Hospital-onset COVID-19 infection surveillance systems: a systematic review.

Hospital-onset COVID-19 infections (HOCIs) are associated with excess morbidity and mortality in patients and healthcare workers. The aim of this review was to explore and describe the current literature in HOCI surveillance. Medline, EMBASE, the Cochrane Database of Systematic Reviews, the Cochrane Register of Controlled Trials, and MedRxiv were searched up to 30 November 2020 using broad search criteria. Articles of HOCI surveillance systems were included. Data describing HOCI definitions, HOCI incidence, types of HOCI identification surveillance systems, and level of system implementation were extracted. A total of 292 citations were identified. Nine studies on HOCI surveillance were included. Six studies reported on the proportion of HOCI among hospitalized COVID-19 patients, which ranged from 0 to 15.2%. Six studies provided HOCI case definitions. Standardized national definitions provided by the UK and US governments were identified. Four studies included healthcare workers in the surveillance. One study articulated a multimodal strategy of infection prevention and control practices including HOCI surveillance. All identified HOCI surveillance systems were implemented at institutional level, with eight studies focusing on all hospital inpatients and one study focusing on patients in the emergency department. Multiple types of surveillance were identified. Four studies reported automated surveillance, of which one included real-time analysis, and one included genomic data. Overall, the study quality was limited by the observational nature with short follow-up periods. In conclusion, HOCI case definitions and surveillance methods were developed pragmatically. Whilst standardized case definitions and surveillance systems are ideal for integration with existing routine surveillance activities and adoption in different settings, we acknowledged the difficulties in establishing such standards in the short-term.

[From the bench to the clinic: The challenge of translating platelet production in vitro]. / Du laboratoire à l'usage clinique : le défi de la production de plaquettes in vitro.

Platelet transfusions, which are currently totally dependent on altruistic donations, are absolutely necessary to the treatment of patients with thrombocytopenia following trauma, surgery or other pathologies (especially malignancies). Producing platelets in vitro represent a major technological and scientific breathrough that would address logistical issues (supply chain, stock holding…) and medical concerns (compatibility and biosafety). The translation of this innovation will need to be accompanied by rigorous quality control, harmonised between laboratory when it comes to functionality and biosafety for use in the clinic.

In vitro-derived platelets: the challenges we will have to face to assess quality and safety.

Platelet transfusions are given to patients in hospital who have a low blood platelet count (thrombocytopenia) either because of major bleeding (following trauma or surgery) or because the bone marrow production of platelets is impaired often due to chemotherapy, infiltration with malignant cells, fibrosis or genetic disorders. We are currently entirely reliant on blood donors as a source of platelets in transfusion medicine. However, the demand for platelets continues to rise, driven by an aging population, advances in medical procedures and ever more aggressive cancer therapies, while the supply of blood donors continues to remain static. In recent years, several groups have made major advances toward the generation of platelets in vitro for human transfusion. Recent successes include results in both generating mature human megakaryocytes as well as in developing bioreactors for extracting platelets from these megakaryocytes. Platelets made in vitro could address several issues inherent to platelets derived from blood donors - the ability to scale up/down more flexibly according to demand and therefore less precarious supply line, reduction of the risk of exposure to infectious agents and finally the possibility of engineering stem cells to reduce immunogenicity. Here we define the quality control tools and suggest measures for implementation across the field for in vitro platelet genesis, to aid collaboration between laboratories and to aid production of the burdens of proof that will eventually be required by regulators for efficacy and biosafety. We will do this firstly, by addressing the quality control of the nucleated cells used to make the platelets with a particular emphasis to safety issues and secondly, we will look at how platelet function measurement are addressed particularly in the context of platelets derived in vitro.

Planning to halve Gram-negative bloodstream infection: getting to grips with healthcare-associated Escherichia coli bloodstream infection sources.

