Showing papers in "American Journal of Therapeutics in 1999"
TL;DR: Calcium citrate is better absorbed than calcium carbonate by approximately 22% to 27%, either on an empty stomach or co-administered with meals.
Abstract: Objective To perform a meta-analysis of data from available published trials comparing the bioavailability of calcium carbonate with that of calcium citrate. Data sources The whole set was comprised of 15 studies involving 184 subjects who underwent measurement of calcium absorption from calcium carbonate and calcium citrate. Category A excluded four studies for lack of physiological relevance, use of a mixed preparation with low content of calcium carbonate, or wide variability in results. Category B was comprised of five studies (from Category A) involving 71 subjects who took calcium supplements on an empty stomach. Category C was comprised of six studies (from Category A) involving 65 subjects who took calcium preparations with meals. Method The meta-analysis of calcium absorption data from calcium carbonate and calcium citrate, with calculation of effect size and 95% confidence intervals. Results Calcium absorption from calcium citrate was consistently significantly higher than that from calcium carbonate by 20.0% in the whole set, by 24.0% in Category A, by 27.2% on an empty stomach, and by 21.6% with meals. Conclusion Calcium citrate is better absorbed than calcium carbonate by approximately 22% to 27%, either on an empty stomach or co-administered with meals.
88 citations
TL;DR: The selective AT (1) receptor antagonist, telmisartan, is extremely effective in the treatment of mild-to-moderate hypertension both as monotherapy and in combination with HCTZ and is at least comparable in efficacy to lisinopril, with a tolerability profile that may offer advantages in terms of a reduced incidence of adverse events.
Abstract: In this study, telmisartan, a new angiotensin AT ( 1 ) receptor antagonist given as monotherapy and in combination with hydrochlorothiazide (HCTZ), was compared with lisinopril as monotherapy and in combination with HCTZ. This 52-week, randomized, multicenter, double-blind, double-dummy, parallel-group, dose-titration study of 578 patients with mild-to-moderate essential hypertension (mean diastolic blood pressure [DBP], >/=95 mm Hg), compared the efficacy and safety of telmisartan (n = 385) with lisinopril (n = 193). Dosage could be increased for both telmisartan (40 --> 80 --> 160 mg) and lisinopril (10 --> 20 --> 40 mg) at each of the first 2 monthly visits if DBP control (<90 mm Hg) had not been established. Once DBP control was established, patients entered the 48-week maintenance period. During this period, the dose of the study drug was fixed, although open-label HCTZ at 12.5 mg or 25 mg was added, when needed, to regain DBP control. At the end of the titration period, DBP control was achieved on monotherapy by 67% and 63% of the telmisartan and lisinopril patients, respectively. At the end of the maintenance period, supine DBP was controlled in 83% and 87% of the telmisartan and lisinopril patients, respectively, with systolic blood pressure over DBP reductions of 23.8/16.6 mm Hg for telmisartan and 19.9/15.6 mm Hg for lisinopril. Treatment-related side effects occurred in fewer telmisartan-treated patients (28%) than in lisinopril-treated patients (40%; P =.001). Significantly fewer patients (P =.018) receiving telmisartan experienced treatment-related cough (3% v 7%), and cough led to discontinuation significantly less often (P =.007) with telmisartan treatment than with lisinopril treatment (0.3% v 3.1%). In addition, two cases of angioedema were observed, both in the lisinopril group. The selective AT (1) receptor antagonist, telmisartan, is extremely effective in the treatment of mild-to-moderate hypertension both as monotherapy and in combination with HCTZ and is at least comparable in efficacy to lisinopril, with a tolerability profile that may offer advantages in terms of a reduced incidence of adverse events.
74 citations
TL;DR: A meta-regression analysis of published studies of omeprazole plus antibiotics (amoxicillin, clarithromycin, or an imidazole derivative) in the treatment of Helicobacter pylori was presented in this paper.
Abstract: This article presents a meta-regression analysis of published studies of omeprazole plus antibiotics (amoxicillin, clarithromycin, or an imidazole derivative) in the treatment of Helicobacter pylori. Eligible studies were all randomized, controlled trials published through April 1996 with 10 or more patients receiving omeprazole plus antibiotics for 5 or more days and testing for H. pylori eradication 4 weeks or more after treatment. Probability of eradication was calculated for each treatment arm, and logistic regression was performed using study characteristics as covariates. Seventy-four studies involving 117 treatment arms with 4,769 patients were identified. The eradication rate was 76% for omeprazole plus clarithromycin and 65% for omeprazole plus amoxicillin dual regimens (P <.0001). Eradication rates for triple regimens were 82%, omeprazole plus amoxicillin plus clarithromycin; 83%, omeprazole plus amoxicillin plus imidazole; and 89%, omeprazole plus clarithromycin plus imidazole. In a multiple logistic regression analysis, significant factors were antibiotic, disease, omeprazole dose, and whether treatment was followed by maintenance omeprazole. A systematic overview of the best available evidence suggests that dual therapy with omeprazole plus clarithromycin is superior to omeprazole plus amoxicillin. Triple therapy is better than dual therapy. Treatment works better on ulcers than on nonulcer dyspepsia. Higher doses of omeprazole give better results. Additional trials exploring higher omeprazole doses for varying durations as well as cost, side effects, and compliance trade-offs with efficacy are recommended.
