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Biomedical subjects

Andrew Whelton

Publications and source records attributed to Andrew Whelton.

At least 19 recordsLinked to original sources
PubMed2006

Clinical implications of nonopioid analgesia for relief of mild-to-moderate pain in patients with or at risk for cardiovascular disease.

Nonopioid analgesics, which include acetaminophen, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2)-specific inhibitors (coxibs), are frequently used for the relief of mild-to-moderate pain. Although all of these agents are effective at controlling pain, inhibition of prostaglandins (PGs) by NSAIDs may result in untoward cardiorenal effects, including hypertension, fluid and electrolyte abnormalities, congestive heart failure, acute renal failure, and nephrotic syndrome. Individuals with an increased risk for cardiorenal effects from NSAIDs (eg, the elderly, and those with hypertension, cardiac disease, or gouty nephropathy) should be monitored for early onset of edema, destabilization of blood pressure control, and/or onset of congestive heart failure when started on NSAID therapy. Because acetaminophen has a different mechanism of action from the conventional NSAIDs, it does not inhibit peripheral PGs at recommended dosing and therefore appears to have a more favorable cardiovascular and gastrointestinal safety profile. This review discusses the effects of acetaminophen, traditional NSAIDs, and coxibs on fluid and electrolytes, blood pressure, congestive heart failure, and renal function, as well as their consequences in patients with or at risk for cardiovascular disease (CVD). It also summarizes information on the mechanisms by which NSAID-induced cardiovascular adverse events develop, and it provides recommendations for the use of nonopioid analgesics for relief of mild-to-moderate pain in patients with or at risk for CVD.

Acetaminophen↗
PubMed2005

The Effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may attenuate the efficacy of antihypertensive agents in high-risk patients. Therefore, we conducted a double-blind, randomized trial to evaluate the effects of celecoxib, rofecoxib, and naproxen on 24-hour blood pressure (BP) in patients with type 2 diabetes, hypertension, and osteoarthritis. METHODS: Patients were randomly assigned to treatment with 200 mg of celecoxib once daily (n = 136), 25 mg of rofecoxib once daily (n = 138), or 500 mg of naproxen twice daily (n = 130) for 12 weeks. Twenty-four-hour ambulatory BP monitoring and validated arthritis efficacy assessments were conducted at randomization and at weeks 6 and 12 of treatment. The primary end point was the mean change from baseline in average 24-hour systolic BP at week 6. RESULTS: Reductions in osteoarthritis symptoms, including pain, mobility, and stiffness, were similar in all treatment groups. The mean +/- SE 24-hour systolic BP following 6 weeks of therapy was increased significantly by rofecoxib (from 130.3 +/- 1.2 to 134.5 +/- 1.4 mm Hg; P < .001) but not by celecoxib (132.0 +/- 1.3 to 131.9 +/- 1.3 mm Hg; P = .54) or naproxen (133.7 +/- 1.5 to 133.0 +/- 1.4 mm Hg; P = .74). The BP difference between rofecoxib and celecoxib was 3.78 mm Hg (95% confidence interval, 1.18-6.38; P = .005); between rofecoxib and naproxen, 3.85 mm Hg (95% confidence interval, 1.15-6.55; P = .005). The proportion of patients with controlled hypertension at baseline who developed ambulatory hypertension by week 6 (24-hour systolic BP>135 mm Hg) was significantly greater with rofecoxib (30%) than with celecoxib (16%) (P = .05) but not significantly greater than with naproxen (19%). CONCLUSIONS: At equally effective doses for osteoarthritis management, treatment with rofecoxib but not celecoxib or naproxen induced a significant increase in 24-hour systolic BP. However, destabilization of hypertension control occurred to some extent in all 3 treatment groups; this phenomenon was seen more often in patients treated with rofecoxib than with the other therapies.

Administration, Oral↗
PubMed2004

Microporous silicon and biosensor development: structural analysis, electrical characterisation and biocapacity evaluation.

