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RENOIR phase 3 rituximab-lenalidomide vs rituximab as maintenance treatment in relapsed/refractory follicular lymphoma.

Maintenance treatment in older patients with relapsed or refractory (R/R) follicular lymphoma (FL) remains an area of investigation. RENOIR was a multicenter, phase 3, open-label randomized trial conducted by the Fondazione Italiana Linfomi (FIL) in older patients with R/R FL after 1 or 2 previous therapies. Patients achieving partial response or complete response (CR) after 4 to 6 cycles of standard rituximab (R)-based chemotherapy were randomized 1:1 to maintenance with R alone (standard arm) or R plus lenalidomide (R2; experimental arm). The primary end point was 2-year progression-free survival (PFS) from randomization, with an expected hazard ratio (HR) of 0.5. A total of 152 patients (median age, 71 years) were enrolled. After induction, 129 (85%) achieved an overall response (CR, 58%) and were randomized to R (n = 65) or R2 (n = 64). At a median follow-up of 68 months, the 2-year PFS was 73% in the R2 arm and 64% in the R arm. An unplanned hypothesis-generating subgroup analysis showed a greater 2-year PFS benefit with R2 in patients aged <70 years: R2, 96% vs R, 69%. Two-year overall survival rates were similar (R2, 80% vs R, 89%). Grade 3/4 adverse events were more frequent in R2, mainly neutropenia and gastrointestinal disorders. In conclusion, the primary end point of the study was not met, and R2 maintenance did not significantly improve 2-year PFS in older patients with R/R FL, although a numerical benefit was observed. R2 showed a more favorable benefit-risk profile in patients aged <70 years, whereas in older patients careful consideration of individual tolerability is warranted. This trial was registered at www.clinicaltrials.gov as NCT02390869.

Humans↗

Preventing neonatal group B streptococcal disease: cost-effectiveness in a health maintenance organization and the impact of delayed hospital discharge for newborns who received intrapartum antibiotics.

OBJECTIVES: To estimate the cost and health benefits of implementing a risk factor-based prevention strategy for early-onset neonatal group B streptococcal (GBS) disease, using baseline assumptions and costs from a health maintenance organization. With the risk factor-based strategy, intrapartum antibiotics (IPAs) would be provided to women with fever, prolonged rupture of membranes, or preterm labor. A second objective was to determine the impact of an increased length of stay for well term infants with mothers who received IPAs. METHODS: We used decision analysis to compare the costs and benefits of the prevention strategy with usual obstetric practice for a cohort of 100 000 women and their newborn infants. We derived baseline values from a previous study based on chart review and automated cost data from a health maintenance organization in Northern California. In sensitivity analyses, we varied baseline assumptions, including additional costs for observing well term infants who received IPAs. RESULTS: If adherence to guidelines were 100%, 17% of mothers would receive IPAs at a cost of $490,000; $1.6 million would be saved by preventing 66 GBS cases (64% reduction). The net savings would be $1.1 million and 61 life-years. The net cost is sensitive to the cost of caring for well infants who received IPAs. If each term infant of a mother who received IPAs had 1 more day of observation than other term infants, there would be a net cost of $8.1 million; the cost per GBS case prevented would be $120,000 and the cost per life-year saved would be $130,000. CONCLUSIONS: Implementation in a health maintenance organization of a risk factor-based strategy to prevent neonatal GBS disease can prevent substantial disease and be cost saving. However, if the length of hospital stay were extended among well term infants whose mothers received IPAs, the strategy would be relatively costly compared with other medical interventions.

Anti-Bacterial Agents↗

Hospital equipment management, maintenance and quality control in the Netherlands.

Before 1970, equipment maintenance and quality control in Dutch hospitals were not organised. There was little or no cooperation between physicians, hospital employees and instrument suppliers. Health services which are not nationalised are funded by non-profit making foundations. There were few regulations covering the supply and maintenance of equipment. However, the country is small enough for there to be considerable contact between instrument engineers. In the past eight years a new situation has arisen where rules are being formulated based on collective experiences. A better understanding has to grow between physicians, nurses and engineers, of each others' needs and possibilities in relation to the use of instruments and the necessity of maintenance. To keep quality on an acceptable level, exaggeration in one direction or another has to be avoided.

