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PubMed2005

Prospective budgeting for home care: making titration work.

OBJECTIVE: To provide a model for prospective budgeting for home care that is plausible, coherent, flexible, and sufficiently tractable that it can serve as a template for practical decision making and to clarify what would be the data requirements and statistical framework to calibrate the model. METHODS: Methods used are standard risk-neutral expected value theory, cost benefit analysis, and the conditional logistic probability model. RESULTS: A simple but effective prospective budgeting model that provides analytic scaffolding for a practical decision support system for home care case managers, consultants, and program evaluators that can improve program equity, efficiency, and effectiveness. DISCUSSION: The author criticizes the well-known Titration Budgeting Model of Weissert, Chernew, and Hirth in terms of its logical and operational problems but then goes on to develop a framework within which the goals of the titration model can be met and home care resources can be more efficiently allocated.

Aged↗
PubMed1985

Prophylaxis of stress ulcers: antacid titration vs. histamine2-receptor blockade.

The near universal occurrence of stress ulcers in critically ill patients emphasizes the need for early and effective prophylaxis. Intraluminal gastric acidity, ischemic insult to the bowel, and the presence of stress factors are the major precipitants of stress ulcers. The use of H2-receptor antagonists vs. antacid titration for stress ulcer prophylaxis is reviewed. The goals of preventive therapy are to eliminate the stress factors and to maintain intragastric pH greater than 5. Hourly gastric pH monitoring and antacid titration are the mainstay of stress ulcer prophylaxis, with high potency antacids being the preferred agents. H2-receptor antagonists may serve as adjuncts in patients requiring large doses of antacids or having acid-base abnormalities from high gastric output states.

Antacids↗
PubMed2005

Use of heated humidification during nasal CPAP titration in obstructive sleep apnoea syndrome.

Nasal symptoms associated with the use of nasal continuous positive airway pressure (nCPAP) in obstructive sleep apnoea (OSA) can adversely impact on patients' tolerance, acceptance and adherence to nCPAP therapy. Regular use of heated humidification is effective in alleviating these symptoms and improve patient comfort. In a randomised, parallel, double-blinded, controlled study, the present authors examined the use of heated humidification during a single night laboratory nCPAP titration in untreated OSA patients and its effect on nasal symptoms, nasal airway resistance (NAR), effective pressure and treatment tolerability and acceptance. Baseline characteristics of subjects (n=70) receiving placebo and humidification were (mean+/-sem): age 51.2+/-2.2 versus 50.6+/-1.6 yrs; body mass index 33.6+/-0.9 versus 35.2+/-0.9 kg.m-2; Epworth Sleepiness Scale 10.8+/-1.0 versus 11.3+/-0.7; and apnoea-hypopnoea index 43.5+/-4.6 versus 44.4+/-4.1 events.h-1. Total inspiratory NAR, before (0.36+/-0.09 (placebo) versus 0.33+/-0.09 kPa.L-1.s-1) and after nCPAP (0.47+/-0.11 versus 0.29+/-0.04 kPa.L-1.s-1) were not significantly different between the groups. No difference was found in the frequency and severity of nasopharyngeal symptoms, therapeutic pressure and subjective response to nCPAP. In conclusion, heated humidification during the initial nasal continuous positive airway pressure titration offers no additional benefit in nasal physiology, symptoms or subjective response to nasal continuous positive airway pressure, and, therefore, should not be routinely recommended.

Adult↗
PubMed1996

Comparison of inhaled salmeterol and individually dose-titrated slow-release theophylline in patients with reversible airway obstruction. European Study Group.

