Medical employment growth,unemployment, and the opportunity cost of health care

This policy note examines the relationship between the growth in the share of the workforce in medical care and the shares of workers who are unemployed, working in services or government employment, or working elsewhere in the economy. These changes provide measures of the opportunity cost of higher medical care spending, the majority of which is on labor. Using state data over the period 1990–2010, we find that, in years of high economy-wide unemployment, growth in medical employment in a state reduces the unemployment rate significantly; it does not appear to displace employment in other services or government employment. In periods of low economy wide-unemployment, the growth in the medical employment share does not reduce unemployment. We argue that the opportunity cost of higher medical care employment may sometimes not be so high in terms of real labor resources, nor in terms of employment for needed government services.     

Molecular analysis of O6-substituted guanine-induced mutagenesis of ras oncogenes.

We have designed an Ha-ras/thymidine kinase (TK) cassette that permits the incorporation of chemically synthesized adducts within specific domains of the rat Ha-ras protooncogene. This cassette has been used to evaluate the mutagenicity of O6-substituted guanine residues, including O6-methylguanine and O6-benzylguanine, incorporated within the 12th codon of this locus. Mutations were monitored by the ability of these modified Ha-ras DNAs to transform Rat4 TK-cells. Our results indicate that both types of O6-substituted guanines are substantially mutagenic, although the methyl substituent induced a 2-fold higher percentage of transformed Rat4 TK+ colonies than its bulkier benzyl analogue. Interestingly, the mutagenicity of both O6-substituted guanines was found to be independent of their relative position within codon 12, therefore suggesting that the specific activation of Ha-ras oncogenes by GGA----GAA mutations in tumors induced by methylating carcinogens might be due to differences in the accessibility of these guanine residues to the carcinogen rather than to a differential rate of repair. Molecular analysis of the mutations induced by these O6-substituted guanines indicated that O6-methylguanine exclusively induced G----A transitions. In contrast, O6-benzylguanine produced G----C and G----T transversions in addition to G----A transitions. These results suggest that O6-methylguanine and its bulkier analogue O6-benzylguanine may induce mutagenesis by different mechanisms.     

Dimethylthiourea reverses sepsis-induced pulmonary hypertension in piglets

Dimethylthiourea (DMTU), a putative hydroxyl radical scavenger, attenuates thromboxane generation and pulmonary hypertension in the piglet model of group B streptococcal (GBS) sepsis. This study tested the hypothesis that DMTU reverses ongoing GBS-induced pulmonary hypertension coincident with decreased thromboxane production. Piglets (n = 15) received a 60 min infusion of GBS (10(-8) cfu/kg/min). Mean pulmonary artery pressure (Ppa), arterial blood gases (ABGs), and thromboxane B2 (TXB) levels were measured at 10 min intervals throughout the study. GBS infusion resulted in a marked increase in pulmonary artery pressure (mean delta Ppa = 31 mm Hg) and a significant decline in PaO2 (mean = -80 torr) within 10 min of beginning the infusion. pH decreased from a mean of 7.47 to 7.37. DMTU, 750 mg/kg, or normal saline vehicle was infused over 10-15 min beginning 10 min after initiating GBS. Ppa decreased significantly within 10 min of DMTU infusion. Piglets receiving vehicle had a slow decline in Ppa. Piglets receiving DMTU also had an improvement in PaO2 and showed no further drop in pH. Piglets receiving vehicle had no improvement in PaO2 and demonstrated a continued decline in pH. TXB levels did not differ between the groups at any time interval. We conclude that DMTU can partially reverse GBS-induced pulmonary hypertension, but may function through mechanisms independent of thromboxane generation.     

Self-refocused adiabatic pulse for spin echo imaging at 7 T

Spin echo pulse sequences are used to produce clinically important T(2) contrast. However, conventional 180° radiofrequency pulses required to generate a spin echo are highly susceptible to the B(1) inhomogeneity at high magnetic fields such as 7 Tesla (7 T), resulting in varying signal and contrast over the region of interest. Adiabatic 180° pulses may be used to replace conventional 180° pulses in spin echo sequences to provide greater immunity to the inhomogeneous B(1) field at 7 T. However, because the spectral profile of an adiabatic 180° pulse has nonlinear phase, pairs of these pulses are needed for proper refocusing, resulting in increased radiofrequency power deposition and long minimum echo times. We used the adiabatic Shinnar Le-Roux method to generate a matched-phase adiabatic 90°-180° pulse pair to obviate the need for a second adiabatic 180° pulse for phase refocusing. The pulse pair was then reformulated into a single self-refocused pulse to minimize the echo time, and phantom and in vivo experiments were performed to validate pulse performance. The self-refocused adiabatic pulse produced transmit profiles that were substantially more uniform than those achieved using a conventional spin echo sequence.     

