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1.
BMJ Open ; 10(1): e031442, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31964662

RESUMO

INTRODUCTION: Guidelines are systematically developed recommendations to assist practitioner and patient decisions about treatments for clinical conditions. High quality and comprehensive systematic reviews and 'overviews of systematic reviews' (overviews) represent the best available evidence. Many guideline developers, such as the WHO and the Australian National Health and Medical Research Council, recommend the use of these research syntheses to underpin guideline recommendations. We aim to evaluate the impact and use of systematic reviews with and without pairwise meta-analysis or network meta-analyses (NMAs) and overviews in clinical practice guideline (CPG) recommendations. METHODS AND ANALYSIS: CPGs will be retrieved from Turning Research Into Practice and Epistemonikos (2017-2018). The retrieved citations will be sorted randomly and then screened sequentially by two independent reviewers until 50 CPGs have been identified. We will include CPGs that provide at least two explicit recommendations for the management of any clinical condition. We will assess whether reviews or overviews were cited in a recommendation as part of the development process for guidelines. Data extraction will be done independently by two authors and compared. We will assess the risk of bias by examining how each guideline developed clinical recommendations. We will calculate the number and frequency of citations of reviews with or without pairwise meta-analysis, reviews with NMAs and overviews, and whether they were systematically or non-systematically developed. Results will be described, tabulated and categorised based on review type (reviews or overviews). CPGs reporting the use of the Grading of Recommendations, Assessment, Development and Evaluation approach will be compared with those using a different system, and pharmacological versus non-pharmacological CPGs will be compared. ETHICS AND DISSEMINATION: No ethics approval is required. We will present at the Cochrane Colloquium and the Guidelines International Network conference.

2.
Cochrane Database Syst Rev ; 1: CD012501, 2020 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-31981471

RESUMO

BACKGROUND: Cerivastatin was the most potent statin until it was withdrawn from the market due to a number of fatalities due to rhabdomyolysis, however, the dose-related magnitude of effect of cerivastatin on blood lipids is not known. OBJECTIVES: Primary objective To quantify the effects of various doses of cerivastatin on the surrogate markers: LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides in children and adults with and without cardiovascular disease. The aim of this review is to examine the pharmacology of cerivastatin by characterizing the dose-related effect and variability of the effect of cerivastatin on surrogate markers. Secondary objectives To quantify the effect of various doses of cerivastatin compared to placebo on withdrawals due to adverse effects. To compare the relative potency of cerivastatin with respect to fluvastatin, atorvastatin and rosuvastatin for LDL cholesterol, total cholesterol, HDL cholesterol and triglycerides. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for RCTs up to March 2019: CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov.We also searched the European Patent Office, FDA.gov, and ProQuest Dissertations & Theses, and contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: RCTs and controlled before-and-after studies evaluating the dose response of different fixed doses of cerivastatin on blood lipids over a duration of three to 12 weeks in participants of any age with and without cardiovascular disease. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility criteria for trials to be included and extracted data. We entered data from RCTs and controlled before-and-after studies into Review Manager 5 as continuous and generic inverse variance data respectively. We collected information on withdrawals due to adverse effects from the RCTs. We assessed all trials using the 'Risk of bias' tool under the categories of sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases. MAIN RESULTS: Fifty trials (19 RCTs and 31 before-and-after studies) evaluated the dose-related efficacy of cerivastatin in 12,877 participants who had their LDL cholesterol measured. The participants were of any age with and without cardiovascular disease and the trials studied cerivastatin effects within a treatment period of three to 12 weeks. Cerivastatin 0.025 mg/day to 0.8 mg/day caused LDL cholesterol decreases of 11.0% to 40.8%, total cholesterol decreases of 8.0% to 28.8% and triglyceride decreases of 9.0% to 21.4%. We judged the certainty of evidence for these effects to be high. Log dose-response data over doses of 2.5 mg to 80 mg revealed strong linear dose-related effects on LDL cholesterol, total cholesterol and triglycerides. When compared to fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin at reducing LDL cholesterol; 233-fold more potent than fluvastatin, 18-fold more potent than atorvastatin and six-fold more potent than rosuvastatin at reducing total cholesterol; and 125-fold more potent than fluvastatin, 11-fold more potent than atorvastatin and 13-fold more potent than rosuvastatin at reducing triglycerides. There was no dose-related effect of cerivastatin on HDL cholesterol, but overall cerivastatin increased HDL cholesterol by 5%. There was a high risk of bias for the outcome withdrawals due to adverse effects, but a low risk of bias for the lipid measurements. Withdrawals due to adverse effects were not different between cerivastatin and placebo in 11 of 19 of these short-term trials (risk ratio 1.09, 95% confidence interval 0.68 to 1.74). AUTHORS' CONCLUSIONS: The LDL cholesterol, total cholesterol, and triglyceride lowering effect of cerivastatin was linearly dependent on dose. Cerivastatin log dose-response data were linear over the commonly prescribed dose range. Based on an informal comparison with fluvastatin, atorvastatin and rosuvastatin, cerivastatin was about 250-fold more potent than fluvastatin, 20-fold more potent than atorvastatin and 5.5-fold more potent than rosuvastatin in reducing LDL cholesterol, and 233-fold greater potency than fluvastatin, 18-fold greater potency than atorvastatin and six-fold greater potency than rosuvastatin at reducing total cholesterol. This review did not provide a good estimate of the incidence of harms associated with cerivastatin because of the short duration of the trials and the lack of reporting of adverse effects in 42% of the RCTs.

