Superior Pain Reduction with Anteromedialization Tibial Tubercle Osteotomy Versus Non-Operative Management for Patellofemoral Osteoarthritis.

PURPOSE: The purpose of this study was to compare the clinical outcomes of patients with patellofemoral osteoar-thritis (PFOA) treated non-operatively with those treated operatively with an unloading anteromedialization tibial tubercle osteotomy (TTO). METHODS: A retrospective chart review was performed to identify patients with isolated PFOA who were either managed non-operatively or surgically with a TTO and who had a minimum follow-up of 2 years. Patients were surveyed with the visual analog scale (VAS) for pain, Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR), Anterior Knee Pain scale (Kujala), and Tegner Activity scale. Statistical analysis included two-sample t-testing, one-way ANOVA, and bivariate analysis. RESULTS: The clinical outcomes of 49 non-operatively managed patients (mean age: 52.7 ± 11.3 years; mean follow-up: 1.7 ± 1.0 years) and 35 operatively managed patients (mean age: 31.8 ± 9.4 years; mean follow-up: 3.5 ± 1.7 years) were assessed. The mean VAS improved sig-nificantly in both groups [6.12 to 4.22 (non-operative), p < 0.0001; 6.94 to 2.45 (TTO); p < 0.0001], with operatively treated patients having significantly lower postoperative pain than non-operatively managed patients at the time of final follow-up [2.45 (TTO) vs. 4.22 (non-operative), p < 0.001]. The mean KOOS-JR score was significantly greater in the operative group at time of final follow-up [78.7 ± 11.6 (TTO) vs. 71.7 ± 17.8 (non-operative), p = 0.035]. There was no significant difference in Kujala or Tegner scores between the treatment groups. Additionally, there was no sig-nificant relationship between the number of intra-articular injections, duration of NSAID use, and number of physical therapy sessions on clinical outcomes in the non-operatively treated group (p > 0.05). CONCLUSIONS: An unloading anteromedialization TTO provides significantly better pain relief and restoration of function compared to non-operative management in the treatment of symptomatic PFOA.

Evaluation of Preoperative Variables that Improve the Predictive Accuracy of the Risk Assessment and Prediction Tool in Primary Total Hip Arthroplasty.

INTRODUCTION: Discharge disposition after total joint arthroplasty may be predictable. Previous literature has attempted to improve upon models such as the Risk Assessment and Prediction Tool (RAPT) in an effort to optimize postoperative planning. The purpose of this study was to determine whether preoperative laboratory values and other previously unstudied demographic factors could improve the predictive accuracy of the RAPT. METHODS: All patients included had RAPT scores in addition to the following preoperative laboratory values: red blood cell count, albumin, and vitamin D. All values were recorded within 90 days of surgery. Demographic variables including marital status, American Society of Anesthesiologists (ASA) scores, body mass index, Charlson Comorbidity Index, and depression were also evaluated. Binary logistic regression was used to determine the significance of each factor in association with discharge disposition. RESULTS: Univariate logistic regression found significant associations between discharge disposition and all original RAPT factors as well as nonmarried patients (P < 0.001), ASA class 3 to 4 (P < 0.001), body mass index >30 kg/m2 (P = 0.065), red blood cell count <4 million/mm3 (P < 0.001), albumin <3.5 g/dL (P < 0.001), Charlson Comorbidity Index (P < 0.001), and a history of depression (P < 0.001). All notable univariate models were used to create a multivariate model with an overall predictive accuracy of 90.1%. CONCLUSIONS: The addition of preoperative laboratory values and additional demographic data to the RAPT may improve its PA. Orthopaedic surgeons could benefit from incorporating these values as part of their discharge planning in THA. Machine learning may be able to identify other factors to make the model even more predictive.

Vaccination for healthy aging.

As the world's population grows older, vaccination is becoming a key strategy for promoting healthy aging. Despite scientific progress in adult vaccine development, obstacles such as immunosenescence and vaccine hesitancy remain. To unlock the potential of adult vaccines fully, we must enhance immunization programs, dispel misinformation, and invest in research that deepens our understanding of aging and immunity.

