Stem Cells for Augmenting Tendon Repair

Tendon healing is fraught with complications such as reruptures and adhesion formation due to the formation of scar tissue at the injury site as opposed to the regeneration of native tissue. Stem cells are an attractive option in developing cell-based therapies to improve tendon healing. However, several questions remain to be answered before stem cells can be used clinically. Specifically, the type of stem cell, the amount of cells, and the proper combination of growth factors or mechanical stimuli to induce differentiation all remain to be seen. This paper outlines the current literature on the use of stem cells for tendon augmentation

Pediatric Asthma: A Global Epidemic

The global prevalence, morbidity and mortality related to childhood asthma among children has increased significantly over the last 40 years. Although asthma is recognized as the most common chronic disease in children, issues of underdiagnosis and undertreatment persist. There are substantial global variations in the prevalence of asthma symptoms in children, with up to 13-fold differences between countries. The rising number of hospital admissions for asthma may reflect an increase in asthma severity, poor disease management and/or the effect of poverty. The financial burden of asthma is relatively high within developed countries (those for which data is available) spending 1 to 2% of their healthcare budget on this condition. Established in 1989, the Global Initiative for Asthma (GINA) attempts to raise awareness about the increasing prevalence of asthma, improve management and reduce the burden of asthma worldwide. Despite global efforts, GINA has not achieved its goal, even among developed nations. There are multiple barriers to reducing the global burden of asthma, including limited access to care and/or medications, and lack of prioritization as a public healthcare priority. In addition, the diversity of healthcare systems worldwide and large differences in access to care require that asthma management guidelines be tailored to local needs

National trends in musculoskeletal urgent care centers: Improved Medicaid access from 2019 to 2023.

Musculoskeletal urgent care centers (MUCCs) are an increasingly common alternative to emergency departments for patients with orthopedic injuries. As there is a lack of longitudinal data regarding MUCCs impact on the emergency health care system, our study seeks to understand recent trends in MUCC growth and their acceptance of Medicaid insurance. Over the last 6 years, at 2-year intervals (2019, 2021, and 2023), we performed a search to identify all MUCCs in the United States. We determined the affiliation and Medicaid acceptance status of all MUCCs, including those that closed/opened between 2019, 2021, and 2023, to analyze trends in MUCC availability and Medicaid acceptance. In 2019, there were 558 MUCCs, which increased to 596 MUCCs in 2021 and then decreased to 555 MUCCs in 2023, representing a growth and then decline of approximately 7%. Overall, since June 2019, 90 MUCCs have opened and 95 MUCCs have closed. Medicaid acceptance increased nationally between 2019 and 2023, from 58% to 71%. Medicaid acceptance increased for both nonaffiliated and privately affiliated MUCCs. Medicaid acceptance has increased nationally from 2019 to 2023, while MUCC availability has gone through a period of growth and then reversion to 2019 levels. As MUCCs have demonstrated limited Medicaid acceptance previously, it is promising that Medicaid acceptance has improved and MUCCs are providing patients with an additional avenue to access orthopedic care

Decay Kinetics of HIV-1 Specific T Cell Responses in Vertically HIV-1 Exposed Seronegative Infants

Objective: The majority of infants born, in developed countries, to HIV-1 positive women are exposed to the HIV-1 virus in utero or peri/post-partum, but are born uninfected. We, and others, have previously shown HIV-1 specific T cell responses in HIV-1 exposed seronegative (HESN) neonates/infants. Our objective in this study was to examine the rate of decay in their HIV-1 specific T cell response over time from birth. Design: Cross-sectional and longitudinal studies of HIV-1 specific T cell responses in HESN infants were performed. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from 18 HIV-1 DNA PCR negative infants born to HIV-1 infected mothers receiving care at the Jacobi Medical Center, Bronx, NY, USA. PBMC were examined for T cell responses to HIV-1 antigens by interferon-gamma (IFN-γ) ELISPOT. Results: PBMC from 15 HESN neonates/infants were analyzed. We observed a decay of HIV-1 specific T cell responses from birth at a rate of −0.599 spot forming unit/106 cells per day, with a median half-life decay rate of 21.38 weeks (13.39–115.8). Conclusion: Our results support the dynamic nature of T cell immunity in the context of a developing immune system. The disparate rate of decay with studies of adults placed on antiretroviral drugs suggests that antigen specific T cell responses are driven by the natural rate of decay of the T cell sub-populations themselves

Baseline resistance to nucleoside reverse transcriptase inhibitors fails to predict virologic response to combination therapy in children (PACTG 338)

