Interprofessional Teamwork: A Qualitative Study on Adapting Central Policies to Local Conditions in a Labour and Delivery Unit.

OBJECTIVES: We record the experiences of staff in a labour, delivery, and obstetric services (LD-OBS) unit in Alberta's largest quaternary medical centre-the Foothills Medical Centre (FMC)-as they navigated hospital policies during the COVID-19 pandemic. We examine how unit leadership applied these policies to better align with care delivery realities while staying true to the interprofessional nature of the unit. METHODS: A total of 12 semi-structured qualitative interviews were conducted with LD-OBS unit staff. Snowball and purposive sampling strategies were used to capture experiences from key informants. Interview transcripts underwent inductive coding. The themes identified through this process were discussed with members of the authorial team until a consensus was reached. RESULTS: FMC LD-OBS team members used 'interprofessional' as a value through which to interpret, adapt, and implement centrally developed COVID-19 policies. These were applied at 3 key moments: reconfiguring the unit, triaging, and rerouting patients, and contesting central personal protective equipment policies. LD-OBS leaders championed the importance of interprofessional collaboration and teamwork in the unit and worked to uphold it as a practice and value. CONCLUSION: The COVID-19 pandemic experience of the FMC LD-OBS unit illustrates the importance of considering interprofessionalism as a core value as policy was developed and implemented. Health authorities, hospitals, and other LD-OBS units may wish to consider how interprofessional work affects policy interpretation among health care teams, and how this may be leveraged to successfully adapt policies to local units, under both pandemic and 'normal' conditions.

Real-world Evidence for Impact of Opioid Agonist Therapy on Nonfatal Overdose in Patients with Opioid Use Disorder during the COVID-19 Pandemic.

OBJECTIVES: The primary objectives of this study were to describe the demographics and clinical characteristics of patients who were treated with buprenorphine extended-release versus buprenorphine-naloxone sublingual tablets versus methadone in a real-world setting and to evaluate the difference in nonfatal overdose events between treatment cohorts. METHODS: This study was a retrospective chart review of patients with opioid use disorder initiating opioid agonist therapy in Canada during the outset of the COVID-19 pandemic (March 11, 2020 to October 31, 2021). Three treatment cohorts were defined by the initial prescribed opioid agonist therapy regimen: buprenorphine extended-release, buprenorphine-naloxone sublingual tablets, and methadone. Baseline characteristics, as well as treatment status, overdose events, and substance use 6 months after treatment initiation were collected using a standardized form. RESULTS: Nine clinics provided data on 379 patient cases. The incidence rate (number of events per 100 person-years) for a self-reported nonfatal overdose was 46.8 (n = 18), 19.3 (n = 10), and 1.7 (n = 1) in the methadone, buprenorphine-naloxone sublingual tablets, and buprenorphine extended-release cohorts, respectively. The risk-adjusted difference for the proportion of patients with nonfatal overdose was 8.59% (95% confidence interval, 3.10-14.08%; P = 0.0022) for methadone versus buprenorphine extended-release and 6.51% (95% confidence interval, 1.46-11.56%; P = 0.0115) for buprenorphine-naloxone sublingual tablets versus buprenorphine extended-release. CONCLUSIONS: Buprenorphine extended-release was associated with lower rates of nonfatal overdose events compared with daily opioid agonist therapy. Given the limitations of this naturalistic, retrospective design, further prospective studies are needed to validate these findings and demonstrate the potential for long-acting opioid agonist therapy in addressing the opioid crisis.

Having Hard Conversations About Racism Within Nursing Education: A Collaborative Process of Developing an Antiracism Action Plan.

BACKGROUND: Multiple events that occurred in the United States in early 2020 prompted a widespread response to address racism that exists within systemic and social structures. Third-year psychiatric nursing students at a small Western Canadian university answered the call to action by initiating a process to address racism within clinical and educational settings in their faculty. METHODS: The researchers used collaborative autoethnography to examine the experience of students and faculty working collaboratively to create a Faculty of Health Studies antiracism action plan. RESULTS: The reflections of the student and faculty researchers highlighted three major themes: what inspired the work of creating an antiracism action plan, doing the work, and lessons learned. CONCLUSION: Engaging in this research provided an opportunity to critically reflect on the process of students and faculty working together in establishing an antiracism action plan. [J Nurs Educ. 2022;61(8):461-468.].

