Erector spinae plane block vs. peri-articular injection for pain control after arthroscopic shoulder surgery: a randomised controlled trial.

Interscalene brachial plexus block is the standard regional analgesic technique for shoulder surgery. Given its adverse effects, alternative techniques have been explored. Reports suggest that the erector spinae plane block may potentially provide effective analgesia following shoulder surgery. However, its analgesic efficacy for shoulder surgery compared with placebo or local anaesthetic infiltration has never been established. We conducted a randomised controlled trial to compare the analgesic efficacy of pre-operative T2 erector spinae plane block with peri-articular infiltration at the end of surgery. Sixty-two patients undergoing arthroscopic shoulder repair were randomly assigned to receive active erector spinae plane block with saline peri-articular injection (n = 31) or active peri-articular injection with saline erector spinae plane block (n = 31) in a blinded double-dummy design. Primary outcome was resting pain score in recovery. Secondary outcomes included pain scores with movement; opioid use; patient satisfaction; adverse effects in hospital; and outcomes at 24 h and 1 month. There was no difference in pain scores in recovery, with a median difference (95%CI) of 0.6 (-1.9-3.1), p = 0.65. Median postoperative oral morphine equivalent utilisation was significantly higher in the erector spinae plane group (21 mg vs. 12 mg; p = 0.028). Itching was observed in 10% of patients who received erector spinae plane block and there was no difference in the incidence of significant nausea and vomiting. Patient satisfaction scores, and pain scores and opioid use at 24 h were similar. At 1 month, six (peri-articular injection) and eight (erector spinae plane block) patients reported persistent pain. Erector spinae plane block was not superior to peri-articular injection for arthroscopic shoulder surgery.

Fragility of results from randomized controlled trials supporting the guidelines for the treatment of osteoporosis: a retrospective analysis.

This is the first report on the fragility of results from randomized controlled trials (RCTs) for the treatment of osteoporosis. The results of aforementioned RCTs appear to depend on a small number of events and are generally statistically fragile. INTRODUCTION: Osteoporosis remains a health concern worldwide. Evidence-based guideline recommendations that are mainly based on results of clinical trials are important to clinical decision-making. The fragility index (FI) is a novel statistical metric to measure the fragility of results from an RCT. Our study aimed to analyze the fragility of the clinical trials referenced in the guidelines for the treatment of osteoporosis. METHODS: Trials were included if they investigated primary osteoporosis, randomized patients to treatment or control in a 1:1 design, and reported fracture outcome as the primary endpoint. The FI and fragility quotient (FQ) were calculated for assessing the robustness of results from the eligible RCTs. An FI was defined as the minimum number of events in the intervention group that needs to change from a non-event to an event in order to render a significant result non-significant (or vice versa). The FQ was calculated by dividing the FI by the sample size of the trial. RESULTS: Of the 372 RCTs identified from the guidelines, 42 were eligible for analyses. Their median FI was 10 (25th-75th percentile [Q1-Q3]: 4-18), with a median FQ of 0.007 (Q1-Q3: 0.0017-0.019). Approximately one third of the RCTs had a FI of less than or equal to 5. There were 17 (40.5%) trials where the number of patients lost to follow-up was greater than the FI. The FI was significantly associated with sample size, journal impact factor, and the percent of patients lost to follow-up. CONCLUSION: Results from some RCTs supporting guideline recommendations for the treatment of osteoporosis depend on a small number of events. The FI and FQ may provide additional, intuitive metrics to help interpret the robustness of trial results.

Exploring changes in bone mass in individuals with a chronic spinal cord injury.

