Surveillance system integration: reporting the results of a global multicountry survey.

OBJECTIVES: Currently, there is no comprehensive picture of the global surveillance landscape. This survey examines the current state of surveillance systems, levels of integration, barriers and opportunities for the integration of surveillance systems at the country level, and the role of national public health institutes (NPHIs). STUDY DESIGN: This was a cross-sectional survey of NPHIs. METHODS: A web-based survey questionnaire was disseminated to 110 NPHIs in 95 countries between July and August 2022. Data were descriptively analysed, stratified by World Health Organization region, World Bank Income Group, and self-reported Integrated Disease Surveillance (IDS) maturity status. RESULTS: Sixty-five NPHIs responded. Systems exist to monitor notifiable diseases and vaccination coverage, but less so for private, pharmaceutical, and food safety sectors. While Ministries of Health usually lead surveillance, in many countries, NPHIs are also involved. Most countries report having partially developed IDS. Surveillance data are frequently inaccessible to the lead public health agency and seldomly integrated into a national public health surveillance system. Common challenges to establishing IDS include information technology system issues, financial constraints, data sharing and ownership limitations, workforce capacity gaps, and data availability. CONCLUSIONS: Public health surveillance systems across the globe, although built on similar principles, are at different levels of maturity but face similar developmental challenges. Leadership, ownership and governance, supporting legal mandates and regulations, as well as adherence to mandates, and enforcement of regulations are critical components of effective surveillance. In many countries, NPHIs play a significant role in integrated disease surveillance.

Posttraumatic Stress, Anxiety, and Depression in COVID-19 Survivors.

OBJECTIVES: This study aims to examine the rates of anxiety, depression, and posttraumatic stress disorder (PTSD) after hospital discharge among COVID-19 survivors and to determine the associated risk factors. METHODS: Adult COVID-19 survivors discharged from hospitals between March 2020 and March 2021 were asked to complete a questionnaire at 4 weeks after discharge. The Chinese version of the 22-item Impact of Event Scale - Revised (IES-R) was used to measure symptoms of PTSD. The 9-item Patient Health Questionnaire (PHQ-9) was used to assess symptoms of major depressive disorder. The 7-item Generalised Anxiety Disorder Scale (GAD-7) was used to measure symptoms of generalised anxiety disorder. The rates of anxiety, depression, and PTSD among discharged patients were determined, as were associations between psychosocial factors and outcome measures and predictors for moderate-tosevere symptoms of anxiety, depression, and PTSD. RESULTS: 96 men and 103 women aged 18 to 81 years returned the completed questionnaire. 12.1% to 20.1% of them reported symptoms of PTSD, anxiety, or depression. Higher symptom severity was associated with higher perceived life threat, lower emotional support, lower disease severity upon admission, and longer hospital stay. Women had more PTSD symptoms than men, particularly when knowing someone under quarantine. CONCLUSION: COVID-19 survivors with higher perceived life threat, lower emotional support, lower disease severity upon admission, and longer hospital stay were associated with higher severity of symptoms of PTSD, anxiety, and depression. Timely intervention should provide to at-risk survivors.

Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.

Second tier non-invasive prenatal testing in a regional prenatal diagnosis service unit: a retrospective analysis and literature review.

INTRODUCTION: The Hong Kong Hospital Authority has newly introduced a new Down's syndrome screening algorithm that offers free-of-charge non-invasive prenatal testing (NIPT) to women who screen as high risk. In preparation for this public-funded second tier NIPT service, the present study was conducted to retrospectively analyse women eligible for NIPT and to review the local literature. METHODS: Our retrospective study included women screened as high risk for Down's syndrome (adjusted term risk ≥1:250) during the period of 1 January 2015 to 31 December 2016. We performed descriptive statistics and multivariable logistic regression to examine the factors associated with women's choice between NIPT and invasive testing. We also reviewed existing local literature about second tier NIPT. RESULTS: The study included 525 women who screened positive: 67% chose NIPT; 31% chose invasive diagnostic tests; and 2% declined further testing. Our literature review showed that in non-research (self-financed NIPT) settings, NIPT uptake rates have been increasing since 2011. Nulliparity, first trimester status, higher education, maternal employment, and conception by assisted reproductive technology are common factors associated with self-financed NIPT after positive screening. Among women choosing NIPT, the rates of abnormal results have typically been around 8% in studies performed in Hong Kong. CONCLUSION: Implementation of second tier NIPT in the public setting is believed to be able to improve quality of care. We expect that the public in Hong Kong will welcome the new policy.

