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Due to shortages of N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic, it is necessary to estimate the number of N95s required for healthcare workers (HCWs) to inform manufacturing targets and resource allocation.
We developed a model to determine the number of N95 respirators needed for HCWs both in a single acute-care hospital and the United States.
For an acute-care hospital with 400 all-cause monthly admissions, the number of N95 respirators needed to manage COVID-19 patients admitted during a month ranges from 113 (95% interpercentile range [IPR], 50–229) if 0.5% of admissions are COVID-19 patients to 22,101 (95% IPR, 5,904–25,881) if 100% of admissions are COVID-19 patients (assuming single use per respirator, and 10 encounters between HCWs and each COVID-19 patient per day). The number of N95s needed decreases to a range of 22 (95% IPR, 10–43) to 4,445 (95% IPR, 1,975–8,684) if each N95 is used for 5 patient encounters. Varying monthly all-cause admissions to 2,000 requires 6,645–13,404 respirators with a 60% COVID-19 admission prevalence, 10 HCW–patient encounters, and reusing N95s 5–10 times. Nationally, the number of N95 respirators needed over the course of the pandemic ranges from 86 million (95% IPR, 37.1–200.6 million) to 1.6 billion (95% IPR, 0.7–3.6 billion) as 5%–90% of the population is exposed (single-use). This number ranges from 17.4 million (95% IPR, 7.3–41 million) to 312.3 million (95% IPR, 131.5–737.3 million) using each respirator for 5 encounters.
We quantified the number of N95 respirators needed for a given acute-care hospital and nationally during the COVID-19 pandemic under varying conditions.
A classic example of microbiome function is its role in nutrient assimilation in both plants and animals, but other less obvious roles are becoming more apparent, particularly in terms of driving infectious and non-infectious disease outcomes and influencing host behaviour. However, numerous biotic and abiotic factors influence the composition of these communities, and host microbiomes can be susceptible to environmental change. How microbial communities will be altered by, and mitigate, the rapid environmental change we can expect in the next few decades remain to be seen. That said, given the enormous range of functional diversity conferred by microbes, there is currently something of a revolution in microbial bioengineering and biotechnology in order to address real-world problems including human and wildlife disease and crop and biofuel production. All of these concepts are explored in further detail throughout the book.
We hypothesized that a computerized clinical decision support tool for Clostridium difficile testing would reduce unnecessary inpatient tests, resulting in fewer laboratory-identified events. Census-adjusted interrupted time-series analyses demonstrated significant reductions of 41% fewer tests and 31% fewer hospital-onset C. difficile infection laboratory-identified events following this intervention.
Recent evidence suggests that exercise plays a role in cognition and that the posterior cingulate cortex (PCC) can be divided into dorsal and ventral subregions based on distinct connectivity patterns.
To examine the effect of physical activity and division of the PCC on brain functional connectivity measures in subjective memory complainers (SMC) carrying the epsilon 4 allele of apolipoprotein E (APOE 4) allele.
Participants were 22 SMC carrying the APOE ɛ4 allele (ɛ4+; mean age 72.18 years) and 58 SMC non-carriers (ɛ4–; mean age 72.79 years). Connectivity of four dorsal and ventral seeds was examined. Relationships between PCC connectivity and physical activity measures were explored.
ɛ4+ individuals showed increased connectivity between the dorsal PCC and dorsolateral prefrontal cortex, and the ventral PCC and supplementary motor area (SMA). Greater levels of physical activity correlated with the magnitude of ventral PCC–SMA connectivity.
The results provide the first evidence that ɛ4+ individuals at increased risk of cognitive decline show distinct alterations in dorsal and ventral PCC functional connectivity.
Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta). The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years. Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo. Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated. Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts. Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models. Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi – macaque model systems and summarizing exciting new progress in this area of research.
