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Biomedical subjects

C H Young

Publications and source records attributed to C H Young.

At least 19 recordsLinked to original sources

Outpatient antidepressant utilization in a Dutch sick fund.

OBJECTIVE: To identify quality improvement opportunities in the management of depression by evaluating patterns of antidepressant use and concurrent use of anxiolytics or sedative/hypnotics among patients who initiated therapy with amitriptyline, fluoxetine, fluvoxamine, or paroxetine. DESIGN: A longitudinal, retrospective study using electronic prescription data from a Dutch sick fund, ZAO Zorgverzekeringen. PATIENTS AND METHODS: The study patients (n = 2,554) initiated therapy between October 1, 1994 and December 31, 1995. Follow-up periods were 6 months (antidepressant use) and 60 days (concurrent anxiolytic and sedative/hypnotic use). RESULTS: The three key findings were as follows: (1) the majority of patients received less than 4 months of therapy (more common for patients receiving amitriptyline); (2) the average daily doses for initial prescriptions for all four study drugs were below the recommended therapeutic minimums for depression (overall and final amitriptyline doses also were consistently low); and (3) the incidence of concurrent anxiolytic and sedative/hypnotic use during days 2-60 after antidepressant therapy initiation was 18.2%. CONCLUSION: The study suggests that patients in this Dutch sick fund were not likely to receive either adequate antidepressant doses or adequate durations of therapy relative to Dutch guidelines for the treatment of depression. These findings are consistent with findings in other Dutch, European, and US studies and may present opportunities for quality improvement.

Ambulatory Care↗

Concomitant use of selective serotonin reuptake inhibitors with other cytochrome P450 2D6 or 3A4 metabolized medications: how often does it really happen?

This study retrospectively examines the one-month concomitant use of cytochrome P450 2D6 or 3A4 metabolized medications in 544,309 patients who were also receiving selective serotonin reuptake inhibitors (SSRIs). Overall, 25.53% of SSRI patients experienced concomitant use with at least one of the 33 studied CYP 2D6 or 3A4 metabolized medications. Certain drugs and drug classes were more likely to be used concurrently among SSRI patients (e.g., benzodiazepines, tricyclic antidepressants, calcium channel blockers). Similarly, of the SSRI patients experiencing concomitant use, this concurrent use was twice as likely with cytochrome P450 medications metabolized by the 3A4 isoenzyme as with those metabolized by the 2D6 isoenzyme. Finally, the vast majority (80.9%) of SSRI patients experiencing concomitant use did so with one CYP 2D6 or 3A4 metabolized medication. In sum, concomitant use generally was not extensive and did not appear to be differential among the fluoxetine, paroxetine, or sertraline patient comparison groups.

1-Naphthylamine↗

Megakaryocyte growth and development factor (MGDF) moderately enhances in-vitro platelet aggregation.

Megakaryocyte growth and development factor (MGDF) is a novel cytokine which promotes the development of immature megakaryocytes into platelets. We tested the hypothesis that MGDF would alter the sensitivity of platelets to aggregating agents as assessed by in-vitro platelet aggregometry. Platelet aggregation in the presence or absence of MGDF was tested with single doses of clinically relevant aggregating agents. A dose-dependent enhancement of the aggregation response to epinephrine was noted in MGDF treated platelets. When a range of concentrations of ADP were used to generate an aggregation dose-response curve, the addition of MGDF to platelet rich plasma shifted the dose response curve to the left. The effect of MGDF on platelet aggregation was partially prevented by the coincubation of platelets with a soluble form of the receptor for MGDF, the extracellular domain of c-mpl. In addition, we demonstrate that exogenous MGDF is able to induce tyrosine phosphorylation of platelet proteins with apparent molecular weights of 85 kDa and 130 kDa. From these data we conclude that exogenously added MGDF moderately increases the sensitivity of platelets to aggregating agents through a mechanism which appears to involve tyrosine phosphorylation of platelet proteins.

Adenosine Diphosphate↗

Anaesthesia and cystic fibrosis.

Cystic fibrosis occurs in 1 in 2000 children and the majority now reach adulthood. The disease is a complex multisystem disorder which is likely to challenge anaesthetists with increasing frequency. In this review the presentation and genetics of the disease are briefly described, followed by a detailed account of the pathophysiology relevant to anaesthesia. The pre-operative assessment and conduct of anaesthesia are discussed and some suggestions made regarding management.

