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At least 1,531 records · Page 85Linked to original sources
PubMed2005

The practice of office-based buprenorphine treatment of opioid dependence: is it associated with new patients entering into treatment?

Office-based buprenorphine holds the promise of bringing patients who have never received pharmacotherapy into treatment. In a cross-sectional and longitudinal analysis, we compared patients entering a clinical trial of buprenorphine in a Primary Care Clinic (PCC) and those entering a local Opioid Treatment Program (OTP) and we compared the clinical characteristics and treatment outcomes of PCC patients with no history of methadone treatment (new-to-treatment) to those with prior methadone treatment. PCC subjects (N=96) were enrolled in a 26-week randomized clinical trial of office-based buprenorphine/naloxone provided in a PCC. OTP subjects (N=94) were enrolled in methadone maintenance during the same time period. PCC subjects compared with OTP subjects were more likely to be male (77% versus 55%, p<0.01), full-time employed (46% versus 15%, p<0.001), have no history of methadone treatment (46% versus 61%, p<0.05), have fewer years of opioid dependence (10 versus 15, p<0.001), and lower rates of injection drug use (IDU) (44% versus 60%, p=0.03). The new-to-treatment PCC subjects were younger (36 years versus 41 years, p=0.001), more likely to be white (77% versus 57%, p=0.04), had fewer years of opioid dependence (7 versus 14, p<0.001), were less likely to have a history of IDU (35% versus 54%, p=0.07), and had lower rates of hepatitis C (25% versus 61%, p=0.002) than subjects with prior methadone treatment. Abstinence and treatment retention were comparable in both groups. The results suggest that office-based treatment of opioid dependence is associated with new types of patients entering into treatment. Treatment outcomes with buprenorphine in a PCC do not vary based on history of prior methadone treatment.

Adolescent↗
PubMed2006

T-cell receptor triggering differentially regulates bim expression in human lymphocytes from healthy individuals and patients with infectious mononucleosis.

Bim, a proapoptotic member of the Bcl-2 protein family, is a major regulator of central and peripheral T-cell deletion. Regulation of Bim activity by T-cell receptor (TCR) triggering is not well understood. We investigated expression of Bim in different subpopulations of ex vivo isolated human T cells from healthy donors and patients with infectious mononucleosis (IM). Upregulation of Bim expression in response to TCR-triggering was observed only in a small proportion of analyzed samples of peripheral blood lymphocytes (PBLs) from healthy donors and only occasionally upon longitudinal analysis of cells isolated from the same individuals. Populations of naive or memory T cells enriched on the basis of CD45RO or CD45RA expression showed only slight and comparable Bim upregulation. In contrast, ex vivo isolated PBLs from IM patients in the acute stage of the disease with significant expansions of CD8+ cells expressed increased levels of Bim, and lymphocytes from the majority of analyzed IM patients exhibited significant upregulation of all major Bim isoforms in response to TCR triggering. These results demonstrate that at least some antigen-induced expansions of human CD8+ T cells are associated with increased levels of Bim, and TCR triggering in effector T lymphocytes may increase Bim activity by upregulation of its expression.

Acute Disease↗
PubMed2004

HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation.

The supply of naive T cells by the thymus normally requires precursor T cell proliferation within the thymus and would be particularly important in the setting of HIV infection when both naive and memory T cells are progressively depleted. As a robust, quantitative index of intrathymic proliferation, the ratio of different T cell receptor excision circles (TRECs), molecular markers of distinct T cell receptor rearrangements occurring at different stages of thymocyte development, was measured in peripheral blood-mononuclear cells (PBMCs). This ratio has the virtue that it is a "signature" of thymic emigrants throughout their entire life and, thus, can be measured in peripheral cell populations that are easy to obtain. Using the new assay, we evaluated the effect of HIV infection on intrathymic precursor T cell proliferation by longitudinal analysis of PBMCs from recently infected individuals. Our findings reveal a substantial reduction in intrathymic proliferation. The analysis also indicates the existence of a compensatory mechanism acting to sustain the numbers of recent thymic emigrants (RTEs) in the periphery.