Influenza increases invasive meningococcal disease risk in temperate countries.

OBJECTIVES: Invasive meningococcal disease (IMD) is a severe bacterial infection that displays wintertime seasonality in temperate countries. Mechanisms driving seasonality are poorly understood and may include environmental conditions and/or respiratory virus infections. We evaluated the contribution of influenza and environmental conditions to IMD risk, using standardized methodology, across multiple geographical regions. METHODS: We evaluated 3276 IMD cases occurring between January 1999 and December 2011 in 11 jurisdictions in Australia, Canada, France and the United States. Effects of environmental exposures and normalized weekly influenza activity on IMD risk were evaluated using a case-crossover design. Meta-analytic methods were used to evaluate homogeneity of effects and to identify sources of between-region heterogeneity. RESULTS: After adjustment for environmental factors, elevated influenza activity at a 2-week lag was associated with increased IMD risk (adjusted odds ratio (OR) per standard deviation increase 1.29; 95% confidence interval, 1.04-1.59). This increase was homogeneous across the jurisdictions studied. By contrast, although associations between environmental exposures and IMD were identified in individual jurisdictions, none was generalizable. CONCLUSIONS: Using a self-matched design that adjusts for both coseasonality and case characteristics, we found that surges in influenza activity result in an acute increase in population-level IMD risk. This effect is seen across diverse geographic regions in North America, France and Australia. The impact of influenza infection on downstream meningococcal risk should be considered a potential benefit of influenza immunization programmes.

Could exotic mosquito-borne diseases emerge in Canada with climate change?

Of the 3,500 species of mosquitoes worldwide, only a small portion carry and transmit the mosquito-borne diseases (MBDs) that cause approximately half a million deaths annually worldwide. The most common exotic MBDs, such as malaria and dengue, are not currently established in Canada, in part because of our relatively harsh climate; however, this situation could evolve with climate change. Mosquitoes native to Canada may become infected with new pathogens and move into new regions within Canada. In addition, new mosquito species may move into Canada from other countries, and these exotic species may bring exotic MBDs as well. With high levels of international travel, including to locations with exotic MBDs, there will be more travel-acquired cases of MBDs. With climate change, there is the potential for exotic mosquito populations to become established in Canada. There is already a small area of Canada where exotic Aedes mosquitoes have become established although, to date, there is no evidence that these carry any exotic (or already endemic) MBDs. The increased risks of spreading MBDs, or introducing exotic MBDs, will need a careful clinical and public health response. Clinicians will need to maintain a high level of awareness of current trends, to promote mosquito bite prevention strategies, and to know the laboratory tests needed for early detection and when to report laboratory results to public health. Public health efforts will need to focus on ongoing active surveillance, public and professional awareness and mosquito control. Canadians need to be aware of the risks of acquiring exotic MBDs while travelling abroad as well as the risk that they could serve as a potential route of introduction for exotic MBDs into Canada when they return home.

Risk assessment strategies for early detection and prediction of infectious disease outbreaks associated with climate change.

