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OBJECTIVE: To conduct a systematic review and meta-analysis of randomized trials that assessed the effect of testosterone use on cardiovascular events and risk factors in men with different degrees of androgen deficiency. METHODS: Librarian-designed search strategies were used to search the MEDLINE (1966 to October 2004), EMBASE (1988 to October 2004), and Cochrane CENTRAL (inception to October 2004) databases. The database search was performed again in March 2005. We also reviewed reference lists from included studies and content expert files. Eligible studies were randomized trials that compared any formulation of commercially available testosterone with placebo and that assessed cardiovascular risk factors (lipid fractions, blood pressure, blood glucose), cardiovascular events (cardiovascular death, nonfatal myocardial infarction, angina or claudication, revascularization, stroke), and cardiovascular surrogate end points (ie, laboratory tests indicative of cardiac or vascular disease). Using a standardized data extraction form, we collected data on participants, testosterone administration, and outcome measures. We assessed study quality with attention to allocation concealment, blinding, and loss to follow-up. RESULTS: The 30 trials included 1642 men, 808 of whom were treated with testosterone. Overall, the trials had limited reporting of methodological features that prevent biased results (only 6 trials reported allocation concealment), enrolled few patients, and were of brief duration (only 4 trials followed up patients for >1 year). The median loss to follow-up across all 30 trials was 9%. Testosterone use in men with low testosterone levels led to inconsequential changes in blood pressure and glycemia and in all lipid fractions (total cholesterol: odds ratio [OR], -0.22; 95% confidence interval [Cl], -0.71 to 0.27; high-density lipoprotein cholesterol: OR, -0.04; 95% Cl, -039 to 0.30; low-density Iipoprotein cholesterol: OR, 0.06; 95% Cl, -0.30 to 0.42; and triglycerides: OR, -0.27; 95% Cl, -0.61 to 0.08); results were similar in patients with low-normal to normal testosterone levels. The OR between testosterone use and any cardiovascular event pooled across trials that reported these events (n=6) was 1.82 (95% Cl, 0.78 to 4.23). Several trials failed to report data on measured outcomes. For reasons we could not explain statistically, the results were inconsistent across trials. CONCLUSION: Currently available evidence weakly supports the inference that testosterone use in men is not associated with important cardiovascular effects. Patients and clinicians need large randomized trials of men at risk for cardiovascular disease to better inform the safety of long-term testosterone use. [ABSTRACT FROM AUTHOR]

Background: Previous studies in long-term care (LTC) have demonstrated that warfarin management is suboptimal with preventable adverse events often occurring as a result of poor International Normalized Ratio (INR) control. To assist LTC teams with the challenge of maintaining residents on warfarin in the therapeutic range (INR of 2.0 to 3.0), we developed an electronic decision support system that was based on a validated algorithm for warfarin dosing. We evaluated the MEDeINR system in a pre-post implementation design by examining the impact on INR control, testing frequency, and experiences of staff in using the system.Methods: For this feasibility study, we piloted the MEDeINR system in six LTC homes in Ontario, Canada. All128 residents (without a prosthetic valve) who were taking warfarin were included. Three-months of INR data prior to MEDeINR was collected via a retrospective chart audit, and three-months of INR data after implementation of MEDeINR was captured in the central computer database. The primary outcomes compared in a pre-post design were time in therapeutic range (TTR) and time in sub/supratherapeutic ranges based on all INR measures for every resident on warfarin. Secondary measures included the number of monthly INR tests/resident and survey/focus-group feedback from the LTC teams.Results: LTC homes in our study had TTR's that were higher than past reports prior to the intervention. Overall, the TTR increased during the MEDeINR phase (65 to 69%), but was only significantly increased for one home (62% to 71%, p < 0.05). The percentage of time in supratherapeutic decreased from 14% to 11%, p = 0.08); there was little change for the subtherapeutic range (21% to 20%, p = 0.66). Overall, the average number of INR tests/30 days decreased from 4.2 to 3.1 (p < 0.0001) per resident after implementation of MEDeINR. Feedback received from LTC clinicians and staff was that the program decreased the work-load, improved confidence in management and decisions, and was generally easy to use.Conclusion: Although LTC homes in our sample had TTR's that were relatively high prior to the intervention, the MEDeINR program represented a useful tool to promote optimal TTR, decrease INR venipunctures, streamline processes, and increase nurse and physician confidence around warfarin management. We have demonstrated that MEDeINR was a practical, usable clinical information system that can be incorporated into the LTC environment. [ABSTRACT FROM AUTHOR]

Background: A care gap exists between recommendations and practice regarding the diagnosis and treatment of osteoporosis in fracture patients. The current study was designed to determine rates and predictors of in-hospital diagnosis and treatment of osteoporosis in patients admitted with fragility hip fractures, and to assess differences in these rates since the outset of the multipronged "Fracture? Think Osteoporosis" (FTOP) Program, which includes education of geriatrics and rehabilitation teams.Methods: This is a retrospective cohort study conducted with data from two Hamilton, Ontario, university-based tertiary-care hospitals, and represents a follow-up to a previous study conducted 8 years earlier. Data pertaining to all 354 patients, age > or = 50, admitted between March 2003 and April 2004, inclusive, with a diagnosis of fragility hip fracture were evaluated. Twelve patients were excluded leaving 342 patients for analysis, with 75% female, mean age 81.Outcomes included: Primary -- In-hospital diagnosis of osteoporosis and/or initiation of anti-resorptive treatment ("new osteoporosis diagnosis/treatment"). Secondary -- In-hospital mortality, BMD referrals, pre-admission osteoporosis diagnosis and treatment.Results: At admission, 27.8% of patients had a pre-existing diagnosis of osteoporosis and/or were taking anti-resorptive treatment. Among patients with no previous osteoporosis diagnosis/treatment: 35.7% received a new diagnosis of osteoporosis, 21% were initiated on anti-resorptive treatment, and 14.3% received a BMD referral. The greatest predictor of new osteoporosis diagnosis/treatment was transfer to a rehabilitation or geriatrics unit: 79.5% of rehabilitation/geriatrics versus 18.5% of patients receiving only orthopedics care met this outcome (p < 0.001).Conclusion: New diagnosis of osteoporosis among patients admitted with hip fracture has improved from 1.8% in the mid 1990's to 35.7%. Initiation of bisphosphonate therapy has likewise improved from 0% to 21%. Although multiple factors have likely contributed, the differential response between rehabilitation/geriatrics versus orthopedics patients suggests that education of the geriatric and rehabilitation teams, including one-on-one and group-based sessions, implemented as part of the FTOP Program, has played a role in this improvement. A significant care gap still exists for patients discharged directly from orthopedic units. The application of targeted inpatient and post-discharge initiatives, such as those that comprise the entire FTOP Program, may be of particular value in this setting. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To conduct a systematic review and meta-analysis of randomized placebo-controlled trials to measure the effect of testosterone use on sexual function in men with sexual dysfunction and varying testosterone levels. METHODS: Librarian-designed search strategies were used to search the MEDLINE (1966 to October 2004), EMBASE (1988 to October 2004), and Cochrane CENTRAL (inception to October 2004) databases. The MEDLINE search was rerun In March 2005. We also reviewed reference lists from included studies and content expert files. We selected randomized placebo-controlled trials of testosterone vs placebo that enrolled men with sexual dysfunction and measured satisfaction with erectile function and libido and overall sexual satisfaction. RESULTS: We included 17 trials (N=862 participants) in this review. Trials that enrolled participants with low testosterone levels showed (1) a moderate nonsignificant and inconsistent effect of testosterone use on satisfaction with erectile function (random-effects pooled effect size, 0.80; 95% confidence interval [Cl], -0.10 to 1.60), (2) a large effect on libido (pooled effect size, 1.31; 95% Cl, 0.40 to 2.25), and (3) no significant effect on overall sexual satisfaction. Trials that enrolled patients with low- normal and normal testosterone levels at baseline showed testosterone that caused (1) a small effect on satisfaction with erectile function (pooled effect size, 0.34; 95% Cl, 0.03 to 0.65), (2) moderate nonsignificant effect on libido (pooled effect size, 0.41; 95% Cl, -0.01 to 0.83), and (3) no significant effect on overall sexual satisfaction. CONCLUSION: Testosterone use in men is associated with small improvements in satisfaction with erectile function and moderate improvements in libido. Unexplained inconsistent results across trials, wide Cls, and possible reporting bias weaken these inferences. [ABSTRACT FROM AUTHOR]