SSR126768A (4-chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)-benzamide, hydrochloride): a new selective and orally active oxytocin receptor antagonist for the prevention of preterm labor

4-chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)benzamide, hydrochloride (SSR126768A), a new potent and selective, orally active oxytocin (OT) receptor antagonist was characterized in several biochemical and pharmacological models. In binding studies, SSR126768A showed nanomolar affinity for rat and human recombinant and native OT receptors (K(i) = 0.44 nM) and exhibited much lower affinity for V(1a), V(1b), and V(2) receptors. In addition, it did not interact with a large number of other receptors, enzymes, and ion channels (1 microM). In autoradiographic experiments performed on at-term human pregnant uterus sections, SSR126768A dose dependently displaced [I(125)]d(CH(2))(5)[Tyr(Me)(2), Thr(4), Orn(8) (125)I-Tyr-NH(2)(9)]VT in situ labeling to OT receptors highly expressed in these tissues. In functional studies, SSR126768A behaved as a full antagonist and potently antagonized OT-induced intracellular Ca(2+) increase (K(i) = 0.50 nM) and prostaglandin release (K(i) = 0.45 nM) in human uterine smooth muscle cells. In rat isolated myometrium, OT-induced uterine contractions were competitively antagonized by SSR126768A (pA(2) = 8.47). Similarly, in human pregnant myometrial strips, SSR126768A inhibited the contractile uterine response to OT. In conscious telemetrated rats, oral administration of SSR126768A (1-10 mg/kg) produced a competitive inhibition of the dose response to OT on uterine contractions up to 24 h at 3 mg/kg p.o.; no tachyphylaxis was observed after 4-day repeated treatment. Finally, SSR126768A (30 mg/kg p.o.) significantly delayed parturition in pregnant rats in labor similar to ritodrine (10 mg/kg p.o.). Thus, SSR126768A is a potent, highly selective, orally active OT receptor antagonist with a long duration of action. This molecule could find therapeutic application as a tocolytic agent for acute and chronic oral management of preterm labor.     

Time‐optimal design for multidimensional and parallel transmit variable‐rate selective excitation

Variable‐rate selective excitation (VERSE) is a radio frequency (RF) pulse reshaping technique. It is most commonly used to reduce the peak magnitude and specific absorption rate (SAR) of RF pulses by reshaping pulses and gradient waveforms to reduce RF magnitude while preserving excitation profiles. In this work, a general time‐optimal VERSE algorithm for multidimensional and parallel transmit pulses is presented. Time optimality is achieved by translating peak RF limits to gradient upper bounds in excitation k‐space. The limits are fed into a time‐optimal gradient waveform design technique. Effective SAR reduction is achieved by reducing peak RF subject to a fixed pulse length. The presented method is different from other VERSE techniques in that it provides a noniterative time‐optimal multidimensional solution, which drastically simplifies VERSE designs. Examples are given for 1D and 2D single channel and 2D parallel transmit pulses. Magn Reson Med, 61:1471–1479, 2009. © 2009 Wiley‐Liss, Inc.     

Getting real performance out of pay-for-performance

Context: Most private and public health insurers are implementing pay‐for‐performance (P4P) programs in an effort to improve the quality of medical care. This article offers a paradigm for evaluating how P4P programs should be structured and how effective they are likely to be. Methods: This article assesses the current comprehensiveness of evidence‐based medicine by estimating the percentage of outpatient medical spending for eighteen medical processes recommended by the Institute of Medicine. Findings: Three conditions must be in place for outcomes‐based P4P programs to improve the quality of care: (1) health insurers must not fully understand what medical processes improve health (i.e., the health production function); (2) providers must know more about the health production function than insurers do; and (3) health insurers must be able to measure a patient's risk‐adjusted health. Only two of these conditions currently exist. Payers appear to have incomplete knowledge of the health production function, and providers appear to know more about the health production function than payers do, but accurate methods of adjusting the risk of a patient's health status are still being developed. Conclusions: This article concludes that in three general situations, P4P will have a different impact on quality and costs and so should be structured differently. When information about patients' health and the health production function is incomplete, as is currently the case, P4P payments should be kept small, should be based on outcomes rather than processes, and should target physicians' practices and health systems. As information improves, P4P incentive payments could be increased, and P4P may become more powerful. Ironically, once information becomes complete, P4P can be replaced entirely by “optimal fee‐for‐service.”     

Premium Variation in the Individual Health Insurance Market

Recent proposals to decrease the number of uninsured in the U.S. indicate that the individual health insurance market's role may increase. Amid fears of possible risk-segmentation in individual insurance, there exists limited information of the functioning of such markets. This paper examines the relationship between expected medical expense and actual paid premiums for households with individual insurance in the 1996–1997 Community Tracking Study's Household Survey. We find that premiums vary less than proportionately with expected expense and vary only with certain risk characteristics. We also explore how the relationship between risk and premiums is affected by local regulations and market characteristics. We find that premiums vary significantly less strongly with risk for persons insured by HMOs and in markets dominated by managed care insurers.