3.
J Clin Epidemiol ; 117: 109-116, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31610216

RESUMO

OBJECTIVES: The aim of the study was to validate search filters for retrieval of clinical practice guidelines (CPGs) in MEDLINE, Embase, and PubMed. STUDY DESIGN AND SETTING: A search for filters for identifying CPGs was conducted in Google and the InterTASC Information Specialists Sub-Group Search Filter Resource. To retrieve a random sample of CPGs to test sensitivity and precision of the filters, we used the TRIP and Epistemonikos databases. The citations were screened independently by two researchers. The sensitivity and precision were calculated. RESULTS: Five search filters were retrieved: two from the Canadian Agency for Drugs and Technologies in Health (CADTH), two from the University of Texas, and one from the MD Anderson Cancer Center Library. A total of 478 records were screened to identify 109 CPGs, which comprised the sample for testing sensitivity and precision. The sensitivity ranged from 87% to 98% for the five search filters and very low precision (<1%) across all databases. CONCLUSION: Knowledge users who are interested in retrieving all relevant CPGs can use the CADTH broad filter with the highest sensitivity. However, our analysis shows that it remains difficult to efficiently identify CPGs because of low precision of five search filters. We recommend searching guideline-specific resources as a more time-efficient approach than searching bibliographic databases.

5.
Vasc Endovascular Surg ; 54(3): 205-213, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31876253

RESUMO

INTRODUCTION: Spinal cord injury (SCI) is a known complication of aortic aneurysm repair. Previous reports indicate that cerebrospinal fluid drainage (CSFD) may reduce incidence of SCI during open aortic aneurysm repair but its utility in endovascular repair remains poorly understood. We performed a systematic review of the literature to examine the protocols and outcomes of CSFD in patients undergoing endovascular aortic aneurysm repair. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were utilized to conduct a systematic literature review. PubMed, Scopus, Ovid, Cochrane, and EMBASE were queried for articles published since 2016 using search terms "(cerebrospinal fluid diversion OR CSF diversion OR lumbar drain OR subarachnoid drain OR spinal) AND (aortic aneurysm AND thoracic AND endovascular OR TEVAR)." Ninety-two articles were identified and screened by 2 independent reviewers, and 23 studies met criteria for full-text review after initial screening. RESULTS: A total of 8 studies met full inclusion criteria for final analysis. Six studies reported incidence of SCI in patients with CSFD and 2 compared SCI incidence between patients with and without CSFD. Protocols for drainage most commonly included draining to a target pressure intra- and postoperatively, between 8 and 12 mm Hg. Incidence of SCI ranged from 0% to 17% in patients with CSFD, and from 0% to 50% in those without CSFD. Rates of CSFD-related complications ranged from <1% to 28%. CONCLUSION: There may be a protective benefit of CSFD in preventing SCI, but there remains significant variation in drain placement protocols. Significant potential bias exists in the reviewed data. Higher quality studies on the role of CSFD in endovascular aortic aneurysm repair are needed.

