Mean Initial Dose Research Articles

Recovery of dynamic balance after additional small divided doses of midazolam given intravenously for sedation

We have previously reported that a dynamic balance test with perturbation stimuli and computerised dynamic posturography sensitively reflected the inhibitory effect on balance of intravenous midazolam sedation given intravenously as a single dose, and recovery time was within 80 min. The purpose of this study was to investigate the recovery of dynamic balance after additional doses of midazolam. Eighteen young adult male volunteers were sedated with midazolam given intravenously. The initial dose was given until the Wilson sedation score reached 3, and an additional dose was given until the same score was obtained 40 min later. They were tested with perturbation stimuli 40, 80, 100, and 120 min after the additional doses had been given. Their recovery time was recorded. The mean (S.D.) initial dose of midazolam was 0.07 (0.005) mg kg −1, and additional doses were 41 (7)% of the initial dose. The serial changes in bispectral index after initial and additional doses were similar. The recovery time for the dynamic balance test (within 80 min) was the same as that recorded in the previous single-dose study. The recovery time of the psychomotor function test was within 75 min. Additional doses of midazolam aiming for a Wilson sedation score of 3 at a dose about 40% of the initial dose and given 40 min after the initial dose are valid in terms of the maintenance of sedation and recovery of dynamic balance. Complete recovery time, including psychomotor function, was within 80 min of the additional dose of the drug.

Long-Term Efficacy of Trilostane Administered Twice Daily in Dogs With Pituitary-Dependent Hyperadrenocorticism

Trilostane is considered an efficacious and safe medication for canine pituitary-dependent hyperadrenocorticism (PDH). Its recommended frequency of administration is once daily. In this prospective study, the efficacy, toxicity, and long-term outcome of trilostane administered twice daily per os were evaluated in 44 dogs with PDH. Mean initial dose was 3.1 mg/kg q 12 hours, and mean final dose was 3.2 mg/kg q 12 hours. The final total daily dose was lower than previously reported for once-daily administration. The mean survival time for affected dogs was 930 days.

Initial Dosing of Paricalcitol Based on PTH Levels in Hemodialysis Patients With Secondary Hyperparathyroidism

Adjustment of the initial dose of paricalcitol in hemodialysis patients with secondary hyperparathyroidism (SHPT) on the basis of severity of SHPT generally is preferred in current practice. Whether the proposed dose, based on the formula baseline intact parathyroid hormone (iPTH [picograms per milliliter]) divided by 80, is the most appropriate has not been assessed adequately. A double-blind randomized trial comparing iPTH/80 dose with the immediately lower iPTH/120 dose was undertaken. Forty-three hemodialysis patients with iPTH levels between 300 and 900 pg/mL (300 and 900 ng/L) were followed up for 12 weeks. The primary outcome was control of iPTH levels within a target range between 150 and 300 pg/mL (150 and 300 ng/L). No difference between the 2 dose groups was noted in time to achieve target iPTH levels of 150 to 300 pg/mL (150 to 300 ng/L). More episodes of excessive decrease in iPTH levels occurred in the iPTH/80 group compared with the iPTH/120 group (P = 0.003). Nine patients in the iPTH/80 group (45%) versus 2 patients in the iPTH/120 group (10%) had iPTH levels less than 150 pg/mL (<150 ng/L) in at least half the measurements performed during the second half of the study (P = 0.034). Increases in calcium levels were greater in the iPTH/80 group at all times during the study (P < 0.05 at weeks 4 and 10). The number of required dose reductions was significantly greater in the iPTH/80 group compared with the iPTH/120 group (P = 0.008). In hemodialysis patients with SHPT, a lower initial dose of iPTH/120 shows efficacy similar to that of the already widely used iPTH/80 scheme in reaching target iPTH levels (150 to 300 pg/mL [150 to 300 ng/L]), with less required dose adjustments, lower increase in calcium levels, and lower cost. In addition, the initial dose of paricalcitol based on the iPTH/80 formula leads significantly more patients to excessive suppression of iPTH (<150 pg/mL [<150 ng/L]) than the iPTH/120 dose.

Concurrent chemotherapy practice patterns for head and neck cancer: What is standard of care?

