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Results for “dose titration”

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PubMed2002

A copula-based model for multivariate non-normal longitudinal data: analysis of a dose titration safety study on a new antidepressant.

A new model for multivariate non-normal longitudinal data is proposed. In a first step, each longitudinal series of data corresponding to a given response is modelled separately using a copula to relate the marginal distributions of the response at each time of observation. In a second step, at each observation time, the conditional (on the past) distributions of each response are related using another copula describing the relationship between the corresponding variables. Note that there is no need to consider the same family of distributions for these response variables. The technique is illustrated in a dose titration safety study on a new antidepressant. The haemodynamic effect on diastolic blood pressure, systolic blood pressure and heart rate is studied. These three responses are measured repeatedly over time on ten healthy volunteers during the dose escalation. The available covariates are sex and the concentration of drug in the plasma at time of measurement.

Antidepressive Agents↗

PubMed2004

Pre-prandial vs. post-prandial capillary glucose measurements as targets for repaglinide dose titration in people with diet-treated or metformin-treated Type 2 diabetes: a randomized controlled clinical trial.

OBJECTIVE: Repaglinide is an oral anti-diabetic agent that has a short duration of action, and is suitable for preventing post-prandial rises in glucose levels. Targeting post-prandial glucose levels may lead to lower HbA(1c) levels and rates of hypoglycaemia than targeting pre-prandial glucose levels. RESEARCH DESIGN AND METHODS: In 42 centres, 193 drug-naive (n = 122) or metformin-treated (n = 71) individuals with Type 2 diabetes were randomly allocated to a 40-day period of repaglinide dose-titration (starting at 0.5 mg three times daily) based on either self-measured pre-prandial or post-prandial glucose levels. They were followed for a further 12 weeks and HbA(1c) and hypoglycaemia rates were recorded. RESULTS: Repaglinide reduced HbA(1c) by 1.25 and 1.07% in the post-prandial and pre-prandial groups, respectively (P for difference = 0.6), and achieved target glucose levels in 80.7 and 66.7%, respectively (P = 0.16). The effect of titration strategy differed by baseline drug therapy, and was more effective in the metformin-treated individuals who experienced a HbA(1c) fall of 0.6 vs. 1.10% with pre-prandial vs. post-prandial titration (P for metformin-allocated group interaction = 0.043). The rate of hypoglycaemia did not differ by group. CONCLUSIONS: In drug-naive individuals with Type 2 diabetes, similar HbA(1c) levels are achieved with repaglinide when dosing is adjusted according to either post-prandial or pre-prandial levels. Conversely, in metformin-treated individuals, repaglinide dosing according to post-prandial levels may lead to better glycaemic control than dosing according to pre-prandial levels.

Adult↗

PubMed1989

Recainam dose titration and pharmacokinetics in patients with resistant arrhythmias.

Recainam, a new antiarrhythmic drug, was evaluated in 20 patients with drug-resistant stable ventricular arrhythmias. Dosage was increased stepwise every 48 to 72 hours until arrhythmia suppression, side effects, or a predetermined maximal dosage occurred. After a pharmacokinetic evaluation, efficacy was confirmed in a double-blind, crossover protocol. One patient had unusable ambulatory ECG data. There were 14 of 19 patients who responded during dose titration; efficacy was confirmed in 11 of 14. The mean effective dosage and trough plasma concentration were 427 mg every 8 hours and 1.83 micrograms/ml, respectively. One patient withdrew because of nausea. Slowing of intraventricular conduction necessitated dosage reduction in two patients. Plasma half-life was 9.4 +/- 4.1 hours, with renal elimination accounting for 62% of oral clearance. However, 66% of the variability in oral drug clearance was the result of nonrenal elimination. Oral recainam at dosages of 300 to 600 mg every 8 hours is effective in some drug-resistant ventricular arrhythmias and is well tolerated.

Administration, Oral↗

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↗

PubMed1990

A dose titration study evaluating terazosin, a selective, once-a-day alpha 1-blocker for the treatment of symptomatic benign prostatic hyperplasia.

