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Long term follow up and analysis of long term survivors in patients treated with paclitaxel-based concurrent chemo/radiation therapy for locally advanced non-small cell lung cancer.

PURPOSE: For patients with locally advanced non-small cell lung cancer (LANSCLC), concurrent chemotherapy/radiation therapy (RT) has become the standard of care. Three multi-institutional phase II studies with paclitaxel-based chemotherapeutic regimen given concurrently with RT for patients with LANSCLC were performed from March of 1994 to May of 1997. We sought to determine mature data from this database of patients, as well as to perform analysis of a cohort of patients who have achieved long term survival (LTS) when treated with this regimen. PATIENTS AND METHODS: Database of these patients was analyzed retrospectively upon longer follow up, with median follow up for the three studies being 498 days (range 11-2905 days, average 780 days). Weight loss limitation for the three studies was liberal: weight loss <10% and <15% 3 months preceding diagnosis (LUN-27 and LUN-63, respectively), and no weight loss limitation for LUN-56. RESULTS: The 4-year overall survival (OS) for the three trials was 16.3%, and 2-year progression free survival (PFS) was 25.7%. Statistical analysis of the long term survivors (OS > 4 years) was performed, and performance status (PS) was found to be a significant factor predictive of LTS. PS of 0 compared to 1 yielded a 2.5-fold increased likelihood of LTS (p = .04). There was also a trend (p = .067) for responders (complete or partial response) to yield a five-fold likelihood of LTS compared to non-responders (stable or progressive disease). CONCLUSION: Our results support the efficacy of combined modality therapy (CMT) for patients with LANSCLC even despite our more liberal weight loss eligibility criteria. Furthermore, our analysis indicates that LTS is more likely to be achievable in patients with PS = 0 compared to 1 when treated with CMT for LANSCLC.

Adult↗

CCR5 promoter polymorphisms, CCR5 59029A and CCR5 59353C, are under represented in HIV-1-infected long-term non-progressors. The Australian Long-Term Non-Progressor Study Group.

OBJECTIVE: To determine the influence of CCR5 promoter polymorphisms on HIV-1 progression to AIDS and to evaluate the interaction between CCR5 structural polymorphisms and those occurring in the regulatory region of the same gene. PARTICIPANTS: Seventy-one HIV-1-infected long-term non-progressors with a CD4+ T cell count of > 500 x 10(6)/I more than 8 years after infection were compared with 75 HIV-1-infected individuals who had progressed to AIDS and/or death within 8 years and with a further 119 HIV-1-positive patients who had CD4+ T cell counts of 200-500 x 10(6)/l. An additional 92 HIV-negative individuals were also studied. METHODS: CCR5 delta32 genotype was determined by PCR with primers spanning the 32 base pair deletion. CCR2-64I, CCR5 59029A/G and CCR5 59353C/T genotypes were determined by PCR followed by restriction fragment length polymorphism analysis. RESULTS: Strong linkage disequilibrium between the CCR5 59029A and CCR5 59353C polymorphic variants was identified. CCR5 59029A and CCR5 59353C homozygotes were found to be significantly under-represented in the long-term non-progressor group as compared with the other HIV-1-positive groups, with the effect being more marked in the absence of the CCR5 delta32 and CCR2 64I mutations. CONCLUSIONS: This study provides the first evidence for an association between CCR5 promoter polymorphisms and long-term asymptomatic HIV-1 infection, with individuals lacking the CCR5 59029A/CCR5 59353C homozygous genotype likely to progress more slowly towards AIDS and/or death.

Acquired Immunodeficiency Syndrome↗

Tradeoff between short-term and long-term adaptation in a changing environment.

We investigate the competition dynamics of two microbial or viral strains that live in an environment that switches periodically between two states. One of the strains is adapted to the long-term environment, but pays a short-term cost, while the other is adapted to the short-term environment and pays a cost in the long term. We explore the tradeoff between these alternative strategies in extensive numerical simulations and present a simple analytic model that can predict the outcome of these competitions as a function of the mutation rate and the time scale of the environmental changes. Our model is relevant for arboviruses, which alternate between different host species on a regular basis.

Adaptation, Physiological↗

A comparison of P-wave duration and dispersion in patients with short-term and long-term atrial fibrillation.

This study compared P-wave duration and dispersion (PD) in patients with short-term ( 48 hours) atrial fibrillation (AF) after cardioversion. We studied 96 consecutive patients with short-term (group A; n:51, age: 61 +/- 11 years) and long-term AF (group B; n:45, age: 64 +/- 10 years). P-wave measurements were calculated from 12-lead electrocardiogram. There was no difference related to clinical characteristics. Left atrial dimension was significantly higher in group B (P =.003). P maximum (124 +/- 12 vs. 113 +/- 11 ms, P =.001) and PD (57 +/- 8 vs. 49 +/- 9 ms, P =.001) were also significantly longer in group B compared with group A, but P minimum did not. In univariate analysis, PD were related to AF duration (P =.002) and left atrial size (P =.02). This relation remained in multivariate analysis (P =.01, P =.02, respectively). P maximum >112 ms and PD >47 ms had accuracy values of 74% and 83% respectively for separating group B. Our results suggest that P wave duration and dispersion is prolonged in patients with long-term AF compared to short-term AF.

Atrial Fibrillation↗

Effect of short-term and long-term antioxidant therapy on primary and secondary ageing neurovascular processes.

Previous studies from our laboratory demonstrated an age-related functional decline in sensory neurones and their modulation of microvascular blood flow (primary ageing processes) that correlated with a deficiency in tissue repair (a secondary ageing process). We also raised the notion of a possible role for free radicals in these age-related changes. The aim of this study was to investigate the impact of antioxidant therapy on modulating sensory neurovascular function and tissue repair with age. Twenty-four-month-old Sprague-Dawley rats were treated with vitamin E for short-term (40 mg/kg, i.p., every other day for 2 weeks) or long-term (for 12 months in advance, 10 g/kg, incorporated in food). These treated rats were assessed for the effectiveness of treatment and tested for their sensory neurovascular function, repair of full-thickness burn, and recovery from hyperalgesia following nerve injury. The results indicate that both short- and long-term vitamin E treatments are effective in improving sensory neurovascular function and in reducing the time required for complete wound closure of full-thickness burn injury. Short-term vitamin E treatment was more effective in protecting against the development of hyperalgesia following nerve injury. An initial increase in wound size and in hyperalgesia was observed in the treated animals, and could reflect possible side effects of the antioxidant therapy and support the importance of free radicals in early stages of the repair process. The data, overall, support the notion that oxidative damage contributes to both primary and secondary ageing processes.

Aging↗

Short-term and long-term survival in patients with alcoholic hepatitis treated with oxandrolone and prednisolone.

A cooperative study was conducted to determine the efficacy of 30 days of treatment with either a glucocorticosteroid (prednisolone) or an anabolic steroid (oxandrolone) in moderate or severe alcoholic hepatitis. One hundred thirty-two patients with moderate disease and 131 with severe disease were randomly assigned to one of three treatments: prednisolone, oxandrolone, or placebo. During the 30 days, mortality in the groups receiving steroid therapy was not significantly different from mortality in the placebo group. Thirteen per cent of the moderately ill patients and 29 per cent of the severely ill patients died. Although neither steroid improved short-term survival, oxandrolone therapy was associated with a beneficial effect on long-term survival. This was especially true in patients with moderate disease: among those who survived for one or two months after the start of treatment the conditional six-month death rate was 3.5 per cent after oxandrolone and 19 to 20 per cent after placebo (P = 0.02). No consistent long-term effect was associated with prednisolone therapy.