5542 Background: The superiority of concurrent high dose cisplatin and radiation (RT) compared to RT alone for pts with locally advanced squamous cell cancer of the head and neck (SCCHN) has been demonstrated in large prospective phase III clinical trials. However, little is known regarding general prescribing patterns for chemotherapy (CT) utilization in combined modality treatment (CMT) for SCCHN. We conducted the present study to gain insight as to whether results from pivotal phase III trials affect utilization of concurrent CT in academic and community centers. Methods: We analyzed individual data from 326 SCCHN pts treated with concurrent CT and RT between 03/2003 and 12/2004 from 53 centers (43 community-based, 7 academic, and 3 VA or military) using electronically captured data from IntelliDose, a chemotherapy order software program. Results: Of 326 total pts, 123 pts (38%) received single agent cisplatin. From this group, 71 (58%) received low dose cisplatin (&lt;74 mg/m2, mean initial dose 67 mg), while 52 patients (42%) received high dose cisplatin (≥ 74 mg/m2, mean initial dose 189 mg). 72 pts (22%) received carboplatin/paclitaxel, 60 pts (18%) received cisplatin /5FU, 18 pts (5.5%) received single agent carboplatin, while 6 pts (1.8%) received cetuximab either alone or in combination with cisplatin. Other infrequently used regimens (each &lt; 5%) cumulatively accounted for 14% of pts treated. Comparison of chemotherapy utilization between academic and community-based practice centers showed no statistical difference with respect to use of high dose cisplatin versus low dose cisplatin, or single agent cisplatin versus non-cisplatin regimens. Conclusions: Despite evidence from phase III studies that concurrent high dose cisplatin is the standard of care for CMT of locally advanced SCCHN, utilization of other regimens, such as weekly low dose cisplatin, are commonly utilized. [Table: see text]

Azathioprine and inhibition of the anticoagulant effect of warfarin: Evidence from a case report and a literature review

Background: Warfarin and azathioprine may be prescribed concurrently in patients requiring both anticoagulation and immunosuppression. However, a potential interaction between the 2 drugs, resulting in an increased warfarin requirement, may be overlooked in clinical practice. Case Summary: A 67-year-old woman was treated with warfarin (initial mean dose, 24 mg/wk [3.5 mg/d]) for >3 years for recurrent deep vein thrombosis associated with systemic lupus erythematosus. Soon after commencing warfarin, azathioprine 150 mg/d was introduced for its steroid-sparing effect. Warfarin was titrated to a mean dose of 60 to 75 mg/wk (8.5–10.5 mg/d) over the next 18 months. Her dose of azathioprine was then increased to 200 mg/d. Subtherapeutic international normalized ratio (INR) levels required an increase in the warfarin dose to a mean of 130 mg/wk (18.5 mg/d). Subsequent discontinuation of azathioprine resulted in a dramatic increase in her INR levels (from 1.8 to 14.0 four weeks after discontinuation). Discussion: A temporal relationship, demonstrating the interaction between warfarin and azathioprine, was evident at various times during therapy for our patient. This case, together with 7 additional published cases, is comprehensively reviewed here using previously described criteria for establishing a definite interaction between warfarin and other drugs. Conclusions: The evidence supports a clinically important inhibitory action of azathioprine on warfarin and calls for closer monitoring of INR levels when azathioprine doses are altered during concurrent administration with warfarin.

Recommended initial loading dose of teicoplanin, established by therapeutic drug monitoring, and outcome in terms of optimal trough level

Teicoplanin has a long serum half-life, and therefore it takes time to reach a steady-state concentration. An initial loading procedure has been recommended for teicoplanin to enable prompt reaching of the optimal serum trough level (10-15 microg/ml). However, the dose of teicoplanin that should be administered to patients with varying renal function levels remains inconclusive. In this study, we monitored the serum concentrations of teicoplanin in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and compared different teicoplanin serum concentrations and their clinical efficacy, investigating the significance of the mean dose administered during the initial 3 days. The study included 48 patients with MRSA pneumonia. The peak and trough concentrations of teicoplanin were determined utilizing a fluorescence polarization immunoassay and a two-compartment Bayesian population model. Teicoplanin was given at a loading dose of 400 or 800 mg on the first day, followed by maintenance doses of 200 or 400 mg. The mean initial dose (MID) over the first 3 days was calculated as: (loading dose + dose on 2nd day + dose on 3rd day)/3. Patients with an MID of 266.7 mg or less (400 mg for loading, 200 mg over the 2nd and 3rd days) did not have a trough level that exceeded 10 microg/ml at the point before the injection on the 4th day. Even in patients with hemodialysis (HD), an MID of 266.7 mg was not enough to provide a trough level of 10 microg/ml. Patients with an MID than 533.3 mg had significantly elevated trough levels, showing better outcomes. A multiple regression formula for predicting trough level before the fourth day of administration is given as: 0.034 + 0.030 x (MID; mg) - 0.057 x creatinine clearance (Ccr; ml/min). These findings suggest that 800 mg as an initial dose, followed by 400 mg maintenance doses over the following 2 days, makes it possible to safely attain an optimal trough level, even in the patients with HD.

