Speech restoration with tracheoesophageal prosthesis after total laryngectomy: An observational study of vocal results, complications and quality of life.

OBJECTIVES: To study voice prosthesis survival, complications, efficacy and impact on quality of life. METHODS: A single-center observational study was performed in patients treated for squamous cell carcinoma of the larynx or hypopharynx by total (pharyngo)-laryngectomy between 2010 and 2015. Study data comprised: maximum phonation time (sec), number of and reasons for prosthesis exchanges (leakage through or around the prosthesis, expulsion or inclusion of the prosthesis), plus 2 quality of life questionnaires (QLQ-C30, QLQ-H&N35) and the Voice Handicap Inventory (VHI 30). RESULTS: Forty-nine patients were included. The most common causes of prosthesis exchange were leakage through (73.2%) or around the prosthesis (18.5%). The median time between exchanges was 4 months. Global quality of life status on the QLQ-C30 was 63.5. Mean maximum phonation time was 7.4sec. Mean VHI was 46/120; 10 patients had a mild voice handicap, 12 moderate and 10 severe. No relation emerged between the number of prosthesis exchanges per year and quality of life. Voice handicap significantly decreased quality of life, with QLQ-C30 72.3 for the 22 patients with mild to moderate voice handicap and 44.2 for the 10 patients with severe voice handicap (P=0.001). CONCLUSION: Voice restoration by tracheoesophageal prosthesis after total (pharyngo)-laryngectomy is a reliable technique that decreases voice handicap and, despite potentially serious complications, has little negative impact on quality of life.

"Shame on you": The impact of shame in body-focused repetitive behaviors and binge eating.

Body-focused repetitive behaviors (BFRBs), such as hair-pulling, skin-picking, and nail-biting, have been associated with difficulties in emotion regulation. Studies have suggested that aversive emotions are important triggers for impulsive behaviors such as BFRBs and binge eating. In particular, shame has been hypothesized to be a key emotion before and after these behaviors, but no experimental studies yet have investigated its impact on BFRBs. We aimed to evaluate the role of shame in BFRB and binge eating episodes and the presence of shame following these behaviors. Eighteen women with BFRBs, 18 with binge eating, and 18 community controls participated in the study. Results showed that an experimental shame condition triggered more shame in the binge eating and BFRB groups than in the control group. In addition, the shame induced condition increased the urge to engage in BFRBs, but not in binge eating. Results showed that participants from the BFRB and the binge eating groups reported more shame after engaging in their pathological behaviors compared to following the neutral condition. Future studies should replicate these findings with larger samples and different shame-inducing conditions.

Hip survival after plain core decompression alone versus bone morphogenetic protein and/or bone marrow reinjection with core decompression for avascular osteonecrosis of the femoral head: a retrospective case control study in ninety two patients.

INTRODUCTION: Injecting bone marrow or bone morphogenetic protein 7 (BMP) during core decompression for avascular osteonecrosis (AVN) may improve survival. We hypothesized that adding a complementary technique (injection of BMP and/or non-concentrated bone marrow) to core decompression would reduce the number of patients requiring a subsequent total hip arthroplasty (THA). METHODS: We retrospectively reviewed 92 cases from 2003 to 2018 with a minimum of 2 years of follow-up and an average follow-up of 64 months (24-204). Twenty-four patients had a core decompression (CD) (26.1% (24/92)), 25 had a CD associated with reinjection of bone marrow and BMP (rhBMP7) (27.2% (25/92)), and 43 patients had a CD with bone marrow reinjection (46.7% (43/92)). RESULTS: Hip survival after CD was 66.3% (61/92) at two years and 59.8% (55/92) at 10 years. CD with bone marrow and BMP reinjection had a better hip survival at ten years (HR: 0.492 (CI95%: 0.254-0.952) p = 0.035). A volume of necrosis greater than 30% (HR = 12.97 (CI95 [3.88-43.3] (p < 0.001))) and a Kerboul angle greater than 60° (HR: 12.5 (CI95 [2.84-54.6] (p < 0.001))) were risk factors for a subsequent THA. CONCLUSIONS: CD is an interesting non-invasive technique to preserve the native hip after AVN of the femoral head. Reinjection of bone marrow and/or BMP improved CD hip survival.