BACKGROUND: A thorough understanding of the local sources, risks, and antibiotic resistance for Escherichia coli bloodstream infection (BSI) is required to focus prevention initiatives and therapy. AIM: To review the sources and antibiotic resistance of healthcare-associated E. coli BSI. METHODS: Sources and antibiotic resistance profiles of all 250 healthcare-associated (post 48 h) E. coli BSIs that occurred within our secondary and tertiary care hospital group from April 2014 to March 2017 were reviewed. Epidemiological associations with urinary source, gastrointestinal source, and febrile neutropenia-related BSIs were analysed using univariable and multivariable binary logistic regression models. FINDINGS: E. coli BSIs increased 9% from 4.0 to 4.4 per 10,000 admissions comparing the 2014/15 and 2016/17 financial years. Eighty-nine cases (36%) had a urinary source; 30 (34%) of these were classified as urinary catheter-associated urinary tract infections (UTIs). Forty-five (18%) were related to febrile neutropenia, and 38 (15%) had a gastrointestinal source. Cases were rarely associated with surgical procedures (11, 4%) or indwelling vascular devices (seven, 3%). Female gender (odds ratio: 2.3; 95% confidence interval: 1.2-4.6) and older age (1.02; 1.00-1.05) were significantly associated with a urinary source. No significant associations were identified for gastrointestinal source or febrile neutropenia-related BSIs. Forty-seven percent of the isolates were resistant to ciprofloxacin, 37% to third-generation cephalosporins, and 22% to gentamicin. CONCLUSION: The gastrointestinal tract and febrile neutropenia together accounted for one-third of E. coli BSI locally but were rare associations nationally. These sources need to be targeted locally to reduce an increasing trend of E. coli BSIs.

Evaluating serial screening cultures to detect carbapenemase-producing Enterobacteriaceae following hospital admission.

BACKGROUND: Carbapenem-producing Enterobacteriaceae (CPE) are on the rise worldwide. National guidelines for the prevention and control of CPE recommend screening for the detection of asymptomatic carriers on admission. AIM: To evaluate the benefit of serial screens for detecting the carriage of CPE and other antibiotic-resistant Gram-negative bacteria following hospital admission. METHODS: All CPE screens, which were cultured on chromogenic media and the presence of a carbapenemase confirmed by polymerase chain reaction, were analysed for a six-month period. National guidelines in England recommend three serial screens for CPE separated by 48 h for admission screening for 'at-risk' patients, during which the patient is isolated. Two screening scenarios were tested. In scenario A, patients received three screens at the specified timepoints, in line with English national guidelines; in scenario B, patients received three consecutive screens, but not necessarily within the specified timepoints, during one admission. General linear models or conditional logistic regression were used to detect any significant change in the rate of carriage. FINDINGS: There was no significant increase in the detected carriage rate of CPE across any of the three timepoints in the scenarios tested. However, there was a significant increase in the detected rate of carriage of Gram-negative bacteria, Enterobacteriaceae, and resistant Enterobacteriaceae (excluding CPE) in scenario B. CONCLUSION: Three serial screens were not useful for the detection of CPE carriage on admission. The increase in the carriage rate of other Gram-negative bacteria may be explained by 'unmasking' of pre-existing carriage, or acquisition. This argues for regular screening of long-stay patients.

Gas exchange kinetics following concentric-eccentric isokinetic arm and leg exercise.

PURPOSE: To evaluate the effects of exercise velocity (60, 150, 240deg∙s-1) and muscle mass (arm vs leg) on changes in gas exchange and arterio-venous oxygen content difference (avDO2) following high-intensity concentric-eccentric isokinetic exercise. METHODS: Fourteen subjects (26.9±3.1years) performed a 3×20-repetition isokinetic exercise protocol. Recovery beat-to-beat cardiac output (CO) and breath-by-breath gas exchange were recorded to determine post-exercise half-time (t1/2) for oxygen uptake (V˙O2pulm), carbon dioxide output (V˙CO2pulm), and ventilation (V˙E). RESULTS: Significant differences of the t1/2 values were identified between 60 and 150deg∙s-1. Significant differences in the t1/2 values were observed between V˙O2pulm and V˙CO2pulm and between V˙CO2pulm and V˙E. The time to attain the first avDO2-peak showed significant differences between arm and leg exercise. CONCLUSIONS: The present study illustrates, that V˙O2pulm kinetics are distorted due to non-linear CO dynamics. Therefore, it has to be taken into account, that V˙O2pulm may not be a valuable surrogate for muscular oxygen uptake kinetics in the recovery phases.