Equipment and Supplies, Hospital↗

Intersection between the regulators of sister chromatid cohesion establishment and maintenance in budding yeast indicates a multi-step mechanism.

Sister chromatid cohesion is established during S phase and maintained until anaphase. The cohesin complex (Mcd1p/Scc1p, Smc1p, Smc3p Irr1p/Scc3p in budding yeast) serves a structural role as it is required at all times when cohesion exists. Pds5p colocalizes temporally and spatially with cohesin on chromosomes but is thought to serve as a regulator of cohesion maintenance during mitosis. In contrast, Ctf7p/Eco1p is required during S phase for establishment but is not required during mitosis. Here we provide genetic and biochemical evidence that the pathways of cohesion establishment and maintenance are intimately linked. Our results show that mutants in ctf7 and pds5 are synthetically lethal. Moreover, over-expression of either CTF7 or PDS5 exhibits reciprocal suppression of the other mutant's temperature sensitivity. The suppression by CTF7 is specific for pds5 mutants as CTF7 over-expression increases the temperature sensitivity of an mcd1 mutant but has no effect on smc1 or smc3 mutants. Three additional findings provide new insights into the process of cohesion establishment. First, over-expression of ctf7 alleles deficient in acetylase activity exhibit significantly reduced suppression of the pds5 mutant but exacerbated toxicity to the mcd1 mutant. Second, using chromosome spreads and chromatin immuno-precipitation, we find either cohesin complex or Pds5p chromosomal localization is altered in ctf7 mutants. Finally, biochemical analysis reveals that Ctf7p and Pds5p coimmunoprecipitate, which physically links these regulators of cohesion establishment and maintenance. We propose a model whereby Ctf7p and Pds5p cooperate to facilitate efficient establishment by mediating changes in cohesin complex on chromosomes after its deposition.

Alleles↗

Aspirin treatment after myocardial infarction: are health maintenance organization members, women, and the elderly undertreated?

In April 1996, we surveyed 539 patients who had suffered a myocardial infarction in 1995 to determine whether the prescription and use of aspirin after myocardial infarction differs by patient age, sex, and type of health insurance. Patients who were insured through one of four health maintenance organizations in major metropolitan areas or by an indemnity plan in 40 states completed the survey. Among the 502 patients with no contraindications to use, 93.8% were prescribed aspirin. Among patients with a prescription and no subsequent contraindications to use, 96.4% were taking aspirin when surveyed. Among aspirin users, 96.5% reported taking aspirin daily. Controlling for other characteristics, 75-year-old patients were 5 percentage points less likely to receive a prescription for aspirin than were 50-year-old patients (P = 0.05). Although not significant at conventional levels, point estimates revealed a prescription rate for women that was 6 percentage points higher than that for men (P = 0.054) and a rate for health maintenance organization members that was 4 percentage points lower than that for patients with indemnity insurance (P = 0.10). Aspirin use was lower among older patients (P = 0.02) but did not differ by gender or type of insurance plan. Health maintenance organization members were just as likely to receive a prescription from a specialist as were those with indemnity insurance (P = 0.92). Based on these results, the rate of aspirin treatment after myocardial infarction may be much higher than previous studies indicate. Concerns that managed care patients and women may be undertreated are not supported by our findings. Although older patients are at risk for undertreatment, this risk is low. Once aspirin is prescribed, selfreported patient compliance with a daily regimen of aspirin is high.

Age Factors↗

The Vaccine Safety Datalink: immunization research in health maintenance organizations in the USA.

The Vaccine Safety Datalink is a collaborative project involving the National Immunization Program of the Centers for Disease Control and Prevention and several large health maintenance organizations in the USA. The project began in 1990 with the primary purpose of rigorously evaluating concerns about the safety of vaccines. Computerized data on vaccination, medical outcome (e.g. outpatient visits, emergency room visits, hospitalizations, and deaths) and covariates (e.g. birth certificates, census data) are prospectively collected and linked under joint protocol at multiple health maintenance organizations for analysis. Approximately 6 million persons (2% of the population of the USA) are now members of health maintenance organizations participating in the Vaccine Safety Datalink, which has proved to be a valuable resource providing important information on a number of vaccine safety issues. The databases and infrastructure created for the Vaccine Safety Datalink have also provided opportunities to address vaccination coverage, cost-effectiveness and other matters connected with immunization as well as matters outside this field.

