Using a sequential explanatory mixed method to evaluate the therapeutic window of opportunity for initiating osteoporosis treatment following fragility fractures.

Interventions targeting patients with recent fragility fracture and their physician were most successful at initiating osteoporosis treatment during the first 12 months. This window of opportunity had already closed after 1 year. The reasons for declining or accepting the intensive intervention were explored in patients still untreated at 12 months. INTRODUCTION: A fragility fracture (FF) event identifies patients most likely to benefit from osteoporosis treatment. Nonetheless, most FF patients go untreated. Our objective was to determine how long an incident FF remains a strong incentive to initiate osteoporosis treatment. METHODS: A total of 1086 men and women over age 50 with a recent FF event were assigned to either standard care (SC), to minimal (MIN), or intensive (INT) interventions targeting patients and their family physician to initiate osteoporosis treatment. Inpatients with FF (mainly hip) evaluated by rheumatologists were also included in a specialized group (SPE; n = 324). At 1 year, untreated patients in both the SC and the MIN groups were offered an INT intervention. The cohort was followed through 48 months. A qualitative analysis of patient-centered decision-making associated with initiation of treatment was conducted. RESULTS: In MIN and INT groups, osteoporosis treatment was initiated in 41.0 and 54.3% of untreated patients by 12 months, respectively, compared to 68.4% in SPE and 18.9% in SC groups; initiation rates drastically dropped thereafter. Over 4863 patient-years of follow-up, the rates of new FF were 3.4 per 100 patient-years, without significant differences between patients with initial major or minor FF, nor between control or intervention groups. Failure by patients and physicians to recognize FF as a sign of underlying bone disease contributed the most to lack of treatment. CONCLUSION: While incident FFs are an ideal opportunity for starting osteoporosis treatment, 1 year later, the therapeutic window of opportunity has already closed.

Combination therapy of interferon Beta-1b and tacrolimus: a pilot safety study.

Tacrolimus is a calcineurin inhibitor which works to induce immune suppression by preventing cytokine transcription and lymphocyte activation. Combining the immunomodulator interferon beta-1b (Betaseron) with the immunosuppressant tacrolimus (Prograf) may have the potential of additive therapeutic benefit through the complementary mechanisms of action of these two therapeutics. In this randomized, open-label, multicenter, two-arm pilot study, the authors examined the safety and tolerability of the combination of interferon beta-1b and tacrolimus in relapsing remitting (RRMS) and secondary progressive (SPMS) multiple sclerosis patients who have failed one or more immunomodulatory therapies. Patients (n = 25) received a combination of interferon beta-1b subcutaneously every other day and oral tacrolimus (low blood level tacrolimus, 1-5 ng/mL, or high blood level tacrolimus, 5-10 ng/mL) for a period of 38 weeks. The combination therapy of interferon beta-1b and tacrolimus over the 10-month period of the study was shown to be safe and relatively well tolerated. There were no unexpected adverse events occurring as the result of the combination therapy. Further study of this combination therapy in patients with multiple sclerosis unresponsive to conventional therapy is warranted.

Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome.

SUMMARY: Eighty children with nephrotic syndrome underwent lumbar spine densitometry and vertebral morphometry soon after glucocorticoid initiation. We found an inverse relationship between glucocorticoid exposure and spine areal bone mineral density (BMD) Z-score and a low rate of vertebral deformities (8%). INTRODUCTION: Vertebral fractures are an under-recognized complication of childhood glucocorticoid-treated illnesses. Our goal was to study the relationships among glucocorticoid exposure, lumbar spine areal BMD (LS BMD), and vertebral shape in glucocorticoid-treated children with new-onset nephrotic syndrome. METHODS: Lateral thoracolumbar spine radiography and LS BMD were performed in 80 children with nephrotic syndrome (median age 4.4 years; 46 boys) within the first 37 days of glucocorticoid therapy. Genant semiquantitative grading was used as the primary method for vertebral morphometry; the algorithm-based qualitative (ABQ) method was used for secondary vertebral deformity analysis. RESULTS: Six of the 78 children with usable radiographs (8%; 95% confidence interval 4 to 16%) manifested a single Genant grade 1 deformity each. All deformities were mild anterior wedging (two at each of T6, T7, and T8). Four of the 78 children (5%; 95% confidence interval 2 to 13%) showed one ABQ sign of fracture each (loss of endplate parallelism; two children at T6 and two at T8). Two of the children with ABQ signs also had a Genant grade 1 deformity in the same vertebral body. None of the children with a Genant or ABQ deformity reported back pain. An inverse relationship was identified between LS BMD Z-score and glucocorticoid exposure. CONCLUSIONS: Although we identified an inverse relationship between steroid exposure and LS BMD soon after glucocorticoid initiation for childhood nephrotic syndrome, there was only a low rate of vertebral deformities. The clinical significance of these findings requires further study.

Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders.

OBJECTIVE: Vertebral fractures are an under-recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy. METHODS: Children were categorized as follows: juvenile dermatomyositis (n = 30), juvenile idiopathic arthritis (n = 28), systemic lupus erythematosus and related conditions (n = 26), systemic arthritis (n = 22), systemic vasculitis (n = 16), and other conditions (n = 12). Thoracolumbar spine radiograph and dual x-ray absorptiometry for lumbar spine (L-spine) areal bone mineral density (BMD) were performed within 30 days of glucocorticoid initiation. Genant semiquantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative glucocorticoid dose, underlying diagnosis, L-spine BMD Z score, and back pain were analyzed for association with vertebral fracture. RESULTS: Thirteen vertebral fractures were noted in 9 children (7%). Of these, 6 patients had a single vertebral fracture and 3 had 2-3 fractures. Fractures were clustered in the mid-thoracic region (69%). Three vertebral fractures (23%) were moderate (grade 2); the others were mild (grade 1). For the entire cohort, mean +/- SD L-spine BMD Z score was significantly different from zero (-0.55 +/- 1.2, P < 0.001) despite a mean height Z score that was similar to the healthy average (0.02 +/- 1.0, P = 0.825). Back pain was highly associated with increased odds for fracture (odds ratio 10.6 [95% confidence interval 2.1-53.8], P = 0.004). CONCLUSION: In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged glucocorticoid exposure.

A survey of Cambodian health-care providers' HIV knowledge, attitudes and intentions to take a sexual history.

Cambodia has one of the highest prevalence rates of HIV in Asia and is scaling up HIV testing. We conducted a cross-sectional survey with 358 health care providers in Phnom Penh, Cambodia to assess readiness for voluntary testing and counselling for HIV. We measured HIV knowledge and attitudes, and predictors of intentions to take a sexual history using the Theory of Planned Behaviour. Over 90% of health care providers correctly answered knowledge questions about HIV transmission, but their attitudes were often not positive towards people living with HIV. The Theory of Planned Behaviour constructs explained 56% of the variance in intention to take a sexual history: the control providers perceive they have over taking a sexual history was the strongest contributor (51%), while social pressure explained a further 3%. Attitudes about taking a sexual history did not contribute to intention. Interventions with Cambodian health care providers should focus on improving skills in sexual history-taking.

Atropine, fentanyl and succinylcholine for non-urgent intubations in newborns.

OBJECTIVE: Describe intubation conditions and adverse events when using atropine fentanyl +/- succinylcholine as premedication. DESIGN: Prospective observational study, as part of a quality improvement initiative. SETTING: Two level 3 neonatal intensive care units in Ottawa, Canada PATIENTS: 60 infants, median 27 weeks gestation, 1023 g at birth were included. INTERVENTIONS: Infants received atropine, fentanyl +/- succinylcholine prior to the intubation. Succinylcholine was given for all infants > or =34 weeks and at the discretion of the physician for those <34 weeks. MAIN OUTCOME MEASURES: The primary outcome was the number of attempts. Secondary outcomes were number of attempts and intubation conditions in infants who received and those who did not receive succinylcholine and safety. RESULTS: The median number of attempts was 2. 91.7% had excellent or good conditions. The median number of attempts for infants who received succinylcholine was lower (1 vs 2) than those who did not. No serious adverse events were noted. 2 cases of difficult bag and mask ventilation after administration of fentanyl were noted. CONCLUSION: Atropine, fentanyl and succinylcholine before non-urgent intubations in newborns has led to a low number of attempts and good intubation conditions with no adverse events.

Reliability assessment of Society for Fetal Urology ultrasound grading system for hydronephrosis.

PURPOSE: The Society for Fetal Urology introduced a subjective grading system for classifying hydronephrosis that has important implications in patient diagnosis, treatment and outcome. The grading system is frequently used to standardize the severity of hydronephrosis, and compare results among patients and centers. Despite widespread use to our knowledge no groups have investigated the reliability of the grading system since its introduction. We assessed the intrarater and interrater reliability of the Society for Fetal Urology grading system for hydronephrosis and examined levels of agreement by the degree of hydronephrosis (grades 0 to 4) and level of experience (staff vs trainee). MATERIALS AND METHODS: A series of 50 pediatric renal ultrasound images from patients with a diagnosis of hydronephrosis were assessed by 4 staff individuals and 4 trainees using the Society for Fetal Urology grading system. Ultrasound images included the kidneys, ureters and bladder to be consistent with practice. After 7 to 14 days each rater repeated the assessment. The nonweighted Cohen kappa statistic was used to estimate intrarater and interrater reliability by Society for Fetal Urology grade and training level. RESULTS: Staff and trainee raters independently assigned Society for Fetal Urology grades to 50 patients (99 renal units). The average number of images per ultrasound was 41, including the right and left kidneys. Overall interrater agreement for staff individuals was substantial for grade 0, moderate for grades 1, 2 and 4, and only slight to fair for grade 3. Intrarater agreement was substantial to almost perfect for staff agreement (range 69% to 94%, kappa 0.56 to 0.89) and trainees (range 63% to 90%, kappa 0.48 to 0.85). CONCLUSIONS: Our study suggests that the Society for Fetal Urology grading system has good intrarater but modest interrater reliability. Individual rater interpretations of the grading system may explain the modest interrater agreement. Proposed modifications to the Society for Fetal Urology classification system, such as distinguishing between diffuse and segmental cortical thinning, may improve reliability.

Decision-making needs of patients with depression: a descriptive study.

The study's purpose was to explore the decision-making needs of patients considering treatment options for their depression. Semi-structured interviews were guided by the Ottawa Decision Support Framework. Of 94 participants, 67 were uncertain about their decision. Common decisions identified were whether or not to take medications, attend support groups, undergo electroconvulsive therapy, and location of care. Those feeling certain were more likely to have made a decision (RR 1.37; 95% CI: 1.05, 1.78). However, 40 patients who had 'made a decision' in the recent past were uncertain about their decision. Compared with those who were certain, the uncertain group felt less informed (2.65 vs. 1.64; P < 0.001), less supported (2.63 vs. 1.88; P < 0.001) and less clear about how they valued the benefits and risks of options (2.57 vs. 1.69; P < 0.001). Other influential factors included concerns about confidentiality, distress from depression, embarrassment, panic attacks and lack of energy. Few patients wanted to defer decision making to their physician (n = 8) or family (n = 1). To support decision making, participants identified the need for: discussions with their psychiatrist, nurse or family doctor; access to printed information; and information provided by health professionals and health societies.

Bisphosphonate therapy for children and adolescents with secondary osteoporosis.

BACKGROUND: Children with chronic illnesses are at increased risk for reductions in bone strength and subsequent fractures (osteoporosis), either due to the impact of the underlying condition on skeletal development or due to the osteotoxic effect of medications (e.g., glucocorticoids) used to treat the chronic illness. Bisphosphonates are being administered with increasing frequency to children with secondary osteoporosis; however, the efficacy and harm of these agents remains unclear. OBJECTIVES: To examine the efficacy and harm of bisphosphonate therapy in the treatment and prevention of secondary osteoporosis in children and adolescents. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Issue 4, 2006), MEDLINE, EMBASE, CINAHL and ISI Web of Science (inception-December 2006). Further literature was identified through expert contact, key author searches, scanning reference lists of included studies, and contacting bisphosphonate manufacturers. SELECTION CRITERIA: Randomized, quasi-randomized, controlled clinical trials, cohort, and case controls of bisphosphonate(s) in children 0-18 years of age with at least one low-trauma fracture event or reductions in bone mineral density in the context of secondary osteoporosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed quality. Case series were used for supplemental harms-related data. MAIN RESULTS: Six RCTs, two CCTs, and one prospective cohort (n=281 children) were included and classified into osteoporosis due to: 1) neuromuscular conditions (one RCT) and 2) chronic illness (five RCTs, two CCTs, one cohort). Bisphosphonates examined were oral alendronate, clodronate, and intravenous (IV) pamidronate. Study quality varied. Harms data from 23 case series (n=241 children) were used. Heterogeneity precluded statistically combining the results. Percent change or Z-score change in lumbar spine areal BMD from baseline were consistently reported. Two studies carried out between-group analyses; one showed no significant difference (using oral alendronate in anorexia nervosa) while the other demonstrated a treatment effect on lumbar spine with IV pamidronate in burn patients. Frequently reported harms included the acute phase reaction, followed by gastrointestinal complaints, and bone/muscle pain. AUTHORS' CONCLUSIONS: The results justify further evaluation of bisphosphonates among children with secondary osteoporosis. However, the evidence does not support bisphosphonates as standard therapy. Short-term (3 years or less) bisphosphonate use appears to be well-tolerated. An accepted criterion for osteoporosis in children, a standardized approach to BMD reporting, and examining functional bone health outcomes (e.g., fracture rates) will allow for appropriate comparisons across studies.