Multimodal CEA-targeted fluorescence and radioguided cytoreductive surgery for peritoneal metastases of colorectal origin.

In patients with colorectal peritoneal metastases scheduled for cytoreductive surgery, accurate preoperative estimation of tumor burden and subsequent intraoperative detection of all tumor deposits remains challenging. In this study (ClinicalTrials.gov NCT03699332) we describe the results of a phase I clinical trial evaluating [111In]In-DOTA-labetuzumab-IRDye800CW, a dual-labeled anti-carcinoembryonic antigen (anti-CEA) antibody conjugate that enables both preoperative imaging and intraoperative radioguidance and fluorescence imaging. Primary study outcomes are safety and feasibility of this multimodal imaging approach. Secondary outcomes are determination of the optimal dose, correlation between tracer uptake and histopathology and effects on clinical strategy. Administration of [111In]In-DOTA-labetuzumab-IRDye800CW is well-tolerated and enables sensitive pre- and intraoperative imaging in patients who receive 10 or 50 mg of the tracer. Preoperative imaging revealed previously undetected lymph node metastases in one patient, and intraoperative fluorescence imaging revealed four previously undetected metastases in two patients. Alteration of clinical strategy based on multimodal imaging occurred in three patients. Thus, multimodal image-guided surgery after administration of this dual-labeled tracer is a promising approach that may aid in decision making before and during cytoreductive surgical procedures.

Use of a point-of-care web-based application to enhance adherence to the CANMAT and ISBD 2018 guidelines for the management of bipolar disorder.

OBJECTIVES: While clinical guidelines exist for the management of bipolar disorder (BD), there are significant challenges to their widespread dissemination and implementation in clinical practice. The Canadian Network of Mood and Anxiety Treatment Improving Patient Care and Outcomes in the Treatment of Bipolar Disorder (C-IMPACT BD) web-based application was developed for use at the point-of-care to improve adherence to guidelines for evidence-based pharmacological management of BD. METHODS: C-IMPACT BD uses a point-of-care practice assessment which, via adaptive questioning of patient-specific information, text/video descriptions of the guidelines, and pop-up prompts delivers personalized, evidence-based treatment recommendations for patients with BD. In order to inform quality improvement of the newly developed tool, a sample of Canadian physicians were invited to use the application and record its influence on their prescribing behavior. RESULTS: Of 375 patients with bipolar I (BD-I) or bipolar II (BD-II) disorder for whom a point-of-care practice assessment was completed, a change in therapy was considered for 225 (60.0%). Prior to completing the assessment, 59.6% of these patients were receiving first-line therapy recommended for their phase of illness. Following the assessment, the overall number of patients for whom a first-line recommended therapy was being considered increased significantly to 76.9% (p = 0.0001). CONCLUSIONS: Outcomes suggest that the C-IMPACT BD web-based application has the potential to improve physician adherence to clinical treatment guidelines. Formal research investigations are warranted to explore the impact of this tool on physician prescribing behavior and patient outcomes.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations.

OBJECTIVES: The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided-a critical gap which the current update aims to address. METHOD: Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion. RESULTS: No agents met threshold for first-line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second-line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second-line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first-line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second-line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first-line, and lithium and olanzapine identified as second-line options. CONCLUSION: The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.

[COVID-EX. Influence of the COVID-19 pandemic on the rate of unplanned extubations (UE) in intensive care units (ICUs): A case-control study]. / COVID-EX. Influence de la pandémie de Covid-19 sur le taux d'extubation non programmée en réanimation : étude castemoins rétrospective.

