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Door to needle times bulls' eye or just bull? The effect of reducing door to needle times on the appropriate administration of thrombolysis: implications and recommendations.

The provision of thrombolysis in a timely fashion is the mainstay of treatment for acute myocardial infarction. With the publication of the National Service Framework (NSF) for Coronary Heart Disease increasing efforts have been put into the reduction of the "pain to needle time". Of the various parts of the patient journey the time delays in hospital are the easiest to resolve. Published research shows that the time taken for the patient to call for help is intractable at present. Therefore, the obvious target for the reduction in the overall time from pain to treatment is the in hospital portion of the delay (the door to needle time). There are several methods that have been recommended for the reduction of the door to needle time. However, the increasing focus on the door to needle time is leading health care providers away from other issues such as the safety and accuracy of assessment by a non-cardiologist. Furthermore, the standards for audit of the door to needle time have not been set by the NSF and this has led to the presentation of selected data and the avoidance of discussing issues of accuracy and appropriateness.

Guideline Adherence↗

Detrimental effect of acute renal failure on the survival of renal allografts: influence of total ischaemia time and anastomosis time.

In a retrospective study the incidence and consequences of acute renal failure were evaluated in 324 renal transplantations performed in our centre. The overall incidence of acute renal failure was 31.2%. In recipients with acute renal failure, patient and graft survival were significantly worse than in those without acute renal failure (P less than 0.02 and P less than 0.0001 respectively). Acute renal failure also increased the morbidity during the first 3 months after transplantation. Three months after transplantation renal function as determined by serum creatinine and proteinuria, was less satisfactory. Factors influencing the incidence of acute renal failure appeared to be: match grade on the AB locus, percentage of antibodies, duration of dialysis, number of blood transfusions prior to transplantation, anastomosis time and total ischaemia time. Recipients transplanted for the first time were less likely to develop acute renal failure, but also for this group total ischaemia time was a prognostic factor for the development of acute renal failure. When recipients were allocated to different classes of total ischaemia time it appeared that the incidence of acute renal failure differed, especially between groups with total ischaemia time 32-36 h (27%) and 36-40 h (38%). The difference in acute renal failure between these groups was also reflected in a difference in graft survival for total ischaemia time less than 36 h and greater than 36 h. Thus, it appears that acute renal failure has a detrimental effect on graft survival and postoperative morbidity in renal transplantation. Total ischaemia time is one of the prognostic factors for the development of acute renal failure. To improve renal transplantation results it is worth attempting to shorten total ischaemia time.

Acute Kidney Injury↗

The Ecarin time is an improved confirmatory test for the Taipan snake venom time in warfarinized patients with lupus anticoagulants.

The Taipan snake venom time using dilute phospholipid as a screening test with a platelet neutralization procedure as a confirmatory test has been shown to be a sensitive and specific approach to detection of lupus anticoagulants. Taipan venom is largely insensitive to the effects of ongoing warfarin anticoagulation and this can be useful in detection of lupus anticoagulants in patients receiving this treatment. This study compared the use of the platelet neutralization procedure with the Ecarin time as confirmatory tests for the Taipan snake venom time, the Ecarin venom fraction being insensitive to both lupus anticoagulants and the effects of oral anticoagulants. Screening and confirmatory test data were assessed for phospholipid dependence by three different mathematical methods and there was no advantage in using the Ecarin time in detection of 'uncomplicated' lupus anticoagulants. In lupus anticoagulant-positive warfarinized patients, the Ecarin time achieved higher detection rates than the platelet neutralization procedure irrespective of the method used to assess correction. The Ecarin time confirmed lupus anticoagulants in all of those samples that generated elevated Taipan snake venom time ratios whereas the platelet neutralization procedure identified only 33%. Taipan snake venom time plus Ecarin time offers good diagnostic precision for lupus anticoagulant detection in a group of patients where lupus anticoagulant identification is difficult due to ongoing anticoagulation.

Blood Coagulation Tests↗

Transfer-function analysis of UFCT myocardial time-density curves by time-varying recursive least squares analysis.

