Treatment decision-making in sickle cell disease patients.

Sickle cell disease (SCD) is a blood disorder with few treatment options currently available. However, in recent years, there has been much progress toward developing new therapies and curative treatments to help patients with SCD. Stem cell transplant remains the only approved curative treatment for SCD, but new clinical trials are being initiated using gene therapy and gene editing. We surveyed patients with sickle cell disease (N=9) about attitudes toward stem cell transplant, gene therapy to add a new healthy gene, gene editing to up-regulate fetal hemoglobin, or gene editing to correct the point mutation. The participants read a fact sheet that included objective information on each curative treatment. When asked which curative treatment each participant would choose, all four options were selected at least once. The most highly selected treatment was gene correction gene editing (N=4). Participants generally agreed that the four treatment options are beneficial but were more mixed in their thoughts on whether the options are dangerous. Reasons for selecting a particular curative treatment were variable, but the most selected reasons were perception of a cure (N=4) or decreased severity (N=4), and not needing a donor (N=4). We are at the beginning stages of understanding how patients with SCD make decisions about curative treatments. Currently, patients may be interested in any of the four possibilities for curative treatments, with gene correction gene editing as the most popular choice. Reasons for choosing one treatment over another are mixed.

Patient physical characteristics and primary care physician decision making in preconception genetic screening.

BACKGROUND: There has been growing emphasis on preconception care as a strategy to improve maternal and child health since the 1980s. Increasingly, development of genetic tests will require primary care providers to make decisions about preconception genetic screening. Limited research has been conducted on how primary care providers interpret patients' characteristics and use constructs, such as ethnicity and race, to decide whom to offer preconception genetic screening. OBJECTIVE: This report assessed the influence of patient characteristics on decisions to offer preconception genetic screening. METHODS: A web-based survey of family physicians was conducted. Physicians reviewed a clinical vignette that was accompanied by a picture of either a black or a white patient. Physicians indicated whether they would offer genetic screening, and if yes, what tests they would offer and what factors influenced their decisions. RESULTS: The majority (69.2%) of physicians reported that they would not offer genetic screening. Respondents who reviewed the vignette accompanied by a picture of the black patient were more likely to offer screening (35% vs. 26%, p = 0.0034) and rated race as more important to their decision to offer testing than those who viewed the picture of the white patient (76% vs. 49%, p < 0.0001). CONCLUSIONS: Our findings suggest that patient race is important to physicians when making decisions about preconception genetic testing and that decision making is influenced by patients' physical characteristics. The reticence of physicians in this sample to offer preconception screening is an important finding for public health and clinical practice.

Proteomic analysis reveals a novel set of cell wall proteins in a transformed tobacco cell culture that synthesises secondary walls as determined by biochemical and morphological parameters.

A cell suspension culture of a tobacco (Nicotiana tabacum L. cv. Petit Havana) cell line derived from a cultivar transformed with the Tcyt gene from Agrobacterium, which leads to high endogenous levels of cytokinin, has been established. This cell line shows increased cell aggregation, elongated cells and a 5-fold increase in wall thickness. If allowed to carry on growing it can form a single mass without shedding cells into the medium. When analysed at an earlier growth stage, these cultures were found to produce improved levels of vascular nodule formation than in other systems that employ exogenous cytokinin. This differentiation was optimised with respect to sucrose and auxin signals in order to induce maximum production of cells with thickened walls and a morphology characteristic of fibre cells and tracheids, in addition to cells that remain meristematic. In order to establish the validity of this system for studying secondary wall formation, the walls and associated biosynthetic changes were analysed in these cells by chemical analysis of the walls, changes in activities of enzymes of xylan and monolignol synthesis, and expression of mRNAs coding for enzymes of lignin biosynthesis. The wall composition of the transformed cells was compared with that determined for primary walls from a typical untransformed tobacco cell line. Recovery of wall material was 50% greater in the transformed culture. In this material a major difference was found in the pectin fraction where there was a distinct difference in size distribution together with a lower level of methylation for the transformed line, which may be related to increased adhesiveness. There were increased amounts of xylan, although the ratio of xyloglucan to xylan content was not substantially different due to the mixture of cell types. There was also an increase in cellulose and phenolic components. Increased activity of enzymes involved in the synthesis of xylan as a marker for the secondary wall occurred around the time of tracheid differentiation and coincided with a broad peak of cinnamyl alcohol dehydrogenase activity. The expression of mRNAs coding for enzymes of the general phenylpropanoid pathway, phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, catechol O-methyl transferase was relatively constitutive in the cultures while transcripts of ferulate 5-hydroxylase, cinnamoyl CoA-reductase, cinnamyl alcohol dehydrogenase and lignin peroxidase were induced. The walls of the transformed cells also showed considerable differences in the subset of extractable proteins from that found in primary walls of tobacco when these were subjected to proteomic analysis. Many of these proteins appear to be novel and not present in primary walls. However an Mr-32,000 chitinase, an Mr-34,000 peroxidase, an Mr-65,000 polyphenoloxidase/laccase and possibly an Mr-68,000 xylanase could be identified as well as structural proteins.

