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Biomedical subjects

J T Farrar

Publications and source records attributed to J T Farrar.

At least 19 recordsLinked to original sources
PubMed2005

Suboptimal physician adherence to quality indicators for the management of gout and asymptomatic hyperuricaemia: results from the UK General Practice Research Database (GPRD).

OBJECTIVES: : To examine adherence to validated quality indicators assessing the quality of allopurinol use in the treatment of gout and asymptomatic hyperuricaemia. METHODS: We determined physician adherence in the UK General Practice Research Database (GPRD) to three validated quality indicators developed to assess the quality of allopurinol prescribing practices. These indicators were developed to assess: (i) dosing in renal impairment; (ii) concomitant use with azathioprine or 6-mercaptopurine; and (iii) use in the treatment of asymptomatic hyperuricaemia. We also examined the association of patient-level factors (sociodemographics, comorbidity, follow-up duration and concomitant medicine use) with the treatment of asymptomatic hyperuricaemia using multivariable logistic regression. RESULTS: Of the 63 105 gout patients, 185 (0.3%) were eligible for Quality Indicator 1 and 52 (0.1%) were eligible for Quality Indicator 2. There were an additional 471 patients with asymptomatic hyperuricaemia eligible for Quality Indicator 3. Rates of practice deviation for the three individual quality indicators ranged from 25 to 57%. Male sex, older age, a history of chronic renal failure, and a greater number of concomitant medications were significantly associated with increased odds of inappropriate treatment for asymptomatic hyperuricaemia. Hypertension and diuretic use were associated with lower odds of this practice. CONCLUSIONS: One-quarter to one-half of all patients eligible for at least one of the validated quality of care indicators were subject to possible allopurinol prescribing error, suggesting that inappropriate prescribing practices are widespread with this agent. Future interventions aimed at reducing inappropriate allopurinol use are needed and should be targeted towards high-risk groups, including older men and those receiving multiple concomitant medications.

Adult↗
PubMed2005

Gout epidemiology: results from the UK General Practice Research Database, 1990-1999.

OBJECTIVE: To examine the epidemiology of gout and gout treatment in the United Kingdom using a large national practice based population. METHODS: Data from the UK General Practice Research Database from 1990 to 1999 were examined. Physician diagnoses and drug codes were used, and trends in gout incidence and treatment examined. Additionally, disease prevalence for the year 1999 was assessed. To examine the association of gout with comorbid disease, the prevalence of select health conditions and drug use was compared with the corresponding prevalences seen in osteoarthritis, adjusting for both age and sex. RESULTS: From 1 January 1990 to 31 December 1999 overall gout incidence remained relatively stable, ranging from a low of 11.9 cases (95% confidence interval (CI) 11.5 to 12.3) in 1991 to a high of 18.0 cases (95% CI 17.6 to 18.4) per 10 000 patient-years in 1994. Gout prevalence in 1999 was 1.4% with rates approaching 7% in men over the age of 65. Drugs used for the treatment of gout remained constant in prevalent cases with the exception of a significant decline in non-steroidal anti-inflammatory drug use over the 10 year follow up. Compared with patients with osteoarthritis, patients with gout were significantly more likely to have cardiovascular disease, hypertension, diabetes, and chronic renal failure, and were more likely to have used diuretics or ciclosporin, or both. CONCLUSION: Although gout is common in the UK, particularly among older men, the incidence of the disease seems to have remained stable during the 1990s.

Adult↗
PubMed2005

Donepezil for dementia in Parkinson's disease: a randomised, double blind, placebo controlled, crossover study.

OBJECTIVE: To study the safety and efficacy of a cholinesterase inhibitor, donepezil hydrochloride, for the treatment of dementia in Parkinson's disease (PD). METHODS: This was a randomised double blind, placebo controlled, crossover study in 22 subjects with PD and dementia. Participants were randomised to receive either donepezil followed by identical placebo, or placebo followed by donepezil. Donepezil was administered at 5-10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAScog). RESULTS: Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the Unified Parkinson's Disease Rating Scale.There was a 1.9 point trend toward better scores on the ADAScog on treatment compared with placebo that was not statistically significant. The secondary cognitive measures showed a statistically significant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Change (CGI) showed a significant 0.37 point improvement on donepezil. No improvement was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover between treatment periods was observed but was not statistically significant. CONCLUSIONS: Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measured by CGI was reflected in only one of the cognitive scales used in this study.