People experience rapid bone loss shortly after a spinal cord injury (SCI), but the long-term bone changes are yet to be confirmed. This study showed that trabecular bone may have reached a steady state, whereas cortical bone continued to decline in people with a chronic SCI (mean time post injury: 15.5 ± 10 years). INTRODUCTION: (1) To explore changes in bone [primary measure: trabecular volumetric bone mineral density (vBMD); secondary measures: cortical vBMD, cortical thickness, cortical cross-sectional area (CSA), and polar moment of inertia] over 2 years in individuals with a chronic spinal cord injury (SCI). (2) To explore whether muscle density changes were potential correlates of the observed bone changes. METHODS: This study is a secondary data analysis of a prospective, observational study involving 70 people with a chronic SCI (≥ 2 years post injury). The study included 4 strata of participants with diverse impairments: (1) Paraplegia (T1-T12) motor complete American Spinal Injury Association Impairment Scale (AIS) A/B (n = 23), (2) Paraplegia motor incomplete AIS C/D (n = 11), (3) Tetraplegia (C2-C8) AIS A/B (n = 22), and (4) Tetraplegia AIS C/D (n = 14). Peripheral quantitative computed tomography scans were taken at the 4% (distal tibia), 38% (diaphyseal tibia), and 66% (muscle cross-sectional area) tibia sites by measuring from the distal to proximal tibia starting at the inferior border of the medial malleolus. The tibia sites were assessed annually over a span of 2 years. Comparisons were made using a paired-samples t test and simple linear regression was used to adjust for sex, time post injury, and bisphosphonate use. RESULTS: We observed no changes in trabecular vBMD at the 4% tibia site, but there was a statistically significant decline in cortical vBMD, cortical thickness, and CSA at the 38% tibia site. Changes in muscle density were not associated with the decreases observed in cortical bone. CONCLUSION: Our findings suggest that individuals with chronic SCI (mean duration of injury: 15.5 ± 10 years) may have reached a plateau in bone loss with respect to trabecular bone, but cortical bone loss can continue well into the chronic stages.

Describing the resource utilisation and costs associated withvertebral fractures: the Build Better Bones with Exercise (B3E) Pilot Trial.

This analysis examined costs/resources of 141 women with vertebral fractures, randomised to a home exercise programme or control group. Total, mean costs and the incremental cost-effectiveness ratio (ICER) were calculated. Quality of life was collected. Cost drivers were caregiver time, medications and adverse events (AEs). Results show adding an exercise programme may reduce the risk of AEs. INTRODUCTION: This exploratory economic analysis examined the health resource utilisation and costs experienced by women with vertebral fractures, and explored the effects of home exercise on those costs. METHODS: Women ≥ 65 years with one or more X-ray-confirmed vertebral fractures were randomised 1:1 to a 12-month home exercise programme or equal attention control group. Clinical and health system resources were collected during monthly phone calls and daily diaries completed by participants. Intervention costs were included. Unit costs were applied to health system resources. Quality of life (QoL) information was collected via EQ-5D-5L at baseline, 6 and 12 months. RESULTS: One hundred and forty-one women were randomised. Overall total costs (CAD 2018) were $664,923 (intervention) and $614,033 (control), respectively. The top three cost drivers were caregiver time ($250,269 and $240,811), medications ($151,000 and $122,145) and AEs ($58,807 and $71,981). The mean cost per intervention participant of $9365 ± $9988 was higher compared with the mean cost per control participant of $8772 ± $9718. The mean EQ-5D index score was higher for the intervention participants (0.81 ± 0.11) compared with that of controls (0.79 ± 0.13). The differences in quality-adjusted life year (QALY) (0.02) and mean cost ($593) were used to calculate the ICER of $29,650. CONCLUSIONS: Women with osteoporosis with a previous fracture experience a number of resources and associated costs that impact their care and quality of life. Caregiver time, medications and AEs are the biggest cost drivers for this population. The next steps would be to expand this feasibility study with more participants, longer-term follow-up and more regional variability.

Study protocol to investigate biomolecular muscle profile as predictors of long-term urinary incontinence in women with gestational diabetes mellitus.

BACKGROUND: Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. METHODS: The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24-26 weeks, with a follow-up at 34-38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24-48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. DISCUSSION: To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

Satisfactory analgesia with minimal emesis in day surgeries: a randomised controlled trial of morphine versus hydromorphone.

