Objective
To determine the effect of alendronate (ALN) and teriparatide on trabecular bone score (TBS) in patients with glucocorticoid‐induced osteoporosis.
Methods
Patients with chronic ...glucocorticoid therapy–induced osteoporosis (median 7.5 mg/day prednisone equivalent for ≥90 days) were randomized to receive oral ALN 10 mg/day (n = 214) or subcutaneous teriparatide 20 μg/day (n = 214) for 36 months; 118 patients in the ALN group and 123 patients in the teriparatide group completed treatment. Dual x‐ray absorptiometry (DXA) results for 53 patients receiving ALN and 56 patients receiving teriparatide who had DXA scans with adequate resolution to perform TBS analysis and completed 36 months of therapy were blindly analyzed for TBS at baseline and 3, 6, 12, 18, 24, and 36 months.
Results
In teriparatide‐treated patients, TBS was significantly increased at 18 months compared to baseline, and by 36 months had increased 3.7% (P < 0.05). In ALN‐treated patients, there was not a significant change in TBS compared to baseline at any time point. Changes in lumbar spine bone mineral density (BMD) measured by DXA in the subgroup with TBS data were similar to BMD results in the overall study population. At 36 months, increases in lumbar spine BMD were 5.5% and 10.3% in patients treated with ALN and teriparatide, respectively.
Conclusion
In patients with glucocorticoid‐induced osteoporosis, both ALN and teriparatide increased lumbar spine BMD. However, trabecular bone score significantly increased with teriparatide but did not significantly change with ALN. The pathogenesis of glucocorticoid‐induced osteoporosis is predominantly reduced bone formation. TBS may represent a sensitive measure to discriminate treatment effects of an anabolic versus an antiresorptive drug in glucocorticoid‐induced osteoporosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cystectomy is a standard treatment for muscle-invasive bladder cancer (MIBC), but it is life-altering. We initiated a phase 2 study in which patients with MIBC received four cycles of gemcitabine, ...cisplatin, plus nivolumab followed by clinical restaging. Patients achieving a clinical complete response (cCR) could proceed without cystectomy. The co-primary objectives were to assess the cCR rate and the positive predictive value of cCR for a composite outcome: 2-year metastasis-free survival in patients forgoing immediate cystectomy or <ypT1N0 in patients electing immediate cystectomy. Seventy-six patients were enrolled; of these, 33 achieved a cCR (43%, 95% confidence interval (CI): 32%, 55%), and 32 of 33 who achieved a cCR opted to forgo immediate cystectomy. The positive predictive value of cCR was 0.97 (95% CI: 0.91, 1), meeting the co-primary objective. The most common adverse events were fatigue, anemia, neutropenia and nausea. Somatic alterations in pre-specified genes (ATM, RB1, FANCC and ERCC2) or increased tumor mutational burden did not improve the positive predictive value of cCR. Exploratory analyses of peripheral blood mass cytometry and soluble protein analytes demonstrated an association between the baseline and on-treatment immune contexture with clinical outcomes. Stringently defined cCR after gemcitabine, cisplatin, plus nivolumab facilitated bladder sparing and warrants further study. ClinicalTrials.gov identifier: NCT03451331 .
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Swab transport systems are used for a variety of specimen types and must maintain organism viability throughout the transport process. The Copan ESwab is a new nylon-flocked swab designed to optimize ...specimen collection and to minimize entrapment of the specimen. We used the quantitative elution method with recommended strains, as described in CLSI document M40-A, to evaluate the ESwab for maintenance of viability of aerobic and anaerobic microorganisms for 0, 6, 24, and 48 h during room temperature and refrigerated temperature storage. The Becton Dickinson CultureSwab MaxV swab and the Remel BactiSwab were used as comparators. The ESwab met CLSI acceptance criteria for all aerobic isolates stored at both temperatures and for all anaerobic isolates stored at refrigerated temperature. The ESwab also met CLSI criteria for four of five anaerobic strains at room temperature. Prevotella melaninogenica was not recovered after 24 or 48 h of room temperature storage with any of the three swab transport systems tested. Overall, the ESwab was equivalent to the Becton Dickinson CultureSwab MaxV swab in organism recovery but recovered more isolates than Remel BactiSwab.
