Does osteoporosis therapy invalidate FRAX for fracture prediction?

Ten-year fracture risk assessment with the fracture risk assessment system (FRAX) is increasingly used to guide treatment decisions. Osteoporosis pharmacotherapy reduces fracture risk, but the effect is greater than can be explained from the increase in bone mineral density (BMD). Whether this invalidates fracture predictions with FRAX is uncertain. A total of 35,764 women (age ≥50 years) and baseline BMD testing (1996–2007) had FRAX probabilities retroactively calculated. A provincial pharmacy database was used to identify osteoporosis medication use. Women were categorized as untreated, current high adherence users [medication possession ratio (MPR) ≥0.80 in the year after BMD testing], current low adherence users (MPR <0.80), and past users. Fractures outcomes to 10 years were established form a population-based health data repository. FRAX and femoral neck BMD alone stratified major osteoporotic and hip fracture risk within untreated and each treated subgroup (all p-values <0.001) with similar area under the receiver operating characteristic curve. In untreated and each treated subgroup, a stepwise gradient in observed 10-year major osteoporotic and hip fracture incidence was found as a function of the predicted probability tertile (all p-values <0.001 for linear trend). Concordance (calibration) plots for major osteoporotic fractures and hip fractures showed good agreement between the predicted and observed 10-year fracture incidence in untreated women and each treated subgroup. Only in the highest risk tertile of women highly adherent to at least 5 years of bisphosphonate use was observed hip fracture risk significantly less than predicted, though major osteoporotic fracture risk was similar to predicted. In summary, this work suggests that the FRAX tool can be used to predict fracture probability in women currently or previously treated for osteoporosis. Although FRAX should not be used to assess the reduction in fracture risk in individuals on treatment, it may still have value for guiding the need for continued treatment or treatment withdrawal     

Bioavailable vitamin D is more tightly linked to mineral metabolism than total vitamin D in incident hemodialysis patients

Prior studies showed conflicting results regarding the association between 25-hydroxyvitamin D (25(OH)D) levels and mineral metabolism in end-stage renal disease. In order to determine whether the bioavailable vitamin D (that fraction not bound to vitamin D-binding protein) associates more strongly with measures of mineral metabolism than total levels, we identified 94 patients with previously measured 25(OH)D and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) from a cohort of incident hemodialysis patients. Vitamin D-binding protein was measured from stored serum samples. Bioavailable 25(OH)D and 1,25(OH)(2)D were determined using previously validated formulae. Associations with demographic factors and measures of mineral metabolism were examined. When compared with whites, black patients had lower levels of total, but not bioavailable, 25(OH)D. Bioavailable, but not total, 25(OH)D and 1,25(OH)(2)D were each significantly correlated with serum calcium. In univariate and multivariate regression analysis, only bioavailable 25(OH)D was significantly associated with parathyroid hormone levels. Hence, bioavailable vitamin D levels are better correlated with measures of mineral metabolism than total levels in patients on hemodialysis.     

Denosumab reduces the risk of osteoporotic fractures in postmenopausal women, particularly in those with moderate to high fracture risk as assessed with FRAX

Denosumab has been shown to reduce the incidence of vertebral, nonvertebral, and hip fractures. The aim of the current study was to determine whether the antifracture efficacy of denosumab was dependent on baseline fracture probability assessed by FRAX. The primary data of the phase 3 FREEDOM study of the effects of denosumab in women with postmenopausal osteoporosis were used to compute country-specific probabilities using the FRAX tool (version 3.2). The outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. At baseline, the median 10-year probability of a major osteoporotic fracture (with bone mineral density) was approximately 15% and for hip fracture was approximately 5% in both groups. In the simplest model adjusted for age and fracture probability, treatment with denosumab over 3 years was associated with a 32% (95% confidence interval [CI] 20% to 42%) decrease in clinical osteoporotic fractures. Denosumab reduced fracture risk to a greater extent in those at moderate to high risk. For example, at 10% probability, denosumab decreased fracture risk by 11% (p = 0.629), whereas at 30% probability (90th percentile of study population) the reduction was 50% (p = 0.001). The reduction in fracture was independent of prior fracture, parental history of hip fracture, or secondary causes of osteoporosis. A low body mass index (BMI) was associated with greater efficacy. Denosumab significantly decreased the risk of clinical osteoporotic fractures in postmenopausal women. Overall, the efficacy of denosumab was greater in those at moderate to high risk of fracture as assessed by FRAX.     

Atrial fibrillation in patients undergoing coronary artery surgery is associated with adverse outcome

Abstract

Background: The aim was to determine the association between atrial fibrillation (AF) and outcome in patients undergoing coronary artery bypass grafting (CABG).

Methods: All patients undergoing CABG between January 2010 and June 2013 were identified in the Swedish Heart Surgery Registry. Outcomes studied were all-cause mortality, cardiovascular mortality, myocardial infarction, congestive heart failure, ischemic stroke, and recurrent AF. Patients with history of AF prior to surgery (preoperative AF) and patients without history of AF but with AF episodes post-surgery (postoperative AF) were compared to patients with no AF using adjusted Cox regression models.