The aim of this study was to compare the clinical efficacy of salmeterol versus theophylline in the treatment of moderate-to-severe asthma. One hundred and eighty nine asthmatic patients (forced expiratory volume in one second (FEV1) or peak expiratory flow (PEF) >50% of predicted) were randomized to receive either salmeterol dry powder, 50 microg b.i.d. via a Diskhaler (n=92) or dose-titrated slow-release theophylline capsules ("Theo-Dur") b.i.d. (n=97), in a double-blind, double-dummy, parallel group study for 4 weeks. Patients had previously been titrated with theophylline to a serum theophylline level of 10-20 microg x mL-1. The median percentage of nights with no asthma symptoms rose from 14% in both groups at baseline to 71% with salmeterol and to 46% with theophylline (p=0.044). There was also a significant increase for salmeterol in the median percentage of nights with no rescue salbutamol use (from 36 to 86%) compared with theophylline (from 71 to 78%; p=0.002). The mean morning PEF increased from 337 L x min-1 in the salmeterol group and 332 L x min-1 in the theophylline group to 372 and 357 L x min-1, respectively. No significant difference between the two treatments was observed for PEF, symptoms or additional salbutamol medication during the day. The incidence of gastrointestinal symptoms (gastric irritation, nausea and vomiting) was greater among patients receiving theophylline (11%) than with salmeterol (3%). These findings suggest that inhaled salmeterol is more effective in relieving symptoms of asthma, and better tolerated than theophylline in patients with moderate-to-severe asthma.

Administration, Inhalation↗
PubMed1993

Intranasal meperidine titration for postoperative pain relief.

A prospective, randomized, double-blind study investigating the efficacy of intranasal meperidine as compared with intravenous (i.v.) administration for postoperative pain relief is described. The study was limited to the initial titration of pain relief during a 2-h period immediately after surgery. Sixty women having undergone a hysterectomy were studied. Initially and when complaining of a pain intensity > or = 40 on the 101-point numerical rating scale (NRS), 30 patients received 6 sprays (27 mg) meperidine intranasally and simultaneously 6 mL NaCl 0.9% i.v. (nasal group); another 30 patients received 6 sprays of NaCl 0.9% intranasally and 6 mL of a diluted meperidine solution (27 mg) i.v. (intravenous group). Patients already having a pain reduction < 40 on the 101-point NRS, received half of the above dose. Meperidine was repeated every 5 min until the patients were pain free or refused further analgesic. Before the onset of meperidine titration and at 5- to 10-min intervals for 2 h thereafter, pain was evaluated with a 101-point NRS and a verbal rating scale. Within 20 and 35 min the pain scores evaluated by the NRS and verbal rating scale decreased in the intravenous and nasal group to a median of zero. The total dose of meperidine was 76.5 mg (range, 40.5-135.0) in the intravenous group and 104.4 mg (range, 27-135.0) in the nasal group (P < 0.05). One patient in each group showed a brief decrease in arterial hemoglobin oxygen saturation to < 90%. No patient complained of pain or burning in the nose.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1994

Anesthetic and hemodynamic effects of single bolus versus incremental titration of hyperbaric spinal lidocaine through microcatheter.

This study examined anesthetic development and hemodynamic changes during two techniques of hyperbaric lidocaine administration through 27-gauge intrathecal catheters for continuous spinal anesthesia in 55 elderly patients undergoing transurethral prostatic resection. Twenty-five patients were randomly assigned to receive hyperbaric lidocaine 5% solution in a single bolus of 75 mg to achieve blockade to approximately T6, and 30 patients to receive hyperbaric lidocaine 2.5% solution in increments of 25 mg to achieve T6 or to a maximum of three doses. Hemodynamic measurements of arterial pressure, heart rate, cardiac output, stroke volume, and ejection fraction were made serially after the induction of spinal anesthesia. Anesthesia failed to spread beyond the sacral region in 9/25 (36%) patients in the single-dose group (SD), but was successfully induced in all patients given titrated doses (TD) at total doses of 50 mg (n = 15) (TD50) and 75 mg (n = 15) (TD75). The mean maximal level of sensory block in all three groups was comparable: T5, T4, and T6 in groups SD, TD50, and TD75, respectively. The onset and progression of sensory block were rapid and similar in the SD and TD50 groups, in contrast to a gradual, stepwise development of block in group TD75. Grade 3 motor block occurred in response to the first dose of 25 mg lidocaine in 7/30 (23%) patients receiving titrated doses, but the overall incidence of leg paralysis did not differ among the three groups by the end of lidocaine dosing. Mean arterial pressure (MAP) decreased significantly relative to baseline in all three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Interaction of bleomycin with deoxyribonucleic acid oligomer: proton nuclear magnetic resonance titration study using novel bleomycin complexes with Ni2+ and VO3+.