A new generation of surveillance strategies is being developed to help detect emerging infections and to identify the increased risks of infectious disease outbreaks that are expected to occur with climate change. These surveillance strategies include event-based surveillance (EBS) systems and risk modelling. The EBS systems use open-source internet data, such as media reports, official reports, and social media (such as Twitter) to detect evidence of an emerging threat, and can be used in conjunction with conventional surveillance systems to enhance early warning of public health threats. More recently, EBS systems include artificial intelligence applications such machine learning and natural language processing to increase the speed, capacity and accuracy of filtering, classifying and analysing health-related internet data. Risk modelling uses statistical and mathematical methods to assess the severity of disease emergence and spread given factors about the host (e.g. number of reported cases), pathogen (e.g. pathogenicity) and environment (e.g. climate suitability for reservoir populations). The types of data in these models are expanding to include health-related information from open-source internet data and information on mobility patterns of humans and goods. This information is helping to identify susceptible populations and predict the pathways from which infections might spread into new areas and new countries. As a powerful addition to traditional surveillance strategies that identify what has already happened, it is anticipated that EBS systems and risk modelling will increasingly be used to inform public health actions to prevent, detect and mitigate the climate change increases in infectious diseases.

A case of cough induced rib fracture with subcutaneous emphysema and pneumothorax.

Coughing is an important reflex mechanism which enhances the clearance of secretions and particulates from the airways, however repetitive muscle strain due to prolonged coughing may cause the uncommon complication of stress fracture of the ribs. The following is an unusual case of cough induced multiple rib fractures associated with subcutaneous emphysema and pneumothorax which was missed in the emergency setting. Delayed diagnosis and treatment would have been avoided if this uncommon condition was considered as a possibility.

Isolated vascular "v" lesions in liver allografts: How to approach this unusual finding.

According to the Banff criteria for kidney allografts, isolated vascular or "v" lesions are defined as intimal inflammation, age-inappropriate fibro-intimal hyperplasia, or both, without the presence of associated interstitial T cell-mediated rejection (TCMR). In general, these lesions portend a worse outcome for kidney allografts, particularly in those where the "v" lesions are identified in patients with coexistent donor specific antibodies (DSA) or later after transplantation. Although affected arteries are rarely sampled in liver allograft biopsies, we identified nine patients at a mean of 1805 days posttransplantation and compared these to matched controls. Almost half (4 of 9) of the study patient biopsies showed inflammatory arteritis associated with focal or diffuse C4d positivity, which was not observed in matched controls. One "v" lesion patient progressed to rejection-related graft failure and two developed moderate/severe TCMR in subsequent biopsies, whereas only one rejection episode occurred in follow-up biopsies, and no rejection-related deaths or graft failures were detected in controls. In conclusion, patients with liver allograft isolated "v" lesions should undergo further evaluation and closer follow-up for impending TCMR and/or underlying co-existent chronic antibody-mediated rejection (AMR).

Injuries and envenomation by exotic pets in Hong Kong.

INTRODUCTION: Exotic pets are increasingly popular in Hong Kong and include fish, amphibians, reptiles, and arthropods. Some of these exotic animals are venomous and may cause injuries to and envenomation of their owners. The clinical experience of emergency physicians in the management of injuries and envenomation by these exotic animals is limited. We reviewed the clinical features and outcomes of injuries and envenomation by exotic pets recorded by the Hong Kong Poison Information Centre. METHODS: We retrospectively retrieved and reviewed cases of injuries and envenomation by exotic pets recorded by the Hong Kong Poison Information Centre from 1 July 2008 to 31 March 2017. RESULTS: There were 15 reported cases of injuries and envenomation by exotic pets during the study period, including snakebite (n=6), fish sting (n=4), scorpion sting (n=2), lizard bite (n=2), and turtle bite (n=1). There were two cases of major effects from the envenomation, seven cases with moderate effects, and six cases with mild effects. All major effects were related to venomous snakebites. There were no mortalities. CONCLUSION: All human injuries from exotic pets arose from reptiles, scorpions, and fish. All cases of major envenomation were inflicted by snakes.

Patterns of kidney injury in pediatric nonkidney solid organ transplant recipients.

