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Biomedical subjects

P Seed

Publications and source records attributed to P Seed.

At least 19 recordsLinked to original sources

The effect of small intramural uterine fibroids on the cumulative outcome of assisted conception.

BACKGROUND: This study aimed to evaluate the effect of small intramural fibroids on the cumulative pregnancy, ongoing pregnancy, live birth and implantation rates after three IVF/ICSI attempts. METHODS: The first three treatment cycles of women enrolled for IVF/ICSI over a 12-month period were analysed. Only patients with small (<or=5 cm) intramural fibroids not encroaching upon the endometrial cavity were included in the fibroid group. Cox's hazards regression was used to estimate the hazard ratio (HR) associated with the presence of intramural fibroids. RESULTS: During the study period, 322 women without fibroids (control group) and 112 women with fibroids (study group) underwent 606 IVF/ICSI cycles. The pregnancy, ongoing pregnancy and live birth rates in the study group were 23.6, 18.8 and 14.8% compared with 32.9, 28.5 and 24% in the control group, respectively (P<0.05). Cox regression analysis showed that the pregnancy rate at each cycle was reduced by 39% (HR=0.61, 95% CI=0.39-0.95, P=0.029) in the study group compared with the control group. The cumulative ongoing pregnancy rate was reduced by 43% (HR=0.57, 95% CI=0.35-0.91, P=0.018), and the cumulative live birth rate was reduced by 47% (HR=0.53, 95% CI=0.32-0.87, P=0.013) in the study group. After adjusting for confounding variables, the presence of fibroids was found to significantly reduce the ongoing pregnancy rate at each cycle of IVF/ICSI by 40% (HR=0.60, 95% CI=0.36-0.99, P=0.048) and the live birth rate at each cycle by 45% (HR=0.55, 95% CI=0.32-0.95, P=0.03). CONCLUSION: Small intramural fibroids are associated with a significant reduction in the cumulative pregnancy, ongoing pregnancy and live birth rates after three IVF/ICSI cycles.

Adult↗

Pituitary suppression in ultrasound-monitored frozen embryo replacement cycles. A randomised study.

BACKGROUND: This study was designed to assess the value of using a gonadotrophin-releasing hormone (GnRH) agonist prior to exogenous steroid supplementation for endometrial preparation in frozen-thawed embryo replacement (FER) cycles. METHODS: A prospective randomized trial of 234 patients undergoing FER cycles was conducted. The study population was randomly divided into two groups according to a computer-generated list. In group A (n = 117), a daily dose of 6 mg of oral estradiol valerate was initiated on menstrual day 1 following pituitary suppression using 400 mcg buserelin acetate daily. In group B (n = 117), the same dose of estradiol valerate was initiated on day 1 of bleeding without prior GnRH agonist therapy. In both groups, ovulation monitoring was not undertaken and progesterone pessaries (800 mg daily) were administrated when the endometrial thickness had reached 8 mm or more with embryo transfer taking place 2 days later. RESULTS: The two groups were comparable with respect to cause of infertility, age at stimulation (32.8 +/- 4 vs 33.2 +/- 3.9 years, P = 0.4), basal FSH level (6.3 +/- 1.7 vs 6.4 +/- 2 IU/l, P = 0.5), number of oocytes collected (16.9 +/- 7.3 vs 16.5 +/- 7.4, P = 0.7) and fertilized normally in the retrieval cycle (11.5 +/- 4.9 vs 11 +/- 4.9, P = 0.4) and number of embryos cryopreserved (6.6 +/- 3.6 vs 6.2 +/- 3.6, P = 0.3). There was no significant difference between the two groups in age at frozen replacement (33.6 +/- 4.2 vs 34 +/- 3.9 years, P = 0.4), duration of the proliferative phase (20.7 +/- 8.6 vs 21 +/- 9.2 days, P = 0.7) and number of thawed embryos replaced (2.3 +/- 0.6 vs 2.2 +/- 0.6, P = 0.2). However, compared with group B, group A achieved significantly higher pregnancy (37.6% vs 24%, OR 1.8, 95%CI 1.1-3.4), clinical pregnancy (24% vs 11.3%, OR 2.5, 95%CI 1.2-5.5) and live birth rates (20% vs 8.5%, OR 2.9, 95%CI 1.2-8). CONCLUSION: Medicated frozen embryo replacement cycles timed by endometrial thickness measurement alone without monitoring or suppression of ovarian activity are associated with reduced outcome.

