Lessons of a hip failure. Register exists in Trent region.
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Arthroplasty, Replacement, Hip↗
Biomedical subjects
K Abrams
Publications and source records attributed to K Abrams.
Safety and fetal outcome of early and midtrimester amniocentesis.
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Abortion, Spontaneous↗
Approximate Bayesian inference for random effects meta-analysis.
Whilst meta-analysis is becoming a more commonplace statistical technique, Bayesian inference in meta-analysis requires complex computational techniques to be routinely applied. We consider simple approximations for the first and second moments of the parameters of a Bayesian random effects model for meta-analysis. These computationally inexpensive methods are based on simple analytical formulae that provide an efficient tool for a qualitative analysis and a quick numerical estimation of posterior quantities. They are shown to lead to sensible approximations in two examples of meta-analyses and to be in broad agreement with the more computationally intensive Gibbs sampling.
Antibiotic Prophylaxis↗
Effect of a low-impact exercise program on bone mineral density in Crohn's disease: a randomized controlled trial.
BACKGROUND & AIMS: Physical exercise increases bone mineral density (BMD) in healthy young adults and slows the rate of bone loss in later life. The aim of this randomized controlled trial was to investigate the effect of exercise on BMD in patients with Crohn's disease. METHODS: A total of 117 patients with Crohn's disease were randomized to a control group or a low-impact exercise program of increasing intensity. BMD (g/cm2) was measured at baseline and 12 months at the hip and spine (L2-L4) by dual energy x-ray absorptiometry. RESULTS: Nonsignificant gains in BMD occurred at the hip and spine in the exercise group compared with controls (P > 0.05). In fully compliant patients, BMD increased by 3.54% (7.95%) at the femoral neck, 2.97% (7.7%) at the spine, 4.1% (10.26%) at Ward's triangle, and 7.77% (8.2%) at the greater trochanter. Compared with controls, gain in BMD at the greater trochanter was statistically significant (difference in means, 4.67; 95% confidence interval, 0.86-8.48; P = 0.02). Increases in BMD were significantly related to the number of exercise sessions completed (femoral neck; r = 0.28; 95% confidence interval, 0.10-0.45; P = 0.04). CONCLUSIONS: Progressive low-impact exercise is a potentially effective method of increasing BMD in Crohn's disease. If sustained, the increases in BMD may reduce the risk of osteoporotic fracture.
Adult↗
Newborn acid-base status and umbilical cord morphology.
OBJECTIVE: To assess the relation between umbilical cord morphology and intrapartum fetal status and umbilical cord blood gases at birth. METHODS: In a prospective study of 134 consecutive newborns and their umbilical cords, relations were investigated between umbilical cord morphologic characteristics (umbilical cord length, number of vascular coils, coiling index, and vessel length index) and intrapartum fetal heart rate (FHR) decelerations, color of amniotic fluid, operative delivery for suspected fetal acidosis, umbilical vessel blood gases, and acid-base status. RESULTS: Statistically significant linear correlations were found between umbilical venous pH and the umbilical cord length (r = 0.30; 95% confidence interval [CI] 0.13, 0.46; P < .001), number of vascular coils (r = 0.27; 95% CI 0.10, 0.43; P = .001), coiling index (r = 0.15; 95% CI 0, 0.33; P = .05), and vessel length index (r = 0.30; 95% CI 0.13, 0.46; P < .001). Statistically significant negative linear correlations were found between the umbilical venous partial pressure of carbon dioxide (PCO2) and cord length (r = -0.34, 95% CI -0.49, -0.17; P < .001), number of vascular coils (r = -0.30, 95% CI -0.46, -0.13; P < .001), coiling index (r = -0.17, 95% CI -0.34, 0; P = .03), and vessel length index (r = -0.34, 95% CI -0.49, -0.17; P < .001). The umbilical artery pH was related to vessel length index and to the number of umbilical vascular coils (r = 0.17, 95% CI 0.03, 0.36; P = .04 and r = 0.17, 95% CI 0.02, 0.35; P = .047, respectively). No relation was found between umbilical cord indices and intrapartum FHR decelerations, meconium staining of the amniotic fluid, or mode of delivery. Placental weight also correlated with umbilical cord length and vessel length index (95% CI 0.15, 0.46; P < .001 and 95% CI 0.05, 0.38; P = .01, respectively), but not with the number of umbilical cord coils or the coiling index. CONCLUSION: Umbilical venous pH and PCO2 and umbilical artery pH are related to umbilical cord morphology. Associated variations in placental morphology or placental blood flow affecting maternal-fetal gas exchange may explain these findings.
