Neonatologist at the Well-Child Clinic: A High-Risk Infant Follow-up Pilot Study.

OBJECTIVE: High-risk infant follow-up (HRIF) is a complex process lacking standardization. We present a simple, single-provider model that proved effective and is well-received by caregivers. STUDY DESIGN: In this study, we measured caregiver use and satisfaction with an HRIF visit attended by an experienced neonatologist in a well-care setting, soon after discharge. RESULTS: One hundred parents participated in the survey. Among the infants of these parents, 78% of infants were seen in the first 3 months of life and 39% within 1 month of discharge. Nutrition (98%) and development (97%) were the most commonly discussed topics, followed by general health (95%), iron supplementation (93%), and head size (90%). Using a 5-point Likert's scale, with 5 being the highest rating, parents responded that the meeting answered their questions (4.7, n = 93), organized their infants' needs (4.6, n = 90), and increased their confidence in caring for their infants (4.65, n = 92). CONCLUSION: HRIF with an experienced neonatologist is an effective means of increasing parents' understanding of their infants' medical needs and confidence in caring for their infants. KEY POINTS: · Meeting with a neonatologist after discharge addressed many crucial aspects of patient care.. · Meeting with a neonatologist after discharge was met with a high level of caregiver satisfaction.. · Neonatal consultation in the community may promote caregiver confidence in caring for their infant.. · Neonatal consultation reduced parental anxiety, especially regarding growth and development..

Increased fracture risk among children diagnosed with attention- deficit/hyperactivity disorder: a large matched cohort study.

To analyse the risk of fractures among children with attention-deficit/hyperactivity disorder (ADHD) compared with matched children without ADHD; and to evaluate the impact of pharmacological treatment. This registry-based cohort study included 31,330 children diagnosed with ADHD and a comparison group of 62,660 children matched by age, sex, population sector and socioeconomic status. Demographic and clinical information was extracted from the electronic database of Meuhedet, a health maintenance organization. Fracture events between 2-18 years of age were identified by coded diagnoses. The overall fracture incidence rate was 334 per 10,000 patient-years (PY) in the ADHD group and 284 per 10,000 PY in the comparison group (p < 0.001). Among boys, the fracture incidence rates were 388 per 10,000 PY and 327 per 10,000 PY (p < 0.001), for the respective groups. Among girls, the rates were lower in both groups compared to boys, but higher in the ADHD compared to the matched group (246 vs 203 per 10,000 PY, p < 0.001). Among the children with ADHD, the hazard ratios (HR) to have a fracture were similar in boys (1.18, 95%CI 1.15-1.22, p < 0.001) and girls (1.22, 95%CI 1.16-1.28, p < 0.001). Children with ADHD were also at increased risk for two and three fractures; the hazard ratios (HRs) were 1.32 (95%CI 1.26-1.38, p < 0.001) and 1.35 (95%CI 1.24-1.46, p < 0.001), respectively. In a multivariable model of the children with ADHD, pharmacological treatment was associated with reduced fracture risk (HR 0.90, 95%CI 0.82-0.98, p < 0.001) after adjustment for sex, resident socioeconomic status and population sector.   Conclusion: Children with ADHD had greater fracture risk than a matched group without ADHD. Pharmacological treatment for ADHD may decrease this risk. What is Known: • Children with attention-deficit/hyperactivity disorder (ADHD) may be more prone to injuries and fractures than children without ADHD. What is New: • Children with ADHD were 1.2 times more likely to have a fracture than children with similar characteristics, without ADHD. The increased risk for fractures was even greater for two and three fractures (hazard ratios 1.32 and 1.35, respectively). • Our study suggests a positive effect of pharmacological treatment for ADHD in reducing fracture risk.

SARS-CoV-2 outbreak in a synagogue community: longevity and strength of anti-SARS-CoV-2 IgG responses.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic is still ongoing along with the global vaccination efforts against it. Here, we aimed to understand the longevity and strength of anti-SARS-CoV-2 IgG responses in a small community (n = 283) six months following local SARS-COV-2 outbreak in March 2020. Three serological assays were compared and neutralisation capability was also determined. Overall 16.6% (47/283) of the participants were seropositive and 89.4% (42/47) of the IgG positives had neutralising antibodies. Most of the symptomatic individuals confirmed as polymerase chain reaction (PCR) positive during the outbreak were seropositive (30/32, 93.8%) and 33.3% of the individuals who quarantined with a PCR confirmed patient had antibodies. Serological assays comparison revealed that Architect (Abbott) targeting the N protein LIASON® (DiaSorin) targeting the S protein and enzyme-linked immunosorbent assay (ELISA) targeting receptor binding domain detected 9.5% (27/283), 17.3% (49/283) and 17% (48/283), respectively, as IgG positives. The latter two assays highly agreed (kappa = 0.89) between each other. In addition, 95%, (19/20, by ELISA) and 90.9% (20/22, with LIASON) and only 71.4% (15/21, by Architect) of individuals that were seropositive in May 2020 were found positive also in September. The unexpected low rate of overall immunity indicates the absence of un-noticed, asymptomatic infections. Lack of overall high correlation between the assays is attributed mainly to target-mediated antibody responses and suggests that using a single serological assay may be misleading.