Techniques which assume linear, time-invariant systems have been used to characterize indicator dilution pairs. As a basis for fully describing the relation between left ventricular (LV) and myocardial (MYC) time-density curves, produced by an intravenous contrast medium as measured by ultrafast CT, the assumption of time invariance was tested using recursive least squares regression and CUSUM, a test for time variability of regression parameters. Using data from anesthetized dogs with concomitant microsphere information, constant and time-varying regression models, MYC(t) = b(t)LV(t-1), were generated from time-density curves of flows from two groups: Group 1 (MBF < 2 ml/min/gm, n = 11) and Group 2 (MBF > 2 ml/min/gm, n = 10). The time-varying regression models had reduced root mean square error: 0.6 +/- 1.1 and 0.5 +/- 0.8 versus 7.3 +/- 3.5 and 4.1 +/- 1.6 for Groups 1 and 2, respectively. Significant time variability (p < 0.05) by CUSUM was found in 9/11 Group 1 models and 7/10 Group 2 models. Myocardial blood volume was estimated as the average value of b(t) over the rising portion of the LV curve. Myocardial blood flow was then calculated as myocardial blood volume divided by coronary transit time, determined from gamma variate fits of the LV and scaled, shifted LV curve, with excellent results over a wide range of flows (r = 0.93, y = 0.92 x + 0.28, range of 0.4 to 6.7 ml/min/gm). These results show that measurements of increased myocardial blood flow are possible with an intravenous contrast media, and that movement of contrast medium from intravascular space to extravascular space occurs during the course of the contrast medium's first pass.

Animals↗

Applying the Cox proportional hazards model when the change time of a binary time-varying covariate is interval censored.

This paper develops methodology for estimation of the effect of a binary time-varying covariate on failure times when the change time of the covariate is interval censored. The motivating example is a study of cytomegalovirus (CMV) disease in patients with human immunodeficiency virus (HIV) disease. We are interested in determining whether CMV shedding predicts an increased hazard for developing active CMV disease. Since a clinical screening test is needed to detect CMV shedding, the time that shedding begins is only known to lie in an interval bounded by the patient's last negative and first positive tests. In a Cox proportional hazards model with a time-varying covariate for CMV shedding, the partial likelihood depends on the covariate status of every individual in the risk set at each failure time. Due to interval censoring, this is not always known. To solve this problem, we use a Monte Carlo EM algorithm with a Gibbs sampler embedded in the E-step. We generate multiple completed data sets by drawing imputed exact shedding times based on the joint likelihood of the shedding times and event times under the Cox model. The method is evaluated using a simulation study and is applied to the data set described above.

AIDS-Related Opportunistic Infections↗

Optimal sampling time after preparation of platelet concentrates for detection of bacterial contamination by quantitative real-time polymerase chain reaction.

BACKGROUND AND OBJECTIVES: A universal quantitative real-time polymerase chain reaction (PCR), based on bacterial 16S rDNA, to detect bacterial contamination of platelet concentrates (PCs), was developed previously and compared with automated culturing. In the present study, this real-time PCR method was evaluated to determine the optimal sampling time for screening of bacterial contamination in PCs. MATERIALS AND METHODS: Routinely prepared PCs were spiked with suspensions of Escherichia coli, Bacillus cereus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Propionibacterium acnes to 1, 10 and 100 colony-forming units (CFU)/ml and stored at room temperature for 7 days. The presence of bacteria in these PCs was monitored by quantitative real-time PCR. As a reference method (additional control), BacT/Alert automated culturing was used. For PCR, 1-ml aliquots were drawn from all (spiked) PCs on days 0, 1, 2, 3, 6 and 7 of storage. As a control, triplicate samples (10 ml) were inoculated into aerobic and anaerobic BacT/Alert culture bottles immediately after spiking (day 0) and after storage for 1, 2, 3, 6 or 7 days. RESULTS: With quantitative real-time PCR, all bacterial species tested were reproducibly detected on day 1 after spiking at original concentrations of 10 and 100 CFU/ml. Bacteria were also detected on day 1 from PCs spiked with an initial concentration of 1 CFU/ml, except for E. coli, which was detected in only one of the three samples and P. aeruginosa, for which analysis was not performed on day 1. With the reference method, bacteria were detected in culture bottles (inoculated on day 0) within a mean time of 20.1 h, with the exception of P. acnes which was detected at a mean time of 102.3 and 49.3 h (for original spiking concentrations of 10 and 100 CFU/ml respectively). CONCLUSIONS: PCR enables the rapid detection of low initial numbers of bacteria in PCs. For reliable detection, our results support that sampling of PCs for real-time PCR screening should not be carried out earlier than 1 day after preparation (48 h after blood collection). Importantly, the real-time PCR approach has the potential to be used before the release of PCs from the blood centre or shortly before they are transfused in the hospital.

