Exploring the Health-Related Quality of Life and the Lived Experience of Adolescents Following Invasive Meningococcal Disease.

BACKGROUND: Data on the health-related quality of life (HRQoL) for invasive meningococcal disease (IMD) survivors, particularly among adolescents and young adults (AYAs), are limited. This study aimed to investigate the in-depth experiences and impacts of IMD on AYAs. METHODS: Participants were recruited from two Australian states, Victoria and South Australia. We conducted qualitative, semi-structured interviews with 30 patients diagnosed with IMD between 2016 and 2021. The interview transcripts were analyzed thematically. RESULTS: Of the participants, 53% were aged 15-19 years old, and 47% were aged 20-24. The majority (70%) were female. Seven themes relating to the participants' experience of IMD were identified: (1) underestimation of the initial symptoms and then rapid escalation of symptoms; (2) reliance on social support for emergency care access; (3) the symptoms prompting seeking medical care varied, with some key symptoms missed; (4) challenges in early medical diagnosis; (5) traumatic and life-changing experience; (6) a lingering impact on HRQoL; and (7) gaps in the continuity of care post-discharge. CONCLUSION: The themes raised by AYA IMD survivors identify multiple areas that can be addressed during their acute illness and recovery. Increasing awareness of meningococcal symptoms for AYAs may help reduce the time between the first symptoms and the first antibiotic dose, although this remains a challenging area for improvement. After the acute illness, conducting HRQoL assessments and providing multidisciplinary support will assist those who require more intensive and ongoing assistance during their recovery.

Quality Indicators for Osteoporosis in Adults: A Review of Performance Measures by the American College of Physicians.

Primary osteoporosis is characterized by decreasing bone mass and density and reduced bone strength that leads to a higher risk for fracture, especially hip and spine fractures. The prevalence of osteoporosis in the United States is estimated at 12.6% for adults older than 50 years. Although it is most frequently diagnosed in White and Asian females, it still affects males and females of all ethnicities. Osteoporosis is considered a major health issue, which has prompted the development and use of several performance measures to assess and improve the effectiveness of screening, diagnosis, and treatment. These performance measures are often used in accountability, public reporting, and/or payment programs. However, the reliability, validity, evidence, attribution, and meaningfulness of performance measures have been questioned. The purpose of this paper is to present a review of current performance measures on osteoporosis and inform physicians, payers, and policymakers in their selection of performance measures for this condition. The Performance Measurement Committee identified 6 osteoporosis performance measures relevant to internal medicine physicians, only 1 of which was found valid at all levels of attribution. This paper also proposes a performance measure concept to address a performance gap for the initial approach to therapy for patients with a new diagnosis of osteoporosis based on the current American College of Physicians guideline.

Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines.

Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10-48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911.

Preparing for Future Pandemics and Public Health Emergencies: An American College of Physicians Policy Position Paper.

The onset of the COVID-19 pandemic revealed significant gaps in the United States' pandemic and public health emergency response system. At the federal level, government responses were undercut by a lack of centralized coordination, inadequately defined responsibilities, and an under-resourced national stockpile. Contradictory and unclear guidance throughout the early months of the pandemic, along with inconsistent funding to public health agencies, also created notable variance in state and local responses. The lack of a coordinated response added pressure to an already overwhelmed health care system, which was forced to resort to rationing care and personal protective equipment, creating moral distress and trauma for health care workers and their patients. Despite these severe shortcomings, the COVID-19 pandemic also highlighted successful policies and approaches, such as Operation Warp Speed, which led to the fastest development and distribution of a vaccine in history. In this position paper, the American College of Physicians (ACP) offers several policy recommendations for enhancing federal, state, and local preparedness for future pandemic and public health emergencies. This policy paper builds on various statements produced by ACP throughout the COVID-19 pandemic, including on the ethical distribution of vaccinations and resources, conditions to resume economic and social activity, and efforts to protect the health and well-being of medical professionals, among others.

Modernizing the United States' Public Health Infrastructure: A Position Paper From the American College of Physicians.

The United States' public health sector plays a crucial role in preventing illness and promoting health. Public health drove massive gains in life expectancy during the 20th century by supporting vaccination campaigns, promoting motor vehicle safety, and preventing and treating tobacco use. However, public health is underfunded and underappreciated, forcing the field to do more with fewer resources. In this position paper, the American College of Physicians (ACP) updates its 2012 policy recommendations on strengthening the nation's public health infrastructure. ACP calls for effective coordination of public health activities, robust and stable year-to-year funding of public health services, a renewed and well-supported public health workforce, action to address health-related dis- and misinformation, modernized public health data systems, and greater coordination between public health and medical sectors.

Comparative B cell and antibody responses induced by adenoviral vectored and mRNA vaccines against COVID-19.

Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. However, adenoviral vectored (AdV) vaccines may be less immunogenic than mRNA vaccines against SARS-CoV-2. We assessed anti-spike and anti-vector immunity among infection-naïve Health Care Workers (HCW) following two doses of AdV (AZD1222) versus mRNA (BNT162b2) vaccine. 183 AdV and 274 mRNA vaccinees enrolled between April and October 2021. Median ages were 42 and 39 years, respectively. Blood was collected at least once, 10-48 days after vaccine dose 2. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p<0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human Adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine due to greater B cell expansion and targeting of the RBD. Pre-existing AdV vector cross-reactive antibodies were boosted following AdV vaccination but had no detectable effect on immunogenicity.

Performance Measures for Physicians Providing Clinical Care Using Telemedicine: A Position Paper From the American College of Physicians.

There has been an exponential growth in the use of telemedicine services to provide clinical care, accelerated by the COVID-19 pandemic. Clinical care delivered via telemedicine has become a major and accepted method of health care delivery for many patients. There is an urgent need to understand quality of care in the telemedicine environment. This American College of Physicians position paper presents 6 recommendations to ensure the appropriate use of performance measures to evaluate quality of clinical care provided in the telemedicine environment.

Health Care During Incarceration: A Policy Position Paper From the American College of Physicians.

The American College of Physicians (ACP) has a long-standing commitment to improving the health of all Americans and opposes any form of discrimination in the delivery of health care services. ACP is committed to working toward fully understanding and supporting the unique needs of the incarcerated population and eliminating health disparities for these persons. In this position paper, ACP offers recommendations to policymakers and administrators to improve the health and well-being of persons incarcerated in adult correctional facilities.

Environmental Health: A Position Paper From the American College of Physicians.

Environmental health refers to the health effects associated with environmental factors, such as air pollution, water contamination, and climate change. Environmental hazards are associated with poor outcomes in common diseases, including diabetes and heart disease. In this position paper, the American College of Physicians (ACP) seeks to inform physicians about environmental health and offers policymakers recommendations to reduce the adverse health consequences of climate change, improve air and water quality, reduce exposure to toxic substances, and address environmental injustice. ACP affirms that all communities, including people of color, people with low income, and marginalized populations, deserve to live in a healthy environment.

Supporting the Health and Well-Being of Indigenous Communities: A Position Paper From the American College of Physicians.

Indigenous peoples in the United States experience many health disparities and barriers to accessing health care services. In addition, Indigenous communities experience poor social drivers of health, including disproportionately high rates of food insecurity, violence, and poverty, among others. These challenges are unsurprising, given historical societal discrimination toward Indigenous peoples and government policies of violence, forced relocation with loss of ancestral home, and erasure of cultures and traditions. Indigenous peoples have displayed resilience that has sustained their communities through these hardships. Through treaties between the federal government and Indigenous nations, the federal government has assumed a trust responsibility to provide for the health and well-being of Indigenous populations through the direct provision of health care services and financial support of tribally operated health systems. However, despite serving a population that has endured substantial historical trauma and subsequent health issues, federal programs serving Indigenous peoples receive inadequate federal funding and substantially fewer resources compared with other federal health care programs. Access to care is further challenged by geographic isolation and health care workforce vacancies. Given the history of Indigenous peoples in the United States and their treatment by the federal government and society, the American College of Physicians (ACP) asserts the federal government must faithfully execute its trust responsibility through increased funding and resources directed toward Indigenous communities and the undertaking of concerted policy efforts to support the health and well-being of Indigenous people. ACP believes that these efforts must be community-driven, Indigenous-led, and culturally appropriate and accepted, and center values of respect and self-determination.

Comparative Evaluation of Microleakage of Zinc Phosphate Cement, Resin-Modified Glass Ionomer, and Two Dual-Cure Resin Cements: In Vitro Study.

Aims: The aim of this study is to evaluate and compare the sealing ability of a new resin cement which was undergoing trial with other three luting cements. Settings and Design: In vitro study. Subjects and Methods: Forty extracted intact human premolars were selected and standardized class 5 preparations for inlays were done at cementoenamel junction of buccal surfaces and direct composite inlay was fabricated. The samples were randomly grouped into 4: Group I luted with Rely X ARC resin cement, Group II with DCRC-10, a new indigenously developed resin cement, Group III with FujiCEM, and Group IV with zinc phosphate. After 24 h storage, samples were thermocycled and immersed in basic fuchsine dye. The longitudinal sections were assessed under a stereomicroscope for microleakage using graded criteria. Statistical Analysis Used: To analyze leakage scores among four groups and between enamel and dentin/cementum margins, Kruskal-Wallis nonparametric test and the Mann-Whitney test at P < 0.05 were used. Results: The dye penetration at cementum/dentin margins showed a statistically significant difference among four groups (P < 0.001). Adhesive luting cements produced lesser leakage scores at both margins than those cemented with zinc phosphate. Conclusions: The indigenously developed resin cement (DCRC-10, Group II) is comparable to that of Group I (RelyX ARC) in terms of its luting efficiency.