6.
Arch Pathol Lab Med ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31825669

RESUMO

CONTEXT.­: Frederick Banting, Charles Best, J. Bertrand Collip, and J. J. R. Macleod contributed to the discovery of insulin in 1921-1922. Recent advances in anatomic pathology, experimental pathology, and clinical pathology were necessary for the research in Toronto, Ontario, Canada, to begin and to succeed. OBJECTIVE.­: To explore the role of pathology and laboratory medicine in laying the foundation for the discovery of insulin. DESIGN.­: Available primary and secondary historical sources were reviewed. RESULTS.­: During a 3-decade period, pathologists, through autopsy pathology and experimental animal studies, were able to provide solid evidence that the pancreatic islets were the source of the internal secretion responsible for proper carbohydrate metabolism. Banting, a surgeon with no previous research experience, read about these studies in a case report with an extensive literature review by pathologist Moses Barron; this piqued Banting's interest and caused him to approach Macleod, a Toronto physiology professor, with an idea that initiated the research. Advances in clinical laboratory medicine, which allowed them to measure blood glucose levels using small blood volumes, were critical to their success. CONCLUSIONS.­: By 1921-1922, the pieces necessary to solve the puzzle were available. The primary reason that the time was ripe for the discovery was because of the contributions of pathologists and laboratory physicians in the preceding 3 decades. As the 100th anniversary approaches, our profession can take pride in its important contributions to the discovery of insulin, which is broadly recognized as one of the most important medical research advances of the 20th century.

7.
Ecol Evol ; 9(22): 12586-12599, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31788199

RESUMO

Due to a long running research bias toward the breeding season, there are major gaps in knowledge on the basic nonbreeding ecology of many species, preventing a full-annual cycle focus in ecology and conservation. Exacerbating this problem is the fact that many species are extremely difficult to detect outside of breeding. Here, we demonstrate a partial solution to this problem by using archival GPS tags to examine the overwintering ecology of a migratory nocturnal bird, the eastern whip-poor-will (Antrostomus vociferous). We deployed tags on 21 individuals and were able to recover 11 (52%) one year later. Tags collected high precision (approx. 10 m) points throughout the nonbreeding period. With continuous time movement models, we used these data to estimate overwintering home ranges. All individuals exhibited at least one bounded home range during this phase of the annual cycle, three of eleven had two wintering locations, and home range area ranged from 0.50 to 10.85 ha. All overwintering home ranges contained closed-canopy forest land cover (42%-100%), and no other land cover type represented >40% of any home range. We found some evidence, with caveats, that total edge within the landscape surrounding the home range was negatively related to home range area. The prevalence of contiguous closed-canopy forest cover in overwintering home ranges contrasts with apparent breeding habitat preferences, which includes clear-cuts and other, more open, habitats. This study is the first to reveal key aspects of overwintering space use in this species by using archival GPS to overcome both logistical and methodological limitations. Expanded use of such technology is critical to gathering basic ecological and distributional data, necessary for achieving a more complete understanding of full-annual cycles of animal populations.