64 citations
TL;DR: Iscador Qu Spezial can be administered safely to immunocompromised patients and increased urea levels and slightly decreased total protein caused by a minor decrease in albumin were observed, and none of the HIV-positive patients progressed in disease stage.
Abstract: Iscador is being used by many patients as unconventional anticancer and immunomodulating therapy. To determine the toxicity profile and biochemical effects of Iscador Qu Spezial (Weleda AG Schwabisch Gmund, Germany) in human immunodeficiency virus (HIV)-positive patients and healthy controls, we performed a phase I/II study. Escalating doses of Iscador Qu Spezial, standardized for its lectin and viscotoxin content, were administered to 16 HIV-positive patients and 8 healthy subjects during a period of 6 to 8 months. Iscador Qu Spezial preparations were administered twice per week subcutaneously in increasing doses (ie, 0.01 mg, 0.1 mg, 1.0 mg, 2.0 mg, 5.0 mg, and 0.1 mg/kg for 2-6 weeks per dose). Drug-related adverse effects were flulike symptoms, gingivitis, fever, local erythema, and eosinophilia. These side effects were never severe. The incidence of systemic adverse events was highest in HIV-positive patients. Furthermore, increased urea levels and slightly decreased total protein caused by a minor decrease in albumin were observed. None of the HIV-positive patients progressed in disease stage. Iscador Qu Spezial can be administered safely to immunocompromised patients.
60 citations
TL;DR: Longer treatment duration prolongs the cost of care, without increasing the cure rate or decreasing the pneumonia recurrence rate, in inpatients with moderately severe community-acquired pneumonia.
Abstract: The objective of this study was to compare the outcome of 7 versus 10 days of antibiotic therapy for inpatients with moderately severe community-acquired pneumonia (CAP). A prospective, randomized, double-blind study with a follow-up period of 42 days was conducted. Fifty-two veterans were treated with 2 days of cefuroxime at 750 mg intravenously every 8 hours followed by group 1, 8 days oral therapy, and group 2, 5 days oral therapy followed by 3 days of placebo. Oral therapy consisted of cefuroxime axetil at 500 mg every 12 hours. No difference was seen in cure rates: 20 of 22 (90.9%) patients in group 1 and 21 of 24 (87.5%) patients in group 2. There were no late recurrences. Potential US cost-savings is $27.2 million. Inpatients with moderately severe CAP can be treated with 2 days of intravenous antibiotics followed by 5 additional days of oral antibiotics. Longer treatment duration prolongs the cost of care, without increasing the cure rate or decreasing the pneumonia recurrence rate.
50 citations
TL;DR: Testosterone is being considered as a therapy for augmenting skeletal muscle strength in patients with congestive heart failure and there may be a role in administering testosterone to return men to normal physiologic range who have low serum levels.
Abstract: There has been much interest in the effect of sex hormones on cardiovascular risk factors and as a therapeutic modality in both men and women. In this article, testosterone is considered as a possible therapy for cardiovascular disease. It has been shown that the level of serum testosterone decreases in men as they age. Healthy men with low testosterone levels have increased cardiovascular risk factors, including high fasting and 2-hour plasma glucose, serum triglycerides, total cholesterol and low-density lipoprotein (LDL) cholesterol, and apo A-I lipoprotein. Injections of testosterone to raise the levels to midnormal range have been shown to decrease total cholesterol and LDL cholesterol, while increasing high-density lipoprotein (HDL) cholesterol. Testosterone affects the clotting system by increasing thromboxane A (2) receptor activity and platelet aggregability. Testosterone has also been shown to augment the fibrinolytic system and antithrombin III activity. In men, testosterone has been shown to have antianginal effects, and endogenous levels have an inverse relationship to systolic blood pressure. Testosterone can be given in oral, injectable, pellet, and transdermal patch forms. There may be a role in administering testosterone to return men to normal physiologic range who have low serum levels. This treatment increases the risk of prostatic cancer, benign prostatism, erythrocytosis, and edema. No long-term studies of the effects of long-term testosterone replacement have been undertaken, so it is difficult to recommend this treatment as yet, but it is being considered as a therapy for augmenting skeletal muscle strength in patients with congestive heart failure.
43 citations
TL;DR: Clinical trials have demonstrated efficacy in Paget's disease of bone and activity against some malignancies, including epithelial ovarian carcinoma, non-squamous cell carcinoma of the cervix, bladder cancer, and non-Hodgkin's lymphoma; other clinical trials underway include studies of sarcoidosis and rheumatoid arthritis.
