Sepsis is common, deadly, and heterogenous. Prior analyses of patients with sepsis and septic shock in New York State showed a risk-adjusted association between more rapid antibiotic administration ...and bundled care completion, but not an intravenous fluid bolus, with reduced in-hospital mortality. However, it is unknown if clinically identifiable sepsis subtypes modify these associations.
Secondary analysis of patients with sepsis and septic shock enrolled in the New York State Department of Health cohort from January 1, 2015 to December 31, 2016. Patients were classified as clinical sepsis subtypes (α, β, γ, δ-types) using the Sepsis ENdotyping in Emergency CAre (SENECA) approach. Exposure variables included time to 3-h sepsis bundle completion, antibiotic administration, and intravenous fluid bolus completion. Then logistic regression models evaluated the interaction between exposures, clinical sepsis subtypes, and in-hospital mortality.
55,169 hospitalizations from 155 hospitals were included (34% α, 30% β, 19% γ, 17% δ). The α-subtype had the lowest (N = 1,905, 10%) and δ-subtype had the highest (N = 3,776, 41%) in-hospital mortality. Each hour to completion of the 3-h bundle (aOR, 1.04 95%CI, 1.02-1.05) and antibiotic initiation (aOR, 1.03 95%CI, 1.02-1.04) was associated with increased risk-adjusted in-hospital mortality. The association differed across subtypes (p-interactions < 0.05). For example, the outcome association for the time to completion of the 3-h bundle was greater in the δ-subtype (aOR, 1.07 95%CI, 1.05-1.10) compared to α-subtype (aOR, 1.02 95%CI, 0.99-1.04). Time to intravenous fluid bolus completion was not associated with risk-adjusted in-hospital mortality (aOR, 0.99 95%CI, 0.97-1.01) and did not differ among subtypes (p-interaction = 0.41).
Timely completion of a 3-h sepsis bundle and antibiotic initiation was associated with reduced risk-adjusted in-hospital mortality, an association modified by clinically identifiable sepsis subtype.
The current study used U.S. national data to examine drinking trends prior to and during the COVID-19 pandemic in 2020, focusing on changes in U.S. young- and middle-adult alcohol prevalence, ...frequency, and drinking contexts and reasons, and whether they differed by age and college status.
Data from 2015 to 2020 from 16,987 young adults (ages 19–30) and 23,584 middle adults (ages 35–55) in the national Monitoring the Future study were used to model historical trends and potential 2020 shifts (data collection April 1 to November 30, 2020) in prevalence (30-day, daily, binge drinking) and frequency (30-day, binge drinking). For young adults, data on drinking contexts and negative affect reasons for drinking were examined. Moderation by age and college status was also tested.
2020 was associated with (1) downward deviation in 30-day (young and middle adults) and binge drinking (young adults) prevalence; (2) upward deviation in daily drinking prevalence (middle adults); (3) among drinkers, upward deviation in frequency of 30-day (young and middle adults) and binge drinking (young adults); and (4) changes in drinking contexts and reasons among drinkers. Among college students, in particular, 2020 was associated with a downward deviation from expected historical trends in drinking prevalence. Upward deviations in daily prevalence and both binge and 30-day drinking frequency were stronger at ages 25–30 (vs. 19–24) and 35–45 (vs. 50–55).
Among U.S. young and middle adults, deviations from expected historical trends in population alcohol use that occurred during the pandemic included decreases in alcohol use prevalence, increases in alcohol use frequency, and increases in the use of alcohol to relax/relieve tension and because of boredom. These shifts were likely due, in part, to drinking while alone and at home—which increased during the pandemic.
•Longer-term alcohol prevalence trends deviated downward in 2020.•Among those who drank, alcohol frequency deviated upward in 2020.•Drinking to relax/relieve tension and because of boredom deviated upward in 2020.
The present research investigated three approaches to the role of norms in the theory of planned behaviour (TPB). Two studies examined the proposed predictors of intentions to engage in household ...recycling (Studies 1 and 2) and reported recycling behaviour (Study 1). Study 1 tested the impact of descriptive and injunctive norms (personal and social) and the moderating role of self‐monitoring on norm ‐ intention relations. Study 2 examined the role of group norms and group identification and the moderating role of collective self on norm ‐ intention relations. Both studies demonstrated support for the TPB and the inclusion of additional normative variables: attitudes; perceived behavioural control; descriptive; and personal injunctive norms (but not social injunctive norm) emerged as significant independent predictors of intentions. There was no evidence that the impact of norms on intentions varied as a function of the dispositional variables of self‐monitoring (Study 1) or the collective self (Study 2). There was support, however, for the social identity approach to attitude ‐ behaviour relations in that group norms predicted recycling intentions, particularly for individuals who identified strongly with the group. The results of these two studies highlight the critical role of social influence processes within the TPB and the attitude ‐ behaviour context.