For some patients who have lost the lower part of an arm, hand transplant offers the possibility of receiving a new limb with varying degrees of sensation and function. This procedure, Vascularized Composite Allotransplantation (VCA), is demanding for patients and their care community and comes with significant risks. As a high-stakes decision, patients interested in VCA are subject to extensive clinical evaluation and eligibility decision making. Patients and their care community must also decide if hand transplant (versus other approaches including rehabilitative therapies with or without prosthesis) is right for them. This decision making is often confusing and practically and emotionally fraught. It is complicated in four ways: by the numerous beneficial and harmful potential effects of hand transplant or other options, the number of people affected by VCA and the diverse or conflicting positions that they may hold, the practical demands and limitations of the patient's life situation, and the existential significance of limb loss and transplant for the patient's being. Patients need support in working through these treatment determining issues. Evaluation does not provide this support. Shared decision making (SDM) is a method of care that helps patients think, talk, and feel their way through to the right course of action for them. However, traditional models of SDM that focus on weighing possible beneficial and harmful effects of treatments are ill-equipped to tackle the heterogeneous issues of VCA. A recent model, Purposeful SDM extends the range of troubling issues that SDM can help support beyond opposing effects, to include conflicting positions, life situations, and existential being. In this paper we explore the pertinence of these issues in VCA, methods of SDM that each require of clinicians, the benefits of supporting patients with the breadth of issues in their unique problematic situations, implications for outcomes and practice, and extend the theory of the Purposeful SDM model itself based on the issues present in hand transplant decision making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Hargraves, Boehmer, Amer, Kennedy, Griffin, Finnie, Montori, Smither, Mardini, Moran and Jowsey-Gregoire.)

Lysosomes and lysosome related organelles (LROs) are dynamic organelles at the intersection of various pathways involved in maintaining cellular hemostasis and regulating cellular functions. Vesicle trafficking of lysosomes and LROs are critical to maintain their functions. The lysosomal trafficking regulator (LYST) is an elusive protein important for the regulation of membrane dynamics and intracellular trafficking of lysosomes and LROs. Mutations to the LYST gene result in Chédiak-Higashi syndrome, an autosomal recessive immunodeficiency characterized by defective granule exocytosis, cytotoxicity, etc. Despite eight decades passing since its initial discovery, a comprehensive understanding of LYST's function in cellular biology remains unresolved. Accumulating evidence suggests that dysregulation of LYST function also manifests in other disease states. Here, we review the available literature to consolidate available scientific endeavors in relation to LYST and discuss its relevance for immunomodulatory therapies, regenerative medicine and cancer applications., Competing Interests: ChB and CaB are co-founders of Lyst Therapeutics, LLC Columbus, OH and did not receive support for the present work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Turner, Che, Mirhaidari, Kennedy, Blum, Rajesh, Zbinden, Breuer, Best and Barker.)

The hidden curriculum (HC), or implicit norms and values within a field or institution, affects faculty at all career stages. This study surveyed affiliates of a junior faculty training program ( n = 12) to assess the importance of HC topics for junior faculty, mentors, and institutional leaders. For non-diverse junior faculty and their mentors, work-life balance, research logistics, and resilience were key HC topics. Coping with bias and assertive communication were emphasized for diverse junior faculty and mentors. Institutional norms and vision were essential for leaders, while networking was important for all groups. Future research should explore HC needs and potential interventions., Competing Interests: The authors have no conflicts of interest to report., (© The Author(s) 2024.)

Background: The optimal duration of antifrailty interventions and how best to deliver them to patients with chronic kidney disease (CKD) is unknown. The aim of this study was to examine the safety, feasibility and preliminary efficacy of a 4-week supervised exercise intervention on frailty in patients with CKD., Methods: We conducted a prospective feasibility study involving patients with ≥stage 3 CKD (1 patient with stage 3 CKD, 7 patients with stage 4 CKD and 17 patients with stage 5 CKD) who were either frail or prefrail according to the physical frailty phenotype and/or had a Short Physical Performance Battery (SPPB) score ≤10. The exercise intervention consisted of two supervised outpatient sessions per week for 4 weeks (eight total sessions). Frailty and other study measures were assessed at baseline and after 4 weeks of exercise., Results: Of the 34 participants who completed the baseline assessment and were included in the analyses, 25 (73.5%) completed the 4-week assessment. Overall, 64.0% of patients were on dialysis and 64.0% had diabetes mellitus. After 4 weeks of exercise, frailty prevalence, total SPPB scores and energy/fatigue scores improved. No adverse study-related outcomes were reported., Conclusions: The 4 weeks of supervised exercise was safe, was associated with an excellent completion rate and improved frailty parameters in CKD patients with CKD. This study provides important preliminary data for a future larger prospective randomized study., Clinical Trialgov: registration : NCT03535584., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Extracorporeal membrane oxygenation is used as a bridge to transplant (ECMO-BTT) in selected patients. The objective of this study was to determine whether 1-year post-transplant and post-ECMO survival are impacted by traditional compared to expanded selection criteria. We performed a retrospective study of patients >17 years who received ECMO as bridge to transplant (BTT) or bridge to transplant decision for lung or combined heart and lung transplantation at the Mayo Clinic Florida and Rochester. Institutional protocol excludes patients >55 years, maintained on steroids, unable to participate in physical therapy, with body mass index >30 or <18.5 kg/m 2 , non-pulmonary end-organ dysfunction, or unmanageable infections from ECMO-BTT. For this study, adherence to this protocol was considered traditional whereas exceptions to the protocol were considered expanded selection criteria. A total of 45 patients received ECMO as bridge therapy. Out of those 29 patients (64%) received ECMO as bridge to transplant and 16 patients (36%) as bridge to transplant decision. The traditional criteria cohort consisted of 15 (33%) patients and expanded criteria cohort consisted of 30 (67%) patients. In the traditional cohort, 9 (60%) of 15 patients were successfully transplanted compared to 16 (53%) of 30 patients in the expanded criteria cohort. No difference in being delisted or dying on the waitlist (OR: 0.58, CI: 0.13-2.58), surviving to 1-year post-transplant (OR: 0.53, CI: 0.03-9.71) or 1-year post-ECMO (OR: 0.77, CI: 0.0.23-2.56) was observed between the traditional criteria and expanded criteria cohorts. At our institution, we did not see differences in odds of 1-year post-transplant and post-ECMO survival between those who met traditional criteria compared to those who did not. Multicenter, prospective studies are needed to evaluate the impact of ECMO-BTT selection criteria., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-13/coif). The authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: Mycoplasma hominis , Ureaplasma urealyticum , and Ureaplasma parvum may cause post-transplant infections in lung transplant recipients. We evaluated routine pretransplant screening for these Mollicutes., Methods: We retrospectively reviewed records of lung transplant recipients at our tri-site institution from 01/01/2015 to 11/15/2019. M. hominis and/or Ureaplasma polymerase chain reaction (PCR) was performed on pretransplant recipient urine specimens and donor bronchial swabs at the time of transplantation. Development of Mollicute infection and hyperammonemia syndrome (HS) was recorded., Results: A total of 268 patients underwent lung transplantation during the study period, of whom 105 were screened with at least 1 Mollicute PCR. Twelve (11%) screened positive; 10 donors, 1 recipient, and 1 both. Among positive donors, 3 were positive for M. hominis , 5 for U. urealyticum , and 4 for U. parvum . Preemptive therapy included doxycycline, levofloxacin, and/or azithromycin administered for 1-12 weeks. Despite therapy, 1 case of M. hominis mediastinitis and 1 case of HS associated with Ureaplasma infection occurred, both donor-derived. Of those screened before transplant, cases with positive screening were more likely ( P < 0.05) to develop Mollicute infection despite treatment (2/12, 17%) than those who screened negative (1/93, 1%)., Conclusions: Pretransplant recipient urine screening had a low yield and was not correlated with post-transplant Mollicute infection, likely because most M. hominis and U. parvum/urealyticum infections in lung transplant recipients are donor-derived. Routine donor bronchus swab PCR for M. hominis , U. urealyticum , and U. parvum followed by preemptive therapy did not obviously impact the overall incidence of Mollicute infection or HS in this cohort., Competing Interests: Potential conflicts of interest. R.P. reports grants from CD Diagnostics, Merck, Contrafect, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, Contrafect, TenNor Therapeutics Limited, and Shionogi. R.P. is or has been a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, Selux Dx, GenMark Diagnostics, PathoQuest, Heraeus Medical, and Qvella; monies are paid to Mayo Clinic. In addition, R.P. has a patent on Bordetella pertussis/parapertussis PCR, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an antibiofilm substance. R.P. receives travel reimbursement from ASM and IDSA, an editor's stipend from ASM and IDSA, and honoraria from the NBME, Up-to-Date, and the Infectious Diseases Board Review Course. The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To describe smoking behaviors and pharmaceutical cessation aid uptake in a population-based Indigenous cohort compared with an age- and sex-matched non-Indigenous cohort., Patients and Methods: Using the health record-linkage system of the Rochester Epidemiology Project (January 1, 2006, to December 31, 2019), smoking data of Indigenous residents of Olmsted County in Minnesota were abstracted to define the smoking prevalence, incidence, cessation, relapse after cessation, and pharmaceutical smoking cessation aid uptake compared with a matched non-Indigenous cohort. Prevalence was analyzed with a modified Poisson regression; cessation and relapse were evaluated with generalized estimating equations. Incidence was evaluated with a Cox proportional hazards model., Results: Smoking prevalence was higher in the Indigenous cohort (39.0% to 47.0%; n=898) than the matched cohort (25.6% to 30.3%; n=1780). Pharmaceutical uptake was higher among the Indigenous cohort (35.8% of n=584 ever smokers vs 16.3% of n=778 ever smokers; P<.001). Smoking cessation events occurred more frequently in the Indigenous cohort (relative risk, 1.10; 95% CI, 1.06 to 1.13; P<.001). Indigenous former smokers were more likely to resume smoking (relative risk, 3.03; 95% CI, 2.93 to 3.14; P<.001) compared with the matched cohort. These findings were independent of socioeconomic status, age, and sex., Conclusion: Smoking in this Indigenous cohort was more prevalent compared with a sex- and age-matched non-Indigenous cohort despite more smoking cessation events and higher use of smoking cessation aids in the Indigenous cohort. The relapse rate after achieving cessation in the Indigenous cohort was more than three times higher than the non-Indigenous cohort. This finding has not been previously described and represents a potential target for relapse prevention efforts in US Indigenous populations., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

