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Biomedical subjects

J L Donovan

Publications and source records attributed to J L Donovan.

At least 37 records · Page 2Linked to original sources

Transurethral prostatic resection or laser therapy for men with acute urinary retention: the ClasP randomized trial.

PURPOSE: Transurethral resection of the prostate is the standard operation for acute urinary retention, although laser prostatectomy is reportedly effective and safe. The ClasP (conservative management, laser, transurethral resection of the prostate) study compared transurethral prostatic resection and noncontact neodymium (Nd):YAG visual laser assisted prostatectomy for treatment of acute urinary retention. MATERIALS AND METHODS: This study was a multicenter randomized controlled trial, analyses were by intention to treat and followup was at 7.5 months after randomization. Primary outcomes were treatment failure, and included International Prostate Symptom Score, International Prostate Symptom Score quality of life score, residual urine and flow rate. Secondary outcomes included complications, and duration of catheterization and hospitalization. RESULTS: A total of 148 men were randomized to transurethral prostatic resection (74) and laser (74). There were fewer treatment failures after prostatic resection (p = 0.008) and fewer men after resection required secondary surgery for poor results (1 versus 7, p = 0.029). Maximum flow rates after transurethral prostatic resection were better than after laser (mean difference 4.4 ml. per second). Comparison of symptom and quality of life scores demonstrated that any clinically significant advantage for laser could be ruled out. Patients stayed a mean of 2 extra days in the hospital after resection. The duration of catheterization was greater after laser but significantly fewer major treatment complications were found with laser therapy. CONCLUSIONS: Transurethral prostatic resection was more effective, resulted in fewer failures than laser treatment and remains the procedure of choice for men with acute urinary retention.

Acute Disease↗

A primer on caffeine pharmacology and its drug interactions in clinical psychopharmacology.

Caffeine in the form of various beverages and as an additive in numerous drug formulations is the most widely consumed drug in the world. Its psychostimulant properties account for much of its popularity. Caffeine has multiple pharmacological effects that influence normal physiological functioning, and it has been suspected of contributing to morbidity. Drug interactions of caffeine with other psychoactive drugs are described. This review summarizes the pharmacology of caffeine and its drug interactions relevant to the practice of clinical psychopharmacology. The impact of caffeine consumption should be considered in planning and assessing responses to pharmacotherapy for mental illness.

Animals↗

Qualitative study of interpretation of reassurance among patients attending rheumatology clinics: "just a touch of arthritis, doctor?".

OBJECTIVES: To examine commonly used methods of reassurance by clinicians and explore their effect on patients. DESIGN: Qualitative study of tape recordings of in-depth, semistructured interviews with patients before and after consultation and of their consultations with doctors. SETTING: NHS specialist rheumatology clinics in two large British cities. PARTICIPANTS: 35 patients selected by consultant rheumatologists from general practitioner referral letters (28 women, 7 men; 24 with inflammatory arthropathies, 11 other rheumatological complaints). MAIN OUTCOME MEASURES: Patients' perceptions of reassurance. RESULTS: Reassurance was an important part of consultations, whether the diagnosis was clear or uncertain. Clinicians tried to reduce anxiety by emphasising the mildness, early stage, or non-seriousness of the disorder and the likelihood that patients would recover. Patients interpreted reassurance in the context of their own views and perceptions. Doctors' emphasis on the mildness or earliness of the condition raised the spectre of future pain and disability rather than providing reassurance. Patients who felt that their problems were properly acknowledged felt more reassured. CONCLUSIONS: Typical patterns of reassurance were not successful because of the differences in perspective of patients and doctors. A key to successful reassurance seemed to be the doctor's ability to acknowledge patients' perspectives of their difficulties.

Adult↗

Unanswered questions in screening for prostate cancer.