8.
Dig Dis Sci ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31797188

RESUMO

Termed by the Lancet, as "potentially the most important medical advance of the twentieth century," therapy with oral rehydration solutions (ORSs) has been essential to reducing mortality in children less than 5 years (under five) with infectious gastroenteritis and diarrhea. The target of the diarrhea-control programs in the 1990s was to achieve ORS use in 80% of diarrhea cases by the year 2000. Nevertheless, nearly 20 years later, global uptake remains limited to only a third of the cases. Our analysis shows that from 1990 to 2017, mean ORS coverage in Countdown countries [the 81 Countdown-to-2030 priority countries, which together account for 95% of maternal deaths and 90% of under-five deaths] increased from ~ 30% to nearly 40%. Flawed government policies, inadequate supplies, and lack of awareness among health workers and communities all contributed to this shortfall in coverage. Moreover, imperfect measurement methodology is implicated in questionable coverage data. A multipronged approach focusing on the manufacture, supply, training, and behavioral change is essential to ensure that ORS is used in all epidemic diarrhea cases globally, especially in the under-five population.

9.
J Pain Res ; 12: 3079-3098, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814752

RESUMO

Background: Chronic postsurgical pain (CPSP) is a surgical complication associated with increased functional disability, psychological distress, and economic costs. The aims of this paper were to prospectively: (1) examine the incidence of CPSP 6 and 12 months after pediatric major surgery; (2) identify pain intensity and pain unpleasantness trajectories before, and up to 12 months after, surgery; (3) identify pre-operative factors that predict pain trajectory group membership; and (4) identify predictors of 12-month functional disability. Methods: This study followed 265 children aged 8-17 years at four time points (pre-surgical [T0], in-hospital [T1], 6 [T2] and 12 [T3] months after surgery). Children and parents completed pain and psychological questionnaires. In-hospital physical activity was monitored using actigraphy. Results and discussion: The incidence of moderate-to-severe CPSP at 6 and 12 months was 35% (95% CI 29.1% to 41.9%) and 38% (95% CI 32.4% to 45.1%), respectively. Three percent (95% CI 1.17% to 6.23%) and 4% (95% CI 1.45% to 6.55%) of children reported using opioids to manage pain at 6 and 12 months, respectively. Growth mixture modeling revealed a two-class trajectory model with a quadratic slope best fit the data for both pain intensity (Bayesian information criterion [BIC] = 3977.03) and pain unpleasantness (BIC = 3644.45) over the 12 months. Preoperative functional disability and cumulative in-hospital opioid consumption predicted pain intensity trajectories. Preoperative functional disability predicted pain unpleasantness trajectories. Preoperative functional disability (OR: 1.05, 95% CI: 1.01 to 1.09) and pain unpleasantness trajectories (OR: 2.59, 95% CI: 1.05 to 6.37) predicted 12-month moderate-to-severe functional disability. Conclusion: Pre-surgical functional disability is the only factor that predicts both 12-month functional disability and the course of pain intensity and pain unpleasantness ratings over the 12-month period.

10.
Neurooncol Pract ; 6(6): 451-462, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832215

RESUMO

Background: Glioblastoma (GBM) is the most common and most malignant glioma. Nonglioblastoma (non-GBM) gliomas (WHO Grades II and III) are invasive and also often fatal. The goal of this study is to determine whether sex differences exist in glioma survival. Methods: Data were obtained from the National Cancer Database (NCDB) for years 2010 to 2014. GBM (WHO Grade IV; N = 2073) and non-GBM (WHO Grades II and III; N = 2963) were defined using the histology grouping of the Central Brain Tumor Registry of the United States. Non-GBM was divided into oligodendrogliomas/mixed gliomas and astrocytomas. Sex differences in survival were analyzed using Kaplan-Meier and multivariable Cox proportional hazards models adjusted for known prognostic variables. Results: There was a female survival advantage in patients with GBM both in the unadjusted (P = .048) and adjusted (P = .003) models. Unadjusted, median survival was 20.1 months (95% CI: 18.7-21.3 months) for women and 17.8 months (95% CI: 16.9-18.7 months) for men. Adjusted, median survival was 20.4 months (95% CI: 18.9-21.6 months) for women and 17.5 months (95% CI: 16.7-18.3 months) for men. When stratifying by age group (18-55 vs 56+ years at diagnosis), this female survival advantage appeared only in the older group, adjusting for covariates (P = .017). Women (44.1%) had a higher proportion of methylated MGMT (O6-methylguanine-DNA methyltransferase) than men (38.4%). No sex differences were found for non-GBM. Conclusions: Using the NCDB data, there was a statistically significant female survival advantage in GBM, but not in non-GBM.