We document and evaluate the use of metapopulation management to conserve a declining population of 217 cheetahs in 40 subpopulations. Metapopulation management resembles a natural metapopulation, ...but dispersal success, demographic rescue effects and genetic viability are enhanced by moving suitable individuals to selected habitat fragments. Unfortunately, history and results of metapopulation management are rarely published. Cheetahs, extirpated from 85% of South Africa, were reintroduced from Namibian and South African ranches into fenced reserves. During 1965–2009 343 cheetahs were reintroduced, yet reserves held only 289 in 2009. Then translocations of free-roaming cheetahs were halted, and numbers dropped to 217 on 40 reserves by 2012. A metapopulation project was launched, and key conservation problems indentified from interviews and records. Thirty-five percent of reserves had no breeding cheetahs, 13% were inbreeding, fence quality was erratic, 3% of cheetahs were sold into captivity annually, and 28% of cheetah mortalities were anthropogenic. Lions accounted for 31% of mortality, perhaps elevated by lion-inexperienced cheetahs and high lion densities. These problems were addressed, and cheetahs were translocated between reserves. Although the median reserve size was only 125 km
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holding four cheetahs, and 80% of reserves were privately owned, in 6 years the metapopulation grew by 51% to 328 cheetahs on 51 reserves, while genetic diversity was managed and monitored. Thus, using metapopulation management, low density species and associated key processes, including carnivory or mega-herbivory, can be conserved in relatively small reserves in regions with dense human populations precluding natural gene flow.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most ...favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. Materials and Methods Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. Results The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. Conclusions The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.
PURPOSE Use of the electronic health record (EHR) during face-to-face clinical encounters affects communication, and prior research has been inconclusive regarding its effect. This survey study ...assessed health care practitioner use of EHR-specific communication skills and patient and practitioner experiences and attitudes regarding EHR use during clinical encounters. METHODS For this US-based study, we distributed previously validated surveys to practitioners and adult patients (aged >18 years) at academic primary care practices from July 1, 2018 through August 31, 2018. The electronic practitioner survey was completed first; a paper survey was administered to patients after appointments. Descriptive statistics were calculated, and the Cochran-Armitage test was used to assess for associations between key variables. RESULTS The practitioner response was 72.9% (43/59); patient response, 45.2% (452/1,000). Practitioners reported maintaining less eye contact (79.1%), listening less carefully (53.5%), focusing less on patients (65.1%), and visits feeling less personal (62.8%). However, patients reported that practitioners provided sufficient eye contact (96.8%) and listened carefully (97.0%); they disagreed that practitioners focused less on them (86.7%) or that visits felt less personal (87.2%). Patients thought EHR use was positive (91.7%); only one-third of practitioners (37.2%) thought that patients would agree with that statement. Practitioners reported stress, burnout, and a lack of sufficient time for EHR documentation. CONCLUSIONS A discrepancy existed in this study between patient and practitioner experiences and attitudes about EHR use, which appeared to negatively affect the experience of health care practitioners but not patients. Organizations should adopt formal strategies to improve practitioner experiences with EHR use. Key words: electronic health record; patient experience; primary health care; communication skills
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Multiphoton microscopy (MPM) is a promising non‐invasive imaging tool for discriminating benign nevi from melanoma. In this study, we establish a MPM morphologic catalogue of common nevi, information ...that will be critical in devising strategies to distinguish them from nevi that are evolving to melanoma that may present with more subtle signs of malignancy. Thirty common melanocytic nevi were imaged in vivo using MPM. Quantitative parameters that can distinguish between different types of nevi were developed and confirmed by examining the histology of eleven of the imaged nevi. MPM features of nevi examined included cytologic morphology of melanocytes in the epidermis and dermis, the size and distribution of nevomelanocytes both within and around nests, the size of rete ridges, and the presence of immune cells in the dermis. Distinguishing features include cytological morphology, the size of nevomelanocytes, the size of nevomelanocyte nests, and the distribution of nevomelanocytes. Notably, these distinguishing characteristics were not easily appreciated in fixed tissues, highlighting essential differences in the morphology of live skin. Taken together, this work provides a morphologic compendium of normal nevi, information that will be critical in future studies directed at identifying melanocytic nevi that are evolving to melanoma.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK