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Background: Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma. Materials and methods: Patients with metastatic pancreatic adenocarcinoma were randomized in a 2:1 fashion to gemcitabine 1000 mg/m² weekly for 3 weeks of a 4-week cycle plus rigosertib 1800 mg/m² via 2-h continuous IV infusions given twice weekly for 3 weeks of a 4-week cycle (RIG + GEM) versus gemcitabine 1000 mg/m² weekly for 3 weeks in a 4-week cycle (GEM). Results: A total of 160 patients were enrolled globally and randomly assigned to RIG + GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG + GEM group versus 6% in the GEM group), hyponatremia (17% versus 4%), and anemia (8% versus 4%). The median overall survival was 6.1 months for RIG + GEM versus 6.4 months for GEM [hazard ratio (HR), 1.24; 95% confidence interval (CI) 0.85-1.81]. The median progression-free survival was 3.4 months for both groups (HR = 0.96; 95% CI 0.68-1.36). The partial response rate was 19% versus 13% for RIG + GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40 cases). Other mutations detected included TP53 (13 cases) and PIK3CA (1 case). No correlation between mutational status and efficacy was detected. Conclusions: The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation. [ABSTRACT FROM AUTHOR]

Objectives: This study explored reasons why older adults with urinary incontinence (UI) do not initiate discussions with or seek treatment for UI from their primary care provider., Design: A randomized, prospective controlled trial involving 41 primary care sites., Setting: Primary care practice sites., Participants: 49 older adults age 60 and older not previously screened for UI by their primary care doctor., Measurements: Demographic data, self-reported bladder-control information using questionnaires, and health status., Results: Adults who did not discuss UI were older, had less-frequent leaking accidents and fewer nighttime voids and were less bothered by UI than those who did. The two main reasons why patients did not seek help were the perceptions that UI was not a big problem (45%) and was a normal part of aging (19%)., Conclusions: Embarrassment or lack of awareness of treatment options were not significant barriers to discussing UI. Adults with a fairly high frequency of UI (average of 1.7 episodes per day) did not view UI as abnormal or a serious medical condition.

Optimal therapy for pancreatic adenocarcinoma requires surgical removal with tumor-free margins. Superior outcomes have been reported for high-volume centers incorporating a multidisciplinary approach. Postoperative ("adjuvant") chemotherapy and radiation should be considered in patients with successfully resected primary tumors. Combined modality treatment with chemotherapy and radiation should be considered for locally advanced, unresectable tumors. Gemcitabine can provide symptom relief and a modest improvement in survival for patients with metastatic disease. Strict attention to relief of symptoms such as pain, depression, anorexia/cachexia, and jaundice is essential in all patients with pancreatic cancer. All patients with pancreatic cancer should be encouraged to enter clinical trials of new therapies, given that long-term survival for all stages remains poor.

We describe the design of the Managing Anti-coagulation Services Trial (MAST), a practice-improvement trial testing whether anticoagulation services are a preferred method of managing anticoagulation for stroke prevention among patients with atrial fibrillation. Most randomized trials within the health care environment are designed as efficacy studies to determine what works under ideal conditions or ideal clinical practice. In contrast, effectiveness trials seek to generalize the results of efficacy studies by determining what works under more typical practice conditions. Practice-improvement trials are effectiveness trials that examine the management of a clinical problem in the context in which care is usually given. Noteworthy features of the MAST include defining the intervention in functional terms and collaboration with managed care organizations.

