Duration of Antiresorptive Effects of Low‐Dose Zoledronate in Osteopenic Postmenopausal Women: A Randomized,Placebo‐Controlled Trial

Annual intravenous administration of 5 mg zoledronate decreases fracture risk, but the optimal dosing regimen for zoledronate has not been determined. We set out to evaluate the antiresorptive effects of a single administration of lower doses of zoledronate. A total of 180 postmenopausal women with osteopenia enrolled in a double‐blind, randomized, placebo‐controlled trial over 2 years at an academic research center. Participants were randomized to a single baseline administration of intravenous zoledronate in doses of 1 mg, 2.5 mg, or 5 mg, or placebo. The primary endpoint was change in bone mineral density(BMD) at the lumbar spine. Secondary endpoints were change in BMD at the proximal femur and total body, and changes in biochemical markers of bone turnover. After 2 years, the change in spine BMD was greater in each of the zoledronate groups than in the placebo group; values are mean (95% confidence interval [CI]) difference versus placebo: zoledronate 1 mg 4.4% [2.7% to 6.1%]; 2.5 mg 5.5% [3.9% to 7.2%]; 5 mg 5.3% [3.8% to 6.7%], p < 0.001 for each dose). Change in BMD at the total hip was greater in each of the zoledronate groups than the placebo group (mean [95% CI] difference versus placebo: zoledronate 1 mg 2.6% [1.5% to 3.7%]; 2.5 mg 4.4% [3.5% to 5.3%]; 5 mg 4.7% [3.7% to 5.7%], p < 0.001 for each dose). Each of the bone turnover markers, β‐C‐terminal telopeptide of type I collagen (β‐CTX) and procollagen type‐I N‐terminal propeptide (P1NP), was lower in each of the 2.5‐mg and 5‐mg zoledronate groups than the placebo group throughout the trial (p < 0.001 versus placebo for each marker for each dose at each time point). For each endpoint, changes were similar in the 2.5‐mg and 5‐mg zoledronate groups, whereas those in the 1‐mg group were smaller than those in the other zoledronate groups. These data demonstrate that single administrations of zoledronate 1 mg or 2.5 mg produce antiresorptive effects that persist for at least 2 years. Trials assessing the antifracture efficacy of intermittent low doses of zoledronate, in particular the 2.5‐mg dose, are justified. © 2014 American Society for Bone and Mineral Research.     

Differential Complication Rates Following Radical Cystectomy in the Irradiated and Nonirradiated Pelvis

Background

Reports suggest that cystectomy following pelvic irradiation is associated with a higher morbidity and mortality than in primary cases. However, such reports are from an era when postcystectomy complication rates were higher than are currently reported.

Objective

This study evaluates perioperative complications and mortality in primary radical and postradiation salvage cystectomy.

Design, setting, and participants

Patients treated with cystectomy for bladder cancer or advanced pelvic malignancies involving the bladder were studied.

Measurements

Perioperative complications and mortality were analysed for 426 primary and 420 salvage cystectomies performed at a single institution between 1970 and 2005.

Results and limitations

The 30- and 60-d mortality in the 2000–2005 cohort were 0% and 1.2%, respectively, in the primary group and 1.4% and 4.3%, respectively, in the salvage cystectomy group. Thirty-day mortality between 1970 and 2005 was not statistically significant in the primary and salvage groups (4.2% and 7.1%, respectively).

Conclusions

This large series from a high-volume centre demonstrates no difference in perioperative mortality in primary or postradiation salvage radical cystectomy. Similarly, there was no significant difference in the incidence of most of the surgical or medical complications in either group, although the stomal stenosis rate was higher postradiation.     

44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.     

Fatty Acids and Bone

Nutritional status is an important determinant of skeletal health. Increased fat mass favorably influences bone mineral density and reduces fracture risk. The mechanisms by which adiposity influences skeletal health include mechanical skeletal loading, the effects of adipocyte and pancreatic β-cell-derived hormones that act on bone, and neuroendocrine outputs from the hypothalamus that respond to peripheral nutritional signals. A growing body of evidence, including the recognition that specific fatty acid receptors are expressed in skeletal tissue, also suggests that fatty acids affect skeletal health. These effects include indirect actions of dietary and circulating fatty acids, mediated by hormonal signals derived from the intestine and pancreas, and direct effects of some fatty acid species on bone cells. Emerging evidence suggests that marrow adipocyte-derived fatty acids might affect skeletal health via paracrine mechanisms. The existing evidence suggests that there is potential for both positive and negative effects of fatty acids on the skeleton, such that the net effect may be context-specific. Careful laboratory and clinical investigation is required to increase our understanding of a potentially important area of skeletal health.     