Two metal complexes of bleomycin (BLM), BLM-Ni2+ and BLM-VO3+ are used for studying interactions between BLM and deoxyribonucleic acid (DNA) by nuclear magnetic resonance. Although these BLMs do not mediate DNA strand scission under the usual conditions, they bind to DNA in the same manner as the active metal complexes of bleomycin (BLM-Fe2+ and BLM-Co3+). A self-complementary dodecanucleotide, d(CCCCAGCTGGGG), having a single site for cleavage was synthesized. d(CCCCAATTGGGG), which contains no -GpC- sequence, was also synthesized. The BLM-metal complexes were shown to bind specifically to the GpC site by circular dichroism and fluorescence titration studies. We assigned all the resonances for imino protons and phosphorus, and most of the nonexchangeable proton resonances of d(CCCCAGCTGGGG). No substantial change in the chemical shifts of these signals was observed upon titration with either BLM-Ni2+ or BLM-VO3+. This result is not consistent with a model of the strong intercalation of the BLMs between the base-pairs. The BLMs bind to DNA in a different manner, and DNA does not change its conformation upon binding with BLMs.

Base Sequence↗
PubMed2001

Abdominal muscle activity in sleep apnea during continuous positive airway pressure titration.

STUDY OBJECTIVES: The aim of this study was to investigate whether presence of expiratory abdominal muscle activity (EAMA) in obstructive sleep apnea syndrome (OSAS) patients during nasal continuous positive airway pressure (nCPAP) is due to either nCPAP overprescription or nCPAP underprescription. DESIGN: Airflow, esophageal pressure (Pes), and gastric pressure (Pga) were routinely measured during polysomnography aimed at determining the optimal nCPAP level, and the magnitude of EAMA was evaluated in relation to the nCPAP level and to the conventional indexes of upper-airway obstruction used during nCPAP titration. PATIENTS: The study was performed 12 patients with OSAS. RESULTS: Six patients displayed sustained EAMA, ie, EAMA lasting > 3 min, and characterized by a decrease in abdominal diameter and a paradoxical rise in Pga during expiration. In all six patients, EAMA decreased gradually as nCPAP neared optimal levels, and then disappeared when the optimal nCPAP level was achieved. The decrease in EAMA as nCPAP increased was associated with an increase in minute ventilation, decreases in both inspiratory and expiratory resistance, a decrease in Pes swing, and the normalization of the inspiratory flow contour. CONCLUSIONS: We conclude that the EAMA observed in some OSAS patients might be an indirect marker of upper-airway obstruction, and that the presence of EAMA during nCPAP titration might indicate a suboptimal nCPAP level rather than a deleterious effect of nCPAP.

Abdominal Muscles↗
PubMed2004

Mandibular advancement titration for obstructive sleep apnea: optimization of the procedure by combining clinical and oximetric parameters.

BACKGROUND: Oral appliances (OAs) have been used for the treatment of obstructive sleep apnea syndrome (OSAS), with different degrees of effectiveness having been shown in previous studies. But, in the absence of a consensual recommendation, the method of the determination of effective mandibular advancement varies from one study to another. STUDY OBJECTIVE: We prospectively evaluated an OA titration protocol based on a combined analysis of symptomatic benefit and oximetric recording to guide the progressive mandibular advancement. SETTING: University hospital sleep disorders center. PATIENTS: Forty patients with OSAS (mean [+/-SD] apnea-hypopnea index [AHI], 46 +/- 21 events per hour) found on baseline polysomnography, who were intolerant of nasal continuous positive airway pressure, completed all aspects of the study. METHODS: Two acrylic appliances connected by Herbst attachments were constructed. The mandible was advanced 1 mm every week until there was a resolution of the symptoms and a reduction in the oxygen desaturation index (ie, the number of desaturations yielding a > 3% fall in pulse oximetric saturation per hour of recording) [ODI] of <10 events per hour of recording or a maximum comfortable limit of advancement was obtained. The final response to OA was evaluated by full polysomnography recording. RESULTS: A complete response (ie, mean AHI, 5 +/- 3 events per hour; mean snoring reduction [SR], 91 +/- 13%; mean Epworth sleepiness scale [ESS] score, 5 +/- 3) was obtained in 63.6% of patients, and a limited response (ie, mean AHI, 21 +/- 11 events per hour; mean SR, 88 +/- 15%; mean ESS, 6 +/- 3) was obtained in 18.2% of patients. Twenty-five percent of mandibular advancements were motivated by an abnormal ODI (ie, 21 +/- 10 events per hour) despite resolution of the symptoms, while 20% were motivated by persistent symptoms with a normal ODI (ie, 6 +/- 2 events per hour). After a mean duration of 17 +/- 4 months, 34 patients declared that they had used the OA 5 +/- 2 days a week for 89 +/- 19% of their sleep time. CONCLUSIONS: A combination of the patient's subjective evaluation and oximetric score improves the effectiveness of the OA titration procedure.