The efficacy and safety of terazosin, a selective long-acting alpha-1-adrenergic blocker, were evaluated in 45 normotensive patients with symptomatic benign prostatic hyperplasia ranging from 50 to 76 years old. All patients underwent a complete urodynamic evaluation and transrectal prostatic ultrasonography before enrollment into the study. The dose of terazosin was titrated to 5 mg. per day for a 1-month interval, provided adverse drug reactions were not observed. Of the patients 39 (87%) completed the dose titration study. The parameters used to assess the effectiveness of terazosin included peak and mean urinary flow rates, micturition symptom scores and the global assessment by the patient of symptomatic improvement. Over-all, the mean systolic and diastolic blood pressures changed by less than 1%. The peak and mean urinary flow rates increased by 42 and 48%, respectively. The obstructive and irritative symptom scores improved by 63 and 35%, respectively. Over-all, 30 of the 45 participants (67%) indicated that the voiding symptoms were markedly improved while on terazosin. Five patients did not complete the dose titration study due to development of adverse drug reactions, including erectile dysfunction (7%), tiredness (7%), light-headedness (4%), palpitations (4%), nasal congestion (2%) and asymptomatic hypotension (2%). There were 25 patients (55%) followed on terazosin for 4 to 10 months (mean 6.5 months). The improvements in urinary flow rates and symptom scores were maintained for this interval. Although this preliminary experience with terazosin is encouraging, the ultimate role of terazosin for the long-term treatment of benign prostatic hyperplasia needs further evaluation.

Adrenergic alpha-Antagonists↗

PubMed2001

A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence.

PURPOSE: We compared the short-term efficacy, safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence. MATERIALS AND METHODS: Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study. Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent randomization to transdermal or oral treatment. Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily. Dose titration was based on anticholinergic symptoms. Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary, a visual analog scale for efficacy and anticholinergic symptoms reported on a questionnaire. Safety monitoring included adverse events and skin tolerability of the transdermal system. RESULTS: A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment. Mean age in the transdermal and oral groups was 64 and 63 years, and 87% and 97% were female, respectively. Daily incontinent episodes decreased in the transdermal and oral groups (7.3 to 2.4 [66%] and 7.4 to 2.6 [72%], respectively, p = 0.39). The visual analog scale reduction in urinary leakage improved from washout in both groups (p <0.0001) with no difference between them (p = 0.9). Dry mouth occurred in significantly fewer patients in the transdermal (38%) compared with those in the oral group (94%, p <0.001). Of the patients in the transdermal group 67% noticed a reduction in dry mouth severity compared with previous oral treatment, and 90% had none or mild skin erythema. CONCLUSIONS: Transdermal delivery of oxybutynin resulted in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence.

Administration, Cutaneous↗

PubMed1989

Terodiline: a dose titrated, multicenter study of the treatment of idiopathic detrusor instability in women.

Idiopathic detrusor instability is a common cause of lower urinary tract symptoms at all ages and in both sexes. Treatment initially is conservative and often includes drug therapy. Terodiline has the theoretical advantage of being a drug with anticholinergic and calcium channel blocking effects. Theoretically, by using a drug with dual action the beneficial effect of reduced detrusor overactivity might occur at a dosage below that likely to lead to the troublesome side effects experienced by patients who take pure anticholinergic agents. A total of 70 female patients completed a study characterized by extremely strict inclusion criteria and a tight protocol. Other novel elements to the study were the extensive use of urinary diaries for symptom evaluation, standardized urodynamic studies agreed upon by the participating centers and the dose titration design of the trial. Terodiline has been demonstrated to be a safe, well tolerated and effective drug in the treatment of idiopathic detrusor instability. Drug treatment led to significant decreases in urinary frequency and incontinence episodes. Pre-micturition symptoms, such as urgency, were markedly reduced and the voided volume was significantly increased. Although there were consistent trends towards greater improvement in the urodynamic measurements, when the terodiline and placebo groups were compared these did not reach statistical significance, partly due to a large improvement in the placebo group. Nevertheless, terodiline has been shown to be a useful drug for conservative management of patients with detrusor instability.