Acid-Base Equilibrium↗
Osteoporosis and determinants of bone density in patients with Crohn's disease.
Low bone mineral density (BMD) is common in patients with Crohn's disease; however, the pathogenesis of bone loss and risk factors for osteoporosis are not established. Our aim was to evaluate the clinical, dietary, and nutritional determinants of BMD in Crohn's disease. A cross-sectional analysis of 117 patients with Crohn's disease was undertaken. All patients underwent a clinical and dietary evaluation including assessment of nutritional state and life-style. BMD was measured at the hip and lumbar spine by dual-energy x-ray absorptiometry; and z scores obtained by comparison with age- and sex-matched normal values for the healthy UK population. Multiple regression analysis was used to assess associations between BMD and potential risk factors, allowing for possible confounding variables. Thirteen (11%) patients had osteoporosis (z score < -2), with osteopenia (z score < -1, > -2) in a further 34 (29%). Patients with jejunal disease had significantly lower BMD at the spine (P = 0.03) and femoral neck (P = 0.02) than those with disease at other sites. Mean BMD was significantly lower at the hip of patients with previous bowel resection (diff in means = 0.53, 95% CI -0.97, -0.08, P = 0.02), but type of surgery was not significant. Active disease, menstrual history, diet, level of physical activity, and smoking were not associated with low bone mass. At the lumbar spine, body weight (P < 0.0001), male sex (P < 0.0001), and current prednisolone use (P < 0.02) were independently predictive of low bone mass. Body weight (P < 0.0001), male sex (P < 0.0001), and cumulative steroid dose (P = 0.02) were predictive at the femoral neck. The major determinants of BMD in Crohn's disease are body weight, current steroid use, and cumulative steroid dose. Men with Crohn's disease are at greatest risk of osteoporosis, with jejunal involvement and previous bowel resection also contributing to the low bone mineral density.
Absorptiometry, Photon↗
Sex hormone status and bone metabolism in men with Crohn's disease.
BACKGROUND: Men with Crohn's disease (CD) are at risk of osteoporosis, but the factors contributing to low bone mineral density and its optimum treatment have not been established. AIM: To investigate the sex hormone status of men with CD, and to establish the influence of sex hormones on their bone metabolism. METHODS: Bone density was measured by dual energy X-ray absorptiometry at the hip and lumbar spine in 48 men with CD. Total serum testosterone and gonadotrophins were measured in all subjects and the free androgen index calculated in men with low or borderline total testosterone. Serum osteocalcin, pro-collagen carboxy-terminal peptide, bone specific alkaline phosphatase and urinary deoxypyridinoline were measured as markers of bone turnover. RESULTS: Eight (17%) men had osteoporosis, and a further 14 (29%) had osteopenia. Three (6%) men had a low free androgen index and normal gonadotrophins consistent with secondary hypogonadism, two of whom had osteopenia of the hip and spine. Age (P = 0.002) and small bowel Crohn's disease (P = 0.02) were the only independent predictors of serum testosterone. There was a significant association between total testosterone and osteocalcin (r = 0.53, 95%, CI: 0.29-0.71, P = 0.0001) which was independent of age and current steroid use (P = 0.0001). CONCLUSIONS: Previously undiagnosed hypogonadism is an uncommon cause of low bone density in men with CD. The independent association between testosterone and the bone formation marker osteocalcin suggests sex hormone status influences bone metabolism in men with CD. The results suggest testosterone replacement might be effective treatment for some men with osteoporosis and Crohn's disease.
Absorptiometry, Photon↗
The effect of rectally administered steroids on bone turnover: a comparative study.
BACKGROUND: Oral glucocorticoids contribute significantly to the risk of osteoporosis in patients with inflammatory bowel disease. Less well established are the effects of rectally administered steroids on bone metabolism. AIM: To investigate the effects of two widely used rectal foam preparations (prednisolone metasulphobenzoate and hydrocortisone acetate) on biochemical markers of bone turnover. METHODS: Twenty-four patients with active inflammatory bowel disease randomly received a standard course of either prednisolone metasulphobenzoate or hydrocortisone acetate for 2 weeks. Biochemical markers of bone turnover were measured before, during and after treatment. Bone formation markers measured were serum osteocalcin (BGP) and bone-specific alkaline phosphatase (BALP). Urinary deoxypyridinoline (DPD) was measured to assess bone resorption. RESULTS: Disease activity scores improved during treatment (difference in mean Powell-Tuck score = 3.4, 95% CI: 2.0-4.8, P < 0.0001) and were similar in both hydrocortisone and prednisolone-treated groups. There was no significant reduction in BALP or BGP during treatment with either steroid preparation, and urinary DPD did not change significantly during treatment. CONCLUSIONS: During a 2-week course of rectal hydrocortisone acetate or prednisolone metasulphobenzoate, there was no significant change in biochemical markers of bone formation or resorption. These results suggest that pharmacological doses of rectal steroid foam preparations do not significantly impair bone turnover in patients with inflammatory bowel disease.
Administration, Rectal↗
Increased bone resorption in patients with Crohn's disease.
BACKGROUND: Patients with Crohn's disease are at risk of osteoporosis and premature fracture. However, the pathophysiology underlying bone loss remains poorly understood and the optimum treatment has not been established. AIM: To investigate mechanisms of bone loss in Crohn's disease using biochemical markers of bone turnover. METHODS: Bone mineral density was measured at the hip and spine using dual-energy X-ray absorptiometry in 117 patients (48 male) with Crohn's disease. Bone turnover was assessed by measuring serum osteocalcin (BGP), pro-collagen carboxy-terminal propeptide (PICP), bone specific alkaline phosphatase (BALP) and urinary deoxypyridinoline (DPD); and compared to age-matched healthy controls (n = 28). RESULTS: Bone mineral density was reduced (z-score < -1) in 48 (41%) patients with Crohn's disease. Mean values for bone formation markers in patients with Crohn's disease were all within the normal reference range (BGP 8.92 (+/- 3.23) ng/mL (normal range 3.4-10.0), BALP 17.6 (+/- 12.6) U/L (normal range 11.6-43.3), PICP 95.1 (+/- 46.5) ng/mL (normal range 69-163)) and were not significantly different to the control population. However, mean urinary DPD was significantly higher in patients with Crohn's disease compared to healthy controls (10.97 (+/- 9.22) nM DPD/mM creatinine vs. 5.02 (+/- 1.03) nM DPD/mM creatinine, difference in means = 5.95, 95% CI: -9.6 to -2.3, P = 0.00001) and compared to the UK reference range DPD levels were increased in 74 (63%) patients. CONCLUSIONS: Bone resorption as evidenced by urinary DPD was frequently increased in patients with Crohn's disease and was significantly higher than in an age-matched control population. The high levels of urinary DPD suggest increased bone collagen degradation may contribute to osteoporosis in patients with Crohn's disease. These results suggest anti-resorptive agents such as the bisphosphonates may be effective treatment for osteoporosis in Crohn's disease.
Adult↗
Audit of patients on oral anticoagulants with International normalized ratios of eight or above.
We reviewed retrospectively the medical records of all patients (n = 77, mean age 74.2) on oral anticoagulants with an International normalized ratio (INR) of eight or above in a 12-month period in the Leicestershire District Health Authority (DHA). From a total of 55,625 INRs, 131 (0.24%) were > or = 8. A major cause of over-anticoagulation was unsatisfactory dose loading during in-hospital commencement of oral anticoagulation. The incidence of major bleeding was 12.9% of total episodes of INR > or = 8 with two haemorrhage-related fatalities. Therapy of major haemorrhage with fresh frozen plasma (FFP) and intravenous (i.v) vitamin K proved effective but was not given in a majority of such cases. In conclusion, improvements in initial dose loading of oral anticoagulation and in the management of major haemorrhage are required. Severely over-anticoagulated patients without obvious bleeding should nevertheless receive small dose vitamin K therapy to reduce the risk of haemorrhage related morbidity and mortality without compromising subsequent oral anti-coagulant control.