11.
Clin Anat ; 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31837170

RESUMO

U.S. Army doctor Daniel Smith Lamb was a significant figure in the history of American pathology during its formative years. For 55 years (1865-1920), Lamb performed hundreds of autopsies in and around Washington, D.C. and personally collected over 1,500 gross pathology specimens for the Army Medical Museum. His work began at the close of the Civil War and continued on through World War I, contributing substantially to gross pathological and histological studies that documented wartime pathology, thus further contributing to the training of Army doctors. Specimens he collected also include material from autopsies he conducted on President James Garfield, his assassin Charles Guiteau, and other historical figures. Under the auspices of the Army Medical Museum, he conducted autopsies across the city of Washington for the museum's collection, many of which survive to this day at the National Museum of Health and Medicine. He served under 12 U.S. Army Surgeons General and 11 Museum Curators and was noted to be a steadying influence during a time of constant leadership changes at that institution. Lamb was known throughout Washington, D.C. as an advocate of medical education for African-Americans and women. While working at the Museum, he simultaneously served for 46 years as professor of anatomy at Howard University (1877-1923). He wrote seminal histories of the institutions with which he was associated and in so doing also contributed significantly to the study of the history of medicine.

12.
Data Brief ; 27: 104666, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31700961

RESUMO

This data article describes data of magnetic stratigraphy and anisotropy of isothermal remanent magnetization (AIRM) from "Magnetic properties of early Pliocene sediments from IODP Site U1467 (Maldives platform) reveal changes in the monsoon system" [1]. Acquisition of isothermal magnetization on pilot samples and anisotropy of isothermal remanent magnetization are reported as raw data; magnetostratigraphic data are reported as characteristic magnetization (ChRM).

13.
J Neurosurg Spine ; : 1-10, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675723

RESUMO

OBJECTIVE: Chordomas of the spine and sacrum are a rare but debilitating cancer and require complex multidisciplinary care. Studies of other such rare cancers have demonstrated an association of high-volume and/or multidisciplinary centers with improved outcomes and survival. Such an association has been proposed for chordomas, but evidence to support this claim is lacking. The authors performed a study to investigate if treatment facility type is associated with patterns of care and survival for patients with spinal and sacral chordomas by assessing records from a US-based cancer database. METHODS: In this observational retrospective cohort study, the authors identified 1266 patients from the National Cancer Database with vertebral column or sacral chordomas diagnosed between 2004 and 2015. The primary study outcome was overall survival, and secondary outcomes included odds of receiving treatment and time to treatment, defined as radiation therapy, surgery, and/or any treatment, including surgery, radiation therapy, chemotherapy, or participation in clinical trials. The results were adjusted for age, sex, race/ethnicity, level of education, income, and Charlson/Deyo score. RESULTS: Of the 1266 patients identified, the mean age at diagnosis was 59.70 years (SD 16.2 years), and the patients were predominantly male (n = 791 [62.50%]). Patients treated at community cancer programs demonstrated an increased risk of death (HR 1.98, 95% CI 1.13-3.47, p = 0.018) when compared to patients treated at academic/research programs (ARPs). The median survival was longest for those treated at ARPs (131.45 months) compared to community cancer programs (79.34 months, 95% CI 48.99-123.17) and comprehensive community cancer programs (CCCPs) (109.34 months, 95% CI 84.76-131.45); 5-year survival rates were 76.08%, 52.71%, and 61.57%, respectively. Patients treated at community cancer programs and CCCPs were less likely to receive any treatment compared to those treated at ARPs (OR 6.05, 95% CI 2.62-13.95, p < 0.0001; OR 3.74, 95% CI 2.23-6.28, p < 0.0001, respectively). Patients treated at CCCPs and community cancer programs were less likely to receive surgery than those treated at ARPs (OR 2.69, 95% CI 1.82-3.97, p = 0.010; OR = 2.64, 95% CI 1.22-5.71, p = 0.014, respectively). Patients were more likely to receive any treatment (OR 0.59, 95% CI 0.40-0.87, p = 0.007) and surgery (OR 0.58, 95% CI 0.38-0.88, p < 0.0001) within 30 days at a CCCP compared to an ARP. There were no differences in odds of receiving radiation therapy or time to radiation by facility type. CONCLUSIONS: Clinical care at an ARP is associated with increased odds of receiving treatment that is associated with improved overall survival for patients with spinal and sacral chordomas, suggesting that ARPs provide the most comprehensive specialized care for patients with this rare and devastating oncological disease.