Adult↗

PubMed1988

Antihypertensive efficacy of cetamolol: a dose-titrated study.

This double-blind, placebo-controlled, randomized multicenter study evaluated the antihypertensive efficacy and safety of cetamolol hydrochloride in 108 patients diagnosed as having mild to moderate hypertension. After a placebo lead-in period, patients received either cetamolol 5-10-15 mg/d (low dose), cetamolol 15-25-50 mg/d (high dose), or placebo, once daily for four weeks. Patients began at the lowest dose and were titrated to higher doses based on the first two assessments of diastolic blood pressure and heart rate, which were conducted each week after double-blind treatment was dispensed. After four weeks of treatment 82.4%, 81.3%, and 93.3% of the low-dose group, high-dose group, and placebo group, respectively, were titrated to the maximum dose level. After four weeks of treatment and 24 hours since the patient's last dose, both cetamolol groups showed a significantly greater (P less than or equal to .05) reduction in supine systolic/diastolic blood pressure (-18.1 +/- 2.3/-9.2 +/- 1.5 mm Hg [low dose] and -17.3 +/- 2.3/-8.3 +/- 1.6 mm Hg [high dose]) than the placebo group (-9.9 +/- 2.5/-3.5 +/- 1.7 mm Hg). In general, the changes in standing (stabilized) systolic and diastolic blood pressure were similar to those seen in supine measurements. Significantly more patients receiving cetamolol than those receiving placebo showed a "good response" (a decrease in diastolic blood pressure of 10 mm Hg or more or measuring less than 90 mm Hg with a decrease of at least 4 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetamides↗

PubMed1997

Immunotherapy with standardized extract of Dermatophagoides pteronyssinus in bronchial asthma: a dose-titration study.

According to the maximum tolerated dose (MTD) achieved, we assessed the changes in clinical and laboratory parameters, induced by specific immunotherapy (SIT), in a group of 43 asthmatic patients sensitized to Dermatophagoides pteronyssinus, over a period of 18 months. A standardized extract (100 Bu/ml; 40 micrograms/ml of Der p 1; 20 micrograms/ml of Der p 2) was used. The patients were divided into two groups: the high-dose immunotherapy (HDI) group (MTD > or = 4 micrograms Der p I) and the conventional immunotherapy (CI) group (MTD < 4 micrograms Der p 1). Changes in clinical severity index, medication, and symptom scores; in cutaneous and conjunctival reactivity; and in the levels of specific IgE, IgG, IgG1, and IgG4 to D. pteronyssinus (Der p 1 and Der p 2) were measured (ELISA monoclonal antibodies). Safety was monitored according to the EAACI guidelines. The range of the MTD was 0.8-16 micrograms of Der p 1. Ninety percent of the patients tolerated a dose of 3.2 micrograms, but only 18% of the patients reached a maintenance dose of 16 micrograms. The medians of the accumulated dose were 197 micrograms of Der p 1 for the HDI group, and 50 micrograms for the CI group. Conjunctival and cutaneous reactivity was significantly lowered (P < 0.001) after SIT, as were the clinical severity score and medication score in both groups, without significant differences between the groups, except for cutaneous reactivity. Levels of specific IgE decreased significantly (P < 0.01) in both groups, again without significant differences between the groups. The range of the increase in medians of specific IgG, IgG1, and IgG4 was 4.4-120-fold for the HDI group and 3-24-fold for the CI group (P < 0.01). The increase in the levels of Der p 1 and Der p 2 IgG4 were correlated to the changes in cutaneous and conjunctival reactivity (P < 0.01). These results show that a maintenance dose of 3.2 micrograms Der p 1 (8 BU) can induce pronounced clinical and immunologic changes with an excellent safety profile.

Adolescent↗

PubMed2004

Dipyridamole and headache--a pilot study of initial dose titration.