Strep A: challenges, opportunities, vaccine-based solutions, and economics.

This collection of articles focuses on Streptococcus pyogenes (Strep A) vaccine research and innovation, with a focus on emerging efforts to understand and estimate the full societal value of Strep A vaccination.

RNA-Seq time-course analysis of neural precursor cell transcriptome in response to herpes simplex Virus-1 infection.

The neurogenic niches within the central nervous system serve as essential reservoirs for neural precursor cells (NPCs), playing a crucial role in neurogenesis. However, these NPCs are particularly vulnerable to infection by the herpes simplex virus 1 (HSV-1). In the present study, we investigated the changes in the transcriptome of NPCs in response to HSV-1 infection using bulk RNA-Seq, compared to those of uninfected samples, at different time points post infection and in the presence or absence of antivirals. The results showed that NPCs upon HSV-1 infection undergo a significant dysregulation of genes playing a crucial role in aspects of neurogenesis, including genes affecting NPC proliferation, migration, and differentiation. Our analysis revealed that the CREB signaling, which plays a crucial role in the regulation of neurogenesis and memory consolidation, was the most consistantly downregulated pathway, even in the presence of antivirals. Additionally, cholesterol biosynthesis was significantly downregulated in HSV-1-infected NPCs. The findings from this study, for the first time, offer insights into the intricate molecular mechanisms that underlie the neurogenesis impairment associated with HSV-1 infection.

Health and Economic Growth: Reconciling the Micro and Macro Evidence.

Economists use micro-based and macro-based approaches to assess the macroeconomic return to population health. The macro-based approach tends to yield estimates that are either negative and close to zero or positive and an order of magnitude larger than the range of estimates derived from the micro-based approach. This presents a micro-macro puzzle regarding the macroeconomic return to health. We reconcile the two approaches by controlling for the indirect effects of health on income per capita, which macro-based approaches usually include but micro-based approaches deliberately omit when isolating the direct income effects of health. Our results show that the macroeconomic return to health lies in the range of plausible microeconomic estimates, demonstrating that both approaches are in fact consistent with one another.

Cost of care for Alzheimer's disease and related dementias in the United States: 2016 to 2060.

Medical and long-term care for Alzheimer's disease and related dementias (ADRDs) can impose a large economic burden on individuals and societies. We estimated the per capita cost of ADRDs care in the in the United States in 2016 and projected future aggregate care costs during 2020-2060. Based on a previously published methodology, we used U.S. Health and Retirement Survey (2010-2016) longitudinal data to estimate formal and informal care costs. In 2016, the estimated per patient cost of formal care was $28,078 (95% confidence interval [CI]: $25,893-$30,433), and informal care cost valued in terms of replacement cost and forgone wages was $36,667 ($34,025-$39,473) and $15,792 ($12,980-$18,713), respectively. Aggregate formal care cost and formal plus informal care cost using replacement cost and forgone wage methods were $196 billion (95% uncertainty range [UR]: $179-$213 billion), $450 billion ($424-$478 billion), and $305 billion ($278-$333 billion), respectively, in 2020. These were projected to increase to $1.4 trillion ($837 billion-$2.2 trillion), $3.3 trillion ($1.9-$5.1 trillion), and $2.2 trillion ($1.3-$3.5 trillion), respectively, in 2060.

Lifecycle model-based evaluation of infant 4CMenB vaccination in the UK.

