Guidance For Clinical Decision Research Articles

Assessing the risk of ovarian malignancy in asymptomatic women with abnormal CA 125 and transvaginal ultrasound scans in the prostate, lung, colorectal, and ovarian screening trial.

To estimate the risk of ovarian malignancy among asymptomatic women with abnormal transvaginal ultrasound scans or CA 125 and to provide guidance to physicians managing these women. A cohort of women from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial with abnormal ovarian results at the initial (T0) and subsequent (T1+) screens were analyzed to estimate which findings were associated with high risk of ovarian cancer. Cancer risks more than 10% were designated as high and risks of 3% or less were designated as low. For the T0 screen, two high-risk categories were identified: CA 125 of 70 or more with negative transvaginal ultrasound scan (positive predictive value [PPV] 15.9%, CI 14.7-17.7%); and positive for both CA 125 and transvaginal ultrasound scan (PPV 25.0%, CI 23.3-27.3%). For T1+ screens, three high-risk categories were identified: negative transvaginal ultrasound scan with change in CA 125 of 45 or more (PPV 29.0%, CI 28.3-30.3%); increase in size of cyst 6 cm or more with negative CA 125 (PPV 13.3%, CI 10.5-18.0%); and positive for both tests (PPV 42.9%, CI 40.0-46.0%). High-risk criteria for T0 provide a sensitivity of 60%, specificity of 96.2%, PPV of 19.7%, and a negative predictive value (NPV) of 99.3%. T1+ criteria yielded a sensitivity of 85.3%, specificity of 95.6%, PPV of 29.6%, and NPV of 99.7%. High-risk categories for predicting risk of cancer in women with abnormal CA 125, transvaginal ultrasound scan, or both at initial and subsequent screens have been identified. The large number of women in this study, the 4-year complete follow-up, and small number of invasive cancers in the low-risk categories provide guidance for clinical decisions regarding need for surgery in these women. II.

Assessment of efficacy of antifungals in experimental models of invasive aspergillosis in an era of emerging resistance: the value of real-time quantitative PCR

Experimental models of invasive aspergillosis (IA) have been used to explore pharmacokinetic and pharmacodynamic (PK/PD) properties of antifungal agents. Survival is still considered the golden standard effect measure but has the disadvantage that a large number of animals are needed to determine the dose-response relationships and PK/PD of antifungals. The feasibility of using fungal load by real-time quantitative PCR (qPCR) as an effect measure has been explored recently. The majority of studies reported convincingly demonstrate a larger dynamic range for qPCR compared to conventional assays. However interpretation and translating the results to guidance in clinical decision making need further study. It is expected that the use of qPCR will become the primary outcome measure for assessment of PK/PD relationships of antifungals in experimental models of IA.

DOSE COEFFICIENTS FOR INTAKES OF RADIONUCLIDES VIA CONTAMINATED WOUNDS

The NCRP Wound Model, which describes the retention of selected radionuclides at the site of a contaminated wound and their uptake into the transfer compartment, has been combined with the ICRP element-specific systemic models for those radionuclides to derive dose coefficients for intakes via contaminated wounds. These coefficients can be used to generate derived regulatory guidance (i.e., the activity in a wound that would result in an effective dose of 20 or 50 mSv, or in some cases, a organ-equivalent dose of 500 mSv) and clinical decision guidance (i.e., activity levels that would indicate the need for consideration of medical intervention to remove activity from the wound site, administration of decorporation therapy or both). Data are provided for 38 radionuclides commonly encountered in various activities such as nuclear weapons, fuel fabrication or recycling, waste disposal, medicine, research, and nuclear power. These include 3H, 14C, 32P, 35S, 59Fe, 57,58,60Co, 85,89,90Sr, 99mTc, 106Ru, 125,129,131I, 134,137Cs, 192Ir, 201Tl, 210Po, 226,228Ra, 228,230,232Th, 234,235,238U, 237Np, 238,239,240,241Pu, 241Am, 242,244Cm, and 252Cf.

Sperm chromatin structure correlates with spontaneous abortion and multiple pregnancy rates in assisted reproduction

The objective of this study was to determine if a relationship exists between sperm parameters, measured by sperm chromatin structure assay (SCSA), and spontaneous abortion and multiple births in couples undergoing assisted reproduction treatment. Retrospective analysis of infertility treatment outcomes and occurrence of spontaneous abortion and multiple births was conducted in 233 couples who underwent treatment by intracytoplasmic sperm injection or intrauterine insemination at the Sher Institute for Reproductive Medicine, between 2001 and 2004. Sperm samples used for treatments were analysed for sperm concentration, sperm motility and two different parameters of SCSA (DNA fragmentation index, DFI, and high DNA stainability, HDS). Pregnancy, spontaneous abortion and multiple birth rates were recorded for all couples. A statistically significant relationship ( P < 0.001) was observed between DFI and spontaneous abortion. However, the correlation between HDS and spontaneous abortion was not statistically significant. Significantly lower levels of DFI were observed in men from couples having triplet pregnancies compared with those in the spontaneous abortion group ( P ⩽ 0.05). It is concluded that the parameters of SCSA correlate significantly with spontaneous abortion and multiple birth and may provide guidance for clinical decision making (number of embryos per transfer) and management of spontaneous abortion-prone cases. The goal of this study was to determine if a relationship exists between the sperm chromatin structure assay (SCSA) and spontaneous abortion and multiple births in couples treated via assisted reproductive technologies such as intra-cytoplasmic sperm injection or intrauterine insemination. SCSA is a test used by fertility clinics to determine if the sperm chromosomes or DNA are properly packaged in the sperm head and are therefore protected from damage that could occur during travel in the female reproductive system. A retrospective analysis of the results of SCSA, infertility treatment outcomes and the occurrence of spontaneous abortions and multiple births was conducted for 233 couples attending an infertility clinic. A statistically significant correlation was found between one of the SCSA parameters and spontaneous abortion. In addition, lower levels of this SCSA parameter were observed in men from couples having triplet pregnancies. We conclude that the parameters of SCSA correlate significantly with spontaneous abortions and multiple births and may provide guidance for clinical decision making, such as number of embryos per transfer or intensive management of spontaneous abortion-prone cases.