Abstract: Injectable gallium (Ga) nitrate, approved in the United States for the treatment of hypercalcemia of malignancy, has been known for more than 2 decades to have immunosuppressive properties. At therapeutic doses, it has few adverse effects, although high-dose infusions may result in severe nephrotoxicity, particularly in patients who are not adequately hydrated, and severe anemia. In animal models, Ga has been shown to have efficacy in the treatment of adjuvant arthritis, type 1 diabetes, experimental autoimmune encephalomyelitis, experimental pulmonary inflammation, cardiac allograft rejection, experimental autoimmune uveitis, endotoxic shock, and systemic lupus erythematosus. Clinical trials have demonstrated efficacy in Paget's disease of bone and activity against some malignancies, including epithelial ovarian carcinoma, non-squamous cell carcinoma of the cervix, bladder cancer, and non-Hodgkin's lymphoma. Other clinical trials underway include studies of sarcoidosis and rheumatoid arthritis. Future studies should be conducted not only in other autoimmune diseases, such as multiple sclerosis, but also in graft-versus-host disease, leprosy, and acquired immunodeficiency syndrome (AIDS).
38 citations
TL;DR: Transdermal clonidine, alone or in combination with other antihypertensive therapies, significantly lowered BP and heart rate in inner-city hypertensive patients and was generally well tolerated.
Abstract: The objective of this study was to assess the efficacy and tolerability of transdermal clonidine in inner-city African-American and Hispanic-American patients with essential hypertension. A multiclinic open-label, prospective trial for 12 weeks was used. Dose titration was based on office blood pres
35 citations
TL;DR: Cetirizine was more effective than loratadine in inhibiting the wheal response to histamine challenge and afforded greater reductions in most individual symptoms assessed daily by the parent.
Abstract: Antihistamines are the pharmacologic cornerstone of treatment for allergic rhinitis. The comparative effects of the newer, more specific H (1) -antagonists cetirizine and loratadine among younger patients are not well characterized. The efficacy and safety of cetirizine and loratadine were compared in a prospective, randomized, double-blind, longitudinal, parallel-group study of 80 children, 2 to 6 years of age, with perennial allergic rhinitis caused by house dust mites or plant pollens (verified by a radioallergosorbent or skin test). Patients received cetirizine or loratadine at 0.2 mg/kg once daily in the morning for 28 days. Histamine skin tests and eosinophil counts from nasal smears were performed at baseline and at the end of treatment. Individual rhinitis symptoms were assessed by the investigator at baseline and on day 28 and by parents at baseline and daily in symptom diaries. Global assessments were made by using a visual analog scale at baseline and at the end of treatment. Cetirizine produced significantly greater inhibition of the wheal response compared with loratadine (P <.0001). Eosinophil counts were improved to a comparable degree with both agents. Cetirizine and loratadine produced comparable improvements in symptoms and according to a global evaluation as assessed by the investigator at the end of treatment. Both agents produced substantial symptomatic relief according to patients' daily diary assessments; however, cetirizine was more effective than loratadine in relieving the symptoms of rhinorrhea, sneezing, nasal obstruction, and nasal pruritus (P <. 0001). Both treatments were well tolerated; two patients receiving cetirizine were dropped from the study because of adverse events. Cetirizine and loratadine provided effective, well-tolerated relief of the symptoms of perennial allergic rhinitis in small children. Cetirizine was more effective than loratadine in inhibiting the wheal response to histamine challenge and afforded greater reductions in most individual symptoms assessed daily by the parent.
31 citations
TL;DR: Overall, AC and TC could be used as effective antidotes in poisoning resulting from ciprofloxacin as well as other broad-spectrum antimicrobial drugs.
Abstract: The in vitro adsorption of ciprofloxacin, a broad-spectrum antimicrobial with actions against a wide variety of microorganisms on activated charcoal (AC) and talc (TC), was investigated at various pH values that simulate the pH of most regions of the gastrointestinal tract. The results of the study indicate that AC and TC adsorbed ciprofloxacin effectively. Adsorption depended on the quantity of the adsorbents used, and for AC adsorption was complete within 2 hours and for TC it was complete within 1 hour with 0.5 g of either of the adsorbents. AC exhibited higher adsorptive capacity for ciprofloxacin than TC. Overall, AC and TC could be used as effective antidotes in poisoning resulting from ciprofloxacin.
31 citations
TL;DR: Four children in whom fenoldopam was used to control MAP in various clinical scenarios, including hypertensive emergencies and urgencies, intraoperative reduction of MAP for controlled hypotension, and control of MAP during extracorporeal membrane oxygenation are presented.
Abstract: Fenoldopam is a direct-acting vasodilator that acts at the postsynaptic dopamine 1 receptors in renal, coronary, cerebral, and splanchnic vasculature resulting in arterial dilation and a lowering of the mean arterial pressure (MAP). Preliminary evidence suggests its efficacy in the treatment of hype
TL;DR: The T-channel-selective calcium channel blocker, mibefradil, reduced afterload and was effective for the symptomatic treatment of hypertension and stable angina pectoris and did not display any relevant negative inotropic or positive chronotropic effect.
Abstract: Basic studies as well as short-term clinical trials of the T-channel-selective calcium channel blocker, mibefradil, are reviewed. The compound reduced afterload and was effective for the symptomatic treatment of hypertension and stable angina pectoris. It did not display any relevant negative inotropic or positive chronotropic effect. Mibefradil has been withdrawn by the manufacturer because of drug interaction at the cytochrome P-450 3A4 enzyme. It is hoped that new T-channel-selective calcium channel blockers will be developed to explore further this promising but so far only preliminarily tested therapeutic possibility.
TL;DR: Neither nebivolol nor atenolol adversely affected lipid or carbohydrate metabolism in normometabolic hypertensive patients and both treatments demonstrated adequate and similar antihypertensive effects and were well tolerated.
Abstract: This was a double-blind, randomized, two-center, active-controlled, prospective, parallel study designed to evaluate the effects of nebivolol at daily doses of 5 mg on lipid and carbohydrate metabolism and on blood pressure in comparison with atenolol at daily doses of 50 mg Normometabolic subjects with mild-to-moderate essential hypertension were recruited for this study, which included a 4-week, single-blind placebo washout phase and a 12-week double-blind treatment phase After 12 weeks of treatment, both drugs demonstrated a significant decrease from baseline in high-density lipoprotein (HDL) apolipoprotein A-I (HDL-apoA-I) (nebivolol, P <02; atenolol, P <05) A significant reduction in HDL cholesterol (HDL-C) from baseline was also observed with nebivolol (P <05) There were no significant differences between the drugs for these parameters, and the ratio low-density lipoprotein cholesterol (LDL-C)-to-HDL-C did not change significantly after 12 weeks of active treatment with nebivolol or atenolol There were no significant changes in total cholesterol, HDL (2) -C, HDL (3) -C, LDL-C, very-low-density lipoprotein cholesterol (VLDL-C), total triglycerides, HDL-triglycerides (TG), LDL-TG, VLDL-TG, total apoB, LDL-B, VLDL-B (including the ratio LDL-C-to-LDL-apoB), or Lp(a) during treatment with both drugs No significant differences in plasma apoA-I and apoC-III as well as in apoA-I-, C-III-containing lipoprotein particles (including the apoC-III ratio) were observed between the drugs, neither before nor after each active treatment There were no significant differences between the drugs or within each treatment group in plasma glucose, insulin, or C-peptide concentrations after a 2-hour oral glucose tolerance test Mean clinic trough sitting systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from 150/98 mm Hg at baseline to 141/90 mm Hg at termination for nebivolol and from 160/99 mm Hg at baseline to 145/88 mm Hg at termination for atenolol No significant between-treatment differences were observed for the mean clinic trough sitting SBP/DBP Both drugs significantly increased the atrial natriuretic factor (ANF) N-terminal plasma levels, whereas no changes were observed in ANF C-terminal plasma concentrations A significant decrease (P < 05) in the plasma adrenocorticotropic hormone levels was observed after administration of both drugs A significant decrease (P <05) in plasma cortisol levels was observed only after atenolol treatment The incidence of adverse events reported during nebivolol treatment was comparable to that observed during atenolol treatment Heart rate was significantly reduced by both drugs There were no significant changes in hematology, biochemistry, or urinalysis studies Neither nebivolol nor atenolol adversely affected lipid or carbohydrate metabolism in normometabolic hypertensive patients Both treatments demonstrated adequate and similar antihypertensive effects and were well tolerated
TL;DR: Calcium citrate supplementation (400 mg of calcium twice daily) averted bone loss and stabilized bone density in the spine, femoral neck, and radial shaft in women relatively soon after menopause, probably due to the inhibition of bone resorption from parathyroid suppression.
Abstract: This placebo-controlled randomized trial was conducted to ascertain the value of calcium citrate supplementation in averting bone loss in 63 postmenopausal women, 57 of whom were early postmenopausal (five years after menopause) and six of whom were mid-postmenopausal (five to ten years after menopause). Bone density data were available for 25 women who took 800 mg of calcium citrate daily and 31 women who received placebo for one to two years. The two groups were similar in baseline age, years postmenopause (3.3 in the calcium citrate group vs 2.7 in the placebo group), height, weight, calcium intake, and L2-L4 bone density. L2-L4 bone density did not change during calcium citrate treatment (+ 1.03% after two years), whereas it declined significantly by -2.38% after two years on placebo (P < .001). Femoral neck bone density did not change in either group. Radial shaft bone density did not change in the calcium citrate group (-0.02% after two years), but it declined significantly in the placebo group (-1.79% after one year and -3.03% after two years, P < .01). The difference in bone density of the L2-L4 vertebrae and radial shaft after two years of treatment was significant between the two groups. An analysis of covariance disclosed no significant effect of calcium citrate on L2-L4 bone density during the first three years after menopause, but a protective effect after three years. Although serum PTH did not change, serum and urinary calcium increased and serum calcitriol and urinary phosphorus decreased in the calcium citrate group, indicative of parathyroid suppression. Serum bone-specific alkaline phosphatase and osteocalcin, and urinary hydroxyproline and N-telopeptide decreased during some calcium citrate treatment periods, indicative of a reduction in bone turnover. Thus, calcium citrate supplementation (400 mg of calcium twice daily) averted bone loss and stabilized bone density in the spine, femoral neck, and radial shaft in women relatively soon after menopause. This bone-sparing action was probably due to the inhibition of bone resorption from parathyroid suppression.