CONTEXT: In ICUs, many patients are intubated. UE is an indicator of the quality of care.Isolation associated with "air" precautions may increase the number of UEs in mechanically ventilated (MV) COVID patients.The main aim of the study was to compare the rate of UE between a COVID-19 period and a control period. The secondary aims were to identify UE risk factors and to study the experience of caregivers during the COVID-19 period. METHOD: The method of choice was a retrospective single center case-control study. MV patients aged ≥ 18 years were eligible in two periods: the control period from 01/02/2020 to 29/02/2020, and the COVID-19 period from 01/03/2020 to 31/03/2020. An anonymous survey was given to ICU caregivers in Vannes Hospital. RESULTS: The UE rate was 17% (n=7) vs. 20% (n=9) control period vs. COVID-19 period (p=0.58), with nocturnal preponderance (75%). A quarter (n=4) of patients fulfill MV weaning criteria at the time of UE. A 71% (n=49) survey response rate was obtained. The COVID-19 period had a higher estimated UE risk for 76% (n=37) of caregivers, who felt that they had a greater workload, difficulties with monitoring, and decreased regular visits to patients' rooms. CONCLUSION: Contrary to the caregiver experience, we reported a similar UE rate over both the COVID-19 period and the control period.

COVID-EX. Influence de la pandémie de Covid-19 sur le taux d'extubation non programmée en réanimation : étude castemoins rétrospective.

CONTEXT: In ICUs, many patients are intubated. UE is an indicator of the quality of care.Isolation associated with "air" precautions may increase the number of UEs in mechanically ventilated (MV) COVID patients.The main aim of the study was to compare the rate of UE between a COVID-19 period and a control period. The secondary aims were to identify UE risk factors and to study the experience of caregivers during the COVID-19 period. METHOD: The method of choice was a retrospective single center case-control study. MV patients aged ≥ 18 years were eligible in two periods: the control period from 01/02/2020 to 29/02/2020, and the COVID-19 period from 01/03/2020 to 31/03/2020. An anonymous survey was given to ICU caregivers in Vannes Hospital. RESULTS: The UE rate was 17% (n=7) vs. 20% (n=9) control period vs. COVID-19 period (p=0.58), with nocturnal preponderance (75%). A quarter (n=4) of patients fulfill MV weaning criteria at the time of UE. A 71% (n=49) survey response rate was obtained. The COVID-19 period had a higher estimated UE risk for 76% (n=37) of caregivers, who felt that they had a greater workload, difficulties with monitoring, and decreased regular visits to patients' rooms. CONCLUSION: Contrary to the caregiver experience, we reported a similar UE rate over both the COVID-19 period and the control period.

Multimodal CEA-Targeted Image-Guided Colorectal Cancer Surgery using 111In-Labeled SGM-101.

PURPOSE: Intraoperative image guidance may aid in clinical decision-making during surgical treatment of colorectal cancer. We developed the dual-labeled carcinoembryonic antigen-targeting tracer, [111In]In-DTPA-SGM-101, for pre- and intraoperative imaging of colorectal cancer. Subsequently, we investigated the tracer in preclinical biodistribution and multimodal image-guided surgery studies, and assessed the clinical feasibility on patient-derived colorectal cancer samples, paving the way for rapid clinical translation. EXPERIMENTAL DESIGN: SGM-101 was conjugated with p-isothiocyanatobenzyl-diethylenetriaminepentaacetic acid (DTPA) and labeled with Indium-111 (111In). The biodistribution of 3, 10, 30, and 100 µg [111In]In-DTPA-SGM-101 was assessed in a dose escalation study in BALB/c nude mice with subcutaneous LS174T human colonic tumors, followed by a study to determine the optimal timepoint for imaging. Mice with intraperitoneal LS174T tumors underwent micro-SPECT/CT imaging and fluorescence image-guided resection. In a final translational experiment, we incubated freshly resected human tumor specimens with the tracer and assessed the tumor-to-adjacent tissue ratio of both signals. RESULTS: The optimal protein dose of [111In]In-DTPA-SGM-101 was 30 µg (tumor-to-blood ratio, 5.8 ± 1.1) and the optimal timepoint for imaging was 72 hours after injection (tumor-to-blood ratio, 5.1 ± 1.0). In mice with intraperitoneal tumors, [111In]In-DTPA-SGM-101 enabled preoperative SPECT/CT imaging and fluorescence image-guided resection. After incubation of human tumor samples, overall fluorescence and radiosignal intensities were higher in tumor areas compared with adjacent nontumor tissue (P < 0.001). CONCLUSIONS: [111In]In-DTPA-SGM-101 showed specific accumulation in colorectal tumors, and enabled micro-SPECT/CT imaging and fluorescence image-guided tumor resection. Thus, [111In]In-DTPA-SGM-101 could be a valuable tool for preoperative SPECT/CT imaging and intraoperative radio-guided localization and fluorescence image-guided resection of colorectal cancer.

