DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis.

Low molecular weight heparins (LMWH) are the standard of care for the treatment of cancer-associated venous thromboembolism (CA-VTE). We performed a systematic review and meta-analysis to compare the effects of direct oral anticoagulants (DOAC) versus LMWH for the treatment of CA-VTE. The primary efficacy and safety outcomes were VTE recurrence and major bleeding (MB). The secondary outcomes were clinically relevant non-MB (CRNMB), all-cause mortality and the net clinical benefit. We searched MEDLINE, EMBASE, CENTRAL and Web of Science (inception-December 2019) and abstracts of relevant conferences (2000-2019) to identify randomized controlled trials comparing DOAC and LMWH for the treatment of CA-VTE. Relative risks (RR) and 95% confidence intervals were estimated (Mantel-Haenszel method, random-effects models). A non-inferiority analysis with a margin of 1.3 for the upper boundary of the RR was conducted for the primary outcomes. From 637 references, we included four publications which encompass three trials (1756 patients). Compared to LMWH, DOAC were associated with a trend for decreased VTE recurrence (RR 0.51; 95%CI 0.25-1.03; p = 0.06; I2 = 51%), whereas MB (RR 1.64; 95%CI 1.00-2.69; p = 0.05; I2 = 0%) and CRNMB (RR 1.83; 95%CI 1.04-3.20; p = 0.03; I2 = 50%) were significantly more frequent with DOAC. Conversely, all-cause mortality (RR 1.06; 95%CI 0.83-1.35; p = 0.64; I2 = 36%) and net clinical benefit (RR 0.74; 95%CI 0.38-1.42; p = 0.36; I2 = 65%) were comparable. DOAC were non-inferior to LMWH in preventing CA-VTE recurrence, but were associated with an increased risk of MB and CRNMB. Further studies are required to confirm these results and inform on the risk/benefit ratio for specific populations.

Efficacy of a Carrageenan gel Against Transmission of Cervical HPV (CATCH): interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial.

OBJECTIVES: To evaluate the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women. METHODS: We conducted a planned interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based gel or a placebo gel to be self-applied every other day for the first month and before and after each intercourse during follow-up. Assessments were performed at 0.5, 1, 3, 6, 9 and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Intention-to-treat analyses were performed. RESULTS: Between January 2013 and June 2017, a total of 280 participants were randomly assigned to the carrageenan (n = 141) or the placebo (n = 139) arm. All participants were included in safety analyses, but three (1%) were excluded from efficacy analyses (HPV results unavailable for two participants in the carrageenan and one participant in the placebo arm). The median follow-up time was 9.2 months (interquartile range, 1.9-13.2 months). A total of 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm became infected by at least one new HPV type (hazard ratio = 0.64, 95% confidence interval = 0.45-0.89, p 0.009). A total of 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p 0.02), none of which was deemed related to the gels. CONCLUSIONS: Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women.

A versatile high-resolution x-ray imager (HRXI) for laser-plasma experiments on OMEGA.

A high-resolution x-ray imager (HRXI) devoted to laser-plasma experiments combines two state-of-the-art technologies developed in France: a high-resolution x-ray microscope and a high-speed x-ray streak camera. The resulting streaked imager achieves spatial and temporal resolutions of approximately 5 microm and approximately 10 ps, respectively. The HXRI has recorded enhanced spatial and temporal resolution radiographs of indirectly driven targets on OMEGA. This paper describes the main features of the instrument and details the activation process on OMEGA (particularly the alignment). Recent results obtained on joint CEA/LLE radiographic OMEGA experiments will also be presented.

High dynamic range streak camera for subpicosecond time-resolved x-ray spectroscopy.

The full characterization of a time resolved x-ray spectrometer is presented. It is based on the coupling of a conical crystal with a subpicosecond x-ray streak camera. The detector is designed to operate in accumulation mode at high repetition rate (up to 1 kHz) allowing signal to noise ratio as high as 10(4):1. Optical switches have been used to limit the jitter induced in the subpicosecond range, demonstrating the very long term stability (a few hours) of the entire device. The data analysis have been developed to get the spectral and temporal resolution of an ultrashort laser-plasma-based x-ray source.

Aids to quitting tobacco use: how important are they outside controlled trials?

BACKGROUND: Although there is good evidence that several pharmacotherapies and counseling can effectively facilitate smoking cessation, there is little information about the use or effectiveness of these or any other quit aids outside of controlled trials. METHODS: A mailed survey with phone follow-up documented the use of various quit aids among 3,122 health plan members who smoke. A multilevel statistical modeling technique controlled for potentially confounding variables. RESULTS: Nearly half (1,513) of these smokers reported a quit attempt during the preceding 6 months. Although 1,036 (33.2%) reported using some type of aid to quitting, primarily nicotine products or bupropion, 10-26% of these "users" did not report an actual quit attempt. Ninety percent of the medication users had a personal cost, averaging $53-$87. Fully 26.9% of those reporting a quit without any type of aid quit for at least 7 days. This rate equals that of users of all types of aids except for nicotine patches and bupropion, both of which had associated 7 or more day quit rates of about 46% (95% CI 39.3-52.2). CONCLUSIONS: Pharmacotherapeutic quit aids are being widely used, even in the absence of significant insurance coverage.