Lipid Management and Cholesterol Goal Attainment in Norway

To document prescribing patterns of lipid-modifying therapies in hypercholesterolemic patients, cholesterol goal attainment, and factors associated with cholesterol goal attainment in Norway. This was a retrospective, observational study using existing computerized patient records at 11 primary healthcare centers in Norway and the Norwegian Patient Register of hospital data. The study population was 3111 patients identified in the primary care database who were prescribed a lipid-modifying therapy between the dates of July 1987 and May 2003 and who were > or = 18 years of age at the time of the first prescription. Of these patients, 1337 patients had uncontrolled lipid measures at baseline. In the analysis of goal attainment, data were available for 877 (28% of the total study population) and 1144 (37%) patients with baseline and follow-up total cholesterol (TC) and/or low-density lipoprotein-cholesterol (LDL-C) levels after 4 and 12 months' treatment, respectively. Initial lipid-modifying therapy (drug and dosage), changes in initial lipid-modifying therapy, cholesterol goal attainment, and factors related to cholesterol goal attainment. Cholesterol treatment goals were defined as LDL-C <3.0 mmol/L and/or TC <5.0 mmol/L (as per the Second Joint Task Force of European Societies on the Prevention of Cardiovascular Disease). The initial lipid-modifying therapy was a HMG-CoA reductase inhibitor (statin) in 98% of patients, most often simvastatin (42%; mean initial dosage = 18.4 mg/day) or atorvastatin (34%; 12.7 mg/day). The median year of treatment initiation was 1999 and the mean duration of follow-up was 39 months. The initial prescription remained unchanged at year 1 for most patients (69%), whereas 17% discontinued drug treatment. Mean TC levels decreased from 7.36 mmol/L at baseline (n = 1337) to 5.31 mmol/L at 12 months (n = 1144; p < 0.05), whereas mean LDL-C levels decreased from 4.98 (n = 847) to 3.08 mmol/L at 12 months (n = 713; p < 0.05). These mean reductions occurred within 3 months of the initial prescription and did not change subsequently. A total of 32.9% of patients who were not at goal at baseline achieved cholesterol goal 12 months after initiating treatment. The factors related to cholesterol goal attainment at 12 months were: baseline TC level (odds ratio [OR] 0.64; 95% CI 0.58, 0.71), treatment with a statin (OR 8.60; 95% CI 1.13, 65.4), diagnosis of diabetes mellitus (OR 2.91; 95% CI 2.01, 4.21), and age (OR 1.02; 95% CI 1.01, 1.03). Lipid-modifying therapy in Norway is dominated by statin monotherapy. In this analysis of primary-care patients, maximal reductions in cholesterol levels were seen within the first 3-4 months after therapy initiation. After 12 months of treatment, 67% of patients remained above recommended cholesterol levels. More effective and well tolerated treatment strategies are needed to improve the probability of patients achieving cholesterol treatment goals.