TL;DR: Significant decreases were found in the number of incidents of excessive daytime sleepiness, headaches on awakening, physician visits, days absent from work, and automobile accidents or near misses with NCPAP therapy.
Abstract: A study was conducted at the Tri-State Sleep Disorders Center of Cincinnati, Ohio, to evaluate both quantitative and qualitative daily function and productivity outcomes of treating obstructive sleep apnea (OSA) with nasal continuous positive airway pressure (NCPAP). This was a prospective outcome study conducted in 316 patients with diagnosed and treated OSA. There were 234 men and 82 women, mean age, 48.79 +/- 0.67 years; weight averaged 250.39 +/- 3.55 pounds; mean pretreatment respiratory disturbance index was 42.9 +/- 1.7 episodes per hour and 2.8 +/- 0.2 episodes per hour with NCPAP treatment. Patients were surveyed by questionnaire, administered on polysomnographic confirmation of OSA and after 6 months of nightly treatment with NCPAP as to their perceptions of their level of daytime functioning and quality of life over the previous 6 months. Main outcome measures included number of incidents of excessive daytime sleepiness; number of headaches on awakening; number of automobile accidents and near-miss automobile accidents; number of days absent from work; number of physician visits; and a series of subjective scales, measuring job productivity, quality of life, general physical and mental condition, short-term memory, and changes in blood pressure. Significant decreases were found in the number of incidents of excessive daytime sleepiness, headaches on awakening, physician visits, days absent from work, and automobile accidents or near misses with NCPAP therapy. Patients also reported subjective increases in productivity, quality of life, physical and mental condition, and short-term memory and reduction in both diastolic and systolic blood pressure. Effective treatment of OSA results in improvement both in preexisting symptoms and in quality of life. Improvement in many of the major problems experienced by patients seeking treatment has important implications for preventive medicine as well as health care cost containment.
TL;DR: The reduction in QTd may explain the reduced sudden death mortality in patients with heart failure who are treated with ACE inhibitor therapy, and the effects of ACE therapy appear early on in terms of repolarization changes.
Abstract: Patients with chronic heart failure (CHF) have an increased risk for sudden death. This increased risk has been associated with increased QT dispersion (QTd), a reflection of the heterogeneity in ventricular repolarization. Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease heart size as well as decreasing morbidity and mortality in moderate-to-severe CHF. The aim of this study was to determine if ACE therapy is associated with a decrease in QTd, a marker for increased electrical instability. Ninety-seven patients were evaluated. The normalized QTd after 2 months of ACE therapy decreased from 16 +/- 4 to 12 +/- 3, a 25% reduction in dispersions. QTd also decreased from 61 +/- 14 to 47 +/- 12 (P < .001) and QTc dispersions decreased from 71 +/- 18 to 52 +/- 14 (P < .001). After 2 months of ACE inhibitor therapy, heart rate slowed significantly (RR intervals 765 +/- 198 before and 838 +/- 186 after ACE). There was a negative correlation between ejection fraction and QTd (r = -0.8; P < .001). The study also found no correlation between ACE level, percent converting enzyme inhibition, and QTd. The effects of ACE therapy appear early on in terms of repolarization changes. The reduction in QTd may explain the reduced sudden death mortality in patients with heart failure who are treated with ACE inhibitor therapy.
TL;DR: New guidelines resulted in improved tetanus prophylaxis at reduced costs in an emergency department, however, guidelines currently in use are misleading.
Abstract: The objective of this study was to assess the impact of an intervention to modify antitetanus prophylaxis of open wounds. This prospective, before-and-after study was conducted in an emergency department of a large metropolitan hospital. Consecutive patients with open wounds were managed according to the World Health Organization (WHO) guidelines before an intervention, then according to new guidelines afterwards. Locally developed guidelines were introduced and backed up by a teaching program, with emphasis on reducing unwarranted human tetanus immunoglobulins and costs. Serum tetanus antitoxins level was measured in postintervention patients mainly to verify the soundness of the intervention, eventually to complete patients' protection during follow-up, and to derive more reliable recommendations for the future. Main outcome measures included the number of treatments conforming to each set of guidelines, the rate of tetanus immunoglobulin prescriptions, and the cost of each strategy. Two groups of 389 and 459 patients were included. Treatment conforming to guidelines increased from 60% to 79%, undertreatment decreased from 31% to 19%, and overtreatment decreased from 9% to 2% (P < 0.001). Tetanus immunoglobulin prescriptions decreased from 23% to 1% (P < 0.001). On the basis of antitoxins level, 60% of 367 postintervention patients were correctly treated, 29% were overtreated, and 11% were undertreated. Nevertheless, with the WHO guidelines, only 49% would have been correctly treated, 39% would have been overtreated (29% with immunoglobulins), and 12% would have been undertreated (P < 0.001). Costs decreased from $32 to $24 per patient. New guidelines resulted in improved tetanus prophylaxis at reduced costs in an emergency department. Because they rely on immunization history, however, guidelines currently in use are misleading. More reliable recommendations, including a test for tetanus antibody status in some cases, are needed.
TL;DR: The effects of nefazodone on CAP and standard sleep architecture in depressed insomniacs and subjective estimates of sleep quality improved throughout the study, but CAP rates did not show a significant improvement.
