Lessons From Influenza Pandemics of the Last 100 Years.

Seasonal influenza is an annual occurrence, but it is the threat of pandemics that produces universal concern. Recurring reports of avian influenza viruses severely affecting humans have served as constant reminders of the potential for another pandemic. Review of features of the 1918 influenza pandemic and subsequent ones helps in identifying areas where attention in planning is critical. Key among such issues are likely risk groups and which interventions to employ. Past pandemics have repeatedly underscored, for example, the vulnerability of groups such as pregnant women and taught other lessons valuable for future preparedness. While a fundamental difficulty in planning for the next pandemic remains their unpredictability and infrequency, this uncertainty can be mitigated, in part, by optimizing the handling of the much more predictable occurrence of seasonal influenza. Improvements in antivirals and novel vaccine formulations are critical in lessening the impact of both pandemic and seasonal influenza.

Available evidence of antibiotic resistance from extended-spectrum ß-lactamase-producing Enterobacteriaceae in paediatric patients in 20 countries: a systematic review and meta-analysis.

OBJECTIVE: To make a systematic review of risk factors, outcomes and prevalence of extended-spectrum ß-lactamase-associated infection in children and young adults in South-East Asia and the Western Pacific. METHODS: Up to June 2018 we searched online databases for published studies of infection with extended-spectrum ß-lactamase-producing Enterobacteriaceae in individuals aged 0-21 years. We included case-control, cohort, cross-sectional and observational studies reporting patients positive and negative for these organisms. For the meta-analysis we used random-effects modelling of risk factors and outcomes for infection, and meta-regression for analysis of subgroups. We mapped the prevalence of these infections in 20 countries and areas using available surveillance data. FINDINGS: Of 6665 articles scanned, we included 40 studies from 11 countries and areas in the meta-analysis. The pooled studies included 2411 samples testing positive and 2874 negative. A higher risk of infection with extended-spectrum ß-lactamase-producing bacteria was associated with previous hospital care, notably intensive care unit stays (pooled odds ratio, OR: 6.5; 95% confidence interval, CI: 3.04 to 13.73); antibiotic exposure (OR: 4.8; 95% CI: 2.25 to 10.27); and certain co-existing conditions. Empirical antibiotic therapy was protective against infection (OR: 0.29; 95% CI: 0.11 to 0.79). Infected patients had longer hospital stays (26 days; 95% CI: 12.81 to 38.89) and higher risk of death (OR: 3.2; 95% CI: 1.82 to 5.80). The population prevalence of infection was high in these regions and surveillance data for children were scarce. CONCLUSION: Antibiotic stewardship policies to prevent infection and encourage appropriate treatment are needed in South-East Asia and the Western Pacific.

Impact of antibiotic stewardship programmes in Asia: a systematic review and meta-analysis.

Background: The use of antibiotic stewardship programmes (ASPs) is increasing in Asia, but their effectiveness in reducing antibiotic consumption and their impact on clinical outcomes is not known. Objectives: To determine the impact of ASPs conducted in Asia on the consumption of antibiotics and on patients' clinical outcomes. Methods: We systematically searched the Embase and Medline (PubMed) databases for studies that compared antibiotic consumption or clinical outcomes of patients in an Asian hospital or clinic with an ASP (intervention) with those in a similar setting without an ASP (control). Meta-analyses of all-cause mortality and hospital-acquired infection (HAI) were performed using random-effects models. Results: The search identified 77 studies of which 22 and 19 reported antibiotic usage and cost, respectively. Among these, 20 (91%) studies reported reduced antibiotic usage and 19 (100%) reported cost savings in the intervention group. Duration of antibiotic therapy was reduced in six of seven studies in association with an ASP. Rates of all-cause mortality and HAI were not significantly different between the intervention and control groups. However, mortality rates were significantly improved by ASPs using drug monitoring, while HAI rates were also improved by ASPs that included infection control or hand hygiene programmes. Conclusions: In Asia, ASPs reduce antibiotic consumption in hospital and clinic settings and do not worsen clinical outcomes. The findings strongly support the broad implementation of antimicrobial stewardship interventions in hospital and clinic settings in Asia.

Ebola virus disease in West Africa--the first 9 months of the epidemic and forward projections.

BACKGROUND: On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a "public health emergency of international concern." METHODS: By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa--Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14. RESULTS: The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R0 ) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total. CONCLUSIONS: These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months.

Cutoff value of Japanese Orthopaedic Association shoulder score in patients with rotator cuff repair: Based on the University of California at Los Angeles shoulder score.