OBJECTIVES: Invasive meningococcal disease, an uncommon but severe disease, imposes catastrophic health and economic burdens. Cost-utility analysis (CUA) assumes separability in lifetime health and economic variables and cannot capture the full value of preventing such burdens. We overcome these limitations with a retrospective societal perspective cost-benefit analysis (CBA) of meningococcal serogroup B vaccination (4CMenB) of one infant cohort in the United Kingdom using a health-augmented lifecycle model (HALM) incorporating health's interactions with consumption, earnings, non-market time and financial risk. METHODS: We used a static Markov model of vaccination's health impact and an HALM to estimate the private willingness to pay (PWTP) for the intrinsic and instrumental value of health under perfect capital markets, financial risk protection in the absence of insurance against permanent disability, parental spillovers, and acute phase disability. We estimated social WTP (SWTP) incorporating social severity preferences. We estimated rates of return that inform health payer reimbursement decisions, finance ministry budgeting decisions, and legislature taxation decisions. An expert Advisory Board investigated the validity of applying the HALM to infant 4CMenB. RESULTS: The PWTP for a 2 + 1 vaccination schedule is £395, comprising £166 of disability insurance value, £79 of positive parental spillover value, £28 in the value of averting acute phase disability, and £122 in residual intrinsic and instrumental value of health. SWTP is £969. CONCLUSIONS: HALM-based CBA provides an empirically richer, more utility-theoretically grounded approach to vaccine evaluation than CUA, demonstrating good value for money for legislatures (based on private values) and for all decision-makers (based on social values).

White matter and literacy: A dynamic system in flux.

Cross-sectional studies have linked differences in white matter tissue properties to reading skills. However, past studies have reported a range of, sometimes conflicting, results. Some studies suggest that white matter properties act as individual-level traits predictive of reading skill, whereas others suggest that reading skill and white matter develop as a function of an individual's educational experience. In the present study, we tested two hypotheses: a) that diffusion properties of the white matter reflect stable brain characteristics that relate to stable individual differences in reading ability or b) that white matter is a dynamic system, linked with learning over time. To answer these questions, we examined the relationship between white matter and reading in a five-year longitudinal dataset and a series of large-scale, single-observation, cross-sectional datasets (N = 14,249 total participants). We find that gains in reading skill correspond to longitudinal changes in the white matter. However, in the cross-sectional datasets, we find no evidence for the hypothesis that individual differences in white matter predict reading skill. These findings highlight the link between dynamic processes in the white matter and learning.

Trajectories and correlates of poor mental health in India over the course of the COVID-19 pandemic: a nationwide survey.

INTRODUCTION: The COVID-19 pandemic had large impacts on mental health; however, most existing evidence is focused on the initial lockdown period and high-income contexts. By assessing trajectories of mental health symptoms in India over 2 years, we aim to understand the effect of later time periods and pandemic characteristics on mental health in a lower-middle income context. METHODS: We used data from the Real-Time Insights of COVID-19 in India cohort study (N=3709). We used covariate-adjusted linear regression models with generalised estimating equations to assess associations between mental health (Patient Health Questionnaire (PHQ-4) score; range 0-12) and pandemic periods as well as pandemic characteristics (COVID-19 cases and deaths, government stringency, self-reported financial impact, COVID-19 infection in the household) and explored effect modification by age, gender and rural/urban residence. RESULTS: Mental health symptoms dropped immediately following the lockdown period but rose again during the delta and omicron waves. Associations between mental health and later pandemic stages were stronger for adults 45 years of age and older (p<0.001). PHQ-4 scores were significantly associated with all pandemic characteristics considered, including estimated COVID-19 deaths (PHQ-4 difference of 0.10 units; 95% CI 0.06 to 0.13), government stringency index (0.14 units; 95% CI 0.11 to 0.18), self-reported major financial impacts (1.20 units; 95% CI 1.09 to 1.32) and COVID-19 infection in the household (0.36 units; 95% CI 0.23 to 0.50). CONCLUSION: While the lockdown period and associated financial stress had the largest mental health impacts on Indian adults, the effects of the pandemic on mental health persisted over time, especially among middle-aged and older adults. Results highlight the importance of investments in mental health supports and services to address the consequences of cyclical waves of infections and disease burden due to COVID-19 or other emerging pandemics.

Meningococcal Disease in the Post-COVID-19 Era: A Time to Prepare.

