Disease In High-income Countries Research Articles

ColiSeq: a multiplex amplicon assay that provides strain level resolution of Escherichia coli directly from clinical specimens.

Escherichia coli is a diverse pathogen, causing a range of disease in humans, from self-limiting diarrhea to urinary tract infections (UTIs). Uropathogenic E. coli (UPEC) is the most frequently observed uropathogen in UTIs, a common disease in high-income countries, incurring billions of dollars yearly in treatment costs. Although E. coli is easily grown and identified in the clinical laboratory, genotyping the pathogen is more complicated, yet critical for reducing the incidence of disease. These goals can be achieved through whole-genome sequencing of E. coli isolates, but this approach is relatively slow and typically requires culturing the pathogen in the laboratory. To genotype E. coli rapidly and inexpensively directly from clinical samples, including but not limited to urine, we developed and validated a multiplex amplicon sequencing assay, called ColiSeq. The assay consists of targets designed for E. coli species confirmation, high resolution genotyping, and mixture deconvolution. To demonstrate its utility, we screened the ColiSeq assay against 230 clinical urine samples collected from a hospital system in Flagstaff, Arizona, USA. A limit of detection analysis demonstrated the ability of ColiSeq to identify E. coli at a concentration of ~2 genomic equivalent (GEs)/mL and to generate high-resolution genotyping at a concentration of 1 × 105 GEs/mL. The results of this study suggest that ColiSeq could be a valuable method to understand the source of UPEC strains and guide infection mitigation efforts. As sequence-based diagnostics become accepted in the clinical laboratory, workflows such as ColiSeq will provide actionable information to improve patient outcomes.IMPORTANCEUrinary tract infections (UTIs), caused primarily by Escherichia coli, create an enormous health care burden in the United States and other high-income countries. The early detection of E. coli from clinical samples, including urine, is important to target therapy and prevent further patient complications. Additionally, understanding the source of E. coli exposure will help with future mitigation efforts. In this study, we developed, tested, and validated an amplicon sequencing assay focused on direct detection of E. coli from urine. The resulting sequence data were demonstrated to provide strain level resolution of the pathogen, not only confirming the presence of E. coli, which can focus treatment efforts, but also providing data needed for source attribution and contact tracing. This assay will generate inexpensive, rapid, and reproducible data that can be deployed by public health agencies to track, diagnose, and potentially mitigate future UTIs caused by E. coli.

Digital Health Interventions in Older Adult Populations Living With Chronic Disease in High-Income Countries: Protocol for a Scoping Review.

Globally, around 80% percent of adults aged 65 years or older are living with at least 1 chronic disease, and 68% percent have 2 or more chronic diseases. Older adults living with chronic diseases require greater health care services, but these health care services are not always easily accessible. Furthermore, the COVID-19 pandemic has resulted in unprecedented changes in the provision of health care services for older adults. During the COVID-19 pandemic, digital health interventions for chronic disease management were developed out of necessity, but the evidence regarding these and developed interventions is lacking. In this scoping review, we aim to identify available digital health interventions such as emails, text messages, voice messages, telephone calls, video calls, mobile apps, and web-based platforms for chronic disease management for older adults in high-income countries. We will follow the Arksey and O'Malley framework to conduct the scoping review. Our full search strategy was developed following a preliminary search on MEDLINE. We will include studies where older adults are at least 65 years of age, living with at least 1 chronic disease (eg, cancer, cardiovascular disease, chronic obstructive pulmonary disease, and diabetes), and residing in high-income countries. Digital health interventions will be broadly defined to include emails, text messages, voice messages, telephone calls, video calls, mobile apps, and web-based platforms. This scoping review is currently ongoing. As of March 2023, our full search strategy has resulted in a total of 9901 records. We completed the screening of titles and abstracts and obtained 442 abstracts for full-text review. We are aiming to complete our full-text review in October 2024, data extraction in November 2024, and data synthesis in December 2024. This scoping review will generate evidence that will contribute to the further development of digital health interventions for future chronic disease management among older adults in high-income countries. More evidence-based research is needed to better understand the feasibility and limitations associated with the use of digital health interventions for this population. These evidence-based findings can then be disseminated to decision-makers and policy makers in other high-income countries. DERR1-10.2196/49130.

Low Levels of Lifetime Pap Test Receipt Among Vulnerable Guatemalans.