Adult↗

Intraobserver and interobserver variation in the sonographic grading of placental maturity.

OBJECTIVES: The appearance of Grannum Grade III changes in the placenta at around 34-36 weeks is a predictor of adverse perinatal outcome, which may be reduced by reporting to the clinician. This has led to the suggestion that the placental grade should be noted during any third-trimester scan. There are no published data on the reproducibility of sonographic Grannum grading of the placenta; the objective of this study was to evaluate intra- and interobserver variation. METHODS: Fifty-five placental images from normal and complicated pregnancies of several different gestational ages were collected between April and October 2001. Three fetal medicine consultants and three experienced sonographers graded the images as 0, I, II, III or ungradeable. They then regraded the same images, presented in a different order and with different codes, 4-6 weeks later. Observers were blinded to their previous grading and to each others'. Weighted kappa (kappa), with linear weights, was used to look for strength of agreement. RESULTS: There was good agreement between the two observations of each placental image for five observers (kappa = 0.61 to 0.90), and moderate agreement for one observer (kappa = 0.56). However, the kappa-values for comparisons between the 15 pairs of observers ranged from 0.24 to 0.69 with six values below 0.41, indicating only fair agreement. This was confirmed by the overall kappa-value of 0.24 between all six observers. The agreement between the observers for Grade III placenta was poor, with an overall kappa-value of 0.09. CONCLUSIONS: Although intraobserver agreement was generally good, interobserver agreement was only fair for all grades and poor for Grade III placenta. This may be an indication that Grannum grading is not reproducible or it may reflect a need for training in those performing grading. Such variation may limit the effectiveness of reporting Grannum grades in clinical practice.

Female↗

Cost-effectiveness of cognitive behavioural therapy, graded exercise and usual care for patients with chronic fatigue in primary care.

BACKGROUND: Chronic fatigue is a common condition, frequently presenting in primary care. The aim of this study was to compare the cost-effectiveness of cognitive behavioural therapy (CBT) and graded exercise therapy (GET), and to compare therapy with usual care plus a self-help booklet (BUC). METHOD: Patients drawn from general practices in South East England were randomized to CBT or GET. The therapy groups were then compared to a group receiving BUC recruited after the randomized phase. The main outcome measure was clinically significant improvements in fatigue. Cost-effectiveness was assessed using the net-benefit approach and cost-effectiveness acceptability curves. RESULTS: Costs were available for 132 patients, and cost-effectiveness results for 130. Costs were dominated by informal care. There were no significant outcome or cost differences between the therapy groups. The combined therapy group had significantly better outcomes than the standard care group, and costs that were on average 149 pounds higher (a non-significant difference). Therapy would have an 81.9% chance of being cost-effective if society were willing to attach a value of around 500 pounds to each four-point improvement in fatigue. CONCLUSION: The cost-effectiveness of cognitive behavioural therapy and graded exercise were similar unless higher values were placed on outcomes, in which case CBT showed improved cost-effectiveness. The cost of providing therapy is higher than usual GP care plus a self-help booklet, but the outcome is better. The strength of this evidence is limited by the use of a non-randomized comparison. The cost-effectiveness of therapy depends on how much society values reductions in fatigue.

Adult↗

The economic cost of chronic fatigue and chronic fatigue syndrome in UK primary care.