Bacteria↗

Changes in reaction time and search time with background luminance in the mesopic range.

Vision relies on both rod and cone signals over a large range of ambient illumination that encompasses a number of common situations. It is important, therefore, to understand how performance changes with light level in functional visual tasks. We measured reaction times and search times using achromatic targets to examine the relationship between latency and luminance contrast as a function of background luminance. Visual search was more robust to changes in luminance than reaction time; search performance could be made invariant by scaling the effects of contrast, but the range of reaction time changed significantly over the mesopic range. We also investigated the extent to which two mesopic visual performance models described the dependence of reaction time and search time on stimulus spectra, using coloured stimuli. The 'effective contrast' model that we examined described the spectral dependence of both reaction time and search time well. A model for mesopic luminous efficiency based on reaction times described the spectral dependence of each response only in conditions where there was little influence of chromatic signals.

Adult↗

Time in health: can we measure individuals' "pure time preferences"?

The time dimension in health is assessed and/or explained using the concept of time preference, i.e., preferences about when things occur or the timing of an outcome. It is believed that an individual's time preference can be relatively easily measured. This paper argues that individuals' responses to time-preference-type questions may represent not only their attitudes toward the timing of events (i.e., the points in time at which they are going to occur) but also their attitudes toward other things, such as the sequence of events (i.e., the order of good and bad events over an individual's lifetime health profile). This paper explains the distinction between the time-preference and sequence-preference concepts. Using two recent empirical studies, it demonstrates the inability to measure individuals' pure time preferences. The implications of this empirical obstacle in the context of medical decision making and health-care program evaluation are discussed.

Attitude to Health↗

Hydrophilic excipients modulate the time lag of time-controlled disintegrating press-coated tablets.

An oral press-coated tablet was developed by means of direct compression to achieve the time-controlled disintegrating or rupturing function with a distinct predetermined lag time. This press-coated tablet containing sodium diclofenac in the inner core was formulated with an outer shell by different weight ratios of hydrophobic polymer of micronized ethylcellulose (EC) powder and hydrophilic excipients such as spray-dried lactose (SDL) or hydroxypropyl methylcellulose (HPMC). The effect of the formulation of an outer shell comprising both hydrophobic polymer and hydrophilic excipients on the time lag of drug release was investigated. The release profile of the press-coated tablet exhibited a time period without drug release (time lag) followed by a rapid and complete release phase, in which the outer shell ruptured or broke into 2 halves. The lag phase was markedly dependent on the weight ratios of EC/SDL or EC/HPMC in the outer shell. Different time lags of the press-coated tablets from 1.0 to 16.3 hours could be modulated by changing the type and amount of the excipients. A semilogarithmic plot of the time lag of the tablet against the weight ratios of EC/SDL or EC/HPMC in the outer shell demonstrated a good linear relationship, with r = 0.976 and r = 0.982, respectively. The predetermined time lag prior to the drug release from a press-coated tablet prepared by using a micronized EC as a retarding coating shell can be adequately scheduled with the addition of hydrophilic excipients according to the time or site requirements.

Compressive Strength↗

Relations between the inflection point on the force-time curve and force-time parameters during static explosive grip.

Individual differences in muscle contractile speed during static explosive muscle contraction are reflected in the developmental phase of the force-time curve. The purposes of this study were to clarify the properties and reliability of the inflection point of force-time, statistically dividing speed during static explosive grip into two phases and to assess the relations between that inflection point and others. Static explosive grip data were measured two times with a 5-min. rest (sampling frequency; 100 Hz). 32 healthy, young men (age: 15.5 +/- 0.8 yr., height: 173.9 +/- 7.3 cm, body mass: 71.5 +/- 11.2 kg) participated. 8 static explosive grip parameters were selected: time of reaching, integrated area, and quotient values of the integrated areas up to 0.25, 0.5, and 1.0 sec. divided by maximal grip force. The inflection point was calculated statistically from two regression lines fitted to a developmental phase and the almost steady-state phase of reaching maximal grip force by applying a two-phase regression model. The reliabilities of maximal grip force, time of reaching 90% of maximal grip force, and the integrated area until 0.5 sec. and 1.0 sec. after the onset of grip were good (ICC=.77 to .93). The time of reaching an inflection force value appeared at 0.3 sec. after the onset of grip, corresponding to 80% of maximal grip force, and the reliabilities of the parameters regarding inflection point were good (ICC=.77 to .95). The time determined by boundary data between the former and the latter regression data set and the regression coefficient during the developmental phase correlated significantly with the time of reaching 90% of maximal grip force, the integrated area, and the quotient values of the integrated areas up to 0.25, 0.5, and 1.0 sec. divided by maximal grip force (rs=-.78 to -.96 and -.75 to 0.88, respectively, p<.05). However, these parameters did not correlate with maximal grip force. A force during the developmental phase and maximal grip force can depend on different physiological factors. The time determined by boundary data between the former and the latter regression data set and the regression coefficient during the developmental phase are useful parameters for evaluating static explosive grip.