Low and middle-income countries, such as Guatemala, shoulder a disproportionate share of cervical cancer, a preventable disease in high income countries. Tangible obstacles, such as lack of access to health care, cultural differences, and insufficient infrastructure, and facilitators, such as being Ladino, married, and educated, have been identified in the literature related to cervical cancer prevention. The aim of this survey was to explore barriers and facilitators to cervical cancer prevention, comparing rural Indigenous and urban Ladino populations. We surveyed 139 women in two health clinics. Participants answered questions about demographic information, cervical cancer knowledge, and health care behaviors. We analyzed survey data with four bivariate models. Our results suggest vulnerable populations, such as rural Indigenous women who are single, illiterate, and lack education, face higher cervical cancer risk. Partnerships should be formed with health promotors and lay midwives to educate and encourage vulnerable populations to prevent cervical cancer.

Risk Prediction and Management of Chronic Kidney Disease in People Living with Type 2 Diabetes Mellitus.

People with type 2 diabetes mellitus have increased risk of chronic kidney disease and atherosclerotic cardiovascular disease. Improved care delivery and implementation of guideline-directed medical therapy have contributed to the declining incidence of atherosclerotic cardiovascular disease in high-income countries. By contrast, the global incidence of chronic kidney disease and associated mortality is either plateaued or increased, leading to escalating direct and indirect medical costs. Given limited resources, better risk stratification approaches to identify people at risk of rapid progression to end-stage kidney disease can reduce therapeutic inertia, facilitate timely interventions and identify the need for early nephrologist referral. Among people with chronic kidney disease G3a and beyond, the kidney failure risk equations (KFRE) have been externally validated and outperformed other risk prediction models. The KFRE can also guide the timing of preparation for kidney replacement therapy with improved healthcare resources planning and may prevent multiple complications and premature mortality among people with chronic kidney disease with and without type 2 diabetes mellitus. The present review summarizes the evidence of KFRE to date and call for future research to validate and evaluate its impact on cardiovascular and mortality outcomes, as well as healthcare resource utilization in multiethnic populations and different healthcare settings.

A Working Definition of Acute Chest Syndrome without the Requirement of Chest X-Rays

Introduction:Sickle Cell Disease (SCD) is a rare genetic disease in high-income countries where most of the cited literature used to guide clinical management emanate from. One of the most serious and potentially fatal complications of SCD is acute chest syndrome (ACS) which requires immediate medical attention. Approximately 50% of individuals with SCD will eventually develop ACS ( Blood 84, 643-649 (1994)). Despite the high frequency of ACS and its associated risk of death, no consensus diagnosis has been established that applies to children and adults living in low-middle income countries, where 95% of the children born with SCD are found. To create a uniform definition of ACS in both low, middle, and high-income countries, we propose using a new ACS definition that does not require a chest X-ray. Additionally, the new ACS definition should have a quantifiable and reproducible physical examination and clinical findings to allow for the reproducibility of the definition in all settings. This definition was developed over several years at Korle Bu Teaching Hospital, Accra Ghana, in pregnant women with SCD. Before we started the multidisciplinary team care in pregnant women with SCD, ACS was the most common cause of maternal death. Subsequently, based on the new ACS definition that did not require a chest X-ray, we developed strategies to prevent, aid early diagnosis, and treat ACS resulting in an 89% relative risk reduction of death. We refer to this new definition as the Korle Bu Teaching Hospital (KBTH)-ACS definition. In this study, we compare the ACS definition in the top 20 cited ACS articles as of July 2023 with our proposed KBTH-ACS definition. Methods:Using Google Scholar, we identified the top 20 cited articles with ACS in children or adults with SCD as primary or secondary outcomes. Each article was reviewed for the presence of the following criteria: chest x-ray, vitals, hemoglobin oxygen saturation, and lung physical exam findings. We compared the definition of ACS in the top 20 cited ACS articles to the KBTH-ACS definition that included the following features: “abnormal findings on lung auscultation and the presence of at least 2 of the following criteria: 1) temperature ≥ 38.0°C, 2) increased respiratory rate greater than the 90th percentile for age, positive chest pain or pulmonary auscultatory findings, 3) hemoglobin oxygen saturation decrease by ≥3% from a documented steady-state value on room air, and 4) a new radiodensity on chest roentgenogram. A diagnosis of pneumonia was considered an ACS episode.”. Results:The 20 most cited ACS articles required radiographical criteria to diagnose ACS. Fourteen of twenty articles included fever in their ACS definition. However, only 4 articles specified any temperature and all specified ≥ 38.5 ºC. A total of 17 articles mentioned the presence of lung or respiratory findings, but only 12 articles specifically identified the pulmonary findings. Among the 12 articles that specified lung findings, 5 included increased respiratory rate (tachypnea) without a specific definition, 2 included abnormal auscultatory findings, and 3 included hypoxemia/hypoxia in their definition. However. One study defined hypoxemia/hypoxia as “transcutaneous oxygen saturation <85% despite supplemental oxygen.”. Another article included “SpO2 of ≥ 3% compared to baseline steady-state values.”. In addition, among the twelve studies that specified respiratory findings, the following were present or absent features: chest pain (n=12), wheezing (n=3), coughing(n=3), and respiratory distress without a formal definition (n=3). No article included pneumonia in the ACS definition nor defined a threshold for tachypnea that was age-adjusted. None of the articles would allow for a direct comparison with the KBTH-ACS definition. Conclusion: All the 20 most cited ACS articles required a chest X-ray with various clinical and physical examination findings. Many of the ACS definitions in these studies were based on clinical impressions that were not quantifiable or reproducible. We propose using the KBTH-ACS definition in future ACS studies to improve generalizability, reproducibility, and genotype and phenotype studies designed to elucidate the genetic variation of lung disease in children and adults with SCD.