A Prospective Study Investigating the Impact of Obesity on the Immune Response to the Quadrivalent Influenza Vaccine in Children and Adolescents.

Obesity can increase the severity of influenza infection. Data are limited regarding immune responses to influenza vaccination in obese children. We aimed to investigate the impact of obesity on quadrivalent influenza vaccine responses in children. Children with obesity (body mass index (BMI) ≥ 95th percentile for age and gender) and children without obesity (BMI < 95th percentile) were enrolled in the study. Blood samples were collected before, 1, and 6 months after influenza vaccination, to measure antibody responses by haemagglutination inhibition (HI) assay. Vaccine immunogenicity outcomes were compared between children with and without obesity. Forty-four children (mean age 13.3 ± 2.1 years, 18 males and 14 with obesity) completed the 6-month study. More than 90% of the participants with and without obesity had seroprotective antibody titres (HI ≥ 40) at both 1 and 6 months following vaccination for each of the four influenza strains (A/H3N2, A/H1N1, B/(Victoria) and B/(Yamagata)). Influenza-specific geometric mean titres at baseline, 1, and 6 months post-vaccination were similar between children with and without obesity for all influenza vaccine strains. Children with and without obesity have robust, sustained antibody responses over 6 months to the quadrivalent influenza vaccine.

Weight status and diets of children aged 1-12 years attending a tertiary public paediatric outpatient clinic.

AIM: To assess the weight status and diets of a sample of paediatric outpatients, explore the relationship between the two and compare child weight status with parental perception of child weight and parents' self-reported weight. METHODS: Parents/carers of 1-12-year-olds attending paediatric outpatients at Flinders Medical Centre, South Australia, between October 2015 and May 2016 completed a demographic and validated age-based dietary questionnaire (toddlers (1-3 years), pre-schoolers (>3 to <5 years) or children (5-12 years)). Dietary risk scores (low/moderate/high/very high) were calculated for toddlers and pre-schoolers and diet quality and food behaviours scores for children. Body mass index (BMI) z-score and weight status were determined from measured height and weight. RESULTS: Of 114 toddlers, 115 pre-schoolers and 250 children, 65% were of a healthy weight, 10% underweight and 25% overweight or obese. Most (~80%) toddlers and pre-schoolers had diets classified as 'moderate' risk, and the diets (35-90%) and behaviours (90%) of most 5-12-year-olds fell short of the guidelines. There was no significant relationship between overall diet risk or quality and BMI z-score. Healthier food behaviours scores were inversely correlated with BMI z-scores (ß -0.061, 95% confidence interval (CI) -0.089, -0.033, P < 0.005). Parents' perception of child weight status was inaccurate. Parent's self-reported weight status was significantly associated with the BMI z-scores of toddlers (ß 0.301, 95% CI 0.189-1.174, P = 0.007) and pre-schoolers (ß 0.220, 95% CI 0.032-0.859, P = 0.035). CONCLUSIONS: Poor diets and high rates of overweight/obesity highlight the need for screening within the paediatric outpatient setting. Parents' own weight status, and their inaccurate perception of their child's, should be considered future intervention targets for improving child and parent health.

Placental mesenchymal stromal cells as an alternative tool for therapeutic angiogenesis.

Dysregulation of angiogenesis is a phenomenon observed in several disorders such as diabetic foot, critical limb ischemia and myocardial infarction. Mesenchymal stromal cells (MSCs) possess angiogenic potential and have recently emerged as a powerful tool for cell therapy to promote angiogenesis. Although bone marrow-derived MSCs are the primary cell of choice, obtaining them has become a challenge. The placenta has become a popular alternative as it is a highly vascular organ, easily available and ethically more favorable with a rich supply of MSCs. Comparatively, placenta-derived MSCs (PMSCs) are clinically promising due to their proliferative, migratory, clonogenic and immunomodulatory properties. PMSCs release a plethora of cytokines and chemokines key to angiogenic signaling and facilitate the possibility of delivering PMSC-derived exosomes as a targeted therapy to promote angiogenesis. However, there still remains the challenge of heterogeneity in the isolated populations, questions on the maternal or fetal origin of these cells and the diversity in previously reported isolation and culture conditions. Nonetheless, the growing rate of clinical trials using PMSCs clearly indicates a shift in favor of PMSCs. The overall aim of the review is to highlight the importance of this rather poorly understood cell type and emphasize the need for further investigations into their angiogenic potential as an alternative source for therapeutic angiogenesis.