Aging↗
PubMed2006

Rapid detection of Epstein-Barr virus DNA by loop-mediated isothermal amplification method.

BACKGROUND: The loop-mediated isothermal amplification (LAMP) method is a novel technique for the amplification of specific DNA sequences. OBJECTIVES: To establish the LAMP method for amplifying Epstein-Barr virus (EBV) DNA and to examine its reliability for the detection of EBV DNA in clinical specimens. STUDY DESIGN: Sera from 108 patients, who were initially suspected of primary EBV infection, were tested by the EBV LAMP method, and the results were compared with those of the real-time PCR assay. Serological examination was regarded as the standard diagnostic method. RESULTS: To diagnose primary EBV infection, the sensitivity of LAMP was 86.4% and the specificity was 100%. The sensitivity of the real-time PCR assay was 84.1% and the specificity was 98.4%. Longitudinal analysis showed that the detection rate of EBV DNA in serum by the LAMP method decreased with time in accordance with the decrease of the EBV load. EBV DNA could not be detected in serum 40 days after onset of symptoms. CONCLUSIONS: These results indicate that the sensitivity and specificity of the LAMP method are comparable to those of real-time PCR and that detecting EBV DNA in serum by this method is potentially useful for diagnosing primary EBV infection.

Child, Preschool↗
PubMed2005

Tibial cancellous bone changes in patients with knee osteoarthritis. A short-term longitudinal study using Fractal Signature Analysis.

OBJECTIVE: To quantify tibial cancellous bone changes over 24 months in patients with medial compartment knee osteoarthritis (OA) subdivided into those with slow or detectable joint space narrowing (JSN). METHOD: Digitised macroradiographs (4x) were obtained at baseline and 24 months from 40 patients (F:26) and subdivided by computerised measurement of minimum medial compartment joint space width (JSW) into those with slow JSN (<0.2 mm/year, n=66) or detectable JSN (>or=0.2 mm/year, n=14) and who had a mean (range) JSW at baseline of 3.89 (1.66-5.48) mm and 3.73 (2.49-5.74) mm, respectively. Fractal Signature Analysis measured longitudinal change in bone structure at four regions of interest (ROI): medial and lateral subchondral (Sc) and subarticular (Sa) regions. RESULTS: Mean (range) JSN for slow and detectable groups was 0.01 (-0.31-0.18) mm/year and 0.44 (0.20-1.01)mm/year, respectively. All ROIs in both groups had significant (P<0.05) decrease in fractal dimension (FD) at most trabecular sizes (vertical: 0.36-1.14 mm; horizontal: 0.36-1.14 mm, excluding the lateral Sa region) over 24 months. There were no between-group differences except at a few trabecular sizes within the Sa regions where the detectable JSN group had significantly (P<0.05) greater decrease in FD compared to the slow JSN group (medial: horizontal sizes 0.54-0.72 mm, 1.02-1.08 mm; lateral: vertical sizes 0.90-1.02 mm). CONCLUSION: Bone loss occurred in all knees with medial compartment OA. Decrease in FD of vertical and horizontal trabeculae was consistent with decrease in trabecular number associated with loss. The pattern of bone loss was similar in knees with slow and detectable JSN.

Aged↗
PubMed2026

Perioperative analgesic efficacy of ultrasound-guided erector spinae plane block and posterior transversus abdominis plane block in paediatric patients undergoing open pyeloplasty: A prospective randomised trial.