Patient satisfaction and discussion of smoking cessation during clinical visits.

OBJECTIVE: To learn whether patients who smoke and who receive smoking cessation information during medical office visits were less likely to be satisfied with the smoking cessation help they received than patients who smoke but who did not receive such information. PATIENTS AND METHODS: A total of 3703 current cigarette smokers were identified by a mailing in November 1998 to 163,596 members of 2 Minnesota health plans, and 2714 (77.3%) responses to a 44-item questionnaire were available for analysis. Using hierarchical analysis to control confounding variables, we assessed the relationship between patient-reported smoking cessation support actions at the last physician visit and satisfaction "with the help received from your doctor about quitting smoking." RESULTS: Smokers were very satisfied (12.0%), satisfied (25.3%), neutral (48.6%), and dissatisfied or very dissatisfied (13.5%) with physician help. After controlling for other characteristics, the 1898 patients who reported that they had been asked about tobacco use or advised to quit during the latest visit had 10 percentage point greater satisfaction ratings and 5 percentage point less dissatisfaction than those not reporting such discussions (P<.001). Smokers reporting no interest in quitting at the time of the latest visit also demonstrated greater satisfaction in association with these actions. CONCLUSION: Smoking cessation interventions during physician visits were associated with increased patient satisfaction with their care among those who smoke. This information should reduce concerns of physicians or nurses about providing tobacco cessation assistance to patients during office visits.

Clinician satisfaction with a preventive services implementation trial. The IMPROVE project.

OBJECT: To discover how attempts to increase the delivery of preventive services affect clinician satisfaction. METHODS: The IMPROVE project was a randomized clinical trial conducted in 44 clinics in and around Minneapolis-St. Paul, Minnesota. Personnel were trained in continuous quality improvement techniques to organize preventive services delivery systems. Satisfaction with delivery of these services and with the sponsoring organizations was measured before the intervention (Time 1), at the end of the intervention (Time 2), and 1 year post-intervention (Time 3). RESULTS: At no time was the intervention associated with a change in the respondents satisfaction with their places of work or with their job roles. Satisfaction with preventive services delivery increased from Time 1 to Time 3 among intervention-clinic respondents. Satisfaction with the IMPROVE project and the efforts of the two managed care organizations to help the clinics deliver preventive services peaked at Time 2 and declined toward baseline at Time 3. Satisfaction with preventive services delivery tended to increase more in the 13 intervention clinics that implemented a preventive services delivery system than in the nine intervention clinics that did not implement a preventive services delivery system (p = 0.15). CONCLUSIONS: Planned organizational change to create systems for preventive services delivery can be associated with increased clinician satisfaction with the way these services are delivered. However, increased satisfaction with preventive services does not necessarily indicate that service delivery rates have increased.

Failure of a continuous quality improvement intervention to increase the delivery of preventive services. A randomized trial.

CONTEXT: Although there has been enormous interest in continuous quality improvement (CQI) as a measure to improve health care, this enthusiasm is based largely on its apparent success in business rather than formal evaluations in health care. OBJECTIVE: To determine whether a managed care organization can increase delivery of eight clinical preventive services by using CQI. DESIGN: Primary care clinics were randomly assigned to improve delivery of preventive services with CQI (intervention group) or to provide usual care (control group). INTERVENTION: Through leadership support, training, consulting, and networking, each intervention clinic was assisted to use CQI multidisciplinary teams to develop and implement systems for delivery of preventive services. SETTING: 44 primary care clinics in greater Minneapolis-St. Paul. PATIENTS: Patients 19 years of age and older completed surveys at baseline (n = 6830) and at follow-up (n = 6431). Medical chart audits were completed on 4777 patients at baseline and 4546 patients at follow-up. MAIN OUTCOME MEASURES: The proportion of patients who were up-to-date (according to chart audit) and the proportion of patients who were offered a service if not up-to-date (according to patient report) for 8 preventive services. RESULTS: Compared with the control group, based on the proportion of patients who were up-to-date, use of only one preventive service--pneumococcal vaccine--increased significantly in the intervention group (17.2% absolute increase from baseline to follow-up compared with a 0.3% absolute increase in the control group, P = 0.003). Similarly, based on patient report of being offered a service if not up-to-date, delivery of only one preventive service--cholesterol testing--significantly increased in the intervention group compared with the control group (4.6% increase vs. 0.4% absolute decrease in the control group; P = 0.006). CONCLUSION: In this trial, CQI methods did not result in clinically important increases in preventive service delivery rates.