An investigation of the fabrication of microporous silicon (MPS) layers as a material for the development of an electrolyte insulator semiconductor (EIS) capacitance sensor has been performed. The goal was to create a high surface area substrate for the immobilisation of biorecognition elements. Structural analysis of MPS layers as a function of key etch parameters, namely implant type (p or n), implant dose, hydrofluoric acid (HF) etch concentration and current density has been performed using scanning electron microscopy (SEM). It was possible to image porous layers with average pore diameter as low as 4 nm. n-type silicon samples had larger pore networks than p-type samples and reducing the silicon resistivity led to a reduction in the pores per microm2. It was found that increasing the HF etch concentration reduced the average pore diameter and increased the pores per microm2. Increasing the current density at which the etch was performed has the same effect. Understanding the effect of these parameters allows the MPS layer to be tuned to match specifications for optimum biocapacity. Different MPS layers were electrically characterised using capacitance-voltage and capacitance-frequency sweeps, in order to determine the effect of porosity on increases in surface area. The measured capacitance increased with increasing pores per microm2. p-type silicon with a boron implant in the back of the wafer, which had been etched in 25% HF in ethanol at a current density of 75 mA/cm2 yielded the highest capacitance signal per unit area. The effect of porosity and pore size on the biocapacity of the samples was also determined. For avidin immobilisation, with pores sizes above 5 nm, as the porosity increased the biocapacity increased. MPS fabricated in p-type silicon with a front and back implant etched in 25% HF at a current density of 25 mA/cm2 was used for the capacitance detection of synthetic oligonucleotides.

Biosensing Techniques↗
PubMed2002

Effects of celecoxib and rofecoxib on blood pressure and edema in patients > or =65 years of age with systemic hypertension and osteoarthritis.

Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), including the cyclooxygenase-2 (COX-2) specific inhibitors, with antihypertensive medication is common practice for many patients with arthritis. This study evaluated the effects of celecoxib 200 mg/day and rofecoxib 25 mg/day on blood pressure (BP) and edema in a 6-week, randomized, parallel-group, double-blind study in patients > or =65 years of age with osteoarthritis who were treated with fixed antihypertensive regimens. One thousand ninety-two patients received study medication (celecoxib, n = 549; rofecoxib, n = 543). Significantly more patients in the rofecoxib group compared with the celecoxib group developed increased systolic BP (change >20 mm Hg plus absolute value > or =140 mm Hg) at any time point (14.9% vs 6.9%, p <0.01). Rofecoxib caused the greatest increase in systolic BP in patients receiving angiotensin-converting enzyme inhibitors or beta blockers, whereas those on calcium channel antagonists or diuretic monotherapy receiving either celecoxib or rofecoxib showed no significant increases in BP. Clinically significant new-onset or worsening edema associated with weight gain developed in a greater percentage of patients in the rofecoxib group (7.7%) compared with the celecoxib group (4.7%) (p <0.05). Thus, in patients with controlled hypertension on a fixed antihypertensive regimen, careful monitoring of BP is warranted after the initiation of celecoxib or rofecoxib therapy.

Age Factors↗
PubMed2002

Comparison of thromboembolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac.

