ABSTRACT
AIM: To provide estimates of the costs of severe and non-severe insulin-related hypoglycaemia in the UK using the Local Impact of Hypoglycaemia Tool. METHODS: Rates of hypoglycaemia were extracted from the UK Hypoglycaemia Study Group observational study. The costs of severe and non-severe hypoglycaemic episodes in insulin-treated adults with Type 1 and Type 2 diabetes were estimated from UK data sources. The rates and costs were then applied to specific populations to give an estimate of the cost of insulin-related hypoglycaemia for the UK, a specific locality, or a user-defined population. User-specific rates and costs could also be applied. RESULTS: The estimated cost of a hypoglycaemic episode can range from as much as £2,152 for severe episodes (for which the patient is admitted to hospital) to as little as £1.67 for non-severe episodes. With a UK population of 64.1 million, the total estimated cost of managing insulin-related hypoglycaemia is £468.0 m per year (£295.9 m for severe episodes, £172.1 m for non-severe episodes). On a local health economy level, using a hypothetical general population of 100 000, the total cost of managing insulin-related hypoglycaemia is estimated to be £730,052 per year (£461,658 for severe and £268,394 for non-severe episodes). CONCLUSIONS: The Local Impact of Hypoglycaemia Tool highlights the economic burden of insulin-related hypoglycaemia. Non-severe episodes are often overlooked because of their low individual cost, but their high frequency makes the cumulative cost substantial. The Local Impact of Hypoglycaemia Tool also shows clinicians and budget-holders the economic impact of lower rates of hypoglycaemia.
Subject(s)
Diabetes Mellitus, Type 1/economics , Diabetes Mellitus, Type 2/economics , Hypoglycemia/economics , Hypoglycemic Agents/economics , Insulin/economics , Cost of Illness , Costs and Cost Analysis , Critical Pathways/economics , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Emergency Medical Services/economics , Health Resources/economics , Humans , Hypoglycemia/chemically induced , Hypoglycemia/therapy , Hypoglycemic Agents/adverse effects , Insulin/adverse effects , Length of Stay/economicsABSTRACT
BACKGROUND: Recent clinical trials in pulmonary arterial hypertension have included World Health Organization functional classes I and II patients. However, the impact of baseline functional class and other measures of severity on outcomes has not been evaluated in detail. METHODS: Outcomes at 12 weeks for patients grouped by functional class, haemodynamics, brain natriuretic peptide (BNP) level and 6-min walk distance (6MWD) were evaluated for patients in the Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter Efficacy Study 1 and 2 (ARIES)-1 and 2 pivotal trials of ambrisentan, a once-daily oral endothelin-1 antagonist. Long-term outcomes in the ARIES-E extension study were also evaluated. RESULTS: At 12 weeks, ambrisentan-treated patients with both early and late functional class showed similar improvement in 6MWD relative to placebo. However, patients with more severe disease tended to have greater improvement in 6MWD after grouping by other measures of severity. This included higher baseline BNP level, shorter baseline 6MWD and more severe baseline haemodynamics (p < 0.05 for BNP and p = NS for other comparisons, analysed as interaction terms). During long-term open label follow-up, maintenance of 6MWD improvement, freedom from clinical worsening and survival were also numerically worse for patients who were functional class III/IV at baseline. CONCLUSIONS: Patients with both less severe and more severe PAH benefited from ambrisentan therapy vs. placebo in 12-week clinical trials and during long-term follow up, but greater improvement vs. placebo was seen for those with higher BNP levels.