Abstract 17828: Sex Differences in Mortality Trends of Rheumatic Heart Disease in High-Income Countries

Introduction: Rheumatic heart disease has traditionally been considered to be more prevalent among females; however, current trends in mortality in each sex are unclear in high-income countries. Hypothesis: We hypothesized that mortality from rheumatic heart disease is higher among females but has improved in both sexes in high-income countries. Methods: We analyzed the WHO mortality database to determine trends in mortality from rheumatic heart disease in the UK, Germany, France, Italy, Japan, Australia, the USA, and Canada from 2000 to 2020. Sex-specific age-standardized mortality rates per 100,000 persons were calculated and compared by using female-to-male ratio. Annual percentage change was analyzed using joinpoint regression. Results: In the most recent year, female sex-specific age-standardized mortality rates were significantly higher in the UK (0.60 vs 0.44), Italy (1.24 vs 0.98), the USA (0.63 vs 0.47) and Canada (0.79 vs 0.57). Over the observation period, there was a trend to deceasing sex-specific age-standardized mortality rates in both sexes in the UK, France, Japan, and USA (p<0.01, respectively) and only in female sex in Italy and Australia (p<0.01, respectively), while the mortality rates in both sexes were constant in Canada and demonstrated increasing trends in Germany. Average female-to-male mortality rates ranged from 1.07 (95% CI, 1.02, 1.11) in France to 1.59 (95% CI, 1.51, 1.67) in the UK and were decreasing toward 1 with statistical significance in all countries (average annual change ranged from -1.6% to -0.6%) except for France. Conclusions: Mortality from rheumatic heart disease in females exhibited a decreasing trend in the 6 studied high-income countries while increasing in Germany and constant in Canada. Female-dominated mortality was becoming less pronounced in the studied high-income countries, with the exception of France, which already had the lowest average female-dominant mortality rates.

Age period cohort analysis of rheumatic heart disease in high-income countries.

Rheumatic heart disease is considered well-controlled in high-income countries; however, its actual trends in mortality remain unclarified. We analyzed trends in mortality from rheumatic heart disease in association with age, period, and birth cohort. We analyzed the WHO mortality database to determine trends in mortality from rheumatic heart disease in the UK, Germany, France, Italy, Japan, Australia, USA, and Canada from 2000 to 2020. We used age-cohort-period modeling to estimate cohort and period effects. Net drift (overall annual percentage change), local drift (annual percentage change in each age group) and heterogeneity were calculated. In the most recent year, crude mortality rates and age-standardized mortality rates ranged from 1.10 in the USA to 6.17 in Germany, and 0.32 (95% CI 0.31-0.34) in Japan and 1.70 (95% CI 1.65-1.75) in Germany, respectively. During the observation period, while Germany had a constant trend in overall annual percentage change, all the other countries had significant decreasing trends (p < 0.0001, respectively). Annual percent change was not homogeneous across each group in all 8 countries (pheterogeneity < 0.0001), with 2 peaks in the younger and older age categories. In Germany, Italy, Australia, and Canada, we found increasing mortality rates among older patients. Improving period and cohort risks for rheumatic heart disease mortality were generally observed, excluding Germany where the period effect was worsening and the cohort effect was constant. Mortality trends from rheumatic heart disease were decreasing in the study high-income countries except for Germany where higher mortality and two peaks in annual percentage change in younger and older age groups warrant further investigation.

Hypofractionation in Breast Cancer Radiotherapy Across World Bank Income Groups: Results of an International Survey.