It has been hypothesized that cyclooxygenase 2 specific inhibitors may increase the risk of cardiovascular (CV) thromboembolic events because of their inhibition of vascular prostacyclin synthesis and lack of an effect on platelet thromboxane A(2) production and aggregation. Thus, we analyzed the data for celecoxib and nonsteroidal anti-inflammatory drugs (NSAIDs) from the Celecoxib Long-term Arthritis Safety Study to determine the incidences of serious CV thromboembolic events. This trial included 3,987 persons randomized to celecoxib 400 mg twice daily (2,320 person-years of exposure) and 3,981 persons randomized to either ibuprofen 800 mg 3 times daily or diclofenac 75 mg twice daily (2,203 person-years). Because acetylsalicylic acid (ASA) use for CV risk prophylaxis (< or =325 mg/day) was permitted, separate analyses were performed for all patients and those not taking ASA. The incidences of serious CV thromboembolic events (myocardial infarction, stroke, CV deaths, and peripheral events) were similar, and not significantly different, between celecoxib and NSAID comparators (combined or individually) for all patients as well as the subgroup of patients not taking ASA. This observation was true both for all serious CV thromboembolic events, as well as for individual events. No increase in myocardial infarction was apparent, even in patients not taking ASA who were candidates for secondary prophylaxis for myocardial infarction. The relative risks for celecoxib versus NSAIDs for serious CV thromboembolic events were 1.1 for all patients and 1.1 for the subgroup of patients not taking ASA (95% confidence interval 0.7 to 1.6 and 0.6 to 1.9, respectively). In addition, the incidences of adverse CV events such as hypertension, edema, and congestive heart failure were similar to, or significantly lower than, NSAID comparators regardless of the use of ASA. Thus, these analyses demonstrate no increased risk of serious CV thromboembolic events associated with celecoxib compared with conventional NSAIDs and therefore do not support the hypothesis of a class adverse effect of cyclooxygenase 2 specific inhibitors on the CV system.

Adult↗
PubMed2002

Physician-reported management of edema and destabilized blood pressure in cyclooxygenase-2-specific inhibitor users with osteoarthritis and treated hypertension.

BACKGROUND: The addition of a nonsteroidal anti-inflammatory drug to the regimen of a patient with treated hypertension can cause a destabilization of blood pressure. OBJECTIVE: The aim of this study was to describe physician-reported management of clinically significant edema and/or destabilized blood pressure in patients with osteoarthritis (OA) and hypertension when initiating therapy with rofecoxib or celecoxib. METHODS: A cross-sectional survey was administered to physicians who attended one of several arthritis consultant programs sponsored by Pharmacia Corporation, with attendees selected by local sales representatives. Each program included a clinical presentation by a physician concerning the cardiorenal safety of celecoxib, followed by a consultative presentation and session led by a Pharmacia Clinical Education Manager. RESULTS: A total of 828 physicians in the following specialties completed the survey: family practice (33.0%), internal medicine (25.0%), orthopedics (15.2%), and rheumatology (11.4%). Responding physicians expected that the majority of patients who experienced edema would contact them (68.4%). They reported that they schedule follow-up visits for blood pressure monitoring 65.6% of the time after initiating a cyclooxygenase-2 (COX-2)-specific inhibitor, with family practitioners and internists most likely to indicate that they would do so and orthopedists least likely. Responding physicians indicated that the presence of edema and destabilized blood pressure generally led to discontinuation of the COX-2-specific inhibitor (58%-82% of the time). Internists and family practitioners were most likely to report that they treat edema by initiating or modifying diuretic therapy (33%-51% of the time). For destabilized blood pressure, an antihypertensive drug was reported to be initiated or modified 40% to 55% of the time by family practitioners and internists, whereas orthopedists indicated that they referred patients to the primary care provider. The COX-2-specific inhibitor prescribed resulted in management differences: physicians indicated that they were more likely to switch from rofecoxib to celecoxib in the event of edema or destabilized blood pressure, whereas they were more likely to adjust the celecoxib dose than the rofecoxib dose. Because the data were captured from convenience samples of physicians attending sponsored meetings, it is possible that respondents provided the answers they thought the sponsor would want. Because this was a cross-sectional survey, reported behavior was not compared with actual behavior. CONCLUSIONS: A significant percentage of physicians reported that they monitor patients with OA and hypertension for the occurrence of destabilized blood pressure and edema after initiation of a COX-2-specific inhibitor. Physicians indicated that they would nearly always intervene when either event is identified.

Celecoxib↗
PubMed2002

Effects of celecoxib on ambulatory blood pressure in hypertensive patients on ACE inhibitors.