Histoire Du Traitement Des Brûlures En France. La Place De L'Hôpital Léon Bérard (Hyères) : Rééducation, Société Savante, Association De Patients.

In the 50s and 60s, before burn centres appeared, burn patients were primarily treated in surgical departments. They were then referred to sanatorium-type institutions, moving towards functional rehabilitation but without a really structured service. In the early 70s, Jean-Pierre Jouglard, Marseille Surgeon, Head of the Burn Treatment Center of the University Hospital of Marseille, collaborated with Dr. Madeleine Malavaud, in an RRF establishment, the Léon Bérard Hospital in Hyères (Var), to create, in 1974, the first French service dedicated to the rehabilitation of burn patients. The Léon Bérard hospital's burn rehabilitation service, which is still active today, helped spread new techniques from the United States of America to France in the 80s, by training young doctors to become rehabilitators. In 1979, it contributed to the creation of the French Society for the Study and Treatment of Burns, enabling patients to compare their experience by promoting the creation of the Association des Brûlés de France in 1983. The Léon Bérard hospital's burn rehabilitation service therefore occupies a prominent place in the history of burn rehabilitation in France.

High-Statistics Measurement of Neutrino Quasielasticlike Scattering at 6 GeV on a Hydrocarbon Target.

We measure neutrino charged-current quasielasticlike scattering on hydrocarbon at high statistics using the wideband Neutrinos at the Main Injector beam with neutrino energy peaked at 6 GeV. The double-differential cross section is reported in terms of muon longitudinal (p_{∥}) and transverse (p_{⊥}) momentum. Cross section contours versus lepton momentum components are approximately described by a conventional generator-based simulation, however, discrepancies are observed for transverse momenta above 0.5 GeV/c for longitudinal momentum ranges 3-5 and 9-20 GeV/c. The single differential cross section versus momentum transfer squared (dσ/dQ_{QE}^{2}) is measured over a four-decade range of Q^{2} that extends to 10 GeV^{2}. The cross section turnover and falloff in the Q^{2} range 0.3-10 GeV^{2} is not fully reproduced by generator predictions that rely on dipole form factors. Our measurement probes the axial-vector content of the hadronic current and complements the electromagnetic form factor data obtained using electron-nucleon elastic scattering. These results help oscillation experiments because they probe the importance of various correlations and final-state interaction effects within the nucleus, which have different effects on the visible energy in detectors.

[Tourette syndrome: Research challenges to improve clinical practice]. / Syndrome de Gilles de la Tourette : défis de la recherche pour améliorer la pratique clinique.

Tourette syndrome is a neurodevelopmental disorder which is characterized by the presence of motor and phonic tics. These tics are generally more prevalent in childhood. Tics typically reach their maximum severity before puberty, around age 10 to 12. In most patients, tic severity usually decreases during late adolescence and adulthood. However, this is not true for all individuals. To date, the developmental trajectory leading to the persistence of tics into adulthood is still poorly understood. There are very few markers that can predict the evolution of tic symptoms from childhood to adulthood. Yet, while we cannot cure Tourette syndrome, it is possible to reduce tic severity with various treatments. The most common treatments are pharmacotherapy and behavioral and cognitive-behavioral therapy. However, there appears to be a limit to the proportion of tics that can be treated, since most treatments offer an average reduction in tics of no more than 50%. Thus, at first, this article reviews recent advances in treatment and symptom progression. Next, we propose some lines of research to improve the management and treatment of people with Tourette syndrome.

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.

Effectiveness of antibacterial prophylaxis during induction chemotherapy in children with acute lymphoblastic leukemia.