BACKGROUND: Chronic fatigue and chronic fatigue syndrome are most often encountered in primary care settings. Given the disabling nature of chronic fatigue it may have a substantial impact on service use and costs as well as on employment. This study estimates this impact. METHOD: Patients presenting to general practitioners with unexplained chronic fatigue were recruited to the study. Service use over a 3 month period was measured and lost employment recorded. These data were used to estimate economic costs. Patients with chronic fatigue syndrome were compared to patients with only chronic fatigue using a multiple regression model with sample differences controlled. RESULTS: The mean total cost of services and lost employment across the sample was Pound Sterling1906 for the 3-month period with formal services accounting for 9.3% of this figure. Service use was higher for patients with chronic fatigue syndrome compared to those with chronic fatigue alone. Total 3-month costs were on average higher for chronic fatigue syndrome (Pound Sterling3515 v. Pound Sterling1176) but when sample differences were taken account of the mean difference was reduced to Pound Sterling1406 (P = 0.086). Over 90% of the cost was accounted for by care provided by friends and family members and by lost employment. Patients with dependants had significantly higher costs than those with none and costs were also significantly higher for greater levels of functional impairment. CONCLUSION: Chronic fatigue imposes substantial economic costs on society, mainly in the form of informal care and lost employment. Treatments need to be developed which recognize these impacts.

Adult↗

Poor response to ovulation induction is a stronger predictor of early menopause than elevated basal FSH: a life table analysis.

BACKGROUND: During the course of assisted reproduction treatment, a number of women exhibit a "poor response" to ovulation induction, or demonstrate an elevated basal FSH level (> or =10 IU/l) at a young age. We sought to determine whether these women are at increased risk of early menopause and poor reproductive performance. METHODS: A retrospective cohort study included 118 "poor responders" with normal basal FSH level (<10 IU/l), 164 women with raised basal FSH (> or =10 IU/l), and 265 controls, who underwent assisted reproduction treatment between 1987 and 1998. All women were < 40 years of age at the time of treatment and had normal menstrual cycles. Participants were sent a postal questionnaire in 2000-2001, seeking information on ovarian function and reproductive performance following cessation of treatment. RESULTS: After adjusting for age and smoking habits, women with poor response and raised basal FSH levels were more likely to experience symptoms of the peri-menopause [hazard ratios 2.4, 95% confidence interval (CI) 1.52-3.78, and 2.76, 95% CI 1.78-4.29 respectively, P = 0.0001]. Poor responders were six times and 23 times more likely to experience the menopause within 10 years of treatment than those with raised basal FSH levels and controls respectively (hazard ratio 5.97 and 23.9, P = 0.015 and 0.002 respectively). Poor responders and those with raised basal FSH levels have half the chance of spontaneous conception after discontinuation of treatment compared with controls (P < 0.007). CONCLUSIONS: Both poor response to ovarian stimulation and raised basal FSH are markers of reduced ovarian reserve and predict an increased risk of early menopause.

Adult↗

Thiopurine methyltransferase activity and the use of azathioprine in inflammatory bowel disease.

BACKGROUND: Azathioprine therapy is discontinued in one-third of patients with inflammatory bowel disease because of toxicity or a lack of clinical response. Patients with thiopurine methyltransferase (TPMT) deficiency are intolerant to azathioprine, whilst carriers are at increased risk of side-effects. AIM: To evaluate the importance of TPMT activity in the management of azathioprine therapy in inflammatory bowel disease. METHODS: Clinical response, adverse effects and haematological parameters were determined and correlated with TPMT enzyme activity and genotype in 106 patients with inflammatory bowel disease. RESULTS: Ninety-six patients had high TPMT activity, and 10 had intermediate activity. Nineteen patients (18%) were intolerant to azathioprine. Fifteen (16%) of those with high TPMT activity were intolerant, compared with five (50%) with intermediate activity [odds ratio (OR), 5.4; 95% confidence interval (CI), 1.5-19.8]. Complete remission was achieved in 63% of cases, and complete or partial remission in 79%. Interestingly, very high TPMT activity (> 14 units/mL red blood cells) was significantly associated with non-response, irrespective of the time on azathioprine (OR, 0.21; 95% CI, 0.07-0.68). TPMT gene mutations correlated with TPMT activity. CONCLUSIONS: Inflammatory bowel disease patients with intermediate TPMT activity have an increased risk of azathioprine toxicity. Conversely, very high TPMT activity predicts treatment failure. TPMT genotype predicted TPMT phenotype in this study.