Nonselective nonsteroidal anti-inflammatory agents have been shown to attenuate the antihypertensive efficacy of ACE inhibitors with average increases in systolic blood pressure (BP) of 5 to 10 mm Hg. Less is known about the specific cyclooxygenase-2 (COX-2) inhibitors now widely used for the treatment of arthritis. The objective of this study was to determine the effects of celecoxib compared with placebo on 24-hour BP levels in ACE inhibitor-treated patients with hypertension. This was a randomized, double-blind, placebo-controlled, parallel-group clinical trial involving 178 men and women (mean age, 53 years) with essential hypertension who were treated and controlled with lisinopril monotherapy (10 to 40 mg daily). Baseline BP values were obtained using 24-hour ambulatory recordings. Patients received either celecoxib, 200 mg twice daily (twice the recommended dose for osteoarthritis) (n=91), or placebo (n=87) for 4 weeks, and changes in the 24-hour BP, body weight, and clinical laboratory parameters were assessed. Mean changes from baseline in the 24-hour systolic and diastolic BP were 2.6/1.5+/-0.9/0.6 mm Hg on celecoxib versus 1.0/0.3+/-1/0.6 mm Hg on placebo (P=0.34 for systolic BP; P=0.45 for diastolic BP). The proportion of patients whose 24-hour BP increased by at least 5, 10, 15, or 20 mm Hg were also similar on celecoxib and placebo. No changes in body weight, serum creatinine, or potassium occurred in either group. Thus, these data demonstrate that high doses of celecoxib have no significant effect on the antihypertensive effect of the ACE inhibitor lisinopril. The placebo-subtracted changes observed in 24-hour BP (1.6/1.2 mm Hg) are less than what has been reported for nonselective nonsteroidal anti-inflammatory agents in ACE inhibitor-treated patients.

Adolescent↗
PubMed2002

Comparison of the baseline cardiovascular risk profile among hypertensive patients prescribed COX-2-specific inhibitors or nonspecific NSAIDs: data from real-life practice.

OBJECTIVE: To evaluate the baseline cardiovascular (CV) risk of hypertensive patients newly starting cyclooxygenase (COX)-2-specific inhibitors (celecoxib or rofecoxib) or nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: Cross-sectional analysis was performed based on real-life practice data contained in the LifeLink Integrated Claims Solutions employer claims database. Patients who newly received treatment of celecoxib, rofecoxib, ibuprofen, naproxen, or diclofenac between January 1, 1999, and September 30, 2000, were identified from the database. Among them, only those who had a stable hypertensive condition for at least 3 consecutive months before the index prescription were included. Baseline characteristics were determined from claims data at the time of the index prescription. RESULTS: A total of 55 396 index prescriptions were identified, which consisted of 20,915 (37.8%) prescriptions for celecoxib, 12,952 (23.4%) for rofecoxib, 10 789 (19.5%) for ibuprofen, 8,840 (16.0%) for naproxen, and 1,900 (3.4%) for diclofenac. Both univariate and multivariate analyses showed that the patients prescribed COX-2-specific inhibitors were older and more likely to be female than those given nonspecific NSAIDs. Patients prescribed COX-2-specific inhibitors had a significantly higher baseline history of and/or current CV conditions, including ischemic heart disease, heart failure, other forms of heart disease, and cerebrovascular diseases or disorders, than patients prescribed nonspecific NSAIDs. The baseline proportion of patients with rheumatoid arthritis was also higher among COX-2-specific inhibitor users. In addition, COX-2-specific inhibitor users at baseline had higher prescription rates for medications that influence blood pressure, including estrogens, certain types of antidepressants, and corticosteroids. CONCLUSION: COX-2-specific inhibitors were prescribed preferentially to patients who, at the time of their index COX-2-specific inhibitor prescription, were at an increased baseline risk of CV events compared with patients prescribed nonspecific NSAIDs. Researchers aiming to compare the incidence of CV events between COX-2-specific inhibitors and nonspecific NSAIDs using observational study designs should take into account the underlying baseline CV risk of the populations being compared.