Aged↗
PubMed2001

Response to first drug trial predicts outcome in childhood temporal lobe epilepsy.

OBJECTIVE: To construct a clinical prediction model for the early identification of children destined to develop refractory temporal lobe epilepsy (TLE) 2 years after epilepsy onset. METHODS: Patients with TLE between 1 and 18 years old seen in the Division of Neurology at Children's Hospital of Philadelphia during 1999 were identified through billing records and chart review. Data were abstracted independently on 5 candidate predictor variables for refractory TLE and on seizure frequency outcome at 2 years after epilepsy onset. RESULTS: One hundred twenty patients met inclusion criteria and had at least 2 years of follow-up. Forty-five of 120 patients (37.5%) had refractory TLE at 2 years after onset, and 75 of 120 (62.5%) were seizure free. Three significant predictors of refractory TLE were found on bivariate analysis: an early risk factor for epilepsy (risk ratio = 3.5 [95% CI 2.2, 5.6]), temporal lobe abnormality on MRI scan (2.9 [95% CI 1.9, 4.6]), and failure of the first antiepileptic drug (AED) trial (16.5 [95% CI 6.3, 43.9]). Logistic regression indicated that the best model to predict refractory TLE contained only the variable "failure of first AED trial," with a positive predictive value of 0.89 (95% CI 0.76, 0.96) and negative predictive value of 0.95 (95% CI 0.87, 0.99) to predict "refractory TLE" at 2 years. CONCLUSIONS: Failure of first AED trial accurately predicts refractory TLE at 2 years after onset, based on retrospective cohort data in children. If verified prospectively and with longer follow-up, this finding should support earlier consideration of surgical options.

Anticonvulsants↗
PubMed2001

Ethnicity influences morphine pharmacokinetics and pharmacodynamics.

OBJECTIVE: Our objective was to evaluate ethnic differences in response to morphine and to determine whether any detectable differences were pharmacokinetically based. METHODS: This cohort study was carried out in a teaching hospital. Sixty-six young, healthy male subjects from 3 ethnic groups (Caucasians, native Indians, and Latinos; n = 22 in each group) consented to participate. All subjects received an intravenous morphine bolus of 0.08 mg/kg followed by 0.002 mg/kg. min infused for 30 minutes. Respiratory response was evaluated with the carbon dioxide rebreathing method before and at 25, 95, 180, and 360 minutes after morphine administration. Vital signs and opioid side effects were recorded, and serial blood samples were analyzed for morphine, morphine-3-glucuronide, and morphine-6-glucuronide (M6G). RESULTS: All 3 groups had suppression of the ventilatory response to hypercapnia, but the degree of blunting of the ventilatory response differed among groups. Compared with Caucasians, native Indians had an additional 18% reduction in ventilatory response after morphine administration (95% confidence interval, -35% to -2%). The incidence of side effects was similar in all groups (P =.18). Caucasians had higher plasma levels of M6G than did native Indians or Latinos. M6G areas under 6-hour concentration-versus-time curve were as follows: Caucasians, 12,065 +/- 4354; native Indians, 8464 +/- 4809; and Latinos, 9156 +/- 3764 ng. min/mL (P =.03). CONCLUSIONS: Ethnicity influences the response to morphine. Native Indians are more susceptible to morphine depression of the ventilatory response than Caucasians, despite the higher serum M6G levels in Caucasians.

Adult↗
PubMed2001

Neuropathic cancer pain: the role of adjuvant analgesics.