BACKGROUND: Pediatric patients receiving induction chemotherapy for newly diagnosed acute lymphoblastic leukemia (ALL) are at high risk of developing life-threatening infections. We investigated whether uniform antibacterial guidelines, including mandatory antibacterial prophylaxis in afebrile patients during induction, decreases the incidence of microbiologically documented bacteremia. METHODS: Between 2012 and 2015, 230 patients with newly diagnosed ALL (aged 1-21) were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 11-001 (DFCI 11-001). Induction therapy, regardless of risk group, included vincristine, prednisone, doxorubicin, methotrexate, and PEG-asparaginase. Afebrile patients received fluoroquinolone prophylaxis at the initiation of induction and those presenting with fever received broad-spectrum antibiotics; antibiotics were continued until blood count recovery. Rates of documented bacteremias and fungal infections on DFCI 11-001 were compared to those on the predecessor protocol (DFCI 05-001), which included the same induction phase without antibiotic prophylaxis guidelines. RESULTS: Sixty-six (28.7%) patients received fluoroquinolone prophylaxis, the remaining patients received broad-spectrum antibiotics. Twenty-four (36.4%) patients on prophylaxis developed fever and seven (10.6%) developed bacteremia. The overall rate of infection during induction on DFCI 11-001 was lower than on DFCl 05-001 (14.3% vs. 26.3%, P < 0.0001) due to a decreased rate of bacteremia (10.9% vs. 24.4%, P < 0.0001). The rate of fungal infections (4.8% vs. 3.6%) and induction death (0.9% vs. 2%) was not significantly different. CONCLUSION: For children with newly diagnosed ALL, uniform antibiotic administration until blood count recovery, including fluoroquinolone prophylaxis for afebrile patients, reduced the incidence of bacteremia during the induction phase. Larger, randomized studies should be performed to confirm these findings.

Impact of genetic polymorphisms determining leukocyte/neutrophil count on chemotherapy toxicity.

Neutropenia and infection are major dose-limiting side effects of chemotherapy. The risk of initial infection and subsequent complications are directly related to the depth and duration of neutropenia. Recent genome-wide association studies identified variants in DARC and CXCL2 genes, and in ORMDL3-GSDMA-CSF3 locus on chromosome 17q21 that influence white blood cell and neutrophil counts in healthy individuals. To investigate whether polymorphisms in these loci in conjunction with chemotherapy may modulate risk of treatment complications, we analyzed 21 SNPs across these genes for an association with chemotherapy-related neutropenia and infection in 286 Caucasian children with acute lymphoblastic leukemia. After correction for multiple testing, DARC polymorphism rs3027012 in 5'-UTR was associated with higher risk of low absolute phagocyte count (APC<500 and <1000 cells per microliter, P=0.001 and P<0.0005, respectively) and hospitalization due to febrile neutropenia (P=0.002). Protective effect was instead seen for DARC rs12075 A to G substitution (P=0.004). The SNP rs3859192 in the GSDMA were associated with hospitalization due to infection (P=0.004); infection was also modulated in the additive manner by the CXCL2 rs16850408 (P=0.002). This study shows for the first time that the variations in DARC, GSDMA and CXCL2 genes may play a role in the onset of chemotherapy complications.

Pathways from senescence to melanoma: focus on MITF sumoylation.

Cutaneous melanoma is a deadly skin cancer that originates from melanocytes. The development of cutaneous melanoma involves a complex interaction between environmental factors, mainly ultraviolet radiation from sunlight, and genetic alterations. Melanoma can also occur from a pre-existing nevus, a benign lesion formed from melanocytes harboring oncogenic mutations that trigger proliferative arrest and senescence entry. Senescence is a potent barrier against tumor progression. As such, the acquisition of mutations that suppress senescence and promote cell division is mandatory for cancer development. This topic appears central to melanoma development because, in humans, several somatic and germline mutations are related to the control of cellular senescence and proliferative activity. Consequently, primary melanoma can be viewed as a paradigm of senescence evasion. In support of this notion, a sumoylation-defective germline mutation in microphthalmia-associated transcription factor (MITF), a master regulator of melanocyte homeostasis, is associated with the development of melanoma. Interestingly, this MITF variant has also been recently reported to negatively impact the program of senescence. This article reviews the genetic alterations that have been shown to be involved in melanoma and that alter the process of senescence to favor melanoma development. Then, the transcription factor MITF and its sumoylation-defective mutant are described. How sumoylation misregulation can change MITF activity and impact the process of senescence is discussed. Finally, the contribution of such information to the development of anti-malignant melanoma strategies is evaluated.

Treatment of highly concentrated tannery wastewater using electrocoagulation: Influence of the quality of aluminium used for the electrode.