Hypofractionated breast radiotherapy has been found to be equivalent to conventional fractionation in many clinical trials. Using data from the European Society for Radiotherapy and Oncology Global Impact of Radiotherapy in Oncology survey, we identified preferences for hypofractionation in breast cancer across World Bank income groups and the perceived facilitators and barriers to its use. An international, electronic survey was administered to radiation oncologists from 2018 to 2019. Demographics, practice characteristics, preferred hypofractionation regimen for specific breast cancer scenarios, and facilitators and barriers to hypofractionation were reported and stratified by World Bank income groups. Variables associated with hypofractionation were assessed using multivariate logistic regression models. One thousand four hundred thirty-four physicians responded: 890 (62%) from high-income countries (HICs), 361 (25%) from upper-middle-income countries (UMICs), 183 (13%) from low- and lower-middle-income countries (LLMICs). Hypofractionation was preferred most frequently in node-negative disease after breast-conserving surgery, with the strongest preference reported in HICs (78% from HICs, 54% from UMICs, and 51% from LLMICs, P < .001). Hypofractionation for node-positive disease postmastectomy was more frequently preferred in LLMICs (28% from HICs, 15% from UMICs, and 35% from LLMICs, P < .001). Curative doses of 2.1 to < 2.5 Gy in 15-16 fractions were most frequently reported, with limited preference for ultra-hypofractionation, but significant variability in palliative dosing. In adjusted analyses, UMICs were significantly less likely than LLMICs to prefer hypofractionation across all curative clinical scenarios, whereas respondents with > 1 million population catchments and with intensity-modulated radiotherapy were more likely to prefer hypofractionation. The most frequently cited facilitators and barriers were published evidence and fear of late toxicity, respectively. Preference for hypofractionation varied for curative indications, with greater acceptance in earlier-stage disease in HICs and in later-stage disease in LLMICs. Targeted educational interventions and greater inclusivity in radiation oncology clinical trials may support greater uptake.

Evidence-based management of pregnant women with sickle cell disease in high-income countries

Globally, patients living with sickle cell disease are now surviving to reproductive age, with life expectancy approaching 50 years in most countries. Thus, reproductive options are now essential for patients living with the condition. However, it can be associated with maternal, delivery, and fetal complications. Outcomes may vary depending on the level of expertise and resources. In this piece we provide an optional guideline for managing sickle cell disease in pregnancy. The therapeutic option of serial exchange prophylactic transfusion has been offered in the context of a clinical trial (TAPS2).

Risk for Mortality with Increasingly Severe Aortic Stenosis: An International Cohort Study

Aortic stenosis (AS) is the most common valvular heart disease in high-income countries. Adjusted for clinical confounders, the risk associated with increasing AS severity across the spectrum of AS severity remains uncertain. The authors conducted an international, multicenter, parallel-cohort study of 217,599 Australian (mean age, 76.0±7.3years; 49.3% women) and 30,865 US (mean age, 77.4±7.3years; 52.2% women) patients aged ≥65years who underwent echocardiography. Patients with previous aortic valve replacement were excluded. The risk of increasing AS severity, quantified by peak aortic velocity (Vmax), was assessed through linkage to 97,576 and 14,481 all-cause deaths in Australia and the United States, respectively. The distribution of AS severity (mean Vmax, 1.7±0.7m/sec) was similar in both cohorts. Compared with those with Vmax of 1.0 to 1.49m/sec, those with Vmax of 2.50 to 2.99m/sec (US cohort) or Vmax of 3.0 to 3.49m/sec (Australian cohort) had a 1.5-fold increase in mortality risk within 10years, adjusting for age, sex, presence of left heart disease, and left ventricular ejection fraction. Overall, the adjusted risk for mortality plateaued (1.75- to 2.25-fold increased risk) above a Vmax of 3.5m/sec. This pattern of mortality persisted despite adjustment for a comprehensive list of comorbidities and treatments within the US cohort. Within large, parallel patient cohorts managed in different health systems, similar patterns of mortality linked to increasingly severe AS were observed. These findings support ongoing clinical trials of aortic valve replacement in patients with nonsevere AS and suggest the need to develop and apply more proactive surveillance strategies in this high-risk population.

Biomarker characterization in endometrial cancer in Italy: first survey data analysis.