Neuropathic pain may be defined as pain related to abnormal somatosensory processing in either the peripheral or central nervous system. This pathophysiologic label is typically applied when the painful symptom is associated with an overt injury to neural structures, is part of a recognized syndrome, or has a dysesthetic quality (usually burning, shooting, or electrical). Most neural injury does not lead to clinically important neuropathic pain, but sometimes even a small degree of tissue injury can precipitate severe pain. In the cancer population, neuropathic pain is often related to compression, direct neoplastic invasion of the peripheral nerves or spinal cord, or to a neuropathy caused by chemotherapy. To manage neuropathic pain in this population, nonopioid adjuvant drugs that are neuroactive or neuromodulatory are often needed to complement opioid therapy. The primary adjuvant analgesics are anticonvulsant and antidepressant medications, but a wide variety of other drugs are also used. To optimize analgesic therapy in patients with neuropathic pain, both opioid and adjuvant analgesics must be used effectively.

Analgesics↗
PubMed2000

Fifty landmark discoveries in gastroenterology during the past 50 years. A brief history of modern gastroenterology at the millennium: Part I. Gastrointestinal procedures and upper gastrointestinal disorders.

During the last half century, many outstanding discoverers have revolutionized the clinical practice and science of gastroenterology. Whereas the scientific results are widely disseminated, the discoverers have received inadequate recognition, and the history of their discoveries is poorly known. At the millennium, a committee selected the 50 landmark discoveries in gastroenterology during the past 50 years. A brief history of each landmark discovery is presented. Part I presents the landmark discoveries in gastrointestinal (GI) procedures and in upper GI disorders. Part II of this presentation, which covers landmark discoveries in other areas of gastroenterology, will publish in Part II of the volume on High Risk Gastrointestinal Bleeding.

Gastroenterology↗
PubMed2000

Fifty landmark discoveries in gastroenterology during the past 50 years. A brief history of modern gastroenterology at the millennium: Part II. Gastrointestinal motility, nutrition, and diseases of the lower gastrointestinal tract, liver, and pancreas.

During the last half century, many outstanding discoveries have revolutionized the clinical practice and science of gastroenterology. Although the scientific results are widely disseminated, the discoverers have received inadequate recognition and the history of their discoveries is largely unstudied and unknown. At the millennium, a committee selected 50 landmark discoveries in gastroenterology during the past 50 years. A brief history of each landmark discovery is presented. Part I was presented in the previous issue of Gastroenterology Clinics of North America. Part II presents landmark discoveries in gastrointerintal (GI) motility, clinical trials, nutrition, and diseases of the lower GI tract, liver, biliary tree, and pancreas.

Endoscopy, Digestive System↗
PubMed2000

What is clinically meaningful: outcome measures in pain clinical trials.

OBJECTIVE: The goal of this analysis is a better understanding of the issues involved in establishing the amount of change in pain that must be reported by subjects, participating in clinical trials and using standard pain scales, to indicate a clinically important difference. DESIGN: A review of the literature and a discussion of relevant concepts are presented. The focus is on outcome measures of pain commonly used in the studies described, including pain intensity, pain relief, global assessment of the medication effect, and requirement for an extra dose of rescue medication to treat a pain episode. The standard analysis statistics used to summarize the data are the central tendency of the groups being compared (i.e., mean, median, or mode), and the proportion of subjects that achieve one or more specific levels of benefit. RESULTS: The analysis of the proportion of responders in the groups being compared allows for a more easily understandable clinical importance of the results. CONCLUSIONS: An analysis of the proportion of responders is a clinically relevant analysis for many pain clinical trials and should be presented for one or more levels of response as appropriate. This will allow the readers to more easily interpret the results and apply them to clinical practice.

Analgesics↗
PubMed1999

The National Institutes of Health chronic prostatitis symptom index: development and validation of a new outcome measure. Chronic Prostatitis Collaborative Research Network.