Adult↗

Effect of a sub-anaesthetic concentration of halothane on the ventilatory response to sustained hypoxia in healthy humans.

We selected nine normal subjects (8M, 1F; aged 25-43 yr) with brisk hypoxic ventilatory responses, and studied their ventilatory response to sustained isocapnic hypoxia (SaO2 82 (SEM 0.1) % for 25 min) in the presence and absence of 0.1% inspired halothane. Halothane had no significant effect on baseline ventilation or gas exchange. In the absence of halothane, ventilation increased initially from mean 7.57 (0.35) litre min-1 to 14.54 (0.91) litre min-1, and decreased subsequently to 10.74 (0.32) litre min-1 during hypoxia (both P < 0.05). In the presence of 0.1% inspired halothane, ventilation increased initially from 7.19 (0.47) litre min-1 to 12.08 (0.99) litre min-1 (P < 0.05), then decreased to 10.12 (0.28) litre min-1 during sustained hypoxia (ns compared with baseline normoxic ventilation). Halothane reduced significantly the initial increase in ventilation (P < 0.05), but did not enhance the subsequent decrease. These results confirm that a sub-anaesthetic concentration of halothane depresses the initial hypoxic ventilatory response; the response during prolonged periods of hypoxia is, however, less than the initial response and is reduced in the presence or absence of a sub-anaesthetic concentration of halothane.

Adult↗

Anterior transperitoneal approach to the upper urinary tract with one-stage bilateral procedure.

A total of 109 unilateral and 4 bilateral upper urinary tract conditions were treated surgically from 1975 to 1985 by the anterior transverse transperitoneal approach; 26 of these were malignant conditions and 87 were benign. The approach gives good access to the kidney, its pedicle and the upper ureter. There is no increased risk of peritonitis or paralytic ileus due to urinary leak. One-stage bilateral surgical procedures were performed in 4 cases. There was no added risk to the patients. It allows both kidneys to recover simultaneously and provides the opportunity of examining the other intra-abdominal organs.

Adolescent↗

Single dose, oral antibiotic cover for transurethral prostatectomy.

A double-blind, randomised, placebo-controlled study was carried out to determine the incidence and significance of bacteriuria in 110 patients undergoing transurethral resection of the prostate (TURP) and to assess the effect of a single pre-operative dose of Ciprofloxacin, a 4-quinolone antibiotic. Fifteen (68%) of the 22 patients in the placebo group with a positive post-operative urine culture subsequently developed a clinically apparent urinary tract infection (UTI) or received antibiotics in view of a positive urine culture. Adequate prostatic concentrations of Ciprofloxacin were achieved in all who received the drug. A significant reduction in the number of positive post-operative urine cultures and urinary tract infections requiring antibiotic therapy was achieved in this group. Six patients (5.5%) developed clinical evidence of septicaemia, 5 of whom were in the placebo group. No organisms resistant to Ciprofloxacin were encountered. Prior to surgery, 19% of all patients were found to have previously unsuspected bacteriuria. Ciprofloxacin tended to reduce the chances of this group developing a UTI or requiring antibiotics. Further, there was a highly significant reduction in post-operative infective complications in those with sterile urine at the time of resection who had received the drug. This study suggests that antibiotic cover for TURP is of clinical benefit. Ciprofloxacin may prove suited to this purpose, although further experience with the drug is still required.

Administration, Oral↗

Phase II study of Zoladex depot in advanced prostatic cancer with special reference to criteria of response and survival.

Zoladex is a potent decapeptide analogue of luteinising hormone releasing hormone (LHRH). The drug is formulated as a 3.6 mg depot dispersed in a matrix of d,l-lactide-glycolide copolymer, which is totally biodegradable. This formula releases drug continuously for at least 28 days and reliably suppresses serum testosterone into the castrate range. The effect of the depot was studied in 29 patients with locally advanced or metastatic carcinoma of the prostate. Average age at entry was 71 years (range 52-87) and follow-up was from 13.5 to 34.5 months (median 23). Endocrine studies showed that medical castration was maintained in all cases. Three patients experienced bone pain in the first month of treatment and two others had temporary nephrostomies for worsening ureteric obstruction. Subjective improvement was seen in 23/28 cases (82%). There were no complete responses, but partial response was seen in 24/28 (85.7%) using our own criteria, 24/28 (85.7%) using the criteria recommended by the British Prostate Group (BPG) and 15/28 (53.6%) using NPCP criteria. Stable disease was seen in 3/28 patients (10.7%) by our own or BPG criteria, and in 12/28 patients (42.9%) according to NPCP criteria. Progression of disease was measurable in 21 patients (72.4%) whatever criteria were applied; 11/29 (37.9%) have died, giving a median survival of 10 months (range 2.4-26). Following these encouraging results, a multicentre randomised comparative study with stilboestrol 3 mg daily is being undertaken.