PURPOSE: Open pyeloplasty in the paediatric population involves extensive tissue dissection and manipulation, resulting in significant postoperative pain. Ultrasound-guided fascial plane blocks have emerged as an important component of multimodal analgesia in abdominal surgeries. This study compared the analgesic efficacy of ultrasound-guided Erector spinae plane block (ESP) and posterior transversus abdominis plane (pTAP) block in children undergoing open pyeloplasty. METHODS: It is a prospective, randomised, double-blind study conducted at a single paediatric centre in a tertiary care hospital in Asia from January 2022 to June 2023. 40 ASA I-II children were randomised to receive either the ESP block (Group E) or the pTAP block (Group T). Both groups received 0.4 ml/kg, 0.2% ropivacaine with 1 mcg/kg dexmedetomidine. Children with an allergy to local anaesthetics, cardiac, renal or hepatic dysfunction and local site infection were excluded. The primary outcome was cumulative 24 h postoperative acetaminophen consumption. Secondary outcomes included the effects on intraoperative hemodynamics, perioperative opioid consumption, FLACC and Watcha scores, time to first rescue analgesia, and any block-related complications. RESULTS: Weight-normalised 24 h postoperative acetaminophen consumption was significantly lower in the ESP group (13.5 &#xb1; 4.7 mg/kg) compared to the pTAP group (25.4 &#xb1; 8.3 mg/kg), with a mean difference of -12 mg/kg (p < 0.001, 95%CI -16 to -7.6). The median time to first rescue analgesia was significantly longer in the ESP group (18 h [95% CI, 18-24]) than in the TAP group (9 h [95% CI, 6-12]), p < 0.001. Although FLACC scores were significantly lower in the ESP group at 30 min and 12 h postoperatively, the overall longitudinal analysis using a linear mixed-effects model showed no significant difference in the trend of FLACC scores over time between the two groups. There were no block-related complications. CONCLUSION: Ultrasound-guided ESPB provides better, longer-lasting analgesia than posterior TAP block in children undergoing open pyeloplasty. Hence, it may serve as an effective component of multimodal pain management in paediatric open pyeloplasty. CTRI REGISTRATION (CTRI/2022/04/041876) DATED 13/04/2022): https://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=67747&EncHid=42257.14515&modid=1&compid=19.

Humans↗
PubMed2004

Quality of life assessment of second-line docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy: results of a prospective, randomized phase III trial.

PURPOSE AND METHODS: Docetaxel second-line chemotherapy for non-small-cell lung cancer (NSCLC) has previously been shown to improve survival significantly compared with best supportive care (BSC). This multicenter phase III trial prospectively investigated quality of life (QOL) in NSCLC patients treated with either second-line docetaxel or BSC. Patients with stage IIIB/IV NSCLC, performance status < or =2, and adequate biochemistry and hematology were eligible if they had received > or =1 platinum-based chemotherapy regimens. Patients were randomized to docetaxel 100 mg/m2 (n=49) or, after protocol amendment, to docetaxel 75 mg/m2 (n=55), or to BSC (n=100), with Lung Cancer Symptom Scale (LCSS) and/or QLQ-C30 (with LC13 module) assessment every 3 weeks. RESULTS: Longitudinal analysis including all available assessments over time showed statistically significant differences in patient-rated pain scores in favor of docetaxel overall (P=0.005) or docetaxel 100 mg/m2 (P=0.003) compared to BSC. Trends in favor of docetaxel were noted on observer-rated scales for fatigue and pain for all docetaxel patients, and for total LCSS score, appetite and fatigue with docetaxel 100 mg/m2. Changes from baseline to the last available assessment (end point) showed significantly (P<0.05) less deterioration in LCSS pain score in patients with docetaxel (75 and 100 mg/m2 combined) than with BSC. An improved mean pain score with docetaxel 100 mg/m2 was contrasted with a deterioration in mean pain score with BSC (P<0.01). There was also significantly less deterioration in the global QOL today score with docetaxel 100 mg/m2 (P<0.01). Similar trends were recorded with QLQ-C30 assessments. CONCLUSIONS: Second-line docetaxel therapy for advanced NSCLC significantly improves survival with a trend towards less deterioration in QOL compared with BSC.

Adult↗
PubMed2006

Incidence and economics of clinical mastitis in five Holstein herds in the Czech Republic.