Results: Among 9,107 identified patients, 8.1% (n?=?737) had preoperative AF, and 25.1% (n?=?2,290) had postoperative AF. Median follow-up was 2.2?years. Compared to no AF, preoperative AF was associated with higher risk of all-cause mortality, adjusted hazard ratio with 95% confidence interval (HR) 1.76 (1.33–2.33); cardiovascular mortality, HR 2.43 (1.68–3.50); and congestive heart failure, HR 2.21 (1.72–2.84). Postoperative AF was associated with risk of all-cause mortality, HR 1.27 (1.01–1.60); cardiovascular mortality, HR 1.52 (1.10–2.11); congestive heart failure, HR 1.47 (1.18–1.83); and recurrent AF, HR 4.38 (2.46–7.78). No significant association was observed between pre- or postoperative AF and risk for myocardial infarction and ischemic stroke.

Conclusions: Approximately 1 in 3 patients undergoing CABG had pre- or postoperative AF. Patients with pre- or postoperative AF were at higher risk of all-cause mortality, cardiovascular mortality, and congestive heart failure, but not of myocardial infarction or ischemic stroke. Postoperative AF was associated with higher risk of recurrent AF.     

Functional and cognitive rehabilitation interventions during intensive care admission: A protocol for a systematic integrative review

Background

Long-term cognitive impairment occurs in up to 60% of intensive care unit (ICU) survivors. Early use of functional and cognitive rehabilitation interventions, while patients are still in ICU, may reduce cognitive decline. We aim to describe the functional and cognitive interventions used during the ICU stay, the healthcare professionals providing interventions, and the potential impact on functional and cognitive rehabilitation.

Method

In this integrative systematic review, we will include empirical qualitative, quantitative, mixed- and multiple-methods studies assessing the use of functional and cognitive rehabilitation provided in ICU. We will identify studies in relevant electronic databases from 2012 to 2022, which will be screened for eligibility by at least two reviewers. Literature reported as narrative reviews and editorials will be excluded. We will assess the impact of interventions evaluating a cognitive and functional function, quality of life, and all-cause mortality at 6–12 months after ICU discharge. The Revised Cochrane risk-of-bias Tool will be used for assessing risk of bias in clinical trials. For observational studies, we will use the National Institutes of Health Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. Furthermore, we will use the critical appraisal skills programme for qualitative studies and the mixed methods appraisal tool for mixed methods studies. We will construct four matrices, including results describing which ICU patients and healthcare professionals were engaged in rehabilitation, which interventions were included in early rehabilitation in ICU, the potential impact on patient outcomes of rehabilitation interventions provided in ICU and a narrative synthesis of themes. A summary of the main results will be reported using modified GRADE methodology.

Impact

This integrative review will inform the feasibility randomised clinical trial testing the development of a complex intervention targeting functional and cognitive rehabilitation for patients in ICU.     

Videocystourethrography with a ring pessary in situ. A clinically useful preoperative investigation for continent women with urogenital prolapse?

The aim of the study was to evaluate the use of a vaginal pessary in the detection of genuine stress incontinence (GSI) in women with urogenital prolapse undergoing urodynamic investigation. Continent women with urogenital prolapse, with or without associated urinary symptoms, were studied. All underwent video-cystourethrography using a standarized protocol. None had evidence of incontinence on provocative testing in the upright position. A well-fitting vaginal ring pessary was inserted to reduce the prolapse and mimic a vaginal repair. The provocative tests were then repeated while the bladder was screened. Seventy women with a mean age 59.0 years (range 34–83) were recruited over a 21-month period: 15 women complained of prolapse alone and 55 had concurrent urinary symptoms; 19 women (27%) developed GSI only following the insertion of a vaginal pessary. The women who became incontinent were significantly older (mean age 63.9 years) than those who remained continent (mean age 56.8 years) (P<0.020). The use of a vaginal pessary increases the detection rate of GSI in continent women with urogenital prolapse undergoing videocystourethrography. These findings are important becasuse women with prolapse and coexisting incontinence should be offered a continence procedure rather than a simple vaginal repair.Editorial Comment: All patients with significant uterovaginal prolapse require preoperative evaluation to rule out the presence of potential stress incontinence. The simplest and best way to perform this preoperatively has yet to be determined, although several methods have been described. These include a cough stress test or cough urethral profile performed with a full bladder with the prolapse reduced with a Sims' speculum, a pessary or vaginal packing. A pad test with the prolapse reduced in a similar fashion has also been used clinically to identify patients at risk for postoperactive potential stress incontinence following correction of pelvic prolapse. The authors present their experience using a ring pessary to reduce the prolapse during videourodynamic evaluation of lower urinary tract function, finding this technique to be effective in identifying patients who leak only with the pessary in place, and therefore, require an incontinence procedure. The pickup rate for this cohort of patients is similar to previous studies using alternative methods of detection. Perhaps the only question yet to be answered is the percentage of patients with negative testing preoperatively, yet who develop urinary incontinence immediately following surgical correction of pelvic relaxation. Only this determination will truly assess the clinical utility of the preoperative methods used to identify potential stress incontinence.     