Prostate cancer fulfils some of the conditions required of a disease that might be managed by population screening. In a cohort of 50- to 60-year-old men, carrying out a rectal examination and prostate specific antigen (PSA) test will detect clinically suspicious areas within the prostate in approximately 5%, and approximately 10% will have a raised PSA. We are however unsure which of the prostate cancers that are known to be present in approximately 30-40% of men aged over 60 years will be detected. Eventually after such screening, around 4% of men with an otherwise normal prostate will be found to have prostate cancers. The use of rectal examination may increase the number of tumours found, but will reduce compliance. The use of free/total PSA ratios will reduce the number of unnecessary biopsies at the expense of missing some tumours. Of more concern, we remain uncertain how effective aggressive local treatment is in altering the natural history of the disease. The risk of a 50-year-old man with a 25 year life expectancy of having microscopic cancer is 42%, of having clinically evident cancer is 9.5%, and of dying of prostate cancer 2.9%. Only a small proportion of cancers known to be present become clinically evident: more men die with prostate cancer than of it. Screening will identify some men with cancer who will not benefit from treatment. It is unclear whether screening would be followed by a reduction in morbidity and mortality. Recent data suggest a screening effect has been observed in the USA with: an increase in incidence, a decrease in men with distant metastases. The small decrease in mortality recently observed (many times smaller than the increase in incidence) may be confounded by inappropriate 'attribution' of cause of death, the detection of men with better prognosis distant metastatic disease responsive to hormonal ablation and changes in social factors such as diet. Future changes may incorporate molecular markers that might aid identification of men best treated aggressively because of a risk of progression. Tests to identify genetic pre-disposition may also allow targeted screening. New treatments and early chemoprevention or dietary strategies will again shift the ground on which these arguments are being rehearsed. The most urgent evidence required concerns the effectiveness of treatment strategies.

Cost of Illness↗

Prostate cancer: to screen or not to screen?

The aim of screening is to identify cancers that are potentially curable; before a programme can be introduced, it must satisfy the requirement that it does more good than harm, particularly in terms of survival and quality of life. Prostate cancer is a common disease in older men and presents a significant burden to health services. Prostatic tumours range from small slow-growing lesions to aggressive tumours that metastasise rapidly, but because the natural history of prostate cancer is poorly understood, there is controversy about which screen-detected lesions will become clinically significant. Current methods of screening involve measurement of serum prostate specific antigen, followed by transrectal ultrasound scanning and biopsy, but these lack adequate specificity and sensitivity. There are three major treatment options for localised disease: radical prostatectomy, radical radiotherapy, and monitoring with treatment if required. There is no randomised controlled trial evidence to suggest a survival advantage of any of these treatments, and each has risks. There is intense speculation about future developments in diagnostic testing, molecular markers of progression, and early chemoprevention, but the central question that remains is whether radical treatments can improve survival and quality of life.

Biopsy, Needle↗

(+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine.

BACKGROUND: Red wine consumption may decrease the risk of coronary heart disease through the actions of its constituent flavonoids. (+)-Catechin is an abundant flavonoid in red wine. OBJECTIVE: The objective was to determine changes in plasma (+)-catechin concentrations after ingestion of a single, moderate serving of dealcoholized red wine reconstituted with either water (DRW) or water and alcohol (ARW). DESIGN: Nine subjects (5 men, 4 women) ingested, in random order, 120 mL DRW on one day and 120 mL ARW on another day. Both the DRW and ARW contained 35 mg (121 micromol) free (+)-catechin. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, and 8 h. Plasma was analyzed by gas chromatography-mass spectrometry for (+)-catechin after enzymatic release of sulfate and glucuronide conjugates. RESULTS: Calcium ions were needed to effectively hydrolyze (+)-catechin conjugates in plasma containing EDTA. Neither the ARW or DRW nor sex affected the area under the curve at 8 h, the maximum concentration (c(max)), or the time it took for plasma total (+)-catechin to reach maximum concentration (t(max)). Pooled mean (+/-SEM) values for the ARW and DRW were as follows: area under the curve, 306.1 +/- 29.5 nmol*h/L; c(max), 76.7 +/- 7.5 nmol/L; and t(max), 1.44 +/- 0.13 h. The half-life of (+)-catechin in plasma was significantly less (P = 0.038) after ingestion of the ARW (3.17 h) than after ingestion of the DRW (4.08 h). CONCLUSIONS: Increases in plasma total (+)-catechin concentrations were not significantly different after single moderate servings of either the ARW or DRW. Alcohol in the ARW hastened the elimination of (+)-catechin from the plasma compartment. (+)-Catechin elimination may represent excretion or conversion to methylated derivatives.