Data on clinical mastitis (CM) collected between 1996 and 2003 on five Holstein dairy farms in the Czech Republic were analyzed. Lactational incidences of CM, averaged across farms and calculated only from cows with complete lactations, were 0.35, 0.45 and 0.57 for the first, second and third plus subsequent lactations, respectively. The mean numbers of CM cases per cow and lactation were 0.63, 0.94 and 1.22, and the incidence of CM cases per cow-year at risk were 0.68, 1.00 and 1.27 for the first, second and third plus subsequent lactations, respectively. Longitudinal analysis of CM prevalence based on daily records showed the highest proportion of infected cows in the first 10 days of lactation. The within-farm incidence of CM cases per cow per year, averaged over lactations, ranged from 0.53 to 1.56 with a mean value of 0.94 in the whole data set. Direct financial losses from CM per cow per year within farm ranged from 43.63 to 84.84 euros. They included losses from discarded milk, cost for drugs, veterinary service, herdsman's time, cost for an extra milking machine and cost for antibiotic drying of cows. The economic value of CM incidence (change in direct losses per cow per year when increasing CM incidence by one case above the average value) ranged from 58.3 to 80.1 euros per CM case per cow per year with the mean value of 62.6 euros per CM case per cow per year in the total data set. Daily prevalence rate of CM was shown to be the best among various indicators of CM susceptibility, because it accounted for the censored character of the data and for repeated cases of CM within lactations. In order to reduce the incidence of clinical mastitis for dairy cattle in the Czech Republic, we recommend that it should be included as a goal in the breeding program.

Animals↗
PubMed2005

Rheumatic complications of human immunodeficiency virus infection in the era of highly active antiretroviral therapy: emergence of a new syndrome of immune reconstitution and changing patterns of disease.

OBJECTIVE: To describe the impact of the introduction of highly active antiretroviral therapy (HAART) on the nature and frequency of rheumatic complications in human immunodeficiency virus (HIV)-infected patients. METHODS: Case report and systematic review of a newly described syndrome of rheumatic immune reconstitution syndrome and prospective longitudinal cohort study analyzing the frequency and nature of rheumatic complications in the setting of HIV infection from 1989 through 2000. RESULTS: A newly described syndrome of either the de novo appearance or the exacerbation of clinically occult autoimmunity following immune reconstitution from HAART is described. Including the present case report, 32 cases have been individually described with sarcoidosis and autoimmune thyroid disease being most common with arthritis and various forms of connective tissue disease making up the rest. The mean onset to their appearance following HAART was nearly 9 months and most resolved with little or no therapy. In addition, a longitudinal analysis of 395 HIV-infected patients from 1989 to 2000 designed to detect the appearance of rheumatic complications has revealed a dramatic decline in certain problems such as reactive arthritis, psoriatic arthritis, and various forms of connective tissue disease. New rheumatic complications possibly due to the effects of longer survival and metabolic derangements associated with this form of therapy are now being described and may become more formidable problems in this population in the future. CONCLUSIONS: HAART has had a profound beneficial effect on survival in HIV-infected patients but has also contributed to both an altered frequency and a different nature of rheumatic complications now being observed in this population. Rheumatologists need to be aware of these changes to provide optimal diagnosis and treatment for this group.

Adult↗
PubMedDate not supplied

The long-term effect of posterolateral fusion in adult isthmic spondylolisthesis: a randomized controlled study.