The goals of vascular composite allotransplantation (VCA) for hand are to maximize functional status and psychosocial wellbeing and to improve quality of life. Candidates are carefully vetted by transplant programs through an extensive evaluation process to exclude those patients with contraindications and to select those that are most likely to attain functional or quality of life benefit from transplant. Patient choice for any treatment, however, requires that candidates be able to understand the risks, benefits, and alternatives before choosing to proceed. This study aimed to understand patients' knowledge and perceptions about treatment options for hand loss, including hand transplant. This study will be used to inform a standardized education approach and develop conversation aids for use by clinicians and patients throughout the treatment decision process. Ten individuals who had experienced hand amputation or had congenital limb loss were interviewed to better understand previous and current decisions about treatment, experiences in adjusting to their treatment, and perceptions about hand VCA. From this qualitative interview data, four findings emerged: (1) knowledge and education around VCA as a treatment option; (2) adaptation of individuals with limb loss; (3) fear of risk associated with transplantation; (4) issues of aging and overuse injuries to existing limbs. Results suggests that there is opportunity for expanding education about all treatment options for patients with new loss, long-term loss, and congenital limb loss. Establishing a baseline of knowledge about all options-prosthetics, rehabilitative strategies, and VCA-can help patients evaluate their values and goals of treatment. Issues associated with aging, including overuse and injury, and adaptability over the life course should be included in considerations about treatment choices. Data indicate the need for routinely assessing patient preferences about treatment choice so patients can plan for their future as they adapt and age and as technology for treatments change. To assure that thorough information is provided for current and future decision-making, education about treatment choices and selection procedures for VCA should be standardized., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Finnie, Griffin, Kennedy, Schaepe, Boehmer, Hargraves, Amer and Jowsey-Gregoire.)

Reconstructive allografts using Vascularized Composite Allotransplantation (VCA) are providing individuals living with upper limb loss and facial disfigurement with new opportunities for a sensate, esthetically acceptable, and functional alternative to current treatment strategies. Important research attention is being paid to how best to assess and screen candidates for VCA, measure optimal patient outcomes, and support patient adherence to lifelong behaviors and medical regimens. Far less attention, however, has been dedicated to the team science required for these complex VCA teams to form, prepare, and provide the highest quality clinical and psychosocial care to those receiving VCA. VCA teams are unique in that they require specialized team members whose scope of practice may not otherwise overlap. The team also needs to constantly negotiate balancing patient safety with multiple risks throughout the transplant process. This study aimed to elucidate the team science needed for this highly innovative and complex area of medicine. Using in-depth qualitative interviews with 14 VCA team members and observations at team meetings, we found that careful consideration of team composition, team structure, and organizational commitment (e.g., local culture and team values; investment of resources) influences team performance and patient outcomes, but that to be efficient and truly effective, teams need to commit to developing processes that foster collaboration. These processes are action-oriented (e.g., communication, leadership), strategic (e.g., planning, training) and interpersonal (e.g., conflict management, trust building). Dedication and commitment to team science allows teams to manage conflict under stress and exercise ways to leverage strengths to provide optimal performance or patient psychosocial and clinical outcomes. This study can provide insight into quality improvement efforts for VCA teams and guidance for other transplant programs that wish to consider expansion into VCA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Griffin, Kennedy, Boehmer, Hargraves, Amer and Jowsey-Gregoire.)

Background: Physical activity and a healthy diet are important in helping to maintain mobility with aging. This umbrella review aims to identify group-based physical activity and/or nutrition interventions for community-dwelling older adults that improve mobility-related outcomes., Methods: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, Sociological Abstracts) were searched from inception to December 2021. Eligibility criteria included systematic reviews exploring the effectiveness of physical activity or structured exercise, alone or combined with nutrition interventions on mobility-related outcomes (aerobic capacity, physical function, balance, falls/safety, muscle strength, health-related quality of life/wellbeing). Interventions must have been delivered in a group setting to community-dwelling older adults aged 55+. Two reviewers independently performed eligibility screening, critical appraisal (using AMSTAR 2) and data extraction. The GRADE approach was used to reflect the certainty of evidence based on the size of the effect within each mobility-related outcome category. Older adult/provider research partners informed data synthesis and results presentation., Results: In total, 62 systematic reviews (1 high, 21 moderate, 40 low/critically low quality) were identified; 53 included physical activity only, and nine included both physical activity and nutritional supplements. No reviews included nutrition interventions alone. Combined aerobic/resistance, general physical activity, and mind-body exercise all improved physical function and balance (moderate-high certainty). Aerobic/resistance training improved aerobic capacity (high certainty). Resistance training and general physical activity improved muscle strength (moderate certainty). Aerobic/resistance training and general physical activity are likely to reduce falls among older adults (moderate certainty). There was no evidence of benefit for nutritional supplementation with physical activity., Conclusions: Group-based physical activity interventions that combine aerobic and resistance, general PA and mind-body exercise can improve measures of mobility in community-dwelling older adults. We found no reviews focused on nutrition only, highlighting a gap in the literature., (© 2022. The Author(s).)

The ability to perform invasive bedside procedures (IBPs) safely and efficiently is a core skill set within critical care medicine. Fellowship training provides a pivotal time for learners to attain baseline proficiency in such procedures to decrease patient complications. The coronavirus disease 2019 pandemic has posed distinct challenges to the traditional model of teaching and supervising IBPs in the intensive care unit, including stewardship of personal protective equipment and limiting health care worker exposure to persons with coronavirus disease 2019. To address these challenges, we piloted a novel method of IBP supervision and teaching using a virtual monitoring system. In this virtual procedural supervision model, the supervising teacher is located outside the patient room, limiting personal protective equipment use and health care worker exposure. An audiovisual monitoring system allowed communication between the teacher and the learner as well as supervisor visualization of the procedural encounter. Virtual supervision was used for central line placement and bronchoscopy in the medical intensive care unit with no complications or instances of the supervisor needing to enter the patient room. Success was felt to depend on camera positioning and preprocedure planning and to be best for advanced learners who would not require tactile feedback. Upper level learners appreciated autonomy granted by this process. Virtual IBP supervision is felt to be a useful tool in specific situations. As with any tool, there are notable strengths and limitations. Success is felt to be optimized when attention is paid to procedural teaching best practices, learner selection, and technological logistics., (© 2021 THE AUTHORS.)