BACKGROUND: Opioids remain the mainstay therapy for post-surgical pain. Although both morphine and hydromorphone are potent analgesics, it has been suggested that hydromorphone is clinically better. Our primary objective was to compare morphine with hydromorphone for achieving satisfactory analgesia with minimal emesis (SAME). METHODS: We performed a multicentre RCT in 402 patients having ambulatory surgery. A random computer-generated allocation, stratified by site, was developed by our pharmacy. Concealment was achieved by allocating patients to study groups by nurses using sequentially coded study medication syringes having equi-analgesic doses, made available in the postoperative recovery room. Patients, health providers, and research personnel were blinded. The operating-room protocol allowed for routine anaesthetic management, excluding the use of study medications. Study medications were administered by recovery nurses as per an algorithm. Analyses utilised the intention-to-treat principle, and regression analyses were used for outcomes as appropriate and using multiple imputation. RESULTS: Of 751 patients, 402 were randomised between morphine (n=199) and hydromorphone (n=203). Baseline and intraoperative variables were comparable across the groups. The odds of achieving SAME were similar between the groups (odds ratio: 1.01; 95% confidence interval: 0.57-1.80). There were no differences in the side-effects of severe itching, respiratory depression, or sedation. Patient satisfaction, discharge times, and post-discharge outcomes, including pain and nausea/vomiting over 24 h, were also comparable. CONCLUSIONS: There was no difference between morphine and hydromorphone regarding analgesia and common side-effects. The appearance of dose-limiting side-effects is idiosyncratic; the clinical decision must be based on individual responses. CLINICAL TRIAL REGISTRATION: NCT02223377.

The prevalence of sarcopenia in community-dwelling older adults, an exploration of differences between studies and within definitions: a systematic review and meta-analyses.

Background: sarcopenia in ageing is a progressive decrease in muscle mass, strength and/or physical function. This review aims to summarise the definitions of sarcopenia in community-dwelling older adults and explore similarities and differences in prevalence estimates by definition. Methods: a systematic review was conducted to identify articles which estimated sarcopenia prevalence in older populations using search terms for sarcopenia and muscle mass. Overall prevalence for each sarcopenia definition was estimated stratified by sex and ethnicity. Secondary analyses explored differences between studies and within definitions, including participant age, muscle mass measurement techniques and thresholds for muscle mass and gait speed. Results: in 109 included articles, eight definitions of sarcopenia were identified. The lowest pooled prevalence estimates came from the European Working Group on Sarcopenia/Asian Working Group on Sarcopenia (12.9%, 95% confidence interval: 9.9-15.9%), International Working Group on Sarcopenia (9.9%, 3.2-16.6%) and Foundation for the National Institutes of Health (18.6%, 11.8-25.5%) definitions. The highest prevalence estimates were for the appendicular lean mass (ALM)/weight (40.4%, 19.5-61.2%), ALM/height (30.4%, 20.4-40.3%), ALM regressed on height and weight (30.4%, 20.4-40.3%) and ALM / body mass index (24.2%, 18.3-30.1%) definitions. Within definitions, the age of study participants and the muscle mass cut points used were substantive sources of between-study differences. Conclusion: estimates of sarcopenia prevalence vary from 9.9 to 40.4%, depending on the definition used. Significant differences in prevalence exist within definitions across populations. This lack of agreement between definitions needs to be better understood before sarcopenia can be appropriately used in a clinical context.

Build better bones with exercise (B3E pilot trial): results of a feasibility study of a multicenter randomized controlled trial of 12 months of home exercise in older women with vertebral fracture.

We pilot-tested a trial of home exercise on individuals with osteoporosis and spine fracture. Our target enrollment was met, though it took longer than expected. Participants stayed in the study and completed the exercise program with no safety concerns. Future trials should expand the inclusion criteria and consider other changes. PURPOSE: Osteoporotic fragility fractures create a substantial human and economic burden. There have been calls for a large randomized controlled trial examining the effect of exercise on fracture incidence. The B3E pilot trial was designed to evaluate the feasibility of a large trial examining the effects of home exercise on individuals at high risk of fracture. METHODS: Community-dwelling women ≥ 65 years with radiographically confirmed vertebral compression fractures were recruited at seven sites in Canada and Australia. We randomized participants in a 1:1 ratio to a 12-month home exercise program or equal attention control group, both delivered by a physiotherapist (PT). Participants received six PT home visits in addition to monthly phone calls from the PT and a blinded research assistant. The primary feasibility outcomes of the study were recruitment rate (20 per site in 1 year), retention rate (75% completion), and intervention adherence rate (60% of weeks meeting exercise goals). Secondary outcomes included falls, fractures and adverse events. RESULTS: One hundred forty-one participants were recruited; an average of 20 per site, though most sites took longer than anticipated. Retention and adherence met the criteria for success: 92% of participants completed the study; average adherence was 66%. The intervention group did not differ significantly in the number of falls (IRR 0.97, 95% CI 0.58 to 1.63) or fragility fractures (OR 1.11, 95% CI 0.60 to 2.05) compared to the control group. There were 18 serious adverse events in the intervention group and 12 in the control group. CONCLUSION: An RCT of home exercise in women with vertebral fractures is feasible but recruitment was a challenge. Suggestions are made for the conduct of future trials.