Centers for Disease Control and Prevention, U.S.↗

Establishing maintenance intervals based on measurement reliability of engineering endpoints.

Methods developed by the metrological community and principles used by the research community were integrated to provide a basis for a periodic maintenance interval analysis system. Engineering endpoints are used as measurement attributes on which to base two primary quality indicators: accuracy and reliability. Also key to establishing appropriate maintenance intervals is the ability to recognize two primary failure modes: random failure and time-related failure. The primary objective of the maintenance program is to avert predictable and preventable device failure, and understanding time-related failures enables service personnel to set intervals accordingly.

Biomedical Engineering↗

Conducting a hospital maintenance department survey.

Maintenance Department employees can be your friends and allies or the source of your biggest headaches. By working with maintenance personnel, the securing of maintenance areas can be made a lot easier.

Data Collection↗

Space maintenance in the primary and mixed dentition.

The maintenance of arch length in the primary, mixed and early permanent dentition is important for the normal development of the occlusion. Premature loss of primary teeth can result in the loss of arch length leading to malocclusion. Space maintenance can often prevent space loss and either prevent the development of a later malocclusion or reduce its severity. The pattern of space loss depends on many factors including age, stage of development, which teeth have been lost, the presence of crowding or spacing, and occlusal relationships. Careful consideration of many factors is required when deciding whether space maintenance is indicated. Radiographs and space analysis can be helpful. Space maintainers can be fixed or removable. Band and loop space maintainers have fewer problems than other types. Frequent follow-ups to check for any problems following space maintainer insertion is recommended.

Age Factors↗

Does your equipment maintenance management program measure up?

Identifying a clear maintenance philosophy is the first step toward choosing the right program for your healthcare organization. The second step is gaining a clear understanding of how proposed savings and improvements will be delivered. The third and last step is requiring that the proposed company or manager have specific tools in place for measuring and analyzing program performance. There are three primary philosophies underlying current equipment management options. These include risk-transfer philosophy (e.g., maintenance insurance, service contracts, multi-vendor and outsource programs), asset management philosophy (e.g., programs delivering a management system based on managed time-and-materials), and internal management (in-house managed programs). The last step in selecting the right program is insisting that proper performance measurements be built into the proposed management program. A well-managed program provides results in three general areas: financial outcomes, operational improvements and process improvements. Financial outcomes are the easiest to measure. Operational and process improvements are more challenging to assess but equally important to the program's overall success. To accurately identify results in these three areas, the overall management program should measure the following eight separate components: procedures and support for department staff; equipment inventory, benchmark costs, and budget guidelines; experienced equipment support team; objective, independent analysis of maintenance events; repair documentation and reporting; vendor relations; equipment acquisition analysis; and recommendations for improvement. Do everything you reasonably can to assure that the selected company can work side-by-side with you, providing objective, measurable advice that is ultimately in your best interest. You will then know that you have been thorough in your marketplace selection and can confidently move into implementation, expecting tangible and successful results.

Benchmarking↗

Feasibility of a telephone survey to recruit health maintenance organization members into a tamoxifen chemoprevention trial.

A large-scale, nationwide tamoxifen chemoprevention trial is currently being planned as a primary preventive strategy against breast cancer. The recruitment of health asymptomatic women into a long-term clinical trial will pose unique recruitment problems. This study examines the feasibility of telephone recruitment from a health maintenance organization population into such a trial. A random sample of 203 women aged 50 and older with a personal family history of breast cancer were contacted by telephone. A structured interview was administered to assess self-perceived risk of breast cancer, willingness to participate in a trial, and anticipated barriers to participation. Of the 203 names generated from the health maintenance organization membership roster 128 (63%) met eligibility criteria and participated in the interview. Forty-five % of the eligible women expressed interest in the tamoxifen trial. Women who felt that their family would support their participation expressed significantly more interest, while concern about possible side effects emerged as potential barriers. We conclude that contact by telephone among health maintenance organization members can identify a significant proportion of women who are interested in primary chemoprevention for breast cancer. Participation rates may be improved by bolstering family support and by addressing concerns about drug toxicity.