Aged↗
PubMed2002

Blood pressure destabilization and related healthcare utilization among hypertensive patients using nonspecific NSAIDs and COX-2-specific inhibitors.

OBJECTIVE: To determine the incremental cost of blood pressure (BP) destabilization among patients with stable hypertension who newly initiate therapy with celecoxib, rofecoxib, or 3 commonly used nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen, diclofenac, or naproxen, based on incidence rates of BP destabilization and costs of BP destabilization events obtained from a single observational data source. METHODS: Historical cohort observational analysis was performed based on real-life practice data that are contained in the LifeLink Integrated Claims Solutions employer claims databases. Patients with stable hypertension who had newly initiated therapy with rofecoxib, celecoxib, ibuprofen, diclofenac, or naproxen between January 1, 1999, and September 30, 2000, were identified from the database. The study consists of 3 components. First, the incidence rate of BP destabilization, based on patients' time of exposure to studied drugs, was estimated. Then, the cost of a BP destabilization event was determined by matching all BP destabilization cases with non-BP destabilization cases and following them for 90 days. The differences in the total costs between cases and controls were considered an estimate of the costs associated with managing the BP destabilization event. Last, the drug-specific incremental costs of BP destabilization of using each treatment were estimated in comparison with celecoxib. Incremental costs of BP destabilization were determined by multiplying the specific excess incidence rate of BP destabilization for each of the specific drugs, relative to celecoxib, by the cost of a BP destabilization event. RESULTS: The adjusted incidence rate of outpatient BP destabilization for celecoxib was 2.27 per 1000 patient-days vs 2.66 for rofecoxib (P < .001) or 2.65 for nonspecific NSAIDs (P < .001). The incremental cost of BP destabilization per patient per day of drug utilization for the study drugs compared with celecoxib were $0.18 for rofecoxib and $0.17 for nonspecific NSAIDs. The higher costs of BP destabilization relative to celecoxib were due to the higher incidence of outpatient BP destabilization associated with the other study drugs. The average incremental healthcare cost for an outpatient BP destabilization event within the first 90 days of the event was $459. The incidence of inpatient BP destabilization among rofecoxib users was significantly higher than among celecoxib users (risk rate = 4.17; 95% Cl, 1.86-9.26; P< .001). Incremental cost was not estimated for inpatient BP destabilization because the sample size was too small to provide a stable result. CONCLUSION: The costs of managing BP destabilization were significantly lower for celecoxib compared with rofecoxib and nonspecific NSAIDs. The observed differences among these anti-inflammatory drugs in the costs of BP destabilization will have a significant impact on the total cost of therapy in patients with stable hypertension. In addition to the monetary cost of BP destabilization, the physical cost to the patient regarding development or exacerbation of this serious medical condition should be considered when choosing cyclooxygenase-2-specific inhibitor and nonspecific NSAID therapies.

Aged↗
PubMed2002

Cost of heart failure among hypertensive users of nonspecific NSAIDs and COX-2-specific inhibitors.