Cognitive bias modification - Priming with an ambiguous homograph is necessary to detect an interpretation training effect

Biases in the interpretation of ambiguous information may have a causal role in producing and maintaining anxiety. Training with repeated exposure to emotionally valenced meanings has been found to produce such a bias, as measured by lexical decisions for targets primed with related emotionally ambiguous homographs. Interpretation bias is thought to occur only when ambiguity causes competition for processing resources, but similar results might occur if valenced training causes a response bias. Twenty participants underwent training, followed by a lexical decision task with no ambiguous primes preceding the target stimuli. No training effect was found, supporting the resource competition explanation for the previous findings.     

Detection of massive transplacental haemorrhage by flow cytometry

Flow cytometry has been shown to be a more accurate and sensitive method than the Kleihauer-Betke test for the measurement of feto-maternal haemorrhage in Rh(D) incompatibility. This report describes the successful use of flow cytometry to detect and monitor the management of a massive transplacental haemorrhage (105 ml) of fetal Rh(D) positive cells in a Rh(D) negative woman. The report highlights the accuracy and reproducibility of the test and the stability of a blood sample when transferred 596 kilometres to a central testing facility.     

Visual impairment in severe and profound sensorineural deafness

The frequency of reversible and irreversible visual impairment was determined in children with severe and profound sensorineural deafness, as subnormal vision can adversely affect their educational and social development. Eighty three of 87 such children attending an audiology service were examined to assess the incidence and severity of visual impairment. Each child underwent a detailed ophthalmic assessment. The criteria for visual impairment were visual acuity < 6/9 Snellen or equivalent and/or abnormal binocular vision. Forty five had a normal ophthalmic examination (54.2%). Twenty nine had visual impairment (34.9%) and nine had ophthalmological abnormalities that did not interfere with vision (10.9%). A higher proportion of children with risk factors for visual pathology demonstrated visual impairment than those in whom there were no risk factors. None the less, 44% of visual impairment was among patients without risk factors. The results underline the need to examine all children with severe and profound sensorineural deafness soon after diagnosis and indicate that children with multiple handicaps have a greater likelihood of visual impairment (11 of 14 cases).     

Early neonatal hypocalcemia in extremely preterm infants. High incidence, early onset, and refractoriness to supraphysiologic doses of calcitriol

Nineteen preterm infants born at or before 32 weeks of gestation were studied to determine the dose of calcitriol that would be effective in the prophylaxis of early neonatal hypocalcemia (serum calcium level, less than 7.0 mg/dL [less than 1.75 mmol/L]). In these infants the course of early neonatal hypocalcemia was not modified by calcitriol administration. Serum 1,25-dihydroxyvitamin D level rose in response to intramuscular administration of calcitriol. The incidence of hypocalcemia in these infants was 37% by 12 hours, 83% by 24 hours, and 89% by 36 hours. Thus, in extremely preterm infants, the incidence of early neonatal hypocalcemia is higher and the onset earlier than in larger preterm infants; furthermore, in these infants the hypocalcemia is refractory even to high doses of calcitriol.     

Endocrinologic events in early pregnancy failure

Fourteen women experiencing early pregnancy failure have been studied during the time of conception and at frequent intervals until spontaneous abortion occurred. Serial measurements of serum estradiol, progesterone, 17α-hydroxyprogesterone, prolactin, human placental lactogen (hPL), and human chorionic gonadotropin (hCG) were determined; regular sonar scanning allowed the time of fetal death to be determined to within 7 days in six patients and a diagnosis of blighted ovum to be made in the remainder. In all patients serum progesterone and estradiol concentrations were within the normal range up to 7 weeks but appeared to decrease from about 8 weeks' gestation whether or not a living fetus was present. The placenta continued to produce hCG and hPL but, despite the continuing presence of hCG, the levels of 17α-hydroxyprogesterone declined to concentrations below those associated with normal pregnancy. These data suggest that the placenta may require a particular stimulus to take over production of progesterone and estradiol.