Lung transplantation in patients with systemic sclerosis (SSc) can be complicated by extrapulmonary manifestations of the disease, leading to concerns regarding posttransplant complications and outcomes., Methods: We conducted a web-based survey of adult lung transplant programs in the United States regarding their practices in patients with SSc., Results: Sixty percent (37/62) of the eligible centers responded to the survey, majority of the respondents were medical directors (81%). Most centers would consider transplanting patients with mild or moderate esophageal disease (92% or 75%, respectively) or gastroparesis (59%). A minority would consider patients with severe esophageal dysmotility (37%), digital ulcers (21%), or low body mass index (19%). Most centers conducted extensive pretransplant gastrointestinal evaluation and use a conservative feeding approach with prolonged nothing by mouth (83%) and postpyloric feeding (89%). Antireflux surgery is commonly considered (40%) with partial fundoplication being the procedure of choice (67%). Most respondents expected similar outcomes of acute or chronic rejection (81% and 51%, respectively), respiratory infections (76%), and 1-year survival (70%)., Conclusions: Most US lung transplant centers do not universally exclude SSc from lung transplant listing, but most support extensive pretransplant gastrointestinal testing and a conservative approach to feeding in the early posttransplant period., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: dance is a mind-body activity that stimulates neuroplasticity. We explored the effect of dance on cognitive function in older adults., Methods: we searched MEDLINE, EMBASE, CENTRAL and PsycInfo databases from inception to August 2020 (PROSPERO:CRD42017057138). Inclusion criteria were (i) randomised controlled trials (ii) older adults (aged ≥ 55 years), (iii) intervention-dance and (iv) outcome-cognitive function. Cognitive domains were classified with the Diagnostic and Statistical Manual of Mental Disorders-5 Neurocognitive Framework. Meta-analyses were performed in RevMan5.3 and certainty of evidence with GradePro., Results: we reviewed 3,997 records and included 11 studies (N = 1,412 participants). Seven studies included only healthy older adults and four included those with mild cognitive impairment (MCI). Dance interventions varied in frequency (1-3×/week), time (35-60 minutes), duration (3-12 months) and type. We found a mean difference (MD) = 1.58 (95% confidence interval [CI) = 0.21-2.95) on the Mini Mental State Examination for global cognitive function (moderate-certainty evidence), and the Wechsler Memory Test for learning and memory had an MD = 3.02 (95% CI = 1.38-4.65; low-certainty evidence). On the Trail Making Test-A for complex attention, MD = 3.07 (95% CI = -0.81 to 6.95; high-certainty evidence) and on the Trail Making Test-B for executive function, MD = -4.12 (95% CI = -21.28 to 13.03; moderate-certainty evidence). Subgroup analyses did not suggest consistently greater effects in older adults with MCI. Evidence is uncertain for language, and no studies evaluated social cognition or perceptual-motor function., Conclusions: dance probably improves global cognitive function and executive function. However, there is little difference in complex attention, and evidence also suggests little effect on learning and memory. Future research is needed to determine the optimal dose and if dance results in greater cognitive benefits than other types of physical activity and exercise., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The population is aging. Although older adults have higher rates of comorbidities and adverse health events, they represent a heterogeneous group with different health trajectories. Frailty, a clinical syndrome of decreased physiological reserve and increased susceptibility to illness and death, has emerged as a potential risk stratification tool in older patients with chronic kidney disease (CKD). Frailty is commonly observed in patients with CKD and associated with numerous adverse outcomes, including falls, decreased quality of life, hospitalizations, and death. Multiple pathologic factors contribute to the development of frailty in patients with CKD, including biological mechanisms of aging and physiological dysregulation. Current interventions to reduce frailty are promising, but additional investigations are needed to determine whether optimizing frailty measures improves renal and overall health outcomes. This review of frailty in CKD examines frailty definitions, the impact of frailty on health outcomes across the CKD spectrum, mechanisms of frailty, and antifrailty interventions (e.g., exercise or senescent cell clearance) tested in CKD patients. In addition, existing knowledge gaps, limitations of current frailty definitions in CKD, and challenges surrounding effective antifrailty strategies in CKD are considered., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Many lung transplant candidates and recipients are older and frailer compared to previous eras. Older patients are at increased risk for pre- and posttransplant mortality, but this risk is not explained by numerical age alone. This manuscript represents the product of the American Society of Transplantation (AST) conference on frailty. Experts in the field reviewed the latest published research on assessment of elderly and frail lung transplant candidates. Physical frailty, often defined as slowness, weakness, low physical activity, shrinking, and exhaustion, and frailty evaluation is an important tool for evaluation of age-associated dysfunction. Another approach is assessment by cumulative deficits, and both types of frailty are common in lung transplant candidates. Frailty is associated with death or delisting before transplant, and may be associated with posttransplant mortality. Sarcopenia, cognitive dysfunction, depression, and nutrition are other important components for patient evaluation. Aging-associated inflammation, telomere dysfunction, and adaptive immune system senescence may also contribute to frailty. Developing tools for frailty assessment and interventions holds promise for improving patient outcomes before and after lung transplantation., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: Research career development awards (CDAs) facilitate development of clinician-scientists. This study compared the academic achievements of individuals in a structured institutional "pre-K" CDA program, the Mayo Clinic Kern Scholars program, with individuals who applied for but were not admitted to the Kern program ("Kern applicants"), and awardees of other unstructured internal CDAs., Methods: This was a longitudinal cohort study of clinicians engaged in research at Mayo Clinic between 2010 and 2019. The primary outcome was time to the 15 th new peer-reviewed publication after the program start, adjusted for baseline number of publications. Secondarily, we described successful awarding of federal funding by the NIH or VA., Results: The median (IQR) number of baseline publications was highest among Kern Scholars compared to Kern Applicants or other CDA awardees [16 (12, 29) vs 5 (1, 11) and 8 (5, 16); P < 0.001]. After adjustment for baseline publications, the time to 15th new publication was significantly shorter for Kern Scholars than for the two comparator groups (P<0.001). Similar findings were observed with total new publications within 5 years (P < 0.001), as well as number of new first-/last-author publications within 5 years (P < 0.001). The overall frequency of K-awards, R-awards (or equivalent), or any funding were similar between groups, with the exception of R03 awards, which were significantly more common among Kern Scholars (P = 0.002)., Conclusion: The Kern Scholars program is a successful training model for clinician-scientists that demonstrated comparatively greater acceleration of scholarly productivity than other internal CDA programs., Competing Interests: The authors have no conflicts of interest to declare., (© The Association for Clinical and Translational Science 2021.)

The vascular endothelium is present in all organs and blood vessels, facilitates the exchange of nutrients and waste throughout different organ systems in the body, and sets the tone for healthy vessel function. Mechanosensitive in nature, the endothelium responds to the magnitude and temporal waveform of shear stress in the vessels. Endothelial dysfunction can lead to atherosclerosis and other diseases. Modeling endothelial function and dysfunction in organ systems in vitro , such as the blood-brain barrier and tissue-engineered blood vessels, requires sourcing endothelial cells (ECs) for these biomedical engineering applications. It can be difficult to source primary, easily renewable ECs that possess the function or dysfunction in question. In contrast, human pluripotent stem cells (hPSCs) can be sourced from donors of interest and renewed almost indefinitely. In this review, we highlight how knowledge of vascular EC development in vivo is used to differentiate induced pluripotent stem cells (iPSC) into ECs. We then describe how iPSC-derived ECs are being used currently in in vitro models of organ function and disease and in vivo applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kennedy, Brown, Abutaleb and Truskey.)