Adult↗

Nocturnal incontinence in women: a hidden problem.

PURPOSE: We determined the prevalence of nocturnal incontinence and its association with other storage symptoms in a community population of women MATERIALS AND METHODS: We mailed the validated self-reporting Bristol female lower urinary tract symptom questionnaire to all 2,641 women 19 years old or older registered at a family physician practice in a major British city and analyzed the results. Main outcome measures were the prevalence of nocturnal incontinence and its correlation with other storage symptoms. RESULTS: A total of 2,075 completed questionnaires (80%) were returned. The overall prevalence of nocturnal incontinence was 5.8%. However, the majority of women had nocturnal incontinence only occasionally and only 1% had it more than a third of the time. The prevalence of nocturnal incontinence increased in a linear fashion with age (chi-square test for linear trend p <0.005). Of the women with nocturnal incontinence 69% considered it troublesome. The odds of nocturnal incontinence were significantly increased when urge and stress incontinence, incontinence with no obvious cause, urgency, straining and nocturia were reported. CONCLUSIONS: Nocturnal incontinence in women is more common than generally supposed and troublesome. The rate of nocturnal incontinence increases with coexisting storage symptoms.

Adult↗

A prospective randomized trial comparing transurethral resection of the prostate and laser therapy in men with chronic urinary retention: The CLasP study.

PURPOSE: We assessed the effectiveness of laser therapy versus transurethral prostatic resection in men with symptomatic chronic urinary retention secondary to benign prostatic enlargement. MATERIALS AND METHODS: This trial was multicenter, pragmatic and randomized. Analysis was done by intent to treat. Laser therapy involved neodymium:YAG noncontact visual prostate ablation, while transurethral prostatic resection was performed by standard electroresection. Patients were included in our study if they reported moderate to severe lower urinary tract symptoms with an International Prostate Symptom Score (I-PSS) of 8 or more, benign prostatic enlargement and a persistent post-void residual urine volume of more than 300 ml. Followup was 7.5 months. Primary outcome measures included the I-PSS, I-PSS quality of life score, maximum urinary flow and post-void residual urine volume. Secondary outcome measures included treatment failure, complications, hospital stay and catheterization time. RESULTS: A total of 82 patients agreed to be randomized to receive laser therapy (38) or transurethral prostatic resection (44). There were significant improvements in all primary outcomes in each group from randomization to followup. Transurethral prostatic resection was significantly better than laser therapy for I-PSS and maximum urinary flow values (p = 0.035 and 0.029, respectively) but there were no differences in post-void residual urine volume and I-PSS quality of life score between the groups. We noted significantly more treatment failures with laser therapy than resection (8 versus 0, p = 0.0014), although only 3 patients required resection after laser therapy because of persistent symptoms. In addition, hospital stay after resection was 2-fold that after laser therapy (ratio of geometric means 2.01, 95% confidence interval 1.54 to 2.61, p <0.0001). However, time to catheter removal was 9 times longer in the laser therapy group (p <0. 0001). Complication rates were significantly higher for transurethral prostatic resection (chi-square 5.05, 1 df, p = 0.025). CONCLUSIONS: Transurethral prostatic resection is more effective than laser ablation in men with chronic urinary retention in terms of symptom score, maximum urinary flow and failure. However, men who underwent resection had significantly more treatment complications and were hospitalized longer than those who received laser therapy. This finding implies that laser ablation therapy may have a role in patients at higher risk who are willing to accept a lower level of effectiveness in exchange for decreased complication rates and hospital stay.

Humans↗

A randomized trial comparing transurethral resection of the prostate, laser therapy and conservative treatment of men with symptoms associated with benign prostatic enlargement: The CLasP study.