Objectives: To examine the relationship of urinary incontinence (UI) and depressive symptoms (DS) in older adults., Design: A randomized, controlled trial to determine the effects of clinical practice guideline implementation on provider attitudes and behavior, and patients' UI, health status, quality of life, and satisfaction with care. Baseline and endpoint data were collected from patients via computer-assisted telephone interviewing., Setting: Forty-one nonacademic primary care practices (PCP) in North Carolina., Participants: A total of 668 community-dwelling adults (age > 60) who had visited the one of the selected PCPs., Intervention: PCPs in the intervention group were given instruction in the detection and management of UI, educational materials for providers and patients, office system supports, and academic detailing., Measurements: The dependent measure was assessed using an eight-item screener for DS. UI (status, frequency, amount), health (physical, mental), and demographic (age, gender, marital status) and self-report information about bladder control served as predictors., Results: Wilcoxon rank sum tests showed that UI status was associated with moderate to severe DS (43% vs 30%, P = .05). Multivariate analyses showed that UI status, physical and mental health, and gender were significant predictors of DS. Among UI adults (n = 230), physical and mental health, life satisfaction, and the perception that UI interfered with daily life were significant predictors of DS., Conclusions: This study provides clear evidence that UI is related to DS in older adults.

Objective: To evaluate the use of the prostate-specific antigen (PSA) test and digital rectal examination (DRE) in prostate cancer screening by primary care physicians., Study Design: Physician survey and retrospective medical record review., Methods: We randomly selected and reviewed the medical records of 3 cross-sectional samples of male patients and surveyed their primary care physicians at 1-year intervals. All the physicians practiced in Colorado. The study spanned 3 years, including late 1992, when the American Cancer Society recommended the use of PSA in a prostate cancer screening guideline., Results: We reviewed the medical records of 4772 male patients and surveyed 109 primary care physicians. We found that PSA testing for men aged 50 or older increased significantly from 1992 to 1994, from 24% in 1992 to 35% in 1993 and 40% in 1994 (overall odds ratio, 2.94; P < .05). Over the same time period, the DRE rate remained relatively unchanged (39% in 1992, 41% in 1993, and 36% in 1994). Overall PSA use was positively associated with patient age greater than 59 years, patient non-smoking status, physician "readiness to change cancer screening behavior," private insurance status, and nonsolo practice. Before the release of a prostate cancer screening guideline, participating physicians cited the American Cancer Society as the organization that most influenced their practice with respect to cancer screening. The magnitude of the reported influence of the American Cancer Society was correlated with the subsequent use of PSA in 1994 by primary care physicians after adjustment for change in DRE and baseline PSA rates, although the association did not reach statistical significance in multivariable regression models., Conclusions: Primary care physicians in Colorado significantly increased their use of the PSA test from 1992 to 1994, during which time the American Cancer Society issued a guideline recommending the use of PSA for prostate cancer screening. The reported influence of the American Cancer Society on cancer screening practices correlated with the subsequent increase in PSA testing.

Objective: The purpose of the study was to test a novel approach to monitoring the adherence of continuous ambulatory peritoneal dialysis (CAPD) patients to their dialysis prescription., Design: A descriptive observational study was done in which exchange behaviors were monitored over a 2-week period of time., Setting: Patients were recruited from an outpatient dialysis center., Participants: A convenience sample of patients undergoing CAPD at Piedmont Dialysis Center in Winston-Salem, North Carolina was recruited for the study. Of 31 CAPD patients, 20 (64.5%) agreed to participate., Measures: Adherence of CAPD patients to their dialysis prescription was monitored using daily logs and an electronic monitoring device (the Medication Event Monitoring System, or MEMS; APREX, Menlo Park, California, U.S.A.). Patients recorded in their logs their exchange activities during the 2-week observation period. Concurrently, patients were instructed to deposit the pull tab from their dialysate bag into a MEMS bottle immediately after performing each exchange. The MEMS bottle was closed with a cap containing a computer chip that recorded the date and time each time the bottle was opened., Results: One individual's MEMS device malfunctioned and thus the data presented in this report are based upon the remaining 19 patients. A significant discrepancy was found between log data and MEMS data, with MEMS data indicating a greater number and percentage of missed exchanges. MEMS data indicated that some patients concentrated their exchange activities during the day, with shortened dwell times between exchanges. Three indices were developed for this study: a measure of the average time spent in noncompliance, and indices of consistency in the timing of exchanges within and between days. Patients who were defined as consistent had lower scores on the noncompliance index compared to patients defined as inconsistent (p = 0.015)., Conclusions: This study describes a methodology that may be useful in assessing adherence to the peritoneal dialysis regimen. Of particular significance is the ability to assess the timing of exchanges over the course of a day. Clinical implications are limited due to issues of data reliability and validity, the short-term nature of the study, the small sample, and the fact that clinical outcomes were not considered in this methodology study. Additional research is needed to further develop this data-collection approach.