Wide variation in tissue, systemic, and drain fluid exposure after oxaliplatin-based HIPEC: results of the GUTOX study.

PURPOSE: In this exploratory study, the effect of postprocedural flushing with crystalloids after oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) on platinum concentrations in peritoneal tissue, blood, and drain fluid was studied. Interpatient variability in oxaliplatin pharmacokinetics and the relation between platinum concentration in peritoneal fluid and platinum exposure in tissue and blood was explored. METHODS: Ten patients with peritoneal carcinomatosis of colorectal origin were treated with HIPEC including postprocedural flushing, followed by ten patients without flushing afterwards. Tissue, peritoneal fluid, blood, and drain fluid samples were collected for measurement of total and ultrafiltered platinum concentrations. RESULTS: Peritoneal tissue concentration and systemic ultrafiltered platinum exposure showed large inter individual variability, ranging from 65 to 1640 µg/g dry weight and 10.5 to 28.0 µg*h/ml, respectively. No effect of flushing was found on geometric mean platinum concentration in peritoneal tissue (348 vs. 356 µg/g dry weight), blood (14.8 vs. 18.1 µg*h/ml), or drain fluid (day 1: 7.6 vs. 7.7 µg/ml; day 2: 1.7 vs. 1.9 µg/ml). The platinum concentration in peritoneal fluid at the start of HIPEC differed twofold between patients and was positively correlated with systemic exposure (p = .04) and peak plasma concentration (p = .04). CONCLUSION: In this exploratory study, no effect was found for postprocedural flushing on platinum concentrations in peritoneal tissue, blood, or drain fluid. BSA-based HIPEC procedure leads to large interpatient variability in platinum exposure in all compartments. The study was registered at ClinicalTrials.gov on 7 December 2017 under registration number NCT03364907.

Battling Associative Stigma in Psychiatric Nursing.

Psychiatric nurses often experience associative stigma. Associative stigma may impact psychiatric nurses' views of their professional identity which ultimately impacts the health care of individuals experiencing mental health concerns. Very little research has been conducted on associative stigma in the western Prairie Provinces, including Manitoba. The authors conducted a secondary analysis on the results of an explanatory sequential mixed methods research study to determine if psychiatric nurses in Manitoba are influenced by associative stigma. Three themes were identified through this analysis, specifically: (1) the perception that RPNs are not "Real" Nurses; (2) lack of recognition of specialized training; and (3) working with a stigmatized population. Associative stigma was intertwined in all of the participants' narratives indicating a need to dismantle associative stigma. Strategies to enhance the public perception of psychiatric nursing and decrease associative stigma within the profession are described.

Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery.