This paper deals with the ability of electrocoagulation (EC) to remove simultaneously COD and chromium from a real chrome tanning wastewater in a batch stirred electro-coagulation cell provided with two aluminium-based electrodes (aluminium/copper/magnesium alloy and pure aluminium). Effects of operating time, current density and initial concentration of Cr(III) and COD have been investigated. The concentrations of pollutants have been successfully reduced to environmentally acceptable levels even if the concentrated effluent requires a long time of treatment of around 6h with a 400A/m(2) current density. The aluminium alloy was found to be more efficient than pure aluminium for removal of COD and chromium. Dilution of the waste has been tested for treatment: high abatement levels could be obtained with shorter time of treatment and lower current densities. Energy consumption of the electrocoagulation process was also discussed. The dilution by half of the concentrated waste leads to a higher abatement performance of both COD and chromium with the best energy efficiency.

The IVAIRE project--a randomized controlled study of the impact of ventilation on indoor air quality and the respiratory symptoms of asthmatic children in single family homes.

UNLABELLED: A randomized controlled trial was carried out to measure the impact of an intervention on ventilation, indoor air contaminants, and asthma symptoms of children. Eighty-three asthmatic children living in low-ventilated homes were followed over 2 years. Several environmental parameters were measured during the summer, fall, and winter. The children were randomized after Year 1 (43 Intervention; 40 Control). The intervention included the installation of either a Heat Recovery Ventilator (HRV) or Energy Recovery Ventilator (ERV). During the fall and winter seasons, there was a significant increase in the mean ventilation rate in the homes of the intervention group. A statistically significant reduction in mean formaldehyde, airborne mold spores, toluene, styrene, limonene, and α-pinene concentrations was observed in the intervention group. There was no significant group difference in change in the number of days with symptoms per 14 days. However, there was a significant decrease in the proportion of children who experienced any wheezing (≥1 episode) and those with ≥4 episodes in the 12-month period in the intervention group. This study indicates that improved ventilation reduces air contaminants and may prevent wheezing. Due to lack of power, a bigger study is needed. PRACTICAL IMPLICATIONS: Positive findings from this study include the fact that, upon recruitment, most of the single family homes with asthmatic children were already equipped with a mechanical ventilation system and had relatively good indoor air quality. However, the 8-h indoor guideline for formaldehyde (50 µg/m3) was frequently exceeded and the ventilation rates were low in most of the homes, even those with a ventilation system. Both ERVs and HRVs were equally effective at increasing air exchange rates above 0.30 ACH and at preventing formaldehyde concentrations from exceeding the 50 µg/m3 guideline during the fall and winter seasons. Furthermore, the ERVs were effective at preventing excessively low relative humidities in the homes. Based on observed difference of risk, intervention to increase ventilation in five sample homes and children would prevent 1 home to exceed the indoor air long-term formaldehyde guideline and prevent 1 asthmatic child experiencing at least one episode of wheezing over a year.

Interleukin-6 deletion in mice driven by aP2-Cre-ERT2 prevents against high-fat diet-induced gain weight and adiposity in female mice.

AIM: Interleukin-6 (IL-6) is a major cytokine controlling body weight and metabolism, but because many types of cells can synthesize and respond to IL-6 considerable uncertainty still exists about the mechanisms underlying IL-6 effects. Therefore, the aim of this study was to analyse the effects of tissue-specific deletion of IL-6 using a fatty acid binding protein (aP2) promoter-Cre inducible system (aP2-Cre-ERT2). METHODS: Tissue-specific IL-6 KO mice (aP2-IL-6 KO mice) were produced upon tamoxifen administration and were fed a high-fat diet (HFD, 58.4% kcal from fat) or a control diet (18%) for 14 weeks. RESULTS: aP2-IL-6 KO female mice on a HFD gained less weight and adiposity than littermate wild-type mice, but these effects were not observed in males. Hypothalamic factors such as NPY and AgRP showed a pattern of expression consistent with this sex-specific phenotype. PGC-1α expression was increased in several tissues in aP2-IL-6 KO female mice, which is compatible with increased energy expenditure. Serum leptin, insulin, glucose, cholesterol and triglycerides levels were increased by HFD, and in females IL-6 deficiency reversed this effect in the case of insulin and cholesterol. HFD induced impaired responses to insulin and glucose tolerance tests, but no significant differences between genotypes were observed. CONCLUSION: The present results demonstrate that deletion of IL-6 driven by aP2-Cre regulates body weight, body fat and metabolism in a sex-specific fashion.