小児におけるエポプロステノール（ＰＧＩ２）持続静注療法時の投与量の検討

The guideline on the dosing of Epoprostenol sodium (PGI2) was established based on data for adults. In order to study the dosing regimen in children in Japan, we followed-up 7 patients under 16 years old with primary pulmonary hypertension (PPH) who received PGI2 and analyzed their doses, hemodynamic parameters and brain natriuretic peptide (BNP) levels. The mean initial dose of PGI2 was 2.0±0.7 ng/kg/min and increases in the PGI2 dosage occurred mostly within 2 weeks of the start of administration. Up to 28 days after starting administration, the mean interval between dose increases was 2.9±3.3 days and the mean dosage increase increment was 0.8±0.4 ng/kg/min. Up to 3 months after starting administration, there was no statistically significant difference in doses between adults and children. Among severe adverse effects reported in acute dose-ranging in Japan, 7 of 18 cases were in children and the initial doses in 4 of them were over 2 ng/kg/min. Based on these findings, appropriate dosing of PGI2 in children is considered to be as follows : 1) The initial dose should be 0.5 ng/kg/min, 2) The dosage increase interval should be over 2 days and the dosage increase increment between 0.5 and 1 ng/kg/min, 3) Up to 3 months, the dose in children may be increased to the same extent as in adults.

Efficacy and Safety of Outpatient Alcohol Detoxification with a Combination of Tiapride/Carbamazepine: Additional Evidence

Few medications have been tested for outpatient alcohol detoxification. Previously we had shown a combination of carbamazepine and tiapride to be effective in an open study. This database is an extension of our previous work. This was an open prospective study to examine the efficacy, practicability and medical safety of a combination of tiapride and carbamazepine in outpatient detoxification of alcohol dependent patients. Patients were carefully screened for relevant neuropsychiatric disorders and then seen on a daily outpatient basis. A total number of 116 consecutively admitted patients entered the programme; 107 (92%) successfully ended the treatment. The mean initial dose for tiapride was 289 mg and for carbamazepine 502 mg. No serious medical complications or adverse events were observed except for one case of delirium tremens. Only four patients dropped out because of side effects. In general medication was well tolerated. Withdrawal symptomatology as indicated by CIWA-A-scores decreased over time. Results from this study give further evidence for a combination of tiapride and the anticonvulsant carbamazepine as an effective and safe treatment for outpatient alcohol detoxification in patients with moderate severity of withdrawal syndrome. Further randomized trials are warranted to examine the efficacy of this combination in outpatient alcohol withdrawal.

Lupus érythémateux chronique : traitement par thalidomide

Thalidomide is the second line treatment of chronic lupus erythematosus. The efficacy of this treatment, the minimal effective doses and tolerance are poorly documented in the literature. We present the data of a single-center retrospective studied among 18 patients with chronic lupus erythematosus, treated with thalidomide from 1998 to 2003. Inclusion criteria were: the presence of clinical lesions evoking the disease, confirmed by histological examination and direct immunofluorescence and treatment with thalidomide for more than 2 months. Mean age on diagnosis was of 35.8 years. Thalidomide had been initiated a mean of 10.6 years after diagnosis of chronic lupus erythematosus. In 13 out of 18 patients, thalidomide had been prescribed because of failure with prior treatments. Fifteen patients were improved by thalidomide (83.3 p. 100), with 11 (61 p. 100) complete and 4 (22 p. 100) partial remissions. Two (11 p. 100) patients were stabilized and treatment failed in one. The mean initial dose was of 100 mg/d (50-150), and maintenance dose was of around 50 mg/d (56 mg/d). The mean follow-up with thalidomide was of 19.4 months. Only one withdrawal due to side effects was reported. The most frequent side effects were: asthenia (33 p. 100), paresthesia (22 p. 100) and weight gain (16.6 p. 100). No side effects were reported in 10 out of 18 patients. This study confirms the efficacy of low dose thalidomide in the treatment of chronic lupus erythematosus. In our experience, tolerance to this treatment is good, the most frequent side effect was asthenia, but usually mild. No significant peripheral neuropathy was noted. The fear of side effects, notably neurological, should not delay initiation of thalidomide in the case of failure with current treatments.

Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients

Mycophenolate mofetil (MMF) introduction with concurrent reduction in calcineurin inhibitors has been shown to be beneficial in chronic allograft nephropathy (CAN) in adults. MMF was introduced to 19 children with CAN 26.3+/-5.8 (range 3.1-82.6) months after transplantation. Patients were followed up for a mean of 13.2+/-2.9 (range 1.2-51.1) months. The mean initial MMF dose was 660+/-56 mg/m2 per day, increased to 1,042+/-73 mg/m2 per day a year later. Cyclosporin was reduced from 138+/-10 mg/m2 per day at MMF introduction, to 116+/-15 mg/m2 per day at 6 months and 107+/-24 mg/m2 per day at 1 year. Six months prior to MMF introduction GFR deteriorated by -32.7+/-7.3 ml/min per 1.73 m2 per year. Six months after the introduction of MMF, GFR improved by +26.2+/-7.1 ml/min per 1.73 m2 per year (P <0.001). The introduction of MMF significantly reduced both the graft rejection rate (P=0.01) and systolic blood pressure (P=0.01), without a significant change in antihypertensive treatment. Haematological parameters did not significantly differ before and after MMF introduction. The introduction of MMF in paediatric renal transplant recipients with CAN may cause a significant improvement in GFR in both the short-term and the long-term and may well have a beneficial effect on systolic blood pressure. MMF has the potential to enable CNI-sparing protocols to be adopted.