BACKGROUND: The Japanese Orthopaedic Association shoulder score cutoff values were calculated in patients with rotator cuff repair using the University of California at Los Angeles shoulder score. METHODS: Overall, 175 patients with rotator cuff repair were subjects in this study. The University of California at Los Angeles and Japanese Orthopaedic Association shoulder scores were evaluated before surgery and at 3, 6, 9, and 12 months after surgery. The cutoff value of the Japanese Orthopaedic Association shoulder score was determined using the 4-stage criteria of the University of California at Los Angeles shoulder score and a University of California at Los Angeles shoulder score of 28 points, which is the boundary between an excellent/good group and a fair/poor group. RESULTS: Both the JOA shoulder and UCLA shoulder scores showed significant improvement at 6, 9, and 12 months from the preoperative scores (p < 0.0001). There was a strong correlation between the total values of the two scores (r = 0.85, p < 0.0001). The cutoff value of the Japanese Orthopaedic Association shoulder score based on the highest accuracy from receiver operating characteristic curve analysis was 83 points. CONCLUSION: A Japanese Orthopaedic Association shoulder score cutoff value of 83 was equivalent to a University of California at Los Angeles shoulder score cutoff value of 28 for distinguishing between excellent/good and fair/poor outcomes after rotator cuff repair.

Longitudinal monitoring reveals the emergence and spread of blaGES-5-harboring carbapenem-resistant Klebsiella quasipneumoniae in a Hong Kong hospital wastewater discharge line.

Testing hospital wastewater (HWW) is potentially an effective, long-term approach for monitoring trends in antimicrobial resistance (AMR) patterns in health care institutions. Over a year, we collected wastewater samples from the clinical and non-clinical sites of a tertiary hospital and from a downstream wastewater treatment plant (WWTP). We focused on the extent of carbapenem resistance among Enterobacteriaceae isolates given their clinical importance. Escherichia coli and Klebsiella spp. were the most frequently isolated Enterobacteriaceae species at all sampling sites. Additionally, a small number of isolates belonging to ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), except K. pneumoniae, were detected. Of the 232 Klebsiella spp. isolates, 100 (43.1 %) were multi-drug resistant (MDR), with 46 being carbapenem-resistant. Most of these carbapenem-resistant isolates were K. quasipneumoniae (CRKQ) (n = 44). All CRKQ isolates were isolated from the wastewater of a clinical site that includes intensive care units, which also yielded significantly more multi-drug resistant isolates compared to all other sampling sites. Among the CRKQ isolates, blaGES-5 genes (n = 42) were the primary genetic determinant of carbapenem resistance. Notably, three different CRKQ isolates, collected within the same month in HWW and the influent and effluent flow of the WWTP, shared >99 % sequence similarity between their blaGES-5 genes and between their flanking regions and upstream integron-integrase region. The influent isolate was phylogenetically close to K. quasipnuemoniae isolates from wastewater collected in Japan. Its blaGES-5 gene and surrounding sequences were > 99 % identical to blaGES-24 genes found in the Japanese isolates. Our results suggest that testing samples from sites located closer to hospitals could support antibiotic stewardship programs compared to samples collected further downstream. Moreover, testing samples collected regularly from WWTPs may reflect the local and global spread of pathogens and their resistances.

Unpacking multi-level governance of antimicrobial resistance policies: the case of Guangdong, China.

Against the backdrop of universal healthcare coverage and pre-existing policies on antimicrobial use, China has adopted a state-governed, multi-level, top-down policy governance approach around an antimicrobial resistance (AMR) national action plan (NAP). The Plan relies on tightening control over antimicrobial prescription and use in human and animal sectors. At the same time, medical doctors and veterinarians operate in an environment of high rates of infectious diseases, multi-drug resistance and poor livestock husbandry. In exploring the way that policy responsibilities are distributed, this study aims to describe how Guangdong as a province adopts national AMR policies in a tightly controlled public policy system and an economy with high disparity. We draw on an analysis of 225 AMR-relevant Chinese policy documents at the national and sub-national levels. We adopt a multi-level governance perspective and apply a temporal sequence framework to identify and analyse documents. To identify policy detail, we conducted keyword analysis using the Consolidated Framework for Implementation Research (CFIR) on policies that conserve antimicrobials. We also identify pre-existing medical and public policies associated with AMR. Our findings highlight the emphasis and policies around antimicrobial use regulation to address AMR in China.

Antimicrobial Resistance Policy Protagonists and Processes-A Qualitative Study of Policy Advocacy and Implementation.

