Since the first reports of a novel severe acute respiratory syndrome (SARS)-like coronavirus in December 2019 in Wuhan, China, there has been intense interest in understanding how severe acute ...respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the human population. Recent debate has coalesced around two competing ideas: a “laboratory escape” scenario and zoonotic emergence. Here, we critically review the current scientific evidence that may help clarify the origin of SARS-CoV-2.
A review of the current literature supports a zoonotic origin for SARS-CoV-2 and emphasizes the need to focus on identifying the exact animal host through collaborative and carefully coordinated studies. This will enable the community to understand the roots of the COVID-19 pandemic as well as better prepare us for future pandemics
Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert ...panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
Social valuation of ecosystem services and public policy alternatives is one of the greatest challenges facing ecological economists today. Frameworks for valuing nature increasingly include ...shared/social values as a distinct category of values. However, the nature of shared/social values, as well as their relationship to other values, has not yet been clearly established and empirical evidence about the importance of shared/social values for valuation of ecosystem services is lacking. To help address these theoretical and empirical limitations, this paper outlines a framework of shared/social values across five dimensions: value concept, provider, intention, scale, and elicitation process. Along these dimensions we identify seven main, non-mutually exclusive types of shared values: transcendental, cultural/societal, communal, group, deliberated and other-regarding values, and value to society. Using a case study of a recent controversial policy on forest ownership in England, we conceptualise the dynamic interplay between shared/social and individual values. The way in which social value is assessed in neoclassical economics is discussed and critiqued, followed by consideration of the relation between shared/social values and Total Economic Value, and a review of deliberative and non-monetary methods for assessing shared/social values. We conclude with a discussion of the importance of shared/social values for decision-making.
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•Individualist valuation approaches obscure and underplay collective meanings and significance ascribed to natural environments•There is a lack of theoretical and empirical clarity on what constitutes shared and social values and how they can be assessed•We provide a theoretical framework to discriminate dimensions of shared/social values and an overview of valuation methods•A shared values approach to valuation can enhance legitimacy, effectiveness and transparency of evidence and help manage risks
Evidence-based guidelines for implementation and measurement of antibiotic stewardship interventions in inpatient populations including long-term care were prepared by a multidisciplinary expert ...panel of the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. The panel included clinicians and investigators representing internal medicine, emergency medicine, microbiology, critical care, surgery, epidemiology, pharmacy, and adult and pediatric infectious diseases specialties. These recommendations address the best approaches for antibiotic stewardship programs to influence the optimal use of antibiotics.
Research and clinical translation in schizophrenia is limited by inconsistent definitions of treatment resistance and response. To address this issue, the authors evaluated current approaches and ...then developed consensus criteria and guidelines.
A systematic review of randomized antipsychotic clinical trials in treatment-resistant schizophrenia was performed, and definitions of treatment resistance were extracted. Subsequently, consensus operationalized criteria were developed through 1) a multiphase, mixed methods approach, 2) identification of key criteria via an online survey, and 3) meetings to achieve consensus.
Of 2,808 studies identified, 42 met inclusion criteria. Of these, 21 studies (50%) did not provide operationalized criteria. In the remaining studies, criteria varied considerably, particularly regarding symptom severity, prior treatment duration, and antipsychotic dosage thresholds; only two studies (5%) utilized the same criteria. The consensus group identified minimum and optimal criteria, employing the following principles: 1) current symptoms of a minimum duration and severity determined by a standardized rating scale; 2) moderate or worse functional impairment; 3) prior treatment consisting of at least two different antipsychotic trials, each for a minimum duration and dosage; 4) systematic monitoring of adherence and meeting of minimum adherence criteria; 5) ideally at least one prospective treatment trial; and 6) criteria that clearly separate responsive from treatment-resistant patients.
There is considerable variation in current approaches to defining treatment resistance in schizophrenia. The authors present consensus guidelines that operationalize criteria for determining and reporting treatment resistance, adequate treatment, and treatment response, providing a benchmark for research and clinical translation.
Positive allosteric modulators (PAMs) of the mu-opioid receptor (MOR) have been hypothesized as potentially safer analgesics than traditional opioid drugs. This is based on the idea that PAMs will ...promote the action of endogenous opioid peptides while preserving their temporal and spatial release patterns and so have an improved therapeutic index. However, this hypothesis has never been tested. Here, we show that a mu-PAM, BMS-986122, enhances the ability of the endogenous opioid Methionine-enkephalin (Met-Enk) to stimulate G protein activity in mouse brain homogenates without activity on its own and to enhance G protein activation to a greater extent than β-arrestin recruitment in Chinese hamster ovary (CHO) cells expressing human mu-opioid receptors. Moreover, BMS-986122 increases the potency of Met-Enk to inhibit GABA release in the periaqueductal gray, an important site for antinociception. We describe in vivo experiments demonstrating that the mu-PAM produces antinociception in mouse models of acute noxious heat pain as well as inflammatory pain. These effects are blocked by MOR antagonists and are consistent with the hypothesis that in vivo mu-PAMs enhance the activity of endogenous opioid peptides. Because BMS-986122 does not bind to the orthosteric site and has no inherent agonist action at endogenously expressed levels of MOR, it produces a reduced level of morphine-like side effects of constipation, reward as measured by conditioned place preference, and respiratory depression. These data provide a rationale for the further exploration of the action and safety of mu-PAMs as an innovative approach to pain management.
Background
Guidelines have changed recently to include genetic counseling (GC) and/or genetic testing (GT) for all men with aggressive prostate cancer (PCa). This study aimed to identify what ...information men with PCa desire before and from GC.
Methods
Focus groups were conducted with men who have PCa. Audio recordings were analyzed for themes related to GT, the information they desired from health care providers, and implications for family members.