Abstract: The standard methods of scoring sleep patterns do not ensure an accurate clinical impression of sleep quality. This is important especially in depressed insomniacs because persistent poor sleep increases the likelihood of recurrent depressive episodes. Changes in cyclic alternating patterns (CAP) in sleep have been shown to reflect corresponding changes in sleep quality. We evaluated the effects of nefazodone on CAP and standard sleep architecture in depressed insomniacs. The study was a single-center, single-blind, 6-week treatment of nefazodone hydrochloride followed by placebo withdrawal in 16 subjects meeting the DSM-IV criteria for depression who had a score of at least 18 on the 17-item Hamilton Depression Rating Scale, with insomnia-related items 4, 5, and 6 having a total score of 3 or greater. A mean daily dose of 339.1 +/- 141.7 mg at endpoint of nefazodone significantly reduced Hamilton Depression Scores from 21.7 +/- 3.0 on baseline to 5.8 +/- 5.3 (P <.05) by the end of the study. Polysomnography showed an improvement in sleep latency and sleep efficiency (P <.05), but no alterations in rapid-eye-movement or slow-wave sleep. Subjective estimates of sleep quality improved throughout the study, but CAP rates did not show a significant improvement. The disparity between CAP rates and sleep quality in depressed insomniacs is discussed.
TL;DR: The experience with amiodarone in two patients who developed postoperative JET after repair of congenital heart defects is described, and dosing regimens and previous experience in patients with JET are reviewed.
Abstract: Junctional ectopic tachycardia (JET) occurs most frequently after operative repair of congenital heart defects. The mechanism is thought to involve direct trauma to the atrioventricular node and His bundle resulting in an ectopic focus. Several therapeutic methods have been described in the pediatric literature with varying degrees of success and complication rates. Because heart rates may exceed 200 to 300 beats per minute, there may be inadequate time for ventricular filling. Ventricular filling can be further compromised because of the asynchrony between the atria and the ventricles. These factors can lead to significant compromise of cardiovascular function in the postoperative patient. We describe our experience with amiodarone in two patients who developed postoperative JET after repair of congenital heart defects. Dosing regimens and previous experience with amiodarone in patients with JET are reviewed.
TL;DR: In clinical practice where the renal function can vary widely, any of the published formulas can give satisfactory results and it is concluded that the Yukawa formula is concise and gives better results in Japanese patients.
Abstract: Seven methods using patient's age, weight, gender, and serum creatinine concentration were evaluated for mathematical and clinical predictive performance in estimating the creatinine clearance of Japanese patients. We compared the measured and estimated creatinine clearance in 179 hospitalized heart failure patients. The Gates equation was the most biased (mean prediction error, 17.9 mL/min), and the Yukawa equation was the most precise (mean absolute prediction error, 10.4 mL/min), followed by the Jelliffe, Bjornsson, Cockcroft and Gault, and Mawer equations. For all methods, precision was less when serum creatinine concentrations of /=0.6 mg/dL were rounded. We conclude that in clinical practice where the renal function can vary widely, any of the published formulas can give satisfactory results. The Yukawa formula is concise and gives better results in Japanese patients.
TL;DR: Nimesulide was as efficacious as piroxicam in reducing the inflammatory indices, and both drugs were equally well tolerated.
Abstract: The efficacy and tolerability profile of nimesulide was assessed in a double-blind, piroxicam-controlled trial in 49 patients with osteoarthritis of the knee joint. Nimesulide was administered orally as 100 mg twice daily, and piroxicam was administered as 20 mg orally in the morning and placebo in
TL;DR: One of the many provisions of the recently enacted Food and Drug Administration Modernization Act (FDAMA) provides for an additional period of market exclusivity in exchange for completed pediatric studies requested by the FDA for certain drugs of potential benefit to the pediatric population.
Abstract: One of the many provisions of the recently enacted Food and Drug Administration Modernization Act (FDAMA) provides for an additional period of market exclusivity in exchange for completed pediatric studies requested by the FDA for certain drugs of potential benefit to the pediatric population. The impetus for this law centers around two facts: Drugs needed in the pediatric population lack labeling for pediatric use, and industry lacks incentive to perform studies to support this additional labeling. Congress has now provided the incentive. The success of the pediatric initiative will rest initially on industry's willingness and readiness to do the studies. This willingness, in turn, will depend on FDAMA's impact on the economics of drug development and the availability of pediatric research capacity, both of which could be affected by the FDA's final rule on the assessment of safety and effectiveness of drugs and biologicals for pediatric patients. This rule will compel firms to conduct pediatric studies similar to the ones encouraged under FDAMA's voluntary pediatric exclusivity program. Although the Act provides for the statutory harmonization of the rule with the Act, whether the effects of the rule on the Act have been fully contemplated is a premise considered in this article. Congress too has much to contemplate as they evaluate the FDA's report, due in less than 2 years, on the public health effectiveness and economic effects of the Act's incentive program in preparation for possible FDAMA II modifications.
TL;DR: A review of various agents used in managing TD and improvements in research design and methodology have been applied to clinical trials, and as a result the stage has been set for advancement in this area of clinical psychiatry.