Detection of epidermal growth factor receptor mutations in plasma by mutant‐enriched PCR assay for prediction of the response to gefitinib in patients with non‐small‐cell lung cancer

The high frequency of epidermal growth factor receptor (EGFR) mutations in tyrosine kinase inhibitor-responsive non-small-cell lung cancer (NSCLC) cases is now well established, highlighting the predictive value of activating EGFR mutations in guiding the clinical use of EGFR-targeted therapies. However, specimen source and methods for EGFR mutation analysis are limited by tissue availability and technical feasibility in clinical application. Therefore, the current study is designed to establish a blood-based approach for the assessment of EGFR mutations in NSCLC patients, in particular the advanced stage, and to test its clinical application. Plasma samples were obtained from the enrolled 134 NSCLC patients. The detection rate of the EGFR exon19 deletions and exon21 L858R was 49.3% (66/134) by the blood-based, mutant-enriched polymerase chain reaction. In the paired tumor and plasma samples, the detected mutant types of each pair respectively by direct sequencing and mutant-enriched polymerase chain reaction were concordant in 17 of 18 (94.4%). In the patients treated with gefitinib as a second-line therapy, those with plasma EGFR mutation have a prolonged median progression-free survival compared with those with EGFR wild type (7.609 vs. 2.877 months, p = 0.002). On comparing the efficacy of gefitinib with that of docetaxel, it was found that the median progression-free survival was significantly longer for patients treated with gefitinib than those with docetaxel in those harboring plasma EGFR mutation (7.609 vs. 3.192 months, p = 0.006). These results suggest that the blood-based EGFR mutations test has the ability to provide a reliable guidance for clinical decision making for the treatment of the advanced NSCLC patients.

Weight development in patients treated with risperidone: a 5‐year naturalistic study

To examine annual weight-development in a sample of 215 psychotic patients treated with risperidone over 5 years. Naturalistic longitudinal study. The sample was more obese than the general population at baseline, but also increased much more in mean body mass index over approximately the same time period, while patients off medication seemed to remain weight stable. Excessive weight gain (>7%) was experienced by 40.2% and was weakly associated with weight at baseline (beta = -0.2%; P = 0.02), while independent of gender, symptoms, years of illness, prolactin levels and nicotine consumption. In patients with complete weight data (n = 87), approximately 72% (3.4 +/- 8.3 kg) of the observed 5 years weight gain (4.7 +/- 11.6 kg) had been accumulated after 2 years. Antipsychotic drug treatment resulted in significant weight gain, which levelled off over time. Unfortunately, few significant predictors of adverse weight development could be identified, leaving little guidance for clinical decision making regarding this specific side-effect.

Proposal of a Classification System for Patients With Neck Pain

It is likely that patients with neck pain are not a homogeneous group, but, instead, consist of a variety of subgroups, each of which may benefit from a specific intervention matched to the patient's signs and symptoms. Studies to date have largely failed to account for this possibility, which may compromise the statistical power of research and ultimately fail to provide guidance for clinical decision making. Classification provides a means of breaking down a larger entity into more homogeneous subgroups of patients, based on examination data. Classification can guide the determination of a patient's prognosis, and the selection of the most appropriate intervention strategy. Classification has received considerable attention in the management of patients with low back pain, and evidence is emerging regarding its benefits. There has been considerably less effort made towards examining classification as it pertains to patients with neck pain. The purpose of this clinical commentary is to examine the current literature and to propose a classification system for patients with neck pain, based on the overall goal of treatment. The approach is based on published evidence when possible and is also informed by clinical experience and expert opinion. Classification decisions are based on the integration of data from a variety of information from the history and physical examination. The end result of the classification process is to determine the treatment approach believed to be most likely to maximize the clinical outcome for an individual patient with neck pain.

Distinguishing prognostic and treatment-predictive information for localized prostate cancer

Objectives To distinguish the concepts of prognostic and treatmentpredictive information for localized prostate cancer. Methods We defined a prognostic factor as one that identifies subgroups associated with differing outcomes in untreated patients. A treatment-predictive factor identifies patients with differing outcomes as a consequence of treatment and is best identified in a large, randomized trial. Outside of such a trial, a treatment-predictive factor can be identified in prognostic subgroups or after adjustment for prognostic factors. Results The distinctions between prognostic and treatment-predictive factors are illustrated by hypothetical examples. Conclusions The practical implication of the distinctions is that prognostic information may not provide reliable treatment-predictive information, that is, additional information may be needed before selection of patients for different treatments can be based on prognostic information. Determination of the relative treatment effect in any prognostic subgroup of patients requires a comparative setting. Until now, identified prognostic factors for localized prostate cancer at best can give guidance for clinical decisions on which patients should not be offered local aggressive therapy if the aim of the therapy is to cure the patient of the disease.