The parkland approach to demands for "futile" treatment

Recent literature in medical ethics has emphasized disputes concerning the relative usefulness or uselessness (futility) of medical treatments. In our institution, these disputes typically arise in the context of critical care, with patients or families requesting or demanding a treatment (such as cardiopulmonary resuscitation) that in the treating physician's view holds no promise of benefit. In the context of revising our general treatment refusal/withdrawal/withholding guidelines, we provided a structure for resolving such disputes in a manner that balances the often conflicting goods of patient/family autonomy, physician autonomy, and institutional responsibility.     

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.     

Sex differences in the distribution of adipose tissue in the Djungarian hamster Phodopus sungorus

Female Djungarian hamsters (Phodopus sungorus) have proportionately more adipose tissue in superficial depots than males of similar age and body composition. In both sexes, the proportion in superficial depots increases with increasing fatness. This species may be useful as a model for human obesity because it becomes as obese as modern humans without genetic, surgical or dietary manipulation and the sex differences in adipose tissue distribution resemble those of humans.     

Size at birth and blood pressure at 3 years of age. The Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC)

The relations between size at birth and blood pressure were examined in a population-based longitudinal study of pregnancy and childbirth in the English county of Avon (the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC)) in 1994-1996. A total of 1,860 singleton children aged 3 years (response rate = 74%) were studied. Both height and body mass index were strongly related to blood pressure. After adjustment for current height and body mass index, birth weight showed a graded inverse relation with both systolic (-1.91 mmHg/kg, 95% CI -2.61 to -1.21 mmHg/kg, p < 0.0001) and diastolic blood pressure (-1.42 mmHg/kg, 95% CI -1.96 to -0.88 mmHg/kg, p < 0.0001) which was similar in boys and girls. Although birth length, head circumference, and ponderal index at birth were also inversely related to blood pressure, these relations disappeared after adjustment for birth weight. The strength of the birth weight-blood pressure relation was not strongly influenced by maternal height or by weight gain in the first year after birth, but was particularly strong in children who were shortest at 3 years of age. While the association between birth weight and blood pressure is consistent with reports from many earlier studies, the absence of independent relations between other measures of size at birth (particularly length:head circumference and ponderal index) and blood pressure does not suggest that undernutrition at a critical period of fetal growth plays an important role. Moreover, accelerated postnatal growth does not seem to underlie the birth weight-blood pressure association.     

Attitudes of Physicians Regarding Receiving and Storing Patients' Genetic Testing Results for Cancer Susceptibility

In order to determine interest in and support for a genetic counseling program for heritable cancers, a four-item questionnaire was sent to 700 physicians in San Diego County likely to encounter patients with significant family histories of cancer. Included in the questionnaire was an item requesting information about physician attitudes and practices regarding their record keeping for patient results of genetic testing for cancer susceptibility. Ninety-two questionnaires were returned for a response rate of 13%. The low response rate introduces caution when interpreting the results, particularly if the physicians most interested in the topic were the most likely to respond. In this light, of note was the marked variability found in the attitudes of respondents regarding where the results of patients' genetic testing results should be placed in relation to the medical record. Whereas one group of physicians would place the testing results into the medical record, just as they would any laboratory test result, other physicians do not even want written notice of the results in order to maintain patient confidentiality. Another group acknowledges the sensitivity of the information, but prefers to store genetic testing results separately, as they would results of HIV testing or history of psychiatric treatment. Genetic testing for cancer susceptibility is associated with patient concerns regarding confidentiality of testing results and fears of the consequences of release of this information to insurance companies. While the small and possibly biased sample must be considered when interpreting the results, the lack of consistency among physicians about where to store genetic testing results in terms of the patient medical record underscores the need for both a consensus statement and legal protection for both patient and physician. Variability in physician practices suggests that the process of obtaining informed consent for genetic testing should include a discussion with the patient about how the confidentiality of test results will be maintained.     

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.     

Attainment of clinical performance targets and improvement in clinical outcomes and resource use in hemodialysis care: a prospective cohort study

Background  

Clinical performance targets are intended to improve patient outcomes in chronic disease through quality improvement, but evidence of an association between multiple target attainment and patient outcomes in routine clinical practice is often lacking.     

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。     

Promising outcomes in teen mothers enrolled in a school-based parent support program and child care center

BACKGROUND: This study described a cohort of teen mothers and their children attending an urban high school with a parent support program and school-based child care center. Specific aims of the study were to describe maternal characteristics and outcomes, and child developmental and health outcomes. METHODS: A volunteer sample of 65 adolescent mothers enrolled in the parent support program and their children were interviewed, surveyed, and assessed. Fifty-three mothers had children enrolled in the school-based child care center and 12 mothers had their children cared for by family members. Maternal characteristics assessed included self-esteem and depressive symptoms, social stressors and support, self-perceived parental competence, parent-child teaching interactions, and subsequent childbearing and maternal educational outcomes. Child outcomes included child developmental assessments and health outcomes. RESULTS: About 33% of teen mothers were mildly to moderately depressed and 39% of the sample had experienced transitional homelessness. Social support networks were small; in the past 12 months, mothers experienced a mean number of 13.2 +/- 11.9 negative life events. Maternal self-report measures and mother-child observation measures indicated positive levels of parental competence. Maternal educational outcomes were positive, and only 6% of mothers had subsequent childbirths within 2 years. The mean scores on developmental assessments of children fell within the normal range, although there were 7 children identified with developmental delays. CONCLUSIONS: For at-risk teen mothers, this parent support program and school-based child care setting appears to offer promising opportunities to help young mothers with parenting, avoid rapid subsequent pregnancies, and stay engaged with school, while their children are cared for in a close and safe environment.     

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.