PURPOSE: We evaluated the effectiveness of a new technology (noncontact laser therapy) versus that of standard surgery (transurethral prostatic resection) and conservative management for lower urinary tract symptoms associated with benign prostatic enlargement. MATERIALS AND METHODS: Men with uncomplicated lower urinary tract symptoms, that is no acute or chronic urinary retention, were randomized to receive laser therapy with a noncontact, side firing neodymium:YAG probe, standard transurethral prostatic resection or conservative management, including monitoring without active intervention, in a large multicenter pragmatic randomized controlled trial called the CLasP study. Primary outcomes were International Prostate Symptom Score (I-PSS), maximum urinary flow rate, a composite measure of success based on I-PSS and maximum urinary flow rate categories, I-PSS quality of life score and post-void residual urine volume. Secondary outcomes included treatment failure, hospital stay and major complications. Followup was 7.5 months after randomization. Intent to treat analysis was done using analysis of covariance, proportional odds models and the Newman-Keuls multiple comparisons procedure. RESULTS: Of symptomatic patients 117, 117 and 106 were randomized to receive laser therapy, transurethral prostatic resection and conservative management, respectively. Baseline characteristics were similar. All primary outcomes indicated that transurethral prostatic resection and laser therapy were superior to conservative management, and resection was superior to laser therapy. As measured by combined improved symptoms and maximum urinary flow, a successful outcome was achieved in 81%, 67% and 15% of men who underwent transurethral prostatic resection, laser therapy and conservative management, respectively. Hospital stay was significantly shorter and complications fewer for laser therapy than for resection but catheters were in place significantly longer. Men treated conservatively did not have deterioration or treatment failure. CONCLUSIONS: Laser therapy and transurethral prostatic resection are effective for decreasing lower urinary tract symptoms and post-void residual urine volume as well as improving quality of life and maximum urinary flow in the short term in men presenting with moderate to severe symptoms. Transurethral prostatic resection is superior to laser therapy in terms of effectiveness but some patients may elect laser therapy due to the shorter hospital stay and lower risk of complications. Conservative management may be acceptable and safe in men with lower urinary tract symptoms since we observed no marked deterioration in the short term.

Aged↗

Scoring the short form ICSmaleSF questionnaire. International Continence Society.

PURPOSE: The International Continence Society (ICS) ICSmale questionnaire was devised to provide a thorough evaluation of the occurrence and bothersomeness of lower urinary tract symptoms and their impact on the lives of men with benign prostatic disease. This report completes the developmental work on the questionnaire, producing the concise short form instrument, ICSmaleSF, with a valid, reliable and scientifically justified scoring system. MATERIALS AND METHODS: Two data sets were used. The short form version of the questionnaire was devised and initially evaluated using data on men with uncomplicated lower urinary tract symptoms who were involved in the CLasP randomized controlled trial comparing laser therapy with transurethral prostatic resection and conservative management or monitoring without active intervention. External validation of the scoring system was undertaken using data from phase II of the ICS benign prostatic hyperplasia (BPH) study, an observational study of outcome in men with lower urinary tract symptoms related to benign prostatic enlargement. All patients completed the developmental version of the ICSmale questionnaire. Parallel analysis on the CLasP data set identified items that were responsive to change or highly problematic, allowing other redundant and overlapping items to be eliminated. Factor analysis and Cronbach's alpha coefficients were used to examine the clustering of items. Regression models were used to investigate the validity of followup scores within and across treatment groups in the CLasP and ICS/BPH studies. RESULTS: The questionnaire, which originally comprised 22 items, was shortened to 11 items in the 2 distinct factors of voiding (ICSmaleVS) and incontinence (ICSmaleIS) symptoms. Cronbach's alpha coefficients were high at 0.76 for ICSmaleVS and 0.78 for ICSmaleIS. A simple additive score was calculated by adding the 5 items in ICSmaleVS and 6 in ICSmaleIS. ICSmaleVS and ICSmaleIS detected expected improvement in the laser therapy and transurethral prostatic resection groups, and stability in the conservative management group within CLasP. Similarly each subscore but particularly ICSmaleVS was sensitive to differences in the outcome of the range of treatments in the ICS/BPH study. While frequency and nocturia were highly problematic and sensitive to change individually, they did not load into the other main factors or correlate with each other. It is suggested that these symptoms should be evaluated separately with the additional inclusion of a single item measure of the impact of lower urinary tract symptoms on daily life. CONCLUSIONS: The ICSmaleSF represents a comprehensive, concise, valid and reliable instrument for evaluating men with lower urinary tract symptoms. Unlike other questionnaires in the field it contains subscores for the domains of voiding and incontinent symptoms as well as the separate consideration of frequency, nocturia and impact on daily life. We hope that it will become the tool of choice for the comprehensive evaluation of treatment of men with lower urinary tract symptoms associated with benign prostatic disease.