The incidence of acute kidney injury (AKI) and its impact on chronic kidney disease (CKD) following pediatric nonkidney solid organ transplantation is unknown. We aimed to determine the incidence of AKI and CKD and examine their relationship among children who received a heart, lung, liver, or multiorgan transplant at the Hospital for Sick Children between 2002 and 2011. AKI was assessed in the first year posttransplant. Among 303 children, perioperative AKI (within the first week) occurred in 67% of children, and AKI after the first week occurred in 36%, with the highest incidence among lung and multiorgan recipients. Twenty-three children (8%) developed CKD after a median follow-up of 3.4 years. Less than 5 children developed end-stage renal disease, all within 65 days posttransplant. Those with 1 AKI episode by 3 months posttransplant had significantly greater risk for developing CKD after adjusting for age, sex, and estimated glomerular filtration rate at transplant (hazard ratio: 2.77, 95% confidence interval, 1.13-6.80, P trend = .008). AKI is common in the first year posttransplant and associated with significantly greater risk of developing CKD. Close monitoring for kidney disease may allow for earlier implementation of kidney-sparing strategies to decrease risk for progression to CKD.

Does Spanish instruction for emergency medicine resident physicians improve patient satisfaction in the emergency department and adherence to medical recommendations?

BACKGROUND: After emergency department (ED) discharge, Spanish-speaking patients with limited English proficiency are less likely than English-proficient patients to be adherent to medical recommendations and are more likely to be dissatisfied with their visit. OBJECTIVES: To determine if integrating a longitudinal medical Spanish and cultural competency curriculum into emergency medicine residency didactics improves patient satisfaction and adherence to medical recommendations in Spanish-speaking patients with limited English proficiency. METHODS: Our ED has two Emergency Medicine Residency Programs, University Campus (UC) and South Campus (SC). SC program incorporates a medical Spanish and cultural competency curriculum into their didactics. Real-time Spanish surveys were collected at SC ED on patients who self-identified as primarily Spanish-speaking during registration and who were treated by resident physicians from both residency programs. Surveys assessed whether the treating resident physician communicated in the patient's native Spanish language. Follow-up phone calls assessed patient satisfaction and adherence to discharge instructions. RESULTS: Sixty-three patients self-identified as primarily Spanish-speaking from August 2014 to July 2015 and were initially included in this pilot study. Complete outcome data were available for 55 patients. Overall, resident physicians spoke Spanish 58% of the time. SC resident physicians spoke Spanish with 66% of the patients versus 45% for UC resident physicians. Patients rated resident physician Spanish ability as very good in 13% of encounters - 17% for SC versus 5% for UC. Patient satisfaction with their ED visit was rated as very good in 35% of encounters - 40% for SC resident physicians versus 25% for UC resident physicians. Of the 13 patients for whom Spanish was the language used during the medical encounter who followed medical recommendations, ten (77%) of these encounters were with SC resident physicians and three (23%) encounters were with UC resident physicians. CONCLUSION: Preliminary data suggest that incorporating Spanish language and cultural competency into residency training has an overall beneficial effect on patient satisfaction and adherence to medical recommendations in Spanish-speaking patients with limited English proficiency.

Prioritizing Zoonotic Diseases: Differences in Perspectives Between Human and Animal Health Professionals in North America.