Introduction: Point of care ultrasound (PoCUS) has become an established tool in the initial management of patients with undifferentiated hypotension in the emergency department (ED). Current established protocols (e.g. RUSH and ACES) were developed by expert user opinion, rather than objective, prospective data. Recently the SHoC Protocol was published, recommending 3 core scans; cardiac, lung, and IVC; plus other scans when indicated clinically. We report the abnormal ultrasound findings from our international multicenter randomized controlled trial, to assess if the recommended 3 core SHoC protocol scans were chosen appropriately for this population. Methods: Recruitment occurred at seven centres in North America (4) and South Africa (3). Screening at triage identified patients (SBP<100 or shock index>1) who were randomized to PoCUS or control (standard care with no PoCUS) groups. All scans were performed by PoCUS-trained physicians within one hour of arrival in the ED. Demographics, clinical details and study findings were collected prospectively. A threshold incidence for positive findings of 10% was established as significant for the purposes of assessing the appropriateness of the core recommendations. Results: 138 patients had a PoCUS screen completed. All patients had cardiac, lung, IVC, aorta, abdominal, and pelvic scans. Reported abnormal findings included hyperdynamic LV function (59; 43%); small collapsing IVC (46; 33%); pericardial effusion (24; 17%); pleural fluid (19; 14%); hypodynamic LV function (15; 11%); large poorly collapsing IVC (13; 9%); peritoneal fluid (13; 9%); and aortic aneurysm (5; 4%). Conclusion: The 3 core SHoC Protocol recommendations included appropriate scans to detect all pathologies recorded at a rate of greater than 10 percent. The 3 most frequent findings were cardiac and IVC abnormalities, followed by lung. It is noted that peritoneal fluid was seen at a rate of 9%. Aortic aneurysms were rare. This data from the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients, supports the use of the prioritized SHoC protocol, though a larger study is required to confirm these findings.
Introduction: Point of care ultrasound (PoCUS) is an established tool in the initial management of patients with undifferentiated hypotension in the emergency department (ED). While PoCUS protocols have been shown to improve early diagnostic accuracy, there is little published evidence for any mortality benefit. We report the findings from our international multicenter randomized controlled trial, assessing the impact of a PoCUS protocol on survival and key clinical outcomes. Methods: Recruitment occurred at 7 centres in North America (4) and South Africa (3). Scans were performed by PoCUS-trained physicians. Screening at triage identified patients (SBP<100 or shock index>1), randomized to PoCUS or control (standard care and no PoCUS) groups. Demographics, clinical details and study findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. The primary outcome measure was 30-day/discharge mortality. Secondary outcome measures included diagnostic accuracy, changes in vital signs, acid-base status, and length of stay. Categorical data was analyzed using Fishers test, and continuous data by Student T test and multi-level log-regression testing. (GraphPad/SPSS) Final chart review was blinded to initial impressions and PoCUS findings. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no difference between groups for the primary outcome of mortality; PoCUS 32/129 (24.8%; 95% CI 14.3-35.3%) vs. Control 32/129 (24.8%; 95% CI 14.3-35.3%); RR 1.00 (95% CI 0.869 to 1.15; p=1.00). There were no differences in the secondary outcomes; ICU and total length of stay. Our sample size has a power of 0.80 (α:0.05) for a moderate effect size. Other secondary outcomes are reported separately. Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We did not find any mortality or length of stay benefits with the use of a PoCUS protocol, though a larger study is required to confirm these findings. While PoCUS may have diagnostic benefits, these may not translate into a survival benefit effect.
Introduction: Point of Care Ultrasound (PoCUS) protocols are commonly used to guide resuscitation for emergency department (ED) patients with undifferentiated non-traumatic hypotension. While PoCUS has been shown to improve early diagnosis, there is a minimal evidence for any outcome benefit. We completed an international multicenter randomized controlled trial (RCT) to assess the impact of a PoCUS protocol on key resuscitation markers in this group. We report diagnostic impact and mortality elsewhere. Methods: The SHoC-ED1 study compared the addition of PoCUS to standard care within the first hour in the treatment of adult patients presenting with undifferentiated hypotension (SBP<100 mmHg or a Shock Index >1.0) with a control group that did not receive PoCUS. Scans were performed by PoCUS-trained physicians. 4 North American, and 3 South African sites participated in the study. Resuscitation outcomes analyzed included volume of fluid administered in the ED, changes in shock index (SI), modified early warning score (MEWS), venous acid-base balance, and lactate, at one and four hours. Comparisons utilized a T-test as well as stratified binomial log-regression to assess for any significant improvement in resuscitation amount the outcomes. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no significant difference in mean total volume of fluid received between the control (1658 ml; 95%CI 1365-1950) and PoCUS groups (1609 ml; 1385-1832; p=0.79). Significant improvements were seen in SI, MEWS, lactate and bicarbonate with resuscitation in both the PoCUS and control groups, however there was no difference between groups. Conclusion: SHOC-ED1 is the first RCT to compare PoCUS to standard of care in hypotensive ED patients. No significant difference in fluid used, or markers of resuscitation was found when comparing the use of a PoCUS protocol to that of standard of care in the resuscitation of patients with undifferentiated hypotension.