Female↗
PubMed1986

Oxygen therapy titrated to raise mixed venous oxygen content in COPD.

Supplemental oxygen therapy delivered at concentrations which increase PaO2 greater than 60 mm Hg often has minimal effects on either pulmonary hemodynamics or the oxygen tension of mixed venous blood (PvO2). Since mixed venous hypoxemia has been shown to contribute to pulmonary vasoconstriction in experimental conditions and is a determinant of survival in chronic obstructive pulmonary disease (COPD), we evaluated the hemodynamic effects of oxygen therapy titrated to raise PvO2 in 12 COPD patients who underwent right heart catheterization. After room air measurements of mean pulmonary artery pressure, cardia output, and pulmonary vascular resistance, they were randomized to either supplemental oxygen therapy given to raise PaO2 greater than or equal to 60 mm Hg (group 1, n = 6) or to raise PvO2 greater than or equal to 36 mm Hg (group 2, n = 6). An oxygen-conserving nasal cannula and oxygen concentrator were used. Baseline PaO2, PvO2, and hemodynamics were identical in each group and hemodynamics after four hours and 48 hours of continuous oxygen therapy were unchanged. Ten patients were catheterized after four months of continuous oxygen therapy (group 1, n = 4; group 2, n = 6). Although PvO2 in group 2 had been raised to normal levels (39.2 +/- 1.2 mm Hg), there was no significant improvement in pulmonary hemodynamics. Our preliminary study suggests that oxygen titrated to raise PvO2 to the normal range has no greater hemodynamic effect than oxygen therapy as it is currently prescribed.

Aged↗
PubMed1987

Titration of continuous positive airway pressure by real-time dual oximetry.

The clinical utility of combined pulse and pulmonary artery oximetry (dual oximetry) in titrating continuous positive airway pressure (CPAP) therapy was tested in 17 patients with acute respiratory failure. The level of CPAP was altered in 2.5 cmH2O increments and decrements, while conventional measurements of cardiopulmonary function and continuous dual oximetry were performed. Then, optimum CPAP levels were selected using both techniques independently. The difference in optimum CPAP determined by the two methods was 0 cmH2O in ten of 17 patients, less than or equal to 2.5 cmH2O in 14 of 17 patients, and 5.0 to 7.5 cmH2O in the remaining three patients. When a difference existed, CPAP level determined with dual oximetry was consistently lower than the level selected by conventional means. The results indicate that the estimates of venous admixture and oxygen utilization coefficient obtained using dual oximetry provide sufficient information for rapid and accurate titration of CPAP in the majority of patients with acute respiratory failure.

Acute Disease↗
PubMed1990

Reliability of pulse oximetry in titrating supplemental oxygen therapy in ventilator-dependent patients.