Patient-related complications from invasive bedside procedures (IBPs) are attributed to the experience and proficiency of the operator. Furthermore, IBP complications by trainees may be due to practice variability and competency among IBP teachers. The use of gaze metrics technology to better understand the behaviors of IBP teachers may aid in the creation of faculty development checklists and, ultimately, reduce procedural complications. Prior research on gaze patterns has focused on the individual performing the procedure, but the goal of this pilot study was to assess gaze behaviors of supervising teachers of IBPs, which is a paradigm shift within procedural education. In this study, pulmonary and critical care medicine fellows placed a central venous catheter on a simulated task trainer as pulmonary and critical care medicine faculty supervised while wearing an eye-tracking device. Both quantitative and qualitative data were obtained. Gaze analysis was divided into 2 areas of interest (ultrasonography and procedure site) and 3 procedural tasks (venous puncture, dilation, and flushing the line). Study findings included the following: (1) calibration was easy and took seconds to complete, (2) the device is relatively comfortable and did not interfere with tasks, (3) a trend toward a higher fixation frequency and dwell time on the ultrasound images during the puncture segment, and (4) variations in fixation frequency on the ultrasound images among supervising IBP teachers. This study documents the feasibility of the eye-tracking device for assessing behaviors of supervisory IBP teachers. There may be a signal suggesting differences in gaze patterns among supervisory teachers, which warrants further study., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Purpose: To describe the frequency, content, dynamics, and patterns of cost conversations in academic medical oncology across tumor types., Patients and Methods: We reviewed 529 audio recordings between May 3, 2012, to September 23, 2014, from a prospective three-site communication study in which patients at any stage of management for any solid tumor malignancy were seen in routine oncology appointments. Recordings were deidentified, transcribed, and flagged for any mention of cost. We coded encounters and used qualitative thematic analysis., Results: Financial issues were discussed in 151 (28%) of 529 recordings. Conversations lasted shorter than 2 minutes on average. Patients/caregivers raised a majority of discussions (106 of 151), and 40% of cost concerns raised by patients/caregivers were not verbally acknowledged by clinicians. Social service referrals were made only six times. Themes from content analysis were related to insurance eligibility/process, work insecurity, cost of drugs, cost used as tool to influence medical decision making, health care-specific costs, and basic needs. Financial concerns influenced oncology work processes via test or medication coverage denials, creating paperwork for clinicians, potentially influencing patient involvement in trials, and leading to medication self-rationing or similar behaviors. Typically, financial concerns were associated with negative emotions., Conclusion: Financial issues were raised in approximately one in four academic oncology visits. These brief conversations were usually initiated by patients/caregivers, went frequently unaddressed by clinicians, and seemed to influence medical decision making and work processes and contribute to distress. Themes identified shed light on the kinds of gaps that must be addressed to help patients with cancer cope with the rising cost of care.

Background: Joint replacement provides significant improvements in pain, physical function, and quality of life in patients with osteoarthritis. With a growing body of evidence indicating that frailty can be treated, it is important to determine whether targeting frailty reduction in hip and knee replacement patients improves post-operative outcomes., Objectives: The primary objective is to examine the feasibility of a parallel group RCT comparing a preoperative multi-modal frailty intervention to usual care in pre-frail/frail older adults undergoing elective unilateral hip or knee replacements. The secondary objectives areTo explore potential efficacy of the multi-modal frailty intervention in improving frailty and mobility between baseline and 6 weeks post-surgery using Fried frailty phenotype and short performance physical battery (SPPB) respectively.To explore potential efficacy of the multi-modal frailty intervention on post-operative healthcare services use., Methods/design: In a parallel group pilot RCT, participants will be recruited from the Regional Joint Assessment Program in Hamilton, Canada. Participants who are (1) ≥ 60 years old; (2) pre-frail (score of 1 or 2) or frail (score of 3-5; Fried frailty phenotype); (3) having elective unilateral hip or knee replacement; and (4) having surgery wait times between 3 and 10 months will be recruited and randomized to either the intervention or usual care group. The multi-modal frailty intervention components will include (1) tailored exercise program (center-based and/or home-based) with education and cognitive behavioral change strategies; (2) protein supplementation; (3) vitamin D supplementation; and (4) medication review. The main comparative analysis will take place at 6 weeks post-operative. The outcome assessors, data entry personnel, and data analysts are blinded to treatment allocation. Assessments: feasibility will be assessed by recruitment rate, retention rate, and data collection completion. Frailty and healthcare use and other clinical outcomes will be assessed. The study outcomes will be collected at the baseline, 1 week pre-operative, and 6 weeks and 6 months post-operative., Discussion: This is the first study to examine the feasibility of multi-modal frailty intervention in pre-frail/frail older adults undergoing hip or knee replacement. This study will inform the planning and designing of multi-modal frailty interventional studies in hip and knee replacement patients., Trial Registration: ClinicalTrials.gov NCT02885337., Competing Interests: Ethical approval for this trial was obtained from the Hamilton Integrated Research Ethics Board London (HiREB) (file #: 2017–1565). All participants provide written informed consent before participating in the trial.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Short telomere syndromes (STSs) are accelerated aging syndromes with multisystemic manifestations that present complex management challenges. In this article, we discuss a single-institution experience in diagnosing and managing patients with inherited STSs. In total, we identified 17 patients with short telomeres, defined by flow-fluorescence in-situ hybridization telomere lengths of less than first centile in granulocytes/lymphocytes OR the presence of a characteristic germline pathogenic variant in the context of a highly suggestive clinical phenotype. Genetic variations in the telomere complex were identified in 6 (35%) patients, with 4 being known pathogenic variants involving TERT (n=2), TERC (n=1), and DKC1 (n=1) genes, while 2 were variants of uncertain significance in TERT and RTEL1 genes. Idiopathic interstitial pneumonia (IIP) (n=12 [71%]), unexplained cytopenias (n=5 [29%]), and cirrhosis (n=2 [12%]) were most frequent clinical phenotypes at diagnosis. At median follow-up of 48 (range, 0-316) months, Kaplan-Meier estimate of overall survival, median (95% CI), was 182 (113, not reached) months. Treatment modalities included lung transplantation for IIP (n=5 [29%]), with 3 patients developing signs of acute cellular rejection (2, grade A2; 1, grade A1); danazol therapy for cytopenias (n=4 [24%]), with only 1 out of 4 patients showing a partial hematologic response; and allogeneic hematopoietic stem cell transplant for progressive bone marrow failure (n=2), with 1 patient dying from transplant-related complications. In summary, patients with STSs present with diverse clinical manifestations and require a multidisciplinary approach to management, with organ-specific transplantation capable of providing clinical benefit., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background : Optimal screening and management of latent tuberculosis infection (LTBI) and active tuberculosis (TB) in solid organ transplant (SOT) candidates and recipients is necessary to prevent morbidity and mortality. Methods : We conducted a cross-sectional survey of TB and transplant experts across the United States reviewing the clinical practice preferences on key management issues related to LTBI and TB in SOT candidates and recipients. Results : Thirty TB and 13 SOT experts were surveyed (response rate = 53.8%). Both groups agreed that tuberculin skin test (TST) and chest x-ray screening in SOT candidates was useful (78.6% and 84.6%, respectively). TST after SOT was not useful for most transplant experts and TB experts (0% vs. 32.1%, respectively), but both groups were split on usefulness of interferon gamma release assays (IGRA) in SOT recipients (42.9% TB experts vs. 46.2% SOT experts). Most experts recommend LTBI treatment prior to SOT if close monitoring is assured (82.1% TB experts vs. 76.9% transplant experts). LTBI treatment with isoniazid was preferred for patients on calcineurin inhibitors. Evaluation for suspected TB in SOT recipients varied, but most TB experts favored sputum testing (88.9%) whereas most transplant experts favored bronchoscopic testing (69.2%). Preferred TB treatment regimens in SOT recipients were similar to regimens recommended for immunocompetent patients. Conclusions : Most TB and transplant experts recommend evaluation and treatment for LTBI in SOT candidates. Liver transplant candidates, however, should only be treated if close monitoring can be assured and after consulting with a hepatologist. Practice preferences varied regarding the initial diagnostic approach for suspected TB in SOT recipients; however, most experts agreed that SOT recipients should receive similar treatments as immunocompetent patients., (© 2018 The Authors.)