The global invasive meningococcal disease (IMD) landscape changed considerably during the COVID-19 pandemic, as evidenced by decreased incidence rates due to COVID-19 mitigation measures, such as limited social contact, physical distancing, mask wearing, and hand washing. Vaccination rates were also lower during the pandemic relative to pre-pandemic levels. Although policymakers may have shifted their focus away from IMD vaccination programs to COVID-19 vaccination programs, strong arguments support implementation and prioritization of IMD vaccination programs; IMD cases have increased in some countries and IMD rates may even have exceeded pre-pandemic levels. Additional concerns include increased susceptibility due to vaccination coverage gaps, increased incidence of other respiratory pathogens, immunity debt from lockdown restrictions, and increased IMD epidemiologic variability. The full range of benefits of widely available and effective meningococcal vaccines needs to be considered, especially in health technology assessments, where the broad benefits of these vaccines are neither accurately quantified nor captured in implementation policy decisions. Importantly, implementation of meningococcal vaccination programs in the current IMD climate also appeals to broader healthcare principles, including preparedness rather than reactive approaches, generally accepted benefit-risk approaches to vaccination, historical precedent, and the World Health Organization's goal of defeating meningitis by 2030. Countries should therefore act swiftly to bolster existing meningococcal vaccination strategies to provide broad coverage across age groups and serogroups given the recent increases in IMD incidence.

Antibiotic consumption for sore throat and the potential effect of a vaccine against group A Streptococcus: a systematic review and modelling study.

BACKGROUND: Antibiotic consumption can lead to antimicrobial resistance and microbiome imbalance. We sought to estimate global antibiotic consumption for sore throat, and the potential reduction in consumption due to effective vaccination against group A Streptococcus (Strep A). METHODS: We reviewed and analysed articles published between January 2000 and February 2022, identified though Clarivate Analytics' Web of Science search platform, with reference to antibiotic prescribing or consumption, sore throat, pharyngitis, or tonsillitis. We then used those analyses, combined with assumptions for the effectiveness, duration of protection, and coverage of a vaccine, to calculate the estimated reduction in antibiotic prescribing due to the introduction of Strep A vaccines. FINDINGS: We identified 101 studies covering 38 countries. The mean prescribing rate for sore throat was approximately 5 courses per 100 population per year, accounting for approximately 5% of all antibiotic consumption. Based on 2020 population estimates for countries with empiric prescribing rates, antibiotic consumption for sore throat was estimated to exceed 37 million courses annually, of which half could be attributable to treatment for Strep A. A vaccine that reduces rates of Strep A infection by 80%, with 80% coverage and 10 year's duration of protection, could avert 2.8 million courses of antibiotics prescribed for sore throat treatment among 5-14 year-olds in countries with observed prescribing rates, increasing to an estimated 7.5 million averted if an effective vaccination program also reduced precautionary prescribing. INTERPRETATION: A vaccine that prevents Strep A throat infections in children may reduce antibiotic prescribing for sore throat by 32-87% depending on changes to prescribing and consumption behaviours. FUNDING: The Wellcome Trust, grant agreement number 215490/Z/19/Z.

A viral lncRNA tethers HSV-1 genomes at the nuclear periphery to establish viral latency.

IMPORTANCE: Herpes simplex virus 1 (HSV-1) establishes lifelong latency in neuronal cells. Following a stressor, the virus reactivates from latency, virus is shed at the periphery and recurrent disease can occur. During latency, the viral lncRNA termed the latency-associated transcript (LAT) is known to accumulate to high abundance. The LAT is known to impact many aspects of latency though the molecular events involved are not well understood. Here, we utilized a human neuronal cell line model of HSV latency and reactivation (LUHMES) to identify the molecular-binding partners of the LAT during latency. We found that the LAT binds to both the cellular protein, TMEM43, and HSV-1 genomes in LUHMES cells. Additionally, we find that knockdown of TMEM43 prior to infection results in a decreased ability of HSV-1 to establish latency. This work highlights a potential mechanism for how the LAT facilitates the establishment of HSV-1 latency in human neurons.

Preoperative Symptom Severity Predicts 5-Year Hip Arthroscopy Outcomes.