Relationship between Initial Quetiapine Dose and Effectiveness as Reflected in Subsequent Mental Health Service Use among Patients with Schizophrenia or Bipolar Disorder

Objective To investigate the association between initial quetiapine dose and effectiveness as gauged by subsequent use of mental health services. Methods Using a health plan database, we identified patients with bipolar disorder or schizophrenia treated with quetiapine monotherapy for at least four consecutive months. The stability of each patient before and after quetiapine treatment was measured by use of mental health services other than antipsychotic drug, measured primarily by charges reported on claims. Regression models controlling for patient differences measured associations between initial quetiapine dose and subsequent mental health service use. Results Commercially insured patients with schizophrenia ( n = 581) or bipolar disorder ( n = 2421) received quetiapine monotherapy at mean (SD) initial daily doses of 237 (198) mg and 147 (171) mg, respectively. Both groups showed negative associations between initial daily dose and subsequent mental health charges. Among patients with schizophrenia, mental health charges decreased by $1.28 for each additional milligram of quetiapine ( P = 0.1097). Among patients with bipolar disorder, there was a significant decrease of $1.31 per additional milligram of quetiapine ( P = 0.0484). For schizophrenia, hospitalizations were reduced by 0.4% for each additional milligram of quetiapine ( P = 0.0189). For bipolar disorder, the association between quetiapine dose and outpatient charges was negative and trended toward significance ( P = 0.074), showing a $0.54 reduction in these charges for each additional milligram of quetiapine; the association with hospitalization was not significant. Conclusions In patients with schizophrenia or bipolar disorder, higher initial doses of quetiapine may be more effective in stabilizing patients as reflected in lower subsequent mental health service use.

Low initial dose of levothyroxine for treatment of congenital hypothyroidism

To evaluate the results of treatment of infants with congenital hypothyroidism (CH) with a low initial dosage of levothyroxine. 138 newborns with primary CH detected by neonatal screening were divided into 3 groups according to levels of serum TSH, TT(3) and TT(4): sub-clinical CH (TSH >50 mU/L), mild CH (TT(4) <54 nmol/L), severe CH (TT(4)<54 nmol/L and TT(3)<1.2 nmol/L). The initial dose of levothyroxine was (3.5 +/-1.0) microg/(kg.d) for sub-clinical CH group, (4.3 +/-0.7)microg/(kg.d) for mild CH group and (4.7 +/- 0.6)microg/(kg.d) for severe CH group. Follow-up evaluation was carried out at 1, 2 and 3 months of age by measuring serum levels of TT(3), TT(4) and TSH. The time, when clinical signs and symptoms were eliminated and serum levels of TT(3), TT(4) and TSH normalized, was recorded. Development Quotient (DQ) testing was performed when CH cases were about 2 years old. The mean initial dose of levothyroxine in 138 cases was (4.3 +/-0.9)microg/(kg.d). In one month the serum TT(3) and TT(4) levels returned to normal, while for TSH levels 67.4 % cases reached normal range in 2 months and 84.1 % in 3 months. Two months after therapy, the levels of TT(3) and TT(4) reached to the upper half of normal range and there were no signs or symptoms of hypothyroidism. The time for all cases in 3 groups to reach the normal clinical and biochemical indicators was similar (P=0.925). The dosage for cases with low circulating thyroxine before treatment was higher than that of the other groups (P<0.01). The average DQ score of 18 cases after treatment was 116.7 +/- 17.0. he levothyroxine dosage of (4.3 +/- 0.9)microg/(kg.d) is appropriate for the initial treatment of the majority of infants with CH. However it is better to individualize the dosage for each case.