BACKGROUND: The association between baseline drug resistance mutations and subsequent increase in viral failure has not been established for HIV-infected children. We evaluated drug resistance mutations at 39 codon sites (21 protease inhibitor (PI) resistant codons and 18 nucleoside reverse transcriptase inhibitor (NRTI) resistant codons) for 92 clinically stable NRTI-experienced, PI-naive HIV-infected children 2 to 17 years of age who were initiating new therapy with ritonavir plus zidovudine (ZDV) and lamivudine or plus stavudine. The association between baseline drug resistance mutations and subsequent viral failure after 12 and 24 weeks of highly active antiretroviral therapy (HAART) was studied. RESULTS: There were few primary PI associated mutations in this PI-naïve population, but 84% had NRTI mutations – codons 215 (66%), 41 (42%), 67 (37%), 210 (33%) and 70 (32%). None of the specific baseline drug resistance mutations were associated with a higher rate of virologic failure after 12 or 24 weeks of HAART. Median week 12 viral load decreased as the total number of NRTI mutations at baseline increased (P = 0.006). Specifically, a higher level of baseline ZDV resistance mutation was associated with a decrease in viral failure after 12 weeks on a ZDV-containing HAART regimen (P = 0.017). CONCLUSION: No increase was seen in the rate of viral failure after HAART associated with the presence of resistance mutations at baseline. This paradoxical result may be due to adherence, replicative capacity, or ZDV hypersusceptibility to the new regimen

Immunological Response to Highly Active Antiretroviral Therapy in Children with Clinically Stable HIV-1 Infection

We studied changes in 60 immunological parameters after the administration of highly active antiretroviral therapy (HAART) in 192 clinically stable antiretroviral drug–experienced HIV-1–infected children 4 months– 17 years old. The studied immunological parameters included standard lymphocyte subsets and lymphocyte surface markers of maturation and activation. The most significant changes during the 48-week study period were seen for CD8+, CD8+ CD62L+ CD45RA+, CD8+ CD38+ HLA-DR+, and CD4+ T cell percentages (P \u3c .0001 for all parameters). These changes suggest that significant decreases in the expression of activation markers and increases in the expression of naive markers in the CD8+ T cell population may be related to better virologic control in these HIV-1–infected children, who had relatively stable immune function at the initiation of HAART. At week 44 of HAART, the major immunological parameters in these HIV-1–infected children moved from baseline values to about halfway to two-thirds of the way toward the values in healthy, uninfected children

Pregnancy in women with perinatally acquired HIV-infection: Outcomes and challenges

This is a retrospective comparison of pregnant women with perinatally acquired HIV-infection (PAH) with a cohort of pregnant women with behaviorally acquired HIV-infection (BAH). PAH cases (11 women) included all pregnant adolescents followed at our HIV clinic from January 2000 to January 2009. BAH cases (27 women) were randomly selected from all deliveries within the study period at the same institution. Demographics, mode of delivery, CD4+ counts, and viral loads (VLs) before, during, and six months postpartum, as well as neonatal outcomes, were reviewed

A Single Center Exploratory Survey of Patients and Nurses on post-Surgical Oral Opioid Delivery Through Patient-Controlled Analgesia