Headache is reported by about one third of patients using dipyridamole (DP) after stroke or TIA. No study has systematically examined if initial dipyridamole titration may affect this headache. We therefore randomised patients to (1) standard aspirin and dipyridamole treatment b.i.d. for 2 weeks or (2) titration with aspirin only in the morning and aspirin and dipyridamole in the evening for 5 days, followed by 9 days of standard aspirin and dipyridamole treatment. Among 57 patients included for analysis, moderate to severe headache was reported by 28% in the standard treatment group and 25% in the titration group (n.s.). Headache for more than two consecutive days occurred in 24% and 11%, respectively. Rescue medication because of headache for more than 2 days was used by 14% and 0% in the respective groups. The cumulative number of days with headache was more than twice as high in the standard treatment group. The total numbers of other side effects were 25 and 11 in the two groups. The observed differences in this pilot study were not statistically significant, but nevertheless suggest that titration with an initially lower dose of dipyridamole may be considered to reduce headache and thereby increase compliance. A larger study is needed to clarify this with sufficient statistical power.

Aged↗

PubMed2006

Does rapid dose titration affect the hepatic safety profile of Bosentan?

RATIONALE: Bosentan, a dual endothelin receptor antagonist, has proven efficacy in pulmonary hypertension. Due to an association with hepatic dysfunction, it is typically initiated at a sub-therapeutic dose for 4 weeks before titration to a therapeutic dose. At our institution some patients have undergone rapid titration, to potentially benefit from therapy earlier. This study assesses the impact of this practice on hepatic safety. METHOD: All patients initiated on bosentan therapy before April 2005 were included. Rapidly titrated patients achieved a therapeutic dose by 3 days, whereas standard titration patients were titrated at 4 weeks. All patients were monitored with monthly liver function tests. RESULTS: 149 patients commenced bosentan, of which 55 were rapidly titrated. At baseline, the two groups were similar in age, BMI, diagnosis, 6-min walking distance, alanine aminotransferase (ALT), cardiac index and pulmonary artery pressures. The rapid group had elevated right atrial pressures (9.7 mm Hg versus 7.4 mm Hg, p = 0.016) and worse WHO functional class (p = 0.008) and included less females (31% versus 69%, p = 0.024). The incidence of hepatic dysfunction in all patients was 12.8% at 12 months. There was no statistical difference in incidence between the rapid and standard groups (4% versus 11% at 3 months, p = 0.211 and 6% versus 15% at 12 months, p = 0.219). Of all patients on bosentan, hepatic dysfunction was most significantly associated with a higher baseline ALT (p = 0.021), female sex (p = 0.003) and underlying connective tissue disease (p = 0.025). Subgroup analysis suggested these factors were not confounders when comparing rapid and standard titration. CONCLUSIONS: Rapid and standard titration of bosentan resulted in similar hepatic safety profiles. Baseline ALT, female sex and the presence of connective tissue disease increased the risk of hepatic dysfunction independent of the titration method used.

Alanine Transaminase↗

PubMed1999

Pharmacokinetic, pharmacodynamic, and safety evaluation of an accelerated dose titration regimen of sotalol in healthy middle-aged subjects.

BACKGROUND: Current labeling recommends that therapy with sotalol be initiated in a monitored setting at 80 mg every 12 hours for 2 to 3 days, followed by 120 to 160 mg every 12 hours for at least 2 days before safety and efficacy can be ascertained and patients discharged. An accelerated titration regimen that shortens hospital stay without compromising patient safety would improve the usefulness of the drug. Although such regimens have been used by clinicians, they have not been formally evaluated. METHODS: Healthy, middle-aged sedentary men and women received sotalol in a double-blind, two-way crossover study with a 2-week washout phase to evaluate an accelerated titration regimen--placebo every 6 hours for four doses, followed by 80 mg sotalol every 6 hours for four doses, then 160 mg sotalol every 12 hours for nine doses--and compare it with the standard titration--placebo alternating with 80 mg sotalol every 6 hours for eight doses, followed by 160 mg sotalol every 12 hours for nine doses. QT intervals, RR intervals, and sotalol concentrations in plasma were measured at specific times throughout the study and during washout in a similar fashion for both regimens. RESULTS: Thirty-four subjects completed both regimens. The target prolongation of QTc (90% of the value achieved at steady state) was achieved 22 1/2 hours sooner with the accelerated titration regimen (P = .0003). There were no cardiovascular adverse events during either loading phase. At no time during the accelerated titration regimen did the sotalol concentrations in plasma or the QTc or RR interval prolongation exceed the values eventually achieved at steady state. The relationship between sotalol concentration and QTc was linear and independent of the regimen. CONCLUSION: The accelerated titration regimen for sotalol can shorten the time to attain the dosage usually required to effectively control arrhythmias, without excessive QT prolongation and the associated increased risk of torsades de pointes. The hospital stay of patients in whom antiarrhythmic therapy with sotalol is initiated can be shortened by 1 day if this accelerated titration regimen is used.