BACKGROUND: Donor retention poses a significant problem to blood collection agencies around the world. Previous research using an augmented theory of planned behavior (TPB) approach has demonstrated ...that attitude, subjective norm, self‐efficacy, moral norm, anticipated regret, donation anxiety from prior blood donations, and self‐identity as a blood donor predicts experienced donors' intentions and that intentions, self‐efficacy, moral norm, and anticipated regret may impact upon people's actual blood donation behavior.
STUDY DESIGN AND METHODS: Established blood donors (n = 263) completed questionnaires assessing standard TPB constructs, anticipated regret, moral norm, donation anxiety, and self‐identity as a blood donor. Three months later, a second questionnaire assessing blood donation behavior in the intervening 3 months was mailed and returned by 182 donors.
RESULTS: With structural equation modeling, the final augmented TPB model provided an excellent fit to the data and included a direct path from intention to behavior and indirect paths to behavior through intention for attitude, self‐efficacy, and anticipated regret. Moral norm, donation anxiety, and donor identity indirectly predicted intention through attitude. In total, 51 percent of the variance in donors' attitudes, 86 percent of variance in donors' intentions, and 70 percent of the variance in donors' behavior were accounted for in the final model.
CONCLUSION: An augmented TPB framework proved efficacious in determining the predictors of the intentions and behavior of established blood donors. Further, this framework highlighted the importance of considering in the future how donors' motivations for donating blood may evolve as a function of the number of prior donations.
The cyanobacterial enzyme CylK assembles the cylindrocyclophane natural products by performing two unusual alkylation reactions, forming new carbon-carbon bonds between aromatic rings and secondary ...alkyl halide substrates. This transformation is unprecedented in biology, and the structure and mechanism of CylK are unknown. Here, we report X-ray crystal structures of CylK, revealing a distinctive fusion of a Ca
-binding domain and a β-propeller fold. We use a mutagenic screening approach to locate CylK's active site at its domain interface, identifying two residues, Arg105 and Tyr473, that are required for catalysis. Anomalous diffraction datasets collected with bound bromide ions, a product analog, suggest that these residues interact with the alkyl halide electrophile. Additional mutagenesis and molecular dynamics simulations implicate Asp440 in activating the nucleophilic aromatic ring. Bioinformatic analysis of CylK homologs from other cyanobacteria establishes that they conserve these key catalytic amino acids, but they are likely associated with divergent reactivity and altered secondary metabolism. By gaining a molecular understanding of this unusual biosynthetic transformation, this work fills a gap in our understanding of how alkyl halides are activated and used by enzymes as biosynthetic intermediates, informing enzyme engineering, catalyst design, and natural product discovery.
BACKGROUND: Donor retention is vital to blood collection agencies. Past research has highlighted the importance of early career behavior for long‐term donor retention, yet research investigating the ...determinants of early donor behavior is scarce. Using an extended Theory of Planned Behavior (TPB), this study sought to identify the predictors of first‐time blood donors' early career retention.
STUDY DESIGN AND METHODS: First‐time donors (n = 256) completed three surveys on blood donation. The standard TPB predictors and self‐identity as a donor were assessed 3 weeks (Time 1) and at 4 months (Time 2) after an initial donation. Path analyses examined the utility of the extended TPB to predict redonation at 4 and 8 months after initial donation.
RESULTS: The extended TPB provided a good fit to the data. Post‐Time 1 and 2 behavior was consistently predicted by intention to redonate. Further, intention was predicted by attitudes, perceived control, and self‐identity (Times 1 and 2). Donors' intentions to redonate at Time 1 were the strongest predictor of intention to donate at Time 2, while donors' behavior at Time 1 strengthened self‐identity as a blood donor at Time 2.
CONCLUSION: An extended TPB framework proved efficacious in revealing the determinants of first‐time donor retention in an initial 8‐month period. The results suggest that collection agencies should intervene to bolster donors' attitudes, perceived control, and identity as a donor during this crucial post–first donation period.
Alcohol consumption is a known risk factor for breast cancer. Because breast cancer survivors are already at risk for recurrence, it is important to understand whether these survivors could benefit ...from survivor-specific recommendations for alcohol consumption.
The purpose of this article was to review primary research specific to alcohol and breast cancer survivors to see whether those who consume alcohol experience more adverse effects.
This literature review examined nine cohort studies specific to breast cancer survivors, alcohol consumption, and risks for breast cancer recurrence, breast cancer-specific mortality, and second primary breast cancers.
Current guideline recommendations of a safe limit of one drink per day or less may not protect breast cancer survivors from cancer- related adverse events. The authors recommend that breast cancer survivors be educated about the associated risks of alcohol consumption so that they can make informed decisions about usage.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Guidelines, policies, and warnings have been applied to reduce the use of medications for behavioral and psychological symptoms of dementia (BPSD). Because of rare dangerous side effects, ...antipsychotics have been singled out in these efforts. However, antipsychotics are still prescribed "off label" to hundreds of thousands of seniors residing in nursing homes and communities. Our objective was to evaluate how and why primary-care physicians (PCPs) employ nonpharmacologic strategies and drugs for BPSD.