Leveraging real-world data to investigate multiple sclerosis disease behavior, prognosis, and treatment.

Randomized controlled clinical trials and real-world observational studies provide complementary information but with different validity. Some clinical questions (disease behavior, prognosis, validation of outcome measures, comparative effectiveness, and long-term safety of therapies) are often better addressed using real-world data reflecting larger, more representative populations. Integration of disease history, clinician-reported outcomes, performance tests, and patient-reported outcome measures during patient encounters; imaging and biospecimen analyses; and data from wearable devices increase dataset utility. However, observational studies utilizing these data are susceptible to many potential sources of bias, creating barriers to acceptance by regulatory agencies and the medical community. Therefore, data standardization and validation within datasets, harmonization across datasets, and application of appropriate analysis methods are important considerations. We review approaches to improve the scope, quality, and analyses of real-world data to advance understanding of multiple sclerosis and its treatment, as an example of opportunities to better support patient care and research.

Cell-based therapeutic strategies for multiple sclerosis.

The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials.

Vision and vision-related outcome measures in multiple sclerosis.

Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis.

A systematic review of the incidence and prevalence of cardiac, cerebrovascular, and peripheral vascular disease in multiple sclerosis.

BACKGROUND: Findings regarding the prevalence of vascular comorbidities in multiple sclerosis (MS) are conflicting. OBJECTIVE: The objective of this review is to estimate the incidence and prevalence of vascular comorbidities and predisposing comorbidities in persons with MS and to assess the quality of the included studies. METHODS: The PubMed, EMBASE, SCOPUS and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles were searched. One reviewer abstracted data using a standardized data collection form, while the second reviewer verified the abstraction. Included studies were assessed qualitatively. Quantitatively, we assessed studies using the I² statistic, and conducted meta-analyses for population-based studies only. RESULTS: The prevalence of hypertension and hyperlipidemia exceeded 10% in the MS population and increased with age. While the prevalence of ischemic heart disease, congestive heart failure, and stroke were less than 5% overall, the prevalence of these conditions exceeded expectations when compared to the general population. Cardiac valvular disease, however, affected the MS population less often than expected. Problems with study quality were common. CONCLUSION: Despite the relatively high prevalence of some vascular comorbidities in the MS population, important gaps exist in our understanding of their epidemiology. Most of our knowledge is based on studies conducted in a small number of regions.

A systematic review of the incidence and prevalence of sleep disorders and seizure disorders in multiple sclerosis.

BACKGROUND: Several studies have suggested that comorbid neurologic disorders are more common than expected in multiple sclerosis (MS). OBJECTIVE: To estimate the incidence and prevalence of comorbid seizure disorders and sleep disorders in persons with MS and to evaluate the quality of studies included. METHODS: The PUBMED, EMBASE, Web of Knowledge, and SCOPUS databases, conference proceedings, and reference lists of retrieved articles were searched. Two reviewers independently screened abstracts to identify relevant articles, followed by full-text review of selected articles. We assessed included studies qualitatively and quantitatively (I² statistic), and conducted meta-analyses among population-based studies. RESULTS: We reviewed 32 studies regarding seizure disorders. Among population-based studies the incidence of seizure disorders was 2.28% (95% CI: 1.11-3.44%), while the prevalence was 3.09% (95% CI: 2.01-4.16%). For sleep disorders we evaluated 18 studies; none were population-based. The prevalence ranged from 0-1.6% for narcolepsy, 14.4-57.5% for restless legs syndrome, 2.22-3.2% for REM behavior disorder, and 7.14-58.1% for obstructive sleep apnea. CONCLUSION: This review suggests that seizure disorders and sleep disorders are common in MS, but highlights gaps in the epidemiological knowledge of these conditions in MS worldwide. Other than central-western Europe and North America, most regions are understudied.