Zoonoses pose a significant burden of illness in North America. Zoonoses represent an additional threat to public health because the natural reservoirs are often animals, particularly wildlife, thus eluding control efforts such as quarantine, vaccination and social distancing. As there are limited resources available, it is necessary to prioritize diseases in order to allocate resources to those posing the greatest public health threat. Many studies have attempted to prioritize zoonoses, but challenges exist. This study uses a quantitative approach, conjoint analysis (CA), to overcome some limitations of traditional disease prioritization exercises. We used CA to conduct a zoonoses prioritization study involving a range of human and animal health professionals across North America; these included epidemiologists, public health practitioners, research scientists, physicians, veterinarians, laboratory technicians and nurses. A total of 699 human health professionals (HHP) and 585 animal health professionals (AHP) participated in this study. We used CA to prioritize 62 zoonotic diseases using 21 criteria. Our findings suggest CA can be used to produce reasonable criteria scores for disease prioritization. The fitted models were satisfactory for both groups with a slightly better fit for AHP compared to HHP (84.4% certainty fit versus 83.6%). Human-related criteria were more influential for HHP in their decision to prioritize zoonoses, while animal-related criteria were more influential for AHP resulting in different disease priority lists. While the differences were not statistically significant, a difference of one or two ranks could be considered important for some individuals. A potential solution to address the varying opinions is discussed. The scientific framework for disease prioritization presented can be revised on a regular basis by updating disease criteria to reflect diseases as they evolve over time; such a framework is of value allowing diseases of highest impact to be identified routinely for resource allocation.

Interaction of MYC with host cell factor-1 is mediated by the evolutionarily conserved Myc box IV motif.

The MYC family of oncogenes encodes a set of three related transcription factors that are overexpressed in many human tumors and contribute to the cancer-related deaths of more than 70,000 Americans every year. MYC proteins drive tumorigenesis by interacting with co-factors that enable them to regulate the expression of thousands of genes linked to cell growth, proliferation, metabolism and genome stability. One effective way to identify critical co-factors required for MYC function has been to focus on sequence motifs within MYC that are conserved throughout evolution, on the assumption that their conservation is driven by protein-protein interactions that are vital for MYC activity. In addition to their DNA-binding domains, MYC proteins carry five regions of high sequence conservation known as Myc boxes (Mb). To date, four of the Mb motifs (MbI, MbII, MbIIIa and MbIIIb) have had a molecular function assigned to them, but the precise role of the remaining Mb, MbIV, and the reason for its preservation in vertebrate Myc proteins, is unknown. Here, we show that MbIV is required for the association of MYC with the abundant transcriptional coregulator host cell factor-1 (HCF-1). We show that the invariant core of MbIV resembles the tetrapeptide HCF-binding motif (HBM) found in many HCF-interaction partners, and demonstrate that MYC interacts with HCF-1 in a manner indistinguishable from the prototypical HBM-containing protein VP16. Finally, we show that rationalized point mutations in MYC that disrupt interaction with HCF-1 attenuate the ability of MYC to drive tumorigenesis in mice. Together, these data expose a molecular function for MbIV and indicate that HCF-1 is an important co-factor for MYC.

Primary spinal oligoastrocytoma mimicking longitudinally extensive transverse myelitis.

Longitudinally extensive transverse myelitis (LETM) is most commonly associated with neuromyelitis optica spectrum disorders (NMOSD). However, a wide range of etiologies may produce longitudinally extensive spinal cord lesions (LESCLs) on imaging. We highlight the case of a patient with a spinal cord tumor whose imaging showed LESCL and was diagnosed with LETM. He did not respond to immunosuppression and subsequently developed a progressive and protracted clinical course. Thoracic cord biopsy performed 6 years after symptom onset showed primary spinal oligoastrocytoma. We discuss the features that should raise suspicion of a neoplasm in the context of LESCL and serve a reminder that not all LESCLs are inflammatory.

High Risk of Graft Failure in Emerging Adult Heart Transplant Recipients.

Emerging adulthood (17-24 years) is a period of high risk for graft failure in kidney transplant. Whether a similar association exists in heart transplant recipients is unknown. We sought to estimate the relative hazards of graft failure at different current ages, compared with patients between 20 and 24 years old. We evaluated 11 473 patients recorded in the Scientific Registry of Transplant Recipients who received a first transplant at <40 years old (1988-2013) and had at least 6 months of graft function. Time-dependent Cox models were used to estimate the association between current age (time-dependent) and failure risk, adjusted for time since transplant and other potential confounders. Failure was defined as death following graft failure or retransplant; observation was censored at death with graft function. There were 2567 failures. Crude age-specific graft failure rates were highest in 21-24 year olds (4.2 per 100 person-years). Compared to individuals with the same time since transplant, 21-24 year olds had significantly higher failure rates than all other age periods except 17-20 years (HR 0.92 [95%CI 0.77, 1.09]) and 25-29 years (0.86 [0.73, 1.03]). Among young first heart transplant recipients, graft failure risks are highest in the period from 17 to 29 years of age.

