Small businesses' changing views on health reform

Our national sample of 750 randomly chosen firms with fewer than 50 employees reveals surprising findings about the traditional views of small business on health care reform. A substantial segment of the small business community is sympathetic to health care reform, including such controversial measures as mandating that all employers contribute to the coverage of their workers, limits on health care spending, and altering the tax treatment of employer contributions for health insurance. Without premium savings, fewer than half of small businesses support the concept of health insurance purchasing cooperatives. With premium savings, a majority support it.     

Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor

Background:

Monoamine reuptake inhibitors exhibit unique clinical profiles that reflect distinct engagement of the central nervous system (CNS) transporters.

Methods:

We used a translational strategy, including rodent pharmacokinetic/pharmacodynamic modeling and positron emission tomography (PET) imaging in humans, to establish the transporter profile of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor.

Results:

TD-9855 was a potent inhibitor of norepinephrine (NE) and serotonin 5-HT uptake in vitro with an inhibitory selectivity of 4- to 10-fold for NE at human and rat transporters. TD-9855 engaged norepinephrine transporters (NET) and serotonin transporters (SERT) in rat spinal cord, with a plasma EC₅₀ of 11.7ng/mL and 50.8ng/mL, respectively, consistent with modest selectivity for NET in vivo.Accounting for species differences in protein binding, the projected human NET and SERT plasma EC₅₀ values were 5.5ng/mL and 23.9ng/mL, respectively. A single-dose, open-label PET study (4–20mg TD-9855, oral) was conducted in eight healthy males using the radiotracers [¹¹C]-3-amino-4- [2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile for SERT and [¹¹C]-(S,S)-methylreboxetine for NET. The long pharmacokinetic half-life (30–40h) of TD-9855 allowed for sequential assessment of SERT and NET occupancy in the same subject. The plasma EC₅₀ for NET was estimated to be 1.21ng/mL, and at doses of greater than 4mg the projected steady-state NET occupancy is high (>75%). After a single oral dose of 20mg, SERT occupancy was 25 (±8)% at a plasma level of 6.35ng/mL.

Conclusions:

These data establish the CNS penetration and transporter profile of TD-9855 and inform the selection of potential doses for future clinical evaluation.     

Clinical multimorbidity and physical function in older adults: a record and health status linkage study in general practice

BACKGROUND: Multiple chronic conditions occurring in the same individual are associated with adverse health outcomes. In family practice, individuals are seen who, over time, may experience many different symptoms, illnesses and chronic diseases. Measures for defining multimorbidity, which incorporate the diverse range of health problems seen in population-based family practice, remain to be developed. We have investigated whether routinely collected consultation data could be used as the basis for a simple classification of multimorbidity that reflects an individual's overall health status. METHODS: Morbidity consultation data for 9,439 English patients aged 50 years and over in an 18-month time period were linked to their self-reported physical health status measured by Short-Form 12 at the end point. Associations between physical function and all-cause multimorbidity counts were estimated relative to single morbidity only, and between physical function and morbidity severity (185 morbidities categorized on four ordinal scales of severity) relative to persons who had not consulted about any of the 185. RESULTS: In the 18-month period, 19% had consulted for a single morbidity and 23% for six or more (a high multimorbidity count). An estimated 24% of poor physical function in the family practice consulting population may be attributable to high multimorbidity. There was an increasing strength of association between poor physical function and increasing severity of multimorbidity on all four severity scales. Estimated associations (adjusted odds ratios) of the most severe morbidity categories with poor physical function were, for each of the four scales, respectively, 5.6 for chronicity [95% confidence interval (CI) 4.4-7.1], 7.0 for time course (4.5-10.6) and 3.6 for health care use (2.0-6.6) and for patient impact (6.7; 5.2-8.8). CONCLUSIONS: Multimorbidity defined by using routinely collected family practice consultation data and classified by count and by severity was associated with poorer physical function. This approach offers the potential for systematic use of routine records to classify multimorbidity and to identify groups with high likelihood of poor physical status for needs assessment and targeted intervention.     

马兜铃酸的倍半萜的酯类化合物VI.绵毛马兜铃中马兜铃酸萜酯I的结构鉴定

从绵毛马兜铃(Aristolocha mannisima Hance)中分得一个马兜铃酸倍半萜的酯类化合物,经红外、紫外、高分辩质谱和多种一维和二维核磁共振谱鉴定,确定了其骨架结构及顺反构型,命名为马兜铃酸萜酯I。     

Development of health‐related quality of life and symptoms in patients with advanced cancer in Greenland

A prospective national cohort study assessed the development of health‐related quality of life (HRQoL) and symptoms in adult patients undergoing treatment and care for advanced cancer in Greenland. HRQol was examined by EORTC QLQ‐C30 version 3.0 questionnaire monthly for 4 months. Changes over time and between‐group comparisons were examined. Of 58 patients included in the study, 47% completed the questionnaire four times. Functioning was generally high, and improved social functioning was observed after 1 and 2 months. The highest symptom score was for fatigue followed by pain and nausea/vomiting. A high score for financial problems remained unchanged during the entire period. Patients with higher income had reduced pain intensity (p = .03) and diarrhoea (p = .05) than patients with income below the poverty line. After 1 month, reduction in pain intensity was observed for Nuuk citizens compared with non‐Nuuk citizens (p = .05). After 2 months, non‐Nuuk citizens reported improved social functioning compared with Nuuk citizens (p = .05). After 3 months, Global Health in Nuuk citizens was improved compared with non‐Nuuk citizens (p = .05). An important clinical finding was that patients’ needs for support are related to social status, and geographical factors should be taken into account when planning palliative care.     

Models of governance in multihospital systems. Implications for hospital and system-level decision-making

This study utilizes data from a national survey of 159 multihospital systems in order to describe the types of governance structures currently being utilized, and to compare the policy making process for various types of decisions in systems with different approaches to governance. Survey results indicate that multihospital systems most often use one of three governance models. Forty-one percent of the systems (including 33% of system hospitals) use a parent holding company model in which there is a system-wide corporate governing board and separate governing boards for each member hospital. Twenty-two percent of systems in the sample (but 47% of all system hospitals) utilize what we have termed a modified parent holding company model in which there is one system-wide governing board, but advisory boards are substituted for governing boards at the local hospital level. Twenty-three percent of the sampled systems (including 11% of system hospitals) use a corporate model in which there is one system-wide governing board but no other governing or advisory boards at either the divisional, regional or local hospital levels. A comparison of systems using these three governance approaches found significant variation in terms of system size, ownership and the geographic proximity of member hospitals. In order to examine the relationship between alternative approaches to governance and patterns of decision-making, the three model types were compared with respect to the percentages of systems reporting that local boards, corporate management and/or system-wide corporate boards have responsibility for decision-making in a number of specific issue areas. Study results indicate that, regardless of model type, corporate boards are most likely to have responsibility for decisions regarding the transfer, pledging and sale of assets; the formation of new companies; purchase of assets greater than $100,000; changes in hospital bylaws; and the appointment of local board members. In contrast corporate management is relatively uninvolved in these issues, again regardless of governance model type. There is substantial variation in the locus of decision-making responsibility by governance model type for a variety of other issues, however, including: hospital-level service additions and deletions; operating and capital budgets; medical staff privileges, hospital-level long-range planning; hospital CEO performance evaluation and the appointment of hospital CEOs.(ABSTRACT TRUNCATED AT 400 WORDS)