Body Mass Index↗

Time and incidence of ovulation and conception rates after incorporating estradiol cypionate into a timed artificial insemination protocol.

Two experiments were conducted to determine the effect of estradiol cypionate (ECP), when incorporated into a conventional GnRH-PGF(2alpha)-GnRH timed artificial insemination protocol (Ovsynch), on systemic estradiol (E(2)), time and incidence of ovulation, luteal development, and conception rate in Holstein cows. Our objective was to determine if administration of 0.25 mg of ECP at the time of the second GnRH injection would effectively synchronize ovulation and increase conception rate. In Experiment 1, lactating Holstein cows (n = 23; 58.7 +/- 1.2 d in milk) were synchronized with PGF(2alpha) (at d -10). Ten days later, Ovsynch was initiated with the administration of 100 mug of GnRH (d 0) followed by PGF(2alpha) on d 7. On d 9, cows were assigned randomly to be treated with either GnRH + 0.25 mg of ECP (OVS-ECP; n = 11) or GnRH and 1 mL of cottonseed oil (OVS-C; n = 12). Ovarian activity was monitored by ultrasonography on d 0, 7, and 9. To determine the time of ovulation, ultrasound examinations were conducted at 12 and 20 h posttreatment and then at least every 3 h until either 36 h posttreatment or ovulation was observed. Blood samples were collected on d 0, 7, 9, and 16 for progesterone analysis. Blood samples also were collected at the time of treatment (d 9, 0 h) and at 6, 12, 20, and 28 h for E(2) analysis. Incidence of ovulation did not differ between treatments. Mean ovulation time relative to the second GnRH administration was similar between treatments. Serum progesterone concentration did not differ between treatments at any time. Serum E(2) concentration was not different at the time of treatment (0 h); however, mean E(2) concentration was greater for the OVS-ECP group at 6 and 12 h after treatment compared with OVS-C. In Experiment 2, lactating dairy cows (n = 333) in 3 commercial herds were randomly assigned to OVS-ECP (n = 169) or OVS-C (n = 164). Cows were inseminated 22 to 24 h posttreatment. Conception rates did not differ between treatments. Estradiol cypionate treatment was successful in increasing serum E(2) when administered at the time of the second dose of GnRH in the Ovsynch protocol. Conception rates, however, were not affected by treatment.

Animals↗

Effect of time to complete remission on subsequent survival and disease-free survival time in AML, RAEB-t, and RAEB.

The authors examined the relationship between the time required to enter complete remission (CR) after a first course of chemotherapy for newly diagnosed acute myeloid leukemia (AML), refractory anemia with excess blasts in transformation (RAEB-t), or refractory anemia with excess blasts (RAEB). They also examined subsequent survival time and disease-free survival time after accounting for cytogenetic status, age, and treatment. The data set consisted of 1101 patients with these diagnoses treated at the M. D. Anderson Cancer Center between 1980 and 1996 for whom outcomes were established after first-course therapy. Of the 1101 patients, 740 (67%) were in CR after this time; 508 of these 740 (69%) have died (80% had disease recurrence before death). The authors used the parametric model of Shen and Thall to estimate, in particular, T(C) (time to CR), T(C,D) (time from CR to death = residual survival after CR), and T(C,R) (residual disease-free survival [DFS] after CR) as functions of the covariates noted above and to estimate the dependence of T(C,D) and T(C,R) on T(C). There was a strong inverse association between T(C) and both T(C,D) and T(C,R) (P <.001 for both) that was independent of cytogenetic status, age, or treatment. The residual survival time of patients who required >50 days to enter CR was closer to the residual survival time of resistant patients than to that of patients known to be in CR within approximately 30 days of the start of treatment. Time to CR is an independent predictor of residual survival and disease-free survival in patients with newly diagnosed AML who achieve CR after 1 course of chemotherapy. (Blood. 2000;95:72-77)

Age Factors↗

Qualitative insights into practice time management: does 'patient-centred time' in practice management offer a portal to improved access?