Pulse oximetry is widely used in the critical care setting, but few studies have examined its usefulness in clinical decision making. One area where pulse oximetry might be useful is in the titration of fractional inspired O2 concentration (FIO2) in ventilator-dependent patients. Unfortunately, documented guidelines for this use do not exist, and in a survey of directors of intensive care units, we found that they employed a wide range of target O2 saturation (SpO2) values. Consequently, we undertook a study to determine if SpO2 could be reliably substituted for measurements of arterial O2 tension (PaO2) when adjusting FIO2 in ventilator-dependent patients. We examined a number of SpO2 target values in 54 critically ill patients aiming for a PaO2 of greater than or equal to 60 mm Hg, while minimizing the risk of O2 toxicity. In white patients, we found that a SpO2 target of 92 percent was reliable in predicting a satisfactory level of oxygenation. However, in black patients, such a SpO2 reading was commonly associated with significant hypoxemia (PaO2 as low as 49 mm Hg), and a higher SpO2 target, 95 percent, was required. In addition, inaccurate oximetry readings (ie, greater than 4 percent difference between SpO2 and direct SaO2 measurements) were more common in black (27 percent) than in white patients (11 percent, p less than 0.05). In conclusion, a SpO2 target of 92 percent was reliable when titrating supplemental O2 in white patients receiving mechanical ventilation; however, in black patients, such a SpO2 reading was commonly associated with significant hypoxemia, and a higher SpO2 target, 95 percent, was required to ensure a satisfactory level of oxygenation.

Black or African American↗
PubMed1991

The day-long antianginal effectiveness of nitroglycerin patches. A double-blind study using dose-titration.

This study was designed to determine the day-long antianginal effectiveness of nitroglycerin patches in the nitrate-exposed patient, as well as the doses required. Eight men with chronic stable angina, a positive treadmill test, and demonstrated responsiveness to long-term oral isosorbide dinitrate were studied after they had been taking effective doses of isosorbide dinitrate three times a day for at least two weeks. Treadmill exercise bouts were performed every 1 to 2 hours over 1 day, after the 8 am application of active nitroglycerin patches in a previously titrated dose, and on another day after application of placebo patches. Mean necessary effective patch dose was 125 sq cm (60 to 220 sq cm). Mean exercise duration to angina rose from 271 to 480 s (p less than 0.001) 1 hour after active patches, while resting systolic blood pressure fell from 122 mm Hg to 100 mm Hg (p less than 0.001). (After placebo patches: +19 s and -2 mm Hg, respectively.) Active patches were superior to placebo throughout the day, but in declining degree (by 94 s at 7 pm, p less than 0.05). Thus, nitroglycerin patches can provide a significant day-long antianginal effect in the patient with long-term exposure to nitrate. However, the need for large doses and individual titration may make this therapy impractical.

Administration, Cutaneous↗
PubMed2004

Characterization of protein-protein interactions by isothermal titration calorimetry.

Isothermal titration calorimetry (ITC) is a powerful technique to study both protein-ligand and protein-protein interactions. This methods chapter is devoted to describing protein-protein interactions, in particular, the association between two different proteins and the self-association of a protein into homodimers. ITC is the only technique that determines directly the thermodynamic parameters of a given reaction: DeltaG, DeltaH, DeltaS, and DeltaCP. Isothermal titration calorimeters have evolved over the years and one of the latest models is the VP-ITC produced by Microcal, Inc. In this chapter we will be describing the general procedure for performing an ITC experiment as well as for the specific cases of porcine pancreatic trypsin binding to soybean trypsin inhibitor and the dissociation of bovine pancreatic alpha-chymotrypsin.

Animals↗
PubMed1984

Active-site titration of horse urinary kallikrein.

Horse urinary kallikrein was titrated with the reagent 4-nitrophenyl 4-guanidino-benzoate. The titration was shown to be dependent upon the concentration of the titrant. This finding, which distinguishes horse urinary kallikrein from other enzymes, is explained by the relatively small ratio between its rate of acylation and deacylation (k2/k3 = 16.8) and by a low affinity of the reagent (Km = 1.16 microM). By an appropriate kinetic treatment, it was possible to establish the relationship between the hydrolysis of 4-nitrophenyl 4-guanidinobenzoate and the actual concentration of the active enzyme.

Animals↗
PubMed2006

Karl Fischer titration and coulometry for measurement of water content in small cartilage specimens.