Omega-3 polyunsaturated fatty acids promote angiogenesis in placenta derived mesenchymal stromal cells.

Enhancement of angiogenesis is solicited in wound repair and regeneration. Mesenchymal stromal cells derived from the placenta (P-MSCs) have an inherent angiogenic potential. Polyunsaturated fatty acids (PUFAs) in turn, specifically the omega-3 (N-3) are essential for growth and development. They are also recommended as dietary supplements during pregnancy. We therefore hypothesized that addition of N-3 PUFAs in P-MSC culture media may enhance their angiogenic potential. Hence, we treated P-MSCs with omega-3 (N-3) fatty acids -Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) at different concentrations and tested their angiogenic potential. We saw an upregulation of both bFGF and VEGFA. We also found enhanced in vitro tube formation ability of P-MSCs treated with DHA: EPA. We then looked at the influence of the conditioned medium (CM) collected from P-MSCs exposed to DHA: EPA on the key effector cells -HUVECs (Human Umbilical Vein derived endothelial cells and their functionality was further confirmed on chick yolk sac membrane. We found that the CM of P-MSCs exposed to DHA: EPA could enhance angiogenesis in both cases. These result were finally validated in an in vivo matrigel plug assay which revealed enhanced migration and vessel formation in CM treated with DHA: EPA. Our data thus reveals for the first time that supplementation with lower concentration of PUFA enhances the angiogenic potential of P-MSCs making them suitable for chronic wound healing applications.

Mesenchymal stromal cells isolated from gestationally diabetic human placenta exhibit insulin resistance, decreased clonogenicity and angiogenesis.

Pregnancy is known to be a diabetogenic state. With sedentary lifestyle and wrong dietary choices, gestational diabetes mellitus is on the rise. This raises a concern as placenta is becoming an acceptable choice, as a source of Mesenchymal Stromal Cells (MSCs). In our current study we questioned whether there exists a difference between MSCs isolated from normal and diabetic (Gd-P-MSCs) placenta, as the health of the cells used in therapy is of prime importance. We isolated and verified the Gd-P-MSCs based on their surface markers and differentiation potential. We looked at viability and proliferation and did not see a difference between the two. We analysed the glucose uptake potential of these cells by assessing the remnant glucose in the media, glucose within the cells by 2-NBDG and by glycogen storage. Despite only a slight downregulation of mRNA expression levels of glucose transporters, Gd-P-MSCs exhibited decreased glucose uptake even upon insulin stimulation and decreased glycogen storage, indicative of an insulin resistant state. We then assessed the colony forming ability of the cells and found a decreased clonogenicity in Gd-P-MSCs. We also examined the angiogenic potential of the cells by tube formation. Gd-P-MSCs showed decreased angiogenic potential when compared to normal cells. Thus we show for the first time, the effect of gestational diabetes on cells isolated from the chorionic villi of term placenta. Gd-P-MSCs are indeed insulin resistant, exhibit decreased clonogenicity and angiogenic potential. The present investigation is of relevance to the choice of sample for MSC isolation for therapeutic purposes.

Hypoxia primed placental mesenchymal stem cells for wound healing.

AIMS: To investigate how Placental Mesenchymal Stem Cells (P-MSCs) would adapt themselves and survive under hypoxic conditions which are prevalent in most injury sites. MAIN METHODS: P-MSCs were isolated from term placenta and characterised under normoxia and hypoxia (2-2.5% O2). Cells were examined for morphology and surface marker variations by flow cytometry analysis. Glucose stimulated insulin secretion was assayed by Insulin ELISA Kit. Gene expression levels were estimated using Real Time PCR for hypoxia inducible factor1 alpha, Insulin (INS), Glucose transporters (GLUT-1, GLUT-2 and GLUT-3), Adhesion Proteins- Integrins, Fibronectin1 (FN1), E-Cadherin (CDH1), and N-Cadherin (CDH2) and angiogenesis marker VEGFA. Immunofluorescence assay was done to confirm the presence of C-Peptide, GLUT 2, E-Cadherin and ITGB3. Adhesion was confirmed assessed on fibronectin binding. KEY FINDINGS: We show that insulin secretion is not hampered under hypoxia. We found an upregulation of glucose transporters under hypoxia indicating enhanced glucose uptake needed to cater to metabolic demands of proliferating cells. Up regulation of adhesion molecules was seen under hypoxia indicative of a favoured environment for retention of cells at the injury site. We also found increased level of angiogenesis of P-MSCs under hypoxia. SIGNIFICANCE: Our present study thus demonstrates for the first time that P-MSCs modulate themselves under hypoxic conditions by secreting insulin, up regulating glucose transporters and adhesion molecules and eventually exhibiting an increased angiogenic potential. We thus infer that priming P-MSCs under hypoxia, could make them more suitable for wound healing applications.