Adrenergic beta-Antagonists↗

PubMed1987

Hydrochlorothiazide with or without amiloride for hypertension in the elderly. A dose-titration study.

The blood pressure response to increasing doses of hydrochlorothiazide with or without amiloride was examined in 130 elderly hypertensive patients. After four weeks of placebo, patients were randomly allocated to increasing doses of hydrochlorothiazide or hydrochlorothiazide with amiloride for 12 weeks using a parallel, double-blind study design. Both hydrochlorothiazide and hydrochlorothiazide with amiloride significantly reduced mean (+/- SEM) baseline supine and standing blood pressure (171 +/- 2/102 +/- 1 and 167 +/- 2/102 +/- 1 mm Hg) to 148 +/- 2/84 +/- 1 and 146 +/- 3/85 +/- 1 mm Hg, respectively, at week 16. Amiloride did not exert any additional antihypertensive effect. Only eight patients required hydrochlorothiazide at 100 mg/d, with the remainder responding to 25 to 50 mg/d. Hydrochlorothiazide decreased mean serum potassium level from 4.3 +/- 0.1 mEq/L (4.3 +/- 0.1 mmol/L) during placebo to 4.0 +/- 0.1 mEq/L (4.0 +/- 0.1 mmol/L) at week 16. Ten patients receiving hydrochlorothiazide developed hypokalemia compared with only two receiving hydrochlorothiazide with amiloride. Relatively low doses of hydrochlorothiazide (25 to 50 mg/d) effectively reduce blood pressure in elderly hypertensive patients. Hypokalemia may occur with hydrochlorothiazide alone but is much less common when hydrochlorothiazide is combined with amiloride.

Aged↗

PubMed1998

Dose titration study of tinzaparin, a low molecular weight heparin, in patients on chronic hemodialysis.

The minimal necessary dose of Innohep (IH) (MNDI) (Innohep [tinzaparin], Leo Pharmaceutical Corp., Ballerup, Denmark) was examined in 40 patients switched from conventional heparin ([CH], Leo Pharmaceutical Corp.) to IH and in 13 patients already treated with IH. Clotting in the venous chamber and in the dialyzer was evaluated on a 4 point scale by visual inspection. IH was administrated as a bolus injection into the arterial side of the dialyzer at the beginning of dialysis sessions. The initial dose of IH was 50% of the total dose of CH used before the study (in respective IU). According to clotting in the venous chamber or dialyzer, the dose of IH was titrated by stepwise changes of 500 IU to the lowest possible dose until 3 subsequent dialysis sessions without clotting were obtained. The total dose of CH (bolus and infusion) before switching was 6,162 +/- 2,100 IU. The bleeding time from the cannulation site after dialysis, in 24 patients with A-V fistulas, was 7.1 +/- 2.8 min(triplicates). Eight patients were excluded before achieving the MNDI, 3 due to bleeding not clearly related to heparinization (1 due to gingival bleeding, 1 to epistaxis, and 1 to sugillations), 1 due to alopecia, 2 due to a need of more than 10,000 IU of IH, and 2 patients due to cessation of treatment resulting from anxiety. After switching over, the MNDI amounted to 66 +/- 26% in respective IU. The conversion IH/CH ratio correlated significantly to the blood flow rate and the type of dialyzer. When compared on 3 subsequent sessions before and after switching to IH, no differences were found in the bleeding time after decannulation and in clotting in the venous chamber while dialyzer clotting fell on the visual scale from an average of 0.36 to 0.19 (p < 0.01). No total clot formation was observed during the study. The MNDI correlated positively to the body weight, blood flow rate, and time on dialysis (with the respective coefficients of correlation of r being 0.58, 0.44, and 0.30, p < 0.05) and was also influenced by the type of dialyzer. The average MNDIs for the Hemoflow-FS hollow-fiber (Fresenius, Bad Homburg, Germany), Lundia PRO plate (Gambro, Lund, Sweden), and Polyflux hollow fiber (Gambro) were 2,571, 3,727, and 5,020 IU (p < 0.01, ANOVA). In patients on chronic hemodialysis, IH given as a bolus of 4,250 IU effectively prevented extracorporeal clotting during dialysis, similarly to CH. However, a considerable individual variation in MNDIs not related to the need for CH was observed, and this necessitates individual dosage adjustments to obtain the optimal prevention of clotting with minimal bleeding risk.