Adult↗
Screening for osteoporosis in Crohn's disease. A detailed evaluation of calcaneal ultrasound.
OBJECTIVES: To compare calcaneal broadband ultrasonic attenuation (BUA) and velocity of sound (VOS) in patients with Crohn's disease with an age-matched control population. The validity of BUA as a screening tool for osteoporosis was evaluated and the relationship between BUA and previous fracture studied. DESIGN: Cross-sectional study. BACKGROUND: Since patients with Crohn's disease are at risk of osteoporosis and premature fracture, routine assessment of bone mineral density (BMD) is recommended. Quantitative ultrasound of the calcaneum is an inexpensive and radiation-free means of assessing bone density which also provides information on bone microstructure. METHODS: BUA (dB/MHz) and VOS (m/s) were measured at the calcaneum (CUBAclinical, McCue Ultrasonics, Winchester, UK) and compared with bone mineral density at the hip and lumbar spine measured by dual-energy X-ray absorptiometry (DEXA); 100 patients (42 men) with Crohn's disease and 52 age-matched healthy controls (23 men) were studied. RESULTS: BUA was significantly reduced in patients with Crohn's disease compared with age-matched controls [76.53 dB/MHz (+/-17.3) vs 87.29 dB/MHz (+/-17.9), difference in means = 10.76, 95% CI -16.67, -4.85, P = 0.0004] and was significantly associated with BMD at the spine (r = 0.49, 95% CI 0.32, 0.63, P< 0.0001) and femoral neck (r = 0.54, 95% CI 0.38, 0.67, P < 0.0001). In the diagnosis of osteoporosis (t score <-2.5) BUA had a sensitivity of 66.7% at the femoral neck, with a specificity of 85.6%; sensitivity of BUA at the spine was 75% with specificity 89%. CONCLUSION: Patients with Crohn's disease have reduced BUA compared with an age-matched control population. Calcaneal BUA is significantly associated with BMD at the hip and spine but the correlation is insufficient to recommend ultrasound as a screening tool for DEXA.
Absorptiometry, Photon↗
Is histological examination of tissue removed by general practitioners always necessary? Before and after comparison of detection rates of serious skin lesions.
OBJECTIVES: To examine whether histological examination of all tissue removed by general practitioners in minor surgery increases the rate of detection of clinically important skin lesions, and to assess the impact of such a policy on pathologists' workload. DESIGN: Before and after comparison. SETTING: Stratified random sample of 257 general practitioner partnerships from the catchment areas of 19 English pathology laboratories. SUBJECTS: Tissue removed in minor surgery by general practitioners during the control period (September 1992 to February 1993) and intervention period (September 1993 to February 1994). INTERVENTION: General practitioners referred to their local pathology laboratory all solid tissue removed in all minor surgery, irrespective of their previous policy. MAIN OUTCOME MEASURES: Numbers of specimens referred for histology by general practitioners during intervention and control periods; numbers of primary malignant melanomas, non-melanoma malignancies, premalignant lesions, and benign lesions. RESULTS: 257/330 partnerships participated (response rate 78%). During the intervention period 5723 specimens were sent, compared with 4430 during the control period. The referral rate increased by an estimated 1.34 specimens per 1000 patient years (95% confidence interval 0.93 to 1.76, P < 0.0001). General practitioners sent 204 specimens that were malignant (including 16 malignant melanomas) in the control period and 188 that were malignant (including 15 malignant melanomas) during the intervention period (change in total number of malignancies, -1.0 per 100,000 patient years (-5.9 to 3.8, non-significant). CONCLUSIONS: The intervention was associated with a substantial increase in laboratory workload, all of which was accounted for by increases in non-serious lesions. This observation should be taken into account when considering the merits of a policy requiring histological examination in every case.
England↗
Differing responses in blood pressure over 24 hours in normotensive women receiving oral or transdermal estrogen replacement therapy.