Subject(s)
Hypertension, Pulmonary/drug therapy , Phenylpropionates/therapeutic use , Pyridazines/therapeutic use , Randomized Controlled Trials as Topic/methods , Female , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/mortality , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Research Design , Severity of Illness Index , Survival Analysis , Treatment OutcomeABSTRACT
More than 30 million men are estimated to have erectile dysfunction (ED) in the United States. Worldwide, ED is estimated to affect more than 150 million men, and that number is expected to exceed 300 million men by the year 2025. The prevalence of ED ranges from 7% in men aged 18-29 years to 85% in men aged 76-85 years. In addition, a recent report showed that 68% of patients with ED aged 18 years and older have at least one comorbid diagnosis of hypertension, hyperlipidaemia, diabetes or depression, and research suggests that ED may be an early indicator of systemic vascular disease. Viagra (sildenafil citrate), the first-in-class phosphodiesterase type 5 (PDE5) inhibitor, was introduced in 1998 for the treatment of ED. In the 7 years since its market launch, more than 750,000 physicians have prescribed sildenafil to more than 23 million men, helping establish an excellent safety and efficacy record. Clinical studies have demonstrated that sildenafil successfully treats ED of varied organic, psychogenic or mixed aetiology, and is effective in men with ED and comorbidities such as hypertension, hyperlipidaemia, diabetes or depression. Sildenafil was a breakthrough medication that addressed a previously unfulfilled medical need. The impact of sildenafil has stimulated academic, clinical and industrial research to better understand the nature of sexual function and develop better treatment and management for sexual dysfunctions such as ED. With the advent of other erectogenic therapies for the treatment of ED, this 7-year update will focus on the unique history and development of sildenafil, its current use and applications and its future directions and indications. Special emphasis is placed on the impact of sildenafil on our understanding of sexual health and on the extensive safety and efficacy data that have been amassed from numerous clinical trials.
Subject(s)
Erectile Dysfunction/drug therapy , Piperazines/therapeutic use , Vasodilator Agents/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/prevention & control , Drug Interactions , Erectile Dysfunction/psychology , Female , Humans , Male , Purines , Sexual Dysfunction, Physiological/drug therapy , Sildenafil Citrate , SulfonesABSTRACT
We studied variability in doxorubicin pharmacokinetics in 24 patients with abnormal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography. The relationship between doxorubicin clearance (dose/AUC) and liver biochemistry tests (AST, bilirubin, albumin, alkaline phosphatase and indocyanine green clearance) was investigated. Patients with a raised bilirubin level had reduced doxorubicin clearance, but there was no clear relationship between the extent of this elevation and the reduction in doxorubicin clearance. Doxorubicin clearance was lower in patients with an isolated increase in AST than in those with normal liver biochemistry, but this difference was not statistically significant. Nevertheless, there was a significant correlation between reduced doxorubicin clearance and both raised serum AST levels and low indocyanine green clearance. These pharmacokinetic data suggest that current dose reductions based solely on the extent to which bilirubin is elevated may not be optimal.
Subject(s)
Antibiotics, Antineoplastic/pharmacokinetics , Doxorubicin/pharmacokinetics , Liver/metabolism , Adult , Aged , Aged, 80 and over , Antibiotics, Antineoplastic/administration & dosage , Aspartate Aminotransferases/metabolism , Bilirubin/metabolism , Doxorubicin/administration & dosage , Female , Humans , Indicators and Reagents/metabolism , Indocyanine Green/metabolism , Male , Metabolic Clearance Rate , Middle AgedABSTRACT
This study was designed to measure whether a single dose of 120 mg pseudoephedrine ingested 120 min before exercise influences performance during 1 h of high-intensity exercise. The effects of exercise on urinary excretion of the drug were also studied. Ten healthy male cyclists were tested on two occasions, separated by at least 7 days, by using a randomly assigned, double-blind, placebo-controlled, crossover design. Exercise performance was tested during a 40-km trial on a laboratory cycle ergometer, and skeletal muscle function was measured during isometric contractions. On a third occasion, subjects ingested 120 mg pseudoephedrine but did not exercise [control (C)]. Pseudoephedrine did not influence either time trial performance [drug (D) vs. placebo: 58.1 +/- 1.4 (SE) vs. 58.7 +/- 1.5 min] or isometric muscle function. Urinary pseudoephedrine concentrations were significantly increased 1 h after exercise (D vs. C: 114.3 +/- 27.2 vs. 35.4 +/- 13.1 micrograms/ml; P < 0.05). Peak plasma pseudoephedrine concentrations (P < 0.05) but not time taken to reach peak plasma concentrations or the area under the plasma pseudoephedrine concentration vs. time curve was significantly increased in the total group with exercise (D vs. C). In three subjects, plasma pseudoephedrine concentrations were not influenced by exercise. Only these subjects showed increased urinary pseudoephedrine excretion during exercise. We conclude that a single therapeutic dose of pseudoephedrine did not have a measurable ergogenic effect during high-intensity exercise of 1-h duration, but plasma drug concentrations and urinary excretion were altered by exercise. These findings have practical relevance to doping control regulations in international sporting competitions.