Introduction: Point of care ultrasonography (PoCUS) is an established tool in the initial management of hypotensive patients in the emergency department (ED). It has been shown rule out certain shock etiologies, and improve diagnostic certainty, however evidence on benefit in the management of hypotensive patients is limited. We report the findings from our international multicenter RCT assessing the impact of a PoCUS protocol on diagnostic accuracy, as well as other key outcomes including mortality, which are reported elsewhere. Methods: Recruitment occurred at 4 North American and 3 Southern African sites. Screening at triage identified patients (SBP<100 mmHg or shock index >1) who were randomized to either PoCUS or control groups. Scans were performed by PoCUS-trained physicians. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. Final chart review was blinded to initial impressions and PoCUS findings. Categorical data was analyzed using Fishers two-tailed test. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. The perceived shock category changed more frequently in the PoCUS group 20/127 (15.7%) vs. control 7/125 (5.6%); RR 2.81 (95% CI 1.23 to 6.42; p=0.0134). There was no significant difference in change of diagnostic impression between groups PoCUS 39/123 (31.7%) vs control 34/124 (27.4%); RR 1.16 (95% CI 0.786 to 1.70; p=0.4879). There was no significant difference in the rate of correct category of shock between PoCUS (118/127; 93%) and control (113/122; 93%); RR 1.00 (95% CI 0.936 to 1.08; p=1.00), or for correct diagnosis; PoCUS 90/127 (70%) vs control 86/122 (70%); RR 0.987 (95% CI 0.671 to 1.45; p=1.00). Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We found that the use of PoCUS did change physicians’ perceived shock category. PoCUS did not improve diagnostic accuracy for category of shock or diagnosis.
Early in the history of schistosomiasis research, children under 5 years of age were known to be infected. Although this problem was recognized over 100 years ago, insufficient action has been taken to address this issue. Under current policy, such infected children only receive their first antiparasitic treatment (praziquantel – PZQ) upon entry into primary school as current mass drug administration programmes typically target school-aged children. For many infected children, they will wait up to 6 years before receiving their first medication and significant schistosomiasis-related morbidity may have already established. This inequity would not be accepted for other diseases. To unveil some of the reasons behind this neglect, it is paramount to understand the intricate historical relationship between schistosomiasis and British Imperial medicine, to underline its lasting influence on today's public health priorities. This review presents a perspective on the historical neglect of paediatric schistosomiasis, focusing on important gaps that persist from the early days after discovery of this parasite. Looking to end this inequity, we address several issues that need to be overcome to move forward towards the lasting success of schistosomiasis control and elimination efforts.
Part of Robert T. Leiper's (1881–1969) lasting legacy in medical helminthology is grounded on his pioneering work on schistosomiasis (Bilharzia). Having undertaken many expeditions to the tropics, his fascination with parasite life cycles typically allowed him to devise simple preventive measures that curtailed transmission. Building on his formative work with others in Africa and Asia, and again in Egypt in 1915, he elucidated the life cycles of African schistosomes. His mandate, then commissioned by the British War Office, was to prevent and break transmission of this disease in British troops. This he did by raising standing orders based on simple water hygiene measures. Whilst feasible in military camp settings, today their routine implementation is sadly out of reach for millions of Africans living in poverty. Whilst we celebrate the centenary of Leiper's research we draw attention to some of his lesser known colleagues, then focus on schistosomiasis in Uganda discussing why expanded access to treatment with praziquantel is needed now. Looking to WHO 2020 targets for neglected tropical diseases, we introduce COUNTDOWN, an implementation research consortium funded by DFID, UK, which fosters the scale-up of interventions and confirm the current relevance of Leiper's original research.
Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate.
The joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009.
There were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2–39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2–22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1–4.1], less so when previously deployed (OR 1.6, 95% CI 1.1–2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8–1.8). Adjustment for a differential ‘healthy warrior effect’ cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status.
Efforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.
Q fever patients are often reported to experience a long-term impaired health status, including fatigue, which can persist for many years. During the large Q fever epidemic in The Netherlands, many patients with a laboratory-confirmed Coxiella burnetii infection were not notified as acute Q fever because they did not fulfil the clinical criteria of the acute Q fever case definition (fever, pneumonia and/or hepatitis). Our study assessed and compared the long-term health status of notified and non-notified Q fever patients at 4 years after onset of illness, using the Nijmegen Clinical Screening Instrument (NCSI). The study included 448 notified and 193 non-notified Q fever patients. The most severely affected subdomain in both patient groups was ‘Fatigue’ (50·5% of the notified and 54·6% of the non-notified patients had severe fatigue). Long-term health status did not differ significantly between the notified and non-notified patient groups, and patients scored worse on all subdomains compared to a healthy reference group. Our findings suggest that the magnitude of the 2007–2009 Q fever outbreak in The Netherlands was underestimated when only notified patients according to the European Union case definition are considered.
The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) has found that the proportional elevation in the US Army enlisted soldier suicide rate during deployment (compared with the never-deployed or previously deployed) is significantly higher among women than men, raising the possibility of gender differences in the adverse psychological effects of deployment.
Person-month survival models based on a consolidated administrative database for active duty enlisted Regular Army soldiers in 2004–2009 (n = 975 057) were used to characterize the gender × deployment interaction predicting suicide. Four explanatory hypotheses were explored involving the proportion of females in each soldier's occupation, the proportion of same-gender soldiers in each soldier's unit, whether the soldier reported sexual assault victimization in the previous 12 months, and the soldier's pre-deployment history of treated mental/behavioral disorders.
The suicide rate of currently deployed women (14.0/100 000 person-years) was 3.1–3.5 times the rates of other (i.e. never-deployed/previously deployed) women. The suicide rate of currently deployed men (22.6/100 000 person-years) was 0.9–1.2 times the rates of other men. The adjusted (for time trends, sociodemographics, and Army career variables) female:male odds ratio comparing the suicide rates of currently deployed v. other women v. men was 2.8 (95% confidence interval 1.1–6.8), became 2.4 after excluding soldiers with Direct Combat Arms occupations, and remained elevated (in the range 1.9–2.8) after adjusting for the hypothesized explanatory variables.
These results are valuable in excluding otherwise plausible hypotheses for the elevated suicide rate of deployed women and point to the importance of expanding future research on the psychological challenges of deployment for women.
We describe the efficacy of enhanced infection control measures, including those recommended in the Centers for Disease Control and Prevention’s 2012 carbapenem-resistant Enterobacteriaceae (CRE) toolkit, to control concurrent outbreaks of carbapenemase-producing Enterobacteriaceae (CPE) and extensively drug-resistant Acinetobacter baumannii (XDR-AB).
Before-after intervention study.
Fifteen-bed surgical trauma intensive care unit (ICU).
We investigated the impact of enhanced infection control measures in response to clusters of CPE and XDR-AB infections in an ICU from April 2009 to March 2010. Polymerase chain reaction was used to detect the presence of blaKPC and resistance plasmids in CRE. Pulsed-field gel electrophoresis was performed to assess XDR-AB clonality. Enhanced infection-control measures were implemented in response to ongoing transmission of CPE and a new outbreak of XDR-AB. Efficacy was evaluated by comparing the incidence rate (IR) of CPE and XDR-AB before and after the implementation of these measures.
The IR of CPE for the 12 months before the implementation of enhanced measures was 7.77 cases per 1,000 patient-days, whereas the IR of XDR-AB for the 3 months before implementation was 6.79 cases per 1,000 patient-days. All examined CPE shared endemic blaKPC resistance plasmids, and 6 of the 7 XDR-AB isolates were clonal. Following institution of enhanced infection control measures, the CPE IR decreased to 1.22 cases per 1,000 patient-days (P = .001), and no more cases of XDR-AB were identified.