Results
Thirty‐seven men with PCa participated in seven focus groups. Nearly all men felt GT was beneficial and impactful for their family and themselves. Most men were unaware of the risks to female relatives associated with hereditary cancer. Participants discussed that genetics should be incorporated at an appropriate time of their diagnostic journey.
Conclusion
This study showed that men valued GC and GT for personal and familial implications, and often did not associate PCa genetics with risk for female relatives to develop cancer. Consideration should be given to the GC timing in regard to where men are in their treatment process. Providers referring patients can leverage patient motivations and utilize their relationship with the patient to determine the appropriate timing and personalize discussion with the patient regarding GC and GT.
The use of optical techniques to interrogate wide ranging samples from semiconductors to biological tissue for rapid analysis and diagnostics has gained wide adoption over the past decades. The ...desire to collect ever more spatially, spectrally and temporally detailed optical signatures for sample characterization has specifically driven a sharp rise in new optical microscopy technologies. Here we present a high-speed optical scanning microscope capable of capturing time resolved images across 512 spectral and 32 time channels in a single acquisition with the potential for ~0.2 frames per second (256 × 256 image pixels). Each pixel in the resulting images contains a detailed data cube for the study of diverse time resolved light driven phenomena. This is enabled by integration of system control electronics and on-chip processing which overcomes the challenges presented by high data volume and low imaging speed, often bottlenecks in previous systems.
This guideline provides evidence-based recommendations on managing benign paroxysmal positional vertigo (BPPV), which is the most common vestibular disorder in adults, with a lifetime prevalence of ...2.4 percent. The guideline targets patients aged 18 years or older with a potential diagnosis of BPPV, evaluated in any setting in which an adult with BPPV would be identified, monitored, or managed. This guideline is intended for all clinicians who are likely to diagnose and manage adults with BPPV.
The primary purposes of this guideline are to improve quality of care and outcomes for BPPV by improving the accurate and efficient diagnosis of BPPV, reducing the inappropriate use of vestibular suppressant medications, decreasing the inappropriate use of ancillary tests such as radiographic imaging and vestibular testing, and to promote the use of effective repositioning maneuvers for treatment. In creating this guideline, the American Academy of Otolaryngology-Head and Neck Surgery Foundation selected a panel representing the fields of audiology, chiropractic medicine, emergency medicine, family medicine, geriatric medicine, internal medicine, neurology, nursing, otolaryngology-head and neck surgery, physical therapy, and physical medicine and rehabilitation.
The panel made strong recommendations that 1) clinicians should diagnose posterior semicircular canal BPPV when vertigo associated with nystagmus is provoked by the Dix-Hallpike maneuver. The panel made recommendations against 1) radiographic imaging, vestibular testing, or both in patients diagnosed with BPPV, unless the diagnosis is uncertain or there are additional symptoms or signs unrelated to BPPV that warrant testing; and 2) routinely treating BPPV with vestibular suppressant medications such as antihistamines or benzodiazepines. The panel made recommendations that 1) if the patient has a history compatible with BPPV and the Dix-Hallpike test is negative, clinicians should perform a supine roll test to assess for lateral semicircular canal BPPV; 2) clinicians should differentiate BPPV from other causes of imbalance, dizziness, and vertigo; 3) clinicians should question patients with BPPV for factors that modify management including impaired mobility or balance, CNS disorders, lack of home support, and increased risk for falling; 4) clinicians should treat patients with posterior canal BPPV with a particle repositioning maneuver (PRM); 5) clinicians should reassess patients within 1 month after an initial period of observation or treatment to confirm symptom resolution; 6) clinicians should evaluate patients with BPPV who are initial treatment failures for persistent BPPV or underlying peripheral vestibular or CNS disorders; and 7) clinicians should counsel patients regarding the impact of BPPV on their safety, the potential for disease recurrence, and the importance of follow-up. The panel offered as options that 1) clinicians may offer vestibular rehabilitation, either self-administered or with a clinician, for the initial treatment of BPPV and 2) clinicians may offer observation as initial management for patients with BPPV and with assurance of follow-up. The panel made no recommendation concerning audiometric testing in patients diagnosed with BPPV.
This clinical practice guideline is not intended as a sole source of guidance in managing benign paroxysmal positional vertigo. Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. The guideline is not intended to replace clinical judgement or establish a protocol for all individuals with this condition, and may not provide the only appropriate approach to diagnosing and managing this problem.
Objectives
To compare the strength of the association between depression and mortality between elderly and younger individuals with diabetes mellitus.
Design
A survival analysis conducted in a ...longitudinal cohort study of persons with diabetes mellitus to test the association between depression and mortality in older (≥65) and younger (18–65) adults.
Setting
Managed care.
Participants
Persons aged 18 and older with diabetes mellitus who participated in the Wave 2 survey of the Translating Research Into Action for Diabetes (TRIAD) Study (N = 3,341).
Measurements
The primary outcome was mortality risk, which was measured as days until death using linked data from the National Death Index. Depression was measured using the Patient Health Questionnaire.
Results
After controlling for age, sex, race and ethnicity, income, and other comorbidities, mortality risk in persons with diabetes mellitus was 49% higher in those with depression than in those without, although results varied according to age. After controlling for the same variables, mortality risk in persons aged 65 and older with depression was 78% greater than in those without. For those younger than 65, the effect of depression on mortality was smaller and not statistically significant.
Conclusion
This analysis suggests that the effect of depression on mortality in persons with diabetes mellitus is most significant for older adults. Because there is evidence in the literature that treatment of depression in elderly adults can lead to lower mortality, these results may suggest that older adults with diabetes mellitus should be considered a high‐priority population for depression screening and treatment.
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