Subject(s)
Ephedrine/metabolism , Ephedrine/pharmacology , Exercise/physiology , Urination/drug effects , Adult , Humans , Hydrogen-Ion Concentration , MaleABSTRACT
We studied the variability in doxorubicin pharmacokinetics in 27 patients, all of whom had normal liver biochemistry tests. Blood samples were collected after the first cycle of single-agent doxorubicin given as an i.v. bolus and plasma levels were measured by high-performance liquid chromatography (HPLC). The relationship of doxorubicin clearance (dose/AUC) with biochemical tests (AST, bilirubin, alkaline phosphatase, albumin, creatinine) and physical characteristics (age, gender, height, weight, tumour type) was investigated. The 6 men had a significantly higher doxorubicin clearance than did the 21 women (median values, 59 and 27 lh-1 m-2, respectively; P = 0.002). Doxorubicin clearance was significantly lower in patients with breast cancer than in those with other tumours (median values, 26 and 53 lh-1 m-2, respectively; P = 0.0008). The other biochemical and physical parameters did not correlate with doxorubicin clearance. However, in multivariate analysis, gender was the only factor predicting doxorubicin clearance (r2 = 40%). The ratio of the AUCs for doxorubicinol and doxorubicin (R) was higher in the men than in the women (median values, 0.62 and 0.36, respectively; P = 0.03). We conclude that gender may be an important determinant of doxorubicin clearance in patients with normal liver biochemistry.
Subject(s)
Antibiotics, Antineoplastic/pharmacokinetics , Doxorubicin/pharmacokinetics , Liver/metabolism , Adult , Aged , Antibiotics, Antineoplastic/blood , Chromatography, High Pressure Liquid , Doxorubicin/blood , Female , Half-Life , Humans , Male , Metabolic Clearance Rate , Middle Aged , Neoplasms/drug therapy , Neoplasms/metabolism , Sex CharacteristicsSubject(s)
Doping in Sports , Ephedrine/urine , Exercise/physiology , Nonprescription Drugs , HumansABSTRACT
Between June 1982 and April 1983, a procedure to coapt the extensor hallucis longus (EHL) to the tibialis anterior was performed in eight post-polio patients to correct drop foot and to enable the EHL to be a more efficient dorsiflexor of ankle. Although at early follow-up, every patient was able to actively dorsiflex the ankle against gravity, at final review, (mean follow-up 7.8 years), only two patients could still do so. Three patients developed a cock-up toe deformity or dorsiflexion deformity of great toe. We have attributed the poor final results to stretching of the coaptation. Use of splints or orthosis for a longer period postoperatively and a more carefully designed physical therapy may have yielded better results. Alternatively, if the EHL is anchored to navicular bone better results may be obtained.
Subject(s)
Foot Deformities, Acquired/surgery , Muscles/surgery , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Foot Deformities, Acquired/etiology , Humans , Leg/surgery , Male , Postpoliomyelitis Syndrome/complications , Tendons/surgery , Treatment OutcomeSubject(s)
Attitude of Health Personnel , Smoking , Female , Humans , Male , Social Control, Formal , South Africa , Students, MedicalABSTRACT
A phase II trial of idarubicin was performed in 24 patients with advanced lymphoma. The drug was administered in a dose of 10-15 mg/m2 i.v. or 15-70 mg/m2 p.o. (single dose) every 3 weeks. There were four partial responses and four minor responses. All but one of the responders had received prior doxorubicin therapy. The toxicities were myelosuppression, nausea and vomiting, and alopecia. Two patients with compromised cardiac function were observed to have further deterioration in the ejection fraction as measured by gated cardiac scan after idarubicin therapy. Further assessment of the activity of idarubicin against lymphoma is recommended in less heavily pretreated patients. The cardiac toxicity should be carefully monitored in future studies.
Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Daunorubicin/analogs & derivatives , Lymphoma/drug therapy , Antibiotics, Antineoplastic/adverse effects , Bone Marrow Diseases/chemically induced , Daunorubicin/adverse effects , Daunorubicin/therapeutic use , Drug Evaluation , Heart Diseases/chemically induced , Humans , IdarubicinABSTRACT
The plasma pharmacokinetics of idarubicin (4-demethoxydaunorubicin) were studied in 20 patients with advanced malignant disease after intravenous (21 occasions) and oral (14 occasions) administration. Idarubicin plasma concentrations were measured by high performance liquid chromatography with fluorescence detection. Pharmacokinetic parameters calculated for the intravenous plasma drug concentration, time data revealed a terminal half-life of 12.9 +/- 6.0 h (mean +/- s.d.), clearance 98.7 +/- 47.3 1 h-1 m-2 and volume of distribution 1533 +/- 536 1 m-2. A bi-exponential equation corresponding to a two compartment open model best fitted the data. Half-life and clearance were not significantly different following oral administration. Bioavailability of oral idarubicin was 0.29 +/- 0.20 (mean +/- s.d.). There was a wide range of bioavailability between and within subjects. Plasma concentrations of idarubicinol (the only metabolite detected) rapidly exceeded those of the parent drug, and exposure to this metabolite was greater than to the parent drug. The mean half-life of idarubicinol was not significantly different after i.v. (63.1 +/- 28.2 h) and oral (45.8 +/- 16.0 h) administration. Much larger amounts of this metabolite were formed following the oral route of administration. This may have implications for the clinical use of this drug as idarubicinol may have appreciable cytotoxic activity.
Subject(s)
Daunorubicin/analogs & derivatives , Neoplasms/drug therapy , Administration, Oral , Adult , Aged , Biological Availability , Daunorubicin/administration & dosage , Daunorubicin/blood , Daunorubicin/therapeutic use , Female , Half-Life , Humans , Idarubicin , Infusions, Intravenous , Kinetics , Male , Middle Aged , Neoplasms/bloodABSTRACT
Oxprenolol in an Oros 8/130 sustained release osmotic pump system (equivalent to 120 mg oxprenolol hydrochloride in a conventional formulation and releasing 8 mg h-1) was given to eight normal young subjects (mean age 23 years) and eight elderly hypertensive patients (mean age 77 years). The plasma concentration-time profiles of oxprenolol were determined over 32 h using gas liquid chromatography after the initial dose and following seven doses. The elderly patients had a significantly higher AUC and maximum plasma oxprenolol concentration following both the first and final doses studied. It is unlikely that this difference is due to a prolonged absorption phase in the elderly patients. Reduced drug clearance seems the most probable explanation.
Subject(s)
Oxprenolol/administration & dosage , Adult , Age Factors , Aged , Blood Proteins/metabolism , Delayed-Action Preparations , Drug Evaluation , Female , Humans , Hypertension/drug therapy , Hypertension/metabolism , Kinetics , Liver/metabolism , Male , Oxprenolol/blood , Oxprenolol/metabolism , Protein BindingABSTRACT
The effect of simultaneous oral administration of 20, 40, or 80 mg domperidone on the pharmacokinetics of an oral 500 mg dose of levodopa was studied in eight normal women. No significant differences in maximum plasma levodopa concentration, the time of its attainment, or the area under the plasma levodopa concentration versus time profile occurred. Domperidone significantly reduced the incidence of adverse gastrointestinal effects due to levodopa administration.
Subject(s)
Domperidone/pharmacology , Levodopa/metabolism , 3,4-Dihydroxyphenylacetic Acid/metabolism , Adult , Female , Half-Life , Humans , Intestinal Absorption/drug effects , KineticsABSTRACT
Flusoxolol (Ro 31-1411) is the pharmacologically active optical isomer of Ro 31-1118, a potent cardioselective beta-adrenoceptor antagonist with partial agonist activity. It was given to 6 healthy volunteers in a single dose, 40 mg, and then in multiple doses, 40 mg daily for 8 days. Plasma concentration data were best described by a linear two-compartment pharmacokinetic model with first order absorption, and the results confirmed linear kinetics. Pharmacokinetic data for flusoxolol were comparable to those for the racemate Ro 31-1118.