14.
Ecol Evol ; 9(19): 11064-11077, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31641455

RESUMO

Climate change is predicted to impact tropical mangrove forests due to decreased rainfall, sea-level rise, and increased seasonality of flooding. Such changes are likely to influence habitat quality for migratory songbirds occupying mangrove wetlands during the tropical dry season. Overwintering habitat quality is known to be associated with fitness in migratory songbirds, yet studies have focused primarily on territorial species. Little is known about the ecology of nonterritorial species that may display more complex movement patterns within and among habitats of differing quality. In this study, we assess within-season survival and movement at two spatio-temporal scales of a nonterritorial overwintering bird, the prothonotary warbler (Protonotaria citrea), that depends on mangroves and tropical lowland forests. Specifically, we (a) estimated within-patch survival and persistence over a six-week period using radio-tagged birds in central Panama and (b) modeled abundance and occupancy dynamics at survey points throughout eastern Panama and northern Colombia as the dry season progressed. We found that site persistence was highest in mangroves; however, the probability of survival did not differ among habitats. The probability of warbler occupancy increased with canopy cover, and wet habitats were least likely to experience local extinction as the dry season progressed. We also found that warbler abundance is highest in forests with the tallest canopies. This study is one of the first to demonstrate habitat-dependent occupancy and movement in a nonterritorial overwintering migrant songbird, and our findings highlight the need to conserve intact, mature mangrove, and lowland forests.

15.
Eur J Pediatr Surg ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600801

RESUMO

INTRODUCTION: There are no evidence-based guidelines on the surgical management of esophageal achalasia (OA) in children. This can be a challenging condition with significant physical and psychological morbidity. Our aim was to identify the most common management modalities and their outcomes. MATERIALS AND METHODS: A systematic review was performed through a literature search of health care databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, aiming at identifying pediatric series discussing the diagnosis and management of OA. Duplicates, case series with < 9 patients, and follow-up of < 1 year were excluded. The included papers were analyzed for diagnostic methods, primary treatment method, complications, follow-up duration, outcome measures recorded, and outcome. RESULTS: Data from 33 papers for 742 children treated for OA was analyzed. Eleven mentioned multiple management modalities. In summary, 25 described Heller's esophagomyotomy (HM), 13 esophageal dilatation (EOD), and 6 peroral esophageal myotomy (POEM). Mean follow-up was 43.7 months (12-180). Outcome measures were heterogeneous. However, analysis of reported success showed a mean success of 78% for HM (p = 1.79 × 10-7), 44.9% for EOD (p = 0.24), and 99.3% for POEM (p = 0.001). Reported complications were 12.8% for HM, 5% for EOD, and 24.4% for POEM. Further interventions were required for 10.9% of HM, 62.3% of EOD, and 0.01% of POEM patient groups. CONCLUSION: Methods of diagnosis and measures of successful outcomes were heterogeneous, limiting the strength of evidence. HM showed superior short-term success rates to EOD. POEM is a promising modality but requires investment in equipment and training. Information about sustainability of response and long-term outcomes is lacking.