Impact of baseline clinical and laboratory features on the risk of thrombosis in children with acute lymphoblastic leukemia: A prospective evaluation.

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) have increased risk of thromboembolism (TE). However, the predictors of ALL-associated TE are as yet uncertain. OBJECTIVE: This exploratory, prospective cohort study evaluated the effects of clinical (age, gender, ALL risk group) and laboratory variables (hematological parameters, ABO blood group, inherited and acquired prothrombotic defects [PDs]) at diagnosis on the development of symptomatic TE (sTE) in children (aged 1 to ≤18) treated on the Dana-Farber Cancer Institute ALL 05-001 study. PROCEDURES: Samples collected prior to the start of ALL therapy were evaluated for genetic and acquired PDs (proteins C and S, antithrombin, procoagulant factors VIII (FVIII:C), IX, XI and von Willebrand factor antigen levels, gene polymorphisms of factor V G1691A, prothrombin gene G20210A and methylene tetrahydrofolate reductase C677T, anticardiolipin antibodies, fasting lipoprotein(a), and homocysteine). RESULTS: Of 131 enrolled patients (mean age [range] 6.4 [1-17] years) 70 were male patients and 20 patients (15%) developed sTE. Acquired or inherited PD had no impact on the risk of sTE. Multivariable analyses identified older age (odds ratio [OR] 1.13; 95% confidence interval [CI]: 1.01, 1.26) and non-O blood group (OR 3.64, 95% CI: 1.06, 12.51) as independent predictors for development of sTE. Patients with circulating blasts had higher odds of developing sTE (OR 6.66; 95% CI: 0.82, 53.85). CONCLUSION: Older age, non-O blood group, and presence of circulating blasts, but not PDs, predicted the risk of sTE during ALL therapy. We recommend evaluation of these novel risk factors in the development of ALL-associated TE. If confirmed, these easily accessible variables at diagnosis can help develop a risk-prediction model for ALL-associated TE.

Agreement between fragility fracture risk assessment algorithms as applied to adults with chronic spinal cord injury.

STUDY DESIGN: Cross-sectional. OBJECTIVES: The objective of the study was to determine and report agreement in fracture risk stratification of adults with spinal cord injury (SCI) using (1) Canadian Association of Radiologists and Osteoporosis Canada (CAROC) and Canadian Fracture Risk Assessment (FRAX) tools with and without areal bone mineral density (aBMD) and (2) SCI-specific fracture thresholds. SETTING: Tertiary rehabilitation center, Ontario, Canada. METHODS: Community-dwelling adults with chronic SCI (n=90, C2-T12, AIS A-D) consented to participation. Femoral neck aBMD values determined 10-year fracture risk (CAROC and FRAX). Knee-region aBMD and distal tibia volumetric BMD values were compared to SCI-specific fracture thresholds. Agreements between CAROC and FRAX risk stratifications, and between fracture threshold risk stratification, were assessed using prevalence- and bias-adjusted Kappa statistics (PABAK). RESULTS: CAROC and FRAX assessment tools showed moderate agreement for post-menopausal women (PABAK=0.56, 95% confidence interval (CI): 0.27, 0.84) and men aged ⩾50 years (PABAK=0.51, 95% CI: 0.34, 0.67), with poor agreement for young men and pre-menopausal women (PABAK⩽0). Excellent agreement was evident between FRAX with and without aBMD in young adults and in those with motor incomplete injury (PABAK=0.86-0.92). In other subgroups, agreement ranged from moderate to substantial (PABAK=0.41-0.73). SCI-specific fracture thresholds (Eser versus Garland) showed poor agreement (PABAK⩽0). CONCLUSION: Fracture risk estimates among individuals with SCI vary substantially with the risk assessment tool. Use of SCI-specific risk factors to identify patients with high fracture risk is recommended until a validated SCI-specific tool for predicting fracture risk is developed.

A systematic review of definitions and reporting of bleeding outcome measures in haemophilia.

