Disparities in routine breast cancer screening for medicaid managed care members with a work-limiting disability

Objective: Examine disparities in routine mammography for women who qualify for Medicaid, because of a work-limiting disability. Methods: Individual-level data were obtained for women enrolled in Massachusetts Medicaid Managed Care plans who met the 2007 Healthcare Effectiveness Data and Information Set (HEDIS) criteria for the breast cancer screening measure (n=35,171). Disability status was determined from Medicaid eligibility records. Mammography screening was modeled using multivariate logistic regression. Separate models for women with and without a disability were also estimated. Results: Although unadjusted breast cancer screening rates were roughly equal for women with and without disability, after adjusting for confounders disability status had a significant negative association with screening mammography (OR=0.74; p Conclusion: Nationwide, rates of routine mammography for Medicaid managed care plans averaged below 50% in 2006. Given that a majority of eligible women served by Medicaid have disabilities, and studies have shown that women with disabilities are more likely to be diagnosed with late stage disease, a focus on improving rates of screening for women with disabilities is overdue

Protocol for a pilot cluster randomised controlled trial of PRoGRAM-A (Preventing gambling-related harm in adolescents):A secondary school-based social network intervention

BackgroundIn the UK, recent evidence of young people and gambling indicates a higher prevalence of gambling in comparison to other addictive behaviours. Engaging in gambling-related behaviour at a young age is associated with short and long-term consequences, including financial, emotional, academic, interpersonal, and physical and mental health detriments; otherwise known as gambling-related harms (GRH). Given the unique vulnerability of this younger group, early interventions aimed at delaying or preventing gambling are critical. PRoGRAM-A (Preventing Gambling-Related Harm in Adolescents) is a school-based, social network intervention to protect young people from future GRH, by delaying or preventing gambling experimentation.MethodsPilot cluster RCT with an embedded process evaluation and health economic scoping study.ParticipantsPRoGRAM-A will be delivered in four schools, with two control schools acting as a comparator. All are secondary schools in Scotland. Baseline surveys were conducted with students in S3 (ages 13–14). Follow-up surveys were conducted with the same cohort, six months post-baseline.InterventionPRoGRAM-A trainers will deliver a 2-day, out-of-school training workshop to Peer supporters. Peer supporters will be nominated by peers among their school year group (S3, age 13–14). Workshops will provide peer supporters with information on four gambling-related topics: (1) what is gambling? (2) gambling and gaming, (3) gambling marketing, (4) identifying harm and reducing risk. Peer supporters will disseminate the information (message diffusion) they have learned among their friends and family over a 10-week period. After the 2-day workshop, PRoGRAM-A trainers will conduct × 3 in-school follow-up sessions with peer supporters to offer support, encouragement, and advice to Peer Supporters as well as monitor and explore the extent of their message diffusion.Primary outcomeThe primary outcome of the pilot cluster RCT (cRCT) will be whether progression to a phase III RCT is justified.DiscussionThis will be the first pilot cluster RCT (cRCT) of an intervention to prevent gambling-related harms among young people within the UK. If findings indicate feasibility and acceptability, funding will be sought for a phase III RCT of effectiveness.Trial registrationResearchregistry8699. Registered 21st February 2023

Peripheral nerve injury results in a biased loss of sensory neuron subpopulations

There is a rich literature describing the loss of dorsal root ganglion (DRG) neurons following peripheral axotomy, but the vulnerability of discrete subpopulations has not yet been characterised. Furthermore, the extent or even presence of neuron loss following injury has recently been challenged. In this study, we have used a range of transgenic recombinase driver mouse lines to genetically label molecularly defined subpopulations of DRG neurons and track their survival following traumatic nerve injury. We find that spared nerve injury leads to a marked loss of cells containing DRG volume and a concomitant loss of small-diameter DRG neurons. Neuron loss occurs unequally across subpopulations and is particularly prevalent in nonpeptidergic nociceptors, marked by expression of Mrgprd. We show that this subpopulation is almost entirely lost following spared nerve injury and severely depleted (by roughly 50%) following sciatic nerve crush. Finally, we used an in vitro model of DRG neuron survival to demonstrate that nonpeptidergic nociceptor loss is likely dependent on the absence of neurotrophic support. Together, these results profile the extent to which DRG neuron subpopulations can survive axotomy, with implications for our understanding of nerve injury-induced plasticity and pain

Evaluation of the protective potential of antibody and T cell responses elicited by a novel preventative vaccine towards respiratory syncytial virus small hydrophobic protein