SummaryObjectiveEndometrial carcinoma (EC) is the most common gynecological malignant disease in high income countries. The 2020 edition of the World Health Organization (WHO) Classification of Tumors of the Female Genital Tract underlines the important clinical implications of the new integrated histo-molecular classification system, in order to correctly define the specific prognostic risk group. This survey analysis will focus on the most commonly adopted immunohistochemical and molecular biomarkers used in daily clinical characterization of a diagnosed endometrial carcinoma in Italian labs.MethodsAn evaluation questionnaire was distributed to 41 Italian pathology laboratories. Normal habits in EC evaluation, especially regarding mismatch repair status (MMR) and microsatellite instability (MSI), were collected. A summary and a descriptive statistical analysis were used to show the current practice of each laboratory.ResultsThe analysis of MMR status by immunohistochemistry (IHC) is carried out on the majority of all EC samples. The most frequent strategy for the analysis of MMR status in EC is IHC of four proteins (PMS2, MSH6, MSH2, MLH1). MSI analysis by molecular method in endometrial cancer is rarer and more restricted to some circumstances. Hypermethylation of the MLH1 promoter by methylation-specific PCR and pyrosequencing was analyzed in case of negative expression of MLH1/PMS2. Also, the analysis of p53 in EC is performed in the majority of cases. POLE mutational profiling is adopted only in a limited number of laboratories. Fifty-five percent of Italian laboratories refer to national/international guidelines when analyzing biomarkers in EC (among those, 45% use the ESGO Guidelines, 18% ASCO-CAP, 18% AIOM, 14% WHO, 5% British Association of Gynaecological Pathologist, 5% ESMO, 5% NCCN).ConclusionsAdoption of guidelines and standardization of pre-analytical and analytical procedures are effective tools for adequate EC prognostic risk stratification and high quality standard of care.

Corticosteroids for the treatment of Kawasaki disease in children.

Kawasaki disease (KD), or mucocutaneous syndrome, is the leading cause of childhood-acquired heart disease in high-income countries. There is much controversy on how best to treat children with KD and in particular who may benefit from additional treatment beyond the standard intravenous immunoglobulin (IVIG) and aspirin, such as the addition of corticosteroids. This is an update of the review first published in 2017. To assess the impact of corticosteroid use on the incidence of coronary artery abnormalities in KD as either first-line or second-line treatment. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and two trials registers to 8 February 2021. We searched the reference lists of relevant articles for additional studies. We selected randomised controlled trials involving children with all severities of KD who were treated with corticosteroids, including different types of corticosteroids, different durations of treatment, and where corticosteroids were used alone or in conjunction with other accepted KD treatments. We included trials using corticosteroids for both first- and second-line treatment. Two review authors independently selected studies, assessed study quality and extracted data using standard Cochrane methods. We performed fixed-effect model meta-analyses with odds ratios (ORs) or mean difference (MD) with 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. We assessed the certainty of the evidence using GRADE. The outcomes of interest were incidence of coronary artery abnormalities, serious adverse events, mortality, duration of acute symptoms (such as fever), time for laboratory parameters to normalise, length of hospital stay and longer-term coronary morbidity. This update identified one new study, therefore the analysis included eight trials consisting of 1877 participants. Seven trials investigated the use of corticosteroids in first-line treatment and one investigated second-line treatment. The trials were all of good methodological quality. On pooled analysis, corticosteroid treatment reduced the subsequent occurrence of coronary artery abnormalities (OR 0.32, 95% CI 0.14 to 0.75; 8 studies, 986 participants; moderate-certainty evidence), without resultant serious adverse events (0 events; 6 studies, 737 participants; moderate-certainty) and mortality (0 events; 8 studies, 1075 participants; moderate-certainty evidence). In addition, corticosteroids reduced the duration of fever (MD -1.34 days, 95% CI -2.24 to -0.45; 3 studies, 290 participants; low-certainty evidence), time for laboratory parameters (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) to normalise (MD -2.80 days, 95% CI -4.38 to -1.22; 1 study, 178 participants; moderate-certainty evidence), and length of hospital stay (MD -1.01 days, 95% CI -1.72 to -0.30; 2 studies, 119 participants; moderate-certainty evidence). None of the included studies reported long-term (greater than one year after disease onset) coronary morbidity. Moderate-certainty evidence shows that use of steroids in the acute phase of KD can be associated with reduced coronary artery abnormalities, reduced inflammatory markers and shorter duration of hospital stay when compared to no corticosteroids. There were no serious adverse events or deaths reported with or without corticosteroid use. Low-certainty evidence shows use of corticosteroids can reduce duration of clinical symptoms (fever and rash). None of the included studies reported on long-term (greater than one year after disease onset) coronary morbidity. Evidence presented in this systematic review agrees with current clinical guidelines on the use of corticosteroids in the first-line treatment in KD.

Current Prognostic and Predictive Biomarkers for Endometrial Cancer in Clinical Practice: Recommendations/Proposal from the Italian Study Group.

Endometrial carcinoma (EC) is the most common gynecological malignant disease in high-income countries, such as European countries and the USA. The 2020 edition of the World Health Organization (WHO) Classification of Tumors of the Female Genital Tract underlines the important clinical implications of the proposed new histomolecular classification system for ECs. In view of the substantial genetic and morphological heterogeneity in ECs, both classical pthological parameters and molecular classifiers have to be integrated in the pathology report. This review will focus on the most commonly adopted immunohistochemical and molecular biomarkers in daily clinical characterization of EC, referring to the most recent published recommendations, guidelines, and expert opinions.