BACKGROUND: Today there is some evidence-based medicine support for a positive short-term treatment effect of fusion in chronic low back pain in spondylolisthesis and in nonspecific degenerative lumbar spine disorders. The long-term effect is, however, unknown. PURPOSE: To determine the long-term outcome of lumbar fusion in adult isthmic spondylolisthesis. STUDY DESIGN: Prospective, randomized controlled study comparing a 1-year exercise program with instrumented and non-instrumented posterolateral fusion with average long-term follow-up of 9 years (range, 5-13). PATIENT SAMPLE: 111 patients aged 18 to 55 years with adult lumbar isthmic spondylolisthesis at L5 or L4 level of all degrees, and at least 1-year's duration of severe lumbar pain with or without sciatica. OUTCOME MEASURES: Pain and functional disability was quantified by pain (VAS), the Disability Rating Index (DRI), the Oswestry Disability Index (ODI) work status, and global assessment of outcome by the patient into much better, better, unchanged or worse. Quality of life was assessed by the SF-36. METHODS: The patients were randomly allocated to treatment with 1) a 1-year exercise program (n=34), 2) posterolateral fusion without pedicle screw instrumentation (n=37), or 3) posterolateral fusion with pedicle screw instrumentation (n=40). Long-term follow-up was obtained in 101 (91%) patients. Nine patients in the exercise group were eventually operated on. RESULTS: Longitudinal analysis: At long-term follow-up pain and functional disability were significantly better than before treatment in both surgical groups. No significant differences were observed between instrumented and non-instrumented patients in any variable studied. In the exercise group the pain was significantly reduced but not the functional disability. Compared with the 2-year follow-up a significant increase in functional disability was observed, as measured by the DRI, but not the ODI, in the surgical group at long term. In the exercise group no significant changes were observed between the 2-year and the long-term follow-up. Cross-sectional analysis: Between the surgical and conservative group no significant differences were observed in any outcome measurement at long-term follow-up except for global assessment, which was significantly better for surgical patients. Of surgical patients 76% classified the overall outcome as much better or better compared with 50% of conservatively treated patients (p=0.015). Quality of life as estimated by the SF-36 at long term was not different between treatment groups in any of the eight domains studied but was considerably lower than for the normal population. CONCLUSIONS: Posterolateral fusion in adult lumbar isthmic spondylolisthesis results ina modestly improved long-term outcome compared with a 1-year exercise program. Although the results show that some of the previously reported short-term improvement is lost at long term, patients with fusion still classify their global outcome as clearly better than conservatively treated patients. Furthermore, because the long-term outcome of the patients conservatively treated most likely reflects the natural course, one can also conclude that no considerable spontaneous improvement should be expected over time in adult patients with symptomatic isthmic spondylolisthesis. Substantial pain, functional disability and a reduced quality of life will in most patients most likely remain unaltered over many years.

Activities of Daily Living↗
PubMed1999

Historic perspectives on the relative contributions of diastolic and systolic blood pressure elevation to cardiovascular risk profile.

The aim of this review was to examine the relative contributions of systolic and diastolic blood pressures to the risk of cardiovascular disease on the basis of epidemiologic evidence from the Framingham Heart Study and the change in attitudes toward systolic blood pressure that occurred during the course of the study. Historic texts were evaluated in comparison with data from the Framingham Heart Study, a prospective longitudinal analysis of the relation between blood pressure and occurrence of subsequent cardiovascular morbidity and mortality rates in a fixed cohort. Historically, systolic hypertension has been considered an innocent accompaniment to arterial stiffening, occurring as a compensatory phenomenon in the elderly. Epidemiologic data show that the development of hypertension is neither inevitable nor beneficial. The data also provide evidence that systolic pressure is more important than diastolic pressure as a determinant of cardiovascular sequelae. Mild or moderate elevations of systolic blood pressure, even when unaccompanied by diastolic pressure elevations, are associated with an increased risk of cardiovascular disease. Risk is increased further by the added presence of related metabolic disturbances such as dyslipidemia, glucose intolerance, insulin resistance, cardiac hypertrophy, and obesity. Over-reliance on diastolic blood pressure in assessing the risk of hypertension can be misleading. Systolic pressure constitutes a powerful predictor of cardiovascular disease and a valuable tool when incorporated within multivariate risk formulas for estimating the conditional probability of coronary and stroke events.

Blood Pressure↗
PubMed2003

Does competitive flow reduce internal thoracic artery graft patency?

BACKGROUND: In coronary arteries with moderate stenosis, competitive flow may lead to internal thoracic artery (ITA) graft occlusion. The goals of this study were to determine if competitive flow reduces ITA patency, and if there is a degree of coronary stenosis below which ITAs should not be used. METHODS: From 1972 to 1999, 50,278 patients underwent primary coronary artery bypass grafting (CABG). Of these, 2,002 had at least one ITA graft and postoperative angiography before coronary reintervention; 2,999 angiograms of 2,121 ITAs were made. Time-related ITA occlusion was modeled using longitudinal analysis to identify its risk factors while accounting for lack of independence introduced by repeated angiography and multiple ITA anastomoses per patient. Proximal coronary stenosis (maximum preoperative stenosis between ITA anastomosis and aorta) was the surrogate for competitive flow. RESULTS: Unadjusted ITA patency was 93%, 89%, 90%, and 92% at 1, 5, 10, and 15 years after CABG. Risk factors associated with ITA occlusion were lesser degree of proximal coronary stenosis (p < 0.0001); longer time from CABG in grafts to non-left anterior descending coronary arteries (p < 0.0001); female sex (p = 0.0003); later date of CABG (p = 0.01); right ITA (p < 0.0001); and smoking (p < 0.0001). In all arteries, as preoperative proximal coronary stenosis decreased, ITA patency declined; however, at no degree of stenosis was there a sharp decline. CONCLUSIONS: Internal thoracic artery patency decreases as coronary competitive flow increases. However, the nature of this relationship indicates ITAs should not be abandoned at moderate grades of stenosis.