The AMPK-SIRT signaling network regulates glucose tolerance under calorie restriction conditions.

AIMS: SIRT1 and AMP-activated protein kinase (AMPK) share common activators, actions and target molecules. Previous studies have suggested that a putative SIRT1-AMPK regulatory network could act as the prime initial sensor for calorie restriction-induced adaptations in skeletal muscle-the major site of insulin-stimulated glucose disposal. Our study aimed to investigate whether a feedback loop exists between AMPK and SIRT1 in skeletal muscle and how this may be involved glucose tolerance. MAIN METHODS: To investigate this, we used skeletal muscle-specific AMPKα1/2 knockout mice (AMPKα1/2(-/-)) fed ad libitum (AL) or a 30% calorie restricted (CR) diet and L6 rat myoblasts incubated with SIRT1 inhibitor (EX527). KEY FINDINGS: CR-AMPKα1/2(-/-) displayed impaired glucose tolerance (*p<0.05), in association with down-regulated SIRT1 and PGC-1α expression (<300% vs. CR-WT, (±±)p<0.01). Moreover, AMPK activity was decreased following SIRT1 inhibition in L6 cells (~0.5-fold vs. control, *p<0.05). SIGNIFICANCE: This study demonstrates that skeletal muscle-specific AMPK deficiency impairs the beneficial effects of CR on glucose tolerance and that these effects may be dependent on reduced SIRT1 levels.

Evaluation of a new panel of six mononucleotide repeat markers for the detection of DNA mismatch repair-deficient tumours.

BACKGROUND: Microsatellite instability (MSI) is a molecular phenotype due to defective DNA mismatch repair (MMR) system. It is used to predict outcome of colorectal tumours and to screen tumours for Lynch syndrome (LS). A pentaplex panel composed of five mononucleotide markers has been largely recommended for determination of the MSI status. However, its sensitivity may be taken in default in occasional situations. The aim of the study was to optimise this panel for the detection of MSI. METHODS: We developed an assay allowing co-amplification of six mononucleotide repeat markers (BAT25, BAT26, BAT40, NR21, NR22, NR27) and one polymorphic dinucleotide marker (D3S1260) in a single reaction. Performances of the new panel were evaluated on a cohort of patients suspected of LS. RESULTS: We demonstrate that our assay is technically as easy to use as the pentaplex assay. The hexaplex panel shows similar performances for the identification of colorectal and non-MSH6-deficient tumours. On the other hand, the hexaplex panel has higher sensitivity for the identification of MSH6-deficient tumours (94.7% vs 84.2%) and MMR-deficient tumours other than colorectal cancer (92.9% vs 85.7%). CONCLUSION: The hexaplex panel could thus be an attractive alternative to the pentaplex panel for the identification of patients with LS.

The Pathogen-annotated Tracking Resource Network (PATRN) system: a web-based resource to aid food safety, regulatory science, and investigations of foodborne pathogens and disease.

Investigation of foodborne diseases requires the capture and analysis of time-sensitive information on microbial pathogens that is derived from multiple analytical methods and sources. The web-based Pathogen-annotated Tracking Resource Network (PATRN) system (www.patrn.net) was developed to address the data aggregation, analysis, and communication needs important to the global food safety community for the investigation of foodborne disease. PATRN incorporates a standard vocabulary for describing isolate metadata and provides a representational schema for a prototypic data exchange standard using a novel data loading wizard for aggregation of assay and attribution information. PATRN currently houses expert-curated, high-quality "foundational datasets" consisting of published experimental results from conventional assays and next generation analysis platforms for isolates of Escherichia coli, Listeria monocytogenes, and Salmonella, Shigella, Vibrio and Cronobacter species. A suite of computational tools for data mining, clustering, and graphical representation is available. Within PATRN, the public curated data repository is complemented by a secure private workspace for user-driven analyses, and for sharing data among collaborators. To demonstrate the data curation, loading wizard features, and analytical capabilities of PATRN, three use-case scenarios are presented. Use-case scenario one is a comparison of the distribution and prevalence of plasmid-encoded virulence factor genes among 249 Cronobacter strains with similar attributes to that of nine Cronobacter isolates from recent cases obtained between March and October, 2010-2011. To highlight PATRN's data management and trend finding tools, analysis of datasets, stored in PATRN as part of an ongoing surveillance project to identify the predominant molecular serogroups among Cronobacter sakazakii isolates observed in the USA is shown. Use-case scenario two demonstrates the secure workspace available for private users to upload and analyze sensitive data, and for collating cross-platform datasets to identify and validate congruent datapoints. SNP datasets from WGS assemblies and pan-genome microarrays are analyzed in a combinatorial fashion to determine relatedness of 33 Salmonella enterica strains to six strains collected as part of an outbreak investigation. Use-case scenario three utilizes published surveillance results that describe the incidence and sources of O157:H7 E. coli isolates associated with a produce pre-harvest surveillance study that occurred during 2002-2006. In summary, PATRN is a web-based integrated platform containing tools for the management, analysis and visualization of data about foodborne pathogens.