Counting the cost of an outbreak of carbapenemase-producing Enterobacteriaceae: an economic evaluation from a hospital perspective.

OBJECTIVE: To perform an economic evaluation on the cost associated with an outbreak of carbapenemase-producing Enterobacteriaceae (CPE). METHODS: We performed an observational economic evaluation of an outbreak of CPE (NDM-producing Klebsiella pneumoniae) affecting 40 patients in a group of five hospitals across three sites in West London. Costs were split into actual expenditure (including anti-infective costs, enhanced CPE screening, contact precautions, temporary ward-based monitors of hand and environmental practice, and environmental decontamination), and 'opportunity cost' (staff time, bed closures and elective surgical missed revenue). Costs are estimated from the hospital perspective over the 10-month duration of the outbreak. RESULTS: The outbreak cost €1.1m over 10 months (range €0.9-1.4m), comprising €312 000 actual expenditure, and €822 000 (range €631 000-€1.1m) in opportunity cost. An additional €153 000 was spent on Estates renovations prompted by the outbreak. Actual expenditure comprised: €54 000 on anti-infectives for 18 patients treated, €94 000 on laboratory costs for screening, €73 000 on contact precautions for 1831 contact precautions patient-days, €42 000 for hydrogen peroxide vapour decontamination of 24 single rooms, €43 000 on 2592 hours of ward-based monitors, and €6000 of expenditure related to ward and bay closures. Opportunity costs comprised: €244 000 related to 1206 lost bed-days (range 366-2562 bed-days, €77 000-€512 000), €349 000 in missed revenue from 72 elective surgical procedures, and €228 000 in staff time (range €205 000-€251 000). Reduced capacity to perform elective surgical procedures related to bed closures (€349 000) represented the greatest cost. CONCLUSIONS: The cost estimates that we present suggest that CPE outbreaks are highly costly.

Reduction in Clostridium difficile infection associated with the introduction of hydrogen peroxide vapour automated room disinfection.

The clinical impact of implementing hydrogen peroxide vapour (HPV) disinfection of rooms vacated by patients with Clostridium difficile infection (CDI) was evaluated. Breakpoint time series analysis indicated a significant reduction (P<0.001) in the CDI rate at the time when HPV disinfection was implemented, resulting in a reduction in the CDI rate from 1.0 to 0.4 cases per 1000 patient-days in the 24 months before HPV usage compared with the first 24 months of HPV usage. HPV should be considered to augment the terminal disinfection of rooms vacated by patients with CDI.

Isolation demand from carbapenemase-producing Enterobacteriaceae screening strategies based on a West London hospital network.

OBJECTIVE: To estimate the isolation demands arising from high-risk specialty-based screening for carbapenemase-producing Enterobacteriaceae (CPE), and the potential fraction of CPE burden detected. METHODS: Clinical specialty groups from three London hospitals were ranked by incidence of carbapenem resistance among Escherichia coli and Klebsiella spp. Contact precaution bed-days were estimated for three screening strategies: Strategy 1, 'circulation science and renal medicine'; Strategy 2, Strategy 1 plus 'specialist services'; and Strategy 3, Strategy 2 plus 'private patients'. Isolation bed occupancy rates and potential CPE detection rates were estimated. RESULTS: Of 99,105 admissions to the three hospitals in Financial Year 2014/15, Strategies 1, 2 and 3 would have screened 4371 (4.4%), 7482 (7.6%), and 13,542 (13.7%) patients, respectively. The specialties' isolation bed occupancy rates varied between 3% and 696% depending on strategy, number of consecutive tests, and whether or not pre-emptive isolation had been applied. Expected detection rates of the potential CPE burden in the hospital network would have varied between 17.1% and 47.5%. CONCLUSIONS: High-risk specialty-based screening has the potential to detect nearly half of the potential CPE burden, and would be more pragmatic than patient-level risk-factor-based screening. Pre-emptive isolation increases isolation requirements substantially. CPE screening strategies need to balance risk and resources.