The small hydrophobic (SH) glycoprotein of human respiratory syncytial virus (RSV) is a transmembrane protein that is poorly accessible by antibodies on the virion but has an ectodomain (SHe) that is accessible and expressed on infected cells. The SHe from RSV strain A has been formulated in DPX, a unique delivery platform containing an adjuvant, and is being evaluated as an RSV vaccine candidate. The proposed mechanism of protection is the immune-mediated clearance of infected cells rather than neutralization of the virion. Our phase I clinical trial data dearly showed that vaccination resulted in robust antibody responses, but it was unclear if these immune responses have any correlation to immune responses to natural infection with RSV. Therefore, we embarked on this study to examine these immune responses in older adults with confirmed RSV infection. We compared vaccine-induced (DPX-RSV(A)) immune responses from participants in a Phase 1 clinical trial to paired acute and convalescent titers from older adults with symptomatic laboratory-confirmed RSV infection. Serum samples were tested for anti-SHe IgG titers and the isotypes determined. T cell responses were evaluated by IFN-gamma ELISPOT. Anti-SHe titers were detected in 8 of 42 (19%) in the acute phase and 16 of 42 (38%) of convalescent serum samples. IgG1, IgG3, and IgA were the prevalent isotypes generated by both vaccination and infection. Antigen-specific T cell responses were detected in 9 of 16 (56%) of vaccinated participants. Depletion of CD4(+) but not CD8(+) T cells abrogated the IFN-gamma ELISPOT response supporting the involvement of CD4(+) T cells in the immune response to vaccination. The data showed that an immune response like that induced by DPX-RSV(A) could be seen in a subset of participants with confirmed RSV infection. These findings show that older adults with clinically significant infection as well as vaccinated adults generate a humoral response to SHe. The induction of both SHe-specific antibody and cellular responses support further clinical development of the DPX-RSV(A) vaccine

Neuronal CRTC-1 Governs Systemic Mitochondrial Metabolism and Lifespan via a Catecholamine Signal

SummaryLow energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell nonautonomously by CRTC-1 in the nervous system. Neuronal CRTC-1/CREB regulates peripheral metabolism antagonistically with the functional PPARα ortholog, NHR-49, drives mitochondrial fragmentation in distal tissues, and suppresses the effects of AMPK on systemic mitochondrial metabolism and longevity via a cell-nonautonomous catecholamine signal. These results demonstrate that while both local and distal mechanisms combine to modulate aging, distal regulation overrides local contribution. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging

Evidence of continued injecting drug use after attaining sustained treatment-induced clearance of the hepatitis C virus: implications for reinfection

Background: People who inject drugs (PWID) are at the greatest risk of hepatitis C virus (HCV) infection, yet are often denied immediate treatment due to fears of on-going risk behaviour. Our principal objective was to examine evidence of continued injecting drug use among PWID following successful treatment for HCV and attainment of a sustained viral response (SVR). Methods: PWID who attained SVR between 1992 and June 2012 were selected from the National Scottish Hepatitis C Clinical Database. Hospitalisation and mortality records were sourced for these patients using record linkage techniques. Our primary outcome variable was any hospitalisation or death, which was indicative of injecting drugs post-SVR. Results: The cohort comprised 1170 PWID (mean age at SVR 39.6y; 76% male). The Kaplan Meier estimate of incurring the primary outcome after three years of SVR was 10.59% (95% CI, 8.75–12.79) After adjusting for confounding, the risk of an injection related hospital episode or death post-SVR was significantly increased with advancing year of SVR: AHR:1.07 per year (95% CI, 1.01–1.14), having a pre-SVR acute alcohol intoxication-related hospital episode: AHR:1.83 (95% CI, 1.29–2.60), and having a pre-SVR opiate or injection-related hospital episode: AHR:2.59 (95% CI, 1.84–3.64). Conclusion: Despite attaining the optimal treatment outcome, these data indicate that an increasing significant minority of PWID continue to inject post-SVR at an intensity which leads to either hospitalisation or death and increased risk of reinfection

Measuring the impact of maternal critical care admission on short- and longer-term maternal and birth outcomes