Anticoagulants↗

PubMed2001

An open-label dose-titration study of the efficacy and tolerability of tizanidine hydrochloride tablets in the prophylaxis of chronic daily headache.

OBJECTIVE: To assess effectiveness and safety of tizanidine hydrochloride tablets for the prophylaxis of chronic daily headache. BACKGROUND: Tizanidine hydrochloride is an alpha2-adrenergic agonist that inhibits the release and effectiveness of norepinephrine at both central sites (eg, the locus ceruleus) and the spinal cord. It acts as a central muscle relaxant and has antinociceptive effects. Preliminary research and retrospective analyses have suggested efficacy in treatment of both chronic tension-type headache and chronic daily headache with migrainous features. DESIGN: Thirty-nine patients with more than 15 headache days per month (33 with migraine, 5 migrainous, 1 chronic tension-type) completed a 4-week baseline, with 31 completing a planned 12 weeks of treatment with tizanidine. Dosing was titrated from 2 mg at bedtime to a median daily dose of 14 mg (mean, 13.5; SD, 4.3; range, 4 to 20, divided over three doses per day) by treatment week 4. RESULTS: The overall headache index through week 12 (headache frequency x average intensity x duration) declined significantly (P<.00000002), with a corresponding increase in mean percentage improvement from 49% for weeks 1 through 4, to 65% for weeks 5 through 8, and 64% for weeks 9 through 12 (P<.0182). During weeks 9 through 12, 67% had improved more than 50% compared to baseline. Overall headache frequency declined from 22.83 to 15.83 days per month (P<.00001), with frequency of severe headaches dropping from 7.52 to 3.58 days per month (P<.000035). Average headache intensity dropped from 1.83 to 1.07 (1-to-5 scale), peak intensity declined from 2.37 to 1.40, and mean duration was reduced from 6.96 to 4.00 hours per headache (P<.00001). Improvement also occurred on visual analog scales of overall headache status, mood, sleep, quality of life (P<.00001), and sexual function (P<.0075); as well as the Beck Depression Inventory-II (P<.00073). Mild-to-moderate adverse events reported by more than 10% of the patients included somnolence, asthenia, and dry mouth. Only 3 patients discontinued treatment due to adverse events: somnolence and dry mouth alone (n = 1), or in combination with either hyperkinesis (n = 1) or constipation (n = 1). One patient had elevated liver enzymes that returned to normal after the drug was discontinued. CONCLUSIONS: The results provide preliminary support for the efficacy, safety, and tolerability of tizanidine in the prophylaxis of chronic daily headache.

Adolescent↗

PubMed1989

Vibrotactile sensation and response to nifedipine dose titration in primary Raynaud's phenomenon.