Aged↗
PubMed2000

Depressive symptoms in users and non-users of depot medroxyprogesterone acetate.

To evaluate the possible effects of depot medroxyprogesterone acetate (DMPA) injectable contraception on depressive symptoms, we conducted a population-based prospective study with women aged 18-39 years old enrolled at a health maintenance organization. At baseline, 183 women used DMPA and 274 were non-users. Data on depressive symptoms and on factors potentially related to DMPA use and depression were collected by questionnaire at 6-month intervals for up to 3 years. In multivariate longitudinal analysis, we found an increased likelihood of reporting depressive symptoms among continuous DMPA users (OR = 1.44; 95% CI = 1.00-2.07) and discontinuers (OR = 1.60; 95% CI = 1.03-2.48) when compared to non-users. Women who discontinued DMPA use had elevated depressive symptoms prior to discontinuation (OR = 2.30; 95% CI = 1.42-3.70) and immediately following discontinuation (OR = 2.46; 95% CI = 1. 46-4.14), and depressive symptoms subsided at subsequent visits relative to non-users. Our prospective analyses found an association between DMPA use and depressive symptoms but further research is needed to determine whether the relationship is causal.

Adolescent↗
PubMed2003

Seminal lead concentrations negatively affect outcomes of artificial insemination.

OBJECTIVE: To determine the relationships among seminal lead levels, acrosome status, and artificial insemination cycle fecundity (AI f) in semen donors. DESIGN: Longitudinal analysis of seminal lead levels, sperm function testing, and fecundity. SETTING: University medical center andrology and research laboratories. PATIENT(S): Semen donors (n = 15) participating in a therapeutic donor insemination program. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Seminal plasma lead levels, acrosome sensitivity to progesterone (P) and voltage-gated potassium channel inhibitors (e.g., charybdotoxin [CBTx]), and AI f. RESULT(S): Seminal plasma lead levels and AI f were strongly negatively correlated. Semen donors were divided into three groups by acrosome response to P: normal (CBTx sensitive [Rs] or CBTx resistant [Rr]: responders) and reduced (nonresponders [NR]) (Rs > Rr >> NR). Seminal lead differed among the three groups (NR > Rr > Rs). Comparison of 330 artificial insemination cycles from four Rs, four Rr, and two NR demonstrated that cycle AI f also differed significantly between groups (Rs >Rr >>NR). CONCLUSION(S): Measurements of seminal plasma lead, P-stimulated acrosome loss, and sensitivity to CBTx may provide prognostic information on the fertility status of potential donors as well as male infertility patients. Such evaluations may assist in donor acceptance, or in the case of patients, in selection of the appropriate treatment regimen.

Acrosome Reaction↗
PubMed1997

The apolipoprotein E epsilon4 allele causes a faster decline of cognitive performances in Down's syndrome subjects.

The apolipoprotein E gene (APOE), located on human chromosome 19, has three common alleles (epsilon2, epsilon3, epsilon4) which encode for the three main isoforms indicated as E2, E3 and E4 respectively. Several findings indicate epsilon4 allele as an important risk factor in both sporadic and familial late-onset Alzheimer's disease (AD). Pathological changes similar to AD are seen in almost all patients with Down's syndrome (DS) aged over 35 (senile plaques, neurofibrillary tangles and neuronal loss); a proportion of these may subsequently develop dementia. Aim of this study is to evaluate the possible pathological role of epsilon4 allele as risk factor for developing AD in a DS population. ApoE epsilon4 allele frequency is not significantly different in DS cases and controls. We found a statistically significant inverse correlation between full scale IQ values and age of patients in the subgroup of DS subjects selected for the presence of at least one epsilon4 allele, while no correlation was observed in DS subjects with other ApoE genotypes. A longitudinal analysis of cognitive performances (available in 38 patients) showed a faster rate of decline in intellectual ability in those subjects carrying at least one epsilon4 allele. Our data support the hypothesis that ApoE epsilon4 allele has a contributory role in accelerating the mental deterioration of AD-type in DS patients.