Elafin drives poor outcome in high-grade serous ovarian cancers and basal-like breast tumors.

High-grade serous ovarian carcinoma (HGSOC) and basal-like breast cancer (BLBC) share many features including TP53 mutations, genomic instability and poor prognosis. We recently reported that Elafin is overexpressed by HGSOC and is associated with poor overall survival. Here, we confirm that Elafin overexpression is associated with shorter survival in 1000 HGSOC patients. Elafin confers a proliferative advantage to tumor cells through the activation of the MAP kinase pathway. This mitogenic effect can be neutralized by RNA interference, specific antibodies and a MEK inhibitor. Elafin expression in patient-derived samples was also associated with chemoresistance and strongly correlates with bcl-xL expression. We extended these findings into the examination of 1100 primary breast tumors and six breast cancer cell lines. We observed that Elafin is overexpressed and secreted specifically by BLBC tumors and cell lines, leading to a similar mitogenic effect through activation of the MAP kinase pathway. Here too, Elafin overexpression is associated with poor overall survival, suggesting that it may serve as a biomarker and therapeutic target in this setting.

Simultaneous liver-pancreas transplantation for cystic fibrosis-related liver disease: a multicenter experience.

BACKGROUND: Diabetes is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). While liver transplantation is well established for CF-related liver disease (CFLD), the role of simultaneous liver-pancreas transplantation is less understood. METHODS: We polled 81 pediatric transplantation centers to identify and characterize subjects who had undergone simultaneous liver-pancreas transplantation and obtain opinions about this procedure in CFLD. RESULTS: Fifty (61.7%) polled transplant centers responded and 94% reported that they would consider simultaneous liver-pancreas transplantation for CFLD and diabetes. A total of 8 patients with simultaneous liver-pancreas transplantation were identified with median follow up of 38 months. All patients had pre-existing diabetes. Exocrine and endocrine pancreatic function was initially restored in all patients with later functional loss in one patient. Body mass index Z-score increased between one year pre-transplantation and one year post-transplantation (P=0.029). CONCLUSIONS: Patients with CFLD undergoing initial assessment for liver transplantation may benefit from consideration of simultaneous liver-pancreas transplantation.

Basiliximab with delayed introduction of calcineurin inhibitors as a renal-sparing protocol following liver transplantation in children with renal impairment.

Renal impairment is frequently compromised in patients with end-stage liver disease and is associated with increased long-term mortality post-LT. In contrast to CNI, basiliximab is an immunosuppressive agent with minimal nephrotoxic potential. This study reviews the experience of a single pediatric liver transplant center's renal-sparing approach with the use of basiliximab and MMF to compensate for delayed entry of CNI in children with renal impairment at the time of organ availability. There were no differences in renal function between pediatric patients with and without pre-LT renal impairment within the first year (cGFR: 135 mL/min/1.73 m2 vs. 144 mL/min/1.73 m2 ; p = 0.56) or at 5-8 yr following LT, (129 mL/min/1.73 m2 vs. 130 mL/min/1.73 m2 ; p = 0.97). In addition, there was no difference in ACR rates (50% vs. 43%, p = 0.62) between patients in the basiliximab group and those patients receiving standard CNI and steroid strategies. The utilization of a renal-sparing approach with basiliximab alongside delayed entry and lower early target trough levels of CNI in children with renal impairment at the time of LT is safe and maintains excellent long-term kidney function.