Humans↗

Analysis of (+)-catechin, (-)-epicatechin and their 3'- and 4'-O-methylated analogs. A comparison of sensitive methods.

(+)-Catechin and (-)-epicatechin are found in many foods and may have important effects on human health. These compounds, like many other catechols, are thought to be converted to methylated metabolites after ingestion. This paper describes the synthesis of the 3'- and 4'-methyl ethers and their unambiguous identification. These products, along with catechin, epicatechin and an internal standard, (+)-taxifolin, were separated using RP-HPLC with ultraviolet, electrochemical and fluorescence detection. The trimethylsilylated derivatives of the seven compounds were also separated by GC with mass spectrometric detection. The limits of detection and selectivity of the analytical methods were compared with respect to their application in complex matrices such as human plasma.

Catechin↗

The responsiveness of the ICSmale questionnaire to outcome: evidence from the ICS-'BPH' study.

OBJECTIVE: To evaluate the responsiveness of the ICSmale questionnaire to the outcome of treatments for lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Consecutive men aged >45 years attending 23 urology centres in 12 countries, with symptoms suggestive of bladder outlet obstruction secondary to benign prostatic hyperplasia (BPH), were recruited to Phase I of the International Continence Society (ICS)-'BPH' study. In Phase II of the ICS-'BPH' study, 355 men in 15 centres in nine countries were followed up, having proceeded to treatment according to clinical practice. All men completed the ICS-'BPH' study questionnaire at baseline and follow-up, including the ICSmale which concerns LUTS and related problems. RESULTS: Patients included in Phase II were similar to those in Phase I according to age and levels of baseline symptoms. Patients received a range of treatments: 32% TURP, 29% drug therapies, 20% watchful waiting, 9% minimally invasive therapies and 10% 'others' (including open prostatectomy). For patients who underwent TURP, most LUTS, including voiding and filling symptoms, were highly statistically significantly better at follow-up than at baseline (P<0.0001). For drug, minimally invasive and 'other' treatments, fewer LUTS were highly statistically significantly better. For those undergoing watchful waiting, no symptoms were significantly different between baseline and follow-up. CONCLUSION: The ICSmale questionnaire, in addition to being psychometrically valid and reliable, is responsive to change in outcome.

Age Factors↗

Catechin is present as metabolites in human plasma after consumption of red wine.

Flavonoids are components of fruits, vegetables and wines. An abundance of flavonoids in the diet is correlated with reduced heart disease mortality, suggesting that they act as protective nutrients. However, little is known about the absorption and metabolism of flavonoids after normal foods are consumed. This study measured the levels of one abundant flavonoid, (+)-catechin, and its metabolites in plasma after five male and four female volunteers consumed 120 mL of red wine (RW) one day and de-alcoholized red wine (DRW) on a separate day. Each wine sample contained 35 +/- 1 mg catechin (mean +/- SEM). Plasma levels of catechin and its metabolite 3'-O-methylcatechin (3'MC) were determined by gas chromatography-mass spectrometry (GC-MS) of the trimethylsilylated (TMS) derivatives. Glucuronide and sulfate conjugates were determined after enzymatic hydrolysis. Before RW or DRW consumption, plasma levels of catechin, 3'MC and all conjugates were <2 nmol/L. After 1 h, average levels of catechin, 3'MC and all conjugates increased to 91 +/- 14 nmol/L (RW) and 81 +/- 11 nmol/L (DRW). At 1 h, 21 +/- 1% of the metabolites were methylated and <2% of catechin and 3'MC were unconjugated. Catechin was present as both a sulfate conjugate and a conjugate containing both glucuronide and sulfate residues. 3'MC was present primarily as a glucuronide conjugate. At every time point, catechin was present almost exclusively as metabolites, and these levels were independent of ethanol. Therefore, if flavonoids are protective nutrients, the active forms are likely to be metabolites, which are far more abundant in plasma than the forms that exist in foods.

Adult↗