INTRODUCTION: Bleeding frequency is an important outcome commonly used in haemophilia studies. There is a variation in practice in how bleeding is measured and defined. AIM: The primary objective of this study was to determine how investigators define and report bleeding outcome measures. METHODS: MEDLINE, EMBASE and the CENTRAL were searched from January 1990 to January 2014. We retrieved all published studies that included patients with haemophilia A or B and reported some measures of bleeding. Two reviewers independently performed title and abstract screening, full-text review and data abstraction of the identified studies. RESULTS: A total of 118 studies fulfilled the inclusion criteria. Study designs were randomized controlled trials (RCT; 14%), cohort (68%), cross-sectional (5%) and others design (11%). The median duration of follow-up (Q1, Q3) was 20 (7.9, 50) months. We found 10 different bleeding outcomes reported [absolute number of bleeding 60 (50.8%) studies, annualized bleeding rate 60 (50.8%) studies, bleed per month 10 (8.5%) studies and others 11 (9.3%) studies]. Of these, 32 (27%) studies reported only mean or median without dispersion and 33 (28%) studies did not report any measures of central tendency (dispersion). CONCLUSIONS: There is substantial variation in definitions and measures of bleeding outcomes in the haemophilia literature. This creates difficulty and limitations in comparing the outcomes between studies and in performing meta-analysis. The haemophilia research community needs to develop a consensus on a clear definition of bleeding and how to address the limitations associated with variations in measures of bleeding between centres and studies.

Lower-extremity muscle atrophy and fat infiltration after chronic spinal cord injury.

BACKGROUND: Atrophy and fatty-infiltration of lower-extremity muscle after spinal cord injury (SCI) predisposes individuals to metabolic disease and related mortality. OBJECTIVES: To determine the magnitude of atrophy and fatty-infiltration of lower-extremity muscles and related factors in a group of individuals with chronic SCI and diverse impairment. METHODS: Muscle cross-sectional area and density were calculated from peripheral quantitative computed tomography scans of the 66% site of the calf of 70 participants with chronic SCI [50 male, mean age 49 (standard deviation 12) years, C2-T12, AIS A-D] and matched controls. Regression models for muscle area and density were formed using 16 potential correlates selected a priori. RESULTS: Participants with motor-complete SCI had ≈ 32% lower muscle area, and ≈ 43% lower muscle density values relative to controls. Participants with motor-incomplete SCI had muscle area and density values that were both ≈ 14% lower than controls. Body mass (+), tetraplegia (+), motor function (+), spasticity (+), vigorous physical activity (+), wheelchair use (-), age (-), and waist circumference (-) were associated with muscle size and/or density in best-fit regression models. CONCLUSIONS: There are modifiable factors related to muscle size, body composition, and activity level that may offer therapeutic targets for preserving metabolic health after chronic SCI.

Exploring the determinants of fracture risk among individuals with spinal cord injury.

UNLABELLED: In this cross-sectional study, we found that areal bone mineral density (aBMD) at the knee and specific tibia bone geometry variables are associated with fragility fractures in men and women with chronic spinal cord injury (SCI). INTRODUCTION: Low aBMD of the hip and knee regions have been associated with fractures among individuals with chronic motor complete SCI; however, it is unclear whether these variables can be used to identify those at risk of fracture. In this cross-sectional study, we examined whether BMD and geometry measures are associated with lower extremity fragility fractures in individuals with chronic SCI. METHODS: Adults with chronic [duration of injury ≥ 2 years] traumatic SCI (C1-L1 American Spinal Cord Injury Association Impairment Scale A-D) reported post injury lower extremity fragility fractures. Dual-energy X-ray absorptiometry (DXA) was used to measure aBMD of the hip, distal femur, and proximal tibia regions, while bone geometry at the tibia was assessed using peripheral quantitative computed tomography (pQCT). Logistic regression and univariate analyses were used to identify whether clinical characteristics or bone geometry variables were associated with fractures. RESULTS: Seventy individuals with SCI [mean age (standard deviation [SD]), 48.8 (11.5); 20 females] reported 19 fragility fractures. Individuals without fractures had significantly greater aBMD of the hip and knee regions and indices of bone geometry. Every SD decrease in aBMD of the distal femur and proximal tibia, trabecular volumetric bone mineral density, and polar moment of inertia was associated with fracture prevalence after adjusting for motor complete injury (odds ratio ranged from 3.2 to 6.1). CONCLUSION: Low knee aBMD and suboptimal bone geometry are significantly associated with fractures. Prospective studies are necessary to confirm the bone parameters reported to predict fracture risk in individuals with low bone mass and chronic SCI.