Aged↗

[Effectiveness of the maintenance operations on the air conditioning systems of a university building in relation to the microbiological quality of the air indoor].

The microbiological quality of the air indoor is influenced from various factors and one of the most important is represented from the maintenance of the conditioning systems. In this study it has been estimated the effectiveness of an intervention of cleaning and maintenance on the systems of conditioning of an university building executing sampling before and after such intervention. The two results were confronted and it is observed as the maintenance of the air conditioners has influenced on the quality of the air indoor.

Air Conditioning↗

The involvement of luteinizing hormone (LH) and Pregnancy-Associated Glycoprotein family (PAG) in pregnancy maintenance in the pig.

The paper presents the effect of in vivo immuno-neutralization of porcine luteinizing hormone (pLH) by species-homologous porcine antiserum (anti-pLH) administrations on pregnancy maintenance and immunodetection of the PAG proteins in precipitated plasma proteins of pregnant gilts. Pregnant gilts were passively immunized with 100 ml of porcine anti-pLH (titer 1:10 000) by multiple intravenous infusions performed from 37(th) to 42(nd) day post coitum (dpc; 12-h intervals). Blood samples of pregnant gilts were taken 12 times daily from 35 until 50 dpc. Concentrations of progesterone (P(4)) and pLH were determined by radioimmunoassays in systemic blood plasma of treated gilts and control pregnant gilts. The immuno-neutralization of peripheral pLH with the use of homologous anti-pLH serum resulted in a significant reduction (p<0.001) of plasma P(4) concentrations in two out of six treated gilts only, but abortion did not occur. In the remaining four passively immunized pregnant gilts, plasma P(4) concentration was increased (p<0.001) and the abortion occurred (47 dpc) only in one of the gilts. In addition, various anti-pPAG sera were purified by sequential adsorptions with endometrial proteins of cyclic gilts. Western blotting demonstrated the expression of the PAG proteins in precipitated plasma proteins of pregnant gilts. In conclusion, the passive immuno-neutralization of porcine LH by species-homologous antiserum (anti-pLH) did not affect the pregnancy maintenance. Thus, the maintenance of mid-pregnancy in gilts may depend also on other than LH luteotrophic factors. In addition, Western analysis of precipitated plasma proteins of pregnant pigs suggests a role of the PAG family during pregnancy in the pig.

Animals↗

Liver enzymes among microelectronics equipment maintenance technicians.

Equipment maintenance workers within the microelectronics industry have opportunities for occupational exposure to a variety of toxic agents. This pilot investigation compares liver enzymes in this population with that of other coworkers. Participants (n = 135) were randomly selected from a medical surveillance program at the manufacturing facility. Nine job categories were examined, including equipment maintenance workers and electronic technicians. Although abnormal liver enzymes were detected among equipment maintenance workers (odds ratio 16.4; P less than .008) and electronic technicians (odds ratio 27; P less than .0005), the numbers of participants were small (n = 8, 10). The data suggest that independent and/or interactive etiologic roles of occupation and alcohol should be further investigated. Early detection of subclinical occupational or recreational hepatotoxicity with appropriate employment of industrial hygiene control technology and/or the reduction of alcohol consumption may provide a means of preventing liver disease.

Adult↗

Consultative geriatric assessment for ambulatory patients. A randomized trial in a health maintenance organization.

Previous studies have shown that comprehensive geriatric assessment and follow-up can improve the health of hospitalized elderly patients. To evaluate the effectiveness of consultative geriatric assessment and limited follow-up for ambulatory patients, we randomized 600 elderly patients who were enrolled in a health maintenance organization into three groups: (1) consultation by a geriatric assessment team, (2) consultation by a "second opinion" internist, and (3) only traditional health maintenance organization services (control patients). The geriatric assessment team identified previously unrecognized problems in 35% of patients and advised changes in medication regimens for more than 40%. Nevertheless, patients who received assessment achieved only a small benefit in cognitive function after 3 months, which was not sustained for 1 year. There was no difference among groups in other measures of health status. Consultative geriatric assessment with limited follow-up did not benefit most older ambulatory patients in a health maintenance organization; if such care can be used effectively for ambulatory patients, it will require either additional targeting or continuing care or both.