Daniyal H Mirza,1,* Lucy Zha,1,* Claudia See,2 Isabella N Paoletti,1 Feng Dai,3 Mark Hocevar,4 Jinlei Li,5 Daniel Wiznia6 1Yale College, New Haven, CT, 06520-8241, USA; 2Yale School of Medicine, New Haven, CT, 06520, USA; 3Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT, 06520, USA; 4Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA; 5Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, 06510, USA; 6Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT, USA; Department of Mechanical Engineering & Materials Science, School of Engineering & Applied Science, Yale University, New Haven, CT, USA*These authors contributed equally to this workCorrespondence: Jinlei Li, Department of Anesthesiology, Yale University School of Medicine, 20 York Street, New Haven, CT, 06510, USA, Tel +1 917-601-6828, Email [email protected]: The most common route of opioid delivery is nurse-administered pills. However, there are numerous challenges such as nursing burden, opioid diversion, medication delay, and patient dissatisfaction. In this study, we conducted two surveys, first to assess patients’ and nurses’ opinions on the current administration of opioids in pill form, followed by their attitudes towards an innovative concept of oral medication delivery based on a medical device currently undergoing research and development within the University, patient-controlled dispenser and deactivator (PCDD) that allows patients to self-administer liquid oral opioids on demand based on physician prescription.Methods: Questionnaires were developed, verified and deployed to assess nurse and post-surgical patient opinions on the current administration of opioids in pill form, as well as the proposed new concept of patient -controlled administration of oral liquid medication via an illustration of PCDD, from September 2022 through July 2023 at a major academic tertiary care center. Quantitative and qualitative data were collected from postoperative patients and nurses from surgical specialties including General Surgery, Surgical Oncology, Trauma Surgery, Orthopedics, and Neurosurgery.Results: Forty-three patients and 53 nurses were interviewed. Seventy percent of patients frequently called nurses for pain medication post-surgery 1– 4 times daily, and 32% of patients were told each day by nurses that they could not receive medication because they were not due yet. Medication delay caused 24% of patients to worry about nursing availability for medication delivery. Likewise, nurses reported that half of patients receive delayed medication (22 minutes median delay time) and half of nursing time was spent administering pain medication. Nurses expressed moderate satisfaction with their current delivery of medication (median satisfaction score 6.5 out of 10). When being introduced to the concept of PCDD via a product illustration, 15% of patients said that they prefer liquid medication and 51% said they prefer PCDD or were interested in trying it.Conclusion: Nurse-administered pills are a common but suboptimal method for postoperative pain management. Based on patient and nurse feedback, patient controlled self-administered liquid oral opioid delivery is conceptually innovative, practically viable and potentially a preferred alternative for timely and less nurse-exhaustive pain management.Keywords: pain management, opioid, survey, nursing, patient-controlled analgesia pum

Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial

Introduction Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs. switching to 3TC/FTC as a “bridging strategy” to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance. Materials & methods Participants with documented nonadherence, M184V mutation, CD4+ T cell count ≥100 cells/mm3 and VF (HIV-1 plasma RNA ≥400 copies/mL (2.6 log10 HIV-1 RNA) were enrolled and randomized to continue failing cART vs. switch to 3TC/FTC. The primary endpoint (time to ≥30% CD4+ T cell decline or development of CDC class C events) at 28-weeks were assessed by Kaplan-Meier (K-M) curves in an intent-to-treat analysis. Results Thirty-three perinatally acquired YLHIV participants (16 continuing cART and 17 3TC/FTC) enrolled in the study. The median age, entry CD4+ T cell count, and viral load were 15 years (Inter-quartile range (IQR) 14–20), 472 cells/mm3 (IQR 384–651), and 4.0 log10HIV-1 RNA copies/ml (IQR 3.2–4.5), respectively. Five participants, all in the 3TC/FTC arm, reached the primary endpoint for absolute CD4+ T cell decline (p = 0.02, exact log-rank test comparing monotherapy to cART). The Kaplan-Meier estimate of probability of primary endpoint on 3TC/FTC at 28 weeks was 0.41 (standard error 0.14). There were no CDC class C events or deaths and no statistically significant difference in frequencies of adverse events between the arms. Conclusions Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4+ count of ≥30%. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. Better alternatives to 3TC/FTC such as ART with higher barriers to resistance and novel adherence and treatment strategies for nonadherent youth are urgently needed

Individual and Contextual Factors of Sexual Risk Behavior in Youth Perinatally Infected with HIV

Abstract This study prospectively examines the effects of maternal and child HIV infection on youth penetrative and unprotected penetrative sex, as well as the role of internal contextual, external contextual, social and self-regulatory factors in influencing the sexual behaviors of HIV?infected (PHIV+), HIV?affected (uninfected with an HIV+ caregiver), and HIV unaffected (uninfected with an HIV? caregiver) youth over time. Data (N=420) were drawn from two longitudinal studies focused on the effects of pediatric or maternal HIV on youth (51% female; 39% PHIV+) and their caregivers (92% female; 46% HIV+). PHIV+ youth were significantly less likely to engage in penetrative sex than HIV? youth at follow-up, after adjusting for contextual, social, and self-regulatory factors. Other individual- and contextual-level factors such as youth alcohol and marijuana use, residing with a biological parent, caregiver employment, caregiver marijuana use, and youth self-concept were also associated with penetrative sex. Youth who used alcohol were significantly more likely to engage in unprotected penetrative sex. Data suggest that, despite contextual, social, and self-regulatory risk factors, PHIV+ youth are less likely to engage in sexual behavior compared to HIV? youth from similar environments. Further research is required to understand delays in sexual activity in PHIV+ youth and also to understand potential factors that promote resiliency, particularly as they age into older adolescence and young adulthood.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98470/1/apc%2E2012%2E0005.pd