The incidence and prevalence of psychiatric disorders in multiple sclerosis: a systematic review.

BACKGROUND: Psychiatric comorbidity is associated with lower quality of life, more fatigue, and reduced adherence to disease-modifying therapy in multiple sclerosis (MS). OBJECTIVES: The objectives of this review are to estimate the incidence and prevalence of selected comorbid psychiatric disorders in MS and evaluate the quality of included studies. METHODS: We searched the PubMed, PsychInfo, SCOPUS, and Web of Knowledge databases and reference lists of retrieved articles. Abstracts were screened for relevance by two independent reviewers, followed by full-text review. Data were abstracted by one reviewer, and verified by a second reviewer. Study quality was evaluated using a standardized tool. For population-based studies we assessed heterogeneity quantitatively using the I² statistic, and conducted meta-analyses. RESULTS: We included 118 studies in this review. Among population-based studies, the prevalence of anxiety was 21.9% (95% CI: 8.76%-35.0%), while it was 14.8% for alcohol abuse, 5.83% for bipolar disorder, 23.7% (95% CI: 17.4%-30.0%) for depression, 2.5% for substance abuse, and 4.3% (95% CI: 0%-10.3%) for psychosis. CONCLUSION: This review confirms that psychiatric comorbidity, particularly depression and anxiety, is common in MS. However, the incidence of psychiatric comorbidity remains understudied. Future comparisons across studies would be enhanced by developing a consistent approach to measuring psychiatric comorbidity, and reporting of age-, sex-, and ethnicity-specific estimates.

A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: overview.

BACKGROUND: Comorbidity is an area of increasing interest in multiple sclerosis (MS). OBJECTIVE: The objective of this review is to estimate the incidence and prevalence of comorbidity in people with MS and assess the quality of included studies. METHODS: We searched the PubMed, SCOPUS, EMBASE and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles. Two reviewers independently screened abstracts. One reviewer abstracted data using a standardized form and the abstraction was verified by a second reviewer. We assessed study quality using a standardized approach. We quantitatively assessed population-based studies using the I² statistic, and conducted random-effects meta-analyses. RESULTS: We included 249 articles. Study designs were variable with respect to source populations, case definitions, methods of ascertainment and approaches to reporting findings. Prevalence was reported more frequently than incidence; estimates for prevalence and incidence varied substantially for all conditions. Heterogeneity was high. CONCLUSION: This review highlights substantial gaps in the epidemiological knowledge of comorbidity in MS worldwide. Little is known about comorbidity in Central or South America, Asia or Africa. Findings in North America and Europe are inconsistent. Future studies should report age-, sex- and ethnicity-specific estimates of incidence and prevalence, and standardize findings to a common population.

A systematic review of the incidence and prevalence of autoimmune disease in multiple sclerosis.

BACKGROUND: As new therapies emerge which increase the risk of autoimmune disease it is increasingly important to understand the incidence of autoimmune disease in multiple sclerosis (MS). OBJECTIVE: The purpose of this review is to estimate the incidence and prevalence of comorbid autoimmune disease in MS. METHODS: The PUBMED, EMBASE, SCOPUS and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles were searched, and abstracts were independently screened by two reviewers. The data were abstracted by one reviewer using a standardized data collection form, and the findings were verified by a second reviewer. We assessed quality of the included studies using a standardized approach and conducted meta-analyses of population-based studies. RESULTS: Sixty-one articles met the inclusion criteria. We observed substantial heterogeneity with respect to the populations studied, methods of ascertaining comorbidity, and reporting of findings. Based solely on population-based studies, the most prevalent autoimmune comorbidities were psoriasis (7.74%) and thyroid disease (6.44%). Our findings also suggest an increased risk of inflammatory bowel disease, likely uveitis and possibly pemphigoid. CONCLUSION: Fewer than half of the studies identified were of high quality. Population-based studies that report age, sex and ethnicity-specific estimates of incidence and prevalence are needed in jurisdictions worldwide.

A systematic review of the incidence and prevalence of cancer in multiple sclerosis.