Primary care guide to managing a breast mass: a legal perspective on risk management.

Failure to diagnose breast cancer in a timely manner is the most common reason for malpractice litigation in the US, and it is the most costly claim made against physicians. Common reasons for delay of diagnosis include unimpressive physical findings, failure to follow up with the patient, and a negative mammogram report. Equally important for quality patient care and for defense against malpractice suits is thorough documentation of history, examination, test results, recommendations, and patient interactions. This article provides guidelines with case studies that stress the importance of effective documentation and communication with the patient and offers recommendations for risk management.

Primary care guide to managing a breast mass: step-by-step workup.

Missed breast cancer is the most common malpractice suit filed in the US. But even without a biopsy of every mass, clinicians can reduce the risk of failed diagnosis to 1% by using a triple-diagnosis method to working up a breast mass, according to these experts, who offer a step-by-step guide. Includes QuickTimeTM video of breast exam. Failure to diagnose breast cancer in a timely manner is the most common reason for malpractice litigation in the US. Unless the potential for false-negative results of physical examination, mammography, ultrasound, and fine-needle aspiration biopsy (FNAB) is recognized, delay in the diagnosis of breast cancer will continue to occur. A systematic, thorough approach to the workup of any breast mass-- including a careful history, clinical breast examination, and documentation--is crucial. Upon detection of a mass, distinguishing the cyst from the solid mass (often by fine-needle aspiration or FNAB) is one of the most important tasks facing the clinician. Although most cysts resolve upon aspiration, solid masses require further workup to rule out cancer. Because of the false-negatives associated with individual methods of diagnosis, the authors recommend the triple-diagnosis method of detection. Simultaneous evaluation of a breast mass using clinical breast examination, radiography, and FNAB can lower the risk of missing cancer to only 1%, effectively reducing the rate of diagnostic failure and increasing the quality of patient care.

Gag rules and trade secrets in managed care contracts. Ethical and legal concerns.

Gag rules-clauses in managed care contracts that prevent physicians from disclosing information that the plan may find disparaging, but that could relate directly to the patient's health-have recently been the subject of ethical condemnation and legislative prohibition. Another serious problem in managed care contracts, trade secrets, or guidelines and quality assurance mechanisms that are imposed on physicians while their origins are shrouded in proprietary secrecy, have by contrast received little attention. Responses to these ethical challenges to the physician's integrity must involve individual physicians, managed care organizations, professional organizations, and public policymakers.

The timely diagnosis of breast cancer. Principles of risk management for primary care providers and surgeons.

Alleged delay in the diagnosis of breast cancer is one of the most common reasons for medical malpractice claims in the United States, accounting for the largest indemnity payments of any single medical condition. Although the diagnosis of breast cancer can be challenging and sometimes difficult, principles of management exist to assist health providers in pursuing a resolution of any breast complaint. Studies have shown that when litigation is pursued for alleged failure to diagnose breast cancer, multiple specialists are named in the suit. In most cases, patients filing claims of alleged failure to diagnose breast cancer are premenopausal, while the majority of women diagnosed with breast cancer are postmenopausal. This reflects, in part, the challenge of diagnosing the disease in women who have difficult clinical exams to interpret, as well as dense parenchyma on mammograms, which decreases the sensitivity of the radiograph interpretation. Principles of risk management to avoid a delay in diagnosis include (1) pursuing every breast complaint to resolution, (2) following breast cancer screening guidelines, (3) establishing an office tracking system for breast cancer screening reminders, (4) tracking results of all mammograms and follow-up studies ordered, (5) referring premenopausal women for the evaluation of any breast mass that persists through a menstrual cycle, (6) considering any asymmetrical breast finding as a cause for concern, (7) referring every woman with a breast finding on physical examination for consultation, regardless of the mammogram report, and (8) carefully documenting patient history, physical exam findings, clinical impression, and follow-up plans.