Addison's disease presenting with muscle spasm.

Primary hypoadrenalism has various causes and protean manifestation. We report a young female patient who presented with severe muscle spasm as her primary complaint. On evaluation she was found to be a case of Addison's disease secondary to adrenal tuberculosis. Her muscle spasm disappeared rapidly with replacement dose of glucocorticoid.

Mitochondrial uncoupling protein 2 in pancreatic ß-cells.

Pancreatic ß-cells have remarkable bioenergetics in which increased glucose supply upregulates the cytosolic ATP/ADP ratio and increases insulin secretion. This arrangement allows glucose-stimulated insulin secretion (GSIS) to be regulated by the coupling efficiency of oxidative phosphorylation. Uncoupling protein 2 (UCP2) modulates coupling efficiency and may regulate GSIS. Initial measurements of GSIS and glucose tolerance in Ucp2(-/-) mice supported this model, but recent studies show confounding effects of genetic background. Importantly, however, the enhancement of GSIS is robustly recapitulated with acute UCP2 knockdown in INS-1E insulinoma cells. UCP2 protein level in these cells is dynamically regulated, over at least a fourfold concentration range, by rapid proteolysis (half-life less than 1 h) opposing regulated gene transcription and mRNA translation. Degradation is catalysed by the cytosolic proteasome in an unprecedented pathway that is currently known to act only on UCP2 and UCP3. Evidence for proteasomal turnover of UCP2 includes sensitivity of degradation to classic proteasome inhibitors in cells, and reconstitution of degradation in vitro in mitochondria incubated with ubiquitin and the cytosolic 26S proteasome. These dynamic changes in UCP2 content may provide a fine level of control over GSIS in ß-cells.

A descriptive profile of elite U.S. women's collegiate field hockey players.

BACKGROUND: The purposes of this study were to develop a descriptive profile and examine the relationships between grip strength, power and sport specific test performance in 37 elite, female collegiate field hockey players (N=8 backs, N=13 forwards, N=4 goalkeepers, N=8 midfield players, N=4 wings). METHODS: The tests included circumference and limb lengths, %body fat, Margaria-Kalamen stair test, 50-yard dash test, Queen's College step test, grip strength, Illinois agility test, field hockey specific skills tests, and a coordination test. RESULTS: Mean (+/-SD) height, weight, percent body fat, and predicted oxygen consumption were 164.26 (+/-5.17) cm, 63.06 (+/-8.60) kg, 17.29 (+/-3.79)% and 42.87 (+/-9.08) ml x kg(-1) x min(-1), respectively. Although the goalkeepers were significantly (p<0.05) heavier and had a higher %body fat, there were no significant differences (p>0.05) between any of the player positions in height, limb length, 50-yard dash time, predicted VO(2max), grip strength, agility, or in the field hockey specific tests. There were no significant (p>0.05) correlations (r=0.03 to -0.13) between right and left grip strength and sport-specific test scores but significant (p<0.05) relationships were found between power and pushing accuracy, as well as between the 50 yard dash and coordination test, pushing power and pushing accuracy. CONCLUSIONS: In profiling a sample of elite collegiate field hockey players in the Unites States, the results of this study indicate that there are similarities amongst the defensive and offensive players with international level field hockey players, and that measures of power and sport specific tests are significantly correlated.

The effects of physical training of functional capacity in adults. Ages 46 to 90: a meta-analysis.