There are a series of possible impediments to the incorporation of new treatment modalities into clinical practice, and any intervention intended to alter practice must consider physicians' motivation and readiness to change. As part of a national survey in the United States, physicians from a variety of specialties were asked whether they were comfortable with, considering changing or expecting to make changes in their screening and treatment practices for a series of eight hypothetical patients at elevated risk of stroke. Readiness to change varied with the type of patient under consideration and with physician specialty, but not with a series of other physician and practice characteristics. Knowledge of physicians' states of readiness to change in combination with data relating to current practices and potential barriers to implementation should aid in targeting educational efforts and in the development of specific interventions to improve stroke prevention.

Background: Because of a strong association between health maintenance visits (HMVs) and cancer screening, knowledge of the predictors of an HMV have implications for screening., Objective: To examine the association of an HMV with patient, physician, and practice characteristics in the primary care setting., Design: A statewide study of cancer screening was conducted in Colorado to determine concordance with the National Cancer Institute's guidelines for screening for breast, cervical, prostate, and skin cancer. Medical records form patients were randomly chosen from primary care practices. Predictors of an HMV were determined by fitting a logistic model to baseline data, adjusting for the cluster sampling of patients within practices., Setting: Nonacademic primary care practices in Colorado., Participants: A total of 5746 patients aged 42 to 74 years from 132 primary care practices., Main Outcome Measure: Whether a patient had an HMV in the previous year., Results: Of all patients, 31% had an HMV in the previous year. Patient characteristics associated with having HMVs included nonsmoking status, odds ratio (OR) (95% confidence interval [CI]) of 1.27 (1.11-1.46), age, and sex. Women aged 50 to 69 years were significantly more likely to have an HMV than men aged 50 to 69 years (OR, 1.30; 95% CI, 1.10-1.54). Among adults aged 70 years and older, there were no significant sex differences in receiving HMVs. Physician and practice characteristics associated with providing HMVs included practice size (> or = 3 full-time physicians) (OR, 1.34; 95% CI, 1.01-1.77), physician contemplation of changing approaches to cancer screening (OR, 1.33; 95% CI, 1.04-1.70), and physician female sex (OR, 1.33; 95% CI, 1.04-1.70). Physician age and specialty (general internist or family physician) were not associated with the level of health maintenance delivery., Conclusion: Certain subgroups, such as smokers, patients in smaller practices, and physicians not yet considering changing their approach to cancer screening, could be targeted in future intervention studies designed to provide preventive services in primary care settings.

Being responsible for medical education places academic health centers at a disadvantage in competing for managed care contracts. Although many suggestions have been made for changing medical education to produce physicians who are better prepared for the managed care environment, few studies have shown how physicians in training can actually contribute to the competitiveness of an academic health center. We present three examples of engaging trainees in projects with a population-based perspective that demonstrate how quality improvement for the academic health center can be operationalized and even led by physicians in training. In addition to gaining experience in a managed care skill that is increasingly important for future employment, physicians in training can simultaneously improve the quality of care delivered through the academic health center.

The purpose of this study was to analyze partial nucleotide sequences and derived peptide sequences of hepatitis E virus (HEV) from two outbreaks of hepatitis E in Africa (Chad 1983-1984; Algeria 1978-1980). A portion of ORF3 and the major portion of ORF2 were amplified by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). The PCR products were sequenced directly or after cloning into the pCRII vector. Sequences were then compared to the corresponding regions of reported full length HEV sequences. In the ORF2 and ORF3 regions, the homology between the Algerian and the Chad isolates at the nucleic acid level was 92 and 95%, respectively. At the peptide level the homology was 98% in both regions. In these regions, both strains are more related to Asian strains at the nucleic acid level (89 to 95%) and at the amino acid level (95 to 100%) than to the Mexico strain. At the peptide level the differences are less apparent. Both African isolates have amino acid changes in common with some reference strains although the Chad isolate has three unique changes. These African strains of HEV, based on the ORF2 and ORF3 phylogenetic trees, appear to be a distinct phylogenetic group, separate from the Mexican and Asian strains.

