Ethical considerations of applications of preimplantation genetic diagnosis in the United States

Preimplantation genetic diagnosis (PGD) was developed to offer diagnosis of genetic disorders prior to initiation of a pregnancy, whereas previously such disorders would be diagnosed at amniocentesis or chorionic villus sampling after a pregnancy had already been undertaken. Such application of this technology is not controversial. But PGD has been used to not only diagnose genetic disorders but also to select for certain other characteristics, and this use of the technique is much more controversial. A case is presented in which PGD was used not only to select against a genetic disorder, but to select for a certain HLA type which matched an affected sibling. The new child's cord blood was transplanted into his affected sister, who subsequently was found to be free of disease. The ethics of "having a child to save a child" are explored, and possible other uses of PGD that lead to eugenic outcomes are considered. The lack of regulation of this technology in the US is contrasted with existing legislation in other countries, and the need for national and international consensus regarding appropriate uses of PGD is emphasized.     

Is terminology used effectively to convey diagnostic certainty in radiology reports?

RATIONALE AND OBJECTIVES: This study was performed to assess the extent of agreement among radiologists and nonradiologists in perception of diagnostic certainty conveyed by words and phrases commonly used in radiology reports. MATERIALS AND METHODS: The study was performed in a large academic radiology department. To determine the commonly used terminology for conveying diagnostic certainty in radiology reports, 12 randomly selected radiologists from six different subspecialties were interviewed. The authors identified the 15 most commonly used words and phrases and included these in random order in a questionnaire sent to all staff radiologists (n = 45) and to 158 referring physicians. Physicians were asked to rank the 15 phrases in order of the diagnostic certainty conveyed by each, from 1 (most certain) to 15 (least certain), using each number only once. The kappa statistic was used to assess agreement in rank order among physicians. RESULTS: The questionnaire response rate was 76% (n = 34) for radiologists and 49% (n = 78) for nonradiologists. There was excellent agreement among radiologists (kappa = 0.95) and nonradiologists (kappa = 0.93) in the rank order for the phrase diagnostic of. Although there was good agreement (kappa = 0.45) among radiologists for the word unlikely, agreement among nonradiologists was poor (kappa = 0.27). There was very poor agreement among all physicians for the rank order of the other 13 phrases. CONCLUSION: Among radiologists and nonradiologists, concordance was poor regarding the diagnostic certainty associated with phrases commonly used in radiology reports. Because poor agreement could lead to suboptimal quality of care, the standardization of terminology would benefit all parties.     

Bone densitometry in children: a critical appraisal

Due to the introduction of new therapeutic regimen aimed at increasing and maintaining bone mass, bone densitometry in children has gained interest. As in all new fields of medicine we expect the interest in bone densitometry in children to increase in the coming years. Children pose a unique problem for those involved in the field of bone densitometry, because as time progresses the measured subject changes in shape and volume. It is therefore of importance that radiologists and clinicians gain insight in the available techniques. It is also important to keep in mind that all bone densitometry techniques have been exclusively designed, developed and validated for use in an adult population. In this article we give an overview of the available techniques and discuss the specific problems that can be expected when these techniques are used in children. In the discussion section general problems regarding bone densitometry in children are presented. Electronic Publication     

Benefit of cervical screening at different ages: evidence from the UK audit of screening histories

While most experts agree that cervical screening is effective, there remains controversy over the most appropriate screening interval. Annual screening is common in North America. In England, some argue for 3-yearly screening while others believe 5-yearly screening is adequate, and the frequency varies from one part of the country to another. Screening histories of 1305 women aged 20-69 years, diagnosed with frankly invasive cervical cancer and 2532 age-matched controls were obtained from UK screening programme databases. Data were analysed in terms of time since last negative, and time since last screening smear. Five-yearly screening offers considerable protection (83%) against cancer at ages 55-69 years and even annual screening offers only modest additional protection (87%). Three-yearly screening offers additional protection (84%) over 5-yearly screening (73%) for cancers at ages 40-54 years, but is almost as good as annual screening (88%). In women aged 20-39 years, even annual screening is not as effective (76%) as 3-yearly screening in older women, and 3 years after screening cancer rates return to those in unscreened women. This calls into question the policy of having a uniform screening interval from age 20 to 64 years and stresses the value of screening in middle-aged women.British Journal of Cancer (2003) 89, 88-93. doi:10.1038/sj.bjc.6600974 www.bjcancer.com     

What Affects Return to Work for Graduates of a Pain Management Program with Chronic Upper Limb Pain?

Chronic upper limb pain often causes work loss, and return to work after pain management is disappointingly low. This study aimed to identify patient characteristics and beliefs contributing to return to work or nonreturn. A total of 103 (66%) ex-patients with CULP, who had completed a pain management program, agreed to telephone interview. Participants were predominantly female and in middle years; 53.4% were working part- or full-time. Their responses were related to pre- and posttreatment psychological and disability variables. Those patients who had returned to work, compared to those who had not, were more likely to have been working shortly before treatment (² = 36.77, p < 0.0000). They were more psychologically robust and were more confident of managing pain (t = 4.55, p < 0.001), and catastrophized less (t = 2.21, p = 0.029). They were also more optimistic about being capable of work (u = 566, p < 0.0001) and of overcoming obstacles to work (u = 889, p = 0.0103). Workers and nonworkers were not differentiated by expectations of support from their immediate line manager, although nonworkers doubted support available from colleagues. Overall, despite generalization of pain management strategies in nonwork activity, return to work depended on specific beliefs concerning work-relevant strategies.     

Costs of poor birth outcomes among privately insured

Despite expansions in the public insurance coverage of pregnant women, concerns over poor birth outcomes remain. Poor birth outcomes occur among publicly and privately insured women, however, thereby imposing excess costs on employers and their insurers. Data from a large sample of privately insured for 1996 are used to examine these outcomes and costs. Almost one-fourth (24.3 percent) of the infants in our matched sample of 12,020 deliveries was premature or had other problems at birth. Costs for these infants accounted for 82 percent of the total $56 million spent on sample infants. The incremental cost of infants with poor birth outcomes versus those with normal, full-terms was approximately $14,600. We found that these relative costs had increased over time due perhaps to the increased technology and intensity of services used to save infant lives. We also found that factors other than maternal and infant complications affected cost variations. For example, employers located in the Northeast, hiring older mothers, and in unionized sectors have higher prenatal, delivery, and infant costs.     

Identification of phenylisoxazolines as novel and viable antibacterial agents active against Gram-positive pathogens

A new and promising group of antibacterial agents, collectively known as the oxazolidinones and exemplified by linezolid (PNU-100766, marketed as Zyvox), have recently emerged as important new therapeutic agents for the treatment of infections caused by Gram-positive bacteria. Because of their significance, extensive synthetic investigations into the structure-activity relationships of the oxazolidinones have been conducted at Pharmacia. One facet of this research effort has focused on the identification of bioisosteric replacements for the usual oxazolidinone A-ring. In this paper we describe studies leading to the identification of antibacterial agents incorporating a novel isoxazoline A-ring surrogate. In a gratifying result, the initial isoxazoline analogue prepared was found to exhibit in vitro antibacterial activity approaching that of the corresponding oxazolidinone progenitor. The synthesis and antibacterial activity profile of a preliminary series of isoxazoline analogues incorporating either a C-C or N-C linkage between their B- and C-rings will be presented. Many of the analogues exhibited interesting levels of antibacterial activity. The piperazine derivative 54 displayed especially promising in vitro activity and in vivo efficacy comparable to the activity and efficacy of linezolid.