Abstract: Tardive dyskinesia (TD) is a source of great concern in psychiatric practice because of the iatrogenic nature of the disorder. It is a serious adverse reaction associated with neuroleptic drug therapy and is characterized by abnormal, involuntary, irregular, repetitive movements of the face and limbs that are purposeless in nature. It develops during exposure to or withdrawal from neuroleptics in patients with a history of neuroleptic use for at least 3 months, or 1 month in patients 60 years or older. To date, the structural or chemical pathology, etiology, and pathophysiology are not well understood, and no consistently effective pharmacological treatment is available. Numerous agents have been used in the management of TD; however, at the present time there are no safe and effective treatments for TD. A review of various agents used in managing TD is presented. Improvements in research design and methodology have been applied to clinical trials, and as a result, the stage has been set for advancement in this area of clinical psychiatry.
TL;DR: The probabilistic model can be used in the medical field to support patient safety decisions before complete data sets can be gathered or in cases in which some key factors are not directly observable.
Abstract: The engineering risk analysis method can be extended to include some human and organizational factors and can be used in the medical domain; this transfer is illustrated by a description of a study of anesthesia patient risk. This study involves first a dynamic analysis of accident risks. The model is then extended by relating the basic events of accident scenarios to the state of the practitioner described by the probability of personal problems that may affect his or her level of competence and alertness. These potential problems, in turn, are linked (by probabilistic relations) to the way the system is managed. This extension of the analytical framework allows assessment of the effect of particular types of practitioner problems and therefore of corresponding risk mitigation measures on the probability of the different accident scenarios. The risk analysis model can then be used as a management tool that permits setting priorities among patient safety measures, based either on the sole benefits of the corresponding decrease of patient risk or on a cost-to-benefit ratio. This probabilistic approach constitutes a departure from the classic risk studies exclusively based on statistical frequencies because it involves both available statistics and expert opinions. It is commonly used in engineering for systems for which there is not enough information at the time when decisions need to be made. I show here how the probabilistic model can be used in the medical field to support patient safety decisions before complete data sets can be gathered or in cases in which some key factors are not directly observable.
TL;DR: This review provides guidelines on how to choose NSAIDs rationally keeping in view the mechanism of tissue injury, the mode of action of NSAIDs, and their adverse effects.
Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of agents with similar action but diverse chemical structures and mechanism of action. There is considerable interpatient variability in the pain relief obtained from NSAIDs even when these agents belong to the same chemical family. The reasons for this interpatient variability include pharmacodynamic actions, pharmacokinetic parameters, or a combination of both. Furthermore, two distinct forms of the key enzyme cyclo-oxygenase (COX) have been identified. The constitutive enzyme COX-1 is found in most tissues and is believed to confer gastric mucosal protective action, and COX-2, the inducible enzyme, is implicated in pain and inflammation. Selective inhibition of COX-1 and COX-2 may allow prediction of drugs' major effects. By definition, NSAIDs are expected to modulate synovial inflammation present in the arthritic joints. Whether NSAIDs can positively influence the progression of arthritic disorders by modifying the underlying pathology remains to be answered. This review provides guidelines on how to choose NSAIDs rationally keeping in view the mechanism of tissue injury, the mode of action of NSAIDs, and their adverse effects.
TL;DR: The correlation coefficient between the expected trough concentration of minocycline in steady-state and the dose per 1 kg body weight was.54, suggesting that dosage should be adjusted by body weight when administered to debilitated elderly patients.
Abstract: A pharmacokinetic study of minocycline was performed in 12 debilitated elderly patients who had suffered from acute bacterial respiratory infections. Serial intravenous administrations of 100 mg minocycline were performed at least 10 times (infused for 1 hour, every 12 hours). Blood samples were obtained at 0, 1, 3, and 10 hours after initiating the first and fifth dose and 1 hour after the ninth dose (total, 9 points). The serum concentrations of unchanged minocycline were measured using high-performance liquid chromatography. The obtained data were analyzed using a two-compartment model in 11 cases and a one-compartment model in 1 case. Other clinical data were also collected simultaneously. The mean age of the subjects was 82 +/- 6 years. The elimination half-lives at beta-phase averaged 25.0 +/- 16.4 hours, the volume of distribution averaged 32.9 +/- 13.4 L, and the total clearance averaged 1.14 +/- 0.49 L/h. The correlation coefficient between the expected trough concentration of minocycline in steady-state and the dose per 1 kg body weight was.54 (P =.06), suggesting that dosage should be adjusted by body weight when administered to debilitated elderly patients. The present data are considered to be important and clinically useful because little information is available concerning the pharmacokinetics of minocycline in elderly patients.
TL;DR: Levels of endogenous CO do not increase in situations in which lactate production is increased, and it is possible that changes in endogenous production of CO may not significantly affect the circulating level of COHb.