Semi-structured interviews analyzed via template, immersion and crystallization, and thematic development of 26 PCPs (16 family practice, 10 general internal medicine) in full time primary-care practice for at least 3 years in Northwestern Virginia.
PCPs described 4 major themes regarding BPSD management: (1) nonpharmacologic methods have substantial barriers; (2) medication use is not constrained by those barriers and is perceived as easy, efficacious, reasonably safe, and appropriate; (3) pharmacologic policies decrease the use of targeted medications, including antipsychotics, but also have unintended consequences such as increased use of alternative risky medications; and (4) PCPs need practical evidence-based guidelines for all aspects of BPSD management.
PCPs continue to prescribe medications because they meet patient-oriented goals and because PCPs perceive drugs, including antipsychotics and their alternatives, to be more effective and less dangerous than evidence suggests. To optimally treat BPSD, PCPs need supportive verified prescribing guidelines and access to nonpharmacologic modalities that are as affordable, available, and efficacious as drugs; these require and deserve significant additional research and payer support. Community PCPs should be included in BPSD policy and guideline development.
The COVID-19 pandemic has increased the burden on health systems, particularly in low- and middle-income countries, where health systems already struggle. To meet health workforce planning needs ...during the pandemic, IntraHealth International used two tools created by the World Health Organization (WHO) Regional Office for Europe. The Health Workforce Estimator (HWFE) allows the estimation of the quantity of health workers needed to treat patients during a surge, and the Adaptt Surge Planning Support Tool helps to predict the timing of a surge in cases and the number of health workers and beds needed for predicted caseload. These tools were adapted to fit the African context in a rapid implementation over 5 weeks in one region in Mali and one region in Kenya with the objective to test the feasibility of adapting these tools, which use a Workload Indicators of Staffing Need (WISN)-inspired human resources management methodology, to obtain daily and surge projections of COVID-19 human resources for health needs.
Using a remote team in the US and in-country teams in Mali and Kenya, IntraHealth enacted a phased plan to gather stakeholder support, collect data related to health systems and COVID-19 cases, populate data into the tools, verify modeled results with results on the ground, enact policy measures to meet projected needs, and conduct national training workshops for the ministries of health.
This phased implementation in Mali and Kenya demonstrated that the WISN approach applied to the Health Workforce Estimator and Adaptt tools can be readily adapted to the local context for African countries to rapidly estimate the number of health workers and beds needed to respond to the predicted COVID-19 pandemic caseload. The results may also be used to give a proxy estimate for needed health supplies-e.g., oxygen, medications, and ventilators. Challenges included accurate and timely data collection and updating data. The success of the pilot can be attributed to the adapted WHO tools, the team composition in both countries, access to human resources data, and early support of the ministries of health, with the expectation that this methodology can be applied to other country contexts.
Modified function of immune cells in nasal secretions may play a role in the enhanced susceptibility to respiratory viruses that is seen in smokers. Innate immune cells in nasal secretions have ...largely been characterized by cellular differentials using morphologic criteria alone, which have successfully identified neutrophils as a significant cell population within nasal lavage fluid (NLF) cells. However, flow cytometry may be a superior method to fully characterize NLF immune cells. We therefore characterized immune cells in NLF by flow cytometry, determined the effects of live attenuated influenza virus (LAIV) on NLF and peripheral blood immune cells, and compared responses in samples obtained from smokers and nonsmokers.
In a prospective observational study, we characterized immune cells in NLF of nonsmokers at baseline using flow cytometry and immunohistochemistry. Nonsmokers and smokers were inoculated with LAIV on day 0 and serial nasal lavages were collected on days 1-4 and day 9 post-LAIV. LAIV-induced changes of NLF cells were characterized using flow cytometry. Cell-free NLF was analyzed for immune mediators by bioassay. Peripheral blood natural killer (NK) cells from nonsmokers and smokers at baseline were stimulated in vitro with LAIV followed by flow cytometric and mediator analyses.
CD45(+)CD56(-)CD16(+) neutrophils and CD45(+)CD56(+) NK cells comprised median 4.62% (range 0.33-14.52) and 23.27% (18.29-33.97), respectively, of non-squamous NLF cells in nonsmokers at baseline. LAIV did not induce changes in total NK cell or neutrophil percentages in either nonsmokers or smokers. Following LAIV inoculation, CD16(+) NK cell percentages and granzyme B levels increased in nonsmokers, and these effects were suppressed in smokers. LAIV inoculation enhanced expression of activating receptor NKG2D and chemokine receptor CXCR3 on peripheral blood NK cells from both nonsmokers and smokers in vitro but did not induce changes in CD16(+) NK cells or granzyme B activity in either group.
These data are the first to identify NK cells as a major immune cell type in the NLF cell population and demonstrate that mucosal NK cell cytotoxic function is suppressed in smokers following LAIV. Altered NK cell function in smokers suggests a potential mechanism that may enhance susceptibility to respiratory viruses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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