OBJECTIVE: To examine the effects of oral and transdermal estrogen replacement therapy (ERT) on ambulatory 24-hour blood pressure (BP) recordings. METHODS: In a nonrandomized, prospective study, 90 normotensive, oophorectomized women, ages 30-59 years, underwent ambulatory 24-hour BP measurements at study entry and after 3 and 6 months of either oral (n = 50) or transdermal (n = 40) ERT. RESULTS: In the women receiving transdermal estrogen, we observed a change in mean nighttime systolic BP of -4.2 mmHg (95% confidence interval [CI] -7.7, -0.7; P = .039) after 6 months, treatment. There was a change in mean daytime diastolic BP after 3 months (-3.3 mmHg; 95% CI -5.5, -0.9; P = .016) and 6 months (-4 mmHg; 95% CI-6.8, -1.2; P = .014), and in mean nighttime diastolic BP after 3 months (-3.8 mmHg; 95% CI -6.6, -0.9; P = .027) and 6 months (-4.4 mmHg; 95% CI -7.1, -1.7; P = .005). No significant BP changes were observed in the women taking oral estrogen. Although the statistical power to detect a change of 4 mmHg at the 5% significance level was 90% for diastolic BP, it was weaker for systolic BP (63%) in this group. However, in more than one-third of the women receiving either treatment, a statistically significant increase in BP was observed. CONCLUSIONS: Transdermal ERT was associated with a reduction in mean ambulatory BP, whereas oral treatment did not alter BP. Although the overall effect of estrogen was to lower BP, individual responses were variable, and BP increased in more than one-third of the women on either treatment. Therefore, long-term monitoring of ambulatory measurements may be required.
Administration, Cutaneous↗
Rectal steroids suppress bone formation in patients with colitis.
BACKGROUND: The aetiology of bone loss in inflammatory bowel disease is multifactorial, but oral corticosteroids are an important contributory factor. Rectally administered steroids are widely used in patients with distal disease, but very little is known about their effect on bone metabolism. The aim of this study was to investigate the effect of a standard course of rectal prednisolone on biochemical markers of bone turnover. METHODS: In a longitudinal study of 10 patients, biochemical markers of bone turnover were measured before, during and after treatment with prednisolone metasulphobenzoate (Predfoam, Pharmax Ltd) 20 mg twice daily for 2 weeks. Bone formation markers measured were serum osteocalcin (BGP), bone-specific alkaline phosphatase (BALP) and procollagen carboxy-terminal propeptide (PICP). Urinary deoxypyridinoline (dPyr) was measured to assess bone resorption. RESULTS: Disease activity scores improved during treatment (difference in mean Powell-Tuck score = 2.3 (+/-13.1), 95% CI: 0.11-4.48, P = 0.04). There was a significant fall in BALP (P = 0.02) during treatment, and a rapid but non-significant fall in BGP (P = 0.19). PICP (0.42), and urinary dPyr (0.30) did not change significantly during treatment. CONCLUSIONS: Following a standard 2-week course of rectal prednisolone metasulphobenzoate, we observed a significant fall in bone-specific alkaline phosphatase activity. These results suggest that bone formation is suppressed in patients with distal colitis treated with pharmacological doses of rectal steroids.
Administration, Rectal↗
The relation of hand skin-fold thickness to bone mineral density in patients with Crohn's disease.