BACKGROUND: There is a progressive decline in the functional capacity (FC) of the cardiovascular system with aging. This deterioration is reflected in a decrease in the maximal oxygen consumption (VO2max). The purpose of this quantitative review was to determine the effects of various components of the exercise prescription on FC in older individuals (ages 46-90 years). METHODS: This study synthesized the results of 27 studies by meta-analysis, which generated a total of 34 effect sizes. Each effect size represented an independent measure of the impact of physical training on maximal oxygen consumption (VO2max). A total of 720 subjects were included in this review. The studies were coded according to intensity, session duration, length of training and mode of exercise. RESULTS: A significant difference was found (p < 0.001) in FC between studies in which the intensity of exercise was > or = to 80% of VO2max compared to those with training intensities of 60-75% of VO2max. A significant difference was found (p < 0.002) for exercise duration; namely, a duration of > or = 30 minutes produced significantly greater improvements in VO2max when compared to an exercise duration less than 30 minutes. There was no significant difference reported in FC between studies that lasted 15 or more weeks in duration compared to those that lasted less than 15 weeks. Finally, there was no significant difference reported in FC in studies that utilized a walk/jog training mode compared to those which utilized cycle ergometry. CONCLUSIONS: Despite the inevitable decline in VO2max with aging, exercise training imparts favorable adaptations in FC in individuals well into their seventh and eighth decades of life.

Epidemiology and predictors of post-concussive syndrome after minor head injury in an emergency population.

OBJECTIVE: To determine if clinical variables or neurobehavioural test (NBT) scores obtained in the ED within 24 hours of minor head injury (MHI) predict the development of postconcussive syndrome (PCS). METHODS: Prospective, observational study of 71 MHI patients and 60 orthopaedic controls. MHI defined as loss of consciousness < 10 minutes or amnesia, GCS 15, no skull fracture or new neurologic focality on PE, and no brain injury on CT (if done). All patients received a seven part NBT battery in the ED. Telephone follow-up was done at 1, 3 and 6 months to determine if patients met the DSM IV definition of PCS. ANALYSIS: Stepwise, multivariate, logistic regression. RESULTS: Predictors of PCS at 1 month were female gender (OR = 7.8; 95% CI = 41.6, 1.98), presence of both retrograde and anterograde amnesia (OR = 0.055; CI = 0.002, 0.47), Digit Span Forward Scores (OR = 0.748; CI = 0.52, 1.03) and Hopkins Verbal Learning A scores (OR = 0.786; CI = 0.65, 0.91); at 3 months, presence of both retrograde and anterograde amnesia (OR = 0.13; CI = 0.0, 0.93), Digit Span Forward Scores (OR = 0.744; CI = 0.58, 0.94). No variables fit the model at 6 months. 92% of males scoring > 25 on Hopkins Verbal Learning A did not have PCS at 1 month, and 89% of females scoring < 9 on Digit Span Forward did have PCS at 1 month. CONCLUSIONS: Gender and two NBTs can help predict PCS after MHI.

Perturbations in morphogen gradients induce budding in hydra.

Lateral grafting of small pieces of midregion tissue into different levels of the hydra body column was done to assess the influence of the host hypostome and basal disc (or, of the underlying morphogenetic gradients) in inducing secondary structures in the transplanted tissue; and also to identify the role, if any, of the induced secondary structures (or, perturbed morphogen gradients) on the pattern of the host. The same midpiece tissue differentiated to a basal disc when grafted near the host hypostome, and to a small hypostome with tentacles when grafted near the host basal disc. Chimeras with induced secondary basal discs showed a phenomenal increase in budding compared to the controls and to the chimeras having induced hypostomes. These results indicate a positive cross-reaction between both organizing regions during patterning in hydra.

Nerve commitment during head regeneration in hydra.

Most important event in head regeneration in hydra is a wave of conversion of many interstitial cells into nerve cells. Experimental evidence lends support to the idea that the commitment of interstitial cells into nerve cells is the first morphogenetic prerequisite for emergence of head structures, when the number of nerve cells increases. This increase in nerve cells is delayed when regeneration occurs at a site lower in the body column.