This study evaluated the efficiency of Karl Fischer titration and coulometry for measurement of water content in small intact and defective cartilage specimens. Cartilage from the main weight-bearing zone of the medial condyle of 38 fresh sheep knees was used. Of these, 20 condyles had an intact cartilage, while defects (14 grade I and 4 grade II) were found in the rest. The mechanical hardness was determined as Shore A. Cartilage specimens of approximately 5 mg were analyzed in special devices for moisture measurement and then continuously heated up to 105 degrees C. The actual measurement was performed in an electric cell (coulometry). An electrode was laminated with hygroscopic phosphorus pentoxide. In the electrochemical reaction, H and O are liberated from the electrode. The requirement for electric energy correlates with the amount of water in the specimen. The water content in intact cartilage was 66.9%. Grade I (72.6%) and grade II (77.8%) defects had significantly higher water content. Significantly higher and faster spontaneous evaporation was observed in cartilage defects at room temperature. The water content and spontaneous water evaporation correlated with significantly lower mechanical hardness. The experimental design (combined method of thermogravimetry, Karl Fischer titration, and coulometry) was sufficient for evaluating the water content in small cartilage specimens. It is also possible to measure the temperature-dependent water liberation from cartilage specimens.

Animals↗
PubMed2004

Investigation of ligand binding to the multidrug resistance protein EmrE by isothermal titration calorimetry.

Escherichia coli multidrug resistance protein E (EmrE) is an integral membrane protein spanning the inner membrane of Escherichia coli that is responsible for this organism's resistance to a variety of lipophilic cations such as quaternary ammonium compounds (QACs) and interchelating dyes. EmrE is a 12-kDa protein of four transmembrane helices considered to be functional as a multimer. It is an efflux transporter that can bind and transport cytoplasmic QACs into the periplasm using the energy of the proton gradient across the inner membrane. Isothermal titration calorimetry provides information about the stoichiometry and thermodynamic properties of protein-ligand interactions, and can be used to monitor the binding of QACs to EmrE in different membrane mimetic environments. In this study the ligand binding to EmrE solubilized in dodecyl maltoside, sodium dodecyl sulfate and reconstituted into small unilamellar vesicles is examined by isothermal titration calorimetry. The binding stoichiometry of EmrE to drug was found to be 1:1, demonstrating that oligomerization of EmrE is not necessary for binding to drug. The binding of EmrE to drug was observed with the dissociation constant (K(D)) in the micromolar range for each of the drugs in any of the membrane mimetic environments. Thermodynamic properties demonstrated this interaction to be enthalpy-driven with similar enthalpies of 8-12 kcal/mol for each of the drugs in any of the membrane mimetics.

Antiporters↗
PubMed2001

An institution-specific heparin titration nomogram: development, validation, and assessment of compliance.

STUDY OBJECTIVE: To develop, validate, and assess compliance with a heparin titration nomogram. DESIGN: Prospective, open-label trial. SETTING: University teaching hospital. SUBJECTS: Patients admitted with heart failure who required therapy with intravenous unfractionated heparin. Intervention. An in vitro concentration-response was determined by measuring activated partial thromboplastin times (aPTTs) on normal pooled plasma containing known concentrations of heparin. The therapeutic aPTT range was determined from the concentration-response by using the therapeutic heparin concentration range of 0.2-0.4 U/ml (protamine neutralization). Patients were consecutively enrolled, and therapy was managed by using the heparin titration nomogram. Paired aPTT-heparin concentrations were obtained, and nomogram validation was performed by comparing the in vitro and the ex vivo concentration-responses with use of linear regression. Nomogram compliance also was assessed. MEASUREMENTS AND MAIN RESULTS: The therapeutic aPTT ranges based on in vitro and ex vivo data were determined to be 45-72 seconds and 47-61 seconds, respectively. The ranges were significantly different (p<0.001). Overall compliance with the nomogram was 88%. CONCLUSION: These results confirm that, even in a relatively homogeneous disease-state patient population, in vitro data do not accurately predict ex vivo data. If in vitro data are used to develop an institution-specific nomogram, a validation procedure should be used to ensure accuracy. Although 100% compliance to a nomogram may not be attainable, it should be expected. Therefore, a compliance rate of 88% is concerning and suggests a need for increased nursing and physician education.

Anticoagulants↗