Erythrocytes infected with malaria parasites often contain membranous vesicles that are presumed to facilitate macromolecule traffic between the parasite and erythrocyte membranes. One such vesicle network, called Maurer's clefts, is expressed in Plasmodium falciparum-infected erythrocytes and contains a 50-kD polypeptide. Using a monoclonal antibody reactive with this polypeptide, we show that hepatic stages of P. falciparum express an epitope common to this blood-stage antigen. In addition, this epitope is cross-reactive with antigens expressed by primate leukocytes and platelets. Such epitopes may induce autoantibodies commonly seen in patients with malaria.

Our objective was to describe the development and validation of an instrument for measuring physician readiness to change cancer screening and counseling. We designed a cross-sectional survey of primary care physicians. Participants were 745 enrollees in the Copic Insurance Company, a physician liability insurer of more than 80% of Colorado's physicians. A large percentage of physicians do not perceive a need to change their screening patterns for eligible patients in both mammography and Pap tests. Approximately one third of the physicians are contemplating screening more of their patients within the next six months for sigmoidoscopy, clinical skin, and oral cavity exams and counseling more of their patients on skin protection and dietary fat. Few physicians are planning significant changes in cancer screening and counseling within the next month. Scales of readiness to change screening and counseling, as well as an overall readiness-to-change scale, had high internal consistency: .81, .65, .84, for screening, counseling, and overall, respectively. We conclude that readiness to change may be a useful construct for determining if and when physicians may be willing to make behavior changes. Moreover, the assessment of physician readiness to change may facilitate the tailoring of interventions designed to foster physician behavior change and improve patient care.

Physicians often fail to provide nationally recommended preventive services for their patients. Addressing this, we have reviewed selected literature on changing physician behavior using the organizational construct of the "readiness for change" transtheoretical model. This model suggests that behavior evolves through stages from precontemplation, to contemplation, to preparation, to initiation, and to maintenance of change. Traditional continuing medical education may affect knowledge and beliefs, but rarely results in behavior change. However, motivational strategies such as practice feedback reports and influential peers can foster stage change. Successful interventions aimed at physicians preparing for change frequently use an office-system approach that targets not only physicians, but office staff and patients as well. Illustrating how the readiness to change model can guide the design and implementation of interventions, we describe strategies being used in a statewide randomized controlled trial to improve cancer prevention counseling and early detection by primary care physicians. The multistage interventions of Partners for Prevention include support from a medical liability carrier, a motivational videotape, a task-delineated office manual, chart flowsheets, patient activation forms, practice feedback reports, a designated prevention coordinator within each practice and regular telephone calls and office visits by project staff.

To be feasible, study designs for most intervention research in primary care settings must limit the number of participating physicians, without sacrificing the statistical power required to test the research hypotheses. A model was developed to examine sample size and statistical power requirements when using the physicians' practice as the unit of analysis. Randomized designs using either matched or unmatched samples of practices were compared under varying conditions. When baseline variability is small or the number of practice pairs is large, matching at best marginally increases power. However, in the typical case when baseline variability is large or the number of practice pairs is small, matching substantially increases the power to find intervention effects with a smaller sample. Thus, matching prior to randomization could improve the design of many intervention studies in primary care settings.