Use of infection control measures described in the Centers for Disease Control and Prevention’s 2012 CRE toolkit was associated with a reduction in the IR of CPE and an interruption in XDR-AB transmission.
The US Army suicide rate has increased sharply in recent years. Identifying significant predictors of Army suicides in Army and Department of Defense (DoD) administrative records might help focus prevention efforts and guide intervention content. Previous studies of administrative data, although documenting significant predictors, were based on limited samples and models. A career history perspective is used here to develop more textured models.
The analysis was carried out as part of the Historical Administrative Data Study (HADS) of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). De-identified data were combined across numerous Army and DoD administrative data systems for all Regular Army soldiers on active duty in 2004–2009. Multivariate associations of sociodemographics and Army career variables with suicide were examined in subgroups defined by time in service, rank and deployment history.
Several novel results were found that could have intervention implications. The most notable of these were significantly elevated suicide rates (69.6–80.0 suicides per 100 000 person-years compared with 18.5 suicides per 100 000 person-years in the total Army) among enlisted soldiers deployed either during their first year of service or with less than expected (based on time in service) junior enlisted rank; a substantially greater rise in suicide among women than men during deployment; and a protective effect of marriage against suicide only during deployment.
A career history approach produces several actionable insights missed in less textured analyses of administrative data predictors. Expansion of analyses to a richer set of predictors might help refine understanding of intervention implications.
Long-term care (LTC) patients are often sent to emergency departments (EDs) by ambulance. In this novel extended care paramedic (ECP) program, specially trained paramedics manage LTC patients on site. The objective of this pilot study was to describe the dispatch and disposition of LTC patients treated by ECPs and emergency paramedics.
Data were collected from consecutive calls to 15 participating LTC facilities for 3 months. Dispatch determinants, transport rates, and relapse rates were described for LTC patients attended by ECPs or emergency paramedics. ECP involvement in end-of-life care was identified.
Of 238 eligible calls, 140 (59%) were attended by an ECP and 98 (41%) by emergency paramedics. Although the top three determinants were the same in each group, the overall distribution of dispatch determinants and acuity differed. In the ECP cohort, 98 of 140 (70%) were treated and released, 33 of 140 (24%) had “facilitated transfer” arranged by an ECP, and 9 of 140 (6%) were immediately transported to the ED by ambulance. In the emergency paramedic cohort, 77 of 98 (79%) were immediately transported to the ED and 21 of 98 (21%) were not transported. In the ECP group, 6 of 98 (6%) patients not transported triggered a 911 call within 48 hours for a related clinical reason, although none of the patients not transported by emergency paramedics relapsed.
ECP involvement in LTC calls was found to reduce transports to the ED with a low rate of relapse. These pilot data generated hypotheses for future study, including determination of appropriate populations for ECP care and analysis of appropriate and safe nontransport.
We present the first sample of diffuse interstellar bands (DIBs) in the nearby galaxy M33. Studying DIBs in other galaxies allows the behaviour of the carriers to be examined under interstellar conditions which can be quite different from those of the Milky Way, and to determine which DIB properties can be used as reliable probes of extragalactic interstellar media. Multi-object spectroscopy of 43 stars in M33 has been performed using Keck/DEIMOS. The stellar spectral types were determined and combined with literature photometry to determine the M33 reddenings E(B-V)M33. Equivalent widths or upper limits have been measured for the λ5780 DIB towards each star. DIBs were detected towards 20 stars, demonstrating that their carriers are abundant in M33. The relationship with reddening is found to be at the upper end of the range observed in the Milky Way. The line of sight towards one star has an unusually strong ratio of DIB equivalent width to E(B-V)M33, and a total of seven DIBs were detected towards this star.
We present a preliminary analysis of a set of optical (3800-8800 Å) high resolution (R = 80,000) spectra for 69 diffuse interstellar band targets. We carried out a sensitive search for interstellar features in the wavelength range 8470-8740 Å that will be covered by the upcoming GAIA mission. We also investigate how the λ8620Å DIB strength varies as a function of other interstellar parameters (other DIBs, E(B-V) and atomic and molecular column densities).