PurposeFactors increasing the risk of maternal critical illness are rising in prevalence in maternity populations. Studies of general critical care populations highlight that severe illness is associated with longer-term physical and psychological morbidity. We aimed to compare short- and longer-term outcomes between women who required critical care admission during pregnancy/puerperium and those who did not. MethodsA cohort study including all women delivering in Scottish hospitals between 01/01/2005-31/12/2018, using national healthcare databases. The primary exposure was Intensive Care Unit (ICU) admission, whilst secondary exposures included High Dependency Unit admission. Outcomes included hospital readmission (1-year post-hospital discharge, 1-year mortality, psychiatric hospital admission, stillbirth and neonatal critical care admission). Multivariable Cox and logistic regression were used to report hazard ratios (HR) and odds ratios (OR) of association between ICU admission and outcomes. ResultsOf 762,918 deliveries, 1,449 (0.18%) women were admitted to ICU, most commonly due to post-partum haemorrhage (225, 15.5%) followed by eclampsia/pre-eclampsia (133, 9.2%). Over-half (53.8%) required mechanical ventilation. One-year hospital readmission was more frequent in women admitted to ICU compared with non-ICU populations (24.5% (n=299) vs 8.9% (n=68,029)). This association persisted after confounder adjustment (HR=1.93, 95%CI 1.33, 2.81, p&lt;0.001). Furthermore, maternal ICU admission was associated with increased 1-year mortality (HR=40.06, 95%CI 24.04,66.76, p&lt;0.001, stillbirth (OR=12.31, 95%CI 7.95,19.08,p&lt;0.001) and neonatal critical care admission (OR=6.99, 95%CI 5.64 ,8.67, p&lt;0.001) after confounder adjustment. ConclusionCritical care admission increases the risk of adverse short-term and long-term maternal, pregnancy and neonatal outcomes. Optimising long-term post-partum care may benefit maternal critical illness survivors.<br/

Antibodies against the gastrin-releasing peptide precursor pro-gastrin-releasing peptide reveal its expression in the mouse spinal dorsal horn

Gastrin-releasing peptide (GRP) in the spinal dorsal horn acts on the GRP receptor, and this signalling mechanism has been strongly implicated in itch. However, the source of GRP in the dorsal horn is not fully understood. For example, the BAC transgenic mouse line GRP::GFP only captures around 25% of GRP-expressing cells, and Grp mRNA is found in several types of excitatory interneuron. A major limitation in attempts to identify GRP-expressing neurons has been that antibodies against GRP cross-react with other neuropeptides, including some that are expressed by primary afferents. Here we have developed two antibodies raised against different parts of the precursor protein, pro-GRP. We show that labelling is specific, and that the antibodies do not cross-react with neuropeptides in primary afferents. Immunoreactivity was strongest in the superficial laminae, and the two antibodies labelled identical structures, including glutamatergic axons and cell bodies. The pattern of pro-GRP-immunoreactivity varied among different neurochemical classes of excitatory interneuron. Cell bodies and axons of all GRP-GFP cells were labelled, confirming reliability of the antibodies. Among the other populations, we found the highest degree of co-expression (&gt;50%) in axons of NPFF-expressing cells, while this was somewhat lower (10–20%) in cells that expressed substance P and NKB, and much lower (&lt;10%) in other classes. Our findings show that these antibodies reliably detect GRP-expressing neurons and axons, and that in addition to the GRP-GFP cells, excitatory interneurons expressing NPFF or substance P are likely to be the main source of GRP in the spinal dorsal horn

Hepatitis C reinfection following treatment induced viral clearance among people who have injected drugs

Background: Although people who inject drugs (PWID) are an important group to receive Hepatitis C Virus (HCV) antiviral therapy, initiation onto treatment remains low. Concerns over reinfection may make clinicians reluctant to treat this group. We examined the risk of HCV reinfection among a cohort of PWID (encompassing all those reporting a history of injecting drug use) from Scotland who achieved a sustained virological response (SVR). Methods: Clinical and laboratory data were used to monitor RNA testing among PWID who attained SVR following therapy between 2000 and 2009. Data were linked to morbidity and mortality records. Follow-up began one year after completion of therapy, ending on 31st December, 2012. Frequency of RNA testing during follow-up was calculated and the incidence of HCV reinfection estimated. Cox proportional hazards regression was used to examine factors associated with HCV reinfection. Results: Among 448 PWID with a SVR, 277 (61.8%) were tested during follow-up, median 4.5 years; 191 (69%) received one RNA test and 86 (31%) received at least two RNA tests. There were seven reinfections over 410 person years generating a reinfection rate of 1.7/100 py (95% CI 0.7–3.5). For PWID who have been hospitalised for an opiate or injection related cause post SVR (11%), the risk of HCV reinfection was greater [AHR = 12.9, 95% CI 2.2–76.0, p = 0.002] and the reinfection rate was 5.7/100 py (95% CI 1.8–13.3). Conclusion: PWID who have been tested, following SVR, for HCV in Scotland appear to be at a low risk of reinfection. Follow-up and monitoring of this population are warranted as treatment is offered more widely