OBJECTIVE: To determine the costs of heart failure in hypertensive patients receiving celecoxib, rofecoxib, and nonspecific nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice. METHODS: Stable hypertensive patients without a history of heart failure and newly treated with celecoxib, rofecoxib, ibuprofen, naproxen, or diclofenac between January 1, 1999, and September 30, 2000, were identified from the LifeLink Integrated Claims Solutions employer database. The incidence rate of inpatient and outpatient heart failure claims was determined based on patients' time of exposure to study drugs after adjusting for confounding factors. The heart failure costs of managing inpatient and outpatient events were estimated as the total healthcare costs for patients with heart failure claims minus the total healthcare costs among matched control groups without heart failure claims. Healthcare costs were computed for the 0 to 30 days and 31 to 90 days following the initial outpatient or inpatient claim. Finally, the excess incidence rate of patients with inpatient and outpatient heart failure claims, relative to celecoxib, were multiplied by the heart failure cost of an inpatient and outpatient event to determine the incremental costs of heart failure associated with each of the study drugs relative to celecoxib. RESULTS: Among 50 940 patients, 707 patients had outpatient heart failure claims and 229 patients had inpatient heart failure claims. In this study, rofecoxib-treated patients were 26% more likely to have an outpatient claim (rate ratio [RR] = 1.26; 95% confidence interval [CI], 1.06-1.48; P= .007) and 52% more likely to have an inpatient claim (RR = 1.52; 95% Cl, 1.15-2.02; P = .003) for heart failure than celecoxib-treated patients. The adjusted RR of heart failure claims was similar between celecoxib and NSAIDs. The average cost of outpatient heart failure was $1054 within 30 days and $221 for the period 31 to 90 days after the initial claim (total 90-day cost of $1275). The cost for a patient with inpatient heart failure was $5966 during the hospitalization. The 90-day posthospitalization heart failure cost was $245 (total 90-day cost of $6,211 for hospitalization and follow-up). The total heart failure-related incremental cost per patient per day of use was $0.15 for rofecoxib and $0.04 for nonspecific NSAIDs relative to celecoxib. CONCLUSION: The additional heart failure costs associated with the use of rofecoxib significantly add to its cost in patients with stable hypertension, relative to celecoxib and nonspecific NSAIDs. The higher heart failure costs of rofecoxib were attributable to the higher incidence of patients with inpatient and outpatient heart failure claims relative to celecoxib and nonspecific NSAID populations being compared.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

COX-2-specific inhibitors and the kidney: effect on hypertension and oedema.

Recent studies have investigated the renal and cardiovascular safety of celecoxib and rofecoxib. Both agents have been studied in long-term safety trials: the Celecoxib Long-Term Safety Study (CLASS) and Vioxx Gastrointestinal Outcomes Research Study (VIGOR). Renal safety was investigated in CLASS and the results indicated that celecoxib (even at the supratherapeutic 800 mg daily doses used in CLASS) is associated with lower rates of renal side effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). The renal safety of celecoxib was also assessed in healthy elderly subjects. In these subjects, celecoxib administration was associated with minimal effects on glomerular filtration rate compared with naproxen, while urinary sodium and prostaglandin E2 excretion were similar. Celecoxib and rofecoxib were compared with each other in two studies of elderly hypertensive patients with osteoarthritis (OA). These patients were treated with usual therapeutic doses of celecoxib (200 mg daily) or rofecoxib (25 mg daily). In the first study, celecoxib treatment had a significantly lower incidence of peripheral oedema than rofecoxib (4.9% versus 9.5%, P = 0.014). The second study confirmed the results of the initial study: the incidence of oedema was again lower with celecoxib than with rofecoxib (4.7% versus 7.7%, P < 0.05). Rofecoxib use was also associated with significantly greater mean and clinically relevant increases in systolic blood pressure than celecoxib. The CLASS study, which evaluated cardiovascular safety, showed that celecoxib treatment was not associated with an increase in myocardial infarction (MI) compared with non-selective NSAIDs (incidence in all patients was 0.3% for celecoxib and 0.3% for conventional NSAIDs). In a 12-week study of celecoxib (the Successive Celecoxib Efficacy and Safety Studies, SUCCESS-1) in more than 13000 patients with OA, combined doses of celecoxib (200 mg and 400 mg daily) and conventional NSAIDs (naproxen 1000 mg daily and diclofenac 100 mg daily) were again associated with similar rates of cardiovascular adverse events, including MI. However, in the VIGOR trial, treatment with rofecoxib was associated with a significantly higher rate of MI compared with naproxen (0.4% compared with 0.1% in the naproxen group, P < 0.05). In summary, celecoxib may have safety and tolerability advantages compared with non-selective NSAIDs studied and may have some cardiorenal benefits compared with rofecoxib.

Cyclooxygenase 2↗
PubMed1996

Atheroembolic Renal Disease.