Adolescent↗
PubMed2000

Use of hydrofluoroalkane propellant delivery system for inhaled albuterol in patients receiving asthma medications.

OBJECTIVE: This study was undertaken to assess drug-use patterns associated with albuterol delivery via a new propellant device compared with conventional chlorofluorocarbon (CFC) metered-dose inhalers (MDIs) in patients taking asthma medications in a population with pharmacy benefits. BACKGROUND: In addition to their ozone-depleting properties, conventional CFC inhalers often deliver inconsistent doses because of loss of prime and temperature instability. A new propellant, hydrofluoroalkane (HFA), incorporates a re-engineered delivery system associated with dosing reproducibility throughout the life of the canister. METHODS: Drug markers associated with management of asthma were used to identify a study cohort of new users of inhaled albuterol from a geographically diverse pharmacyclaims database from July 1, 1997, through December 31, 1997. A population of 282,879 members was identified over the 20-month follow-up period. In addition, a subset of chronic albuterol inhaler users (> or = 12 months; n = 96,879) was also identified to support a longitudinal analysis. Disease severity was controlled for by use of inhaled corticosteroids (ICS). To control for canisters received via physician office samples, HFA patient use was corrected by a physician-based canister adjustment based on HFA sample data. RESULTS: A total of 53.1% of participants were women and 46.1% were men; most of the population (72.5%) was <65 years of age. Canister use for HFA patients was consistently lower (2.7+/-3.2 vs 5.4+/-6.7) than for CFC MDIs for the entire cohort over the 20-month assessment period. This difference was consistently observed for albuterol canister use in patients with and without concomitant ICS use (3.3+/-3.8 HFA vs 7.2+/-7.5 CFC for ICS users and 2.1+/-2.1 HFA vs 4.1+/-5.7 CFC for non-ICS users). Time to next prescription also was longer for HFA patients than for CFC patients (61.6+/-50.9 days HFA vs 47.3+/-40.8 days CFC). When duration of therapy and physician samples associated with product launch were controlled for, similar differences were consistently observed. CFC patients used, on average, 1.3 more canisters per year than did HFA patients (P < 0.001), averaging 10.7 canisters (95% CI, 10.6 to 10.7), compared with 9.4 canisters used by HFA patients (95% CI, 8.9 to 9.9). Further analyses indicated that this finding was consistent when ICS use was controlled for (CFC plus ICS mean, 11.9 canisters vs HFA plus ICS mean, 10.4 canisters; P < 0.001). CONCLUSION: This study provides useful information about the effect of use of a new albuterol delivery system on asthma inhaler management. These data suggest that CFC patients use an average of 1.3 more canisters per year compared with HFA patients independent of asthma severity as measured by ICS use. This improvement in dosing characteristics has the potential to translate into enhanced economic outcomes.

Administration, Inhalation↗
PubMed2000

Costimulatory mechanisms in the elderly.

Aging is associated with the progressive increase of T cells that lack expression of the CD28 costimulatory molecule. Because CD28/B7 signal transduction is required for proliferation, T cells lacking CD28 gene expression are incapable of clonal expansion. To determine whether CD28- T cells are a separate lineage or, alternatively, are the progeny of formerly CD28+ T cells, we performed cell culture longitudinal analysis on the same population of T cells over time. Repeated antigen-induced T cell division ultimately leads to irreversible cell cycle arrest, shortened telomeres, loss of telomerase inducibility, and total absence of expression of CD28. This in vitro model has elucidated a novel facet of T cell biology that may explain the increased incidence of infection and cancer in the elderly.

Aging↗