Adult↗

A prospective controlled study of the effect of intramural uterine fibroids on the outcome of assisted conception.

BACKGROUND: Although uterine fibroids occur in 30% of women and are associated with a degree of subfertility, the effect of intramural fibroids on the outcome of IVF or ICSI treatment has not been prospectively studied. METHODS: Data were prospectively collected on 434 women undergoing IVF/ICSI in the assisted conception unit of an inner London teaching hospital. Patients were assessed for the presence of fibroids by transvaginal ultrasound and hysterosonography or hysteroscopy where appropriate. RESULTS: During the study period, 112 women with (study), and 322 women without (controls), intramural fibroids were treated. Patients were similar regarding the cause and duration of their infertility, number of previous treatments, and basal serum FSH concentration. Women in the study group were on average 2 years older (36.4 versus 34.6 years; P < 0.01). There was no significant difference in the duration of ovarian stimulation or gonadotrophin requirement, number of follicles developed, oocytes collected, embryos available for transfer or replaced. When analysing only women with intramural fibroids of < or =5 cm in size (n = 106) pregnancy, implantation and ongoing pregnancy rates were significantly reduced: 23.3, 11.9 and 15.1 respectively compared with 34.1, 20.2 and 28.3% in the control group (P = 0.016, P = 0.018 and P = 0.003). The mean size of the largest fibroids was 2.3 cm (90% range 2.1-2.5 cm). Logistic regression analysis demonstrated that the presence of intramural fibroids was one of the significant variables affecting the chance of an ongoing pregnancy, even after controlling for the number of embryos available for replacement and increasing age, particularly age > or =40 years, odds ratio 0.46 (CI 0.24-0.88; P = 0.019). CONCLUSION: This study demonstrated that an intramural fibroid halves the chances of an ongoing pregnancy following assisted conception.

Embryo Implantation↗

Chronic fatigue in general practice: economic evaluation of counselling versus cognitive behaviour therapy.

BACKGROUND: There is a paucity of evidence relating to the cost-effectiveness of alternative treatment responses to chronic fatigue. AIM: To compare the relative costs and outcomes of counselling versus cognitive behaviour therapy (CBT) provided in primary care settings for the treatment of fatigue. DESIGN OF STUDY: A randomised controlled trial incorporating a cost-consequences analysis. SETTING: One hundred and twenty-nine patients from 10 general practices across London and the South Thames region who had experienced symptoms of fatigue for at least three months. METHOD: An economic analysis was performed to measure costs of therapy, other use of health services, informal care-giving, and lost employment. The principal outcome measure was the Fatigue Questionnaire; secondary measures were the Hospital Anxiety and Depression Scale and a social adjustment scale. RESULTS: Although the mean cost of treatment was higher for the CBT group (164 Pounds, standard deviation = 67) than the counselling group (109 Pounds, SD = 49; 95% confidence interval = 35 to 76, P < 0.001), a comparison of change scores between baseline and six-month assessment revealed no statistically significant differences between the two groups in terms of aggregate health care costs, patient and family costs or incremental cost-effectiveness (cost per unit of improvement on the fatigue score). CONCLUSIONS: Counselling and CBT both led to improvements in fatigue and related symptoms, while slightly reducing informal care and lost productivity costs. Counselling represents a less costly (and more widely available) intervention but no overall cost-effectiveness advantage was found for either form of therapy.

Adolescent↗

Chronic fatigue in general practice: is counselling as good as cognitive behaviour therapy? A UK randomised trial.