Determinants of masked hypertension in hypertensive patients treated in a primary care setting.

BACKGROUND: Recent data suggest that masked hypertension (MH) carries a cardiovascular risk similar to that of uncontrolled hypertension. AIMS: The objective of this study was to determine the prevalence and determinants of MH in patients treated for hypertension in a Canadian primary care setting. METHODS: Office blood pressure (OBP) was measured at baseline and after 3 months of valsartan-based therapy in 5636 hypertensive patients who had recorded their home blood pressure monitoring (HBPM) for seven consecutive days at month 3 using an Omron HEM-711 apparatus. MH was defined in nondiabetic patients as an OBP <140/90 mmHg and an HBPM ≥135/85 mmHg, and in those with diabetes as an OBP <130/80 mmHg and an HBPM ≥125/75 mmHg. RESULTS: Of the 5636 patients, 1025 had diabetes. OBP was controlled at 3 months in 268 (26.1%) of them, but 167 (62.3%) had MH. OBP was controlled in 2728 (59.1%) of the 4611 patients without diabetes, and 935 (34.3%) of them had MH. Overall, 1102 patients had MH, representing 36.8% of patients with controlled OBP and 19.6% of the entire hypertensive study population. Stepwise multiple logistic regression analysis in nondiabetic patients with controlled OBP at 3 months revealed that older age, male sex, higher body mass index and higher office systolic blood pressure were determinants of MH. CONCLUSION: Our results indicate that one of five hypertensive patients and more than one of three with controlled OBP will have MH. MH is associated with other cardiovascular risk factors, such as diabetes, and in nondiabetics, with male sex, older age and obesity.

A community-based clinical trial of Intra-Venous zOledRonic acid once Yearly in comparison to oral bisphosphonates in postmenopausal women with osteoporosis: the IVORY trial Methodological considerations.

BACKGROUND: Zoledronic acid is an intravenous once yearly bisphosphonate that has been shown to be effective and safe in improving BMD (bone mineral density) and reducing fracture risk in controlled clinical trials. IVORY is a Canadian post marketing study aiming at assessing real-life effectiveness, health care resource utilization, safety and compliance to treatment with zoledronic acid in comparison to orally administered bisphosphonates (OBP). METHODS: IVORY is a prospective two cohort observational study of patients treated with zoledronic acid or OBP. Eligible patients are postmenopausal females, >45 years old with osteoporosis for whom initiation of treatment with OBP or zoledronic acid is indicated. Subjects will be followed for four years. Outcomes are the change in lumbar spine, femoral neck and total hip BMD and the incidence of fractures. The study cohort will consist of 920 patients treated with zoledronic acid and 460 treated with OBP. Additional comparisons will be based on external standardization to the population of Quebec patients treated with OBP. DISCUSSION: Post Marketing Observational Studies (PMOS) are essential for the assessment of real-life effectiveness and population based benefit-risk ratios. The effect of access to care, compliance, adherence to guidelines, patient comorbidity and concomitant medication use could only be assessed with observational studies. IVORY will provide information about true life effectiveness, benefit-risk ratios, cost-effectiveness and barriers to the process-outcome optimization. The results will have implications for decision makers and health care stakeholders regarding the management of osteoporosis in Canada.