Subject(s)
Adrenergic beta-Antagonists/metabolism , Propanolamines/metabolism , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/blood , Adult , Humans , Kinetics , Male , Phenoxypropanolamines , Physical Exertion , Propanolamines/administration & dosage , Propanolamines/bloodABSTRACT
The plasma cortisol response to 0.25 mg tetracosactrin given by intramuscular injection was suppressed by nine oral doses of 200 mg ketoconazole given 12 hourly to nine normal female subjects. No effect was noted following a single 200 mg oral dose of ketoconazole. This suppressive effect was reversible within at least 5 days of discontinuation of ketoconazole.
Subject(s)
Adrenal Cortex/drug effects , Ketoconazole/administration & dosage , Adrenal Cortex Function Tests , Adult , Cosyntropin , Female , Humans , Hydrocortisone/blood , Ketoconazole/pharmacology , Time FactorsSubject(s)
Disabled Persons , Nurses , Patient Advocacy , Female , Humans , Interprofessional Relations , ParaplegiaABSTRACT
Persistent effects of a short course of intra-articular dextran sulphate, dextrans, or chondroitin sulphate were examined in rabbit knees. Only dextran sulphate produced gross arthritis, associated with high synovial acid phosphatase and beta-glucuronidase activities. Synovial degradative capacity in synovium-cartilage cocultures was increased 2-fold by dextran sulphate and 1.5-fold by chondroitin sulphate treatments. Stimulation of cartilage breakdown in vitro paralleled the content of synovial marker enzyme at death of the animal, but the 2 responses could be dissociated.
Subject(s)
Arthritis/chemically induced , Chondroitin Sulfates , Chondroitin , Dextrans , Animals , Arthritis/metabolism , Cartilage, Articular/metabolism , Chondroitin/analogs & derivatives , Culture Techniques , Knee Joint , Proteoglycans/metabolism , Rabbits , Sulfates , Synovial Membrane/enzymologyABSTRACT
We assessed the accuracy of clinical evaluation, arthrography, and arthroscopy in the diagnosis of meniscal lesions in fifty knees in which arthrotomy was performed for disabling symptoms after evaluation by these three methods. At surgery, forty-seven menisci were removed, of which forty-four were abnormal and three were normal. In three patients with normal menisci, loose bodies were found in two and the exploration was negative in one. In the forty-four knees with a meniscal lesion, a correct diagnosis was made clinically forty time, arthrographically thirty-nine times, and arthroscopically thirty-two times. Most errors occurred in the knees with posterior horn lesions of the medial meniscus. Clinical diagnosis was least accurate for lesions of the lateral meniscus (four missed) and arthroscopy was least accurate for lesions of the posterior horn of the medial meniscus (ten missed). Arthrography appeared to provide collateral evidence of lesions not seen directly. Based on this study it was concluded that even with negative findings by arthroscopy and arthrography it still may be necessary occasionally to remove a meniscus on the basis of the clinical evaluation.
Subject(s)
Knee Injuries/diagnosis , Tibial Meniscus Injuries , Adult , Aged , Diagnostic Errors , Endoscopy , Evaluation Studies as Topic , Female , Humans , Knee Injuries/diagnostic imaging , Male , Menisci, Tibial/diagnostic imaging , Middle Aged , RadiographyABSTRACT
Between 1953 and 1974 the author made psychiatric examinations for the prosecution of 400 persons, 367 males and 33 females, accused of the murders of 307 victims, 194 males and 113 females. The 367 males were accused of 273 murders, 172 male and 101 female victims, and the 33 females were accused of 34 murders, 22 male and 13 females victims. The salient features amongst the accused were maleness, youthfulness, the causal importance of alcohol, the rarity of suicide after murder an the high percentage of psychiatrically normal persons: in these last two respects the picture differed from that reported in England and Wales. The normality of these Scottish accused was further shown by the finding that in the decade 1965 to 1974 no material psychiatric abnormality was seen in 90 per cent of the males examined.