Clinical Trials as Topic↗

Resection of the head of the pancreas in Finland: effects of hospital and surgeon on short-term and long-term results.

BACKGROUND: To study the effect of hospital volume and surgeon volume on postoperative hospital mortality, morbidity and long-term survival after resection of the head of the pancreas in a nationwide study (case record study), taking into a consideration risk factors found important in series based on experience in one hospital. METHOD: The case record investigation of 374 patients identified from the National Hospital Discharge Database as having undergone resection of the head of the pancreas between 1990 and 1994 in Finland. RESULTS: The records of 350 patients were obtained for analysis. Operations were performed in 33 hospitals by 98 surgeons (average 2.1/year/hospital and 0.7/year/surgeon). Hospital mortality was 36/350 (10%), increasing from 4 and 7 to 13% with decreasing hospital volume from > 10 and 5-10 to < 5 respectively (P < 0.05) and increasing from 3 and 10 to 14% with decreasing surgeon volume from > 3 and 1-3 to < 1, respectively (P < 0.05). Most deaths were caused by surgical or technical complications (31/36 = 86%). Besides hospital mortality, postoperative complications, re-operations and hospital stay were also affected by surgeon volume. In the univariate analysis, also the age of the patient had an effect on the hospital mortality, and preoperative biliary stenting on the uncomplicated recovery, but in the multivariate analysis hospital mortality was independently affected by age (OR 0.94, P = 0.004) and surgeon volume (OR 1.3, P = 0.04), re-operations by surgeon volume (OR 1.10, P = 0.05) and hospital volume (OR 1.03, P = 0.05), postoperative complications by using the preoperative stent (OR 0.45, P = 0.02). Long-term survival was dependent on the histology of the specimen and by uncomplicated recovery, but not by hospital volume or surgeon volume. CONCLUSION: To decrease postoperative morbidity, mortality and hospital stay, pancreatic head surgery needs to be concentrated to only a few hospitals and to a few surgeons.

Databases, Factual↗

Effects of short-term and long-term administration of procaine hydrochloride and mepivacaine hydrochloride on hexobarbital-induced sleeping times in mice.

Investigations were performed to determine the effects of short-and long-term pretreatment with procaine and mepivacaine on hexobarbital-induced sleeping times in mice. It was found that short-term preadministration with procaine (40 mg/kg) and mepivacine (40 and 60 mg/kg) significantly increased hexobarbital-induced sleeping time, but long-term pretreatment had no effect.

Animals↗

The assaulted nurse: short-term and long-term responses.

The purpose of this prospective study was to identify attitudinal changes and to describe the emotional, cognitive, social, and biophysiological short- and long-term reactions of nursing staff being physically assaulted by a patient. Sixty-one assaulted nursing staff at the University of California Los Angeles Neuropsychiatric Institute comprised the sample. Responses to the assault were elicited through weekly self-report questionnaires and interviews at week 1 and week 6. Follow-up questionnaires were completed at 6 months to 1 year following the assault. Sixty-seven percent (41/61) of the staff met the "responder" criteria during week 1. Eighteen percent (11/61) of the assaulted staff continued to experience moderate to severe responses 6 weeks following the assault. Long-term follow-up showed that 21% (8/39) of the staff were responders at 6 months, and 16% (4/25) were responders at 1 year. Two overall trends were evident: an overall decrease in the frequency of moderate to severe responses in each of the four categories from weeks 1 to 6, with increases during weeks 3 and 4, and a higher frequency of moderate, rather than intense and severe, responses throughout the 6 week period. No significant changes in attitudes were found. The data support the need for formalized clinical, educational, and administrative programs to assist staff in coping with this stressful work experience.

Attitude of Health Personnel↗

Tolerability and efficacy of naratriptan tablets with long-term treatment (6 months). Naratriptan Long-term Study Group.