PURPOSE: Chronic abacterial prostatitis is a syndrome characterized by pelvic pain and voiding symptoms, which is poorly defined, poorly understood, poorly treated and bothersome. Research and clinical efforts to help men with this syndrome have been hampered by the absence of a widely accepted, reliable and valid instrument to measure symptoms and quality of life impact. We developed a psychometrically valid index of symptoms and quality of life impact for men with chronic prostatitis. MATERIALS AND METHODS: We conducted a structured literature review of previous work to provide a foundation for the new instrument. We then conducted a series of focus groups comprising chronic prostatitis patients at 4 centers in North America, in which we identified the most important symptoms and effects of the condition. The results were used to create an initial draft of 55 questions that were used for formal cognitive testing on chronic prostatitis patients at the same centers. After expert panel review formal validation testing of a revised 21-item draft was performed in a diverse group of chronic prostatitis patients and 2 control groups of benign prostatic hyperplasia patients and healthy men. Based on this validation study, the index was finalized. RESULTS: Analysis yielded an index of 9 items that address 3 different aspects of the chronic prostatitis experience. The primary component was pain, which we captured in 4 items focused on location, severity and frequency. Urinary function, another important component of symptoms, was captured in 2 items (1 irritative and 1 obstructive). Quality of life impact was captured with 3 items about the effect of symptoms on daily activities. The 9 items had high test-retest reliability (r = 0.83 to 0.93) and internal consistency (alpha = 0.86 to 0.91). All but the urinary items discriminated well between men with and without chronic prostatitis. CONCLUSIONS: The National Institutes of Health chronic prostatitis symptom index provides a valid outcome measure for men with chronic prostatitis. The index is psychometrically robust, easily self-administered and highly discriminative. It was formally developed and psychometrically validated, and may be useful in clinical practice as well as research protocols.

Chronic Disease↗
PubMed1998

Oral transmucosal fentanyl citrate: randomized, double-blinded, placebo-controlled trial for treatment of breakthrough pain in cancer patients.

BACKGROUND: Patients with cancer frequently experience episodes of acute pain, i.e., breakthrough pain, superimposed on their chronic pain. Breakthrough pain is usually treated with short-acting oral opioids, most of which provide some relief after 15-20 minutes, with peak effects after 30-45 minutes. Oral transmucosal fentanyl citrate (OTFC), a unique formulation of the opioid fentanyl, has been shown to provide meaningful pain relief within 5 minutes in patients following surgery. We conducted a multicenter, randomized, double-blinded, placebo-controlled trial of OTFC for cancer-related breakthrough pain. METHODS: Patients who were 18 years of age or older, receiving the equivalent of at least 60 mg oral morphine or at least 50 microg transdermal fentanyl per day for chronic cancer-related pain, and experiencing at least one episode of breakthrough pain per day were studied. After titration to an effective OTFC dose, subjects were given 10 randomly ordered treatment units (seven OTFC units and three placebo units) in the form of identical lozenges. If acceptable pain relief was not achieved within 30 minutes, subjects were instructed to take their previous breakthrough pain medication (i.e., rescue medication). Pain intensity, pain relief, and use of rescue medication were evaluated at 15-minute intervals over a 60-minute period. RESULTS: Eighty-nine of 92 patients who received the randomized treatment were assessable (i.e., treated with at least one unit of OTFC and one unit of placebo). OTFC produced significantly larger changes in pain intensity and better pain relief than placebo at all time points (two-sided P<.0001). Episodes treated with placebo required the use of rescue medication more often than episodes treated with OTFC (34% versus 15%; relative risk = 2.27; 95% confidence interval = 1.51-3.26; two-sided P<.0001). CONCLUSIONS: OTFC appears effective in the treatment of cancer-related breakthrough pain.

Administration, Oral↗
PubMed1996

Severe sudden visual loss caused by pseudotumor cerebri and lumboperitoneal shunt failure.

PURPOSE: Severe vistral acuity loss associated with pseudotumor cerebri is usually caused by chronic optic disk edema or a retinal abnormality. METHODS: We treated a women, with known pseudotumor cerebri treated with a lumboperitoneal shunt, who developed acute pallied optic disk swelling and visual acuity of R.E.: no light perception and L.E.: 20/70 in association with lumboperitoneal shunt failure. There were no contributory retinal lesions. RESULTS: The patient underwent optic nerve sheath fenestration and lumboperitoneal shunt revision. Visual acuity improved to 20/20 in both eyes. The papilledema resolved. CONCLUSION: The severe sudden visual loss was attributed to axoplasmic stasis and optic nerve ischemia associated with a sudden rise in intracranial pressure.

Adult↗