Treating asthma with omega-3 fatty acids: where is the evidence? A systematic review.

BACKGROUND: Considerable interest exists in the potential therapeutic value of dietary supplementation with the omega-3 fatty acids. Given the interplay between pro-inflammatory omega-6 fatty acids, and the less pro-inflammatory omega-3 fatty acids, it has been thought that the latter could play a key role in treating or preventing asthma. The purpose was to systematically review the scientific-medical literature in order to identify, appraise, and synthesize the evidence for possible treatment effects of omega-3 fatty acids in asthma. METHODS: Medline, Premedline, Embase, Cochrane Central Register of Controlled Trials, CAB Health, and, Dissertation Abstracts were searched to April 2003. We included randomized controlled trials (RCT's) of subjects of any age that used any foods or extracts containing omega-3 fatty acids as treatment or prevention for asthma. Data included all asthma related outcomes, potential covariates, characteristics of the study, design, population, intervention/exposure, comparators, and co interventions. RESULTS: Ten RCT's were found pertinent to the present report. CONCLUSION: Given the largely inconsistent picture within and across respiratory outcomes, it is impossible to determine whether or not omega-3 fatty acids are an efficacious adjuvant or monotherapy for children or adults. Based on this systematic review we recommend a large randomized controlled study of the effects of high-dose encapsulated omega-3 fatty acids on ventilatory and inflammatory measures of asthma controlling diet and other asthma risk factors. This review was limited because Meta-analysis was considered inappropriate due to missing data; poorly or heterogeneously defined populations, interventions, intervention-comparator combinations, and outcomes. In addition, small sample sizes made it impossible to meaningfully assess the impact on clinical outcomes of co-variables. Last, few significant effects were found.

Glucose tolerance of offspring of mother with gestational diabetes mellitus in a low-risk population.

AIMS: To describe the prevalence of impaired glucose tolerance and obesity in offspring of mothers whose pregnancies were complicated by gestational diabetes mellitus (GDM) in a low-risk population and to investigate the effect on these outcomes of minimal intervention compared with tight control for management of GDM. METHODS: Eighty-nine children (mean age 9.1 years, 93% Caucasian) were recruited through a follow-up study of women previously involved in a randomized controlled trial of minimal intervention (control group) vs. tight glycaemic control (treatment group) for GDM. Fasting blood glucose (FBG) and 2-h glucose tolerance tests (2hGTT) were performed on offspring and body mass index (BMI) calculated. Glucose tolerance and BMI of treatment groups were compared using non-inferiority tests (non-inferiority margin -15%). RESULTS: Of those offspring, 6.9% (5/72) had abnormal glucose metabolism [four children had impaired glucose tolerance (IGT) and one had Type 2 diabetes mellitus (DM) (all Caucasian)]. Of the four children with IGT, three were male, three had normal BMI, and three had a family history of Type 2 diabetes. Of the 71 offspring who underwent 2hGTT, 25/25 (100%) of the control offspring and 46/46 (100%) of the treatment offspring had normal FBG (FBG < 5.7 mmol/l). Twenty-five of 25 (100%) of control and 42/46 (91.3%) of the treatment offspring had normal glucose tolerance (2hGTT < 7.8 mmol/l) (% difference 8.7, 95% CI -5.6, 20.3). BMI < 85th percentile was found in 25/33 (75.8%) of the treatment group and 44/52 (84.6%) of the control group (difference in percentage -8.9, 95% CI -27.2, 7.8). CONCLUSIONS: School-age children of mothers with GDM are at risk of IGT and overweight, even if from a low-risk ethnic population. FBG was not adequate for screening this population. Minimal intervention for glycaemic control in GDM pregnancies appears to be as effective as tight control for preventing IGT in childhood but not for preventing obesity.