IMPROVE: bridge over troubled waters.

BACKGROUND: The original collaborative project was described in a 1995 Journal article titled "Competing HMOs Collaborate to Improve Preventive Services." IMPROVE (IMproving PRevention through Organization, Vision, and Empowerment) was a large randomized controlled trial using continuous quality improvement to implement clinical systems to improve the delivery of adult preventive services in primary care settings. The project was funded by the Agency for Health Care Policy and Research and initiated as a collaboration between two health maintenance organizations (HMOs) in the Twin Cities: Health Partners and Blue Plus. METHODOLOGY: Forty-four clinics were recruited for the study. Initially the 22 intervention clinics received the multifaceted intervention of leadership support, training on CQI and prevention systems, and consultation and networking opportunities. Next, the comparison clinics received similar assistance, and other clinics were invited into the collaboration. Ultimately, 57 clinics were involved in the project. Multiple collaborations--among clinics, leaders, and HMOs--developed during the project. STATUS: Despite turmoil in the environment during the project, many benefits have been described, including enhanced leadership, growth of systems thinking, better change management skills, and collaboration of competing organizations. SUMMARY: The IMPROVE collaboration survived and flourished in a very competitive market. It was viewed positively by clinicians, medical clinics, and HMOs, and its benefits have extended into the community.

The case of the missing clinical preventive services systems.

OBJECTIVE: To examine the presence and comprehensiveness of organized processes and systems in a sample of primary care clinics shown to have high variation in rates of providing preventive services. DESIGN: Survey study. SETTING: 44 primary care clinics recruited for a scientific trial of a quality improvement intervention to improve preventive services. PARTICIPANTS: 647 clinicians and nurses. MEASUREMENTS: The presence of 10 organized prevention processes for eight adult preventive services as reported by those clinicians and nurses on a detailed written survey. RESULTS: In more than 50% of clinics, 7 of the 10 prevention processes were reported to be absent for all eight services. Only the follow-up process was commonly present; this was also the only process that was usually present for most applicable services. CONCLUSIONS: The paucity of recognizable organized processes to support the systematic delivery of adult preventive services in clinics with highly varying rates of providing these services supports the idea that lack of systems may be an important source of the variability and low rates. Most of the existing processes are fragmented and do not function across multiple preventive services.

Primary care, process improvement, and turmoil.

The current health care environment in the United States is in turmoil, especially in regions that are further ahead in the transition from free-for-service to managed care. This article examines turmoil within primary care during a health-maintenance-organization-sponsored and federally funded randomized trial of using continuous quality improvement for adult clinical preventive services. The external and internal changes in structure and leadership occurring in primary care clinics are profound and prevalent. The sponsors of the project have responded to the turmoil by encouraging greater leadership involvement within the clinic and by supporting more skill building for change management.

Side effects associated with influenza vaccination in healthy working adults. A randomized, placebo-controlled trial.

BACKGROUND: Concern about side effects is a barrier to influenza vaccination. This randomized, double-blind, placebo-controlled trial assessed side effects following vaccination among healthy working adults. METHODS: Healthy working adults were recruited during October and November 1994 and were randomized to receive influenza vaccine or placebo injections. Local and systemic symptoms during the week following the injection were evaluated through structured telephone interviews. RESULTS: Of 849 subjects enrolled in the study, 425 received a placebo and 424 received influenza vaccine. Baseline characteristics were similar between the groups, and 99% of subjects completed interviews to assess side effects after the study injection. No differences were seen between the 2 groups for the systemic symptoms of fever, myalgias, fatigue, malaise, or headaches. Overall, 35.2% of placebo and 34.1% of vaccine recipients reported at least 1 of these systemic symptoms (P = .78, chi 2). Vaccine recipients reported a higher rate of arm soreness at the injection site than did placebo recipients (63.8% vs 24.1%, P < .001). Local reactions were mild in both groups and infrequently resulted in decreased use of the arm. After logistic regression, female sex (odds ratio [OR], 1.5;95% confidence interval [CI], 1.1-2.1), age younger than 40 years (OR, 1.6;95% CI, 1.2-2.2), and coincidental upper respiratory tract illness (OR, 4.6; 95% CI, 3.2-6.6) were independently associated with higher rates of systemic symptoms. In the multivariate model, vaccine again was not associated with systemic symptoms (OR, 0.9; 95% CI, 0.7-1.2). CONCLUSIONS: Influenza vaccination of healthy working adults is not associated with higher rates of systemic symptoms when compared with placebo injection. These findings should be useful to physicians and other health care providers as they counsel patients to take advantage of an important opportunity for disease prevention and health protection.