This open-label study was conducted to examine the long-term tolerability and efficacy of the novel 5HT1 agonist naratriptan tablets 2.5 mg used to treat all migraine attacks for 6 months. Patients could reduce the dose to 1 mg in the event of intolerable adverse events. The results demonstrate that the majority (median 83%) of attacks treated with naratriptan tablets 2.5 mg were not associated with an adverse event. Among attacks treated with naratriptan tablets 2.5 mg (+ optional 2.5 mg for headache recurrence), the most frequently reported adverse event was nausea (4% of attacks after a single naratriptan dose). Both the overall incidence of adverse events and the incidences of specific adverse events were no higher during months 4-6 of treatment compared with months 1-3. Only 5 of 414 patients elected to reduce their naratriptan dose to 1 mg. Headache relief 4 h postdose was reported in a mean of 68% of 6770 moderate or severe migraine attacks treated with naratriptan tablets 2.5 mg. The median number of naratriptan tablets used per attack was 1.0 (mean 1.25); patients treated only a median 7% of attacks (mean 13%) with a 2nd naratriptan tablet for headache recurrence. Patients rated naratriptan tablets as good or excellent in 61% of 7566 treated attacks. In summary, the data from this study demonstrate that naratriptan tablets 2.5 mg were very well tolerated and effective for the acute treatment of migraine for 6 months in a situation closely resembling actual clinical use.

Adolescent↗

The short-term and long-term amelioration of academic and motivational deficiencies among low-achieving inner-city adolescents.

56 low-achieving seventh-grade students in a predominantly black, inner-city junior high school were randomly assigned to one of four groups (SMART, PUSH, Standard Reading, or Nonintervention). The highly structured, school-based SMART program employed nonprofessional tutors to improve the academic skills and attitudes of the adolescents. The home-based PUSH program involved parents in restructuring the home environment to foster educational development. The Standard Reading group was the usual school reading class, and the Nonintervention group did not receive any special remediation. A battery of standardized educational and attitudinal tests was administered to each student (a) immediately before assignment to groups, (b) immediately after termination of the 10-week programs, and (c) at 6-month follow-up. Results from the 4 x 3 analysis of variance clearly demonstrated the short- and long-term efficacy of the SMART program and the long-term efficacy of the PUSH program. Each produced substantial increases in both the acquisition of fundamental academic skills and achievement motivation. Implications of these findings and directions for future research are discussed.

Achievement↗

The myelosuppressive effect of recombinant interferon gamma in short-term and long-term marrow cultures.

The effect of a highly purified human gamma IFN (r-gamma-IFN) on the growth of haemopoietic progenitors was examined in soft agar assays and in long-term bone marrow cultures. r-gamma-IFN reduced colony formation by progenitor cells of the granulocyte/macrophage lineage (GM-CFC), the erythroid lineage (BFU-E) and multipotent cells (GEMM-CFC), and suppressed haemopoiesis in long-term culture in a dose-related fashion. At high doses (1000 units/ml) r-gamma-IFN appeared to be toxic to the stromal cells of the bone marrow.

Bone Marrow↗

[Neoadjuvant androgen deprivation preceding to radical prostatectomy--its role in short-term and long-term outcomes].

Neoadjuvant androgen deprivation has been demonstrated to reduce the risk of surgical margin positivity and lymphnode metastasis, and facilitate a thorough prostatectomy. On the contrary, no long-term studies have proved the beneficial effects of preoperative therapy on patients' survival. A multicenter randomized study in Japan comparing neoadjuvant therapy and immediate surgery (control) was conducted. All the patients were to receive hormonal therapy for 2 years. The results confirmed the short-term efficacy of neoadjuvent hormonal treatment, and no significant difference in clinical relapse rate (5.6% (5/90) in neoadjuvant group versus 11.6% (10/86) in control group), nor PSA relapse rate (13.3% versus 17.4%) at 2 years posttreatment; however in stage C cancer there was a tendency of a lower clinical relapse rate in neoadjuvant group (9.5%: 2/21) than the control (30.4%: 7/23). These data provide no obvious evidence for favorable long-term outcomes in neoadjuvant group, although a possibility that stage C cancer benefits from the treatment remains to be explored.