Image-guided surgery can aid in achieving complete tumor resection. The development and assessment of tumor-targeted imaging probes for near-infrared fluorescence image-guided surgery relies mainly on preclinical models, but the translation to clinical use remains challenging. In the current study, we introduce and evaluate the application of a dual-labelled tumor-targeting antibody for ex vivo incubation of freshly resected human tumor specimens and assessed the tumor-to-adjacent tissue ratio of the detectable signals. Immediately after surgical resection, peritoneal tumors of colorectal origin were placed in cold medium. Subsequently, tumors were incubated with 111In-DOTA-hMN-14-IRDye800CW, an anti-carcinoembryonic antigen (CEA) antibody with a fluorescent and radioactive label. Tumors were then washed, fixed, and analyzed for the presence and location of tumor cells, CEA expression, fluorescence, and radioactivity. Twenty-six of 29 tumor samples obtained from 10 patients contained malignant cells. Overall, fluorescence intensity was higher in tumor areas compared to adjacent non-tumor tissue parts (p < 0.001). The average fluorescence tumor-to-background ratio was 11.8 ± 9.1:1. A similar ratio was found in the autoradiographic analyses. Incubation with a non-specific control antibody confirmed that tumor targeting of our tracer was CEA-specific. Our results demonstrate the feasibility of this tracer for multimodal image-guided surgery. Furthermore, this ex vivo incubation method may help to bridge the gap between preclinical research and clinical application of new agents for radioactive, near infrared fluorescence or multimodal imaging studies.

Educating the Educators: Determining the Uniqueness of Psychiatric Nursing Practice to Inform Psychiatric Nurse Education.

A study regarding the role and uniqueness of psychiatric nursing was conducted with 94 participants from Manitoba, Canada. The primary theme of comprehensive knowledge of mental health, mental illness, and addictions was foundational for the application of the sub-themes of therapeutic relationship, holistic approach, recovery orientation, stigma reduction, and advocacy for change. Values, beliefs, and attitudes towards people with mental illness and addictions need to be instilled in psychiatric nursing students throughout their educational program to provide high quality, compassionate, and safe care. Implications for incorporation of the theme and sub-themes into psychiatric nursing curriculum are described in the paper.

Immunohistochemical selection of biomarkers for tumor-targeted image-guided surgery of myxofibrosarcoma.

Myxofibrosarcoma(MFS) is the most common soft tissue sarcoma(STS) in elderly patients. Surgical resection remains the main treatment modality but tumor borders can be difficult to delineate with conventional clinical methods. Incomplete resections are a common problem and local recurrence remains a clinical issue. A technique that has shown great potential in improving surgical treatment of solid tumors is tumor targeted imaging and image-guided surgery with near-infrared fluorescence. To facilitate this technique, it is essential to identify a biomarker that is highly and homogenously expressed on tumor cells, while being absent on healthy non-malignant tissue. The purpose of this study was to identify suitable molecular targets for tumor-targeted imaging of myxofibrosarcoma. Ten potential molecular targets for tumor targeted imaging were investigated with immunohistochemical analysis in myxofibrosarcoma tissue (n = 34). Results were quantified according to the immunoreactive score(IRS). Moderate expression rates were found for uPAR, PDGFRa and EMA/MUC1. High expression rates of VEGF and TEM1 were seen. Strong expression was most common for TEM1 (88.2%). These results confirms that TEM1 is a suitable target for tumor-targeted imaging of myxofibrosarcoma. Keywords Image-guided surgery; Immunohistochemistry; Molecular imaging; Myxofibrosarcoma; Soft tissue sarcoma; Tumor endothelial marker 1(TEM1), Vascular endothelial growth factor (VEGF).

Neoadjuvant Chemotherapy for Locally Advanced T4 Colon Cancer: A Nationwide Propensity-Score Matched Cohort Analysis.

INTRODUCTION: Neoadjuvant chemotherapy (CT) for locally advanced colon cancer (LACC) could potentially lead to tumor shrinkage, eradication of micrometastases, and prevention of tumor cell shedding during surgery. This retrospective study investigates the surgical and oncological outcomes of preoperative CT for LACC. METHODS: Using the Netherlands Cancer Registry, data of patients with stage II or III colon cancer, diagnosed between 2008 and 2016 was collected. A propensity score matching (PSM; 1:2) was performed and compared patients with clinical tumor (cT) 4 colon cancer who were treated with neoadjuvant CT to patients with cT4 colon cancer treated with adjuvant CT (Fig. 1). RESULTS: A total of 192 patients treated with neoadjuvant CT were compared to 1,954 patients that received adjuvant CT. After PSM, 149 patients in the neoadjuvant group were compared to 298 patients in the control group. No significant differences were found in baseline characteristics after PSM. After neoadjuvant CT, a significant response was observed in 13 (9%) patients with 5 (4%) patients showing a complete response. Complete resection margins (R0) were achieved in 77% in the neoadjuvant group versus 86% in the adjuvant treated group (p = 0.037). Significantly less tumor positive lymph nodes were found in the neoadjuvant group (median 0 vs. 2, p < 0.001). Major complication rates and 5-year overall survival did not differ between both groups (67-65%, p = 0.87). CONCLUSION: Neoadjuvant CT seems safe and feasible with similar long-term survival compared to patients who are treated with adjuvant CT.