BACKGROUND: Different sets of literature suggest how aspects of practice time management can limit access to general practitioner (GP) care. Researchers have not organised this knowledge into a unified framework that can enhance understanding of barriers to, and opportunities for, improved access. AIM: To suggest a framework conceptualising how differences in professional and cultural understanding of practice time management in Auckland, New Zealand, influence access to GP care for children with chronic asthma. DESIGN OF STUDY: A qualitative study involving selective sampling, semi-structured interviews on barriers to access, and a general inductive approach. SETTING: Twenty-nine key informants and ten mothers of children with chronic, moderate to severe asthma and poor access to GP care in Auckland. METHOD: Development of a framework from themes describing barriers associated with, and needs for, practice time management. The themes were independently identified by two authors from transcribed interviews and confirmed through informant checking. Themes from key informant and patient interviews were triangulated with each other and with published literature. RESULTS: The framework distinguishes 'practice-centred time' from 'patient-centred time.' A predominance of 'practice-centred time' and an unmet opportunity for 'patient-centred time' are suggested by the persistence of five barriers to accessing GP care: limited hours of opening; traditional appointment systems; practice intolerance of missed appointments; long waiting times in the practice; and inadequate consultation lengths. None of the barriers is specific to asthmatic children. CONCLUSION: A unified framework was suggested for understanding how the organisation of practice work time can influence access to GP care by groups including asthmatic children.

Adult↗

Time delay-adjusted survival benefit of angioplasty over thrombolysis in acute myocardial infarction: influence of time from symptom onset.

BACKGROUND: The time-to-treatment is a critical determinant of outcome after acute myocardial infarction. We investigated the relationship between the primary angioplasty (PCI)-related time delay and the benefit of PCI over thrombolytic therapy (TT), considering the time elapsing from symptom onset in 21 randomized trials comparing PCI to TT. METHODS: PCI-related time delay was calculated as the median of the "door-to-balloon" time minus the median of the "door-to-needle" time. The survival benefit was defined as the difference between 30-day mortality after TT and after PCI. The relationships between time delay and benefit were assessed by linear regression. RESULTS: PCI-related time delay ranged from 7 to 104 min. Linear regression showed that at a PCI-related delay of 75 min, PCI and TT yielded equivalent reductions in mortality (p = 0.03). When the trials with the longest and shortest delays were excluded, the benefit of PCI over TT was nullified after a delay of 62 min, and every additional 10-min delay produced a 1.1% increase in mortality (p = 0.01). When trials with a symptom duration < 6 hours (median 130 min) were considered, PCI-related delay still correlated with an absolute risk reduction in 30-day mortality with a time to equipoise of 57 min (p = 0.03). Lack of correlation (p = 0.85) was observed in trials enrolling patients within 12 hours of symptom onset (median 185 min). CONCLUSIONS: Our analysis suggests that PCI-related delay substantially modifies the benefit of PCI over TT, particularly in case of patients presenting early following symptom onset.

Angioplasty↗

Influence of time interval between administration of chloramphenicol and thiamylal on the sleeping time of mice.

The influence of the time interval between chloramphenicol and thiamylal administrations on the sleeping time of mice was studied. Two hundred 20- to 25-g mice were given (intraperitoneally) chloramphenicol or isotonic saline solution and then thiamylal at different time intervals between drugs. The duration of anesthesia was measured as the time between the loss and the return of the righting reflex. The results indicated that in mice given chloramphenicol simultaneously with thiamylal (0 time interval), the sleeping time was increased by a factor of about 10 as compared with the sleeping time in mice given thiamylal alone. As the time interval between administrations of thiamylal and chloramphenicol was increased (from 0.25 to 4 hours), the prolongation of sleeping time decreased correspondingly.

Animals↗