The clinical response to two doses of sustained-release nifedipine was assessed during a double-blind, randomized, placebo-controlled trial in 22 patients with primary Raynaud's phenomenon. Nifedipine at doses of 20 mg and 40 mg daily reduced the mean number of attacks by 40% compared with placebo with no significant differences between the two doses in the number of attacks or their severity. Unwanted effects were more common and more persistent with the higher dose of nifedipine. Fingertip vibrotactile thresholds measured at 31.5 and 125 Hz were unchanged by treatment with nifedipine. There was, however, a correlation between the pretreatment threshold at 125 Hz and the response to treatment with nifedipine, the most favorable responses occurring in patients with the lowest thresholds.

Adolescent↗

PubMed1995

Subcutaneous epoetin beta in renal anemia: an open multicenter dose titration study of patients on continuous peritoneal dialysis.

OBJECTIVE: To establish dose requirements (target hemoglobin > 100 g/L) and safety of subcutaneously administered epoetin beta. DESIGN: Open multicenter study. PATIENTS: Forty-five anemic patients (21 female, 24 male; mean age 55 years; range 20-79 years) who had been on continuous peritoneal dialysis for 1-157 months (mean 24 months). Thirty patients required blood transfusions during the year prior to the study. Mean hemoglobin concentration pretreatment was 75 g/L (range 57-89 g/L). INTERVENTION: After a pretreatment period of two weeks, 60 IU kg-1 week-1 divided into three weekly doses of epoetin beta was administered subcutaneously. The dose was increased by 60 IU kg-1 week-1 after ten weeks, and when necessary, every fourth week in patients with hemoglobin levels below 100 g/L. MAIN OUTCOME MEASURES: Hemoglobin concentration. Analysis of factors affecting the response to epoetin beta. Safety of epoetin beta. RESULTS: Thirty-eight of the 45 patients completed six months and 21 patients completed one year in the study. Twenty-six patients reached hemoglobin 100 g/L within six months and 8 patients did later on. The mean hemoglobin concentration after three months was 93 g/L (range 64-144 g/L) and after six months was 99 g/L (range 59-130 g/L; mean epoetin beta dose 122 IU kg-1 week-1). During the second six-month period of the study, hemoglobin levels were stable in most patients. After one year, the mean hemoglobin was 110 g/L (range 84-153 g/L) and the mean epoetin beta dose was 107 IU kg-1 week-1. Prolonged correction time and impaired response to epoetin were observed in patients with infections or hemorrhages and in patients with low hemoglobin concentration before starting epoetin treatment. Iron deficiency was controlled by iron supplementation, either orally or, in 10 patients, intravenously. Increased blood pressure, requiring intensified antihypertensive treatment, was observed in 13 patients. CONCLUSIONS: Continuous peritoneal dialysis patients with moderate anemia (Hb 75-90 g/L) and without complicating disorders can be managed with subcutaneous doses of epoetin < 120 IU kg-1 week-1. The epoetin beta dose should be adjusted after the first month of treatment since most patients required higher doses than the initial 60 IU kg-1 week-1.

Anemia↗

PubMed2001

Viability of Sarcocystis neurona sporocysts and dose titration in gamma-interferon knockout mice.

Gamma-interferon knockout mice have become the model animal used for studies on Sarcocystis neurona. In order to determine the viability of S. neurona sporocysts and to evaluate the course of the disease in these mice, sporocysts were collected from opossums (Didelphis virginiana), processed, and stored for varying periods of time. Gamma-interferon knockout mice were then inoculated orally with different isolates at different doses. These animals were observed daily for clinical signs until they died or it appeared necessary to humanely euthanize them. 15 of 17 (88%) mice died or showed clinical signs consistent with neurologic disease. The clinical neurologic symptoms observed in these mice appeared to be similar to those observed in horses. 15 of 17 (88%) mice were euthanized or dead by day 35 and organisms were observed in the brains of 13 of 17 (77%) mice. Dose appeared not to effect clinical signs, but did effect the amount of time in which the course of disease was completed with some isolates. The minimum effective dose in this study was 500 orally inoculated sporocysts. Efforts to titrate to smaller doses were not attempted. Direct correlation can be made between molecularly characterized S. neurona sporocysts and their ability to cause neurologic disease in gamma-interferon knockout mice.

Animals↗