BACKGROUND: Studies of cancer incidence and prevalence in multiple sclerosis (MS) have produced conflicting results. OBJECTIVE: To estimate the incidence and prevalence of cancer in persons with MS and review the quality of included studies. METHODS: We searched the PUBMED, SCOPUS, Web of Knowledge, and EMBASE databases, conference proceedings, and reference lists of all articles retrieved. Abstracts were screened for relevance by two reviewers. Data from included articles were captured using a standardized form, and the abstraction was verified by a second reviewer. We assessed quality of the included studies. We quantitatively assessed studies using the I (2) statistic, and conducted meta-analyses for population-based studies. RESULTS: We identified 38 studies. Estimates for incidence and prevalence varied substantially for most cancers. In population-based studies, cervical, breast, and digestive cancers had the highest incidence. The risk of meningiomas and urinary system cancers appeared higher than expected, while the risks of pancreatic, ovarian, prostate and testicular cancer were lower than expected. CONCLUSION: The complexity of understanding cancer risk in MS is augmented by inconsistencies in study design, and the relative paucity of age, sex and ethnicity-specific risk estimates from which the strong impact of age on the incidence of cancers can be assessed.

The incidence and prevalence of comorbid gastrointestinal, musculoskeletal, ocular, pulmonary, and renal disorders in multiple sclerosis: a systematic review.

BACKGROUND: As new disease-modifying therapies emerge a better knowledge of the risk of comorbid disease in multiple sclerosis (MS) is needed. OBJECTIVE: To estimate the incidence and prevalence of comorbid gastrointestinal, musculoskeletal, ocular, pulmonary, and renal disorders in MS. METHODS: We systematically reviewed the world literature by searching PUBMED, EMBASE, SCOPUS, the Web of Knowledge, and reference lists of retrieved articles. For selected articles, one reviewer abstracted data using a standardized form. The abstraction was verified by a second reviewer. The quality of all selected studies was assessed. For population-based studies we quantitatively assessed studies using the I² statistic, and conducted random effects meta-analyses. RESULTS: Study designs were heterogeneous with respect to populations, case definitions, and methods of ascertainment. Incidence of the studied comorbidities was rarely reported. Irritable bowel syndrome and chronic lung disease had a prevalence of more than 10% in the MS population. Irritable bowel syndrome, fibromyalgia, cataracts and glaucoma were more common than expected in the MS population. CONCLUSION: Although they have been the subject of less study than other comorbidities, irritable bowel syndrome, arthritis, and chronic lung disease are common in the MS population and occur more often than expected when compared to the general population.

Pregnancy, sex and hormonal factors in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is influenced by pregnancy, sex and hormonal factors. OBJECTIVES: A comprehensive understanding of the role of pregnancy, sex and hormonal factors can provide insights into disease mechanisms, and new therapeutic developments and can provide improved patient care and treatment. METHODS: Based on an international conference of experts and a comprehensive PubMed search for publications on these areas in MS, we provide a review of what is known about the impact of these factors on disease demographics, etiology, pathophysiology and clinical course and outcomes. RESULTS AND CONCLUSIONS: Recommendations are provided for counseling and management of people with MS before conception, during pregnancy and after delivery. The use of disease-modifying and symptomatic therapies in pregnancy is problematic and such treatments are normally discontinued. Available knowledge about the impact of treatment on the mother, fetus and newborn is discussed. Recommendations for future research to fill knowledge gaps and clarify inconsistencies in available data are made.

Risk evaluation and monitoring in multiple sclerosis therapeutics.

BACKGROUND: Risk for multiple sclerosis (MS) disease-modifying therapies (DMT) must be assessed on an ongoing basis. Early concerns regarding the first-approved DMTs for MS have been mitigated, but recently licensed therapies have been linked to possibly greater risks. OBJECTIVES: The objective of this review is to discuss risk assessment in MS therapeutics based on an international workshop and comprehensive literature search and recommend strategies for risk assessment/monitoring. RESULTS: Assessment and perception of therapeutic risks vary between patients, doctors and regulators. Acceptability of risk depends on the magnitude of risk and the demonstrated clinical benefits of any agent. Safety signals must be distinguishable from chance occurrences in a clinical trial and in long-term use of medications. Post-marketing research is crucial for assessing longer-term safety in large patient cohorts. Reporting of adverse events is becoming more proactive, allowing more rapid identification of risks. Communication about therapeutic risks and their relationship to clinical benefit must involve patients in shared decision making. CONCLUSIONS: It is difficult to produce a general risk-assessment algorithm for all MS therapies. Specific algorithms are required for each DMT in every treated-patient population. New and evolving risks must be evaluated and communicated rapidly to allow patients and physicians to be well informed and able to share treatment decisions.

Pediatric antibiotic stewardship programs in Europe: a pilot survey among delegates of The European Academy of Pediatrics.