Antimicrobial resistance (AMR) fundamentally weakens societal foundations economically and in health care. The development of well-considered policies against AMR is important. However, in many places, AMR policy implementation remains elusive. This study aims to identify enablers and deterrents as well as processes and conditions in AMR policy advocacy. It also aims to identify AMR implementation conditions where AMR national policies are adopted and, to a certain extent, formulated and implemented. This study adopts qualitative research methodology and applies the Grounded Theory Framework to identify thematic findings from interviews conducted in China, Japan, Norway, the United Kingdom (UK), and the United States of America (US). It was identified that AMR policy protagonists are critical to filtering AMR issues and identifying policies "fit to prioritize" and "fit to implement". They have helped move policy prioritization needles in the UK and the US and engaged in diplomatic efforts in the UK. In these cases, no clientelism was considered. In the US, protagonists who talked to the right decision-makers in the right office at the right time both moved AMR issues from individuals to institutional agenda and from social norms to policy agenda. To conclude, there are three thematic policy conditions that are significant to AMR policy advocacy and implementation: committed personal championship, institutionalization of policies, and social norms facilitate AMR policy advocacy and implementation.

Clinical outcome in patients with hand lesions associated with complex regional pain syndrome after arthroscopic rotator cuff repair.

BACKGROUND: Complex regional pain syndrome (CRPS)-related hand lesions are one of the complications following arthroscopic rotator cuff repair (ARCR). This study aimed to investigate the clinical outcomes of patients with CRPS-related hand lesions following ARCR. METHODS: Altogether, 103 patients with ARCR were included in this study (mean age, 63.6±8.2 years; 66 males and 37 females; follow-up period, preoperative to 12 months postoperative). Clinical assessment included the Japanese Orthopaedic Association (JOA) score, University of California, Los Angeles (UCLA) score, Constant score, 36-item short form health survey (SF-36) score, and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score from preoperative to 12 months postoperatively. The patients were either assigned to the CRPS group or non-CRPS group depending on CRPS diagnosis until the final follow-up, and clinical outcomes were then compared between the groups. RESULTS: Of 103 patients, 20 (19.4%) had CRPS-related hand lesions that developed entirely within 2 months postoperatively. Both groups showed significant improvement in JOA, UCLA, and Constant scores preoperatively to 12 months postoperatively (P<0.001). Comparisons between the two groups were not significantly different, except for SF-36 "general health perception" (P<0.05) at 12 months postoperatively. At final follow-up, three patients had residual CRPS-related hand lesions with limited range of motion and finger edema. CONCLUSIONS: CRPS-related hand lesions developed in 19.4% of patients following ARCR. Shoulder or upper-limb function improved in most cases at 12 months, with satisfactory SF-36 patient-based evaluation results. Patients with residual CRPS-related hand lesions at the last follow-up require long-term follow-up.

Metagenomic Survey Reveals More Diverse and Abundant Antibiotic Resistance Genes in Municipal Wastewater Than Hospital Wastewater.

Alongside antibiotic resistance, co-selection of antibiotics, biocides, and metal resistance is a growing concern. While hospital wastewater is considered a hotspot for antibiotic-resistant bacteria (ARB) and genes (ARGs), the scenario in India, one of the biggest consumers of antibiotics, remains poorly described. In this study, we used metagenomic sequencing to characterize ARGs and biocide/metal resistance genes (BMRGs) in four wastewater treatment plants (WWTPs) in Jaipur City of India. We observed a significantly lower richness and abundance of ARGs in the influent of a WWTP exclusively receiving hospital wastewater when compared to other three WWTPs involving municipal wastewater treatment. Several tetracycline and macrolide-lincosamide-streptogramin resistance genes were enriched in influents of these three municipal wastewater-related treatment plants, whereas hospital wastewater had a higher abundance of genes conferring resistance to disinfectant-related compounds such as synergize and wex-cide-128, reflecting the patterns of antibiotic/disinfectant use. Of note, in the wastewater system with more chemicals, there was a strong correlation between the numbers of ARGs and BMRGs potentially harbored by common hosts. Our study highlights significant influxes of ARGs from non-hospital sources in Jaipur City, and thus more attention should be paid on the emergence of ARGs in general communities.

Building a multisystemic understanding of societal resilience to the COVID-19 pandemic.

The current global systemic crisis reveals how globalised societies are unprepared to face a pandemic. Beyond the dramatic loss of human life, the COVID-19 pandemic has triggered widespread disturbances in health, social, economic, environmental and governance systems in many countries across the world. Resilience describes the capacities of natural and human systems to prevent, react to and recover from shocks. Societal resilience to the current COVID-19 pandemic relates to the ability of societies in maintaining their core functions while minimising the impact of the pandemic and other societal effects. Drawing on the emerging evidence about resilience in health, social, economic, environmental and governance systems, this paper delineates a multisystemic understanding of societal resilience to COVID-19. Such an understanding provides the foundation for an integrated approach to build societal resilience to current and future pandemics.

National action to combat AMR: a One-Health approach to assess policy priorities in action plans.