Competing HMOs collaborate to improve preventive services.

BACKGROUND: In July 1993, an unusual collaboration developed between competing managed care plans and with competing primary care clinics as part of a federally funded research grant (IMPROVE from the Agency for Health Care Policy and Research). The goal of this collaboration is to scientifically test the ability of an health maintenance organization (HMO) to improve the delivery of eight adult preventive services by training and facilitating the use of continuous quality improvement and prevention systems by contracted private primary clinics. METHODOLOGY: In order to conduct this effectiveness study, it was necessary for two HMOs to come to a structural and functional understanding of how to operate jointly. Investigators recruited 44 private clinics for a randomized controlled trial in which 22 are being assisted in improving the process used to deliver these preventive services and 22 are being left alone as comparison clinics. The intervention is a train-the-trainer and consultation approach focused on clinics as collaborating customers. The comparison will be based on repeated surveys of patients and clinic personnel as well as chart audits to measure changes in systems and prevention rates. SUMMARY: Although this project was made possible by a number of unusual favorable factors, it can serve as a model for support of the clinician leadership that is essential to true health care delivery reform.

The effectiveness of vaccination against influenza in healthy, working adults.

BACKGROUND: Although influenza causes substantial morbidity and mortality in all age groups, current recommendations emphasize annual immunization for people at high risk for complications of influenza. We conducted a double-blind, placebo-controlled trial of vaccination against influenza in healthy, working adults. METHODS: In the fall of 1994, we recruited working adults from 18 to 64 years of age from in and around the Minneapolis-St. Paul area and randomly assigned them to receive either influenza vaccine or placebo injections. The primary study outcomes included upper respiratory illnesses, absenteeism from work because of upper respiratory illnesses, and visits to physicians' offices for upper respiratory illnesses. The economic benefits of vaccination were analyzed by estimating the direct and indirect costs associated with immunization and with upper respiratory illnesses. RESULTS: We enrolled a total of 849 subjects. Baseline characteristics were similar in the two groups. During the follow-up period, consisting of the 1994-1995 influenza season (December 1, 1994, through March 31, 1995), those who received the vaccine reported 25 percent fewer episodes of upper respiratory illness than those who received the placebo (105 vs. 140 episodes per 100 subjects, P < 0.001), 43 percent fewer days of sick leave from work due to upper respiratory illness (70 vs. 122 days per 100 subjects, P = 0.001), and 44 percent fewer visits to physicians' offices for upper respiratory illnesses (31 vs. 55 visits per 100 subjects, P = 0.004). The cost savings were estimated to be $46.85 per person vaccinated. CONCLUSIONS: Vaccination against influenza has substantial health-related and economic benefits for healthy, working adults.

A comparison of an alcohol-based and a siloxane-based peri-wound skin protectant.

A report of a study which evaluated two products designed to protect the skin surrounding wounds.

Drug latentiation by gamma-glutamyl transpeptidase.

The N-gamma-glutamyl derivatives of L-thiazolidine-4-carboxylic acid, 4-aminobutyric acid, 1-aminocyclopentanecarboxylic acid, 2-aminophenol, and p-fluoro-L-phenylalanine (compounds 6, 8, 9, 10, and 12, respectively) were synthesized using the synthon phthaloylglutamic anhydride. Their relative rates of cleavage by the enzyme gamma-glutamyl transpeptidase (gamma-GT) were determined in order to evaluate the possibility for their selective release by this enzyme which is elevated in certain pathological conditions. Compounds 6, 8, and 9 were not readily solvolyzed by gamma-GT, but compounds 10 and 12, as well as the N-gamma-glutamylated derivatives of 3- and 4-aminophenol, were readily cleaved.

Simultaneous plasma levels determination of mexiletine and one of its metabolites by electron capture gas-liquid chromatography.

A sensitive and specific electron capture gas-liquid chromatographic method is developed for the determination in human plasma both of mexiletine and of one of its hydroxymethyl metabolites appearing progressively during the kinetics and the presence of which is characterized by mass spectrometry. This method involves the use of two internal standards and the extraction of the drug and of its metabolite from alkaline plasma with diethyl ether followed by back extraction into sulfuric acid (0.2 N) for clean-up procedure and re-extraction by diethyl ether. The limits of detection of the heptafluorobutyryl derivatives of mexiletine and of its metabolite are 20 and 7 ng/ml of plasma, respectively. The preliminary results of the pharmacokinetic study performed in a cardiological unit after single oral administration and during long-term oral maintenance therapy are described in this paper. The method makes it possible to get a better knowledge of the kinetic behaviour of mexiletine and of its metabolite and contributes to the understanding of the origins of the variable pharmacokinetics of mexiletine in patients.