Androgen Antagonists↗

Short-term and long-term sick-leave in Sweden: relationships with social circumstances, working conditions and gender.

The primary aim of the study was to analyse similarities and differences between repeated spells of short-term sick-leave (more than 3 spells of less than 7 days' duration in a 12-month period) and long-term absence through sickness (at least 1 spell of more than 59 days' duration in a 12-month period) in relation to variables representing certain social circumstances and aspects of the work situation. Particular attention was paid to gender differences. The study, which had a cross-sectional design, employed data from the surveys of living conditions (ULF) conducted by Statistics Sweden over the period 1986-89. The study group comprised 13,828 employed persons between the ages of 16 and 65. The results suggested the existence of a common mechanism by which a variety of factors are related to the taking of both repeated short spells and long-term sick-leave; gender differences with regard to the effect of working conditions on the taking of sick-leave may be incorrectly estimated if factors related to occupational structure are not taken into consideration; a less than additive effect of physical job demands and repeated short spells of sick-leave on subjective health was found.

Absenteeism↗

Acquired immune dysfunction in cats with experimentally induced feline immunodeficiency virus infection: comparison of short-term and long-term infections.

Specific pathogen-free domestic cats with experimentally induced feline immunodeficiency virus (FIV) infections of short duration (less than or equal to 10 months) exhibited depressed total leukocyte and neutrophil numbers and a marginally decreased lymphocyte proliferative response to pokeweed mitogen (PWM), while cats with infections of more lengthy duration (greater than or equal to 25 months) exhibited normal leukocyte and neutrophil numbers but a dramatic loss of responsiveness to both PWM and concanavalin A (Con A). Cats with short-term infections exhibited a decrease in the percentage of CD4+ lymphocytes in peripheral blood and a corresponding depression of the CD4+:CD8+ ratio. Cats with long-term infections exhibited a similar but more profound perturbation of the CD4+ lymphocyte subset that also included a decrease in the absolute number of CD4+ cells. The decreased responsiveness to Con A and PWM in cats infected long term paralleled the decline in CD4+ cell counts, and the duration of infection was directly correlated with the decrease in the percentage of CD4+ cells. These data provide evidence supporting the hypothesis that FIV is the cause of an immune dysfunction in cats, with distinct similarities to that produced by human immunodeficiency virus (HIV) in people.

Acquired Immunodeficiency Syndrome↗

The impact of obesity on the short-term and long-term outcomes after percutaneous coronary intervention: the obesity paradox?

OBJECTIVES: The purpose of this study was to assess the impact of body mass index (BMI) on the short- and long-term outcomes after percutaneous coronary intervention (PCI). BACKGROUND: Obesity is associated with advanced coronary artery disease (CAD). However, the relation between BMI and outcome after PCI remains controversial. METHODS: We studied 9,633 consecutive patients who underwent PCI between January 1994 and December 1999. Patients were divided into three groups according to BMI: normal, BMI between 18.5 and 24.9 (n = 1,923); overweight, BMI between 25 and 30 (n = 4,813); and obese, BMI >30 (n = 2,897). RESULTS: Obese patients were significantly younger and had consistently worse baseline clinical characteristics than normal or overweight patients, with a higher incidence of hypertension, diabetes, hypercholesterolemia and smoking history (p < 0.0001). Despite similar angiographic success rates among the three groups, normal BMI patients had a higher incidence of major in-hospital complications, including cardiac death (p = 0.001). At one-year follow-up, overall mortality rates were significantly higher for normal BMI patients compared with overweight or obese patients (p < 0.0001). Myocardial infarction and revascularization rates did not differ among the three groups. By multivariate Cox regression analysis, diabetes, hypertension, age, BMI and left ventricular function were independent predictors of long-term mortality. CONCLUSIONS: In patients with known CAD who undergo PCI, very lean patients (BMI <18.5) and those with BMI within the normal range are at the highest risk for in-hospital complications and cardiac death and for increased one-year mortality.