Cholesterol emboli are being increasingly recognized as an important cause of renal dysfunction in an aging US population. Irregularly shaped atheroemboli typically cause partial obstruction of small renal vessels resulting in ischemia. A vasculitis-like picture often evolves with an inflammatory reaction and giant cell formation. Cholesterol emboli may be temporally related to vascular manipulation, anticoagulant, or thrombolytic drug use. Spontaneous cases have been reported. Patients with cholesterol emboli may present with a spectrum of acute renal failure varying from mild and asymptomatic to life-threatening disease. The differential diagnosis includes radiocontrast nephropathy, endocarditis with left-sided emboli, vasculitis, and thrombotic emboli. The physical examination findings suggestive of cholesterol emboli include extrarenal emboli and livedo reticularis. The urinalysis is typically unremarkable. Some patients have hematuria and/or non-nephrotic proteinuria. Serology and hematology results may suggest an inflammatory-like picture with elevated erythrocyte sedimentation rate, hypocomplementemia, eosinophilia, and eosinophiluria. In the setting of a clear precipitating factor and suggestive physical findings, cholesterol emboli can be established purely on clinical grounds. Demonstration of cholesterol crystals by biopsy of the kidney, skin (if lesion present), or muscle is diagnostic in unexplained cases. The kidney is the organ most frequently involved in this order. Therapy is supportive with particular emphasis on management of hypertension and hypercholesterolemia.

Journal Article↗
PubMed1996

Long-Term Treatment with Oral Torsemide and Its Effect on Body Weight and Fluid Balance in Patients with Chronic Renal Insufficiency.

Long-term treatment with oral torsemide was studied to determine its effectiveness in maintaining steady-state fluid balance in patients with chronic renal insufficiency by using a placebo-controlled, double-blind, random-off design. Patients with stable chronic renal insufficiency were initially titrated and then stabilized on torsemide. Once stabilized on torsemide, patients were randomly assigned in a double-blind fashion to continue on their titrated dose of torsemide or to receive a placebo. Of the 82 patients enrolled in the study, 68 were randomized to torsemide (n = 34) or placebo (n = 34). Patients who received the placebo showed a significantly greater (p < 0.001) mean increase in body weight (3.55 lb) than did patients who remained on torsemide (0.46 lb). Approximately two-thirds of the weight gain observed in the placebo group occurred during the first 3 days after randomization. Patients continued to receive treatment unless they developed fluid accumulation that was considered deleterious to their clinical state as determined by the investigator. In the placebo group a greater number of patients discontinued treatment because of weight gain or fluid accumulation. The mean number of days on treatment after randomization was significantly higher (p < 0.001) for patients who received torsemide (26 days) than for patients who received the placebo (16 days). The lack of weight gain in the torsemide group was associated with a higher percentage of patients who showed no change or an improvement in peripheral edema status (79%) than in placebo patients (35%). No patient was withdrawn from the study because of hyperkalemia or hypokalemia. The adverse effects reported during the study were as anticipated for patients with chronic renal insufficiency that is often complicated by other underlying illnesses.

Journal Article↗
PubMed1995

Effects of Misoprostol on Nonsteroidal Anti-Inflammatory Drug-Induced Renal Insufficiency in Patients with Stable Chronic Renal Failure: A Double-Blind, Crossover Study.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have the ability to induce acute deterioration in renal function by inhibiting the production of vasodilatory prostaglandins, thereby disrupting intrarenal hemodynamic balance in patients with stable, mild, chronic renal failure. Misoprostol is a synthetic prostaglandin E-1 analog suitable for oral administration and is widely used in conjunction with NSAIDs to prevent another NSAID-induced complication, gastric ulcers. This investigation utilized a prospective double-blind, randomized, placebo-controlled crossover study designed to evaluate the possible renal protective effects of misoprostol on the renal function of patients with mild, stable, chronic renal failure, who intercurrently ingested ibuprofen 800 mg 8H or indomethacin 25 mg 8H. The mean baseline glomerular filtration rate of the patients who participated in the study was 53 ml/min (misoprostol)/55 ml/min (placebo), and 57 ml/min (misoprostol)/57 ml/min (placebo) in Study I (ibuprofen) and Study II (indomethacin), respectively. At this level of renal functional impairment, the use of the selected NSAIDs did not produce further significant impairment of renal function; hence, a renal protective role for misoprostol could not be demonstrated. To solve the question posed in our study, it will be necessary to conduct future investigations utilizing a recruitment GFR and serum creatinine values in the range of 35 ml/min and less and 2.0 mg/dl and greater, respectively.