Mycobacterium abscessus complex ( MAbsC ) disease in lung transplant recipients is increasingly being recognized as an important cause of graft function decline and suboptimal outcomes. Lung transplant recipients appear to be at the highest risk of MAbsC among solid organ transplant recipients, as they have more intense immunosuppression, and the organisms preferentially inhabit the lungs. MAbsC is the most resistant species of rapidly growing mycobacteria and difficult to treat, causing considerable mortality and morbidity in immunocompetent and immunosuppressed patients. Herein we describe the risk factors, epidemiology, clinical features, diagnostics, and treatment strategies of MAbsC in lung transplant recipients., Competing Interests: Conflict of interest: None of the authors have any conflict of interest.

Background: The objectives of this study were to determine: 1) the prevalence of frailty using Fried's phenotype method and the Short Performance Physical Battery (SPPB), 2) agreement between frailty assessment methods, 3) the feasibility of assessing frailty using Fried's phenotype method and the SPPB., Methods: This cross-sectional study was conducted at a geriatric out-patient clinic in Hamilton, Canada. A research assistant conducted all frailty assessments. Patients were classified as non-frail, pre-frail or frail according to Fried's phenotype method and the SPPB. Agreement among methods is reported using the Cohen kappa statistic (standard error). Feasibility data included the percent of eligible participants agreeing to attempt the frailty assessments (criterion for feasibility: ≥90% of patients agreeing to the frailty assessment), equipment required, and safety considerations. A p-value of <0.05 is considered significant., Results: A total of 110 participants (92%) and 109 participants (91%) agreed to attempt Fried's phenotype method and SPPB, respectively. No adverse events occurred during any assessments. According to Fried's phenotype method, the prevalence of frailty and pre-frailty was 35% and 56%, respectively, and according to the SPPB, the prevalence of frailty and pre-frailty was 50% and 35%, respectively. There was fair to moderate agreement between methods for determining which participants were frail (0.488 [0.082], p < 0.001) and pre-frail (0.272 [0.084], p = 0.002)., Conclusions: Frailty and pre-frailty are common in this geriatric outpatient population, and there is fair to moderate agreement between Fried's phenotype method and the SPPB. Over 90% of the patients who were eligible for the study agreed to attempt the frailty assessments, demonstrating that according to our feasibility criteria, frailty can be assessed in this patient population. Assessing frailty may help clinicians identify high-risk patients and tailor interventions based on baseline frailty characteristics.

Background: Frailty is a common syndrome affecting 5-17% of community-dwelling older adults. Various interventions are used to prevent or treat frailty. Given the diversity of singular and multi-faceted frailty interventions, not all of them have been compared in head-to-head studies. Network meta-analyses provide an approach to simultaneous consideration of the relative effectiveness of multiple treatment alternatives. This systematic review and network meta-analysis of RCTs aims to determine the comparative effect of interventions targeting the prevention or treatment of frailty., Method: We will identify relevant RCTs, in any language and publication date, by a systematic search of databases including MEDLINE, EMBASE, CINAHL, AMED, the Cochrane Central Registry of Controlled Trials (CENTRAL), HealthSTAR, DARE, PsychINFO, PEDro, SCOPUS, and Scielo. Duplicate title and abstract and full-text screening will be performed. Authors will extract data and assess risk of bias (using the Cochrane Risk of Bias tool) of eligible studies. The review interventions will include (1) physical activity only, (2) physical activity with protein supplementation or other nutritional supplementation, (3) psychosocial intervention, (4) medication management, (5) pharmacotherapy, and (6) multi-faceted intervention (defined as an intervention that combine physical activity and/or nutrition with any of the following: (1) psychosocial intervention, (2) medication management, and (3) pharmacotherapy). Our primary outcome is difference in change of physical frailty from baseline measured by a reliable and valid frailty measure. Secondary outcomes and the assessments are (1) cognition, (2) short physical performance battery, (3) any other physical performance measure, (4) treatment cost, (5) quality of life, and (6) any adverse outcome. We will conduct a network meta-analysis using a Bayesian hierarchical model. We will also estimate the ranking probabilities for all treatments at each possible rank for each intervention and will assess the certainty of the estimates of effect using GRADE approach., Discussion: To the best of our knowledge, this will be the first systematic review and network meta-analysis considering the direct and indirect effect of interventions targeting frailty prevention or treatment. Given the established high prevalence and socio-economic burden of frailty, there is an urgent need for a high-quality systematic review to inform evidence-based management of frailty., Systematic Review Registration: PROSPERO 2016 CRD42016037465 .

Obliterative bronchiolitis (OB) is a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). Our objective was to perform a systematic review and meta-analysis of the impact of azithromycin on change in forced expiratory volume in 1 second (FEV 1 ). We searched MEDLINE, EMBASE, Web of Science, Cochrane CENTRAL and Scopus databases and included studies that compared azithromycin with placebo or no intervention in the treatment of OB or bronchiolitis obliterans syndrome (BOS) in patients who had undergone allogeneic HSCT. Ninety-one unique publications were identified, and 4 studies met inclusion criteria, with a total of 90 patients. Changes in FEV 1 were measured between 12 and 24 weeks after initiation of treatment. The meta-analysis demonstrated a mean increase in FEV 1 of 30 mL (95% confidence interval, -260 to +330 mL; P = .82) after initiation of azithromycin. One patient death was reported but not attributed to azithromycin therapy. In conclusion, current evidence can neither support nor refute the use of azithromycin in the treatment of patients who develop OB/BOS after HSCT. Further studies are needed to determine whether azithromycin is beneficial for the treatment of OB/BOS in this setting., Competing Interests: None, (Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Physical frailty is associated with significant morbidity and mortality in community-dwelling older adults. Burden in informal caregivers of older adults causes significant physical and psychological distress. However, the relationship between these two clinical phenomena has not been extensively studied. This cross-sectional study evaluated the relationship between physical frailty of community-dwelling older adults attending an outpatient geriatric clinic and the subjective burden reported by their informal caregivers., Methods: We measured the following characteristics of 45 patient-caregiver dyads attending an outpatient geriatric assessment clinic: Physical frailty using the Fried Frail Scale (FFS); self-reported independence in activities of daily living (ADL) using the Katz Index; clinical diagnosis of dementia; and subjective caregiver burden using the short 12-item version of the Zarit Burden Interview (ZBI). Multivariable linear regression was performed with FFS, Katz Index score, gender, age, and diagnosis of dementia as independent variables, and ZBI score as the dependent variable., Results: Only physical frailty significantly predicted caregiver burden (β = 8.98 95% confidence interval [CI]: 2.15, 15.82)., Conclusions: Physical frailty is independently associated with caregiver burden in a population of community-dwelling older adults. Despite limitations related to sample size and lack of data about caregiver characteristics, this study suggests that the relationship between physical frailty and caregiver burden merits further study.

Background: Osteoporosis is a major global health problem, especially among long-term care (LTC) facilities. Despite the availability of effective clinical guidelines to prevent osteoporosis and bone fractures, few LTC homes actually adhere to these practical recommendations. The purpose of this study was to identify barriers to the implementation of evidence-based practices for osteoporosis and fracture prevention in LTC facilities and elicit practical strategies to address these barriers., Methods: We performed a qualitative analysis of action plans formulated by Professional Advisory Committee (PAC) teams at 12 LTC homes in the intervention arm of the Vitamin D and Osteoporosis Study (ViDOS) in Ontario, Canada. PAC teams were comprised of medical directors, administrators, directors of care, pharmacists, dietitians, and other staff. Thematic content analysis was performed to identify the key themes emerging from the action plans., Results: LTC teams identified several barriers, including lack of educational information and resources prior to the ViDOS intervention, difficulty obtaining required patient information for fracture risk assessment, and inconsistent prescribing of vitamin D and calcium at the time of admission. The most frequently suggested recommendations was to establish and adhere to standard admission orders regarding vitamin D, calcium, and osteoporosis therapies, improve the use of electronic medical records for osteoporosis and fracture risk assessment, and require bone health as a topic at quarterly reviews and multidisciplinary conferences., Conclusions: This qualitative study identified several important barriers and practical recommendations for improving the implementation of osteoporosis and fracture prevention guidelines in LTC settings.