Age Factors↗

Relationship between short-term and long-term blood pressure variabilities in essential hypertensives.

This study was designed to analyse the relationship between the different blood pressure (BP) variabilities obtained in a non-invasive way and to determine the potential contribution of aging, severity of hypertension and increased ventricular mass to these different BP variabilities. Two hundred and six hypertensive patients underwent a 24-h ambulatory BP measurement (ABPM) as well as a photoplethysmographic BP recording and a standard echocardiography. Nocturnal BP fall and standard deviations of hourly mean BP levels as well as post-prandial fall in BP were calculated from the 24-h ABPM and were considered as indexes of long-term variability. Baroreflex sensitivity (BRS) and spectral powers of systolic BP, diastolic BP and heart rate (HR) over the low frequency band (LF: 0.05--0.14 Hz) were obtained from photoplethysmographic recording and were used as indexes of short-term variability. Short-term variability indexes were shown to be significantly related to those of long-term variability. A decrease in LF spectral powers was associated with a particular profile characterised by an attenuation of nocturnal BP fall, an increase of daytime BP standard deviations, an increase in post-prandial BP fall, a decrease in BRS and to a lesser extent, a diminution in night-time HR standard deviation. Moreover, a negative significant relationship was found between standard deviation of daytime systolic BP and both night systolic BP fall and BRS. Age and nocturnal BP level were associated with all BP variability disorders, whereas left ventricular hypertrophy was associated only with a decrease in LF spectral powers and in night BP fall, and an increase in standard deviation of daytime BP. Finally, LF spectral power of SBP was identified as independently predicted by age and night SBP fall. Journal of Human Hypertension (2001) 15, 41-48

Adult↗

Peripheral signals conveying metabolic information to the brain: short-term and long-term regulation of food intake and energy homeostasis.

Numerous peripheral signals contribute to the regulation of food intake and energy homeostasis. Mechano- and chemoreceptors signaling the presence and energy density of food in the gastrointestinal (GI) tract contribute to satiety in the immediate postprandial period. Changes in circulating glucose concentrations appear to elicit meal initiation and termination by regulating activity of specific hypothalamic neurons that respond to glucose. Other nutrients (e.g., amino acids and fatty acids) and GI peptide hormones, most notably cholecystokinin, are also involved in short-term regulation of food intake. However, the energy density of food and short-term hormonal signals by themselves are insufficient to produce sustained changes in energy balance and body adiposity. Rather, these signals interact with long-term regulators (i.e., insulin, leptin, and possibly the orexigenic gastric peptide, ghrelin) to maintain energy homeostasis. Insulin and leptin are transported into the brain where they modulate expression of hypothalamic neuropeptides known to regulate feeding behavior and body weight. Circulating insulin and leptin concentrations are proportional to body fat content; however, their secretion and circulating levels are also influenced by recent energy intake and dietary macronutrient content. Insulin and leptin concentrations decrease during fasting and energy-restricted diets, independent of body fat changes, ensuring that feeding is triggered before body energy stores become depleted. Dietary fat and fructose do not stimulate insulin secretion and leptin production. Therefore, attenuated production of insulin and leptin could lead to increased energy intake and contribute to weight gain and obesity during long-term consumption of diets high in fat and/or fructose. Transcription of the leptin gene and leptin secretion are regulated by insulin-mediated increases of glucose utilization and appear to require aerobic metabolism of glucose beyond pyruvate. Other adipocyte-derived hormones and proteins that regulate adipocyte metabolism, including acylation stimulating protein, adiponectin, diacylglycerol acyltransferase, and perilipin, are likely to have significant roles in energy homeostasis.

Adipocytes↗