BACKGROUND: Fatigue is a common symptom for which patients consult their doctors in primary care. With usual medical management the majority of patients report that their symptoms persist and become chronic. There is little evidence for the effectiveness of any fatigue management in primary care. AIM: To compare the effectiveness of cognitive behaviour therapy (CBT) with counselling for patients with chronic fatigue and to describe satisfaction with care. DESIGN OF STUDY: Randomised trial with parallel group design. SETTING: Ten general practices located in London and the South Thames region of the United Kingdom recruited patients to the trial between 1996 and 1998. Patients came from a wide range of socioeconomic backgrounds and lived in urban, suburban, and rural areas. METHOD: Data were collected before randomisation, after treatment, and six months later. Patients were offered six sessions of up to one hour each of either CBT or counselling. Outcomes include: self-report of fatigue symptoms six months later, anxiety and depression, symptom attributions, social adjustment and patients' satisfaction with care. RESULTS: One hundred and sixty patients with chronic fatigue entered the trial, 45 (28%) met research criteria for chronic fatigue syndrome; 129 completed follow-up. All patients met Chalder et al's standard criteria for fatigue. Mean fatigue scores were 23 on entry (at baseline) and 15 at six months' follow-up. Sixty-one (47%) patients no longer met standard criteria for fatigue after six months. There was no significant difference in effect between the two therapies on fatigue (1.04 [95% CI = -1.7 to 3.7]), anxiety and depression or social adjustment outcomes for all patients and for the subgroup with chronic fatigue syndrome. Use of antidepressants and consultations with the doctor decreased after therapy but there were no differences between groups. CONCLUSION: Counselling and CBT were equivalent in effect for patients with chronic fatigue in primary care. The choice between therapies can therefore depend on other considerations, such as cost and accessibility.

Adolescent↗

Does the antenatal detection of small-for-gestational-age babies influence their two-year outcomes?

The aim of this paper is to determine whether antenatal detection of small-for-gestational-age (SGA) babies influences 2-year outcomes. All low-birth-weight (<2,500g) infants born in South-EastThames region, England from September 1, 1992 to August 31, 1993 were identified at birth. Antenatal "suspicion" and ultrasound assessment confirming growth restriction was categorized as "detection" of SGA. Postnatally, infants were classified as SGA if they had a birth weight for given gestation below the 10th centile. At 2 years, those below 32 weeks' gestation and a random 25% sample of infants of 32 weeks' gestation or more underwent pediatric assessments. Of 49,787 births, 3,456 (6.9%) were of low birth weight. One thousand four hundred and fifty one (42.5%) were SGA, of whom 611 (42%) were detected antenatally by ultrasound scan. At 2 years, 1,008 (75.8%) of 1,358 expected infants were assessed, 379 (37.6%) were SGA at birth, and 188 (49.6%) were confirmed antenatally. Although undetected infants had higher mean birth weights and gestational ages, they had a higher proportion of perinatal deaths (12.6 vs. 6.4%, RR 1.96: CI 1.32-2.86) than detected infants. At 2 years, detected SGA infants had smaller head circumferences (p = 0.026), a higher prevalence of febrile convulsions (8.0 vs. 3.1 %: p = 0.040) and lower scores on the locomotor (DQA) scale of Griffith's developmental test (p = 0.021) compared with undetected SGA infants. Despite detected SGA fetuses having lower weights and gestation at birth than undetected fetuses, they had significantly lower mortality without a parallel increase in severe 2-year neuro-developmental, clinical, or growth morbidity.

Cohort Studies↗

Cervical lesions are associated with human papillomavirus type 16 intratypic variants that have high transcriptional activity and increased usage of common mammalian codons.

Human papillomavirus type 16 (HPV-16) is a major cause of cervical neoplasia, but only a minority of HPV-16 infections result in cancer. Whether particular HPV-16 variants are associated with cervical disease has not yet been clearly established. An investigation of whether cervical neoplasia is associated with infection with HPV-16 intratypic variants was undertaken by using RFLP analyses in a study of 100 HPV-16 DNA-positive women with or without neoplasia. RFLP variant 2 was positively associated [odds ratio (OR)=2.57] and variant 5 was negatively associated with disease (OR=0.2). Variant 1, which resembles the reference isolate of HPV-16, was found at a similar prevalence among those with and without neoplasia. Variants 1 and 2 were also more likely to be associated with detectable viral mRNA than variant 5 (respectively P=0.03 and P=0.00). When HPV-16 E5 ORFs in 50 clones from 36 clinical samples were sequenced, 19 variant HPV-16 E5 DNA sequences were identified. Twelve of these DNA sequences encoded variant E5 amino acid sequences, 10 of which were novel. Whilst the associations between HPV-16 E5 RFLP variants and neoplasia could not be attributed to differences in amino acid sequences, correlation was observed in codon usage. DNA sequences of RFLP variant 2 (associated with greatest OR for neoplasia) had a significantly greater usage of common mammalian codons compared with RFLP pattern 1 variants.