Journal Article↗
PubMed1994

A Study Design for Comparing the Effects of Missing Daily Doses of Antihypertensive Drugs.

In this double-blind, 6-week study comparing once-daily oral betaxolol and atenolol, the study design allowed the effects of simulated drug noncompliance to be examined. Overall similar blood pressure and heart rate responses were seen in 114 patients with mild-to-moderate hypertension. Similarly, there was no statistically significant difference in percentage of patients achieving goal diastolic blood pressure reductions at the end of 6 weeks of active therapy (betaxolol, 87%, 46/53; atenolol, 82%, 44/54), and safety results overall were similar. However, when patients randomly received placebo for two consecutive treatment days in either the fifth or sixth week of the study to simulate the effect of missing doses, magnitude and duration of effect on systolic blood pressure (p = 0.006), diastolic blood pressure (p = 0.02) and heart rate (p = 0.001) were significantly greater for betaxolol than atenolol as calculated from 28-h ambulatory blood pressure monitoring data. Although betaxolol and atenolol monotherapy are equally effective in controlling blood pressure when taken consistently, the blood pressure and heart rate response with betaxolol is significantly superior for at least 24 h after missing a dose, an important consideration related to patient noncompliance. These results are compatible with the different elimination half-lives of each drug.

Journal Article↗
PubMedDate not supplied

Effects of the cyclooxygenase-2 specific inhibitor valdecoxib versus nonsteroidal antiinflammatory agents and placebo on cardiovascular thrombotic events in patients with arthritis.

There have been concerns that the risk of cardiovascular thrombotic events may be higher with cyclooxygenase (COX)-2-specific inhibitors than nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We evaluated cardiovascular event data for valdecoxib, a new COX-2-specific inhibitor in approximately 8000 patients with osteoarthritis and rheumatoid arthritis treated with this agent in randomized clinical trials. The incidence of cardiovascular thrombotic events (cardiac, cerebrovascular and peripheral vascular, or arterial thrombotic) was determined by analyzing pooled valdecoxib (10-80 mg daily), nonselective NSAID (diclofenac 75 mg bid, ibuprofen 800 mg tid, or naproxen 500 mg bid) and placebo data from 10 randomized osteoarthritis and rheumatoid arthritis trials that were 6-52 weeks in duration. The incidence rates of events were determined in all patients (n = 7934) and in users of low-dose (< or =325 mg daily) aspirin (n = 1051) and nonusers of aspirin (n = 6883). Crude and exposure-adjusted incidences of thrombotic events were similar for valdecoxib, NSAIDs, and placebo. The risk of serious thrombotic events was also similar for each valdecoxib dose. Thrombotic risk was consistently higher for users of aspirin users than nonusers of aspirin (placebo, 1.4% vs. 0%; valdecoxib, 1.7% vs. 0.2%; NSAIDs, 1.9% vs. 0.5%). The rates of events in users of aspirin were similar for all 3 treatment groups and across valdecoxib doses. Short- and intermediate-term treatment with therapeutic (10 or 20 mg daily) and supratherapeutic (40 or 80 mg daily) valdecoxib doses was not associated with an increased incidence of thrombotic events relative to nonselective NSAIDs or placebo in osteoarthritis and rheumatoid arthritis patients in controlled clinical trials.

Adolescent↗