OBJECTIVES: In healthy postmenopausal women, the association of skin-fold thickness (SFT) with bone mineral density (BMD) is well described, and a low SFT is a useful predictor of osteoporosis. In this study the association between hand SFT and BMD in patients with Crohn's disease was assessed; and the potential for hand SFT as a screening test for osteoporosis evaluated. DESIGN/METHODS: In a cross-sectional study, BMD was measured at the hip and lumbar spine by dual energy x-ray absorptiometry (DEXA). SFT was measured on the dorsum of the right hand using Holtain Tanner Whitehouse calipers. One hundred and seventeen patients (48 male) with Crohn's disease and 50 (25 male) controls were studied. RESULTS: There was a significant correlation between hand SFT and BMD (expressed as t scores) at all four measured sites (lumbar spine r = 0.41, P < 0.0001, 95% CI 0.25-0.55, Ward's triangle r = 0.38, P < 0.0001, 95% CI 0.21-0.53, trochanter r = 0.33, P < 0.0001, 95% CI 0.16-0.48, femoral neck r = 0.38, P < 0.0001, 95% CI 0.21-0.53). On stepwise regression analysis, the association remained significant after correcting for age, weight, menstrual status and current steroid use (P < 0.05). Hand SFT was significantly lower in patients with Crohn's disease than controls (difference in means 0.51 mm, 95% CI 0.3-0.72, P < 0.0001). Mean hand SFT was significantly lower in patients with osteoporosis compared to patients with normal BMD (difference in means 0.74 mm, 95% CI 0.33-1.15, P < 0.001), as was that of osteopenic patients compared to patients with normal BMD (difference in means 0.28 mm, 95% CI 0.01-0.55, P < 0.05). In the diagnosis of osteoporosis, the sensitivity of hand SFT ranged from 29% to 93%, with specificities of 54% to 95%. CONCLUSIONS: Hand SFT is independently associated with BMD in Crohn's disease and is lower than in age-matched healthy subjects. Hand SFT in combination with other easily measurable confounding variables might be useful in screening for osteoporosis in patients with Crohn's disease.
Adult↗
A Bayesian approach to Weibull survival models--application to a cancer clinical trial.
In this paper we outline a class of fully parametric proportional hazards models, in which the baseline hazard is assumed to be a power transform of the time scale, corresponding to assuming that survival times follow a Weibull distribution. Such a class of models allows for the possibility of time varying hazard rates, but assumes a constant hazard ratio. We outline how Bayesian inference proceeds for such a class of models using asymptotic approximations which require only the ability to maximize the joint log posterior density. We apply these models to a clinical trial to assess the efficacy of neutron therapy compared to conventional treatment for patients with tumours of the pelvic region. In this trial there was prior information about the log hazard ratio both in terms of elicited clinical beliefs and the results of previous studies. Finally, we consider a number of extensions to this class of models, in particular the use of alternative baseline functions, and the extension to multi-state data.
Bayes Theorem↗
The beneficial effects of oral nifedipine on cyclosporin-treated renal transplant recipients--a randomised prospective study.
The aim of this study was to test the hypothesis that nifedipine will improve graft survival in cyclosporin A (CyA)-treated renal transplant recipients. One hundred and forty-seven patients were randomised to one of three regimens. Group A received CyA, 7 mg/kg per day, and prednisolone; group B followed the same regimen as group A plus oral nifedipine and group C received CyA, 4 mg/kg per day, prednisolone and azathioprine. Calcium channel blockers were avoided in groups A and C. The crude 2-year (P = 0.0223) and 4-year (P = 0.0181) graft survival was significantly better in group B (86% and 81%, respectively) than in group A (75% and 63%, respectively). Delayed initial function was seen least frequently in group B (10.2%) compared to groups A (31%) and C (28%; P < 0.01). Group B also experienced fewer rejection episodes than groups A and C (P < 0.05). We conclude that the combination of oral nifedipine and CyA significantly improves initial graft function, rejection frequency and long term graft survival.
Administration, Oral↗
Endometrial responses to hormone replacement therapy: the bleeding pattern.
Little information is available concerning the response of the endometrium to exogenous sex steroid therapy, particularly in the post-menopausal state. In this study we examined the variability of the bleeding pattern in 103 post-menopausal women receiving cyclical sequential combined hormone replacement therapy (HRT) over 6 months. All patients kept menstrual diary cards to record the onset, duration and subjective assessment of the severity of bleeding. We defined a cycle as starting from the commencement of treatment till the day of onset of bleeding. Two groups were identified amongst 99 women who experienced bleeding: those with a mean cycle length of 29 or more days (late bleeders, n = 50) and those with shorter mean cycle length (early bleeders, n = 49). The former were characterized by less variability in cycle length and bleeding that was of shorter duration. Four women experienced no bleeding. There were no significant differences between the two groups in age, year since the menopause, weight, height, body mass index (BMI), parity, or in the previous use of HRT. The only significant difference was in their smoking habits. This suggests a possible link of a hypo-oestrogenic state to poor cycle control.
Adult↗