Abstract: Endogenous carbon monoxide (CO) is produced in the degradation of heme by heme oxygenase. Studies have shown that hypoxia induces heme oxygenase production of CO in vascular tissue. Because elevated plasma lactate levels are associated with tissue hypoxia, we determined if there was any correlation between lactate and carboxyhemoglobin (COHb) levels in a group of critically ill patients with a high likelihood of hypoxia. In a 7.5-month period, 5322 simultaneous arterial COHb and lactate measurements were performed routinely on 183 patients with a blood gas analyzer in the Department of Veterans Affairs Medical Center, Bronx, New York, Surgical Intensive Care Unit. Sixty-one percent of the patients had elevated lactate levels (> 2.5mmol/L), and 46% had elevated COHb levels (> 1.5%). Lactate levels ranged from 0.12 to 22.7 mmol/L and COHb levels from 0% to 4.8%. There was no correlation between lactate and COHb levels (r = .07 with P < .0001). Levels of endogenous CO do not increase in situations in which lactate production is increased. It is possible that changes in endogenous production of CO may not significantly affect the circulating level of COHb. Although readily available, COHb levels do not seem to be clinically useful as markers of critical illness.
TL;DR: Transesophageal atrial stimulation was applied in 56 patients to terminate atrial flutter and procainamide is more efficacious than digoxin (P < 0.05) in facilitating cardioversion by transesophagal stimulation.
Abstract: Transesophageal atrial stimulation was applied in 56 patients to terminate atrial flutter. Extrastimulation and atrial burst techniques were applied using programmable stimulator (Medtronic 5328) and hexapolar esophageal electrode catheters. Thirty patients were randomized to receive digoxin pretreatment (group A), and 26 patients were randomized to receive procainamide pretreatment (group B). Efficacy of each pretreatment was evaluated by observing the change in the rhythm. In group A, transesophageal pacemaker therapy successfully converted atrial flutter to sinus rhythm in 13 patients and to atrial fibrillation in 14 patients, whereas the arrhythmia remained unchanged in the 3 remaining patients in the digitalized group. In group B, after procainamide pretreatment, sinus rhythm appeared in 19 and atrial fibrillation in 5, and no change was observed in the remaining 2 patients. Procainamide is more efficacious than digoxin (P < 0.05) in facilitating cardioversion by transesophageal stimulation.
TL;DR: The main goal of treatment is to improve patient comfort by accelerating the rate of gastric emptying, which may be achieved through dietary changes and the use of prokinetic agents.
Abstract: Gastroparesis, defined as delayed gastric emptying because of abnormal gastric motility in the absence of mechanical outlet obstruction, is a common problem causing significant morbidity. Although many cases are caused by diabetes, more than 90 different conditions are known to interfere with normal gastric motor function (Scand J Gastroenterol 1995;30[suppl]:7-16). Patients may present with nausea, vomiting, heartburn, early satiety, or postprandial pain. The current gold standard for quantifying gastric emptying is nuclear scintigraphy. The main goal of treatment is to improve patient comfort by accelerating the rate of gastric emptying, which may be achieved through dietary changes and the use of prokinetic agents. In rare instances, relief can only be obtained with surgical intervention. This report reviews the pathophysiology, clinical presentation, evaluation, and treatment of patients with gastroparesis, an understanding of which will lead to more effective patient care.
TL;DR: Once daily administration of fosinopril at 20 and 40 mg was safe and well tolerated, provided a sustained beneficial hemodynamic effect, improved left ventricular performance, and reduced symptoms of dyspnea, resulting in a reduced need for supplemental diuretic therapy.
Abstract: The objective of this study was to evaluate the hemodynamic and clinical effects of fosinopril in patients with heart failure. This was a prospective, multicenter, double-blind, randomized, parallel-group study. Patients 18 to 80 years of age who were receiving diuretics with a systolic blood pressure (SBP) > or = 90 mm Hg, New York Heart Association (NYHA) functional class II-IV, left ventricular ejection fraction or = 18 mm Hg, and a cardiac index (CI) or = 90 mm Hg were re-randomized to 10 weeks of double-blind fosinopril at 1, 20, or 40 mg once daily. Hemodynamic monitoring was repeated at the last visit, beginning at 24 hours postdose (trough) and continuing for 12 hours thereafter. Significant decreases in preload (PCWP) and afterload (mean arterial blood pressure [MABP] and systemic vascular resistance [SVR]) were evident 3 to 4 hours after a single dose of fosinopril at 20 and 40 mg and continuing for up to 8 to 12 hours postdose for PCWP and SVR and for up to 24 hours postdose for MABP (P < or = .05 v placebo and baseline). Sustained decreases in PCWP, MABP, SVR, and heart rate and increases in CI and stroke volume index were observed after 10 weeks of treatment with fosinopril at 20 and 40 mg once daily (P < or = .05 v 1 mg group for PCWP and MABP at most time points and P < or = .05 v baseline for other parameters at most time points). Dose-related trends toward reduced supplemental diuretic use (P = .027) and reduced symptoms of dyspnea (P = .008) were observed with the 20-mg and 40-mg fosinopril dose groups. Once daily administration of fosinopril at 20 and 40 mg was safe and well tolerated, provided a sustained beneficial hemodynamic effect, improved left ventricular performance, and reduced symptoms of dyspnea, resulting in a reduced need for supplemental diuretic therapy.