Amino Acid Sequence↗

Do hospital fall prevention programs work? A systematic review.

OBJECTIVES: To analyze published hospital fall prevention programs to determine whether there is any effect on fall rates. To review the methodological quality of those programs and the range of interventions used. To provide directions for further research. DESIGN: Systematic review of published hospital fall prevention programs. Meta-analysis. METHODS: Keyword searches of Medline, CINAHL, monographs, and secondary references. All papers were included that described fall rates before and during intervention. Risk ratios and 95% Confidence Intervals (95% CI) were estimated and random effects meta-analysis employed. Begg's test was applied to detect possible publication bias. Separate meta-analysis regressions were performed to determine whether individual components of multifaceted interventions were effective. RESULTS: A total of 21 papers met the criteria (18 from North America), although only 10 contained sufficient data to allow calculation of confidence intervals. A rate ratio of <1 indicates a reduction in the fall rate, resulting from an intervention. Three were randomized controlled trials (pooled rate ratio 1.0 (CI 0.60, 1.68)), seven prospective studies with historical control (0.76 (CI 0.65, 0.88)). Pooled effect rate ratio from these 10 studies was 0.79 (CI 0.69, 0.89). The remaining 11 studies were prospective studies with historical control describing fall rates only. Individual components of interventions showed no significant benefit. DISCUSSION: The pooled effect of about 25% reduction in the fall rate may be a result of intervention but may also be biased by studies that used historical controls not allowing for historical trends in the fall rate before and during the intervention. The randomized controlled trials apparent lack of effect might be due to a change in practice when patients and controls were in the same unit at the same time during a study. Studies did not analyze compliance with the intervention or opportunity costs resulting from the intervention. Research and clinical programs in hospital fall prevention should pay more attention to study design and the nature of interventions.

Accidental Falls↗

Radiation exposure of the families of outpatients treated with radioiodine (iodine-131) for hyperthyroidism.

Patients who receive radioiodine (iodine-131) treatment for hyperthyroidism (195-800 MBq) emit radiation and represent a potential hazard to other individuals. Critical groups amongst the public are fellow travellers on the patient's journey home from hospital and members of the patient's family, particularly young children. The dose which members of the public are allowed to receive as a result of a patient's treatment has been reduced in Europe following recently revised recommendations from ICRP. The annual public dose limit is 1 mSv, though adult members of the patient's family are allowed to receive higher doses, with the proviso that a limit of 5 mSv should not be exceeded over 5 years. Unless the doses received during out-patient administration of radioiodine can be demonstrated to comply with these new limits, hospitalisation of patients will be necessary. The radiation doses received by family members (35 adults and 87 children) of patients treated with radioiodine at five UK hospitals were measured using thermoluminescent dosimeters mounted in wrist bands. Families were given advice (according to current practice) from their treatment centre about limiting close contact with the patient for a period of time after treatment. Doses measured over 3-6 weeks were adjusted to give an estimate of values which might have been expected if the dosimeters had been worn indefinitely. Thirty-five passengers accompanying patients home after treatment also recorded the dose received during the journey using electronic (digital) personal dosimeters. For the "adjusted" doses to infinity, 97% of adults complied with a 5-mSv dose limit (range:0.2-5.8 mSv) and 89% of children with a 1-mSv limit (range: 0.2-7.2 mSv). However 6 of 17 children aged 3 years or less had an adjusted dose which exceeded this 1 mSv limit. The dose received by adults during travel was small in comparison with the total dose received. The median travel dose was 0.03 mSv for 1 h travel (range: 2 microSv-0.52 mSv for 1 h of travel time). These data suggest that hyperthyroid patients can continue to be treated with radioiodine on an out-patient basis, if given appropriate radiation protection advice. However, particular consideration needs to be given to children aged 3 years or younger. Admission to hospital is not warranted on radiation protection grounds.

Adolescent↗