A Frailty Index predicts 10-year fracture risk in adults age 25 years and older: results from the Canadian Multicentre Osteoporosis Study (CaMos).

UNLABELLED: We created a 30-item Frailty Index in the Canadian Multicentre Osteoporosis Study. A Frailty Index is a sensitive measure that can quantify fracture risk according to degree of frailty. Our results indicated that at any age, frailty was an important independent risk factor for fracture over 10 years. INTRODUCTION: In later life, frailty has been linked to fractures. It is likely that the antecedents of fracture are seen across the life course, in ways not entirely captured by traditional osteoporosis risk factors. Using data collected from the prospective, population-based Canadian Multicentre Osteoporosis Study (CaMos), we created the 30-item CaMos Frailty Index and examined whether it was associated with incident fractures over 10 years. METHODS: All CaMos participants aged 25 years and older (n = 9,423) were included in the analysis. To examine the relationship between baseline Frailty Index scores and incident fractures, a competing risk proportional sub-distribution hazards model was used with death considered a competing risk. Analyses were adjusted for age, sex, body mass index, education level, femoral neck T-score, and antiresorptive therapy. RESULTS: At baseline, the mean age was 62.1 years [standard deviation (SD) 13.4], and 69.4 % were women. The mean Frailty Index score was 0.13 (SD 0.11), ranging from 0 to 0.66. For every 0.10 increase in Frailty Index scores (approximately one SD), the hazard ratio was 1.25 (p < 0.001) for all fractures, 1.18 (p = 0.043) for hip fractures, and 1.30 (p ≤ 0.001) for clinical vertebral fractures. CONCLUSION: The CaMos Frailty Index quantified fracture risk according to degree of frailty. Irrespective of age and bone mineral density, the Frailty Index was associated with hip, vertebral, and all-type clinical fractures. Predicting late onset illnesses may have to consider overall health status and not just traditional risk factors.

The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression.

Candidate gene and genome-wide association studies have not identified common variants, which are reliably associated with depression. The recent identification of obesity predisposing genes that are highly expressed in the brain raises the possibility of their genetic contribution to depression. As variation in the intron 1 of the fat mass- and obesity-associated (FTO) gene contributes to polygenic obesity, we assessed the possibility that FTO gene may contribute to depression in a cross-sectional multi-ethnic sample of 6561 depression cases and 21,932 controls selected from the EpiDREAM, INTERHEART, DeCC (depression case-control study) and Cohorte Lausannoise (CoLaus) studies. Major depression was defined according to DSM IV diagnostic criteria. Association analyses were performed under the additive genetic model. A meta-analysis of the four studies showed a significant inverse association between the obesity risk FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P=3 × 10(-4)) adjusted for age, sex, ethnicity/population structure and body-mass index (BMI) with no significant between-study heterogeneity (I(2)=0%, P=0.63). The FTO rs9939609 A variant was also associated with increased BMI in the four studies (ß 0.30 (0.08, 0.51), P=0.0064) adjusted for age, sex and ethnicity/population structure. In conclusion, we provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI. This study highlights the potential importance of obesity predisposing genes on depression.

Patient data meta-analysis of Post-Authorization Safety Surveillance (PASS) studies of haemophilia A patients treated with rAHF-PFM.

UNLABELLED: A Post-Authorization Safety Study (PASS) global program was designed to assess safety and effectiveness of rAHF-PFM (ADVATE) use in haemophilia patients in routine clinical settings. The main aim of this project was to estimate the rate of inhibitors and other adverse events across ADVATE-PASS studies by meta-analysing individual patient data (IPD). Eligible Studies: PASS studies conducted in different countries, between 2003 and 2013, for which IPD were provided. Eligible patients: haemophilia A patients with baseline FVIII:C < 5%, with a known number of prior exposure days (EDs). PRIMARY OUTCOME: de novo inhibitors in severe, previously treated patients (PTPs) with > 150 EDs. SECONDARY OUTCOMES: de novo inhibitors according to prior exposure and disease severity; other adverse events; annualized bleeding rate (ABR). ANALYSIS: random-effects logistic regression. Five of seven registered ADVATE-PASS (Australia, Europe, Japan, Italy and USA) and 1188 patients were included (median follow-up 384 days). Among severe PTPs with > 150 EDs, 1/669 developed de novo inhibitors (1.5 per 1000; 95% confidence interval [CI] 0.2, 10.6 per 1000). Among all patients included in the PASS studies, 21 developed any type of inhibitors (2.0%, 95% CI: 0.8%, 4.7%). Less than 1% of patients presented with other serious adverse events possibly related to ADVATE. The overall median ABR was 3.83 bleeds/year (first, third quartiles: 0.60, 12.90); 1.66 (0, 4.78) in the 557 patients continuously on prophylaxis ≥ twice/week. Meta-analysing PASS data from different countries confirmed the overall favourable safety and effectiveness profile of ADVATE in routine clinical settings.