Cysteine Conjugate beta-Lyase-Dependent Metabolism of Compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene) in Human Subjects Anesthetized with Sevoflurane and in Rats Given Compound A

Background: Sevoflurane undergoes Baralyme- or soda lime-catalyzed degradation in the anesthesia circuit to yield compound A (2-[fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene), which is nephrotoxic in rats and undergoes metabolism via the cysteine conjugate beta-lyase pathway in those animals. The objective of these experiments was to test the hypothesis that compound A undergoes beta-lyase-dependent metabolism in humans.

Methods: Human volunteers were anesthetized with sevoflurane (1.25 minimum alveolar concentration, 3%, 2 l/min, 8 h) and thereby exposed to compound A. Urine was collected at 24-h intervals for 72 h after anesthesia. Rats, which served as a positive control, were given compound A intraperitoneally, and urine was collected for 24 h afterward. Human and rat urine samples were analyzed by19 F nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry for the presence of compound A metabolites.

Results: Analysis of human and rat urine showed the presence of the compound A metabolites [S-[2-(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-N-acetyl-L-cysteine, (E)- and (Z)-S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-N-acetyl-L-cyst eine, 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid, 3,3,3-trifluorolactic acid, and inorganic fluoride. The presence of 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid and 3,3,3-trifluorolactic acid in human urine was confirmed by gas chromatography-mass spectrometry.     

Endoscopic surgery of inverted papillomas under image guidance--a prospective study of 42 consecutive cases at a Danish university clinic.

BACKGROUND: To evaluate the feasibility of endoscopic surgery with image guidance in the treatment of inverted papillomas. STUDY DESIGN AND SETTING: This prospective cohort study comprised 42 consecutive patients with biopsy-confirmed inverted papillomas that were diagnosed between 1998 and 2003. All patients were treated by the first author (C.B.). Image guidance based on preacquired CT scans of the patients was used to assist the surgeon aiming at endoscopic resection of inverted papilloma. The success of the surgery was judged primarily by the recurrence rate and the treatment morbidity. RESULTS: The study group consisted of 30 males and 12 females with a median age of 61 years. The follow-up period ranged from 9 months to 69 months (median, 37 months). The only additional procedure performed was the Caldwell-Luc procedure (8 cases). Recurrence was diagnosed in 10 cases (24%), all in the original tumor site. Eight of these had undergone previous surgery for inverted papilloma. The recurrences were predominantly located in the maxillary or in the frontal sinus (8 cases). In 2 cases, the recurrence was simply removed endoscopically while performing the biopsy procedure. All recurrences were identified within the first 9 months. Associated malignancy was not shown. No severe complications occurred. CONCLUSIONS: A treatment based on endoscopic resection with image guidance appears to offer a safe treatment modality of inverted papilloma with insignificant morbidity. Predominantly cases with nonmedial involvement of the maxillary sinus still require a supplement with the Caldwell Luc procedure. Although all the recurrences were found within 9 months postoperatively, later recurrences cannot be excluded. Long-term follow-up is recommended.     

Total knee arthroplasty and high tibial osteotomy in osteoarthritis--results of a survey in traumatic surgery and orthopedic clinics

AIM: Knee arthroplasties, both total (TKA) and unicondylar, as well as high tibial osteotomy (HTO) represent the main treatment options in severe osteoarthritis of the knee. The aim of this study was to collect detailed information regarding the current treatment strategies in Germany. METHODS: 220 departments of orthopaedic surgery and 250 departments of trauma surgery were asked about their treatment strategies in an anonymous nation-wide survey regarding the different operative procedures in HTO, TKA, revision TKA and related issues. Univariate analyses were performed and means, medians and rates were calculated. RESULTS: Questionnaire forms were answered by 54 % of the departments. The survey represents 31 138 TKA for the year 2002. In the mean 137 TKA were performed in each department. Posterior cruciate ligament retaining components were used in 67 %, resurfacing of the patella was performed in 19 % of cases. The incidence of revision TKA is about 10 % compared to the primary TKA cases. In comparison to a different survey from the year 1995, the absolute number of primary and revision TKA has increased by a factor of nearly three. Compared to the number of TKA, the proportion of HTO has declined to 12 % and the number of unicondylar knee arthroplasties represents 7 % of all cases. CONCLUSION: In the surgical treatment of severe osteoarthritis, TKA shows a highly increasing number, whereas HTO is decreasing. An increasing number of revision TKA can be observed. There is trend towards the cemented implantation technique. Patella resurfacing is not performed routinely in most German hospitals.