16.
J Am Med Dir Assoc ; 20(11): 1362-1366, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31588024

RESUMO

The Ethics Subcommittee of AMDA-The Society for Post-Acute and Long-Term Care Medicine ("The Society") presents arguments for and against Stopping Eating and Drinking by Advance Directives (SED by AD). SED by AD is a type of advance directive in which a proxy is instructed to stop offering food and fluids to a person when they reach a certain stage of dementia. Although most conversations regarding SED by AD focus on patient autonomy and the right to determine one's care, we propose that the ethical principle of justice-the obligation to treat all individuals equally regardless of race, gender, and physical or cognitive ability-is the decisive principle in this controversy. We also suggest that implementing SED by AD can violate a physician's obligation to beneficence and nonmaleficence. On the other hand, we identify with the families of our patients who see the refusal to follow an advance directive as an injustice of the highest order. In the end, The Society is convinced that no choice can be made here without practicing an injustice: if one refuses to implement SED by AD, one violates the autonomy of the person who drew up the advance directive. If, on the other hand, one refuses food and fluid to a resident who still accepts food, one risks practicing an injustice against that person as they are now. Recognizing that we have the greatest responsibility to our patients as they present to us in the residential setting, The Society recommends against implementing SED by AD in residents who still accept food and fluids, implementing instead, a policy of comfort feeding for those with advanced dementia.

17.
J Feline Med Surg ; : 1098612X19875831, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566070

RESUMO

OBJECTIVES: Phage-gonadotropin-releasing hormone (GnRH) constructs with potential contraceptive properties were generated in our previous study via selection from a phage display library using neutralizing GnRH antibodies as selection targets. In mice, these constructs invoked the production of antibodies against GnRH and suppressed serum testosterone. The goal of this study was to evaluate this vaccine against GnRH for its potential to suppress reproductive characteristics in cats. METHODS: Sexually mature male cats were injected with a phage-GnRH vaccine using the following treatment groups: (1) single phage-GnRH vaccine with adjuvant; (2) phage-GnRH vaccine without adjuvant and half-dose booster 1 month later; or (3) phage-GnRH vaccine with adjuvant and two half-dose boosters with adjuvant 3 and 6 months later. Anti-GnRH antibodies and serum testosterone, testicular volume and sperm characteristics were evaluated monthly for 7-9 months. RESULTS: All cats developed anti-GnRH antibodies following immunization. Serum antibody titers increased significantly after booster immunizations. In group 3, serum testosterone was suppressed 8 months after primary immunization. Total testicular volume decreased in group 1 by 24-42% and in group 3 by 15-36% at 7 months after immunization, indicating potential gonadal atrophy. Vacuolation of epididymides was observed histologically. Although all cats produced sperm at the conclusion of the study, normal morphology was decreased as much as 38%. Phage alone produced no local or systemic reactions. Immunization of phage with AdjuVac produced unacceptable injection site reactions. CONCLUSIONS AND RELEVANCE: Our phage-based vaccine against GnRH demonstrated a potential for fertility impairment in cats. Future research is required to optimize vaccine regimens and identify animal age groups most responsive to the vaccine. If permanent contraception (highly desirable in feral and shelter cats) cannot be achieved, the vaccine has a potential use in zoo animals or pets where multiple administrations are more practical and/or reversible infertility is desirable.