PURPOSE: Thisstudy sought to assessthe prognostic effect of preoperative symptom severity on hip arthroscopy outcomes for femoroacetabular impingement syndrome (FAI). METHODS: Patients undergoing hip arthroscopy between September 2012 and July 2014 for FAI with a minimum of 5-year clinical outcomes were compiled. Patient reported outcomes (PROs) including modified Harris Hip Score (mHHS) and Nonarthritic Hip Score (NAHS) were collected. High and low preoperative function (PF) subgroups were created using baseline population median mHHS (43.3) as a threshold with PROs below the median score indicating low preoperative function and vice versa for scores above the median. Kaplan-Meier analysis, Cox proportional modeling, analysis of variance (ANOVA), and linear regressions were used for analysis. RESULTS: One hundred five of 131 eligible patients(80.2% inclusion; age: 42.6 ± 1.4 years; body mass index: 25.3 ± 0.4 kg/m2 ) met the study criteria. The 5-year survival-torevision rate (85% versus 61%, p = 0.013) and survivalto-arthroplasty rate (95% vs. 82%, p = 0.022) were greater in the high versus low PF group. ANOVA demonstrated the high versus low PF group had higher baseline (mHHS: 52.7 ± 1.4 vs. 36.1 ± 1.1, p < 0.001; NAHS: 57.4 ± 1.6 vs. 39.3 ± 1.2, p < 0.001) and 1-year (mHHS: 91.9 ± 1.8 vs. 79.5 ± 2.7, p < 0.001; NAHS: 91.7 ± 1.6 vs. 80.8 ± 2.5, p < 0.001) outcomes. High versus low PF achieved higher Minimal Clinically Important Difference (77% vs. 57%, p = 0.026) at 5-years. High versus low PF achieved higher Patient Acceptable Symptomatic State rates at 1 year (79% vs. 47%, p < 0.001) and 5 years (66% vs. 45%, p = 0.032). Linear regression demonstrated body mass index (mHHS: p = 0.002; NAHS: p = 0.005), pincer resection (mHHS: p = 0.046), and preoperative symptom severity (mHHS: p = 0.001; NAHS: p = 0.002) to be predictors of 5-year change in PROs. CONCLUSION: Preoperative symptom severity is a reliable prognostic indicator of clinical survival rates and PROs after hip arthroscopy for FAI. Subjects with high PF are likely to have increased longevity of the index procedure while maintaining excellent PASS and MCID rates mid-term as opposed to those with low PF.

Public economic gains from tax-financed investments in childhood immunization in the United States.

The emergence of COVID-19 has displayed the importance of immunization and the need for continued public investment in vaccination programs. Globally, national vaccination programs rely heavily on tax-financed expenditure, requiring upfront investments and ongoing financial commitments. To evaluate annual public investments, we conducted a fiscal analysis that quantifies the public economic consequences to government in the United States attributable to childhood vaccination. To estimate the change in net government revenue, we developed a decision-analytic model that quantifies lifetime tax revenues and transfers based on changes in morbidity and mortality arising from vaccination of the 2017 U.S. birth cohort. Reductions in deaths and comorbid conditions attributed to pediatric vaccines were used to derive gross lifetime earnings gains, tax revenue gains attributed to averted morbidity and mortality avoided, disability transfer cost savings, and averted special education costs associated with each vaccine. Our analysis indicates a fiscal dividend of $41.7 billion from vaccinating this cohort. The bulk of this gain for government reflects avoiding the loss of $30.6 billion in present-value tax revenues. All pediatric vaccines raise tax revenues by reducing vaccine-preventable morbidity and mortality in amounts ranging from $7.3 million (hepatitis A) to $20.3 billion (diphtheria) over the life course. Based on public investments in pediatric vaccines, a benefit-cost ratio of 17.8 was calculated for each dollar invested in childhood immunization. The public economic yield attributed to childhood vaccination in the U.S. is significant from a government perspective, providing fiscal justification for ongoing investment.