Little is known about the overall trend and prioritisations of past and current antimicrobial resistance (AMR) policies. Here we introduce a quantitative method to analyse AMR policies. The AMR-Policy Analysis Coding Toolkit (AMR-PACT) uses several categorical variables. Thirteen AMR action plans from five countries (China, Japan, Norway, the UK and the USA) were used to develop the tool and identify possible values for each variable. The scope and capability of AMR-PACT is demonstrated through the 2015 WHO's Global Action Plan and 2017 Hong Kong AMR Action Plan (HKAP). Majority of policies were aimed at either human or animal sector with less attention given to the environment, plant or food sector. Both plans shared the same two strategic focus areas, namely the conservation of antibiotics and the improved surveillance of resistance. There were no policies dedicated to improving access to antibiotics in the HKAP. These empirical results provide useful insights into the priorities and gaps of AMR policies. The method proposed here can help understand countries' priorities regarding AMR, support the creation of AMR policy database and foster innovative policymaking.

Factors Affecting Return to Work in Patients Undergoing Arthroscopic Rotator Cuff Repair.

OBJECTIVE: Although clinical outcomes after arthroscopic rotator cuff repair are generally favorable, postoperative return to work is also an important issue. This study aimed to assess clinical outcomes and clarify the factors affecting return to work in patients who had undergone arthroscopic rotator cuff repair. METHODS: In total, 63 patients who had undergone arthroscopic rotator cuff repair were included in this study. Clinical assessment was performed using Japanese Orthopaedic Association (JOA) scores, along with measurements of pain, range of motion, muscle strength, cuff integrity, and fatty infiltration. Depending on their return-to-work status at the final follow-up, subjects were assigned to either the complete return group (the patient returned to work) or the incomplete return group (the patient had quit or had changed their occupation at final follow-up). Various clinical parameters affecting the return to work outcome were examined through univariate and multivariate analyses. RESULTS: Of the 63 subjects, 42 belonged to the complete return group and 21 belonged to the incomplete return group. Therefore, the working capability recovery rate following arthroscopic rotator cuff repair was 66.7%. Both groups showed significant improvement from their preoperative status, but there were statistically significant differences in JOA scores between the groups at 9 and 12 months postoperatively (P <0.01). Multivariate stepwise logistic regression analysis showed that heavy work and female sex were significantly adversely associated with return to work (P <0.05). CONCLUSION: The working capability recovery rate following arthroscopic rotator cuff repair was 66.7%, and the preoperative factors affecting recovery of working capability were heavy work and female sex.

Improving the estimation of the global burden of antimicrobial resistant infections.

Estimating the global burden of disease from infections caused by pathogens that have acquired antimicrobial resistance (AMR) is essential for resource allocation and to inform AMR action plans at national and global levels. However, the scarcity of robust and accepted methods to determine burden is widely acknowledged. In this Personal View, we discuss the underlying assumptions, characteristics, limitations, and comparability of the approaches used to quantify mortality from AMR bacterial infections. We show that the global burdens of AMR estimated in previous studies are not comparable because of their different methodological approaches, assumptions, and data used to generate the estimates. The analytical frameworks from previous studies are inadequate, and we conclude that a new approach to the estimation of deaths caused by AMR infection is needed. The innovation of a new approach will require the development of mechanisms to systematically collect a clinical dataset of substantial breadth and quality to support the accurate assessment of burden, combined with decision-making and resource allocation for interventions against AMR. We define key actions required and call for innovative thinking and solutions to address these problems.

Influenza-associated deaths among children in the United States, 2003-2004.

BACKGROUND: Although influenza is common among children, pediatric mortality related to laboratory-confirmed influenza has not been assessed nationally. METHODS: During the 2003-2004 influenza season, we requested that state health departments report any death associated with laboratory-confirmed influenza in a U.S. resident younger than 18 years of age. Case reports, medical records, and autopsy reports were reviewed, and available influenza-virus isolates were analyzed at the Centers for Disease Control and Prevention. RESULTS: One hundred fifty-three influenza-associated deaths among children were reported by 40 state health departments. The median age of the children was three years, and 96 of them (63 percent) were younger than five years old. Forty-seven of the children (31 percent) died outside a hospital setting, and 45 (29 percent) died within three days after the onset of illness. Bacterial coinfections were identified in 24 of the 102 children tested (24 percent). Thirty-three percent of the children had an underlying condition recognized to increase the risk of influenza-related complications, and 20 percent had other chronic conditions; 47 percent had previously been healthy. Chronic neurologic or neuromuscular conditions were present in one third. The mortality rate was highest among children younger than six months of age (0.88 per 100,000 children; 95 percent confidence interval, 0.52 to 1.39 per 100,000). CONCLUSIONS: A substantial number of influenza-associated deaths occurred among U.S. children during the 2003-2004 influenza season. High priority should be given to improvements in influenza-vaccine coverage and improvements in the diagnosis and treatment of influenza to reduce childhood mortality from influenza.