Aged↗

Hospitalization and mortality rates for peptic ulcers: a comparison of a large health maintenance organization and United States data.

Hospital discharge and mortality rates for peptic ulcer disease from 1970-1980 for a large Health Maintenance Organization, the Kaiser-Permanente Medical Care Program of Southern California, are compared with the corresponding rates for the United States. The Kaiser-Permanente Medical Care Program hospitalization and mortality age-adjusted rates for ulcers are well below the national rates. In comparison with the 25%-31% decline in the national ulcer hospitalization rate, the Kaiser-Permanente Medical Care Program rate has been relatively stable. Most of the decline in national ulcer hospitalizations is due to a decrease in hospitalizations for uncomplicated cases. The Kaiser-Permanente Medical Care Program uncomplicated hospitalization rates are less than 25% of the national rate after age-adjustment and have been relatively stable over time. The age-adjusted Kaiser-Permanente Medical Care Program rates for ulcers with hemorrhages and perforations are 77% of the national data. These data suggest that part of the decline in national hospitalization rates for peptic ulcer disease may be due to changes in medical management and hospitalization criteria. In addition, this study supports the results of other studies which show that hospitalization rates are lower in Health Maintenance Organizations than in non-Health Maintenance Organizations with no apparent adverse impact on outcome.

Adolescent↗

Dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus vulgaris.

OBJECTIVE: To determine the effect of dapsone on glucocorticoid-dependent patients with active or maintenance-phase pemphigus vulgaris. DESIGN: Retrospective study of consecutive patients treated with dapsone. SETTING: University of Pennsylvania, Philadelphia (a tertiary referral hospital). Patients We observed 9 consecutive adult patients with pemphigus vulgaris being treated with immunosuppressants who were unable to taper prednisone use without abrupt worsening of their disease.Interventions Dapsone treatment added to prednisone and other immunosuppressive therapy. Main Outcome Measure Steroid dosage. RESULTS: All patients were unable to taper their steroid dose during the 3 months prior to the initiation of dapsone therapy or had active disease that was not well controlled by prednisone prior to dapsone treatment. With the exception of 1 patient with uncontrolled disease, all 9 patients were able to taper their steroid dose below the adrenal replacement level during dapsone treatment. Maintenance-phase patients taking 15 mg/d or more of prednisone (n = 5) experienced a mean +/- SEM drop of 67% +/- 7.1% in prednisone dose by 4 months of maximal dapsone treatment and an 84% +/- 3.5% drop in prednisone dose after 8 months of dapsone treatment. CONCLUSIONS: These retrospective study findings suggest that dapsone reduces steroid dependence in patients with pemphigus vulgaris, provided they are in the maintenance phase of their disease. These data support the need for a prospective, randomized trial to confirm these findings.

Adult↗

Computer-based documentation: effect on parent and physician satisfaction during a pediatric health maintenance encounter.

OBJECTIVE: To investigate the impact of a computer-based documentation (CBD) tool on parent and physician satisfaction with a pediatric health maintenance encounter. DESIGN: The project used a preintervention and postintervention design. The preintervention group visits used paper-based forms for data entry, whereas the postintervention visits used CBD. At the conclusion of each encounter, both the physician and the parent completed a survey that assessed their perceptions of the encounter's quality. SETTING: Urban hospital-based pediatric teaching clinic. PARTICIPANTS: Parents and physicians of children 18 months and younger. MAIN OUTCOME MEASURES: Parent and physician satisfaction with 7 components of a health maintenance encounter (interim history, social history, anticipatory guidance, developmental assessment, physical examination, assessment, and plan). RESULTS: There was no change in overall parent or physician satisfaction in the areas of communication or physician helpfulness. Physicians using CBD were less likely to agree that they provided clear explanations but were also less likely to agree that they "acted bossy during the visit." There was no correlation between physician and parent satisfaction or between physician satisfaction and pattern of CBD use. However, there was a strong correlation between physicians' satisfaction and the extent to which they found CBD helpful (Spearman rho = 0.29, P<.001). CONCLUSIONS: The introduction of CBD into the health maintenance encounter did not affect measured aspects of parent or physician satisfaction; these results support its continued use in that setting.

Attitude to Computers↗