Telemedicine Acceptance Among Older Adult Patients With Cancer: Scoping Review.

BackgroundCancer is likely to remain the most prevalent noncommunicable disease in high-income countries with an older population. Interestingly, no review of attitudes toward telemedicine among older adults has been performed. This is likely to be the group most affected by both cancer and the increasing use of technology in health care.ObjectiveWe aimed to map research on the acceptance of telemedicine among older adults who are cancer patients.MethodsWe conducted a scoping review. PubMed, EMBASE, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials were systematically searched from inception to September 2020. Articles were included if the study population had a mean or median age ≥65 years, with cancer diagnoses and if the study assessed patients’ acceptance of a telemedicine intervention. Quantitative, qualitative, and mixed method studies were included.ResultsOut of a total of 887 articles that were identified, 19 were included in the review. Interventions were delivered via telephone, videoconference, web portal, mobile app, wearable technology, and text messaging and included teleconsultation, monitoring and follow-up, psychosocial support and nursing care, and prompts. The most often cited facilitating factor was convenience. Other facilitators included an increase in telemedicine care accessibility, previous positive experiences of telemedicine, appropriate technical knowledge and support, decreased cost, physician recommendations, and privacy conferred by the telemedicine intervention. Barriers include a preference for conventional care along with negative perceptions of telemedicine, concerns about technical difficulties, and confidentiality concerns in the adoption of telemedicine.ConclusionsNone of the studies explored the ability of tailored interventions to address facilitators and barriers of the acceptance of telemedicine in order to increase its adoption by older adults. Facilitators and barriers will likely differ across different cultural contexts and by type of telemedicine; however, this is a gap in current knowledge. In-depth studies are necessary to determine if interventions could potentially address the barriers identified in this review, to increase acceptability.

A Narrative Review on Pediatric Scurvy: The Last Twenty Years.

Scurvy is a well-known clinical condition caused by vitamin C deficiency. Although considered a rare disease in high-income countries, it has been recently increasingly reported in children, especially in those with abnormal dietary habits, mental or physical disabilities. We performed an extensive review of the literature analyzing studies published in the last 20 years focusing on clinical features, differential diagnosis and diagnostic delay. Fifteen articles were selected, collectively reporting a total of 166 children. Because of the wide clinical spectrum (musculoskeletal complaints and/or mucocutaneous lesions or systemic symptoms), scurvy can mimic several conditions, including autoimmune diseases, infections, and neoplasia. In addition, frequent findings such as normal nutritional status, anemia or elevated inflammatory markers may guide clinicians towards the abovementioned misdiagnoses. Scurvy should be considered in patients presenting with musculoskeletal complaints, not only in those with risk factors but also in healthy children. A focused dietary history and a careful physical examination, assessing other signs of vitamin C deficiency, are mandatory in these patients. When suspected, the dosage of serum vitamin C is the diagnostic gold standard; furthermore, imaging studies, performed by an expert radiologist, can reveal the typical features of scurvy. Only early diagnosis can avoid unnecessary investigations and potentially fatal complications of the disease.

Mitral regurgitation management: a systematic review of clinical practice guidelines and recommendations.

Multiple guidelines exist for the diagnosis and management of mitral regurgitation (MR), the second most common valvular heart disease in high-income countries, with recommendations that do not always match. We systematically reviewed guidelines on diagnosis and management of MR, highlighting similarities and differences to guide clinical decision-making. We searched national and international guidelines in MEDLINE and EMBASE (1 June 2010 to 1 September 2021), the Guidelines International Network, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, and websites of relevant organizations. Two reviewers independently screened the abstracts and identified articles of interest. Guidelines that were rigorously developed (as assessed with the Appraisal of Guidelines for Research and Evaluation II instrument) were retained for analysis. Five guidelines were retained. There was consensus on a multidisciplinary approach from the heart team and for the definition and grading of severe primary MR. There was general agreement on the thresholds for intervention in symptomatic and asymptomatic primary MR; however, discrepancies were present. There was agreement on optimization of medical therapy in severe secondary MR and intervention in patients symptomatic despite optimal medical therapy, but no consensus on the choice of intervention (surgical repair/replacement vs. transcatheter approach). Cut-offs for high-risk intervention in MR, risk stratification of progressive MR, and guidance on mixed valvular disease were sparse.

Economic and modeling evidence for tuberculosis preventive therapy among people living with HIV: A systematic review and meta-analysis.