18.
Med Care ; 57(11): 875-881, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31567859

RESUMO

OBJECTIVE: Until recently, the options for summarizing Canadian patient complexity were limited to health risk predictive modeling tools developed outside of Canada. This study aims to validate a new model created by the Canadian Institute for Health Information (CIHI) for Canada's health care environment. RESEARCH DESIGN: This was a cohort study. SUBJECTS: The rolling population eligible for coverage under Ontario's Universal Provincial Health Insurance Program in the fiscal years (FYs) 2006/2007-2016/2017 (12-13 million annually) comprised the subjects. MEASURES: To evaluate model performance, we compared predicted cost risk at the individual level, on the basis of diagnosis history, with estimates of actual patient-level cost using "out-of-the-box" cost weights created by running the CIHI software "as is." We next considered whether performance could be improved by recalibrating the model weights, censoring outliers, or adding prior cost. RESULTS: We were able to closely match model performance reported by CIHI for their 2010-2012 development sample (concurrent R=48.0%; prospective R=8.9%) and show that performance improved over time (concurrent R=51.9%; prospective R=9.7% in 2014-2016). Recalibrating the model did not substantively affect prospective period performance, even with the addition of prior cost and censoring of cost outliers. However, censoring substantively improved concurrent period explanatory power (from R=53.6% to 66.7%). CONCLUSIONS: We validated the CIHI model for 2 periods, FYs 2010/2011-2012/2013 and FYs 2014/2015-2016/2017. Out-of-the-box model performance for Ontario was as good as that reported by CIHI for the development sample based on 3-province data (British Columbia, Alberta, and Ontario). We found that performance was robust to variations in model specification, data sources, and time.


Assuntos
Custos de Cuidados de Saúde/estatística & dados numéricos , Modelos Econômicos , Medição de Risco/métodos , Estatística como Assunto/métodos , Cobertura Universal do Seguro de Saúde/economia , Canadá , Estudos de Coortes , Humanos
19.
Chem Commun (Camb) ; 55(82): 12312-12315, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31559993

RESUMO

Water soluble squaramide macrocycles (MSQs) display high sulfate binding affinities in aqueous DMSO mixtures. The introduction of pyridine spacers into the macrocycles resulted in increased sulfate binding affinity in comparison to compounds with benzene spacers. [3]MSQ 6 was found to be a selective ligand for SO42- in highly competitive conditions and over a wide pH range (3.2-14).

20.
Genome Res ; 29(12): 2073-2087, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31537640

RESUMO

The most widely appreciated role of DNA is to encode protein, yet the exact portion of the human genome that is translated remains to be ascertained. We previously developed PhyloCSF, a widely used tool to identify evolutionary signatures of protein-coding regions using multispecies genome alignments. Here, we present the first whole-genome PhyloCSF prediction tracks for human, mouse, chicken, fly, worm, and mosquito. We develop a workflow that uses machine learning to predict novel conserved protein-coding regions and efficiently guide their manual curation. We analyze more than 1000 high-scoring human PhyloCSF regions and confidently add 144 conserved protein-coding genes to the GENCODE gene set, as well as additional coding regions within 236 previously annotated protein-coding genes, and 169 pseudogenes, most of them disabled after primates diverged. The majority of these represent new discoveries, including 70 previously undetected protein-coding genes. The novel coding genes are additionally supported by single-nucleotide variant evidence indicative of continued purifying selection in the human lineage, coding-exon splicing evidence from new GENCODE transcripts using next-generation transcriptomic data sets, and mass spectrometry evidence of translation for several new genes. Our discoveries required simultaneous comparative annotation of other vertebrate genomes, which we show is essential to remove spurious ORFs and to distinguish coding from pseudogene regions. Our new coding regions help elucidate disease-associated regions by revealing that 118 GWAS variants previously thought to be noncoding are in fact protein altering. Altogether, our PhyloCSF data sets and algorithms will help researchers seeking to interpret these genomes, while our new annotations present exciting loci for further experimental characterization.

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