Recombinant Factor VIIa for Rapid Reversal of Warfarin Anticoagulation in Acute Intracranial Hemorrhage

To assess the effects of recombinant factor VIIa (rFVIIa) on hemorrhage volume and functional outcomes in warfarin-related acute intracranial hemorrhage (ICH), which has a 30-day mortality of more than 50%. We reviewed the clinical, laboratory, and radiographic features of a consecutive series of 7 patients (median age, 87 years; 5 women) with symptomatic, nontraumatic warfarin-related acute ICH treated with intravenous rFVIIa at St. Luke's Hospital in Jacksonville, Fla, between December 2002 and September 2003. Prestroke baseline functional status was assessed with the modified Rankin Scale. Outcome was assessed with the Glasgow Outcome Scale. The international normalized ratio decreased from a mean of 2.7 before administration of rFVIIa to 1.08 after administration of rFVIIa. The median prestroke score on the modified Rankin Scale was zero. The median presenting score on the Glasgow Coma Scale was 14 (range, 4-15). The mean time from onset to treatment was 6.2 hours. The mean initial dose of rFVIIa was 62.1 microg/kg. One patient underwent placement of an external ventricular drain, and another underwent craniotomy and hematoma evacuation. Five of the 7 patients survived and were dismissed from the hospital with severe disability (Glasgow Outcome Scale, 3); 2 patients died during hospitalization. Intravenous bolus administration of rFVIIa can rapidly lower the international normalized ratio and appears to be safe for patients with warfarin-related ICH. Prospective controlled studies are needed to determine whether rFVIIa can prevent hematoma expansion and improve neurologic outcomes in patients with warfarin-related ICH.

Longitudinal analysis of the use of etanercept versus infliximab determined from medical chart audit.

To describe the dosing of etanercept and infliximab for the treatment of rheumatoid arthritis (RA). Adult patients with a diagnosis of RA who were treated with either etanercept or infliximab between 1999 and 2002 were selected from 16 rheumatology practices in the western and southeastern United States. Patients with a terminal illness or those receiving a tumor necrosis factor (TNF)-alpha inhibitor for an indication other than RA were excluded. Data were collected through a review of the patient medical records. Data collected on each patient included demographics, concurrent disease-modifying antirheumatic drug therapy, TNF-alpha inhibitor dose, frequency, duration of TNF-alpha inhibitor therapy, and discontinuation of TNF-alpha inhibitor therapy. A total of 244 patients were included in the evaluation (etanercept only [n=128; 52%], infliximab only [n=89; 36%], both [n=27; 11%]). The mean age of these patients was 55.1+/-13.3 years, 54.9+/-13.5 years, and 52.8+/-14.0 years, respectively; the mean duration of RA was 13.3 +/- 8.8 years, 13.4+/-8.0 years, and 14.0 +/- 9.9 years, respectively. Female patients constituted 70% of the sample. Health maintenance organization insurance was the most common form of medical insurance (45.8%), followed by Medicare (22.3%). The mean duration of follow-up for etanercept and infliximab treatment was 29.3+/-14.1 months and 14.8+/-6.9 months, respectively. Among patients who were still receiving therapy at the time of review, the mean initial and last etanercept doses were 25.0 mg versus 25.8 mg (P=0.16); the mean initial and last infliximab doses were 3.38 mg/kg versus 4.51 mg/kg (P<0.001). The dosing of etanercept and infliximab therapy was consistent with the approved labeling of both medications.

Changes in Height, Weight, and Body Mass Index in Children with Craniopharyngioma after Three Years of Growth Hormone Therapy: Analysis of KIGS (Pfizer International Growth Database)

Extreme degrees of obesity may occur in association with hypothalamic tumors, usually after surgical intervention. This phenomenon has been reported to occur in as many as 25-75% of children undergoing extensive surgical extirpation of craniopharyngiomas (Cranio). Because less is known about the auxology of children with Cranio with milder alterations in growth, we undertook a 3-yr longitudinal analysis, using the KIGS database (Pfizer International Growth Database), to study their growth patterns and evolution of weight. We compared the effect of GH therapy on height, weight, and body mass index (BMI) in 199 prepubertal children with diagnosed Cranio treated by surgery and/or radiotherapy to two other groups of children with other causes of organic GH deficiency (OGHD): one with postsurgical and/or postirradiated OGHD (OGHD + S/I; n = 92) and the other with OGHD not due to Cranio and not having undergone either surgery or irradiation (OGHD - S/I; n = 85). At the start of GH therapy, 1) mean chronological (P < 0.0001) and bone (P = 0.0002) ages were youngest in OGHD - S/I and oldest in OGHD + S/I; 2) the mean height sd score (SDS) was lowest in OGHD - S/I and comparably higher in the other two groups (P < 0.0001); 3) mean weight and BMI SDS were greatest in Cranio and least in OGHD - S/I (both P < 0.0001); and 4) the mean initial GH dose prescribed was highest in OGHD - S/I and comparable in the other two groups (P < 0.0001). After 3 yr of GH therapy, 1) mean bone age remained youngest in OGHD - S/I and oldest in OGHD + S/I (P < 0.0001); 2) mean height SDS was highest in Cranio and comparably lower in the other two groups (P = 0.0159); 3) mean weight and BMI SDS remained greatest in Cranio and least in OGHD - S/I (P < 0.0001 and P = 0.0003, respectively); and 4) the mean GH dose remained highest in the OGHD - S/I group and least in the Cranio group (P = 0.0082). There were statistically significant increases within each group between the start of treatment and after 3 yr of GH therapy in height and weight, but not in BMI SDS. Lastly, after 3 yr of GH treatment, children in the Cranio group continued to have disproportionately heavier weight and higher BMI (with the greatest values in those with lower stimulated peak GH concentrations) compared with members of the other two groups, with no salutary effect of GH treatment on weight SDS and a mild improvement in BMI SDS. After S/I treatment, children with Cranio are disproportionately prone to varying degrees of weight gain compared with children with other forms of OGHD. In the present cohort of prepubertal children with Cranio, GH therapy induced excellent linear growth, but failed to have an ameliorative effect on weight gain and had only a slight beneficial effect on BMI gain. Because affected children may have resultant significant long-term medical morbidity and diminished quality of life, it is critical that the mechanism of this phenomenon be determined to devise helpful preventive or therapeutic interventions.

Análisis de una serie de 55 pacientes con arteritis de células gigantes confirmada por biopsia

Our main aim with this study is to establish the epidemiologic and clinical features, treatment response and complications of a group composed of 55 patients with biopsy proven temporal arteritis in a local hospital. Retrospective study based on clinical records revision of patients diagnosed of giant cell arteritis (GCA) made by temporal artery biopsy between 1989 and 2001. The approximated annual incidence of GCA in our area is 4.1 cases per 100,000 persons over the age of 50. The mean age at diagnostic was 74 years and the 78,2% were women. The most common symptom at diagnostic was headache (81.5%) followed by systemic manifestations (74.1%) and later we found jaw claudication (32,7%), visual impairment (30.2%), isquemic manifestations (17%). Polymyalgia rheumatica was associated to GCA in 49.1% of cases. The temporal artery explorations was abnormal in the 76.9% of patients. The mean initial dose of corticoids was 69 mg prednisone per day, with a half dose reduction time of .5 months. In spite of that, 24,1% of patients relapsed during the first year. The 38% of patients did some complications during the corticosteroid treatment. The ESR was lower 50 mm in 12.7% of patients; it was anaemia in the 37.7% and thrombocytosis in 32,1%. In these last patients we detected a relation between thrombocytosis and specific visual impairment. The incidence of GCA in our area is low. The results of our series aren't different from others publicated before in clinical manifestations, there is a prevalence of female sex and there is a relation between specific visual impairment and the presence of thrombocytosis.

Polyethylene glycol for constipation in children younger than eighteen months old.

Polyethylene glycol (PEG) is a safe and effective treatment for constipation in children older than 18 months. Data on its safety and efficacy in infants are lacking. The goal of this study was to determine safety, efficacy, and optimal dose of polyethylene glycol powder for treatment of constipation in patients younger than 18 months. The authors reviewed the charts of patients younger than 18 months treated with PEG 3350 for constipation. The initial dose, effective maintenance dose, response to therapy, duration of therapy, and side effects were recorded. Twenty-eight patients younger than 18 months of age treated with PEG were identified (3, age 0-5 months; 9, age 6-11 months; 16, age 12-17 months). Mean duration of therapy was 6.2 +/- 5 months (range, 3 weeks-21 months). Mean initial dose was 0.88 g/kg/day (range, 0.26-2.14 g/kg/day). Mean effective maintenance dose was 0.78 g/kg/day (range, 0.26-1.26 g/kg/day). PEG relieved constipation in 97.6% of patients. One infant experienced increased gas per rectum and four others experienced transient diarrhea that resolved after adjusting the dose. Oral powdered polyethylene glycol at a maintenance dose of 0.78 g/kg/day is safe and effective for patients younger than 18 months. Dose and safety profiles are similar for those reported in older children.

Polyethylene Glycol for Constipation in Children Younger Than Eighteen Months Old

ABSTRACTBackground:Polyethylene glycol (PEG) is a safe and effective treatment for constipation in children older than 18 months. Data on its safety and efficacy in infants are lacking. The goal of this study was to determine safety, efficacy, and optimal dose of polyethylene glycol powder for treatment of constipation in patients younger than 18 months.Methods:The authors reviewed the charts of patients younger than 18 months treated with PEG 3350 for constipation. The initial dose, effective maintenance dose, response to therapy, duration of therapy, and side effects were recorded.Results:Twenty‐eight patients younger than 18 months of age treated with PEG were identified (3, age 0–5 months; 9, age 6–11 months; 16, age 12–17 months). Mean duration of therapy was 6.2 ± 5 months (range, 3 weeks–21 months). Mean initial dose was 0.88 g/kg/day (range, 0.26–2.14 g/kg/day). Mean effective maintenance dose was 0.78 g/kg/day (range, 0.26–1.26 g/kg/day). PEG relieved constipation in 97.6% of patients. One infant experienced increased gas per rectum and four others experienced transient diarrhea that resolved after adjusting the dose.Conclusion:Oral powdered polyethylene glycol at a maintenance dose of 0.78 g/kg/day is safe and effective for patients younger than 18 months. Dose and safety profiles are similar for those reported in older children.

Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms: Relationships with capecitabine (X) pharmacodynamics in advanced breast cancer (ABC) patients (pts)

2062 Background: TS expression and reduced folate levels significantly influence fluoropyrimidine pharmacodynamics. X is a highly effective oral fluoropyrimidine carbamate with proven single agent activity for the treatment of ABC, which improves survival when added to docetaxel. We prospectively analyzed the impact of gene polymorphisms potentially linked to TS expression and 5–10 methylenetetrahydrofolate concentrations (MTHFR gene) on toxicity and response in X-treated ABC pts. Methods: TS gene polymorphisms in the 5' (28 base pair tandem repeats) and 3' (6 base pair deletion) regions were analyzed by PCR. C677T and A1298C MTHFR gene polymorphisms were determined by melting curve analyses (LightCycler). We analyzed DNA from mononuclear cells of 57 pts with ABC, median age 57 (36–79), 60% multiple metastatic sites, prior treatment: 88% anthracycline, 70% taxane and 21% 5-FU, current treatment setting: 21% pts first, 47% second line. Mean initial dose of X was 1048 mg/m2 twice-daily d1–14 every 3 weeks, median number of cycles 7 (1–15). Results: 3'TS genotype (26 pts 110/110, 27 pts 104/110, 4 pts 104/104), C677T MTHFR genotype (22 pts wt/wt, 24 pts wt/mut, 11 pts mut/mut) and A1298C MTHFR genotype (33 pts wt/wt, 19 pts wt/mut, 5 pts mut/mut) were not correlated to any X-related toxicities (WHO criteria grade 0–1 vs 2–4 at 1st cycle). In contrast, 5'TS genotype (11 pts 2R2R, 23 pts 2R3R, 21 pts 3R3R) was significantly linked to hand-foot syndrome and nausea-vomiting (Fisher's Exact test: both p = 0.03). 3R3R pts had less toxicity. Response to treatment was assessed after the 3rd cycle (21% progression, 50% stabilization, 27% partial, 2% complete responses). Clinical benefit (i.e. stabilization or response vs progression) was not linked to any TS or MTHFR gene polymorphisms. Conclusion: Constitutional TS polymorphism in the 5' region may be predictive of X pharmacodynamics, but needs confirmation in a prospective study. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Hoffmann-La Roche Hoffmann-La Roche