Cost-effectiveness analysis of health tapestry, a complex primary care program for older adults: a post-hoc analysis.

BACKGROUND: We initially reported on the cost-effectiveness of a 6-month randomized controlled implementation trial which evaluated Health TAPESTRY, a primary care program for older adults, at the McMaster Family Health Team (FHT) site and 5 other FHT sites in Ontario, Canada. While there were no statistically significant between-group differences in outcomes at month 6 post randomization, positive outcomes were observed at the McMaster FHT site, which recruited 40% (204/512) of the participants. The objective of this post-hoc study was to determine the cost-effectiveness of Health TAPESTRY based on data from the McMaster FHT site. METHODS: Costs included the cost to implement Health TAPESTRY at McMaster as well as healthcare resource consumed, which were costed using publicly available sources. Health-related-quality-of-life was evaluated with the EQ-5L-5L at baseline and at month 6 post randomization. Quality-adjusted-life-years (QALYs) were calculated under an-area-under the curve approach. Unadjusted and adjusted regression analyses (two independent regression analyses on costs and QALYs, seemingly unrelated regression [SUR], net benefit regression) as well as difference-in-difference and propensity score matching (PSM) methods, were used to deal with the non-randomized nature of the trial. Sampling uncertainty inherent to the trial data was estimated using non-parametric bootstrapping. The return on investment (ROI) associated with Health TAPESTRY was calculated. All costs were reported in 2021 Canadian dollars. RESULTS: With an intervention cost of $293/patient, Health TAPESTRY was the preferred strategy in the unadjusted and adjusted analyses. The results of our bootstrap analyses indicated that Health TAPESTRY was cost-effective compared to usual care at commonly accepted WTP thresholds. For example, if decision makers were willing to pay $50,000 per QALY gained, the probability of Health TAPESTRY to be cost effective compared to usual care varied from 0.72 (unadjusted analysis) to 0.96 (SUR) when using a WTP of $50,000/QALY gained. The DID and ROI analyses indicated that Health Tapestry generated a positive ROI. CONCLUSION: Health TAPESTRY was the preferred strategy when implemented at the McMaster FHT. We caution care in interpreting the results because of the post-hoc nature of the analyses and limited sample size based on one site.

Estimating the excess costs for patients with incident fractures, prevalent fractures, and nonfracture osteoporosis.

SUMMARY: Based on a population age 50+, significant excess costs relative to matched controls exist for patients with incident fractures that are similar in relative magnitude to other chronic diseases such as stroke or heart disease. Prevalent fractures also have significant excess costs that are similar in relative magnitude to asthma/chronic obstructive pulmonary disease. INTRODUCTION: Cost of illness studies for osteoporosis that only include incident fractures may ignore the long-term cost of prevalent fractures and primary preventive care. We estimated the excess costs for patients with incident fractures, prevalent fractures, and nonfracture osteoporosis relative to matched controls. METHODS: Men and women age 50+ were selected from administrative records in the province of Manitoba, Canada for the fiscal year 2007-2008. Three types of cases were identified: (1) patients with incident fractures in the current year (2007-2008), (2) patients with prevalent fractures in previous years (1995-2007), and (3) nonfracture osteoporosis patients identified by specific pharmacotherapy or low bone mineral density. Excess resource utilization and costs were estimated by subtracting control means from case means. RESULTS: Seventy-three percent of provincial population age 50+ (52 % of all men and 91 % of all women) were included (121,937 cases, 162,171 controls). There were 3,776 cases with incident fracture (1,273 men and 2,503 women), 43,406 cases with prevalent fractures (15,784 men and 27,622 women) and 74,755 nonfracture osteoporosis cases (7,705 men and 67,050 women). All incident fractures had significant excess costs. Incident hip fractures had the highest excess cost: men $44,963 (95 % CI: $38,498-51,428) and women $45,715 (95 % CI: $36,998-54,433). Prevalent fractures (other than miscellaneous or wrist fractures) also had significant excess costs. No significant excess costs existed for nonfracture osteoporosis. CONCLUSION: Significant excess costs exist for patients with incident fractures and with prevalent hip, vertebral, humerus, multiple, and traumatic fractures. Ignoring prevalent fractures underestimate the true cost of osteoporosis.

