, the volunteer adopted a short wake/sleep cycle (150/75 min) resulting in a low sleep pressure condition to counteract the homeostatic pressure and investigate the circadian process. Performances were evaluated by a simple reaction time task and a Go/Nogo task repeated every 3H45. RESULTS: In the SD condition, inhibitory motor control (i.e., ability to inhibit an inappropriate response) was impaired by extended wakefulness equally in both age groups (P<.01). Sustained attention (i.e. ability to respond accurately to appropriate stimuli) on the executive task decreased under sleep deprivation in both groups, and even more in young participants (P<.05). In the NAP condition, age did not influence the time course of inhibitory motor control or sustained attention. In the SD and NAP conditions, older participants had a less fluctuating reaction time performance across time of day than young participants (P<.001). CONCLUSION: Aging could be a protective factor against the effects of extended wakefulness especially on sustained attention failures due to an attenuation of sleep pressure with duration of time awake

Depression follow-up monitoring with the PHQ-9: open cluster-randomised controlled trial

Background: Outcome monitoring of depression is recommended but lacks evidence of patient benefit in primary care. Aim: To test monitoring depression using the PHQ-9 questionnaire with patient feedback. Design and setting: Open cluster-randomised controlled trial in 141 group practices. Method: Adults with new depressive episodes were recruited through records searches and opportunistically. Exclusion criteria: dementia, psychosis, substance misuse, suicide risk. The PHQ-9 questionnaire was to be administered soon after diagnosis, and 10-35 days later. Primary outcome: Beck Depression Inventory (BDI-II) score at 12 weeks. Secondary outcomes: BDI-II at 26 weeks; Work and Social Adjustment Scale and EuroQol EQ-5D-5L quality of life at 12 and 26 weeks; antidepressant treatment, mental health service use, adverse events, and Medical Informant Satisfaction Scale over 26 weeks. Results: 302 intervention arm patients were recruited and 227 controls. At 12 weeks 252 (83.4%) and 195 (85.9%) were followed-up respectively. Only 41% of intervention arm patients had a GP follow-up PHQ-9 recorded. There was no significant difference in BDI-II score at 12 weeks (mean difference -0.46; 95% CI -2.16,1.26), adjusted for baseline depression, baseline anxiety, sociodemographic factors, and clustering by practice). EQ-5D-5L quality of life scores were higher in the intervention arm at 26 weeks (adjusted mean difference 0.053; 95% CI 0.093,0.013). A clinically significant difference in depression at 26 weeks could not be ruled out. No significant differences were found in social functioning, adverse events, or satisfaction. In a per-protocol analysis, antidepressant use and mental health contacts were significantly greater in intervention arm patients with a recorded follow-up PHQ-9. Conclusions: No evidence was found of improved depression outcome at 12 weeks from monitoring. The findings of possible benefits over 26 weeks warrant replication, investigating possible mechanisms, preferably with automated delivery of monitoring and more instructive feedback