Structural Urbanism Contributes To Poorer Health Outcomes For Rural America.

Rural populations disproportionately suffer from adverse health outcomes, including poorer health and higher age-adjusted mortality. We argue that these disparities are due in part to declining health care provider availability and accessibility in rural communities. Rural challenges are exacerbated by "structural urbanism"-elements of the current public health and health care systems that disadvantage rural communities. We suggest that biases in current models of health care funding, which treat health care as a service for an individual rather than as infrastructure for a population, are innately biased in favor of large populations. Until this bias is recognized, the development of viable models for care across the rural-urban continuum cannot move forward.

Encapsulation of folic acid in copper-alginate hydrogels and it's slow in vitro release in physiological pH condition.

Folic acid (FA) is an essential micronutrient but its delivery and bioavailability is a problem due to its inherent instability at various conditions. A robust protective encapsulation system for folic acid is highly desirable. This work reports the use of the divalent copper in complex with alginate as a strong encapsulation system for folic acid. Using gel spherification technique, hydrogels were formed upon dropwise addition of sodium alginate solution in a copper bath. In the presence of folic acid, encapsulation was achieved as evidenced by the yellow coloration, intact surface morphology (SEM), the presence of nitrogen (23.08% N; EDX), and thermal gravimetric degradation for folic acid (28% FA; TGA). The spherical hydrogels do not burst upon 2 m-drop test and remain intact at pH 1.2 with no evident release of folic acid indicating stability of the encapsulation system at the abdominal gastric condition. The copper alginate acted as gastro-resistant material and slow release of folic acid occurs only at pH > 5 especially at simulated intestinal conditions (pH 8.2). The study indicates the potential of copper alginates as a protective encapsulant to ensure stability and slow release of FA in simulated physiological pH conditions.

Effect of pioglitazone on bone mineral density in patients with nonalcoholic steatohepatitis: A 36-month clinical trial.

BACKGROUND: The effects of pioglitazone on bone metabolism are unclear. This study evaluated the long-term effects of pioglitazone on bone mineral density (BMD) and bone metabolism in patients with prediabetes or type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). METHODS: Ninety-two patients with prediabetes or T2DM and biopsy-proven NASH with BMD and baseline biochemical bone measurements were included. Patients (mean [±SEM] age 51 ± 1 years, 71% male, mean body mass index 34.5 ± 0.5 kg/m2 ) were randomly assigned to pioglitazone (45 mg/day) or placebo for 18 months, followed by an 18-month open-label pioglitazone treatment phase. Baseline, 18- and 36-month evaluations included plasma vitamin D and bone turnover biomarker levels, and BMD measurements at the spine, femoral neck, total hip, and one-third radius. RESULTS: After 18 months of pioglitazone treatment, there were no differences in BMD versus placebo at either the femoral neck (P =0.87), total hip (P =0.78), or one-third radius (P =0.44); however, bone density decreased at the level of the spine with pioglitazone (-3.5%; P =0.002). During the extension phase (18-36 months), patients had no further decreases in BMD or plasma biomarkers of bone turnover during pioglitazone treatment. No patient experienced a low-energy bone fracture. CONCLUSIONS: Treatment of patients with prediabetes or T2DM with pioglitazone for up to 3 years was associated with decreased BMD at the level of the lumbar spine. This reduction in BMD at the lumbar spine at 18 months versus placebo suggests an early deleterious effect of pioglitazone on bone metabolism.