Human immunodeficiency virus (HIV) is the strongest known risk factor for tuberculosis (TB) through its impairment of T-cell immunity. Tuberculosis preventive treatment (TPT) is recommended for people living with HIV (PLHIV) by the World Health Organization, as it significantly reduces the risk of developing TB disease. We conducted a systematic review and meta-analysis of modeling studies to summarize projected costs, risks, benefits, and impacts of TPT use among PLHIV on TB-related outcomes. We searched MEDLINE, Embase, and Web of Science from inception until December 31, 2020. Two reviewers independently screened titles, abstracts, and full texts; extracted data; and assessed quality. Extracted data were summarized using descriptive analysis. We performed quantile regression and random effects meta-analysis to describe trends in cost, effectiveness, and cost-effectiveness outcomes across studies and identified key determinants of these outcomes. Our search identified 6,615 titles; 61 full texts were included in the final review. Of the 61 included studies, 31 reported both cost and effectiveness outcomes. A total of 41 were set in low- and middle-income countries (LMICs), while 12 were set in high-income countries (HICs); 2 were set in both. Most studies considered isoniazid (INH)-based regimens 6 to 2 months long (n = 45), or longer than 12 months (n = 11). Model parameters and assumptions varied widely between studies. Despite this, all studies found that providing TPT to PLHIV was predicted to be effective at averting TB disease. No TPT regimen was substantially more effective at averting TB disease than any other. The cost of providing TPT and subsequent downstream costs (e.g. post-TPT health systems costs) were estimated to be less than $1,500 (2020 USD) per person in 85% of studies that reported cost outcomes (n = 36), regardless of study setting. All cost-effectiveness analyses concluded that providing TPT to PLHIV was potentially cost-effective compared to not providing TPT. In quantitative analyses, country income classification, consideration of antiretroviral therapy (ART) use, and TPT regimen use significantly impacted cost-effectiveness. Studies evaluating TPT in HICs suggested that TPT may be more effective at preventing TB disease than studies evaluating TPT in LMICs; pooled incremental net monetary benefit, given a willingness-to-pay threshold of country-level per capita gross domestic product (GDP), was $271 in LMICs (95% confidence interval [CI] -$81 to $622, p = 0.12) and was $2,568 in HICs (-$32,115 to $37,251, p = 0.52). Similarly, TPT appeared to be more effective at averting TB disease in HICs; pooled percent reduction in active TB incidence was 20% (13% to 27%, p < 0.001) in LMICs and 37% (-34% to 100%, p = 0.13) in HICs. Key limitations of this review included the heterogeneity of input parameters and assumptions from included studies, which limited pooling of effect estimates, inconsistent reporting of model parameters, which limited sample sizes of quantitative analyses, and database bias toward English publications. The body of literature related to modeling TPT among PLHIV is large and heterogeneous, making comparisons across studies difficult. Despite this variability, all studies in all settings concluded that providing TPT to PLHIV is potentially effective and cost-effective for preventing TB disease.

Rotavirus vaccines: progress and new developments

ABSTRACT Introduction Rotavirus is the primary cause of severe acute gastroenteritis among children under the age of five globally, leading to 128,500 to 215,000 vaccine-preventable deaths annually. There are six licensed oral, live-attenuated rotavirus vaccines: four vaccines pre-qualified for global use by WHO, and two country-specific vaccines. Expansion of rotavirus vaccines into national immunization programs worldwide has led to a 59% decrease in rotavirus hospitalizations and 36% decrease in diarrhea deaths due to rotavirus in vaccine-introducing countries. Areas covered This review describes the current rotavirus vaccines in use, global coverage, vaccine efficacy from clinical trials, and vaccine effectiveness and impact from post-licensure evaluations. Vaccine safety, particularly as it relates to the risk of intussusception, is also summarized. Additionally, an overview of candidate vaccines in the pipeline is provided. Expert opinion Considerable evidence over the past decade has demonstrated high effectiveness (80–90%) of rotavirus vaccines at preventing severe rotavirus disease in high-income countries, although the effectiveness has been lower (40–70%) in low-to-middle-income countries. Surveillance and research should continue to explore modifiable factors that influence vaccine effectiveness, strengthen data to better evaluate newer rotavirus vaccines, and aid in the development of future vaccines that can overcome the limitations of current vaccines.