Background: Antimicrobial resistance (AMR) is one of the leading causes of morbidity and mortality worldwide. Efforts to promote the judicious use of antibiotics and contain AMR are a priority of several medical organizations, including the WHO. One effective way to achieve this goal is the deployment of antibiotic stewardship programs (ASPs). This study aimed to survey the current situation of pediatric ASPs in European countries and establish a baseline for future attempts to harmonize pediatric ASPs and antibiotic use in Europe. Methods: A web-based survey was conducted among national delegates of the European Academy of Paediatrics (EAP). The survey assessed the presence of pediatric ASPs in the representatives' countries in the inpatient and outpatient settings, the staff included in the programs, and their detailed activities regarding antibiotic use. Results: Of the 41 EAP delegates surveyed, 27 (66%) responded. Inpatient pediatric ASPs were reported in 74% (20/27) countries, and outpatient programs in 48% (13/27), with considerable variability in their composition and activities. Guidelines for managing pediatric infectious diseases were available in nearly all countries (96%), with those for neonatal infections (96%), pneumonia (93%), urinary tract (89%), peri-operative (82%), and soft tissue (70%) infections being the most common. Pediatric ASPs were reported at the national (63%), institutional (41%), and regional/local (<15%) levels. Pediatricians with infectious disease training (62%) and microbiologists (58%) were the most common members of the program personnel, followed by physician leaders (46%), infectious disease/infection control physicians (39%), pharmacists (31%), and medical director representatives (15%). Activities of the pediatric ASPs included educational programs (85%), monitoring and reporting of antibiotic use (70%) and resistance (67%), periodic audits with feedback (44%), prior approval (44%), and post-prescription review of selected antibiotic agents (33%). Conclusion: Although pediatric ASPs exist in most European countries, their composition and activities vary considerably across countries. Initiatives to harmonize comprehensive pediatric ASPs across Europe are needed.

Entrustable Professional Activities for the Training of Postgraduate Primary Care Pediatricians.

PROBLEM: Competency-based training is a model of medical education program that uses an organized framework of competencies to develop entrustable professional activities (EPAs) for each specialty. Implementation of EPAs varies by medical specialty and country. Although national models for primary care pediatrics have been suggested in the past, standardized EPAs have not been established. APPROACH: The authors, all members of the curriculum working group of the European Confederation of Primary Care Paediatricians, describe the development and design of a training model based on EPAs specifically for pediatricians in primary care. The objective was to facilitate and disseminate a training model that standardizes and improves training in primary care pediatrics. They aimed to make the model flexible enough so that it can be adapted to different training models and different European health systems. OUTCOMES: Between May 2017 and December 2019, the authors developed a framework that includes 7 domains of competencies for the training in pediatric primary care and a set of 11 core EPAs to guide the learning process. They structured each EPA as follows: title, activity profile, domains of competence, competencies within each domain, required knowledge and skills, learning objectives described in terms of outcomes, and a 3-stage rating supervision scale to evaluate the level of performance. NEXT STEPS: The next step is the progressive implementation of these EPAs into the postgraduate primary care pediatrics training programs of European health systems. To support this implementation, the authors intend to develop training videos to assist in daily teaching of the EPAs. The authors will also develop a pan-European online resident forum designed specifically to facilitate EPA learning by sharing and discussing clinical cases. They plan to launch a pilot study on the use of the EPAs in primary care health centers in 6 European countries.

Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria.

New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.

A Guide to Implementing Immune Checkpoint Inhibitors within a Cancer Program: Experience from a Large Canadian Community Centre.

The increased use of immune checkpoint inhibitors across cancer programs has created the need for standardized patient assessment, education, monitoring, and management of immune-related adverse events (irAEs). At William Osler Health System in Brampton, Ontario, a practical step-wise approach detailing the implementation of cancer immunotherapy in routine practice was developed. The approach focuses on four key steps: (1) identification of patient educators; (2) development of patient education materials; (3) development of patient monitoring tools; (4) involvement and education of multidisciplinary teams. Here, we provide an in-depth description of what was included in each step and how we integrated the different elements of the program. For each step, resources, tools, and materials that may be useful for patients, healthcare providers, and multidisciplinary teams were developed or modified based on existing materials. At our centre, the program led to improved patient comprehension of irAEs, the ability to act on symptoms (patient self-efficacy), and low rates of emergency room visits at first presentation for irAEs. We recognize that centres may need to tailor the approaches to their institutional policies and encourage centres to adapt and modify the forms and tools according to their needs and requirements.