Background: Few studies have systematically examined whether knowledge translation (KT) strategies can be successfully implemented within the long-term care (LTC) setting. In this study, we examined the effectiveness of a multifaceted, interdisciplinary KT intervention for improving the prescribing of vitamin D, calcium and osteoporosis medications over 12-months., Methods: We conducted a pilot, cluster randomized controlled trial in 40 LTC homes (21 control; 19 intervention) in Ontario, Canada. LTC homes were eligible if they had more than one prescribing physician and received services from a large pharmacy provider. Participants were interdisciplinary care teams (physicians, nurses, consultant pharmacists, and other staff) who met quarterly. Intervention homes participated in three educational meetings over 12 months, including a standardized presentation led by expert opinion leaders, action planning for quality improvement, and audit and feedback review. Control homes did not receive any additional intervention. Resident-level prescribing and clinical outcomes were collected from the pharmacy database; data collectors and analysts were blinded. In addition to feasibility measures, study outcomes were the proportion of residents taking vitamin D (≥800 IU/daily; primary), calcium ≥500 mg/day and osteoporosis medications (high-risk residents) over 12 months. Data were analyzed using the generalized estimating equations technique accounting for clustering within the LTC homes., Results: At baseline, 5,478 residents, mean age 84.4 (standard deviation (SD) 10.9), 71% female, resided in 40 LTC homes, mean size = 137 beds (SD 76.7). In the intention-to-treat analysis (21 control; 19 intervention clusters), the intervention resulted in a significantly greater increase in prescribing from baseline to 12 months between intervention versus control arms for vitamin D (odds ratio (OR) 1.82, 95% confidence interval (CI): 1.12, 2.96) and calcium (OR 1.33, 95% CI: 1.01, 1.74), but not for osteoporosis medications (OR 1.17, 95% CI: 0.91, 1.51). In secondary analyses, excluding seven nonparticipating intervention homes, ORs were 3.06 (95% CI: 2.18, 4.29), 1.57 (95% CI: 1.12, 2.21), 1.20 (95% CI: 0.90, 1.60) for vitamin D, calcium and osteoporosis medications, respectively., Conclusions: Our KT intervention significantly improved the prescribing of vitamin D and calcium and is a model that could potentially be applied to other areas requiring quality improvement., Trial Registration: ClinicalTrials.gov: NCT01398527 . Registered: 19 July 2011.

Early goal-directed therapy (EGDT) consists of early, aggressive fluid resuscitation and is known to improve survival in sepsis. It is unknown how often EGDT leads to subsequent fluid overload and whether post-EGDT fluid overload affects patients' outcomes. Our hypothesis was that patients with sepsis treated with EGDT were at risk for fluid overload and that fluid overload would be associated with adverse outcomes. We conducted a retrospective cohort of 405 consecutive patients admitted with severe sepsis and septic shock to the medical intensive care unit of a tertiary care academic hospital from January 2008 to December 2009. Baseline demographics, daily weights, fluid status, clinical or radiographic evidence of fluid overload, and medical interventions (thoracentesis, paracentesis, diuretic use, and ultrafiltration) were abstracted, and associations explored using univariate and multivariate logistic and linear regression analyses. At day 1, 67% of patients developed evidence of fluid overload, and in 48%, fluid overload persisted to day 3. Interrater agreement for presence of fluid overload was substantial (κ = 0.7). An increased trend in weight was noted in those with persistent clinical and radiologic evidence of fluid overload, but not with recorded positive fluid balance. When adjusted for baseline severity of illness, fluid overload was associated with increased use of fluid-related medical interventions (thoracentesis and diuretics) and hospital mortality (odds ratio, 1.92; confidence interval, 1.16-3.22). In patients with severe sepsis and septic shock treated with EGDT, clinical evidence of persistent fluid overload is common and is associated with increased use of medical interventions and hospital mortality.

Background: POEMS syndrome is a plasma cell disorder manifested by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes. Pulmonary morbidity includes restriction, decreased diffusing capacity for carbon monoxide (DLCO), respiratory muscle weakness, abnormal imaging, and pulmonary hypertension. Autologous peripheral blood stem cell transplantation (aPBSCT) is an effective treatment for POEMS syndrome. It is unknown if aPBSCT improves pulmonary morbidity. We hypothesize pulmonary morbidity will improve following aPBSCT., Methods: Retrospective cohort study of POEMS syndrome aPBSCT recipients from 2000 to 2010. Demographic, pulmonary function test (PFT), echocardiogram, cytokine, and imaging data at baseline and after aPBSCT were abstracted. Pre- and post-transplant data were compared using Wilcoxon signed-rank and McNemar's tests., Results: 53 patients met criteria. Median improvements in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) after transplant were 180, 315 and 350 ml respectively (median follow-up of 1.1 years). DLCO, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) improved by a median of 11, 12.5 and 10% predicted respectively. RVSP and chest imaging also improved. Vascular endothelial growth factor and IL-6 decreased by a median of 334 and 2 pg/ml respectively. All comparisons were statistically significant. Longitudinal data demonstrated stability in FEV1, MEP, and TLC and continued improvement in FVC, MIP and DLCO on subsequent PFTs (median follow-up 26.5 months)., Conclusion: Patients with POEMS syndrome treated with aPBSCT have significant improvement in PFTs, respiratory muscle strength, imaging, and post-transplant IL-6. The improvement in PFTs persists during long-term follow-up., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Streptococcus suis is an emerging swine-associated zoonotic agent that can cause meningitis and septicemia in humans. We present, to our knowledge, the first case of S. suis arthroplasty infection and streptococcal toxic shock-like syndrome due to an nonencapsulated serotype 5 strain in North America., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: The majority of frail elderly who live in long-term care (LTC) are not treated for osteoporosis despite their high risk for fragility fractures. Clinical Practice Guidelines for the diagnosis and management of osteoporosis provide guidance for the management of individuals 50 years and older at risk for fractures, however, they cannot benefit LTC residents if physicians perceive barriers to their application. Our objectives are to explore current practices to fracture risk assessment by LTC physicians and describe barriers to applying the recently published Osteoporosis Canada practice guidelines for fracture assessment and prevention in LTC., Methods: A cross-sectional survey was conducted with the Ontario Long-Term Care Physicians Association using an online questionnaire. The survey included questions that addressed members' attitudes, knowledge, and behaviour with respect to fracture risk assessment in LTC. Closed-ended responses were analyzed using descriptive statistics and thematic framework analysis for open-ended responses., Results: We contacted 347 LTC physicians; 25% submitted completed surveys (81% men, mean age 60 (Standard Deviation [SD] 11) years, average 32 [SD 11] years in practice). Of the surveyed physicians, 87% considered prevention of fragility fractures to be important, but a minority (34%) reported using validated fracture risk assessment tools, while 33% did not use any. Clinical risk factors recommended by the OC guidelines for assessing fracture risk considered applicable included; glucocorticoid use (99%), fall history (93%), age (92%), and fracture history (91%). Recommended clinical measurements considered applicable included: weight (84%), thyroid-stimulating hormone (78%) and creatinine (73%) measurements, height (61%), and Get-Up-and-Go test (60%). Perceived barriers to assessing fracture risk included difficulty acquiring necessary information, lack of access to tests (bone mineral density, x-rays) or obtaining medical history; resource constraints, and a sentiment that assessing fracture risk is futile in this population because of short life expectancy and polypharmacy., Conclusion: Perceived barriers to fracture risk assessment and osteoporosis management in LTC have not changed recently, contributing in part to the ongoing care gap in osteoporosis management. Our findings highlight the importance to adapt guidelines to be applicable to the LTC environment, and to develop partnerships with stakeholders to facilitate their use in clinical practice.

Introduction: Idiopathic acute eosinophilic pneumonia (AEP) is characterized by hypoxemia, pulmonary infiltrates and pulmonary eosinophilia. Data is limited and the purpose of this study is to better understand this disorder., Methods: A search of the computerized patient records from January 1, 1997 to October 15, 2010 for patients with suspicion of "eosinophilic pneumonia" was conducted. Included patients were 18 years or older with an acute febrile illness, hypoxemia, diffuse pulmonary infiltrates on imaging, and pulmonary eosinophilia. Patients were excluded with other known causes of pulmonary eosinophilia., Results: Of 195 patients with pulmonary eosinophilia, 8 patients had "definite" or "probable" and 4 patients had "possible" idiopathic AEP. Three patients were categorized as "probable" idiopathic AEP due to exceeding expected maximal 30-day symptom duration and/or a maximal recorded temperature less than 38 °C. Four patients were defined as "possible" idiopathic AEP given histories of polymyalgia rheumatica, eczema or allergic rhinitis. Of the 8 included patients, 63% were male with a median age of 53. Median duration of symptoms was 21 days. Median nadir oxygen saturation was 83%. Median eosinophil count on bronchoalveolar lavage was 36%. Two patients required intubation. Two patients were current smokers, one of whom had reported a change in smoking habits. All patients were treated with steroids (median of two months)., Conclusions: As diagnostic methods and pharmacologic knowledge improve, the number of patients meeting criteria for idiopathic AEP remains small. Much remains to be learned about this truly rare condition, and current criteria may exclude milder presentations of the disease.