Is funding source related to study reporting quality in obesity or nutrition randomized control trials in top-tier medical journals?

BACKGROUND: Faithful and complete reporting of trial results is essential to the validity of the scientific literature. An earlier systematic study of randomized controlled trials (RCTs) found that industry-funded RCTs appeared to be reported with greater quality than non-industry-funded RCTs. The aim of this study was to examine the association between systematic differences in reporting quality and funding status (that is, industry funding vs non-industry funding) among recent obesity and nutrition RCTs published in top-tier medical journals. METHODS: Thirty-eight obesity or nutrition intervention RCT articles were selected from high-profile, general medical journals (The Lancet, Annals of Internal Medicine, JAMA and the British Medical Journal) published between 2000 and 2007. Paired papers were selected from the same journal published in the same year, one with and the other without industry funding. The following identifying information was redacted: journal, title, authors, funding source and institution(s). Then three raters independently and blindly rated each paper according to the Chalmers method, and total reporting quality scores were calculated. FINDINGS: The inter-rater reliability (Cronbach's alpha) was 0.82 (95% confidence interval = 0.80-0.84). The total mean (M) and s.d. of Chalmers Index quality score (out of a possible 100) for industry-funded studies were M = 84.5, s.d. = 7.04 and for non-industry-funded studies they were M = 79.4, s.d. = 13.00. A Wilcoxon matched-pairs signed-ranks test indicates no significant rank difference in the distributions of total quality scores between funding sources, Z = -0.966, P = 0.334 (two tailed). INTERPRETATION: Recently published RCTs on nutrition and obesity that appear in top-tier journals seem to be equivalent in quality of reporting, regardless of funding source. This may be a result of recent reporting of quality statements and efforts of journal editors to raise all papers to a common standard.

Estimation of the lifetime risk of hip fracture for women and men in Canada.

UNLABELLED: In Canada in 2008, based on current rates of fracture and mortality, a woman or man at age 50 years will have a projected lifetime risk of fracture of 12.1% and 4.6%, respectively, and 8.9% and 6.7% after incorporating declining rates of hip fracture and increases in longevity. INTRODUCTION: In 1989, the lifetime risk of hip fractures in Canada was 14.0% (women) and 5.2% (men). Since then, there have been changes in rates of hip fracture and increased longevity. We update these estimates to 2008 adjusted for these trends, and in addition, we estimated the lifetime risk of first hip fracture. METHODS: We used national administrative data from fiscal year April 1, 2007 to March 31, 2008 to identify all hip fractures in Canada. We estimated the crude lifetime risk of hip fracture for age 50 years to end of life using life tables. We projected lifetime risk incorporating national trends in hip fracture and increased longevity from Poisson regressions. Finally, we removed the percentage of second hip fractures to estimate the lifetime risk of first hip fracture. RESULTS: From April 1, 2007 to March 31, 2008, there were 21,687 hip fractures, 15,742 (72.6%) in women and 5,945 (27.4%) in men. For women and men, the crude lifetime risk was 12.1% (95%CI, 12.1, 12.2%) and 4.6% (95%CI, 4.5, 4.7%), respectively. When trends in mortality and hip fractures were both incorporated, the lifetime risk of hip fracture were 8.9% (95%CI, 2.3, 15.4%) and 6.7% (95%CI, 1.2, 12.2%). The lifetime risks for first hip fracture were 7.3% (95%CI, 0.8, 13.9%) and 6.2% (95%CI, 0.7, 11.7%). CONCLUSIONS: The lifetime risk of hip fracture has fallen from 1989 to 2008 for women and men. Adjustments for trends in mortality and rates of hip fracture with removing second fractures produced non-significant differences in estimates.