Aged↗

Pharmacokinetic and endocrinological parameters of a slow-release depot preparation of the GnRH analogue ICI 118630 (zoladex) compared with a subcutaneous bolus and continuous subcutaneous infusion of the same drug in patients with prostatic cancer.

Seventeen patients with advanced prostatic cancer were treated with the gonadotrophin-releasing hormone analogue DSer (tBU)6 AzaGly 10 GnRH (ICI 118630), either as a constant SC infusion, or in the form of a monthly SC slowrelease depot formulation, in which case patients were randomised to receive one of three doses. Six of these patients also received a 250-microgram SC bolus of ICI 118630, for pharmacokinetic studies, before starting the infusion or the depot. Drug levels were measured using a double-antibody radioimmunoassay. In contrast to the SC infusion, which gave a smooth serum 118630 level profile, drug release from the depot preparation was not constant, levels varying in a predictable manner throughout each 28-day period, reaching a peak proportional to the dose of ICI 118630 received, between days 15 and 18 of each cycle. With all methods of administration there was an initial rise in LH, usually followed by a rise in testosterone, after which the SC infusion and the depot were both effective in reducing serum LH to basal levels and testosterone into the castrate range within 1 month. It is too early to make any assessment of clinical response; however, depot treatment was well tolerated: Four patients experienced an initial flare in bone pain, probably related to the initial rise in testosterone, and twelve patients experienced flushing; one patient with pre-existing hydronephrosis and hydroureter developed renal failure, possibly related to a tumour flare reaction. No patients have experienced cardiovascular side effects or local reaction.

Buserelin↗

Rotavirus infection in a geriatric population.

An outbreak of gastroenteritis affected 19 of 34 geriatric patients and four of 23 staff assigned to the ward in a period of 3 1/2 weeks in January 1980. Fourteen of the 19 patients with gastroenteritis (17 were tested properly) and four of the ten asymptomatic patients (five asymptomatic patients were not tested) showed evidence of rotavirus infection by virus positivity and/or a significant antibody response to rotavirus. One of the four staff members with gastroenteritis showed serologic evidence (three were tested) of rotavirus infection. Nine of the 18 asymptomatic staff members (two remaining staff members were not tested) showed a fourfold rise in antibody to rotavirus but four had antibody titers of 1:32 or more. The patients had diarrhea for a mean of 2.6 days. Most of them had five or fewer diarrheal stools in one day. Six patients had a severe illness and two died. Thirteen of 15 symptomatic patients who had serum samples, collected during the acute and convalescent phases, tested manifested high titers (greater than or equal to 1:32) of complement-fixing antibody to rotavirus antigen.

Adult↗

Selective serotonin reuptake inhibitor utilization patterns: consistency across research designs.

We examined the impact of commonly applied selection criteria on the ability of patients who are initiating antidepressant therapy to reach a stable pattern, which was defined as receipt of only the initial agent at the initial dose for 90 or more consecutive days. Patients in a large US prescription database who initiated fluoxetine, paroxetine, or sertraline therapy between February and April of 1995 were categorized as with (typical design) and without (relaxed design) commonly applied selection criteria. The percentage of patients achieving a stable pattern was then determined. We found that this percentage was significantly higher with the relaxed design (typical, 28.8%; relaxed, 32.4%) and for patients initiating fluoxetine therapy (>5.5% higher than for those initiating paroxetine or sertraline therapy). The results for fluoxetine were consistent across designs, whereas comparisons between paroxetine and sertraline yielded mixed results. Therefore, the relative relationship of the stable pattern is robust across designs for fluoxetine but not for paroxetine and sertraline. Further, application of commonly applied selection criteria may make a sample less representative and reduce the measured rates of stable antidepressant use, potentially leading to underestimation of the benefits of pharmacotherapy.

Adult↗