Sialic acid on human erythrocytes is involved in invasion by the human malaria parasite, Plasmodium falciparum. Mouse erythrocytes were used as a reagent to explore the question of whether erythrocyte sialic acid functions as a nonspecific negative charge or whether the sialic acid is a necessary structural part of the receptor for merozoites. Human erythrocytes contain N-acetylneuraminic acid (Neu5Ac), whereas mouse erythrocytes, which are also invaded by P. falciparum merozoites, contain 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac2) and N-glycoloylneuraminic acid (Neu5Gc), in addition to Neu5Ac. We compared the effects of sialidase and influenza C virus esterase treatments of mouse erythrocytes on invasion and the binding of a 175-kDa P. falciparum protein (EBA-175), a sialic acid-dependent malaria ligand implicated in the invasion process. Sialidase-treated mouse erythrocytes were refractory to invasion by P. falciparum merozoites and failed to bind EBA-175. Influenza C virus esterase, which converts Neu5,9Ac2 to Neu5Ac, increased both invasion efficiency and EBA-175 binding to mouse erythrocytes. Thus, the parasite and EBA-175 discriminate between Neu5Ac and Neu5,9Ac2, that is, the C-9 acetyl group interferes with EBA-175 binding and invasion by P. falciparum merozoites. This indicates that sialic acid is part of a receptor for invasion.

In the 72 cases of cryoglobulinemia reviewed, erythematous to purpuric macules or papules were present in 92%. Infarction, hemorrhagic crusts, and ulcers were present in 10% to 25% of the patients and were relatively more common in type I cryoglobulinemia than in the other types. Postinflammatory hyperpigmentation was noted in 40%. Lesions on the leg were common in all types of cryoglobulinemia; however, lesions on the head and mucosal surfaces suggested type I cryoglobulinemia. Histopathologic features were classified as vasculitis in 50%, inflammatory or noninflammatory purpura in 15%, noninflammatory hyaline thrombosis in 10%, and postinflammatory sequelae in 10%. Noninflammatory hyaline thrombosis was relatively more frequent in type I. Thus erythematous to purpuric lesions on the legs and leukocytoclastic vasculitis are the common cutaneous findings in cryoglobulinemia. Type I cryoglobulinemia is suggested by noninflammatory hyaline thrombosis, cutaneous infarction, hemorrhagic crusts, skin ulcerations, and lesions of the head and neck and of oral or nasal mucosa.

Anesthesia for cutaneous surgery on the foot is often achieved by local infiltration. However, procedures that involve large surface areas are anesthetized more effectively with peripheral nerve blocks. This discussion of peripheral nerve blocks for the feet includes an overview of the relevant sensory innervation, a brief discussion of local anesthetics, a description of the techniques, and representative cases.

To evaluate the effects of social support and home urine monitoring on success with dietary sodium reduction, 114 essential hypertensive adults and a household partner were recruited. One of the pair was required to be the food preparer. Patients with their partners were randomly assigned to either an active or passive partner condition. During dietary counseling in the active condition, both patient and partner were involved in instructions to change their diet to reduce their daily sodium intake to 80 mmol or less. In the passive condition, the partners were present during the dietary counseling, but no effort was made to involve them directly in the instruction or to encourage them to make personal dietary changes. Patients and active partners collected two 24-hr urine collections between each of the first two counseling sessions and received feedback on the sodium results by a telephone call. In the passive partner condition, only patients collected urine for feedback. At the end of the 6 week instructional period, all patients and partners collected a 24-hr urine and had their blood pressure assessed. Half of each group was also randomly assigned to have access to a system for periodic home-monitoring of urine for sodium content during a 3-month period beginning at week 6 of the study (immediate). The delayed feedback group received the home-monitoring three months after completion of the dietary instruction. All patients, but only active partners, used the feedback system during their assignment periods and collected a 24-hr urine monthly between 6 and 30 weeks of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