Background: Knowledge translation (KT) research in long-term care (LTC) is still in its early stages. This protocol describes the evaluation of a multifaceted, interdisciplinary KT intervention aimed at integrating evidence-based osteoporosis and fracture prevention strategies into LTC care processes., Methods and Design: The Vitamin D and Osteoporosis Study (ViDOS) is underway in 40 LTC homes (n = 19 intervention, n = 21 control) across Ontario, Canada. The primary objectives of this study are to assess the feasibility of delivering the KT intervention, and clinically, to increase the percent of LTC residents prescribed ≥800 IU of vitamin D daily. Eligibility criteria are LTC homes that are serviced by our partner pharmacy provider and have more than one prescribing physician. The target audience within each LTC home is the Professional Advisory Committee (PAC), an interdisciplinary team who meets quarterly. The key elements of the intervention are three interactive educational sessions led by an expert opinion leader, action planning using a quality improvement cycle, audit and feedback reports, nominated internal champions, and reminders/point-of-care tools. Control homes do not receive any intervention, however both intervention and control homes received educational materials as part of the Ontario Osteoporosis Strategy. Primary outcomes are feasibility measures (recruitment, retention, attendance at educational sessions, action plan items identified and initiated, internal champions identified, performance reports provided and reviewed), and vitamin D (≥800 IU/daily) prescribing at 6 and 12 months. Secondary outcomes include the proportion of residents prescribed calcium supplements and osteoporosis medications, and falls and fractures. Qualitative methods will examine the experience of the LTC team with the KT intervention. Homes are centrally randomized to intervention and control groups in blocks of variable size using a computer generated allocation sequence. Randomization is stratified by home size and profit/nonprofit status. Prescribing data retrieval and analysis are performed by blinded personnel., Discussion: Our study will contribute to an improved understanding of the feasibility and acceptability of a multifaceted intervention aimed at translating knowledge to LTC practitioners. Lessons learned from this study will be valuable in guiding future research and understanding the complexities of translating knowledge in LTC.

Background: There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients. The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels., Methods: In this randomized controlled study, patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario, Canada. Participants were randomized to one of three loading dose groups: placebo; 50,000 IU vitamin D2; or 100,000 IU D2. Following a placebo/loading dose, all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days. Serum 25-hydroxy vitamin D (25-OHD) was measured at baseline, discharge from acute care (approximately 4-weeks), and 3-months., Results: Sixty-five patients were enrolled in the study (44% male). An immediate rise in 25-OHD occurred in the 100,000 group, however there were no significant differences in 25-OHD between the placebo, 50,000 and 100,000 loading dose groups after 4-weeks (69.3, 84.5, 75.6 nmol/L, p = 0.15) and 3-months (86.7, 84.2, 73.3 nmol/L, p = 0.09), respectively. At the end of the study, approximately 75% of the placebo and 50,000 groups had reached the target therapeutic range (75 nmol/L), and 44% of the 100,000 group., Conclusions: In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture, our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2. At the end of the study, all three groups were equally effective in attaining improvement in 25-OHD levels. Given that a daily dose of 1,000 IU vitamin D3 (with or without a loading dose) resulted in at least 25% of patients having suboptimal vitamin D status, patients with acute hip fracture may benefit from a higher daily dose of vitamin D., Trial Registration: Clinical Trials # NCT00424619.

Background: Fractures have largely been assessed by their impact on quality of life or health care costs. We conducted this study to evaluate the relation between fractures and mortality., Methods: A total of 7753 randomly selected people (2187 men and 5566 women) aged 50 years and older from across Canada participated in a 5-year observational cohort study. Incident fractures were identified on the basis of validated self-report and were classified by type (vertebral, pelvic, forearm or wrist, rib, hip and "other"). We subdivided fracture groups by the year in which the fracture occurred during follow-up; those occurring in the fourth and fifth years were grouped together. We examined the relation between the time of the incident fracture and death., Results: Compared with participants who had no fracture during follow-up, those who had a vertebral fracture in the second year were at increased risk of death (adjusted hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1-6.6); also at risk were those who had a hip fracture during the first year (adjusted HR 3.2, 95% CI 1.4-7.4). Among women, the risk of death was increased for those with a vertebral fracture during the first year (adjusted HR 3.7, 95% CI 1.1-12.8) or the second year of follow-up (adjusted HR 3.2, 95% CI 1.2-8.1). The risk of death was also increased among women with hip fracture during the first year of follow-up (adjusted HR 3.0, 95% CI 1.0-8.7)., Interpretation: Vertebral and hip fractures are associated with an increased risk of death. Interventions that reduce the incidence of these fractures need to be implemented to improve survival.

Pneumocystis species are opportunistic fungal pathogens that cause severe pneumonia in immunocompromised hosts. Recent evidence has suggested that unidentified proteases are involved in Pneumocystis life cycle regulation. Proteolytically active ADAM (named for "a disintegrin and metalloprotease") family molecules have been identified in some fungal organisms, such as Aspergillus fumigatus and Schizosaccharomyces pombe, and some have been shown to participate in life cycle regulation. Accordingly, we sought to characterize ADAM-like molecules in the fungal opportunistic pathogen, Pneumocystis carinii (PcADAM). After an in silico search of the P. carinii genomic sequencing project identified a 329-bp partial sequence with homology to known ADAM proteins, the full-length PcADAM sequence was obtained by PCR extension cloning, yielding a final coding sequence of 1,650 bp. Sequence analysis detected the presence of a typical ADAM catalytic active site (HEXXHXXGXXHD). Expression of PcADAM over the Pneumocystis life cycle was analyzed by Northern blot. Southern and contour-clamped homogenous electronic field blot analysis demonstrated its presence in the P. carinii genome. Expression of PcADAM was observed to be increased in Pneumocystis cysts compared to trophic forms. The full-length gene was subsequently cloned and heterologously expressed in Saccharomyces cerevisiae. Purified PcADAMp protein was proteolytically active in casein zymography, requiring divalent zinc. Furthermore, native PcADAMp extracted directly from freshly isolated Pneumocystis organisms also exhibited protease activity. This is the first report of protease activity attributable to a specific, characterized protein in the clinically important opportunistic fungal pathogen Pneumocystis.

Background: Vertebral fractures in patients with cystic fibrosis (CF) may contribute to an accelerated decline in lung function and can be a contraindication to lung transplantation. In this study, we examined longitudinal change in bone mineral density (BMD) and the prevalence of vertebral fractures in adult CF patients, without lung-transplant, attending a Canadian specialty clinic., Methods: Retrospective chart review of all patients attending an Adult Cystic Fibrosis Clinic at Hamilton Health Sciences in Hamilton, Canada. Forty-nine of 56 adults met inclusion criteria. Chest radiographs were graded by consensus approach using Genant's semi-quantitative method to identify and grade fractured vertebrae. Dual x-ray absorptiometry (DXA) scans were also reviewed., Results: The mean age of the cohort was 25.2 years (SD 9.4), 43% were male. The mean body mass index (BMI) was 19.8 (2.8) for males and 21.7 (5.1) for females. At baseline, the rate of at least one vertebral fracture was 16.3%; rising to 21.3% (prevalent and incident) after a 3-year follow-up. The mean BMD T-or Z-scores at baseline were -0.80 (SD 1.1) at the lumbar spine, -0.57 (SD 0.97) at the proximal femur, and -0.71 (SD 1.1) at the whole body. Over approximately 4-years, the mean percent change in BMD was -1.93% at the proximal femur and -0.73% at the lumbar spine., Conclusion: Approximately one in five CF patients demonstrated at least one or more vertebral fractures. Moderate declines in BMD were observed. Given the high rate of vertebral fractures noted in this cohort of adult CF patients, and the negative impact they have on compromised lung functioning, regular screening for vertebral fractures should be considered on routine chest radiographs.