Long-Term Outcomes After Group B Streptococcal Disease in Infancy

Source: Horváth-Puhó E, van Kassel MN, P Gonçalves BP, et al. Mortality, neurodevelopmental impairments, and economic outcomes after invasive group B streptococcal disease in early infancy in Denmark and the Netherlands: a national matched cohort study. Lancet Child Adolesc Health. 2021;5(6):398-407; doi: 10.1016/S2352-4642(21)00022-5Investigators from multiple institutions conducted a matched cohort study to assess the long-term health outcomes among infants with invasive group B streptococcal disease (iGBS). Data for this study were obtained from national registries in Denmark and the Netherlands. Data from Danish children born from 1997–2017 and Dutch children born 2000–2017 were included.Children with iGBS, defined as GBS sepsis, meningitis, or pneumonia by the age of 89 days, were identified using ICD-10 codes within Denmark’s Medical Birth and National Patient Registries and positive culture results within the Netherlands’ Reference Laboratory for Bacterial Meningitis. Age of iGBS onset was calculated using the first hospital admission date for iGBS disease and categorized as early (0-6 days) or late onset (7-89 days). Children without iGBS were randomly selected from similar administrative databases and matched 10:1 to each child with iGBS on sex, birth month and year, and gestational age.All children were followed from birth until death, emigration, or the end of the study period. Investigators computed the mortality risk during the first 3 months and 5 years of life using data from the Danish Civil Registration system and Dutch Municipal Personal Records Database. Five-year mortality rates were compared among children with and without iGBS disease. Among those who survived the first 3 months of life, investigators calculated the risk of neurodevelopment impairments (NDI) by age 10 years among children with and without iGBS disease using ICD-10 codes for mental, behavioral, and nervous system disorders in the Danish National Patient Registry and use of special educational support in national databases in the Netherlands.There were 2,258 children identified as having iGBS disease and 22,462 matched children without iGBS disease. Among children with iGBS disease, 86% of Danish children and 64% of Dutch children had early onset disease (EOD). Mortality risk in the first 3 months was 2.3% (95% Confidence Interval [C I], 1. 7, 3. 2) in Denmark and 7.6% (95% CI, 5.6, 9.5) in the Netherlands. The 5-year mortality risk was significantly higher in Dutch children with (vs without) iGBS disease (hazard ratio, 3.97; 95% CI, 2.89, 5.46). There was an overall increased risk of NDI by age 10 years in both Denmark (relative risk [RR], 1.77; 95% CI, 1.44, 2.18) and the Netherlands (RR, 2.28; 95% CI, 1.64, 3.17).The investigators conclude that iGBS disease in infancy is associated with increased mortality and higher risk of NDI in later childhood.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Group B streptococci are estimated to cause more than 300,000 cases of neonatal disease annually, resulting in about 90,000 deaths worldwide.1 The current researchers are the first to quantify the long-term effects on survivors of iGBS disease in high-income countries that use intrapartum antibiotic prophylaxis (IAP) and have advanced neonatal care. The burden of iGBS disease is likely higher in low-income countries where these resources are not available.2The prevalence of EOD and late-onset disease (LOD) in Denmark and the Netherlands was stable over the study period and EOD predominated. In contrast, EOD has declined and now occurs less frequently than does LOD in the US. (See AAP Grand Rounds. 2019;41[5]:51.)3,4 It is not clear why a decline was not noted in these European countries. However, not all mothers are screened, and maternal GBS cultures may be falsely negative.3 As noted in the US study, almost 50% of EOD disease occurs in newborns without any known risk factors.3The World Health Organization has identified GBS as a high priority for the development of a vaccine.5 Developing a GBS vaccine has been challenging because its capsular polysaccharides are poorly immunogenic.6 However, Absalon et al7 recently reported that a novel hexavalent GBS conjugate vaccine was safe and elicited robust immune responses that persisted 6 months after vaccination in a randomized trial in healthy, non-pregnant adults. Additional studies in pregnant women to assess safety and passive antibody transfer to the neonate are needed.The burden of iGBS disease remains high despite IAP and advanced neonatal care. Further development and evaluation of GBS vaccines in pregnant women is a public health priority.

Global epidemiology of valvular heart disease.

Valvular heart disease (VHD) is a major contributor to loss of physical function, quality of life and longevity. The epidemiology of VHD varies substantially around the world, with a predominance of functional and degenerative disease in high-income countries, and a predominance of rheumatic heart disease in low-income and middle-income countries. Reflecting this distribution, rheumatic heart disease remains by far the most common manifestation of VHD worldwide and affects approximately 41 million people. By contrast, the prevalence of calcific aortic stenosis and degenerative mitral valve disease is 9 and 24 million people, respectively. Despite a reduction in global mortality related to rheumatic heart disease since 1900, the death rate has remained fairly static since 2000. Meanwhile, deaths from calcific aortic stenosis have continued to rise in the past 20 years. Epidemiological data on other important acquired and congenital forms of VHD are limited. An ageing population and advances in therapies make an examination of the changing global epidemiology of VHD crucial for advances in clinical practice and formulation of health policy. In this Review, we discuss the global burden of VHD, geographical variation in the presentation and clinical management, and temporal trends in disease burden.