A prerequisite for the completion of a clinical trial is the accrual of adequate numbers of patients. It is estimated that over 90-95% of all cancer patients are now treated in their local communities by practicing oncologists and are not seen by primary investigators at teaching hospitals. One risk of this trend is decreased patient enrollment into clinical trials. The private practitioner often lacks the academic oncologist's incentives to participate in clinical research. The Hoosier Oncology Group (HOG) is composed of community medical and radiation oncologists (85%) and Indiana University faculty members (15%). In an effort to improve patient enrollment onto clinical cancer research trials, HOG has attempted to identify 1) the major obstacles to patient enrollment by community oncologists and 2) potential aids to overcome such obstacles. One hundred fourteen members were surveyed and 75 responded (66%). The major obstacles were, in descending order: time demands on both the oncologist and his staff; explaining clinical trials to patients; completing flow sheets; perceived increased cost to the patient; remembering protocols; adhering to a rigid protocol. Aids identified as potentially most helpful were, in descending order: pocket-sized synopses of protocols; computer generated, individualized prompts; the availability of a clinical trials specialist to explain the clinical trial to patients and assist in obtaining informed consent; the availability of a video tape which could be used to explain clinical trials to patients. These aids are being implemented with the attempt to systemically study their impact on patient accrual.

Cigarette smoking is the leading cause of preventable death and disease in the United States. Because dental personnel treat millions of patients who are cigarette smokers, they have a unique opportunity to help persons quit the smoking habit. Effectively designed, office-based programs should involve all or most dental team members and contain the following components: a procedure that identifies smokers and records changes in their smoking status, a personal evaluation of each smoker's motivation to quit, an assessment of the degree of nicotine dependence experienced by potential quitters, the prescription of nicotine polacrilex therapy for appropriate candidates, personalized counseling commensurate with each patient's level of quitting readiness and, an effective system that ensures consistent patient follow-up and support.

A 28-yera-old woman with an intrauterine device (IUD) was admitted to hospital with signs of incomplete abortion. The IUD was removed and curettage revealed necrotic infected decidua with no trophoblastic cells or chorionic villi. The patient subsequently developed multiple abscesses in the right ovary. The mechanism of development of ovarian abscesses in patients with IUD or with infected incomplete abortion is discussed.

To examine the effect of modest dietary sodium ion restriction in treated hypertensive individuals, we studied 114 hypertensive patients undergoing individualized dietary counseling with a research dietitian to achieve reduction in dietary sodium ion intake. A significant reduction in mean sodium ion intake was achieved after the first of three lessons and was maintained for 30 weeks with no change in potassium ion intake. Significant falls in blood pressure and body weight were observed with no significant correlations noted between the two variables, implying independence of these effects. Individuals compliant with the dietary sodium ion restriction goal (urinary excretion, less than or equal to 80 mmol/d [less than or equal to 80 mEq/24 h]) were more likely to have a reduction in number of medications than those not reaching that goal. Ninety-eight of the 114 patients completed the entire 30 weeks. Patients who dropped out tended to have lower diastolic blood pressures and required fewer medications for blood pressure control than those who completed the 30 weeks. For these reasons, patients in the former group may have been less highly motivated to complete the study. These observations suggest that modest dietary sodium ion restriction is feasible in treated hypertensive patients and that adherence to such a regimen may permit blood pressure control with fewer medications.

In order to increase physicians' adherence to recommended standards of medical care and to examine factors presumed to contribute to such changes, we conducted a randomized, controlled trial using reading materials targeted to specific practice recommendations. Seventy-nine internal medicine residents completed baseline questionnaires stating their intentions to follow 13 common preventive care actions. They were randomly assigned to receive one of two different sets of readings covering these care actions. Thus, each physician was in the experimental group for one set of readings (A or B) while serving as a control for the other set. The impact of the reading was determined by: the physicians' knowledge of the recommended care actions detailed in the combined readings, their post-reading intentions, and clinical behavior when faced with patients having indications for the recommended actions. The 73 residents (92%) who read the material judged 39% of the information to be new and 72% useful. Residents had significantly better performance on the knowledge questions based on their own readings than did their control group peers for both sets of readings. For the Group A physicians, reading significantly (P less than 0.05) increased intentions to follow one of the seven clinical actions while Group B residents increased their intentions in three out of six. Step-wise multiple regression analyses were used to predict physicians' post-reading adherence to the recommended actions. For the Group A actions, pre-reading actions accounted for most of the variance in their post-reading actions.(ABSTRACT TRUNCATED AT 250 WORDS)